Brain Stem

We're finally at the starting gate in learning about the brain. Serious discoveries will be forthcoming in genomics, developmental behaviors, disease inhibition, and the brain's interaction with the body. The brain is the last frontier in medicine, uncharted territory that commands the attention of any true explorer. To read more about health-related topics on the Global Province, also see Stitch in Time.

"This was my first experience of transcranial direct-current stimulation, or tDCS—a portable, cheap, low-tech procedure that involves sending a low electric current (up to two milliamps) to the brain. Research into tDCS is in its early stages. A number of studies suggest that it may improve learning, vigilance, intelligence, and working memory, as well as relieve chronic pain and the symptoms of depression, fibromyalgia, Parkinson's, and schizophrenia. However, the studies have been so small and heterogeneous that meta-analyses have failed to prove any conclusive effects, and long-term risks have not been established. The treatment has yet to receive F.D.A. approval, although a few hospitals, including Beth Israel, in New York, and Beth Israel Deaconess, in Boston, have used it to treat chronic pain and depression." "Electrified: Adventures in Transcranial Direct-current Stimulation," New Yorker, April 6, 2015, pp.24-41. Finally electric shock therapy is turning respectable.

"More is not better when it comes to synapses, for sure, and pruning is absolutely essential," said Lisa Boulanger, a molecular biologist at Princeton who was not involved in the research. "If it was overgrowth, you'd expect them to be different from the start, but because the synapse difference comes on so late, it's probably pruning."

Dr. Sulzer's team also found biomarkers and proteins in the brains with autism that reflected malfunctions in the system of clearing out old and degraded cells, a process called autophagy.

"They showed that these markers of autophagy decrease in autism-afflicted brains," said Eric Klann, a professor of neural science at New York University. "Without autophagy, this pruning can't take place." (8-27-14)

A code talker in World War II, using the Navajo language to befuddle Japanese intelligence agents, Chester Nez , who just passed away, had a tough life in and out of war. He surmounted his bad dreams with traditional Indian spirit healing:

"Prohibited, like all the men of the 382nd, from discussing his service, Mr. Nez was plagued by nightmares and spent more than five months in a San Francisco military hospital.

My condition was so severe I went psycho, he said in a 2005 lecture. I lost my mind.

Yet of the returned code talkers, he considered himself among the lucky ones. Some turned to drinking or just gave up, Mr. Nez said in an interview last year. His father came to his rescue, explaining that his nightmares were caused by the spirits of dead Japanese. Mr. Nez underwent a traditional healing ceremony, and the dreams largely ceased.” (6-18-14)

‘Our brains are constantly, subtly being primed in fascinating ways by our physical surroundings. “

“Researchers suggest that being high up, or the mere act of ascending, reminds us of lofty ways of thinking and behaving.”

“Jan Gehls studies of street edges provide evidence. Gehl and others have found that if a street features uniform facades with hardly any doors, variety, or functions, people move past as quickly as possible. But if a street features varied facades, lots of openings, and a high density of functions per block, people walk more slowly. They pause more often. People are actually more likely to stop and make cell phone calls in front of lively facades than in front of dead ones.” (1-01-14)

“The wicked delight over that turn of events has a German name so apt weve adopted it in English. Schadenfreude, or harm-joy, is the pleasure derived from anothers misfortune, and Richard H. Smith, a University of Kentucky psychology professor, has built a career around studying it and other social emotions. He previously edited an anthology about envy, a close sibling to schadenfreude.”

“But life doesn’t always turn out that way, and when we encounter someone who is more chosen, beloved or esteemed than we are, our natural instinct is to tear them down to our level. If this illicit desire is fulfilled by happenstance, schadenfreude ensues. Clive James captured the feeling in a poem that takes its title from its first line: The book of my enemy has been remaindered/ And I am pleased.” See "Our Pleasure in Others' Misfortune," New York Times, December 23, 2013. http://www.nytimes.com/2013/12/24/science/the-joy-of-pain-and-what-we-get-out-of-it.html (01-01-14)

”Dr. David Hubel, who was half of an enduring scientific team that won a Nobel Prize for explaining how the brain assembles information from the eye’s retina to produce detailed visual images of the world, died on Sunday in Lincoln, Mass.,” according to the New York Times.

“Dr. Hubel’s and Dr. Wiesel’s work further showed that sensory deprivation early in life can permanently alter the brain’s ability to process images. Their findings led to a better understanding of how to treat certain visual birth defects.”

“By measuring the electrical impulses of cells in the visual cortex, the scientists discovered that cells respond to straight lines, movement and contrast — features that delineate objects in the environment. They further found that some cells fire rapidly in response to horizontal lines, while other cells prefer vertical lines or angles. Cells with similar functions are organized into columns, they said, tiny computational machines that relay information to a higher region of the brain, where a visual image is formed.”

“David and Torsten did more than open up the study of the primary visual cortex; they laid the basis of all that was to follow in the sensory systems,” Dr. Eric R. Kandel, a Nobel laureate, wrote in a recent commentary about their research. “Together this body of work stands as one of the great biological achievements of the 20th century.” (10-9-13)

”Consider the biology of depression. We are beginning to discern the outlines of a complex neural circuit that becomes disordered in depressive illnesses. Helen Mayberg, at Emory University, and other scientists used brain-scanning techniques to identify several components of this circuit, two of which are particularly important.

One is Area 25 (the subcallosal cingulate region), which mediates our unconscious and motor responses to emotional stress; the other is the right anterior insula, a region where self-awareness and interpersonal experience come together.

These two regions connect to the hypothalamus, which plays a role in basic functions like sleep, appetite and libido, and to three other important regions of the brain: the amygdala, which evaluates emotional salience; the hippocampus, which is concerned with memory; and the prefrontal cortex, which is the seat of executive function and self-esteem. All of these regions can be disturbed in depressive illnesses.

In a recent study of people with depression, Professor Mayberg gave each person one of two types of treatment: cognitive behavioral therapy, a form of psychotherapy that trains people to view their feelings in more positive terms, or an antidepressant medication. She found that people who started with below-average baseline activity in the right anterior insula responded well to cognitive behavioral therapy, but not to the antidepressant. People with above-average activity responded to the antidepressant, but not to cognitive behavioral therapy. Thus, Professor Mayberg found that she could predict a depressed persons response to specific treatments from the baseline activity in the right anterior insula.

These results show us four very important things about the biology of mental disorders. First, the neural circuits disturbed by psychiatric disorders are likely to be very complex.

Second, we can identify specific, measurable markers of a mental disorder, and those biomarkers can predict the outcome of two different treatments: psychotherapy and medication.

Third, psychotherapy is a biological treatment, a brain therapy. It produces lasting, detectable physical changes in our brain, much as learning does.

And fourth, the effects of psychotherapy can be studied empirically. Aaron Beck, who pioneered the use of cognitive behavioral therapy, long insisted that psychotherapy has an empirical basis, that it is a science. Other forms of psychotherapy have been slower to move in this direction, in part because a number of psychotherapists believed that human behavior is too difficult to study in scientific terms.” (Erik Kandel on “The New Science of Mind”) (9-11-13)

“Story C. Landis, the director of the National Institute of Neurological Disorders and Stroke, said that when she heard Mr. Obamas speech, she thought he was referring to an existing National Institutes of Health project to map the static human brain. But he wasnt, she said. He was referring to a new project to map the active human brain that the N.I.H. hopes to fund next year.”
“The initiative will be organized by the Office of Science and Technology Policy, according to scientists who have participated in planning meetings.

The National Institutes of Health, the Defense Advanced Research Projects Agency and the National Science Foundation will also participate in the project, the scientists said, as will private foundations like the Howard Hughes Medical Institute in Chevy Chase, Md., and the Allen Institute for Brain Science in Seattle."

As we have said on a host of occasions, the medical mandarins, often in Boston, have frequently embraced theories about neurological complaints that are either just plain wrong or hopelessly incomplete. Nowhere has this been true than with Alzheimer's. The party line is that amyloid outcroppings of one form or another are the main causal factor behind the disease and that the problem is to bring them to heel. Unfortunately drugs directed at amyloids simply have not done much to help sufferers. The ever-maverick Australians meanwhile have done some interesting work. One researcher has pursued a line of attack that looks at metallic deposits.

As we have said, Wischik is as passionate about tau as others are about amyloids, and he feels it is the key to Alzheimer’s. Now trials are about to put his theory to the test. This update simply expands our knowledge about Wischik.

“After years on the sidelines, Dr. Wischik, who now lives in Scotland, sees this as tau's big moment. The company he co-founded 10 years ago, TauRx Pharmaceuticals Ltd., has developed an experimental Alzheimer's drug that it will begin testing in the coming weeks in two large clinical trials. Slowly, other companies are boosting investment in tau research, too. This summer, Roche Holding AG ROG.VX +0.31%bought the rights to a type of experimental tau drug from Switzerland's closely held AC Immune SA.” (Wall Street Journal, November 10-11, 2012)

“Dr. Buee, the longtime tau researcher in France, says Johnson & Johnson asked him to provide advice on tau last year, and that he's currently discussing a tau research contract with a big pharmaceutical company. (A Johnson & Johnson spokeswoman says the company invited Dr. Buee and other scientists to a meeting to discuss a range of approaches to fighting Alzheimer's.)

“With its new clinical trial program under way, TauRx is the first company to test a tau-targeted drug against Alzheimer's in a large human study, known in the industry as a phase 3 trial.” (April 24, 2013)

Published April 4 in the journal Neurology, the findings add to the growing body of evidence that regular consumption of some flavonoids can have a marked effect on human health. Recent studies have shown that these compounds can offer protection against a wide range of diseases including heart disease, hypertension, some cancers and dementia.

This latest study is the first study in humans to show that flavonoids can protect neurons against diseases of the brain such as Parkinson's.

Around 130,000 men and women took part in the research. More than 800 had developed Parkinson's disease within 20 years of follow-up. After a detailed analysis of their diets and adjusting for age and lifestyle, male participants who ate the most flavonoids were shown to be 40 per cent less likely to develop the disease than those who ate the least. No similar link was found for total flavonoid intake in women.

Prof Gao said: "Interestingly, anthocyanins and berry fruits, which are rich in anthocyanins, seem to be associated with a lower risk of Parkinson's disease in pooled analyses. Participants who consumed one or more portions of berry fruits each week were around 25 per cent less likely to develop Parkinson's disease, relative to those who did not eat berry fruits. Given the other potential health effects of berry fruits, such as lowering risk of hypertension as reported in our previous studies, it is good to regularly add these fruits to your diet."

Flavonoids are a group of naturally occurring, bioactive compounds found in many plant-based foods and drinks. In this study the main protective effect was from higher intake of anthocyanins, which are present in berries and other fruits and vegetables including aubergines, blackcurrants and blackberries. Those who consumed the most anthocyanins had a 24 per cent reduction in risk of developing Parkinson's disease and strawberries and blueberries were the top two sources in the US diet. (Science Daily)

"One suggestion that does pop up from time to time is that the process which leads to autism involves faulty mitochondria. The mitochondria are a cell's powerpacks. They disassemble sugar molecules and turn the energy thus liberated into a form that biochemical machinery can use. Mitochondrial faults could be caused by broken genes, by environmental effects, or by a combination of the two."

"The mitochondria of the autistic children also leaked damaging oxygen-rich chemicals such as hydrogen peroxide. These are a normal by-product of mitochondrial activity, but are usually mopped up by special enzymes before they can escape and cause harm—for instance, by damaging a cell's DNA. The level of hydrogen peroxide in the cells of autistic children was twice that found in non-autists. Such high levels suggest the brains of autistic children are exposed to a lot of oxidative stress, something that would probably cause cumulative damage."

These results have to be taken with a grain of salt. Mitochrondrial faults only show up in a few autistic cases, so they cannot explain all autistic cases. And the sample sizes of tests done to test this correlation have been small thus far.

"Although all but forgotten by America's 20 million would-be yoginis, clad in their finest Lulemon, Vikekananda was the Bengali monk who introduced the word "yoga" into the national conversation. In 1893, outfitted in a red, flowing turban and yellow robes belted by a scarlet sash, he had delivered a show-stopping speech in Chicago. The event was the tony Parliament of Religions…."

"Vivekananda's genius was to simplify Vedantic thought to a few accessible teachings that Westerners found irresistible."

"It wasn't until after an electrifying lecture by Vivekananda at Harvard's Graduatre Philosophical Club on March 25, 1896, that Eastern Philosophy departments became a staple of Ivy League Colleges."

"India has scheduled a yearlong party to commemorate the 150th anniversary of Vivekananda's birth, beginning on January 12, 2013.

The Annenberg Foundation has sponsored a set of short modules that help teachers explain the mind to youngish students. They were produced by Colorado State University in 1999. We are probably a bit puzzled as to why there is segment on aging, since this series is geared for younger people.

As reported in the Wall Street Journal, a new report "showed that compared to nonobese mothers, those who were obese before pregnancy had a 60% increase in the likelihood of having a child with autism and a doubling in risk of having a child with another type of cognitive or behavioral delay.

The risk was even more pronounced when mothers who had high blood pressure or diabetes before or during pregnancy were included in the analysis.

Mindblindness explores once again the opaqueness with which the autistic must struggle. Here is MIT's blurb about the book:

"How empathetic are you? Most of us interact with other people-- family, friends, co-workers, strangers--by an unwritten set of rules based solely on our ability to "mind read" a situation. That is, to be intuitively aware of others around us and respond accordingly. Those who have autism have a difficult time mindreading. What comes naturally or intuitively to people without autism often must be taught like a set of concrete rules to those with autism. Mindblindness by Simon Baron-Cohen, Professor of Developmental Psychopathology at the University of Cambridge and Director of the Autism Research Centre in Cambridge, explores this notion of mindreading. In his book, Baron-Cohen challenges his readers to see the world differently."

Almost any modern drug has serious side effects that really don't get identified until years after the drug has come to market. Now that sort of news is dribbling in about the statins, which perk up the heart but also, it seems, cause some brain impairment, particularly of the memory. We think there are other subtle, long-term statin downsides that have yet to be confirmed by more research.

"Statins are the most prescribed drugs in the world, and there is no doubt that for people at high risk of cardiovascular problems, the drugs lower not only cholesterol but also the risk of heart attack and stroke. But for years doctors have been fielding reports from patients that the drugs leave them feeling "fuzzy," and unable to remember small and big things, like where they left the car, a favorite poem or a recently memorized presentation. Last week, the Food and Drug Administration finally acknowledged what many patients and doctors have believed for a long time: Statin drugs carry a risk of cognitive side effects. The agency also warned users about diabetes risk and muscle pain."

"Daily doses of a drug used to treat Parkinson's disease significantly improved function in severely brain-injured people thought to be beyond the reach of treatment…," but the improvements were modest. New York Times, March 1, 2012, P.A.16.

"Some 50,000 to 100,000 Americans live in states of partial consciousness, and perhaps 15,000 in an unresponsive "vegetative" condition. According to the Department of Defense, more than 6,000 veterans have had severe brain injuries since 2000 and would potentially benefit from this therapy"

"Monkeys suffering from Parkinson's disease show a marked improvement when human embryonic stem cells are implanted in their brains, in what a Japanese researcher said Wednesday was a world first. Takahashi said at the time of the implant about 35 percent of the stem cells had already grown into dopamine neuron cells, with around 10 percent still alive after a year. He said he wants to improve the effectiveness of the treatment by increasing the survival rate of dopamine neuron cells to 70 percent. "The challenge before applying it to a clinical study is to raise the number of dopamine neuron cells and to prevent the development of tumors," he said The report on this stem cell application comes from Jun Takahashi of Kyoto University.

"Scientists have developed a new cancer-killing virus that significantly prolonged the life of mice with glioblastoma, an aggressive form of brain cancer in humans. Wall Street Journal, November 15, 2011, p. D3. "Researchers in Ohio used a herpes simplex virus type I to develop an oncolytic virus called 34.SENVE. The virus was engineered to replicate in cells with high levels of nestin, a protein present in glioblastomas and certain other cancers, including prostate, pancreatic and breast. The virus also carries an antiangiogenic gene that inhibits blood-vessel growth in tumors." See Molecular Therapy, 25 October 2011.

We've heard often enough of Bostonians afflicted with S.A.D. (Seasonably Affective Disorder), bouts of depression brought on by the dark days of winter. Sometimes they sit in front of bright lamps to drive away the blues. But many white collar professionals use it as an excuse to bounce off to the Caribbean, excusing a week or so away from work as a necessary therapeutic exercise.

Focused flashes, however, appear to be what the doctor ordered for more serious neurological complaints. Karl Deisseroth, based at the Clark Center of Stanford University, is busy proving how, "using light in the brain, we may be able to switch depression, sociability and other seemingly ungovernable behaviors on and off." Wall Street Journal, November 19-20, 2011, p.C20. He is active in the field of 'optogenetics.' "The field combines the use of light and genetics to micromanage living tissue, including neurons in the brain. It could change our treatment of diseases ranging from epilepsy and Parkinson's to anxiety and autism."

Light sensitive proteins taken from nature are inserted in the brain and lasers are connected to remedy neuron problems. As used in mice, the technique precisely hits afflicted brain areas.

"Researchers with UCLA's Jonsson Comprehensive Cancer Center have developed and used a high-throughput molecular screening approach that identifies and characterizes chemical compounds that can target the stem cells that are responsible for creating deadly brain tumors."

"After testing more than 31,000 compounds from seven chemical libraries in an initial screen, the team came up with 694 that showed some activity against the brain cancer stem cells. After further narrowing the field down to 168 compounds, they decided to focus on four in future studies because they most successfully inhibited the brain cancer stem cells, Kornblum said." See "A Molecular Screening Approach to Identify and Characterize Inhibitors of Glioblastoma Stem Cells"

Shirley Wang suggests that there is some slight progress in understanding Lou Gehrig's Disease. "ALS is a progressive, fatal disease in which motor neurons are destroyed and patients gradually lose the ability to move their bodies and even to breathe. The disease typically occurs in people between 40 and 60 years old and most patients die from respiratory problems within three to five years after their symptoms start, according to the National Institutes of Health."

"In research published online last month by the journal Nature, Teepu Siddique, a professor of neurology at Northwestern University's Feinberg School of Medicine, and his colleagues appear to have found a key protein that they say could be the answer to why the toxic proteins accumulate. The researchers identified a mutation, or a misfolding, in a protein called ubiquilin 2 that renders it ineffective. Normally, ubiquilin 2 clears out from neurons other proteins that aren't working properly. The research team's finding suggests that the ineffective ubiquilin 2 fails to remove toxic proteins from the system, allowing other proteins to accumulate"

"At the University of Chicago, Raymond Roos, a neurology professor and director of the ALS Clinic, is also studying how to clear misfolded proteins from the body. He and his colleagues have been investigating another "housekeeping" pathway known as the unfolded-protein response, or UPR, a chain of reactions that aims either to fix malfunctioning proteins or, if that fails, to kill them off. "

David Eagleman is a bright you neuroscientist who has added punctuation to all the twists and turns German philosophy took from Immanuel Kant forward. That is, the Germans have been busy showing us all the ways in which we do not know about things. Eagleman even goes them one better. His version of the unconscious drives 90% of human decision-making, the conscious playing a small role in affairs. In other words, we are driven by forces we do not understand. This is the naked gist of his new book Incognito. And at other times, he suggests that we simply don’t know about 90% of the universe, which means 90% of everything. With this epistemology and this kind of metaphysics, one could become nihilistic and despairing. Instead, Eagleman tells to be open to the possibilities and the alternate theories of scientific explanation, at least until the facts crowd out less likely hypotheses. This sounds like a very healthy agnosticism. (06-22-11)

V.S. Ramachandran, a gifted neuroscientist, is just out with The Tell-Tale Brain: A Neuroscientist’s Quest for What Makes Us Human. The Times reviewer, Anthony Gottleib, shows how Ramachandran portrays the workings of the brain by looking at cases of its malfunctions. Looking into what happens when it goes awry, he can then map how it does function when it is working right. He pushes the thesis that mirror neurons are a central catalyst in correct brain function, an idea that is quite controversial and has been refuted in many quarters.
“Cotard syndrome is one of many unusual mental afflictions Ramachandran discusses in his new book, The Tell-Tale Brain. He also looks at Capgras syndrome (when a person believes those around him have been replaced by imposters), apraxia (when a person cannot mimic simple gestures), and telephone syndrome (when a person is comatose but can somehow converse on the phone).” (Scientific American, December 24, 2010)
”His book is intermittently fascinating, but is not important in the way of Iain McGilchrist The Master and His Emissary (Yale, £10.99), last year’s magisterial study of the brain’s two opposed hemispheres, which it nicely (though unintentionally) complements – even to the extent of using some of the same illustrations” (Guardian, 7 January 2011) (02-09-11)

“Biological waste material normally is broken down by the part of the cell known as the lysosome. If something goes wrong in the process, toxins, made up largely of various proteins, start to build up and cause cells to deteriorate and die.” (“Key to Alzheimer’s: Waste in Cells,” Wall Street Journal, December 28, 2010, p. D2. “Ralph Nixon, professor of psychiatry and cell biology at New York University’s Langone Medical Center and the Nathan Kline Institute,” says experiments with Alzheimer’s afflicted mice support this theory. By beefing up the enzyme action, they prevented “cognitive decline in the animals….” “Traditional drug development in Alzheimer’s disease is taking too narrow an approach by focusing intensively on the build-up of amyloid beta-protein in the brain, Dr. Nixon says. That’s because amyloid, although important, is just one of the many toxic proteins that swell the neurons when the lysosomal system breaks down.” It is felt that the same problem—waste build-up—may play an important part in TaySachs, Gaucher, Huntington’s, and Niemann-Pick Type C. Also active in this realm are David C. Rubinsztein at Cambridge Institute of Medical Research and Yiannis A. Ioannou at New York’s Mount Sinai School of Medicine. It has long been clear to many that the focus on amyloids just was not the right approach to Alzheimer’s. Many chronic diseases of older patients result from the slow accumulation of foreign bodies that retard normal bodily functions. The body it seems requires catharsis. For that matter, so does the brain. (02-09-11)

The Wall Street Journal (January 11, 2011, p. D3) did a round up on the use of electricity and magnets to treat mental ailments. Techniques include use of electricity, magnets, ultrasound, and infrared waves. Mostly they are used for depression, but they show promise, too, “for treating obsessive-compulsive disorder, panic disorders, schizophrenia, addictions and memory problems.” “Of the new brain-stimulation therapies, the most developed is Transcranial Magnetic Stimulation (TMS)…A technician holds a magnetic coil against the patient’s forehead.” “Peer-reviewed studies show that TMS results in remission in about 30% of depressed patients, only half the rate of ECT but twice as good as a placebo.” “With Vagus Nerve Stimulation (VNS), a pacemaker-like device is implanted near the base of the neck to deliver mild electrical pulses to the vagus nerve……” “In Deep Brain Stimulation (DBS), a pair of electrodes is implanted in the brain …connected by wires to a pair of pulsing devices in the chest.” This has been used worldwide to treat Parkinson’s. More scholarly articles about this whole field are now beginning to appear, such as those in a relatively young publication called Brain Stimulation. (01-26-11)

Update: Expanding Uses of DBS
“Now researchers are pushing the boundaries of the treatment by investigating it for use against other conditions. DBS may have particular benefit for children suffering from epilepsy, according to Andre Machado, the director of Cleveland Clinic's Center for Neurological Restoration, who conducted Ms. Cisar's operation and who is studying the use of DBS to treat pain and stroke.” “Ms. Cisar's surgery illustrates the intricacies involved with major brain surgery. Dystonia is the third-most-common movement disorder in the U.S., behind Parkinson's and essential tremor and affects about 300,000 Americans, according to the American Dystonia Society. Doctors don't know the cause in Ms. Cisar's case, but say it isn't genetic.” (10-9-13)

In “Meet Dr. Freud,” Evan Osnos discusses the decline of Freudian psychotherapy in these United States, but more importantly, its rise in China. One Elise Snyder, whose affair with Victor Rosen, a onetime president of the American Psychoanalytic Association, sparked a scandal and whose offbeat campaign to keep Freud alive and relevant in the United States annoyed many of her co-practitioners, has led the charge into China, trolling afar from her chair as associate clinical professor at Yale. Interestingly the demand for therapy has far outstripped the small supply of talent, though Snyder and her colleagues are gradually training locals in Freudian technique. It is interesting culturally that psychotherapy should take such deep root in China and that this is all transpiring without supervision from the Ministry of Health which is otherwise busily engaged in overhauling and expanding healthcare in China. There’s a special twist in China. Much of the one on one work is also done on video Skype, quite a different format in which to bring together therapist and patient. We are aware of video surgery and other distance type treatment in the United States, but have not heard whether it has been extended to the mental health arena. New Yorker, January 20, 2011, pp54-63. (1-12-11)

273. Stress and Everything Else
“Stress Doesn’t Kill Us—But It Makes Everything that Does Kill Us Much Worse, “ Wired, pp.130-137; 146. “While stress doesn’t cause any single disease—in fact, the causal link between stress and ulcers has been largely disproved-it makes most diseases signficantly worse.” Robert Sapolsky, who has devoted himself to the study of stress, “is working on a vaccinelike treatment for stress.” “Unfortunately a swollen amygdala means that we’re more likely to notice potential threats in the first place, which means we spend more time in a state of anxiety.” Early threats can cause one to become wired for stress, in the amygdale, and over- attuned to look for dangers and risks.. Stress begets more stress and very permanent stress. “But emerging evidence suggests that the effects of chronic stress are worse for some people—especially those at the bottom of any given pecking order.” In other words, it’s tough for those at the bottom of a hierarchy or food chain. The thought is that stress levels are very intense for those who feel they are not in control of their work flow and the pace at which they respond to demands. “Stress is a chemistry problem. When people feel stressed, a tiny circuit in the base of their brain triggers the release of glucocorticoids, a family of stress hormones that puts the body in a heightened state of alert.” When they linger in the system, as it happens in chronic stress situations, bodily damage accumulates. Gradually this induces neuron breakdown and changes in the nature of the brain itself. Sapolsky has been experimenting with a modified herpes simplex virus to get at the glucocoricoids by generating neuroprotective proteins—with success in rodent experiments.
The problem is, of course, that there’s no talk of modifying society to relieve the feelings of powerlessness of those in its lower depths. There’s the rub. If more and more people feel like victims, nothing the medics do will help much. (09-01-10)

272. Thinks
David Lodge authored Thinks in 2001. An entertaining novel about academia, it is also Lodge’s foray into cognitive neuroscience. Part of the counterpoint is the different meanings and feelings we have about consciousness, depending on whether we operate in the embryonic neuroscience world or within the conventions of the novel. At question are what we mean by consciousness, when is consciousness at work or turned off, and how little we know in the end about what’s going on inside the heads of those with whom we are in close correspondence. What we do see is compelling outbursts of instinctive behavior that break through the norms of society but then watch as both conventional habits and mindsets determine that life goes on pretty much as it was yesterday. In other words, despite all the thinking and all the states of hyper-consciousness, the unconscious asserts itself pretty well. The novel’s heroine reflects at one point: “This idea of the self is under attack today, not only in scientific discussion of consciousness, but in the humanities too.” At the end of the day we suppose Lodge is asking whether neuroscience, but the whole of modern thinking as well, is practicing a kind of reductionism that is leading us nowhere. At that point we have betrayed the brain’s purpose which is to help us function in this cosmos. This is a world full of brave wave activity amidst, in the end, a rather static society. Consciousness has become detached from purpose and activity. (06-30-10)

“ ‘Mad Pride’ Fights a Stigma,” New York Times, May 11, 2008, pp.St1-2. “Mad pride events, organized by loosely connected groups in at least seven countries including Australia, South Africa and the United States, draw thousands of participants, said David W. Oaks, the director of MindFreedom International, a nonprofit group in Eugene, Ore., the tracks the events and says that it has 10,000 members.” “Members of the mad pride movement do not always agree on their aims and intentions. For some, the objective is to continue the destigmatization of mental illness.” Others are promoting psychotropic drugs, and some want to share their struggles and successes with other sufferers. Those afflicted with bipolar disorder and schizophrenia feel a need to speak out. Other groups that bind together the afflicted include the Icarus Project, Mad Tea Party in Chicago, and the Freedom Center in Northampton, Massachusetts. In the broadest terms, there is a broad interest amongst the emotionally and mentally afflicted in the United States in speaking out about their problems, in dispelling the taint attaching to mental illness in our society, and in finding other ways to handle their afflictions, since the professional psychiatry/psychology community cannot really deal with their troubles. (06-02-10)

“A team of scientists, based mainly at Stanford University, developed a test that was about 90 percent accurate in distinguishing the blood of people with Alzheimer’s from the blood of those without the disease.” New York Times, October 15, 2007, P. A10. This test looked at the presence or lack thereof of 18 communication proteins in the blood. Work continues, as investigators look at various blood proteins as precursors of Alzheimer’s. Researchers in Georgia, for instance, have found that as the concentration of two specific proteins that are involved in the immune response increases” …” the severity of dementia increases.” (05-19-10)

In rat experiments, Princeton researchers have shown that younger brain cells, created when the rodents were running, “generally remained quiet.” “The ‘cells born from running’..appeared to have been ‘specifically buffeted from exposure to a stressful experience.” “Stress Relief,” New York Times, November 22, 2009, p. 16. “ ‘It looks more and more like the positive stress of exercise prepares cells and structures and pathways within the brain so that they’re more equipped to handle stress in other forms,’ says Michael Hopkins, a graduate student affiliated with the Neurobiology of Learning and Memory Laboratory at Dartmouth…” In other words, it is thought that exercise is a sedative for our nerves, if the exercise is repeated over long enough periods. (05-05-10)

“In subtle patterns of brain cells, researchers are exploring empathy—an essential intuition that helps us understand our fellow human beings.” See “How Your Brain Allows You to Talk in Another’s Shoes,” Wall Street Journal, August 17, 2007, P. B1.
“ ‘ The mirror system gives us some kind of open-mindedness, a propensity to understand others and other cultures,’ said neuroscientist Marco Iacoboni at the University of California, Los Angeles, who is pioneering the study of these cells in the brain.” “Located in the brain’s motor cortex, which orchestrates movement and muscle control, the cells fire when we perform an action and also when we watch someone else do the same thing…” triggering in us a hint of what that other person is feeling. Dr. Iacoboni has authored a book on this very subject called Mirroring People: The New Science of How We Connect with People. “Among those diagnosed with autism, this mirror of neurons may be broken, independent research groups at the University of Montreal and the University of California, San Diego, recently reported.” (04-07-10)

“Exposure in the womb to high levels of testosterone…increases the risk of developing autistic traits during childhood….” Financial Times, September 12, 2007, p. 4. Simon Baron-Cohen, the UK’s leading autism expert, says the 8-year study proves a linkage, but does not demonstrate that testosterone exposure causes autism. “Profess Baron-Cohen said the results were consistent with his theory that autism is a manifestation of ‘extreme male’ behavior.” There is, we should add, considerable debate about his results and his ‘extreme male’ model. Separately Cohen and his Cambridge associates have looked at 27 genes they feel are pivotal in Asperger’s and autism related complaints. We would point readers to Autism Research for more citations from the prolific Baron-Cohen. (04-07-10)

“Now a new study that uses Framingham to analyse loneliness has found that it spreads like a communicable disease.” The Economist, December 12, 2009, pp.90-91. “They report in the Journal of Personality and Social Psychology that loneliness formed in clusters of people, and that once one person in a social network started expressing feelings of loneliness, others within the same network would start to feel the same way.” “The reasons for the spread, the team argues, is because loneliness causes people to act towards others in a less generous and more negative fashion.” Framingham is the locale of the famous heart study that got the Harvard health crowd over-focused on cholesterol as the prime mover in heart disease, a notion that has been discredited as we get a fuller picture of what makes the ticker fail. (02-24-10)

265. Wired on the Brain
The often suggestive but frequently jumbled Wired magazine(April 2009, pp.88ff.) reviews Paul Allen’s (he’s the money man and co-founder of Microsoft) ambitious effort to map the brain. With robots and other systems processes, scientists at the Allen Institute have speeded up the process. Even with improved tools, the brain is proving ever more complicated: as they peel back one layer, new complexities and new levels of detail emerge, not unlike, we suppose, moving from the molecular to the atomic world, or from cells to genes and then beyond. Moreover, as the mapping progresses, they learn that each brain is unique, and mapping one is no certain roadmap for another. So the faster they run, the more the goal recedes. See our initial announcement of the Atlas on Brain Stem. (09-09-09)

264. Plasticity
Every once in a while editors earn their money. Usually they are down in the weeds, miss the point, and feed their readers popcorn. But then there’s a breakthrough. “The Innovators Issue,” The New Yorker, May 11, 2009 was an absolute winner. It deserves to be framed, and the bestus of the best was “Brain Games: The Marco Polo of Neuroscience.” It treated Dr. Vilayanur S. Ramachandran, the behavioral neurologist who is the director of the Center for Brain and Cognition at the University of California San Diego. “Ramachandran and other researchers have shown that the brain is what scientists called “plastic”--it can reorganize itself. The interrelationship of different parts of the brain to each other and to parts of the body can be changed for therapeutic effect. “Until the mid-nineteen-nineties, Ramachandran’s speciality was visual perception, but…” “he made the switch to neurology in mid-career.” “In 1994, Ramachandran published a paper in Nature that is now considered a landmark in the field of neuroplasticicity. He described experiments in which “The high resolution MEG scans clearly showed that in the brains of arm amputees the area associated with the face had invaded the area associated with the missing arm—‘the first direct demonstration of massive reorganization of sensory maps in the adult human brain.’” Through optical tricks—mirrors, in fact—he has devised a means to relieve unpleasant symptoms that are tied up with unusual brain organizations. Ramachandran and his colleagues have also since speculated “that autism was caused by a deficit in the mirror-neuron system,’ a hypothesis that runs afoul of mainstream autism research which is heavily invested in cerebellum complications. (Elsewhere on the site we have discussed strongly held notions about Alzheimer’s and autism, most of which we think are rather flawed since they neither come to terms with our body chemistry nor the dynamic nature of our nervous communication system). As his theory about autism gets more play, there have been increasing efforts to bring plasticity into play in the potential treatments of neurological complaints. (08-26-09)

“Bilingual babies are precocious decision-makers.” Economist, April 18, 2009, p.87. Bilingual babies, it was found in Trieste where it is common to learn both Italian and Slovenian, have to develop a mental agility or heightened ‘executive function’ in the their brains in order to shift freely between languages. The study, by researchers Agnes Kovacs and Jacques Mehler at the International School of Advance Studies, looked at 40 ‘preverbal’ seven-month-olds. (08-12-09)

Update: DoubleSpeak Victorious
Ellen Bialystok has spent 40 years “learning … how bilingualism sharpens the mind.” (New York Times, May 31, 2011, p. D2). Apparently “the regular use of two languages appears to delay the onset of Alzheimer’s disease systems.” Bilingual children, she has also discovered, show a better ability “to attend to important information and ignore the less important.” Bilinguals can also handle multitasking better than monolinguals. (7/7/11)

262. Good Things Come to Those Who Wait
“Good Things Come to Those Who Wait,” and we’re not talking about Heinz ketchup. We’re not even sure that patience is a virtue, but Walter Mischel at Stamford believes that kids who have a propensity for delaying gratification tend to make out better in life. Once Mischel began analzying the results, he noticed that low delayers, the children who rang the bell quickly, seemed more likely to have behavioral problems, both in school and at home.” “Don’!” New Yorker, May 18, 2009, pp. 26-32. Ozlem Ayduk at Berkeley “found that low-delaying adults have a significantly higher body-mass index and are more likely to have had problems with drugs...” Those with high delay abilities have learned to trick themselves out of speedily pursuing a desired object, using all sort of tactics to forget, for instance, a marshmellow or something else they lust after. “In adults, this skill (avoiding thinking about a desire) is often referred to as metacognition, or thinking about thinking, and it’s what allows people to outsmart their shortcomings.” Mischel hopes to look at a number of mental perturbations—such as OCD and attention deficit disorder—to see if they can be helped through attention control. (06-24-09)

Back on January 18, 2001, the Harvard Gazette reported that “Alzheimer’s Vaccine Looks Promising: Brain Deterioration Slowed by Nose Drops.” At that time Harvard had tried the drops on mice, and sundry vaccine trials of a minor sort had been used at many other locations. As it happens, the vaccine did not progress very fast, as indicated in a Gazette article of October 20, 2005. “A vaccine has been developed against the proteins that cause the amyloid plaques, Selkoe said. Though it failed in trials, partial results obtained indicated that after just two injections patients' brains were partly cleared of the plaques.” Much of the delay has been blamed on lack of Government funding, and drug company aversion to the sundry risks involved in vaccine development. The researchers do not mention that their fundamental assumptions may be wrong. (05-20-09)

260. All About Obsession
Obsession: A History goes back a few centuries to trace the movement of ‘obsession’ away from a malady just perceived as an oddity to a two-side phenomena where it is simultaneously thought of as an illness and as the goad the produces many discoveries, scientific and otherwise. Economist, November 1, 2008, p. 96. In a couple of decades, obsessive-compulsive behavior has gone from a rare ailment—one in 2000 in 1973 to 2 or 3 people in 100. As we have said elsewhere, our understanding of the obsessive compulsive mechanism is not very advanced, nor have we done as much work as we could on harnessing the creativity and focus of obsessives for the benefit of society. (04-01-09)

259. Rewiring Autistic Children
Amy O’Dell, who has an autistic child, has a school where a pot pourri of techniques are used to get autistic kids to forge new connections in their heads. Forbes, May 5, 2008, pp.54-58. “This is Jacob’s Ladder, the school O’Dell founded in 1999 to treat children with neurological disorders.” Most have severe autism. Her work stems from the theory that the brain is plastic and can be reworked to form new connections. There are no clinical studies substantiating this, but others have had successes with Alzheimer’s patients and autistics using computer games and other such stimulants. (03-04-09)

258. Bad Memory: Sweet Amnesia
Those who are readers of Proust will remember that he had an awfully keen memory. Those who have lovingly followed his voluminous writing on recapturing the past marvel at the completeness with which he recalled the madeleine of youth such that it kindled all his senses. Ironically, now, we are learning that sugar then and sugar now actually clogs our memories and makes it harder and harder to recall anything. The negative power of glucose, particularly as we age, is tackled in “Blood Sugar Control Linked to Memory Decline,” New York Times, December 31, 2008. “The study, by researchers at Columbia University Medical Center and funded in part by the National Institute on Aging, was published in the December issue of Annals of Neurology.” “The ability to regulate glucose starts deteriorating by the third or fourth decade of life….Since glucose regulation is improved with physical activity, Dr. Small said, ‘We have a behavioral recommendation—physical exercise.’” “They found a correlation between elevated blood glucose levels and reduced cerebral blood volume, or blood flow, in the dentate gyrus, an indication of reduced metabolic activity and function in that region of the brain.” (02-04-09)

257.The Infinite Mind
The Infinite Mind is an absolutely foolish name for a radio series, just the sort of thing euphemistic types in public broadcasting like to drum up. Big oceanic names to label small puddles. But it works, and we occasionally take a look at its offerings. “The Infinite Mind program peeping-toms into the inner workings of the human mind through interviews with various medical professionals, artists, and those coping with mental illness. Guests of the program have included everyone from comedienne Margaret Cho to left-handed boxers, or ‘southpaws,’ as they are known in the business. Recent programs have included shows on the nature of altruism, shoplifting, Tourette's syndrome, and internal body clocks,” according to the Scout Report. (9/10/08)

256. Finding Your Bliss
It’s an inspiration and one-half to read about Jill Bolte Taylor, formerly a neuroscientist at Harvard and now creatively semi-retired in Bloomington, Indiana, not far from the university. On December 10, 1996, at age 37, she had a stroke which more or less shut down her left temporal lobe—and all sorts of functionality—but nonetheless left her feeling great, as if she had discovered Nirvana (See the New York Times, May 25, 2008, pp. ST1& 7. Lost, for the moment, was her ability to speak, the capacity to decipher letters and numbers, even the connections to recognize her mother who, incidentally, nursed her back to health. All this she has recounted in her memoir, My Stroke of Insight. Surgery and eight years of recovery were required for her to bring back her whole brain. “Her message, that people can choose to live a more peaceful, spiritual life by sidestepping their left brain, has resonated widely.” She has talked about her experience at the TED Conference and her thoughts can also be found on Oprah Winfrey’s website. The kids in the 1960s were only prophetic when they talked about following their bliss. (7/16/08)

255. American Psychiatry Up To 1900
The National Institutes of Health provides an online history of medicine, “Diseases of the Mind” forming one part. It is more of a chronicle, than a history, sketchy at best. After we admit that this is lightweight, we can still salute a couple of facets. It provides a short list of seminal 19th-century figures in psychiatry—as well as some flavor of the debates that stalked this field in that period. To be more complete, we would have to see something on America’s unique contribution to the discipline. (7/2/08)

254. Brain Pattern Behind OCD
“Cambridge researchers have discovered that individuals with obsessive compulsive disorder (OCD) and their close family members have distinctive patterns in their brain structure. This is the first time that scientists have associated an anatomical trait with familial risk for the disorder.” “Lara Menzies, in the Brain Mapping Unit at the University of Cambridge, explains, ‘Impaired brain function in the areas of the brain associated with stopping motor responses may contribute to the compulsive and repetitive behaviours that are characteristic of OCD. These brain changes appear to run in families and may represent a genetic risk factor for developing the condition. The current diagnosis of OCD available to psychiatrists is subjective and therefore knowledge of the underlying causes may lead to better diagnosis and ultimately improved clinical treatments.’” (University of Cambridge Press Release, 16 November 2007). Also see “Neurocognitive endophenotypes of obsessive-compulsive disorder,” Brain, December 2007. (6/18/08)

253. Molecule to Inhibit Alzheimer’s
Arun Ghosh, a Purdue professor, designed the molecule that could allow for intervention in Alzheimer’s early stages. “The molecule, called a beta-secretase inhibitor, prevents the first step in a chain of events that leads to amyloid plaque formation in the brain. This plaque formation creates fibrous clumps of toxic proteins that are believed to cause the devastating symptoms of Alzheimer’s.” Stage one work showed a single dose of the drug produced a greater than 60 percent reduction of plasma amyloid beta. “CoMentis plans to begin a phase II clinical study of the drug, oral CTS-21166, in Alzheimer's patients in 2008.” (Purdue News Release, January 17, 2008.) We caution readers that plaque seems to be more of a symptom than a part of the disease mechanism, so it remains to be seen if its reduction positively affects the disease itself. We suggest a look at Ghosh publications. (5/14/08)

252. Brain Oxygen Monitor
“A new noninvasive diagnostic technology could give doctors the single most important sign of brain health: oxygen saturation. Made by an Israeli company called OrNim and slated for trials on patients in U.S. hospitals later this year, the technology, called targeted oximetry, could do what standard pulse oximeters can’t.” “OrNim’s new device uses a technique called ultrasonic light tagging to isolate and monitor an area of tissue the size of a sugar cube located between 1 and 2.5 centimeters under the skin. The probe, which rests on the scalp, contains three laser light sources of different wavelengths, a light detector, and an ultrasonic emitter.” See the MIT Technology Review, January 29, 2008. (5/14/08)

251. Rip Van Winkles
We’re inclined to think many brain-afflicted patients are beyond the pale, without consciousness, not sentient, since they are without utterance, and seemingly immune to stimulus. Brain scans are revealing, however, that so-called vegetative people are often more brain-active than we believe, as reported by Jerome Groopman in “Silent Minds,” New Yorker, October 15, 2007, pp.38-43. A British neuroscientist, Adrian Owen, at the University of Cambridge has scanned several dozen people since 1997, sometimes detecting signs of recognition to auditory stimuli. The prognosis, however, with patients suffering from oxygen deprivation is much worse than that of those afflicted by head injuries. (4/30/08)

250. The Age of Indecision
An awesome amount of research painfully proves the obvious. The elderly, says a recent body of work, have a hard time making decisions and are prone to poor judgments. Natalie Denberg at the University of Iowa led the research team. For more on this, read “Brain Deficits In Older Adults Affect Decisions, Increase Vulnerability” from TS-Si News Service, 15 January 2008. Also see, “The orbitofrontal cortex, real-world decision making, and normal aging.” Denburg NL, Cole CA, Hernandez M, Yamada TH, Tranel D, Bechara A, Wallace RB. Ann. N.Y. Acad. Sci. 1121: 480–498 (2007). doi: 10.1196/annals.1401.031. The interesting question, of course, is what keeps seniors in good running condition, and what kinds of things inhibit such deterioration. Clearly the brain has to be used to keep in tune. (4/16/08)

249. Shrink Show
TV shows about the brain and psychiatry continue to edge into TV niche markets. The latest is “In Treatment,” which is to be shown 9:30-10:00 PM on HBO, five nights a week. “The drama, about a highly principled successful psychotherapist … and five of his patients—not to mention the therapist’s own therapist” is to run for nine weeks. See “Secrets and Lies,” Wall Street Journal, January 25, 2008, p. W6. The Journal reviewer is fascinated by the series, but the San Francisco Chronicle considers it a snooze, probably telling us a great deal about both newspapers, both cities, and both reviewers. (4/2/08)

248. Garlic and Brain Cancer?
“Numerous studies provide evidence that garlic and its organo-sulfur compounds are effective inhibitors of the cancer process, most notably for prostate and stomach cancers. For the first time, those compounds have been identified as effective against glioblastoma, a type of brain tumor equivalent to a death sentence within a short period after diagnosis.” “Cancer cells are known to have an incredibly high metabolism, as they require much energy to divide cells for rapid growth. In this study, it has been shown that garlic compounds produce reactive oxygen species in rapidly growing brain cancer cells, essentially gorging them to death with activation of multiple death cascades.” “As for those who seek to take advantage of any potential anti-cancer benefits from garlic now, certain rules apply. Ray said people should cut and peel a piece of fresh garlic and let it sit for fifteen minutes before eating or cooking it. This amount of time is needed to release an enzyme (allinase) that produces these anti-cancer compounds. Both Ray and Banik caution the public in eating too much garlic, noting that too much of it can cause diarrhea, allergies, internal bleeding, and bad breath and body odor, among other problems, so it is important to monitor garlic consumption.” As usual, we are a long ways away from an effective botanical, and the claims for garlic always get a little overblown. See Press Release, Medical University of South Carolina, 27 August 2007. (3/12/08)

247. HerdSell
“Now researchers are investigating how ‘swarm intelligence’ (that is, how ants, bees, or any social animal, including humans, behave in a crowd) can be used to influence what people buy” (The Economist, November 12, 2006, p. 90). Please understand that The Economist folks got it exactly backwards here. With ‘swarm intelligence” the crowd is immensely smarter than any of the individuals who, on their own, may be dumb or worse. What the writer means to speak about here is “lemming behavior” where all the creatures in a crowd march over a cliff, nudged on by the leaders of the pack. Zeeshan-ul-hassan Usmani, a computer scientist at Princeton, and Ronaldo Menezes of the Florida Institute of Technology have tried to capitalize on the tendency of consumers to buy what is perceived as popular. What they do, with scanners, is show each individual consumer how many of his co-shoppers in the store at the moment have bought the product he is looking at. Fact is, this idea is still in test, although both Wal-Mart and Tesco were slated to give it a whirl. Matthew Salganik, formerly of Columbia University and now at Princeton, has shown that consumers may be inclined to buy or download songs that have been shown to be quite popular. RanKing RanQueen, a convenience chain in Japan, only sells very popular goods, and the rankings are updated weekly. “Icosystems … in Cambridge, Massachusetts” aims to use social networking to bolster sales. In general, the key is to get the ranking or popularity of a good communicated to enough people. Menezes has published widely on ‘swarm intelligence.’ See the PBS program on RanKing RanQueen. (3/12/08)

We have hinted at the importance of swarm intelligence in human beings, animals, and social insects in many places on the Global Province. We suspect that we should pay closer attention to bee smarts and also the impressive powers of honey, the output of bees at work. The latest interest is in “Bees as Biodetectives,” June 29, 2010,

“Volker Liebig, a chemist for Orga Lab, who analyzes honey samples twice a year for the Dusseldorf and six other German airports, said results showed the absence of substances that the lab tested for, like certain hydrocarbons and heavy metals, and the honey ‘was comparable to honey produced in areas without any industrial activity.’”

Using bees to test for pollution is still in its infancy, but it is not implausible. Other insects have been used to gauge water quality. (3-29-11)

246. Brain Institute a Good Idea? Maybe
“David Fitzpatrick, a professor of neurobiology at Duke University, has been named the first director of the new interdisciplinary Institute for Brain, Mind, Genes, and Behavior.” “Duke’s research into brain function is now spread across a number of units on campus, including the Department of Psychology and Neuroscience, the Department of Neurobiology, the Department of Psychiatry and Behavioral Sciences, the Center For Cognitive Neuroscience, the Department of Pharmacology, the Biomedical Engineering Department, the Center For Brain Imaging And Analysis, the Conte Center For The Neuroscience Of Depression, the Preston Robert Tisch Brain Tumor Center, the Center For Neuroeconomic Studies and parts of the Institute For Genome Sciences And Policy.” The idea, of course, is to leverage Duke’s ‘brain’ commitment through coordination. We would have to question, of course, whether he will have the power and the will to hammer heads together to achieve some common goals. The American intelligence community, for instance, has nominally had some direction and coordination since the creation of the CIA; but the intelligence units in Government, particularly in the Defense Department, have very much gone their own way. More importantly, we would suggest, the disciplines being coordinated don’t have a wide enough compass. Chemistry, for instance, has a great deal to do with real progress in neuroscience, yet only a handful of brain scientists can find their way around a molecule. (2/27/08)

245. How Brains Create New Cells
“Researchers at Sahlgrenska University Hospital in Göteborg have discovered how stem cells produced in a ‘nursery’ deep inside the brain then migrate into other parts of the brain, maturing into nerve cells on the way.” “Working with colleagues from New Zealand, the Swedish researchers traced the pathway from the subventricular zone deep within the brain (where neural stem cells are created) to the olfactory bulb in the limbic system, where the stem cells change into nerve cells.” See “Human Neuroblasts Migrate to the Olfactory Bulb via a Lateral Ventricular Extension,” Science, March 2, 2007, Vol. 315. no. 5816, pp. 1243-49. (2/13/08)

244. Fast Uppers
“A McGill University study has found that a new class of drugs known as serotonin4 (5-HT4) receptor agonists may take effect four to seven times faster than traditional selective serotonin reuptake inhibitors (SSRIs). The study, led by former McGill post-doctoral fellow in psychiatry Guillaume Lucas with his supervisor, the late Dr. Guy Debonnel, was published in the September 6 issue of the journal Neuron” (McGill University News Release, September 5, 2007). See “Serotonin4 (5-HT4) Receptor Agonists Are Putative Antidepressants with a Rapid Onset of Action,” Neuron, September 6, 2007. “These findings point out 5-HT4 receptor agonists as a putative class of antidepressants with a rapid onset of action.” (1/30/08)

243. Loneliness Molecule
“Now, in the first study of its kind, published in the current issue of the journal Genome Biology, UCLA researchers have identified a distinct pattern of gene expression in immune cells from people who experience chronically high levels of loneliness. The findings suggest that feelings of social isolation are linked to alterations in the activity of genes that drive inflammation, the first response of the immune system. The study provides a molecular framework for understanding why social factors are linked to an increased risk of heart disease, viral infections and cancer.

Having previously established that lonely people suffer from higher mortality than people who are not lonely, researchers are now trying to determine whether that risk is a result of reduced social resources, such as physical or economic assistance, or is due to the biological impact of social isolation on the functioning of the human body” (UCLA News Release, September 13, 2007). See “Social Regulation of Gene Expression in Human Leukocytes,” Genome Biology, Vol 8, Issue 9, R189. “Impaired transcription of glucocorticoid response genes and increased activity of pro-inflammatory transcription control pathways provide a functional genomic explanation for elevated risk of inflammatory disease in individuals who experience chronically high levels of subjective social isolation.” (1/23/08)

242. Alzheimer's Drug Effectiveness
Jeffrey L. Cummings is usefully focused, in our opinion, on the effectiveness of the panoply of drugs coming to market for treatment of Alzheimer’s. To wit, he indicates this is quite a challenge, since some of the drugs being offered are only affecting symptoms of the disease, and not modifying the structure and mechanism of the disease. He has authored “Challenges to Demonstrating Disease-Modifying Effects in Alzheimer’s Disease Clinical Trials.” It is also useful to look at this editorial “Searching for Methods to Prevent, Detect, and Treat Alzheimer’s Disease,” American Journal of Psychiatry, April 2005, 645-647. Cummings head up UCLA’s Alzheimer’s Disease Research Center, one of the larger programs in the country. (1/2/08)

241. Shoring up the Brain
Many efforts are afoot to make the brain more resilient. “Duke University chemists are developing ways to bind up iron in the brain to combat the neurological devastation of Parkinson’s and Alzheimer’s diseases. The key is to weed out potentially destructive forms of iron that generate harmful free radicals while leaving benign forms of iron alone to carry out vital functions in the body.” “The pro-chelators that Franz described contain phenols that wear chemical ‘masks’ around themselves to keep them from binding with benign forms of iron or other metals, such as those found in some essential enzymes. But the presence of excessive amounts of hydrogen peroxide will trigger an unmasking, allowing the phenols to sop up and inactivate the bad iron.” See “A Pro-Chelator Triggered by Hydrogen Peroxide Inhibits Iron-Promoted Hydroxyl Radical Formation,” Journal of the American Chemical Society, September 2006.

As well, researchers think they may have developed a vaccine that can ward off brain tumors. “Duke researchers are using a vaccine to hopefully prevent recurrence of the most common and deadly type of brain tumors. As opposed to most other cancer treatments, the vaccine does not have negative side effects. So far, the trial has shown promising results.” Duke and M.D. Anderson researchers have held promising trials, though it’s not certain whether chemo or the vaccine offer the best course of treatment. (12/5/07)

240. Dopamine and ADHD
“A team led by Dr. Nora Vokow, director of the NIH’s National Institute of Drug Abuse, documented decreased dopamine activity in the brains of a group of adults with ADHD.” See the Wall Street Journal, August 7, 2007, p. D3. “A second team..led by Dr. Philip Shaw of the NIH’s National Institute of Mental Health NIH’s National Insitute of Mental Health … used … MRI..exams to look at the brain structure of children with and without ADHD.” See “Depressed Dopamine Activity in Caudate and Preliminary Evidence of Limbic Involvement in Adults With Attention-Deficit/Hyperactivity Disorder.” In general, there is a need to study much more carefully the chemistry behind various brain disorders. (11/14/07)

239. Gatekeeper of the Mind
“Amy Arnsten, a medical school neurobiologist, has for the first time isolated its molecular lock-and-key mechanism, gaining insight into one possible cause of the cognitive deterioration associated with mental illness and old age.” Exploring how guanfacine works which is used to treat ADHD, she found that it “inhibited a brain messenger called cyclic AMP. Cells in the prefrontal cortex “contain gatekeepers called HCN channels… Cyclic AMP locks and unlocks these channels.” When open, electric signals cannot be transmitted. See Yale Alumni Magazine, July/August 2007, p. 25. See “Study Offers Glimpse of Molecules that Keep Memories Alive,” NIMH, July 2, 2007. (10/17/07)

238. RNA Interference
“Tests of (a new) therapy at Harvard Medical School in Boston found that a simple injection was able to cure mice of a potentially fatal brain disease.” The hope is to do human trials in 5 years, with the view of attacking a wide range of brain diseases. “The team used a powerful new technique called RNA interference to silence faulty genes or viruses that cause brain diseases. The principle of gene silencing is simple: scientists build tiny strands of the genetic material called RNA which, when injected into cells, latch on to problematic genes and smother them, effectively shutting them down.” See Harvard Medical Focus, March 10, 2006, “RNA Sequence Restrains Fatal Encephalitis,” for more on this work and on RNA interference.

“Therapies based on RNA interference have become the next great hope for medicine, and a large number are either in or about to start early clinical trials in humans. The technique earned its discoverers, the US researchers Andrew Fire and Craig Mello, the Nobel prize in medicine or physiology last year.” See the Guardian, June 18, 2007, p. 9. (10/10/07)

238. Dreams Are Back
Dreams are back. Not the bountiful, exhilarating variety, but rather the troublesome kind. Often they recapture people who have passed away. “Big dreams are once again on the minds of psychologists as part of a larger trend toward studying dreams as meaningful representations of our concerns and emotions. ‘Big dreams are transformative,’ Roger Knudson, director of the Ph.D. program in clinical psychology at Miami University of Ohio, said in a telephone interview. The dreaming imagination does not just harvest images from remembered experience, he said. It has a ‘poetic creativity’ that connects the dots and ‘deforms the given,’ turning scattered memories and emotions into vivid, experiential vignettes that can help us to reflect on our lives” (New York Times, July 3, 2007).

“Deirdre Barrett, assistant professor of psychology at the Harvard Medical School and editor in chief of the journal Dreaming, wrote the first significant study on dreams about the dead. She collected dream reports from two sample groups totaling 245 people at the University of North Carolina, Chapel Hill, and found 77 such dreams. Her findings were published in the 1992 issue of Omega: The Journal of Death and Dying. (10/3/07)

237. Coping with Brain Injury
Coma, a Liz Garbus documentary about brain injury from HBO, was aired on July 3, 2007. “Ms. Garbus follows four patients at the Center for Head Injuries at the John F. Kennedy Medical Center in Edison, N.J., in the aftermath of devastating accidents…” (New York Times, July 3, 2007, p. B10). The documentary follows the partial recoveries of 4 patients from brain injury and the toll this process takes on the patients’ families. “We learn the drastic differences between a conscious state, a minimally conscious state and a persistent vegetative state,” says Kevin McDonough of United Features. (9/19/07)

236. The Ice Man Cometh
“Writing in the May Issue of Evolutionary Psychology, they reported that volunteers yawned more often in situations in which their brains were likely to be warmer” (New York Times, July 3, 2007, p. D6). Of course, we suspect anybody who has done basic training in the Army could have saved Andrew Gallup, a psychology prof at SUNY, Albany all the work and conjecture. The Army runs you in the cold, then takes you into a small classroom that’s plenty warm: you yawn bigtime. “The two conditions thought to promote brain cooling (nasal breathing and forehead cooling) practically eliminated contagious yawning.” In particular, when participants were prompted to put an icepack on the forehead or to breathe through the nose, continuous yawning halted. Mouth breathing or warm packs had the opposite effect. Incidentally, studied efforts at brain cooling—such as breathing—seem also to provide relief to sufferers from a variety of neurological ticks such as OCD and ADD, etc. See “Yawning as a Brain Cooling Mechanism.” (9/12/07)

235. Peptides and Alzheimer’s
Researchers have found that a specific imbalance between two peptides may be the cause of the fatal neurological disease that affects more than five million people in the United States. “We have found that two peptides, Aβ42 and Aβ40, must be in balance for normal function,” said Chunyu Wang, lead researcher and assistant professor of biology at Rensselaer. If correct, the addition of Aβ40 may stop the disease’s development. These two peptides have been previously found in deposits, called senile plaques or amyloid plaques, in brains afflicted with Alzheimer’s disease. These plaques, mainly composed of Aβ42 fibrils, are a hallmark of Alzheimer’s disease. Using NMR data, Wang found that as Aβ40 levels increased, the aggregation of Aβ42 fibrils sharply decreased, protecting benign Aβ42 monomers. Wang’s experiments show that when there is 15 times more Aβ40 than Aβ42, the formation of Aβ42 fibrils is almost completely stopped. See the RPI News Release, May 29, 2007. (9/5/07)

234. Alzheimer’s Markers
“Over the past two years, rival scientists in the U.S. and Europe have identified a series of proteins, known as biomarkers, whose presence in blood or spinal fluid may indicate whether a patient has Alzheimer’s, the most common form of dementia” (Wall Street Journal, December 12, 2006, pp. D1, D4, and D5). As readers Brain Stem may have surmised, the editors of this section are hardly enthusiastic about pursuing a genetic and/or MRI track in researching neurological complaints. However, we do believe this is the correct path for detection and pre-detection of the several complaints of the brain. Plenty of research papers have identified a host of biomarkers for this disease. “In February, Swedish scientists published a five-year study in the journal Lancet Neurology, describing how the relative progression to Alzheimer’s disease … was significantly increased if their spinal fluid contained abnormal amounts of the same three biomarker proteins, known as b-amyloid, total tau and phosphorylated-tau.” Researchers at King’s College in London have discovered 15 biomarkers associated with Alzheimer’s. Proteome Sciences and Nanosphere are both working the marker problem. A Cornell study has identified some 23 markers for the disease.

Biomarkers are becoming all the rage, and new tests are springing up rapidly that identify sundry diseases, particularly several forms of cancer. But genetics is less successful at offering cures, once disease is discovered. (7/11/07)

233. Colleges—High Anxiety
The American College Health Association does surveys of student health with some regularity, which it makes available in its National College Health Assessments. We would caution readers to take these results with a grain of salt, but nonetheless the trend is unmistakable. Both stress and depression have risen considerably over the last decade, both because of what student populations bring to college and because of the atmospherics at colleges. When we visit college health departments, we find that many have staffed up considerably to handle mental and emotional problems, though we find these mental health activities are not well administered and college administrations are rather divorced from what goes in their health departments. In the 2006 survey the Assessment covered approximately 95000 students at 117 schools. Students reported the following feelings at least once during the year: feeling overwhelmed by what they had to do, 93.4%; feeling so depressed it was difficult to function, 43.8%; contemplating suicide, 9.3%; feeling exhausted, 91.5%. (7/4/07)

232. Stairmaster Memory
Researchers may have established a direct connection between exercise and memory maintenance as we grow older. “The researchers, led by Dr. Scott A. Small, an associate professor of neurology at the Columbia University Medical Center, looked at changes in the brains of volunteers who worked out on exercise equipment. The researchers were trying to confirm the findings of earlier research they did involving mice. When the mice exercised, blood flow increased to a part of the brain called the hippocampus, and more specifically to the dentate gyrate. In post-mortems, the researchers found evidence of neuron growth in the dentate gyrate.” “But using 11 volunteers, an M.R.I. machine and equipment like treadmills, the researchers were able to see whether blood flow increased to the same part of the brain in humans as it had in mice. It did, suggesting that working out may help produce neurons in a part of the hippocampus that loses them disproportionately as people age” (New York Times, March 20, 2007, p. D6).

Also see “New Reason to Hit the Gym: Fighting Memory Loss,” press release of Columbia University Medical Center, March 12, 2007. “Exercise, the researchers found, targets a region of the brain within the hippocampus, known as the dentate gyrus, which underlies normal age-related memory decline that begins around age 30 for most adults.” “Our next step is to identify the exercise regimen that is most beneficial to improve cognition and reduce normal memory loss, so that physicians may be able to prescribe specific types of exercise to improve memory,” said Dr. Small, who is also a research scholar at the Columbia University Taub Institute for Research on Alzheimer’s Disease and the Aging Brain. (6/6/07)

231. NeuroLaw
Emerging theory about brain process and neurological development is creating clouds and ambiguity for judges and eroding the givens of legal process. Elizabeth Loftus, professor of psychology and criminology at UC Irvine and Richard Steinberg, a Detroit lawyer, challenge Judge Reggie Walton’s exclusion of expert testimony in the Scooter Libby case in “If Memory Serves,” Wall Street Journal, March 9, 2007, p. A14. Libby claimed, in defense, that bad memory, not willful intent, caused him to make mistakes in his Grand Jury testimony. The judge held, in the end, that memory ‘science’ is not really a science, using this reasoning to bar testimony from Robert Bjork, also of UCLA.

Nonetheless, Jeffrey Rosen—in “The Brain on the Stand,” New York Times Magazine, March 11, 2007, pp. 48 and following—makes clear that the use of expert witnesses and brain imaging studies is on the rise throughout courtrooms, with one Florida court even saying that the failure to admit neuroimaging evidence during capital sentencing may create grounds for reversal. This wordy article does not merit a full reading, but it does let us know a new trend is in the making. (5/30/07)

230. Good Bacteria
The presence of certain kinds of bacteria may, in fact, lower depression. Mary O'Brien, an oncologist at the Royal Marsden Hospital in London, tried out “an experimental treatment for lung cancer that involved inoculating patients with MYCOBACTERIUM VACCAE. This is a harmless relative of the bugs that cause tuberculosis and leprosy that had, in this case, been rendered even more harmless by killing it. When Dr O'Brien gave the inoculation, she observed not only fewer symptoms of the cancer, but also an improvement in her patients’ emotional health, vitality and general cognitive function” (Economist, April 4, 2007). Chris Lowry of Bristol University has further investigated this phenomenon. Experimenting with mice, he found that cytokine levels rose, which in turn could act on sensory cells which in turn release serotonin. This offers the intriguing possibility of treating depression with bacteria and, further, it may explain the rise of certain diseases which may flourish in the absence on myco-vaccae. See Journal of Neuroscience. (5/23/07)

229. Second Generation Atypicals (SGA)
A host of commentary on both sides of the Atlantic has boiled up about second generation anti-psychotics. Many researchers have been working this problem, wondering about their effectiveness, costs, and risks. There’s at least a consensus now that second generation are no more effective, and maybe less effective, than first (FGA). Some believe second-generation drugs demonstrate more dangerous side effects. Some of the NIH studies emphasize that the newer drugs inflict huge costs without any commensurate upside. One popular treatment of this subject “In Antipsychotics, Newer Isn't Better: Drug Find Shocks Researchers,” Washington Post, October 3, 2006, p. A1 summarizes a British study led by Peter Jones of Cambridge University concluding that “schizophrenia patients do as well, or perhaps even better, on older psychiatric drugs compared with newer and far costlier medications.” Jeffrey Liebermann of Columbia and others have been directing subsequent very broad NIH studies that apparently reach much the same conclusion. Separately, of course, it has been noted that no really good drug for schizophrenia has come on the market, and that a whole raft of supportive treatment mechanisms are still state of the art for its treatment. (5/16/07)

228. Schizophrenia Algorithms
Vanderbilt University has furthered advanced algorithms used in schizophrenia treatment Earlier work headed by Dr. Kenneth Jobson had already paved the way with some successes on medication regulation. In 2000 Dr. Herbert Meltzer of Vanderbilt joined the effort. A new Web-based tool is now available to help clinicians determine the best medication for patients with schizophrenia. An international team led by Meltzer completed the new algorithms, or step-by-step protocols, in late 2004 to provide clinicians with help on their treatment decisions. Meltzer speculated that following the algorithms could save up to 40% of drug costs and give practical guidance to those who don’t fully know the literature or who cannot spend much time with patients. Further it was thought that controlling polypharmacy would improve patient outcomes. The literature, however, continues to reveal problematic results with schizophrenia drug treatments. See our entry on “Second Generation Atypicals (SGA).” (5/9/07)

227. Learning While You Sleep
Max Planck researchers in Heidelberg are investigating communication between memory areas during sleep. Their study offers the hitherto strongest proof that new information is transferred between the hippocampus, the short term memory area, and the cerebral cortex during sleep. It has been difficult up to now to use experiments to examine the brain processes that create memory. The scientists in Heidelberg developed an innovative experimental approach especially for this purpose. They succeeded in measuring the membrane potential of individual interneurones (neurones that suppress the activity of the hippocampus) in anaethetised mice. At the same time, they recorded the field potential of thousands of nerve cells in the cerebral cortex. This allowed them to link the behaviour of the individual nerve cells with that of the cerebral cortex. The researchers discovered that the interneurones they examined are active at almost the same time as the field potential of the cerebral cortex. There was just a slight delay, like an echo. Thomas Hahn, Bert Sakmann & Mayank R. Mehta, “‘Phase-locking of hippocampal interneurons’ membrane potential to neocortical up-down states,” Nature Neuroscience. (5/2/07)

226. Cornelia deLange Syndrome (CdLS) and Retardation
Ian D. Krantz at Children’s Hospital in Philadelpha has long been at work uncovering the genetic apparatus behind Cornelia deLange syndrome, a multisystem geneticdisease that affects an estimated one in 10,000 children. In 2004 a team led by him learned that the NIPBL gene caused mutations in roughly half of known CdLS cases. In the present study, Dr. Krantz and Dr. Laird Jackson of Drexel University found that mutations in two other genes, SMC3 and SMC1A, cause about 5 percent of CdLS cases. But the two new genes, as well, look more generally to be a pathway to mental retardation. “In these cohesin complex proteins, the strongest effect seems to be in brain development,” said Dr. Krantz.

Drs. Krantz and Jackson together maintain the world’s largest database of patients with CdLS. The current study screened 115 patients who did not have mutations in the NIPBL gene, but who were judged to have CdLS or a milder variant of the disease, based on evaluations by clinical geneticists. “Gene Found for Rare Disorder May Reveal New Pathway in Mental Retardation,” Press Release, Children’s Hospital of Philadelphia, February 5, 2007. For abstract, see the American Journal of Human Genetics. (4/25/07)

225. Chewing Gum and Walking
Lyndon Johnson said that Gerry Ford couldn’t chew gum and walk at the same time. But it turns out that multi-tasking is pretty darn hard for everybody. Paul E. Dux and René Marois at Vanderbilt have found that when it comes to handling two things at once, your brain, while fast, isn’t that fast. See “Neural bottleneck found that thwarts multi-tasking,” Vanderbilt University Press Release, January 18, 2007. Their research revealed that the central bottleneck was caused by the inability of the lateral frontal and prefrontal cortex, and also the superior frontal cortex, to process the two tasks at once. Both areas have been shown in previous experiments to play a critical role in cognitive control. “Neural activity seemed to be delayed for the second task when the two tasks were presented nearly simultaneously – within 300 milliseconds of each other,” Marois said. See Neuron, vol. 52, pp. 1109-1120, 21 December 2006. (4/18/07)

224. Addiction Central
“Damage to a silver-dollar sized spot deep in the brain seems to wipe out the urge to smoke.” Known as the insula, scientists theorize that is the brain center for addiction. “The insula seems to be where the brain turns physical reactions in to feelings,” so it appears to act as a headquarters for cravings. Research on the insula, funded by the NDA, was led by Dr. Antoine Bechara at the University of Southern California. See WSJ, January 26, 2007, p. B5. Also see “Damage to Specific Part of the Brain May Make Smokers ‘Forget’ to Smoke,” NIH News Release, January 25, 2007. (3/28/07)

223. The Phobias of Allan Shawn
“As he notes in his remarkable new memoir, Wish I Could Be There, the composer Allen Shawn suffers from a veritable rainbow of phobias: ‘In probing the consequences and possible causes of his phobias, Mr. Shawn has written a brave, eccentric and utterly compelling book that’s as revelatory and candid as anything ever written by Joan Didion, and as humane and scientifically fascinating as any one of Oliver Sacks’s case studies.” See “Recalling a Literary Family, and Phobias,” New York Times, January 30, 2007. Son of William Shawn, longtime editor of the New Yorker, and brother of Wallace Shawn, the actor, Shawn attributes some of his tortures to separation from his autistic sister Mary at an early age. “These fears amplified his own ‘terror of mental illness’—the fear that, being Mary’s twin, he too was somehow damaged or different.”

“In addition, the Shawn household, with its emphasis on discretion and denial, seems to have been an “incubating environment” for future phobias, a petri dish of unspoken emotions. The author’s father carried on a four-decade extramarital affair, and his reticence about his complicated double life (“it wasn’t uncommon for him to eat, or at least, attend four or even five meals a day to accommodate all the important people in his life”) created an atmosphere in which secrecy and repression flourished.” (3/21/07)

222. Brain on Brain
Sharon Begley, science columnist at the Wall Street Journal, has a book out Train Your Mind, Change Your Brain. In a January 19 column in the WSJ, she does a column of snippets from the new book. We know, she says, that the body’s chemistry and physics acts on the brain. The Dalai Lama wondered if the reverse were true. “Could it work the other way around? That is, in addition to the brain giving rise to thoughts and hopes and beliefs and emotions that add up to this thing we call the mind, maybe the mind also acts back on the brain to cause physical changes in the very matter that created it. If so, then pure thought would change the brain's activity, its circuits or even its structure.” “But the brain changes that were discovered in the first rounds of the neuroplasticity revolution reflected input from the outside world. For instance, certain synthesized speech can alter the auditory cortex of dyslexic kids in a way that lets their brains hear previously garbled syllables; intensely practiced movements can alter the motor cortex of stroke patients and allow them to move once paralyzed arms or legs. The kind of change the Dalai Lama asked about was different. It would come from inside.” “Cognitive-behavior therapy muted overactivity in the frontal cortex, the seat of reasoning, logic, analysis and higher thought. The antidepressant raised activity there. Cognitive-behavior therapy raised activity in the limbic system, the brain’s emotion center. The drug lowered activity there. With cognitive therapy, says Dr. Mayberg [Helen Mayberg of the University of Toronto], the brain is rewired ‘to adopt different thinking circuits.’” “The discovery that neuroplasticity cannot occur without attention has important implications. If a skill becomes so routine you can do it on autopilot, practicing it will no longer change the brain. And if you take up mental exercises to keep your brain young, they will not be as effective if you become able to do them without paying much attention.” (3/14/07)

221. Amnesia and the Future
We have long known that damage to the hippocampus produces loss of past memories, a condition to which we apply the term ‘amnesia.’ But the losses of amnesia are much greater, limiting the afflicted’s ability to see or imagine the future. Eleanor McGuire and her associates at the Wellcome Trust have long been exploring this very territory. Now Karl Szpunar and colleagues at Washington University in St. Louis have published on how the ‘imaging’ mechanism works. Their article “Imaging pinpoints brain regions that “see the future” summarizes sum of the study’s conclusions, which are published online by the National Academy of the Sciences:

Our findings provide compelling support for the idea that memory and future thought are highly interrelated and help explain why future thought may be impossible without memories.

The study clearly demonstrates that the neural network underlying future thought is not isolated in the brain’s frontal cortex, as some have speculated. Although the frontal lobes play a well-documented role in carrying out future-oriented executive operations, such as anticipation, planning and monitoring, the spark for these activities may well be the very process of envisioning oneself in a specific future event, an activity based within and reliant upon the same neurally distributed network used to retrieve autobiographical memories.

Second, within this neural network, patterns of activity suggest that the visual and spatial context for our imagined future often is pieced together using our past experiences, including memories of specific body movements and visual perspective changes—data stored as we navigated through similar settings in the past.

220. Plaque Busters
For several years, dedicated neuroscientists, well apart from the crowd, have been telling us the plaque does not tell the story for Alzheimer’s. Sharon Begley, author of one of the better columns in the Wall Street Journal, has touched on this and, lately, has delivered two salvos making this point, both on November 17 and November 24:

As I described last week, the belief that amyloid plaques are the chief cause of this disease so dominated Alzheimer’s research that it became “orthodoxy,” says Zaven Khachaturian, who oversaw Alzheimer’s funding at the National Institute on Aging from 1977 to 1995. “Having one view prevail is harmful; it becomes a belief system, not science.”

Orthodoxy also stifles research on other culprits. “Where the field made its mistake was in trying to make everything fit one common [amyloid] pathway,” says Robert Mahley, president of the J. David Gladstone Institutes, San Francisco. “We've got to realize there are multiple ways you can wind up with [Alzheimer’s].”

She goes on to mention a few of the enzyme and gene theories that may shed some light on the disease. What she makes clear and what we should understand is that standard orthodoxy has slowed discovery on this fast-spreading disease. We are particularly aware of research that has been shoved aside in the Boston medical community, but a similar lack of open-mindedness has shut down innovative thinking in many other ports of call. When we asked one researcher in the South what he thought of a particular line of thinking that looked hard at brain chemistry, he said, “We don’t get into offbeat things like that. We can’t get any Government funding for anything out of the mainstream.”

The Economist (July 29, 2006, pp. 71-72) looks at the dimensions of the problem and the lack of progress. “At the moment, 4.5 million Americans have Alzheimer’s. By 2050 … that number will have trebled.” Plaques (beta and tangles) are still the key manifestations of the disease and, hence, the central focus still in investigations. There are a host of attempts to slow the progress of the disease, some of which we have enumerated in “New Strategies for Blocking Alzheimer’s.” This is only one field where lockstep thinking is slowing scientific discovery. (2/28/07)

As we have mentioned many times, researchers have tended to focus on one simple gene or explanation in trying to discover the key to Alzheimer's, Parkinson's, autism, and a host of neurological diseases. Our suspicion is that the disease mechanism in each instance is infinitely more complicated than investigators can imagine, and that researchers have not even perceived the correct disease model that would help lead to advances. Alzheimer's research is now trying to see whether the focus should be amyloids or not. Current drug tests at Elan, Pfizer, Johnson & Johnson, and others are viewed as "a referendum on the prevailing theory in Alzheimer's drug development, which focuses on sticky clumps of protein known as beta amyloid that build up in the brain."(Wall Street Journal, July 16, 2012, p.B1). What seems evident to us is that amyloid is one of many wastes, which also includes metallic outputs, that the system cannot process. The disease condition, in our view, is evidence that the system is not ridding itself of sundry excretions. (08/22/12)

219. Use It or Lose It
“Keeping mentally agile protects against dementia but until now no one has known exactly why” (Economist, October 21, 2006, p. 91). Rats, it is revealed, grow thousands of brain cells every day, but only retain them if used; otherwise, they die off in a couple of weeks. For the longest while scientists thought that we did not grow new cells—that we only had those with which we came to this party. But now they know we grow a lot, many in the hippocampus, the center for remembering events. Tracey Shors of Rutgers and her colleagues found that neurons are retained if used, and, maturing, get wired into networks if they are involved in complex learning chores. For more on this, see the vita of Dr. Shors. There is still considerable dispute, however, as to what extent brain exercise helps deteriorating brains. (2/21/07)

218. Chemo Hurts
We are intimately familiar with cancer survivors who say that their brains are very, very cloudy for about a year after their last intravenous feed by the oncologists. Now researchers have come along to prove the obvious. “Researchers at the University of California, Los Angeles, took PET scans of the brains of 34 women as they performed short-term memory tests. Those who had received chemotherapy five to 10 years earlier required significantly more blood flow in a region associated with short-term memory than healthy women or those who only had surgery to treat the cancer” (Boston Globe, October 9, 2006, pp. C1-2). “No therapy is currently proven to prevent or treat chemo brain, though ongoing clinical studies are testing ginkgo biloba and Alzheimer’s therapies as potential remedies….” See Neurology Reviews.com. (2/14/07)

217. Post-Prozac Depression Drugs
Pfizer, Sanofi-Aventis, and others “are targeting a system of brain chemicals that are involved in the body’s response to stress.” See “Targeting Depression,” Wall Street Journal, December 14, 2006, pp. B1 and B6. These include Bristol’s CRF 1 Antagonist, Novartis Agomelatine, Novartis Metabotropic glutamate receptor 5 Antagonist, and Concept’s Mifepristone. Existing remedies only help half of all depression patients and often have unpleasant side effects. They target neurotransmitters, acting on proteins from only about 20 of the approximately 15,000 genes in the brain. “Part of the problem is that the biology of depression isn’t well understood, even compared with other psychiatric diseases.” Stress, it seems, ultimately leads to the production of CRF, leading to release of hormones including cortisol that seems to induce depression. Cortisol may damage nerve cell connections and prevent nerve growth. Targacept is studying mecamylamine, a blood pressure drug it got from Merck, seeing whether it will block receptors and control mood fluctuation. As usual, there is the threat of side effects, particularly to the liver. (2/7/07)

216. 3 Lbs.
CBS is out with a new TV drama about—of all things—brain surgeons. It stars the fabulous Stanley Tucci, but it already may be terminal. The Boston Herald says, in a review echoed by many others, that it “needs some medical help.” Dr. Hanson (Tucci) is brainy, talented, and, of course, fouled up. He suffers from hallucinations, but we think the writers are just projecting their own complaint onto their main character. Associated Content notes: “The series takes place in a cutting-edge[,] fantastically chic neurological surgical facility in New York City. Apparently the drama of brain surgery itself was not complex enough for the show’s producers, so they set the two main characters, Dr. Hanson and Dr. Seger, against each other with diametrically opposed philosophies about how to approach their patients. At least the writers have infused the drama with a touch of humor to break up all the staring at brain x-rays. The entire neurological wing of the hospital is decorated with the pattern of nerves that map the brain. They’re on the walls, on the rugs, even on the privacy curtains. It makes for a busy background.” You know, the neurosurgeons and neurologists we know are pretty entertaining and don’t require all this made-up makeup. Too bad CBS tarted it up. (1/17/07)

215. Cognitive Decline
Sharon Begley points out that we can get rather muddled about what produces brain decline (Wall Street Journal, April 28, 2006, p. B1). Many think that those in brain-active jobs ward off dementia; more likely, says Ms. Begley, they have well-fortified brains in the first place, and that they are armored against decline. Mental exercise does not necessarily correlate with mental preservation, despite the games dreamed up by neurologists and others to keep you humming—many of which are mentioned on Global Province. So one should approach MindFit from Israel, Nintendo’s Brain Age, and My Brain Trainer with a grain of salt. They only seem to help the brain along if you keep upping the ante, challenging the mind with tougher and tougher mental exercises. Begley notes that other forms of training—cardiovascular fitness exercise, for instance—do seem to tune up the brain at the same time. Merzenich, out in San Francisco, whom we discussed in “Old Brains Don’t Die; They Just Fade Away,” offers data suggesting his system may—we stress may—offer more enduring effects. (1/10/07)

214. Off-Label Alzheimer’s Drugs
Gradually, more tentative drug approaches to Alzheimer’s are emerging. We have previously discussed this in “Enhancers and Inhibitors.” Drugs originally approved for diabetes, prostate-cancer, and anti-inflammation are now in late stage trials for Alzheimer’s. See the Wall Street Journal, October 17, 2006, pp. D1 and D2. “The four drugs currently approved … Aricept, Exelon, Razadyne, and Namenda … are a huge business,” but they really only relieve symptoms and do not treat the underlying mechanism of the disease. “Some of the most promising results to date involve Flurizan, which is derived from an anti-inflammatory and is being tested by Myriad Technologies. The drug targets an enzyme, called gamma secretase, that is believed to play a role in the build-up of amyloid.” “Researchers also tout Alzhemed, a drug being developed by a Canadian company, Neurochem Inc….” It has stabilized the condition for long periods of time in a number of patients. (12/13/06)

213. Narcolepsy
Either one gets too much sleep or no sleep at all. We are just beginning to take a look at Narcolepsy. For starters, we will recommend Stanford’s Center for Narcolepsy. (Somehow this reminds us that the people at UC Berkeley used to say, “There are some bright people down at Stanford. But they have baked brains.” Maybe so). We find its historical material a little useful, though we are not able to evaluate its focus on hypocretins. We would, of course, like to see more research on the site from other institutions. It probably helps to look at the Narcolepsy Network in order to get a wider scan of the field. We are bemused by the Sleep Foundation’s site. You can look into the Midwest’s view of the problem at the University of Illinois-Chicago Center for Narcolepsy. (11/22/06)

212. Chez Scaruffi
You cannot be in the brain business and fail to look at Piero Scaruffi. He is perhaps most renowned for his music site but Thymos is a must for anyone who wants to think about cognition. We have just begun to explore it. Perhaps a good starting point is his Annotated Bibliography of the Mind, which covers a fair patch of the literature on consciousness. He’s a poet and freelance critic as well. If you need to get away from his catalog of cognition, visit his cluster of other sites and strands.

We admire most the fact that he has made his sites, and the collection of knowledge and thinking they represent, his real job. Occasionally he still darts in and out of computer and artificial intelligence work to keep body and soul together, but he has dedicated himself to his interest in knowledge, some of which he has relayed in print in such works as A History of Rock Music: 1951-2000 and Thinking about Thought: A Primer on the New Science of Mind, Towards a Unified Understanding of Mind, Life and Matter. (11/15/06)

211. Tuning Up the Brain with Sleep
At a recent meeting of “the Organisation for Human Brain Mapping in Florence, Italy, Giulio Tononi of the University of Wisconsin theorized that after extensive learning the brain grows increasingly inefficient. “Sleep prunes back the grey matter so that, come the morning, the brain is once again economical to run. If this pruning cannot take place, the organ becomes less and less efficient, and dire consequences result.” See “The Big Sleep,” Economist, July 8, 2006, pp.73-74. Indeed, this proposition supports the notion we put forward in “The Big Sleep” that the exhaustive regimen schools are now inflicting on our kids is a clear impediment to learning.

“Even at rest, the brain is costly to run, consuming 20% of the body’s energy production.” Traditionally sleep researchers have focused on REM sleep which only comprises only 20% of a night’s store. But actually brain restoration seems to take place during the other 80% that we have not examined so closely. The slow waves that sweep across the brain during this period are thought to tone down the synapses that are forged and expand during the day—“reducing their size, chemical activity and electrical activity….”

“The researchers’ discovery finds an intriguing echo in a human disease called Morvan’s syndrome. This is a rare brain disorder that is caused by an autoimmune response which destroys the human equivalents of ion channels that are affected in the mutant fruit fly. Patients with Morvan’s syndrome suffer from severe insomnia and have been known to go for months without sleeping. Eventually, this extreme sleep deprivation kills them.”

210. Parasites and Brain Development
Fred Gage of the Salk Institute thinks that brain junk in the DNA—the 95% that is not genes—may play a part in brain development. See the Economist, June 18, 2005, pp.76-77. “One of the most puzzling sorts of junk, though, is something known as Line-1 retrotransposon.” Resembling retroviruses, they jump from chromosome to chromosome. Generally, it makes up 20% of the human genome. Some, “instead of being destroyed … have been subverted … to create complexity in the brain,” theorizes Gage. They are active in “precursor cells,” altering the course of cell development. For more, see “Jumping Genes.” (10/25/06)

209. Parenting Rewires the Brain
“Fatherhood increases the nerve connections in the region of the brain that controls goal-driven behaviour—at least, it does in marmosets.” It has long been known that it causes changes in females, causing a greater number of neural connections. Elizabeth Gould of Princeton did research in this specific area, and allied research has been done by Craig Kinsley at University of Richmond. See Nature, 24 August 2006, pp. 850-51. (10/18/06)

208. Electro-Shock
Electric shock treatments are being selectively revived. See the Economist, June 3, 2006, pp. 78-79. “Vagus-nerve stimulatin … was originally developed to treat severe epilepsy.” Even where it does not lessen number of seizures, epilectics “reported feeling much better after receiving the implant.” This has led to its application in depression and in 2005 the FDA approved it for use where all else fails. Its effects are reported to be long lasting. It builds on the idea of deep-brains stimulation which is a more complicated procedure, the vagus insert being much easier to do. It does, however, require a fairly long course of treatment—at least 3 months-for the palliative effects to take hold. (10/11/06)

207. Fifty-Percent Cuts in Brain Injury Funding
House and Senate bills prospectively will cut funding for the Defense and Veterans Brain Injury Center from $14 million to $7 million. The Pentagon had only asked for $7 million and has not been responsive to Congress when asked whether it needed more. The Defense Department has put a blanket on its staff, preventing it from commenting on the issue. Officials at Walter Reed, where the center is located, had indicated they needed $19 million to handle rising case loads. It is our understanding that Senators Dick Durban and George Allen are separately plumping for a richer budget. See the daily.cos for September 5, 2006. (10/4/06)

206. Stuttering
We receive reports of some modest progress on stuttering. Like autism and many other neurological complaints, it is no longer regarded as an environmentally induced form of behavior, but instead is taken to be genetic and neurological in nature. In “To Fight Stuttering, Doctors Take a Close Look at the Brain,” New York Times, September 12, 2006, pp. D1 and D6, various hypotheses and possibilities are forwarded. “Dr. Maguire, a psychiatrist at the University of California, Irvine, wants to cure the ailment that afflicts him and an estimated three million Americans.” Indevus Pharmaceuticals announced in May encouraging results from a large clinical trial with its drug pagoclone. “Men who stutter outnumber women by a ratio of about 4 to 1, for reasons not known.” “Brain imaging studies have shown that the brains of people who stammer behave differently from those of people who don’t when it comes to processing speech.” For non-stutterers speech processing is a left brain activity. Stutterers, on the other hand, show an unusually large amount of right brain activity. Because of a heavily afflicted family in the Cameroons, Dennis Drayna, at the National Institute on Deafness and Other Communiccation Disorders, has narrowed the genetic search to “a stretch of Chromosome 1 containing 50 to 60 genes.” “Another study using families from Pakistanwith large numbers of stutterers found a region on Chromosome 12….” Some stutterers have been helped by devices, such as SpeechEasy, a feedback mechanism costing about $5,000 from Janus Development Group of Greenville, North Carolina which feeds the speaker’s voice back to him with a slight delay in a different pitch: the choral effect helps the stutterer. Maguire has also done small trials with two schizophrenia drugs, Risperdal and Zyprexa. (9/20/06)

205. Half of a Brain
There is an outpouring of literature on hemispherectomy, most recently in “The Deepest Cut,” New Yorker, July 3, 2006. “The first recorded hemispherectomy was performed, in 1888, on a dog by Friedrich Goltz, a prominent German physiologist. (Apparently, the post-op animal exhibited the same personality and a minimal reduction in intelligence.) In humans, the operation was pioneered by Walter Dandy, a Johns Hopkins neurosurgeon, who, in 1923, performed his first hemispherectomy on a patient with an aggressive brain tumor in the right hemisphere” “The hemispherectomy’s resurgence in popularity is largely the work of John Freeman, a pediatric neurologist who has been at Johns Hopkins nearly his entire career.” “If Freeman revived the practice of hemispherectomies, their leading practitioner has been Ben Carson, who joined Johns Hopkins in 1984 and, at thirty-two, became the youngest head of pediatric neurosurgery in the nation.” “Carson has now performed more than a hundred hemispherectomies. One of his oldest patients had the surgery in his thirties.”

“The brain’s remarkable capacity for recovery has long fascinated scientists. Bradley Schlaggar, a pediatric neurologist and a professor at Washington University in St. Louis, told me about an experiment that he conducted for his Ph.D. He transplanted the visual cortex from an embryonic rat’s brain into the brain of a newborn rat, placing it in the spot occupied by the somatosensory cortex, which is responsible for such bodily sensations as pressure and temperature. Once the second rat had grown up, Schlaggar took a look at its brain and discovered that the transplanted chunk of visual cortex was functioning as a somatosensory cortex.”

As remarkable as the John Hopkins account in the New Yorker is Half a Brain Is Enough: The Story of Nico. Here, “Antonio Battro, a distinguished neuroscientist and educationalist, describes his work with Nico over several years and explains how a boy with only half a brain has developed into a bright child with relatively minor physical and mental impairment.” Half the story is that the brains of both children and adults can be removed, and that the patients survive. The other half of the story is that they survive so well: somehow half the brain fills in for the half that’s been removed, with broad functionality returning to the patient, such that the recovering patient in time can drive cars, learn, and undertake a reasonably normal lifestyle. (9/13/06)

204. Death of Eric Schopler
Eric Schopler, an autism pioneer, died on July 7, 2006. Rejecting Bettleheim, who tended to think autistic children were the products of untoward parenting, he recognized it as a specific brain disorder. More importantly, we think, he developed the TEACCH program in North Carolina which, starting in 1966, helped parents and caregivers by understanding that autistics did not learn in traditional ways but could develop, especially with carefully designed interventions by parents and others. Needless to say, he is represented on every serious reading list about autism, such as Teaam’s in Mississippi. (8/30/06)

203. Update on Huntington’s Disease
“Huntington’s disease (HD) is an inherited neurodegenerative disorder caused by an expanded CAG repeat in the gene coding for a protein called huntingtin. George Huntington was the first to describe the disease in his paper On Chorea, which was published in 1872.” “Approximately 1 out of 10,000 people in the United States have HD.” “Petersen et al. (1998) proposed four models of neuron loss in HD: excitotoxicity, oxidative loss, impaired energy metabolism, and apoptosis.” “The two studies mentioned in detail above concerning potential treatments for HD contribute to the understanding of the pathological mechanism of the disease. Although cystamine treatment rescued neuron loss in the striatum of the HD animal model, motor function did not improve. However, gene silencing was able to restore motor recovery without rescuing striatal neuron loss. These results indicate that the abnormalities of motor function seen in HD are due to neuronal dysfunction, and not necessarily neuron loss.” See “Recent Advances Regarding Striatal Vulnerability and Treatment of Huntington’s Disease,” The Washington and Lee Journal of Science, Winter 2006, pp 5-8.

We suggest that readers consult the Huntington’s Disease Advocacy Center for a host of literature on the subject. Also, Asa Peterson at Lund University in Sweden seems to have done seminal work on Huntington’s (asa.petersen@med.lu.se, Neuronal Survival, Hs 66, BMC A 10). (8/23/06)

202. Spontaneous Re-Wiring
“Doctors Say Man’s Brain Rewired Itself,” Associated Press, July 3, 2006. “The research on Wallis, published Monday in the Journal of Clinical Investigation, was led by imaging expert Henning Voss and neurologist Dr. Nicholas Schiff at the Weill Medical College of Cornell University in New York City and included doctors at JFK Medical Center in Edison, N.J. Wallis was 19 when he suffered a traumatic brain injury that left him briefly in a coma and then in a minimally conscious state, in which he was awake but uncommunicative other than occasional nods and grunts, for more than 19 years.” Finally he is more in touch with the world and able to carry on minimal functions.

“‘The nerve fibers from the cells were severed, but the cells themselves remained intact,’ unlike Schiavo, whose brain cells had died, said Dr. James Bernat, a neurologist at Dartmouth-Hitchcock Medical Center in New Hampshire, who reviewed the research.” For a long, personal account of all the Wallis family has experienced, read “Mute for 19 Years, He Helps Reveal Brain’s Mysteries,” New York Times, July 4, 2006, pp1ff. For an abstract of “Tracking the Recovery of Consciousness from Coma,” see the Journal of Clinical Investigation, July 3, 2006. Again and again, we are learning that nerve cell regeneration is possible, although we do not understand its mechanism. As well, the brain has shown marvelous recuperative powers, restoring functionality even when large parts of it are cut away. (8/16/06)

201. Deja Vecu
A variant of déjà vu has given researchers a more complex understanding of the memory mechanism. Called “deja vecu,” a term coined by Swiss psychologist Art Funkhouser, a it describes a condition where certain subjects experience the sensation of déjà vu, of having seen something before, when they meet some phenomena which they could not have previously encountered. See The New York Times, July 2, 2006, pp. 38-43.

Canadian psychologist Endel Tulving had previously broken memories into two categories—episodic and semantic. Semantic broadly relates to the idea of recalling a piece of data we have committed to memory. Episodic is when “we actually re-experience the events themselves,” reliving some experience that we went through before. Episodic memories are more complex, using different parts of the brain, to conjure up memory but also to interpret it as something we have experienced.

Chris Moulin at Leeds University and, earlier, David Schacter of Harvard both had reported on individuals who felt strongly familiar with people, newspaper accounts, and other subject matter with which they had no possible connection.

“Alan Brown, a psychologist at Southern Methodist University and and the author of The Déjà Vu Experience, the most comprehensive book on the topic,” thinks about 2/3 of the population experience feelings of déjà vu at one time or another.

“Brain scans of” those experiencing deja vecu “revealed abnormal levels of atrophy, or cell death, in their temporal lobes. Moulin knew that epilectics whose seizures centered in their temporal lobes often experience a minutes-long ‘dreamy state’ similar to déjà vu prior to their seizures. Moulin and Conway concluded that … the deja vecu of their patients was similarly located in the temporal lobes…. If the circuit was ‘continuously active,’ it would keep feeding the brain that feeling of recollection, without any real memory attached.” (8/9/06)

200. Brainstorming B.S.
Most of these sessions don’t work. People are erratic: they cannot suddenly open their creative floodgates at a scheduled meeting. Some claim “brainstorming sessions come in handy to distribute blame in the event of failure.” See “Brainstorming Works Best if People Scramble for Ideas on Their Own,” Wall Street Journal, June 13, 2006, p. B1. “The popularity of brainstorming results in part from corporate America’s knee-jerk faith in teams.” “Typically, group brainstormers perform at about half the level they would if they brainstormed alone.” (8/2/06)

199. Keenly Impaired
“People with schizophrenia see more clearly by ignoring visual context” (The Economist, October 29, 2005, p. 84). “A team of researchers led by Steven Dakin of University College London set out to find a test in which schizophrenia sufferers would do well.” Schizoids tend to perform poorly on almost any test. Presented with a visual illusion, chronic schizophrenics could see much more clearly than a control group of normally functioning people. “This might be part of a more general failure to deal appropriately with context.” “The research seems to confirm the guess of Dr. Beuler (the Swiss psychiatrist who coined the schizophrenia term in the first place), who described schizophrenia sufferers as ‘flooded with an undifferentiated mass of incoming sensory data.’” We would further note for researchers that there are a variety of conditions, going well beyond schizophrenia, where the sufferers show visual dexterity that puts ordinary mortals to shame. (8/2/06)

198. ReProgramming the Brain
“I was lying on my back in a large white plastic f.M.R.I. machine that uses ingenious new software, peering up through 3-D goggles at a small screen. I was experiencing a clinical demonstration of a new technology—real-time function neuroimaging—using in a Stanford University study, now in its second phase, that allows subjects to see their own brain activity while feeling pain and to try to change that brain activity to control their pain” (Melanie Thernstrom, “My Pain, My Brain,” The New York Times Magazine, May 14, 2006, pp. 50-55). “Unlike acute pain, chronic pain is now thought to be a disease of the central nervous system that may or may not correlate with any tissue damage but involves an errant reprogramming in the brain and spinal cord.” “Rather, pain is a complex, adaptive network involving 5 or 10 areas of the brain transmitting information back and forth.” There are pain-perception and pain-modulation systems—chronic pain seems to come from overactive perception or dormant modulation. “The area of the brain that the scanner focuses on is the rostral anterior cingulated cortex (rACC) … [which] plays a critical role in the awareness of the nastiness of pain.” (7/19/06)

197. Sound Algorithm
“Humans have 200 million light receptors in their eyes, 10 to 20 million receptors devoted to smell, but only 8,000 dedicated to sound. Yet despite this miniscule number, the auditory system is the fastest of the five senses. Researchers credit this discrepancy to a series of lightning-fast calculations in the brain that translate minimal input into maximal understanding.” “Marcelo Magnasco … has published a paper that may prove to be a sound-analysis breakthrough, featuring a mathematical method or ‘algorithm’ that’s far more nuanced at transforming sound into a visual representation than current methods. ‘This outperforms everything in the market as a general method of sound analysis,’ Magnasco says.”

“The applications are immense, and can be used in most fields of to pick up. Radar and sonar both depend on this kind of time-frequency analysis, as does speech-recognition software. Medical tests such as electroencephalograms (EEGs), which measure multiple, discrete brainwaves use it, too. Geologists use time-frequency data to determine the composition of the ground under a surveyor’s feet, and an angler’s fishfinder uses the method to determine the water’s depth and locate schools of fish. But current methods are far from exact, so the algorithm has plenty of potential opportunities.” See Rockefeller University News Release, June 7, 2006 and Proceedings of the National Academy of Sciences 103 (16): 6094-6099 (April 18, 2006). (7/12/06)

196. Minimally Invasive Brain Surgery
“Aneurysms, blocked blood vessels and more can be treated using minimally invasive techniques, preventing deadly or disabling strokes, say U-M experts” (University of Michigan Health System News Release, July 3, 2006). “One of the newest options is the first device designed to help doctors open up clogged blood vessels in the brain. Called the Wingspan intracranial stent, it’s a tiny wire mesh tube that can be fed into the body through an incision in the leg, threaded up through the blood vessels in the chest and neck, and inserted into the brain.” “It’s designed for patients with a condition called intracranial stenosis, or cerebral atherosclerosis: a narrowing or hardening of the arteries in the brain. The condition is linked to the same factors—high cholesterol, high blood pressure, smoking, obesity, diabetes—that play a role in many heart attacks. Just like in the heart, the condition causes narrowing or blockage in brain blood vessels.”

“Another new technology just became available for patients with AVMs, which occur in more than 300,000 Americans and can also rupture suddenly and cause permanent disability or death. This new treatment is a liquid material called Onyx that can be injected directly into the AVM through a tiny tube that is fed into the brain through the bloodstream. The liquid quickly solidifies and cuts off the blood flow into the AVM, reducing the risk of rupture. It can also be used in aneurysms. After the procedure, the AVM can be more safely removed in open surgery if needed.” (7/5/06)

195. Just Blade Runners
Katrina Firlik, a Connecticut neurosurgeon, is just out with Another Day in the Frontal Lobe: A Brain Surgeon Exposes Life on the Inside. “Good neurosurgeons (who, by the way, spend more time operating on spines than they do on brains) like to keep things simple” (“Maybe Brain Surgeons Aren’t as Smart as You Thought,” New York Times, May 12, 2006, p. B33. Firlik’s book dwells heavily on her life and career, but it also gives a pretty good tour of the brain surgery world. The review of the book by William Grimes in the Times is not terribly profound, and it more or less suggests that brain surgery is no less, no more complicated than other forms of surgical endeavor. It does make clear that Firlik is a fairly vivid writer who can communicate about her world in terms the layperson can surely understand. (6/28/06)

193. Mapping the Mind—in Detail
Julie H. Simpson of the University of Wisconsin is doing a street map of the mind—in this case a fruit fly’s mind—a project that probably will go on the rest of her life. “With each slide, Simpson inches closer to one of science’s more monumental goals: producing a functional map as precise as a street map—first of the fly, eventually of humans.” This will permit much more targeted treatments for the sundry diseases and disorders of the mind. See Forbes, November 14, 2005, pp. 89-90. There are a dozen or so labs looking at neural circuitry of fruit flies, but Simpson is working a wider canvas than most. Most are looking at a narrow brain function: she has chosen to chart motor control which encompasses a lot of behaviors. (6/7/06)

192. Nano-Hamsters
“Hamster Study Shows Nanofibers Knit Severed Neurons Together, Restore Vision,” Scientific American, March 14, 2006. Researchers at MIT, the University of Hong Kong, and others cut a channel in the optic nerve of 53 newly born hamsters. “The wounds of 10 of the pups were then treated with 10 microliters of a solution composed of 99 percent water and 1 percent of a special ionic peptide. These short amino acids are capable of creating a molecular scaffold that can bridge such gaps.” Within 24 hours, the cuts began to close, and in 30 days they were virtually healed. This was again tried with adult hamsters, and significant vision returned to them. See Scientific American. Also see the Proceedings of the National Academy of Sciences. (5/31/06)

191. Teacher Education in Finland
The Finnish education system, whatever its dilemmas, gets the very highest marks when compared with the offerings of other nations in Europe and around the world. For this reason it is stimulating to see what has been going on there in teacher education. To this end, we recommend Hannele Niemi’s “Teacher Education in Finland: Current Trends and Future Scenarios.” There we learn that circa 1995 national law began to introduce more flexibility into curriculum as well as teacher education. The author notes that even insular Finland must, like every other country, take account of a rapid changing society which means adding strategic and tactical flexibility to its processes in order for the nation to keep up with the times. This contrasts, for instance, with the practices of several U.S. states that mandate detailed copious requirements that schools must adhere to, so-called standards and standardized practices which are retarding education 1-12, even with increased funding. It is noted that the Finnish teacher understands that he or she must be committed to a life-long pattern of re-education. Apparently, as in the U.S., teachers above the primary grades are experiencing a great deal of burn-out, leading to rapid turnover in their ranks. There still is stability in teacher employment in the primary grades.

The history of education in almost every country, however, is littered with tales of intractable systems that fail to change at a rate that will keep up with the transformation society is undergoing: Finland, today, has the same complaint. This is reinforced by the fact that central government controls so much of what is going on: rapid fire innovation only occurs on a grassroots, local basis. Disappointingly, the article does not come to terms with the high stress atmosphere that characterizes schools every where today. That has led to a rash of student depression and even sporadic outbreaks of suicide.

Finland has been a world leader in public health—and in a number of other social areas. We would like to better understand the interconnection of health and education, since broad-scale education, often outside the schools, is a principal driver of better health and containment of medical expenses. At the margin, some think tanks such as Rand have been looking at school violence more systematically but have not given enough weight to system-induced stress. In the late 90s more tentative efforts to integrate mental health activities into schools began to take off. UCLA, for instance, is active in this area. But it’s not clear these efforts have gotten enough traction. (5/24/06)

Update: Great Kids and Good Teachers
“What Makes Finnish Kids So Smart,” Wall Street Journal, February 29, 2008 probes why Finnish kids score higher than everybody else academically.” The Finns won attention with their performances in triennial tests sponsored by the Organization for Economic Cooperation and Development, a group funded by 30 countries that monitors social and economic trends. In the most recent test, which focused on science, Finland's students placed first in science and near the top in math and reading, according to results released late last year. An unofficial tally of Finland's combined scores puts it in first place overall, says Andreas Schleicher, who directs the OECD’s test, known as the Programme for International Student Assessment, or PISA.”
“Finnish teachers pick books and customize lessons as they shape students to national standards. ‘In most countries, education feels like a car factory. In Finland, the teachers are the entrepreneurs,’ says Mr. Schleicher, of the Paris-based OECD, which began the international student test in 2000.”

One explanation for the Finns’ success is their love of reading. Parents of newborns receive a government-paid gift pack that includes a picture book. Some libraries are attached to shopping malls, and a book bus travels to more remote neighborhoods like a Good Humor truck.”

“With a largely homogeneous population, teachers have few students who don’t speak Finnish. In the U.S., about 8% of students are learning English, according to the Education Department. There are fewer disparities in education and income levels among Finns. Finland separates students for the last three years of high school based on grades; 53% go to high school and the rest enter vocational school. (All 15-year-old students took the PISA test.) Finland has a high-school dropout rate of about 4%—or 10% at vocational schools—compared with roughly 25% in the U.S., according to their respective education departments.”

“Taking away the competition of getting into the ‘right schools’ allows Finnish children to enjoy a less-pressured childhood. While many U.S. parents worry about enrolling their toddlers in academically oriented preschools, the Finns don't begin school until age 7, a year later than most U.S. first-graders.”

190. New Strategies for Blocking Alzheimer’s
“Recently … researchers have made tremendous progress toward understanding the molecular events that appear to trigger [Alzheimer’s], and they are now exploring a variety of strategies for slowing or halting these destructive processes” (“Shutting Down Alzheimer’s,” Scientific American, May 2006). Even with the potential risks that inhibitors may pose, researchers are moving forward a host of drugs that may slow and stop amyloid development:

High doses of gamma-secretase inhibitors cause severe toxic effects in mice as a consequence of disrupting the Notch signal, raising serious concerns about this potential therapy. Nevertheless, a drug candidate developed by pharmaceutical maker Eli Lilly has passed safety tests in volunteers. (This kind of test is called a phase I clinical trial.) The compound is now poised to enter the next level of testing (phase II) in patients with early Alzheimer’s. Moreover, researchers have identified molecules that modulate gamma-secretase so that A-beta production is blocked without affecting the cleavage of Notch. These molecules do not interact with gamma-secretase’s aspartic acids; instead they bind elsewhere on the enzyme and alter its shape.

Another strategy for combating Alzheimer’s is to clear the brain of toxic assemblies of A-beta after the peptide is produced. One approach is active immunization, which involves recruiting the patient’s own immune system to attack A-beta. In 1999 Dale B. Schenk and his colleagues at Elan Corporation in South San Francisco made a groundbreaking discovery: injecting A-beta into mice genetically engineered to develop amyloid plaques stimulated an immune response that prevented the plaques from forming in the brains of young mice and cleared plaques already present in older mice.

Other researchers are pursuing nonimmunological strategies to stop the aggregation of A-beta. Several companies have identified compounds that interact directly with A-beta to keep the peptide dissolved in the fluid outside brain neurons, preventing the formation of harmful clumps. Neurochem in Quebec is developing Alzhemed, a small molecule that apparently mimics heparin, the natural anticoagulant. In blood, heparin prevents platelets from gathering into clots, but when this polysaccharide binds to A-beta, it makes the peptide more likely to form deposits.

Scientists are also trying to develop therapies that will prevent development of Tau, the other sore spot beside A-beta in the Alzheimer’s equation, looking into impact of statins on Alzheimer’s and looking into cell therapy that would inhibit loss of neurons. The encouraging aspect of all these developments is that scientists are not looking for one cure to do everything, but, rather, are trying a variety of approaches. It is highly doubtful that there is one magic bullet that will deal with complex genetic structures. (5/17/06)

189. Old Brains Don’t Die; They Just Fade Away
“[N]ew techniques show that most regions hold on to their neurons (and even 70-year olds produce new neurons), with little or no loss in the hippocampus, where memories form, or the frontal cortex, site of such executive functions as planning and judgment” (Wall Street Journal, March 3, 2006, p. B1). Of course, less physical and social activity on the part of the aged, and the less challenging environments oldsters live in, impair production of neurons and maintenance of neural circuitry. The evidence seems to point to the fact that older brains can be retrained through pertinent exercises to retain their functionality.

In “Sharp as a Tack,” Forbes, March 27, 2006, the work of Michael Merzenick, a neuroscientist at the University of California San Francisco, is explored. “In the mid-1980s Merzenich started to prove the opposite, that brains are ‘plastic,’ malleable, reprogrammable, capable of steady improvement through carefully designed exercises.” “Merzenich, whose brain has been in use for 63 years, has wisely put his research work on sale. All he asks for is 40 hours of your time and $495 for the software from Posit Science, the company he cofounded in San Francisco three years ago. You sit in front of a computer, listen and respond to Posit’s video-game-like program, which forces you to reconstruct stories and word sequences and distinguish between rising and falling tones. When the ear is attentive and working hard, it funnels clearer information to brain centers that handle memory and perception. Merzenich claims his software enables the brain, according to cognitive testing, to perform as if it were ten years younger.”

In “Studies on Dementia Often Confuse Causes with Consequences,” Wall Street Journal, April 28, 2006, p.1, Sharon Begley gives a balanced view of this topic, accepting the fact that skills training can aid aging brains, but there is a quick loss of performance if the training exercises are omitted. Correctly, too, she perceives that other forms of training—that don’t directly involved brain work, are important to brain agility, such as cardiovascular exercise. Also, she notes that challenged people tend to have better sustained brain function than people who have cashed in their chips and become too laid back.

We remember well a chap we knew in the early 80s who, nearing retirement, got a grant from the Ford Foundation and became the oldest freshman at Harvard. He thought, wrongly we think, that you cannot do much about the body, but that you can recharge the brain. Our observation would be that the two go hand in hand, and that you don’t get one without the other. He, incidentally, had never gotten a college education, but had paid for his kids to go to the best universities in the land, so he thought he deserved his chance at bat. It was a bizarre experience, since the grad students and teachers were fixated on getting ahead, and his fellow students were fastened on getting grades. Only he had the luxury of trying to get an education. For the Ford Foundation, he only had to write a paper about the experience.

Recharging the brain of oldsters has a great deal more significance than it appears. In fact, we are not going to have enough workers in the years ahead and oldsters will have to fill the gap. As well, we cannot afford for them to retire, and will need them in our workforce so that they do not bankrupt our benefits pool. Workers of the future will be doing more and more service/knowledge jobs that require active brains. See “Prematurely Retired.” (5/10/06)

188. The Potamkin Prize
The Potamkin Prize awards, given since 1988, provide a reasonable history of the advances on Alzheimer’s and other forms of dementia that have unfolded over a relatively brief period. In the early stages the honorees were involved with basic research that tried to describe the disease mechanism. With the turn of the century, researchers are looking more closely at treatments, trying to do something to at least stall the dementia progress. The family of Luba Potamkin worked in concert with the American Academy of Neurology to establish a $100,000 award for high level recognition of breakthroughs. We have been impressed at the wide swathe of institutions represented by the winners: nobody has a monopoly on neurological discovery. (5/3/06)

187. Flexing Your Brain
The literature is now littered with hypotheses that say the brain can be stretched and be rewired, overcoming the deterioration of age and other mental defects, even surging beyond the capabilities that were apparent there at birth. We have referred to the “Flexible Brain.” A few years back Larry Katz et. al. came out with Keep Your Brain Alive, offering 83 neurobic exercises. Nancy Andreasen’s The Creating Brain provides a more ambitious regime, offering not only agility but creativity.

But we think the Japanese are really onto something. See “Nintendo’s Brain-Training Game Targets Older Players,” Wall Street Journal, February 23, 2006, pp. B1 and B4. “Japan’s hottest videograme is about to hit the U.S … it’s a bunch of word and math problems with a distinctly no-thrills title: Brain Age: Train Your Brain in Minutes a Day.” Nintendo President Satoru Iwata read a book by neuroscientist Ryuta Kawashima two years ago that showed how you could sharpen your brain doing simple math problems. Having studied test subjects in his lab, Nintendo programmers have devised a hand-held game that includes drills that stimulate the brain most. Overseas is critical for Nintendo, which typically gets 75% of its revenues offshore. “Brain Age flashes questions on one screen, while the player writes answers on the other.” The player, in effect, takes timed drills.

“Brain imaging has shown that, after just a few weeks of training, the pattern of activity in older brains actually starts to look like that in younger brains.” Different kinds of drills relate to different forms of activity—short term memory, information processing, etc. Drills for one activity don’t spill over into other activities. Nintendo has definitely penetrated older segments of its home market, well beyond teen age enthusiasts.

“The version of the game that will go on sales in the U.S. on April 1 (2006) will include counting, memory and reading drills, as well as soduku….” Sleeker iterations of the DS or DoubleScreen are on the way. The revive-your-brain market is open for the taking. (4/26/06)

Update: Nintendo Goes to School
We used to regard Nintendo as an agent of dumbness, something to keep out of the house, along with Sony’s Playstation. But the company has turned things on end. Nintendo’s DS, as we have said above, has the games, but it also has exercises to recharge the brain. And now we learn it has invaded Japan’s schools, but not our own. “Nintendo DS Goes to School in Japan,” Wall Street Journal, July 11, 2007, pp. A1 and A10. Indeed, this very much fits in with the continued inventiveness of Japan’s toy industry about which we remarked in “Innovative Toys.” “Behind the fastest selling portable videogame player in Japan is an unusual shift in the culture of gadgets: People are clamoring for it not just for games, but also to keep a household budget, play the guitar, and study the Buddhist scripture Heart Sutra. Since its introduction in 2004, the DS, which responds in writing and speech, has spurred software makers to fill the Japanese market with an eclectic array of reference guides, digital books and study tools.” “Based in Kyoto, Nintendo has sold nearly 18 million DS units in Japan, more than triple the sales of rival Sony Corp.’s Playstation Portable….” It has penetrated schools because it is inexpensive compared to computers, and is teacher-friendly. In one junior high school, teachers found that “nearly 80% of students who used the DS each day mastered junior-high-level competence in English vocabulary, compared with just 18% before.” (10/24/07)

186. Optimism Harvard
Harvard students have turned out in droves for Tal Ben-Shahar's "Positive Psychology" course this semester. See The Boston Globe, March 10, 2006. No less than 855 students are enrolled.

“‘In the last several years, positive psychology classes have cropped up on more than 100 campuses around the country,’ said Shane Lopez, an associate professor at the University of Kansas, who recently co-wrote a positive psychology textbook. But with such an enormous course enrollment, Tal D. Ben-Shahar, the lecturer who teaches Harvard’s course, ‘is the leader of the pack right now’ Lopez said.”

“Marty Seligman, the University of Pennsylvania professor who is considered the father of positive psychology for his scholarship and efforts to promote it, said he saw a similar groundswell when he offered a course in 2003.”

“Positive psychology” was apparently coined by Abraham Maslow, every business professor’s favorite psychologist. In the end, it all reminds you of that good old song, “Accentuate the Positive” (Ac-cent-tchu-ate The Positive), a gem from those old masters Johnny Mercer and Harold Arlen:

You’ve got to accentuate the positive
Eliminate the negative
And latch on to the affirmative
Don't mess with Mister In-Between

We are now getting a rush of books on “happiness,” but they still generally dwell on how to get rid of negatives instead of telling us how to accentuate positives. Be-Shahar, Seligman, and others in perhaps a 100 colleges around America are watered down behaviorists trying to stonewall the negative. (4/19/06)

185. Watching the Brain Develop
“Howard Hughes Medical Institute researchers have developed sophisticated microscopy techniques that permit them to watch how the brains of live mice are rewired as the mice learn to adapt to new experiences. Their studies show that rewiring of the brain involves the formation and elimination of synapses, the connections between neurons. The technique offers a new way to examine how learning can spur changes in the organization of neuronal connections in the brain. The researchers, postdoctoral fellow Josh Trachtenberg, graduate student Brian Chen and Karel Svoboda, a Howard Hughes Medical Institute investigator at Cold Spring Harbor Laboratory, published their findings in the December 19/26, 2002, issue of the journal Nature…. To study those kinds of changes in a living animal, Svoboda and his colleagues started with transgenic mice that were engineered to produce green fluorescent protein within neurons in a portion of the brain that processes tactile sensory inputs from the whiskers. To observe changes in these neurons at high resolution, the scientists constructed a 2-photon laser scanning microscope. This microscope uses an infrared laser to excite green fluorescent protein in neurons, deep in the brain, through a tiny glass window installed in a portion of the mouse’s skull.” Science Daily has recently reprinted this 2002 news release from the Howard Hughes Institute. Importantly, it helps us understand that the brain is constantly remaking itself, often due to external stimulus. (4/12/06)

184. Whisker Brains
“Neuroscientists at the McGovern Institute for Brain Research at MIT have discovered an exquisite micro-map of the brain. It’s the size of the period at the end of this sentence, and it’s in a most unexpected place—connected to the whiskers on a rat’s face. “‘This study is a great counter example to the prevailing view that only the visual cortex has beautiful, overlapping, multiplexed maps,’” said Christopher Moore, a principal investigator at the McGovern Institute.” We find this MIT investigation provocative, because, in effect, it confirms the evolving understanding of how widely intelligence is distributed in the body and that comprehension is not all confined to what we commonly called the brain. (4/5/06)

183. Alzheimer’s and PLD1
“Most current Alzheimer’s drugs target molecules responsible for memory formation. But while helpful at slowing and even reversing memory loss, this approach doesn’t address the root of the problem: plaques that build amid brain cells, causing them to weaken and die.

In back-to-back papers published online, Rockefeller University scientists established possible new targets for drugs. In the Proceedings of the National Academy of Sciences, Dongming Cai and other Rockefeller scientists, in the research group led by Paul Greengard, now say that a protein called PLD1 may be a target for new drugs that better treat—or even prevent—Alzheimer’s. PLD1, the scientists say, plays two major roles in the cellular processes that lead to damaged brain cells in Alzheimer’s disease. First, PLD1 regulates the shuttling of beta-amyloid precursor protein (beta-APP), a large molecule produced naturally in the body and found in many different cells, including brain cells. Second, PLD1 inhibits formation of beta-amyloid, the protein fragment responsible for the brain plaques found in Alzheimer’s patients, by altering the function of an enzyme called gamma-secretase.” From a Rockefeller University News Release, 10 February 2006. We would caution readers that scientists don’t know if the plaque is a root cause or just a symptom. (3/29/06)

Plaque fighter. Rockefeller University scientists say that a protein called PLD1 may be a target for new drugs that better treat Alzheimer’s disease. Among their findings: impairment of neurite outgrowth (left) in mouse brain cells that mimic the early-onset disease found in humans was reversed by adding PLD1 (right).

182. Schizophrenia.com
We find Schizophrenia.com to be a very rich site, indeed. It covers a variety of needs and interests. Particularly valuable for us is the section entitled “Schizophrenia Biology and Genetics.” Should you run through the section on researchers, you will find that investigators now have a much better idea of what they don’t know. In general they now suspect that the affliction is really a host of conditions that tend to look alike at the macro level. But it probably stems from a host of causes, the brain having taken multiple assaults from external forces. And the wiring foul ups that cause it vary so widely that scans and other technical devices may show circuitry in far different parts of the brain are amiss from patient to patient. Says Dr Michael Flaum out at the University of Iowa, “People are starting to recognize this illness is unlikely to be explained by pathology in any single part of the brain. It’s much more likely to involve abnormalities in complex circuitry. The brain works as a unit. Everything is connected to everything else, and what we really need to be looking at more is abnormality in the circuitry level.”

The volunteers who maintain this site are either afflicted with schizophrenia or come from families that have been touched by it. As in so many diseases, it is patients and their families who are interested enough to transfer knowledge, drive research, and urge new treatments that are a major catalyst for medical change and progress. The writers, however, are skilled health writers. (3/15/06)

181. The Philosophical Mr. Turing
“Despite his immersion in engineering details, Turing’s fascination with computing was essentially philosophical. ‘I am more interested in the possibility of producing models of the action of the brain than in the practical applications of computing,’ he wrote.” See Code-Breaker, The New Yorker, February 6, 2006, pp.84-89. The awesomely brilliant Alan Turing invented the Bombe machine to crack the German military codes in WWII, arguably saving Britain from defeat. As much as anybody, he can be credited as well with the creation of the modern computer. He worked with the great theoretical physicist John von Neumann and the philosopher Ludwig Wittgenstein, an Austrian star at Cambridge. What’s interesting is that he accomplished his feats as a byproduct of his attempts to replicate human intelligence, plowing a huge amount of earth before he died of suicide at age 43. As we are discovering now in our neurological investigations, it is researchers such as Turing who can cross over many disciplines that best illuminate the complexities of the brain. For more on Turing, see The Alan Turing Homepage and Wikipedia on Turing. (3/8/06)

180. Dementia and Hibernation
“The brain stores information in neurononal networks. The chemical connections between neurons, called synapses, are thought to be critical to the formation of those networks and hence the laying down of memories. In 2003 a group led by Thomas Arendt of the University of Leipzig in Germany showed that the number of synapses in the hippocampus, a brain structure crucial for learning and memory, falls during hibernation. … All that changes within two or three hours of an animal emerging from hibernation, when a wave of new growth ensures that the number of synapses in the hippocampus soars beyond even pre-hibernation levels” (Economist, February 4, 2006, p.72). “Dr. Arendt’s group has made the startling discovery that hibernating brains accumulate a protein called hyperphosphorylated tau … also in the neurons that degenerate in the brains of people with Alzheimer’s.” Some think it is a cause of lesions, and others feel that it is really an agent generated to protect neurons. At the end of hibernation this protein clears away, and it is possible that the understanding of its comings and goings in the human brain would be helpful to understanding various disease mechanisms. (3/1/06)

179. Meandering Around the Brain
The Alzheimer’s Association has put together a tour called “Inside the Brain,”which everyone should take because it is a reasonably good Dick-and-Jane visual primer on this disease, although it does not forcibly communicate that we still do not know very much about the disease mechanism. This site, and the sites it links to, also provide a reasonable picture of the organization of the brain. (3/1/06)

178. Is Singularity Upon Us?
In Ubiquity , Ray Kursweil speculates that a better brain is close at hand: “We'll have sufficient hardware to recreate human intelligence pretty soon. We’ll have it in a supercomputer by 2010. A thousand dollars of computation will equal the 10,000 trillion calculations per second that I estimate is necessary to emulate the human brain by 2020. The software side will take a little longer. In order to achieve the algorithms of human intelligence, we need to actually reverse-engineer the human brain, understand its principles of operation. And there again, not surprisingly, we see exponential growth where we are doubling the spatial resolution of brain scanning every year, and doubling the information that we're gathering about the brain every year.” (2/22/06)“

177. P11, Serotonin, and Depression
“Alterations in 5-HT1B Receptor Function by p11 in Depression-Like States,” which appears in the January 6, 2006 issue of Science, is riddled with significance. Most objective observers realize that we really do not have a clue as to how anti-depressants work, that they do not work very well, and that they are very crude drugs that are used promiscuously. The side effects are uncharted, and we have long been puzzled as to why it takes so long for them to kick in beneficially, although negative side effects often show up quickly. Now we are finally getting some hints as to how serotonin really gets activated:

“We have shown that a gene called p11 is involved in the multiple complex changes that underlie depression,” says Per Svenningsson, a research assistant professor and first-author on the paper. “Our findings demonstrate that patients with depression, and mice that model this disease, have decreased levels of p11 protein, and they suggest that drugs that increase p11 are likely to have anti-depressant properties.”

“We have found that the serotonin 1B receptor [5-hydroxytryptamine (5-HT1B) receptor] interacts with p11. p11 increases localization of 5-HT1B receptors at the cell surface. p11 is increased in rodent brains by antidepressants or electroconvulsive therapy, but decreased in an animal model of depressed patients depression and in brain tissue from depressed patients.”

In general, one suspects that we may be able to reduce anti-depressants dosages as we better understand the mechanism providing depression relief. Drugs that elevate p11 may be in the offing. Rockefeller University and the Karolinska Institute were involved with this research. (2/15/06)

176. Gold and Alzheimer’s
Chemists in Chile and Spain believe a combination of nano-gold particles and radiation may lay waste to fibrils and plaque that have been tied to Alzheimer’s. “Using test tube studies, the scientists attached gold nanoparticles to a group of beta amyloid fibrils, incubated the resulting mixture for several days and then exposed it to weak microwave fields for several hours. The energy levels of the fields were six times smaller than that of conventional cell phones and unlikely to harm healthy cells, the researchers say. The fibrils subsequently dissolved and remained dissolved for at least one week after being irradiated, indicating that the treatment was not only effective at breaking up the fibrils but also resulted in a lower tendency of the proteins to re-aggregate, according to the researchers.” See ScienceDaily. (2/8/06)

175. Blood Flows and Alzheimer’s
“In a paper to appear in the February (2006) issue of Nature Neuroscience and now available on-line, scientists at the University of Rochester Medical Center demonstrate that star-shaped brain cells known as astrocytes play a direct role in controlling blood flow in the brain, a crucial process that allows parts of the brain to burst into activity when needed. The finding is intriguing for a disease like Alzheimer’s, which has long been considered a disease of brain cells known as neurons, and certainly not astrocytes.” See ScienceDaily. (2/1/06)

174. Alzheimer By-Ways
Gina Kolata’s “A Glimmer of Hope for Fading Minds,” New York Times, April 13, 2004, pp. F1 and F6 examines off-label uses of drugs intended for other diseases that seem to be inhibiting Alzheimer’s. The statins, for instance, intended to lower cholesterol and fight heart disease, appear to lead to a lower incidence of Alzheimer’s. “Other researchers are trying to see whether drugs that can reduce inflammation can slow the progression of the disease.” There have also been experiments in using drugs/immunizations to clear beta-amyloid plaque from the brain, but the side effects have been risky, and much of this work has been halted. Autopsies, however, show an amazing reduction in plaque. (1/25/06)

173. Regaining Body Control
“Then, in July 2001 at age 52, Ms. Schneider began to get her life back. Electrodes were surgically inserted in her brain and attached by wires to two pacemakers implanted in her chest…. Within eight weeks Ms. Schneider was a new person … and she now shows no outward signs of a movement disorder” (New York Times, November 8, 2005, p. D7). Movement disorders can result from a variety of stimuli, ranging from diseases to oxygen starvation to drug side effects. “Exactly what goes awry in the brain is unknown, but Dr. Bressman’s team has identified some genes that result in dystonia, including one for generalized dystonia that arises in children.” “The long list of hyperkinetic disorders include dystonia … restless leg syndrome; tics; blepharospasm … and essential tremor.” (1/25/06)

172. The Amazing Power of Suggestion
“Recent brain studies of people who are susceptible to suggestion indicate that when they act on the suggestions their brain show profound changes in how they process information” (New York Times, November 22, 2005, pp.D1 and D4). Perceptions here can be manipulated by expectations (suggestions). Hypnosis has a long history, to include its uses for medical problems, but nobody quite ever has known how it works. “This brain structure would also explain hypnosis, which is all about creating such formidable top-down processing that suggestions overcome reality.” That is, the interpretative parts of the brain generate so much feedback that they overcome and distort the sensory data that normally drives perceptions. “According to decades of research, 10 to 15 percent of adults are highly hypnotizable,” but up to age 12, perhaps 80 to 85 percent of children are easily hypnotizable. (1/25/06)

171. Alzheimer’s Library
“For nearly twenty years, Mayeux, a neurologist, epidemiologist, and co-director of the Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, has been compiling the world’s most comprehensive genetic library of family with Alzheimer’s, in an effort to uncover the biological origins of a disease that affects 4.5 million Americans” (Sue Halpern on “The Gene Hunters,” The New Yorker, December 12, 2005, pp.84-93). The subjects are primarily Dominicans, many from the Washington Heights neighborhood where the Taub is located. There are two types of Alzheimer’s: early-onset, which can be traced to a simple mutated gene, and late-onset, which hits those 65 and older. Late-onset is complex, stemming from a combination of genes, only one of which has been identified. And it is hoped that Mayeux’s gene library will help uncover one or more of the rest. Mayeux is involved with a host of neurological activities at Columbia as well.

“He is also an adroit administrator, overseeing a staff of a hundred and eighty-five neurologists, geneticists, psychologists, epidemiologists, data-entry clerks, cell biologists, genetic counselors, and animal modelers spread over five floors of the hospital building as well as a clinic at Columbia’s Neurological Institute.” The size of the team is striking, but what is truly remarkable is the range of disciplines necessary to achieve a breakthrough. Mayeux himself is a professor of neurology, psychiatry, and epidemiology. Mayeux’s team, as well as researchers at the University of Toronto and Boston University, have identified a promising gene for late-onset and are now trying to understand the variable ways that it may produce disease. In theory, anyway, the researchers have moved a bit closer to some findings that may help with late-onset disease. Some drug discovery experiments are now underway, but as Scott Small, a principal researcher says, “Right now, we’re two years into a ten-year process.” So close but so far. (1/25/06)

170. Genius under the Microscope
In “Marked by Genius,” Christopher Chabris of Harvard’s Department of Psychology, does an uncommonly fine review of Nancy Andreasen’s The Creating Brain. “Her laboratory of the University of Iowa was one of the first to use modern MRI technology and IQ testing methods to confirm the suspicion that more intelligent people tend to have larger brains.” A biological psychiatrist, she studies what goes wrong with the brain during mental illness, but she has a special interest “in extraordinary creative genius. Such genius has long been associated with serious mental illness, especially schizophrenia and drug abuse.” In the 70s and 80s, based on studies of visiting faculty of the Iowa Writers Workshop, she “showed that mental illness was indeed much more prevalent in the creative achievers.” “But surprisingly, the disease most associated with creativity was not psychosis but depression, especially bipolar disorder (manic depression).” Loosely interpreted, both psychosis and creativity require loose connections between the conceptual structures of the brain, accounting for their close association. (1/18/06)

Update: Drugs and Brain Rot To some extent, Nancy Andreasen works hard at telling us what we already sort of know. Last Fall in the Times (September 16, 2008, p.D2), she announced “the big finding is that people with schizophrenia are losing brain tissue at a much more rapid rate than healthy people of a comparable age.” And, the more drugs you use, the more brain tissue you lose. That is, many conditions in the brain and elsewhere are due to accelerated deterioration. And drugs, by implication, are given out much too promiscuously. Ms. Andreasen had told us that she had moved her focus to creativity, but it is clear that she still has a hand in the schizophrenia game. (09-30-09)

169. Clutter Confusion
“Scientists have long known that the ability to pick out a target in a complex scene suffers when there are loads of things you are not looking for.” See “Why Airport Screeners Sometimes Don’t Spot Guns, Knives, Scissors,” Wall Street Journal, December 30, 2005, p. A11. Airport screeners may miss target items when they are surrounded by other very similar items. As well, they also easily miss targets with slight variances from what they have in mind: they might hone in on a Beretta, but miss another handgun, say a Smith & Wesson. Cognitive scientist J. David Smith writes about this problem in “Learning, Memory and Cognition” (Journal of Experimental Psychology, vol. 31, no. 6), which is summarized in Monitor on Psychology. (1/18/06)

168. Angst Association
Anxiety Disorders Association of America: here one can learn about the most common anxiety disorders, such as panic disorder, social phobia, and post-traumatic stress disorder. “Getting Help” advises on how to find a therapist and other useful information. Sadly, the site does not provide information on current research nor on how a lay person should evaluate the several medications being ladled out rather freely for such problems. (1/11/06)

167. On Not Taking the Old or the New
“Older drugs for treating mental disorders carry a higher risk of death among elderly patients than a newer generation of medicines used to treat the conditions….” “The Food and Drug Administration warned this year that elderly patient with mental illness who use an array of newer antipsychotic drugs—including brand names such as Zyprexa and Risperdol—were at greater risk of death than those taking no drugs.” In that study, the FDA did not include older drugs in the phenothiazine and buterophenome classes “with brand names such as Thorazine and Haldol.” See the Wall Street Journal, December 1, 2005, p. D7. Philip Wang of Brigham and Women’s Hospital in Boston took a look at the older drugs, his results published in the New England Journal of Medicine.” They’re worse than the new drugs. The anti-psychotics are prescribed widely with as many as ¼ of patients in some nursing homes using them. More restraint in their use seems to be indicated. (1/11/06)

166. Born Dualists
Yale has many Blooms, but not many Roses. There’s Harold Bloom, who is part of a literature of literary criticism that’s as potent as the literature it examines. Paul Bloom is a Yale cognitive psychologist who believes that we come into this world making with a epistemological structure that distinguishes between body and soul from the get-go. It’s not something that’s learned: the supernatural capacity—the distinction between brain/soul and body, spirit vs. material—are built into the human machine. Even if, in his own belief, they are just a continuum, not separate and alien parts of the human make-up. Says Bloom in Edge:

In the domain of bodies, most of us accept that common sense is wrong. We concede that apparently solid objects are actually mostly empty space, consisting of tiny particles and fields of energy. Perhaps the same sort of reconciliation will happen in the domain of souls, and it will come to be broadly recognized that our dualist belief system, though intuitively appealing, is factually mistaken. Perhaps we will all come to agree with Richard Dawkins and Daniel Dennett and join the side of the “brights”: those who reject the supernatural and endorse the world-view established by science.

But I am skeptical. The notion that our souls are flesh is profoundly troubling to many, as it clashes with religion. Dualism and religion are not the same: You can be dualist without holding any other religious beliefs, and you can hold religious beliefs without being dualist. But they almost always go together. And some very popular religious views rest on a dualist foundation, such as the belief that people survive the destruction of their bodies. If you give up on dualism, this is what you lose.

However, the onlooker can ask whether it will help or hinder us to resolve the dualism argument one way or another. We still don’t much understand how our minds/spirits and our bodies interact with one another. We do know that the tendency to discount mind, soul, etc. (as has happened throughout psychiatry) has led to skewed treatment patterns in medicine. (1/4/06)

165. The Anti-Depressants
Not one peer-reviewed article really can link serotonin deficiency to any mental disorder. Sharon Begley (Wall Street Journal, November 18, 2005, p. B1) underlines this point in reporting on some findings of scientists in the online journal PLOS Medicine, December 2005, “Serotonin and Depression: A Disconnect Between the Advertisements and the Scientific Literature.” Derick Lowe, a medicinal chemist, says on his blog, “I can confidently state that we know just slightly more than jack” about the workings of anti-depressants. In any event, it’s pretty clear that we know almost nothing about how anti-depressants work. His “Rewiring the Brain” is a thoughtful consideration of this whole topic. When you witness the hit and miss ways pharma-psychiatrists administer these drugs, you become aware that we are plagued with questions about drug effectiveness, side effects, and long term impact.

Curiously, many of the drugs do not have an effect to well after serotonin levels have risen in those taking medications. Begley and others speculate that the neurogenesis, or the birth of neurons, is more strongly associated with depression relief. Begley further speculates that the somewhat cavalier use of drugs has led to a drop in the use of psychotherapy for emotional disease, not a desirable outcome, particularly in adolescent patients. (1/4/06)

164. Smoking Brain
While no sensible person would urge anyone, much less emotionally afflicted people, to take up cigarettes or marijuana, we must note that there are ample hints that both nicotine and marijuana, generally at low dosages, can have a therapeutic effect. Like Prozac, HU210, a synthetic cannabinoid, has been shown to promote brain cell growth by as much as 40% in rats. Xia Zhang at the University of Saskatchewan notes, however, that more research would be needed to see whether it could someday be used to treat depression in human beings. See his “Cannabinoids promote embryonic and adult hippocampus neurogenesis and produce anxiolytic- and antidepressant-like effects.”

A raft of studies suggests that sundry cannabinoid compounds can help with a potpourri of conditions ranging from ALS (amyothropic lateral sclerois), Parkinson’s, severe pain, and even obesity. Mary Abboud of California Pacific Medical Center in San Francisco believes THC might extend lives of ALS sufferers by as much as 3 years, while riluzole, the FDA approved drug now, adds on average only two months to the lifecycle. Andrea Giuffrida at the University Health Science Center in San Antonio apparently finds, at least in mice, that WIN 55212-2 could stave off the death of cells that generate dopamine, the critical element that becomes depleted in Parkinson’s victims. See SFN release on marijuana-like compounds, October 26, 2004.

A “Marijuana Ingredient May Stall Decline from Alzheimer’s.” This finding arose in studies from the Cajal Institute and Complutense University in Madrid, led by Maria de Ceballos. See “Prevention of Alzheimer's Disease Pathology by Cannabinoids: Neuroprotection Mediated by Blockade of Microglial Activation,” February 23, 2005.

Nicotine may, in some instance, improve memory and counter certain diseases. In some experiments with rats, those treated with nicotine perform better on certain functions than a control group. In addition, “Nicotine appears to repair learning and memory deficits caused by hypothyroidism, although it doesn’t appear to improve learning and memory in normal animals.” See SFN release about new studies on nicotine, November 11, 2003.

163. -new- Neuroscience at John Hopkins
On November 11, 2005, John Hopkins celebrated its first century in the brain business with a symposium entitled “Discovery and Hope: A Celebration of Brain Science” along with a dinner at the local Renaissance Hotel. “On Nov. 10, the Department of Neurology”held “a symposium featuring Hopkins scientists and neurologists in honor of its upcoming 35th anniversary.” See “John Hopkins Celebrates Its First Century of Neuroscience.”

“The first formal brain studies at Johns Hopkins started in 1906 when Harvey Cushing became the first director of neurosurgery. His research established that hormones secreted from the brain's pituitary gland promote growth. Walter Dandy, who succeeded Cushing, figured out in 1918 that air could be used to enable X-rays of the brain. His technique remained the best way to see into the skull to identify brain tumors and other problems until the invention of computer aided tomography (CAT) in 1972.”

Today “four major areas of investigation occupy the time of brain scientists at Hopkins: Cellular and Molecular Neuroscience; Systems, Cognitive, and Computational Neuroscience; Developmental Neuroscience; and Neurobiology of Disease.”

“At its inception, Hopkins’ neuroscience department was one of the first in the nation, and today it is the largest of the basic science departments at the School of Medicine, with 25 primary faculty. Another 78 Hopkins faculty have secondary or joint appointments in neuroscience, including two dozen or so whose primary appointments are in the departments of Neurology, Neurosurgery or Psychiatry. In the Department of Neurology, there are roughly 75 primary faculty, in the Department of Neurosurgery, 24. The Department of Psychiatry, founded almost 100 years ago, boasts 139 full-time faculty with primary appointments.” For more on this event, see Johns Hopkins Medicine. To read about Sol Snyder, who founded the department, go to “Research as an Art Form.” For a history of neuroscience at Hopkins, see Neuron, “Neuroscience at Hopkins,” October 20, 2005, pp. 201-211, written by Snyder, the retiring chairman. (12/28/05)

162. Brain Sit Ups in Japan
“Recently, an increasing number of local governments and private-sector organizations have taken measures to encourage mental exercise as a means of preventing the onset of dementia” (http://web-japan.org/trends/science/sci041222.html). Tokyo’s Shinagawa District began an “Active Brain Wellness Classroom” in July 2004. “The contents of the course are based on the research of Kawashima Ryuta, a professor of neuroscience at Tohoku University. Participants conduct simple mathematical calculations and read aloud passages from novels—activities that stimulate their frontal cortex and can prevent dementia.” Tokyo’s Toshima District and Anjo City in Aichi Prefecture also have programs. There are several efforts to test the efficacy of such elder age projects. (12/21/05)

161. Schizophrenia Research Forum
This website resembles in so many ways the Alzheimer’s Research Forum, and, in fact, was started in 2003 with assistance from Alzforum founder June Kinoshita. Many people from ARF have moved over to this new endeavor. Somehow it seems ironic to read about a Schizophrenia social at a recent meeting of the Society for Neuroscience in Washington, but, one when gets over chuckling, one can only rejoice that this young group has a clear sense of community that will serve as a catalyst for the researchers it is abetting. We are looking forward to getting on top of schizophrenia research trends. (12/21/05)

160. The Power of Placebos
“The placebo effect, long considered nothing more than psychological suggestibility, does now appear to be genuine” (The Economist, August 27, 2005, pp.64-65). “The effect is especially strong in hard-to-pin-down illnesses and conditions such as depression (where up to half of people can get better on a sugar pill) and pain.” Jon-Kar Zubieta and colleagues at the University of Michigan-Ann Arbor noted moderation of pain with a placebo even as pain-making solution was injected in subjects. “What he found was that when the placebo was being administered—and the subjects were informed when it was—their brains released significantly more endorphins, the brain’s natural painkillers. The researchers knew this because they had introduced a radioactive tracer that selectively binds to the same type of receptor in the brain, the mu-opioid variety, as the endorphins. More of the tracer was floating around unbound, suggesting the receptor sites were occupied by the endorphins.” He used positron emission photography to make this determination. See “Placebo Effects Mediated by Endogenous Opioid Activity on µ-Opioid Receptors,” Journal of Neuroscience, August 2005 and “Neurobiological Mechanisms of the Placebo Effect,” Journal of Neuroscience, November 2005. Interestingly, this hearkens back to William James, philosopher-psychologist, who so forcibly talked about the “will to believe.” (12/21/05)

159. Personalized Drug Prescriptions
“The age of personalized medicine is on the way.” About 40 of the 50 psychiatrists at the Mayo Clinic use genetic tests to help choose which drugs to prescribe, says Dr. David A. Mrazek, chairman of psychiatry at Mayo.” See the New York Times, November 8, 2005, pp. D1-D6. Specific, genetically targeted drugs are not in the offing in the next 5 years, however, according to “Dr. Gualberto Ruaho, president of Genomas, a company working on genetic tests for drug use.” At stake is not only the ability to prescribe for drug effectiveness but drug safety. Some users of Paxil, for instance, have not been able to metabolize the drug satisfactorily, leading to toxic and sometimes fatal results. “Dr. Mrazek of the Mayo Clinic said he used the tests to help choose antidepressants, particularly for children. There has been concern that some children can turn suicidal or aggressive on antidepressants….” For those troubled by Prozac or Paxil (involving the 2D6 enzyme) he may prescribe Celexa or Lexapro (primarily metabolized by the 2C19 enzyme). Few offer such genetic tests though the pharmacogenomics laboratory at the University of Louisville performed 3500 to 5000 in the last year. (12/14/05)

158. Human Connectome
Olaf Sporns of Indiana University and two co-authors (one from Wisconsin and one from Dusseldorft) talk about their attempt to map the structure of the brain in “The Human Connectome: A Structural Description of the Human Brain” as published in Plos Computatonal Biology. “While some databases or collations of large-scale anatomical connection patterns exist for other mammalian species, there is currently no connection matrix of the human brain, nor is there a coordinated research effort to collect, archive, and disseminate this important information. We propose a research strategy to achieve this goal, and discuss its potential impact.” “The human connectome could potentially have a major impact on our understanding of brain damage and subsequent recovery. The effects of developmental variations or abnormalities, traumatic brain injury, or neurodegenerative disease can all be captured as specific structural variants of the human connectome.” (12/14/05)

157. The World’s Fastest Neurologist
Doing his medicine all along, Roger Bannister was the first runner in the world to break the four minute barrier on May 6, 1954 at Oxford. As a physician and scientist, he had minutely researched the mechanical aspects of running and developed training procedures built around his knowledge of the body. (Read about his training methods at Nevada Track Stats.) Later at the British Empire Games, he bested John Landy, an Australian who had broken his record not long after the Oxford race. His autobiography, The First Four Minutes, was published in 1955, and later re-issued as Four Minute Mile.

On the fiftieth anniversary of his run, the BBC asked him if the victory was the most significant event of his life. He replied, no. “He rather saw his subsequent forty years of practicing as neurologist and some of the new procedures he introduced as being more significant.”

Today, Sir Roger Bannister is Director of the National Hospital for Nervous Diseases in London and is editor of Autonomic Failure, a textbook on clinical disorders of the autonomic nervous system. As well, he is editor/author, along with Lord Walter Russell Brain, of Brain and Bannister’s Clinical Neurology. He withdrew from private practice and limited himself to research after a serious auto accident which also ended his running. This was in 1975, the year in which Queen Elizabeth knighted him. His other books include Fair Play.

At that stage there were no methods of testing for diseases of the autonomic nervous system. We saw all kinds of patients who might have these kinds of diseases and created a battery of tests. At the same time, the method of assaying chemicals like noradrenaline that are released by nerve endings were being developed, so one had a direct biochemical way of measuring the activity of this system. I developed it with colleagues in London at the same time that NIH in Bethesda were also doing it. I was near the leading edge, and set up Autonomic Research Society. Now there are similar research societies in the United State and other countries. At this time I was traveling very widely and speaking at medical conferences on these areas, and I wrote the first textbook on diseases of the autonomic nervous system. It’s now in its fourth edition.” (12/7/05)

156. Exercise and Senility
A study at the Karolinska Institute, the results of which were published in Lancet Neurology, checked for dementia and/or Alzheimher’s in 500 patients over 65 whose exercise has been monitored for 35 years. Those exercising twice a week had a 50 percent lower chance of developing dementia and 60 percent less chance of Alzheimer’s. For more on exercise and senility, see the International Herald Tribune and the Alzheimer’s Association. (11/30/05)

155. Psychiatry and the Auto-Immune System
Serguei Fetissov of the Karolinska Institute in Sweden has tied the auto-immune system to anorexia nervosa and bulimia. There is the suspicion that a host of mental disorders can arise from autoantibodies, which have gone astray and attacked human tissue. See “Molecular Self-Loathing,” The Economist, October 1, 2005, pp.75-76. Of course, it has become awfully popular to blame a host of ailments on wayward immunity systems, another trend that is a bit overdone. Fetissov suggests that melanocortins that carry messages between nerve cells in the brain suffer from the assault. “Two common gut bacteria, Escherichia coli and Helicobacter pylori” as well as influenza-A virus may generate antibodies that act against the melanocortin proteins. The same mechanism might be at work in other ailments, particularly obsessive-compulsive disorder, but also schizophrenia and Tourette’s syndrome. See, as well, “Autoantibodies against Neuropeptides are Associated with Psychological Traits in Eating Disorders,” Proceedings of the National Academy of Sciences, October 11, 2005, pp. 14865-14870. (11/30/05)

154. Anti-Bursting
“Epileptic fits appear to be neural bursts that have run of control. Such fits can currently be controlled only by drugs.” Daniel Wagenaar of Caltech along with Steven Potter and Radhika Madhavan of Georgia Tech have set out to defeat bursting. “After a series of experiments involving various numbers of electrodes and various frequencies of stimulation, they have found that using an array of 25 electrodes and a stimulation rate of 50 pulses a second produces the desired suppression, but only if the electrodes themselves are out of synch with each other…. And, once bursting is suppressed this way, the neurons revert rapidly to normal behaviour.” They have now joined with Robert Gross of the Emory School of Medicine, an expert at implanting stimulating electrodes in the brain, with a view to having electrodes at the ready whenever a fit begins. See The Economist, February 5, 2005, p. 75. See also the abstract at The Journal of Neuroscience, January 19, 2005, “Controlling Bursting in Cortical Cultures with Closed-Loop Multi-Electrode Stimulation.” What we are discovering here is that more sophisticated electroshock, once damned by society, is becoming very useful. All sorts of electro-simulative therapies are gaining currency. (11/23/05)

153. Toys to Diagnose Autism?
“Brian Scassellati is a robotics researcher in Yale’s computer-science department” who has built simple, robotic toys to see how normal and autistic children respond to them. In particular autistic children will gaze quite differently at robots than normal children. In addition, “Researchers at Yale, and many other places, are designing robots and tools such as videogames to teach socializing skills to autistic children.” See “Smart, Robotic Toys May One Day Diagnose Autism at Early Age,” Wall Street Journal, October 26, 2005, p. B1. (11/16/05)

152. Robots for Stroke Victims
MIT scientists have created a group of machines that help stroke victims regain mobility by retraining limbs and stimulating brain activity. Professors Hogan and Krebs first introduced a machine in 1999 to help arm and shoulder movement. Since they have come up with machines for wrist and hand as well as an “Anklebot” for the ankle and lower leg. Robotic therapy machines can take victims “through as many as 1,500 repetitions within a typical one-hour session.” This type of therapy has revealed that patients can experience improvement even years after the occurrence of a stroke and that it can also cause significant pain reduction. Interactive Motion Technologies Inc. has commercialized the MIT prototypes. See the Wall Street Journal, August 21, 2005, p. B38. (11/2/05)

151. Asthma and Stress
Richard J. Davidson at the University of Wisconsin reveals, in a paper to be published in the September 13 issue of The Proceedings of the National Academy of Sciences, that a specific part of the brain activates wheezing in asthmatics who are under emotional stress. Subjects under stress demonstrated greater inflammation when inhaling allergens; brain scans suggest the stimulus may come from a specific part of the brain. See the New York Times, September 6, 1005, p. D8. (10/26/05)

150. The Brain Marches on
Two genes linked to brain size have evolved substantially over the last 60,000 years. The finding is discussed by Bruce T. Lahn of the University of Chicago in Science. Apparently the report on these genes (microcephalin and ASPM), known as alleles, also implies that their development has led to increased brain function, a claim generating much controversy. In fact, it is not entirely clear that the genes relate either to brain size or cognitive function, and there may be other genes related to size in certain populations lacking these particular genes. See the New York Times, September 9, 2005, p. A14. Also see www.uchospitals.edu/news/2004/20041229-brain-evolution.html. (10/19/05)

149. Seeing, Hearing, and Smelling the World
The Howard Hughes Medical Institute has cleverly put a simple little primer about the senses on its website (www.hhmi.org/senses). Other foundations and government agencies should take note, particularly those involved with neuroscience. This is an outstanding way to bring an out-of-the-way institution to the notice of the general public. (10/12/05)

148. Quick Read on Anti-Depressives
“Patients with depression usually suffer through four to six weeks on an anti-depressant before they can tell if it’s doing the job….” “Aspect Medical Systems has developed a brain-wave reader that, based on early tests, could determine the efficacy in a week.” Basically the software and sensor package measures changes in brain wave activity. See Biospectral Index technology at www.aspectmedical.com/products/why_bis.mspx. It is also perceived that the same technology may be useful in early stage detection of Alzheimer’s. See www.wired.com/news/medtech/0,1286,68650,00.html.

Meanwhile a firm in North Carolina has been promoting an easy-to-use technology to do a fast assessment (30 minutes) of brain function. CNS Vital Signs (www.cnsvs.com) can record data and provide interpretation to spot a number of brain complaints—concussion, Alzheimer’s, ADD Disorder, etc. It’s the brainchild of Dr. Tom Gualtieri (out of UNC-Chapel Hill) and Alan Boyd (out of Duke). The system is also being used to test sundry experimental therapies. “The concussion-testing industry leader is a Pittsburgh-based firm, ImPACT Applications Inc. See www.impacttest.com. See The Herald Sun, July 25, 2005, pp. A1-A2. See CNS publications for more explication at www.cnsvs.com/index.php?option=content&task=view&id=43&Itemid=60. (10/5/05)

147. International Brain Research Organization
IBRO was created back in 1960 as the world was becoming more integrated. It’s the network that weaves together global neuroscience. We are not entirely clear how well the Society for Neuroscience, created in 1970 to knit together neurologists in the States, meshes its activities with the global body. See http://apu.sfn.org. We are often on IBRO’s site when we want to look at the history of some neurological matter, such as early discoveries on receptors. See www.ibro.info/Pub_Main_Display.asp?Main_ID=11. (9/28/05)

146. Spices and Rotten Odors
Kensaku Mori and colleagues at the University of Tokyo have deciphered how spices cover up the smell of spoiled foods with neural help from the brain. Apparently both the rotten foods and the spices activate the same olfactory bulb—at least amongst the rats with which they experimented.

“Smell is intimately related to how human beings taste food but has long remained the most enigmatic of our senses. The average human nose can detect nearly 10,000 distinct scents, a feat that requires about 1,000 olfactory genes, or roughly 3 per cent of the human genome.”

To some extent, this discovery builds on the work of Richard Axel and Linda Buck who won a Nobel in 2004 for their work on smell. “In 1991 the two scientists jointly published a fundamental paper in which they described the large family of 1,000 olfactorygenes.” See www.foodnavigatorusa.com/productnews/news.asp?id=55559&k=scientists-unravel-spice. See also, “Detection and Masking of Spoiled Food Smells by Odor Maps in the Olfactory Bulb” at www.jneurosci.org/cgi/content/abstract/24/40/8690. (9/28/05)

145. Model of the Brain
“The first serious attempt to build a computer model of the brain has just begun” (The Economist, June 11, 2005, pp. 75-76). “IBM and the Ecole Polytechnique Fédérale de Lausanne (EPFL), in Switzerland, propose to start by replicating ‘in silico,’ as the jargon has it, one of the brain's building blocks.” “In a partnership announced on June 6th, the two organisations said they would be working together to build a simulation of a structure known as a neocortical column on a type of IBM supercomputer that is currently used to study the molecular functioning of genes. If that works, they plan to use future, more powerful computers to link such simulated columns together into something that mimics a brain.” Such columns together make up the intelligence of the brain. The EPFL’s task will be to model how the columns work, tapping into its Brain Mind Institute’s very ample data on how the neocortex functions. Charles Moore, IBM’s leader in the project, thinks in 15 years or so researchers will be able to emulate activity of the whole brain, rather than just a column. (9/21/05)

144. Doubly Tasty
“Researchers at Yale, the John B. Pierce Laboratory, and University of Dresden … got 11 volunteers to lie inside magnetic brain scanners with separate straws leading to the fronts of their noses … and the back (above the palate).” “Four odors were pumped in: butanol, farnesol … lavender and chocolate.” Only chocolate activated two different regions,” lighting up both pleasure-anticipation and food-reward neurons. “Prof. Dana Small of the Yale team said it suggested that the brain changed smell perceptions based on eating….” This relates to Dr. Small’s interest in food addictions. See the New York Times, August 23, 2005, p. D1. Also see http://webcenter.health.webmd.netscape.com/content/
article/110/109599.htm. Small, incidentally, has been looking at chocolate’s neuron outputs for a long while www.mcgill.ca/reporter/34/01/kaleidoscope. (9/21/05)

143. Crick and Consciousness
Crick’s last paper before his death in 2004 proposes to explain the neurological basis of consciousness. See The Economist, July 30, 2005, p. 71. Along with collaborator Christof Koch of the California Institute of Technology, he published his thesis in the Philosophical Transactions of the Royal Society. “The part of the brain” that caught their interest was “the claustrum, a thin sheet of grey matter that lies concealed beneath part of the cortex….” In effect, they found that all regions of the cortex are tied together to the claustrum, so that sundry messages could be tied together there in a unified whole—consciousness. Of course, now the thesis has to be proven. See more on this and Crick’s book The Astonishing Hypothesis at www.princeton.edu/~freshman/science/crick/
ast.html. (9/14/05)

142. Heart and Mind
The things you do to avoid heart disease and cancer also help keep your brain in high gear. Or so says Jane Brody in “What’s Good for the Heart is Good for the Head,” New York Times, March 22, 2005, p. D8. Her nostrums include eating right, staying socially connected, and keeping mentally active: all seem to inhibit the onset of dementia. “Dr. Laurel Coleman, a geriatric physician in Augusta, ME” suggests “an overlap between vascular disease in the brain and what happens to the brain in people who develop Alzheimer’s.” Risk factors for heart disease track those for dementia. (9/7/05)

141. Hot Wired: Double Brained
“Two brains are better than one,” and it takes at least two to keep men in motion, “one at the top of the spinal cord and the hidden but powerful grain in the gut known as the enteric nervous system” (“The Other Brain, the One with Butterflies, Also Deals with Many Woes,” The New York Times, August 23, 2005, pp. D5 and D8). The close interrelationship between the two suggests that brain mood can strongly affect digestion, and, in turn, the digestive process has side effects in brain process. Dr. Michael D. Gershon, author of The Second Brain and chairman of the department of anatomy and cell biology at Columbia, “coined the term ‘second brain’ in 1996.” See book abstract at www.hosppract.com/issues/1999/07/gershon.htm.

“The enteric nervous system was first described in 1921 by Dr. J.N. Langley, a British physician who believed that it was one of three parts … of the automatic nervous system, which controls involuntary behaviors like breathing and circulation.” Dr. Gershon revived his thinking and was widely mocked at first. To learn about Langley and receptors, see www.ibro.info/Pub_Main_Display.asp?Main_ID=277; also, see www.uni-graz.at/
~binder/science/historyofreceptors.html.

“It turns out that irritable bowel syndrome, like depression, is at least in part a function of changes in the serotonin system. In this case, it is too much serotonin rather than too little. … People with irritable bowel syndrome to not have enough SERT, so they wind up with too much serotonin floating around, causing diarrhea” (i.e., serotonin transporter). The presence of the “second brain” plays a significant part in a range of both digestive and psychological disorders.

The identification of “two brains” is rife with implications. Not only does it further our understanding of the direct collaboration between brain/neural activity and other bodily functions, but it also makes us begin to view distributed intelligence as a human trait—and a clear model of how computer systems should operate. Centralization in computerdom not only creates overload but it makes the system very vulnerable to attacks from outside agents. (8/31/05)

140. Déjà vu All Over Again
“[N]ew research on memory has opened a promising window on the phenomenon, providing both a possible explanations for the sensation and novel ways to create and measure it.” Dr. Alan Brown reviews the history of the ‘déjà vu’ field in The Déjà vu Experience: Essays in Cognitive Psychology. “Déjà vu appears to be more common when people are exhausted or stressed, conditions that are known to cloud short- and long-term memory….” The same conditions can give vent to “jamais vu,” the condition where familiar objects seem totally unfamiliar. Basically data unconsciously imprinted on the brain at some point can make a scene or experience seem very familiar at a later date, even if one has not really encountered the scene or experience before. For some of us, however, life is full of “presque vu,” a state when you get old enough and so full of extraneous data that everything seems like you may have seen it, almost seen it, but you are not quite sure.

139. Brain Dance
“All of which makes Mr. McGregor just the right person to tackle a dance inspired by ataxia, a neurological condition, often degenerative, that inhibits the body’s ability to coordinate movement. … ‘AtaXia’ is how Mr. McGregor styles the title of the hourlong production he has made for his Random Dance, a resident troupe at Sadlers Wells.” This grew out “of a six-month project between Mr. McGregor and a handful of neuroscientists from the department of experimental psychology at Cambridge University. “The choreography that resulted from these sessions rides waves of painful instability and ferocious dysfunction. The movement erupts in jerks and jolts…” (New York Times, July 17, 2005, p. AR30). To learn about Ataxia, see www.ataxia.org. For more on Sadler’s AtaXia, see www.sadlerswells.com/whats_on/2003_2004/random.asp. See press briefing to learn about Cambridge University staff involved with this project at www.sadlerswells.com/downloads/press/random_pr04.doc. (8/17/05)

138. A Drink a Day
A study shows that a drink or day (or less) helps prevent cognitive decline in women. Researchers from Harvard Medical School, Harvard Public Health, and Brigham and Women’s Hospital in Boston compared brain function in 11,000 nurses with assorted drinking regimes. Moderate drinkers fared better than heavy drinkers, or those who did not drink at all. Of course, it is not clear whether it was the drinking habits or some other habits of the moderate tipplers that led to a 20% lesser rate in the risk of decline. See the Wall Street Journal, January 20, 2005, p. D5. Also see “Effects of Modern Alcohol Consumption on Cognitive Function in Women” in the New England Journal of Medicine, January 20, 2005. The nurses had been tracked for a number of health issues since 1976, though this particular study ran from 1995-2001 with a follow-up two years later.

137. Memory Loss: Plastic Sieve
Neil MacLusky, a neurobiologist at Helen Hayes Hospital in New York City, along with Yale researchers, have published results from a study in the Environmetnal Health Perspectives, showing that BPA (key ingredient in polycarbonates plastics) “caused a significant decline in synapse formation in the hippocampus of female rats” (Yale Alumni Magazine, July/August 2005, p. 23). BPA plastics are widely used in a variety of drinking liquid containers, some 6 billion pounds of BPA produced annually. In other words, as a potent “inhibitor of estradiol,” a natural estrogen, BPA may significantly affect this memory center in the brain. For further details on the research, see http://ehp.niehs.nih.gov/docs/
2005/7633/abstract.html. (8/3/05)

136. Cool Customers
“People with certain kinds of brain damage may make better investment decisions.” This stems from research conducted at Carnegie Mellon, Stanford, and the University of Iowa appearing in Psychological Science. See “Investment Behavior and the Negative Side of Emotion” at www.blackwell-synergy.com/doi/abs/10.1111/j.0956-7976.2005.01553.x?
cookieSet=1. In this particular study, those who were brain damaged demonstrated an absence of fear, avoiding the risk averse behavior shown by the normal range of human beings (Wall Street Journal, July 21, 2005, pg. D1 and D2). This article expands on the growing body of theory in behavioral economics and neuroeconomics. Previously, in other risk and decision studies, psychologists have revealed that we tend to use different parts of our brain for near-term and long-term decisions, with emotion often coming more into play for matters involving some immediacy. Of course, we always knew that bankers, hedge fund operators, and actuaries had too much ice water in their veins. (8/3/05)

135. Brain Function and Brain Injury
This is an educational site, although it is obviously put together by a chap who is in the lawsuit business, where you can see illustrations of parts of the brain, quickly grasp their raison d’etre, and then see some highlights on what can go wrong with them. It is a Brain Site for dummies, helping a lay person more than the usual sort of guides of this sort. All this seems to have been put together by an aggressive attorney at something called the Brain Injury Law Office. You can learn more about Attorney Johnson and his sites at http://gordonjohnson.com. His glossary of terms is helpful to an initiate (www.waiting.
com/glossary.html). The main part of his site for those wanting to look at the brain and avoid the self promotion is www.waiting.com/waitingabouttbi.html. For more Brain-Made-Simple type information, see http://en.wikipedia.org/wiki/Brainstem. (7/27/05)

134. Mirror Neurons
“Empathy with others seems to be due to a type of brain cell called a mirror neuron” (The Economist, May 14, 2005, pp. 81-82). Dr. Christian Keysers, “who works at the University of Groningen, in the Netherlands, is one of a band of neurologists that is studying them.” The neurons in a limited percentage of ‘action-sensitive’ cells will get excited not only in situations that bring on disgust, fear, etc., but also in human beings or various animals who confront other members of their species experiencing the same sensation. We will feel fear, for instance, when we sense it in others, because of our empathy cells.

This further raises the question of where one can feel and anticipate what others are thinking about. Marco Iacoboni of the University of California’s Public Library of Science Biology and Leonardo Fogassi—and group members Giacomo Rizzolatti and Vittorio Gallese—of the University of Parma (Science) have explored this dimension in recent papers.

“The idea that a lack of mirror-neuron activity is at least part of the cause of autism has also received support recently.” Dr. Vilayayanur Ramachandran at the University of California San Diego detected a lack of mu-supression (mu-waves) in autistics (Cognitive Brain Research). Additionally Hugo Theoret at Harvard (Current Biology) found, in another study, that “the mirror neurons” in autistic volunteers “failed to respond to the hand actions of others in the same way that those of” controls did. (7/20/05)

133. Genetic Disease and High Intelligence
“A team of scientists at the University of Utah has proposed that the unusual pattern of genetic diseases seen among Jews of central or northern European origin, or Ashkenazim, is the result of natural selection for enhanced intellectual ability” (See the New York Times, June 3, 2005.) “Ashkenazic diseases like Tay-Sachs, they say, are a side effect of genes that promote intelligence.” The theory here is that, in the face of environmental crisis—i.e., Jews being restricted to occupations requiring high intelligence—mutations will select out for intelligence even if the same genes promote a raft of diseases. However, scientists in the Bay Area have an opposing view of how such diseases came about. (7/6/05)

Update: Ashkenazi Intelligence
For more on high intelligence of Ashkenazi, see “Natural Genius?,” The Economist, June 6, 2005, pp. 75-76. Gregory Cochran, along with Jason Hardy and Henry Harpending of the University of Utah, in an upcoming edition of the Journal of Biosocial Science, will go into theory of how natural selection led to higher intelligence. Askkenazi in the West (e.g., Freud) are known for making disproportionate contributions to intellectual life, and, as well, have been more subject than most to a raft of genetic diseases, but the two phenomena have not previously been related to each other by scientists. Jews historically have been driven into high intelligence occupations, and they have suffered from inbreeding. “Genes that promote intelligence in an individual when present as a single copy create disease when present as a double copy.” The theory is that extra cell growth is the driver of the genetic nerve diseases, but that the same growth promotes extra connections between brain cells and, hence, better brain output. (8/10/05)

132. Hormone Bolsters Trust
Scientists have long known that oxytocin, present in the body during childbirth and lactation, creates close feelings and mating among sundry mammals. Dr. Ernest Fehr, an economist at the University of Zurich and lead author on a paper from a research team there, thinks the hormone may help those who are pathologically distrustful. Using students, the researchers tested the inclination to make investments in an experimental game. Those inhaling oxytocin, on average, invested 17 percent more than those in a placebo group, and 45 percent of the inhalers invested all their money, as opposed to 21 percent in the control group. The practical implications in terms of future treatments is still unclear. See the New York Times, June 2, 2005; http://news.bbc.co.uk/2/hi/
health/4599299.stm; and “Oxytocin Increases Trust in Humans, Nature, June 2, 2005 (www.nature.com/nature/journal/v435/n7042/abs/nature03701.html). (7/6/05)

131. Companion Drug for Psychotherapy
“Recently … a tuberculosis drug with surprising effects on the brain has given psychiatrists hope…. The drug, D-cycloserine, an antibiotic, does nothing to soothe panic or calm nerves. Instead, it increases learning and memory, and may help people overcome their fears faster….” It is being used in studies on treating fear of heights as well as anorexia. “Studies have shown that a glutamate receptor in the amygdala, a part of the brain that governs emotion, plays a part in learning to adjust to threatening stimuli…. D-cycloserine is known to act on these receptors….” The drug, then, positively affects learning, not anxiety. See the New York Times, March 22, 2005, p. D8. (6/22/05)

130. The Wages of Schizophrenia
“He worked as a commercial diver, retrieving cement samples of Seatec International hundreds of feet beneath the often turbulent South China Sea. … Diagnosed with schizophrenia in 1987, MacPhee began taking entrepreneurial classes at Niagra College in Ontario, and developed a business plan for a magazine called Schizophrenia Digest. … He introduced the publication in Canada, editing from his father’s home in Ontario.” Having gotten up to 25,000 readers in Canada, he launched an edition in the U.S. in 2003, moving his base to Buffalo. “With a circulation of 50,000, the U.S. edition … brought in $500,000 in 2004 from subscription and ad sales, earning 94% of its ad revenues from pharmaceutical companies.” Now William McPhee has introduced bp Magazine for bipolar patients and their families, already at breakeven with a circulation of 50,000. See Fortune Small Business, May 2005, p. 50. See www.schizophreniadigest.com and www.bphope.com. (6/15/05)

129. More on Nerve Regeneration
Though all our biology tests say nerves cannot be regenerated, we keep finding examples to the contrary. Now the Schepens Eye Research Institute (www.theschepens.org) has used “genetic manipulation” to bring back optic nerves in laboratory mice. Next, it wants to see how much vision was restored as a consequence. See Business Week, March 21, 2005, p. 83. Also see www.theschepens.org/df_chenrelease.htm and the Journal of Cell Science, March 1, 2005. (6/1/05)

128. Train Hard and Then Don’t
“Professor Christina of the University of North Carolina, Greensboro, has one word for duffers who regularly go out to the driving range with a bucket of balls and hit driver after driver after driver. That word is … stop.” See “How to Practice,” Wall Street Journal, April 18, 2005, p. R3. Says Teresa Dall of North Carolina Agricultural & Technical University, Greensboro, “If you practice with periodic rests, you’ll have more success than if you practice for hours on end….” See Teresa K. Dail and Robert W. Christina, “Distribution of Practice and Metacognition in Learning and Long-Term Retention of a Discrete Motor Task,” Research Quarterly for Exercise and Sport, pp. 148-55. The brain apparently requires a consolidation period to fasten connections between neurons in the brain where the exercise pattern becomes implanted. (6/1/05)

127. Mental Health Portal
This portal of the National Institutes of Health provides numerous links to mental health resources as well as posting current bits of news in the mental health field (www.nlm.nih.
gov/medlineplus/mentalhealth.html). You do have to know what you are looking for, though, because it is just a collection, and it does not highlight more significant developments. (5/2505)

126. All About Autism
In our Letters section, we review the state of our knowledge about autism. Despite all the shouting, we still know extremely little about it. Further, we suspect the scientific community is not looking hard enough for the environmental factors that probably lie behind the surge in cases amongst newborns. This explosion has fueled recent public interest in autism, but, as well, curiosity about neurological complaints and the brain—medicine’s last frontier—has also brought attention to the disease. See www.global
province.com/letters/3-23-05.htm. (5/18/05)

Update: Defining Autism: A useful short review called “Autism Inflation” by Jerome Kagan and Robert Pozen will help the inquirer separate autism from a host of related afflictions (Forbes, June 6, 2005). The authors suggest using rather concrete biological (instead of behavioral) criteria for autism. “A larger brain, as revealed in MRI scans, is one sign.” Second, “some autistics do not show the expected wave form when they hear a change in a spoken syllable (e.g., from ‘pa’ to ‘ba’). This suggests that there is something deficient in language perception.” And third, an examination of the cerebrospinal fluid may reveal abnormally high concentrations of either gangliosides or serotonin. The authors think that an effort to pinpoint the biological basis of autism symptoms may lead to new and differentiated treatments for this malady. (7/13/05)

125. The Many Fathers of Neoroscience
Just like good ideas, and the earthly children of the gods, neuroscience can claim a host of fathers, with nobody having an absolute claim on its paternity. We will cast our votes for a couple of fellows here. First, Sir Charles Scott Sherrington set forth “Sherrington’s Law,” “which states that for every neural activation of a muscle, there is a corresponding inhibition of the opposing muscle. Sherrington is also known for the study of the synapse, a word which he coined for the then-theoretical connecting point of the neurons” (Wikipedia). He did considerable work with cholera, tetanus, and diphtheria, was a philosopher, and a poet as well. Among his works are Integrative Action of the Nervous System, The Brain and its Mechanism, Man on His Nature, and The Reflex Activity of the Spinal Cord. He won the Nobel Prize in 1932 (http://nobelprize.org/medicine/laureates/1932/
sherrington-bio.html).

But we could easily choose Santiago Ramon y Cajal. He is known for proving that neurons, or nerve cells, are the fundamental elements of the nervous system. Starting off in artistic directions, he eventually made his way into science. Using and improving on a silver nitrate staining technique from the Italian Golgi, he did conclusive studies in Barcelona that led to his definitive proof of neuron theory in 1889. (Oddly enough, he had previously been in the opposing camp of thought—the single “network” theory.) Cajal and Golgi shared the Nobel Prize in 1906. Like Sherrington, he made a multitude of contributions to the field. See http://nobelprize.org/medicine/laureates/1906.

It is impressive that Sherrington and Cajal made so many discoveries in neuroscience but that their interests and contributions ranged well beyond neuroscience. Generalists seem to outdo specialists at every turn. (5/11/05)

124. Sleep Without Drugs
“Behavorial Therapies Teach Insomniacs to Snooze Without Relying on Drugs. … An estimated 10% to 15% of the population suffers from chronic insomnia, according to the National Institutes of Health. … One of the most promising treatments is a form of talk therapy used in many areas of mental health known as cognitive behavioral therapy, or CBT.” There is also a new drug from Sepracor called Lunesta, a sleeping pill approved for long-term use. See the Wall Street Journal, March 29, 2005, pp. D1 and D3. (5/4/05)

123. Memory Book
“Benny Cooperman, the invention of the Canadian mystery writer Howard Engel, has fallen victim to a rare brain disorder, alexia sine agraphia” in the latest adventure called “Memory Book.” “Benny’s failed memory, his near inability to read and his unfortunate new proclivity to brush his teeth with shaving cream” cannot stop him from finding the chap who had bludgeoned him and murdered another. A victim of a stroke, Engel himself has “alexia sine agraphia” described by Oliver Sachs as “‘pure word madness’ resulting from an interruption of signals between the parts of the brain that receive visual data from the eye and those that decipher language.” See the New York Times, April 4, 2005, pp. B1 and B6.

Increasingly, mental disability is becoming cultural grist for writers, dramatists, and others in the arts. Tony Shalhoub, the taxi driver in the show about Nantucket called Wings, which is now in rerun, has starred for several seasons in a very successful TV series featuring an insightful detective named Monk with obsessive compulsive behavior. See www.usa
network.com/series/monk. Neurological disorders are slowly moving to center stage in our society. (4/27/05)

122. Rewiring the Body
Business Week (March 7, 2005, pp. 74-82) did an extensive survey on neurostimulation called “Rewiring the Body.” High-tech implants acting on the nervous system are shown to have impact on epilepsy, depression, bladder incontinence, chronic leg pain, deafness, migraine headaches, post-stroke paralysis, Parkinson’s etc. Some companies mentioned are Boston Scientific, Johnson and Johnson (Guidant), Medtronic, Advanced Neuromodulation Systems, Cyberonics, Neuropace, Northstar Neuroscience, and Transneuronix. Some project that “sales of noncardiac pulse generators should balloon from $1.6 billion today to $10 billion in 10 to 15 years….” Scientists do not know the specifics of how the implantables work on the nervous system—only that they are effective. (4/27/05)

121. Viruses and Mental Illness
See our entry on Pandas, which tries to link strep and OCD. Dr. Alan Brown at Columbia University is probing the connections between flu in pregnancy and subsequent schizophrenic offspring. Dr. Ian Lipkin and Norwegian researchers are looking at the relationship between viruses and autism, as well as looking for other autism causes. Dr. Mae Sobol at Children’s Hospital in Omaha, Nebraska is trying to see if strep also is a precipitant of anorexia nervosa. See “Researchers Probe for Viral Link to Mental Illness,” Wall Street Journal, March 29, 2005, p. D4. (4/20/05)

120. Sundry Tic Suppression Efforts-Tourette’s
Jane Brody of the New York Times (January 18, 2005, p. D7) reports on various efforts to contain the tics associated with Tourette’s. One is “deep brain stimulation,” with electrodes implanted in the brain being tied to a pacemaker in the chest. This technique has also been used with Parkinson’s. The use of botox (botulinum toxin) has temporarily frozen muscle groups associated with tics, the effect lasting several months. Drugs for this application include “alpha-adrenergic agonists like guanfacine (Tenex), neuroleptics like haloperidol (Haldol) and benzodiazepine clonazepam (Klonopin).” Perhaps 1 in 2000, maybe 1 in a 100, children have tic disorders. For more on Tourette’s, see the Tourette Syndrome Association at www.tsa-usa.org. (4/20/05)

Update: Electrodes for Depression
Deep-brain stimulation is also being used in other settings. Toronto Western Hospital in Canada has a pilot study going. The work is based on the discovery by Dr. Helen Mayberg “that an area of the brain called the subgenual cingulated is overactive in patients with depression.” This technique dampens neural activity. It also stimulated activity in the “frontal cortex, the hypothalamus and the brainstem. Of the 121 million people worldwide taken to be depression afflicted, a quarter, give or take, do not respond to any treatment, the electrode and battery implant being a godsend. See The Economist, March 5, 2005, pp.78-79. Also see Neuron, www.neuron.org/content/article/abstract?uid=
PIIS089662730500156X&highlight=helen%20mayberg. (6/8/05)

119. Optimism Pays
Dutch scientists tracked 941 generally healthy people for 9 years, and found that those who described themselves as highly optimistic “had a 55% lower risk of death from all causes and a 23% lower risk of death from heart disease that those who were highly pessimistic.” See Business Week, November 15, 2004, p. 91. These cheery results appeared in the November 2004 Archives of GeneralPsychiatry at http://archpsyc.
amaassn.org/cgi/content/abstract/61/11/1126. cThis AMA publication merits continuous examination, particularly by those looking for a chemical basis of behavior. See http://archpsyc.ama-assn.org/about_current.dtl. (4/13/05)

118. Pandas
“Two new studies are examining a potential link between the bacteria that cause strep throat and the onset of obsessive-compulsive behavior in some children.” See The Wall Street Journal, November 2, 2004, p. D7. “Researchers believe that Pandas (pediatric autoimmune neuro disorders linked to strep) is one of several conditions resulting from antibodies attacking the basal ganglia,” all resulting from untreated strep. In some children, OCD waxes and wanes with the onset or departure of strep infections. The term Pandas was coined by Dr. Susan Swedo, an NIMH researcher, who is probing the connection between OCD and strep. (4/13/05)

Update: Strep and ODD. We have previously noted that there is a small but vocal fraternity that believes there is a direct connection between physical illnesses of various sorts and such disorders as autism and obsessive compulsive disorder in items 121 and in the original entry above. We ourselves believe there is much to be gained by much more research on the part bacterial and viral infections and environmental influences play in a host of conditions. This line of thinking is slipping into the mainstream with the New York Times Magazine (May 22, 2005, pp. 65-69), which in a further explication of the Pandas theory relating to rapid-onset O.C.D., asks “Can You Catch Obsessive-Compulsive Disorder.” Judith Rapoport, a child psychiatrist who authored The Boy Who Couldn’t Stop Washing, buys into the strep bacteria argument, and a particular advocate is Susan E. Swedo at the National Institute of Mental Health whom we mentioned previously. Roger Kurlan at the University of Rochester and Edward L. Kaplan at the University of Minnesota don’t buy into the theory, tending to believe, rather, that any kind of infection tends to accentuate a pre-existing OCD condition. In general researchers are pretty well defended against theses that promote infectious or chemical bases of OCD and other conditions. (6/29/05)

117. NBC on Autism
Bob Wright, chief cook and bottle washer at General Electric’s broadcasting operations, has just orchestrated a series of programs on autism, all stemming from his and his wife’s discovery that they had an autistic grandchild. The programs ran on the Today Show and on CNBC during the week of February 21. So far the biggest impetus for a broader national effort on autism has come from grassroots initiatives on the part of affected parents and relatives. Learn more about the autism specials in these webpages: www.msnbc.
msn.com/id/6844737; www.msnbc.msn.com/id/6899179 (resources on autism); www.msnbc.msn.com/id/6994474/site/newsweek; www.msnbc.msn.com/id/7024923 (Bob Wright on autism). (4/5/05)

116. Mercury, Alzheimer’s, and Autism
We have previously pointed out that not enough attention has been paid to the linkage between metals and Alzheimer’s, though Dr. Ashley Bush of Australia has pursued that line of investigation. (See more on Bush on Brain Stem.) We should note as well that sundry investigators and lay individuals are quite convinced of the relationship of mercury ingestion and Alzheimer’s and autism. For mercury and Alzheimer’s, see “Relation Between Mercury and Alzheimer’s Disease?,” which casts doubt on any such relationship (www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=119239
17&dopt=Abstract). A fairly reasonable article on the debate can be found in the Seattle Times at www.mult-sclerosis.org/news/May2002/TheMercuryDebate.html. Usually those who connect up autism with mercury believe the problem arises in vaccinations, especially spray type vaccines (www0.bbc.co.uk/radio4/news/fileon4/transcripts/
20030624_autism.pdf).

Mainstream thinking generally is scornful of any linkage between mercury, metals, etc. and brain degeneration, and, indeed, no conclusive evidence has been offered. By and large, most research is pursuing a genetic basis for both conditions, and yet that does not seem to offer a good enough explanation of the rising incidence of these diseases. The chemical basis of many neurological conditions probably deserves greater funding and focus. Unfortunately neurological investigators generally lack any real grounding in biochemistry. For more on the connection between vaccines and autism, see Stitch in Time.

Despite the doubts running through the scientific community about mercury’s health impact, troubling studies continue to emerge that say it has a definite effect on the brain and huge costs for our economy. On this argument, see “Public Health and Economic Consequences of Methymercury Toxicity to the Developing Brain,” http://ehp.niehs.nih.gov/docs/2005/7743/abstract.html. (3/30/05)

115. Looking for One's Memory
Cathryn Jacobson Ramin’s “In Search of Lost Time,” New York Times Magazine, December 5, 2004, pp. 76-81 deals with the author’s memory loss and her efforts to deal with it through a memory regimen and more. In her thirties she began to find that her mind was just not clicking in the same way. Just before she turned 45, she realized that she had forgotten the title of a film (plus more) that she had just seen with her husband. She went to see Dr. Gary Small, director of UCLA’s Center on Aging and author of The Memory Bible. Enrolling in a study he was doing, she found out that she had average memory impairment for her age. Apparently brain cholesterol to promote myelin growth accelerates from youth, but reaches a point in one’s thirties where it produces a protein toxic for myelin and other membranes in the brain. After tests for deterioration and various attempts to sharpen the memory, she discovered in fact that her loss was not so much due to brain degeneration but to brain damage suffered much earlier in life. Talking with her brother, she uncovered a number of early whacks she took on the head that probably accounted for her later impairment.

It is more common than is realized for early concussive effects to show up in later brain impairment, so, signally, much breakdown we attribute to age is actually due to events that occurred much earlier in life. Wear your helmets. Adderall immediately brought new focus to her brain, but found that it simultaneously dulled some aspects of life, taking away some of the mental twists and turns she commonly enjoyed. (3/23/05)

114. Choline
Choline, a vitamin B-like compound, is found to be a critical ingredient in embryonic brain development. In high demand by the fetus during pregnancy, the mother may not have adequate supplies during that stage. To this end, eggs, meat, milk are critical diet elements for pregnant women. It helps form a neurotransmitter as well as aiding in critical brain cell subdivision. Choline, along with folic acid, therefore, plays a key role in avoiding birth defects. See The Wall Street Journal, October 26, 2004, p. D3. (3/16/05)

113. Mind Wide Open
Steven Johnson, making himself the subject of examination, looks into the operations of his own brain and lays his discoveries out in Mind Wide Open: Your Brain and the Neuroscience of Everyday Life. “With the help of a new neurofeedback device called Attention Trainer, he learns how to control his own brainwaves (this is now used with Attention Deficit Disorder children as a way to get their brains to focus as a substitute for Ritalin).” He learns that the supercomputer model is probably not a good way of looking at the brain, as the psyche turns out to be a battleground of competing forces, rather than a harmoniously unified system. (From a review in The Guardian, May 15, 2004). (3/16/05)

112. Arizona Pursues Alzheimer’s Genes
Numerous researchers are in the hunt for such genes. One joint study involves Kronos Science Laboratories (www.kronoslaboratory.com) and the non-profit Translational Genomics Research Institute (www.tgen.org). Kronos hopes to develop a blood test to screen for Alzheimer’s risk factors that it wants to put on the market in 3 years. Scientists have already identified the apoE gene as one risk factor, but it only accounts for 30% of total risk. The joint study will examine blood and brain tissue from 1,000 known to have had the disease, comparing results to 1,000 who have not had disease. See The Wall Street Journal, February 24, 2005, p. D4. (3/9/05)

111. Autism: Focus on Brain Growth and Inflammation
At an autism summit held in Malibu under auspices of Cure Autism Now Foundation, sundry neuroscientists claimed a more coherent picture of autism development is now emerging. “In autism, subtle brain abnormalities are present from birth. Infants and toddlers move their bodies differently. From 6 months to 2 years, their heads grow much too fast. Parts of their brain have too many connections, while other parts are underconnected…. Moreover, their brains show signs of chronic inflammation in the same areas that show excessive growth. The inflammation appears to last a lifetime.” See The New York Times, February 8, 2005, p. D6. After 9 months, the white matter “goes haywire. By 2 years, excessive white matter is found in the frontal lobes, the cerebellum and association areas, where higher-order processing occurs.” The right side of the brain is particularly affected, and the two hemispheres are poorly connected. In large part, the circuitry is just not working right, with local areas over-connected, and long-range networks under-connected. (3/9/05)

110. Autism and Allergies
Kaiser Permanente research looking at data on 88,000 children show mothers suffering from asthma, allergies, or certain types of skin disease (notably psoriasis) have a higher risk of giving birth to an autistic child. The study, published in the Archives of Pediatrics and Adolescent Medicine, wonders if there is common genetic basis for allergy and autism which would explain the linkage. Or if the mother’s system may produce more cytokines, leading to inflammation and fetal brain damage. See The Wall Street Journal, February 8, 2005, p. D6. (3/2/05)

109. Rockin’ and Rollin’
“Project Maia, based in Martigny, Switzerland, has unveiled technology that allows people to guide a tiny robot wheelchair by thought alone, through a cap studded with electrodes that read brainwaves.” “Human thoughts create impulses in specific areas of the brain…. Project Maia’s device utilizes electroencephalograms to quickly convert those signals into a corresponding action in the wheelchair.” See Business Week, November 15, 2004, p. 91 and www.loria.fr/equipes/maia/rapports/ra2003.pdf. Also see IDIAP Research Institute at www.idiap.ch. (2/15/05)

108. Brain Re-training
Neuroscience Solutions is designing videogame-like software to help seniors build new brain synapses, a possible dike against Alzheimer’s and other age-related brain degeneration. See www.neurso.com. In summer 2005, it is expected to sell the first of five versions. There will be a professional iteration for doctors to administer ($1,000 or so) and a do-it-yourself pack at about $500. Reputedly it will also publish research documenting results in early 2005. See Fortune Small Business, Dec.-Jan. 2004-2005, p. 68. (1/26/05)

107. Amusia, Aphasia, Amygdala
James Gorman writes amusingly in The New York Times about the 3 “A’s” above without reaching any particular conclusion (January 11, 2005, p. D5). First, he finds himself infatuated with the amygdala, not because it is the seat of fear and emotion named after the Greek word for almond, but simply because he likes the ring of the word. He is taken, too, with the idea of earworms which are tunes that lodge themselves in our heads and play over and over again: he wonders if the word amygdala, tucked so firmly in his circuitry like a computer cookie, is an earworm equivalent for him in the world of words.

“Damage to the brain can interfere with spoken language—aphasia. But it can also harm the ability to hear and produce melody.” This is amusia. He wonders if they both do not stem from lesions in some common part of the brain. Yet you can have one complaint without the other—good in speech and horrible in music, good in music and defective in speech. “Lesions to the brain can cause terrifying losses, like the one described in the Journal of Neurology, Neurosurgery & Psychiatry in 2002 about an amateur musician who suffered aphasia that receded, leaving speech intact.” However, “Music made him feel uncomfortable.”

The amygdala has nothing to do with aphasia or amusia, but his very fixation with the word reminds him humorously of the tangled web many lesion sufferers weave with words and music. (1/26/05)

106. De-plaquing
When amyloid beta peptide plaque was removed from the brains of mice, nerve cells lost their swelling and regained their normal structure. This suggests that amyloid plaque is at least associated with Alzheimer’s brain malfunction, though it does not prove that the plaque is in fact the cause of the disease—a continuing matter of debate. See USA Today, 20 January 2005, Associated Press Dispatch, commenting on research of Dave Holtzman and Robert Brendza at Washington University in St. Louis (www.usatoday.
com/news/health/2005-01-20-plaque-clearing_x.htm.) “In just three days, there were 20 to 25 per cent reductions in the number or size of the existing swellings,” Brendza said. Very active in Alzheimer’s and an award winner for his research, Holtzman heads up neurology at Washington University. See www.alzforum.org/com/res/detail.asp
?id={87123187-533C-41A7-A50B-8BB392B782CF}. (1/26/05)

105. Addictive Foods
Dr. Gene-Jack Wang is using positron-emissions tomography to study over-eaters. His thesis: “Overeaters consume more food than is good for them to get a kick that dopamine delivers – the same reason that cokeheads snort cocaine.” See www.bnl.gov/medical/
Personel/Wang/Wang.htm. “Overeaters have a … shortage of dopamine receptors, but researchers don’t know if that is an inherited difference, one developed by overeating or a combination of the two.”

There is sundry research afoot to see if various drugs can turn off brain centers that support appetite. Lawyers are following the research, aware that the trail of data may create culpability for food companies if certain ingredients like fat and sugar are found to stimulate neural processes that lead to excessive appetite. Forbes, January 10, 2005, pp. 63-67. Philosophically, this investigation is simply one more chapter in the unwritten book about our “addictive society.” Working on aspects of this problem are Ann Kelley of the University of Wisconsin, Adam Drewnowski at the University of Washington, and Jeffrey Friedman at Rockefeller University. (1/26/05)

104. Faceless in the Crowd
“To people with prosopagnosia, the instant someone leaves their sight the memory of that person’s face is blank” or, at best, a muddle. “The effects of prosopagnosia can be so bad that people with severe cases cannot recognise their own parents or children.” A paper by Brad Duchaine and Ken Nakayama of Harvard University which will be published in the Journal of Cognitive Neuroscience makes clear that people who have the ailment can remember other differentiating features of people, even if faces are a blur to them. “That confirms the idea that faces are handled differently in the brain from other objects.” Another study in Neuron by Galit Yovel and Nancy Kanwisher of MIT showed heightened activity in the fusiform face area (FFA) of the brain when subjects were looking at faces, suggesting that it specifically is where people handle facial recognition. See The Economist, December 4, 2004, pp. 81-82.

103. The Dictionary of Disorder
Alix Spiegel’s “The Dictionary of Disorder,” New Yorker, January 3, 2005, pp. 56-63 is most interesting for those of us interested in the evolution of psychiatry. The lingo of this trade has always and still is subject to such imprecision that different practitioners commonly, throughout the 20^th century, have rendered different diagnoses at the same time when looking at one patient, or when looking at a group of patients with roughly the same symptoms. The DSM (Diagnostic and Statistical Manual of Mental Disorders) came along in 1952, but only when Robert Spitzer out of Columbia took over as its director did this volume achieve any rigor or wide respect. Of course, as the DSM achieved wide sales and authority due to his work, members of the trade jealously horned into the act and eventually ejected him from the driver’s seat, putting a more pliable sort in the chair. Nonetheless, Spitzer by what he wrote and by what he rejected deeply shaped the psychiatric field during the latter half of the 20th century. When he took on the DSM, nobody wanted the job. Today it’s a highly desired job, and descriptive psychiatry is perceived as an important element in the psychiatric universe, and it is a step that will bring psychiatry somewhat closer to the goal of becoming modestly scientific. Spitzer brought a little commonsense to disease nomenclature, which is an achievement in itself when you consider that several of the chieftains in this trade are impractical, fuzzy headed, and even a little mad.

102. Neurons at the Wheel
Rat neurons on top of a multi-electrode array have been hooked up to a desktop computer and a flight simulator to control vertical and horizontal movements of the simulated aircraft. Thomas DeMarse, professor of biomedical engineering at the University of Florida, is using this primitive “brain” project to see how neurons communicate with one another with a view to devising novel computer architectures. This is an outgrowth of work done on the Animat project with Steve Potter (www.neuro.gatech.edu/groups/
potter/potter.html) at Georgia Tech where rat neurons were used to control virtual objects and robots. See www.wired.com/news/medtech/0%2C1286%2C65438%2C00.html. For more on Animat, see www.its.caltech.edu/~jsnc/2000/JSNC2000/abstracts/
tdanimat.html.

101. Recharging the Brain
“At least 40 potential cognitive enhancers are currently in clinical development, says Harry Tracy, publisher of NeuroInvestment….” There is naturally some question as to what such drugs can do for the seriously impaired, but there is at least the thought that those with slowing brains can get a tune up. A leading company in the field is Memory Phamaceuticals, headed by Nobel prize winner Eric Kandel, who has long studied memory and learning with the help of Aplysia, a big sea slug whose neurons are easy to study. His company, as well as Helicon Therapeutics, is working on compounds that makes neural pathways work better. Saegis Pharmaceuticals is puttering with compounds that act on different aspects of neural chemistry, and, indeed, there are doubters about the relevance of the CREB protein that forms the basis of Kandel’s work. Cephalon’s modafinil, a drug to raise alertness, achieved $290 million in sales in 2003, and its off-label uses plus a potential application for attention deficit will probably continue to stimulate sales growth. See “Supercharging the Brain,” Economist Technology Quarterly, September 18, 2004, pp. 27-29.

100. Depression Gene
Dr. Marc Caron and Dr. Xiaodong Zhang, biologists at Duke’s Medical Center, just published in Neuron findings, based on a limited sample, that link “a mutation of a single gene” that substantially reduced production of serontin by the brain cells of those where it is found. High levels of serontin lead to better moods, and often, lower production is associated with sour moods and depression.” See the New York Times, December 10, 2004, p. A27. However, we always urge researchers to carefully scrutinize results coming out of the Duke facility. If the results hold up, this gene (TPH2) difficulty may explain why certain patients with depression symptoms do not respond to drug treatment, since there seems to be a correlation between those with this particular defect and those for whom serontin-inducers are ineffective. See also the Wall Street Journal, December 10, 2004, p. B3.

99. Brain Scans Gone Crazy
We have already cited numerous studies based on brain scans—functional magnetic-resonance imaging. FMRI has become every neurologist’s plaything. Just back from a meeting of the Society for Neuroscience in San Diego, The Economist (October 30, 2004, p. 83) concludes that this technology “has revolutionized the study of the human brain.” New scan studies are popping up about practically everything. Princeton University’s Jonathan Cohen has come to grips with why human beings make different choices when presented with the same options, finding that those seeking immediate gratification exhibit high activity in the limbic/emotional part of the brain, and those accepting delay for higher rewards use “thinking” sections such as the prefrontal cortex. Tubingen’s Klaus Mathiak demonstrated that video game players tapped into their anterior cingulate cortexes when dealing with violent game encounters, brain activity that parallels what happens in real aggression situations.

Meanwhile, Drs. Joshua Freedman and Marco Iacoboni of UCLA have been looking at the brains of Democrats and Republicans to understand how they react to the two presidential candidates. “When viewing their favorite candidates, all showed increased activity in the region implicated in empathy. And when viewing the opposition, all had increased blood flow in the region where humans consciously assert control over emotions….” Their scanning also indicated some differences between the brain activity of Democrats and Republicans (Associated Press, 28 October 2004).

98. The Well-Wired Monk
Sharon Begley of the Wall Street Journal (November 5, 1004, p. B1) reports that brain scans (employing functional magnetic resonance imaging) reveal that monks with a history of intense meditation (over 10,000 hours) show much higher rates of high-frequency brain activity. “Activity in the left prefrontal cortex (the seat of positive emotions such as happiness) swamped activity in the right prefrontal (site of negative emotions and anxiety).” A study on this is to be published in the Proceedings of the National Academy of Sciences. Surely this will lead to bumper stickers urging us to “Meditate, Don’t Medicate.”

97. The Biology of Autism
Dr. Marcel Just of Carnegie Mellon and Dr. Nancy Minshew of the University of Pittsburgh, using functional, magnetic-resonance imaging (fMRI), traced operational differences in Broca’s and Wernicke’s areas (which deal with language) of the brains of autists as compared with non-autists. Just posits that there is less connectivity in the brains of autistic persons. See The Economist, August 7, 2004, p. 66 and the publication Brain. Also see http://itre.cis.upenn.edu/~myl/languagelog/archives/001292.html for more on this topic. The article cited is in the August issue of Brain (see www.brain.oupjournals.
org).

96. The Stylish Neurologist
The very well decked out Dr. Teena Shetty is pursuing a fellowship in neuromuscular disease at Mass General and Brigham and Women’s Hospitals in Boston. Clearly the sight of her puts more bounce in the step of patient and doctor alike. See The New York Times, Style Section, September 12, 2004, p. St 3. This reminds us that we met a lady doctor on staff at one Boston institution who asked our opinion of a new suit she was buying at Brooks on Newbury to get ready for a major presentation to her colleagues (www.newbury-st.com/asp/merdtl.asp?id=406). Au couture scholarship. When you go up to visit the medicine men in Boston, we recommend a trip along Newbury Street in any event—to get away from it all. Chances are you will meet some doctors of all trades similarly escaping from the studied seriousness that afflicts Boston. All the usual suspects (Armani, Burberrys) are nearby plus some originals (Louis Boston on Berkeley). See www.newbury-st.com. Teena likes Newbury Street and Chestnut Hill Mall, which, we suppose, gives you a map of this neurologist’s brain.

95. Valuable Aspect
Aspect Medical Systems (ASMP), a leader in brain monitoring technology, may be up for grabs (see www.aspectms.com). Boston Scientific, big in the drug-coated stent business and in other aspects of cardiology, has already paid up for a chunk of the company. Boston Scientific and others are recognizing that brain disease and development is medicine’s last frontier, still an open growth opportunity as other medical sectors become competitive and crowded. See Business Week, October 2, 2004, p. 123. BIS, its monitoring system, helps manage patient’s consciousness during surgery and control anesthesia. It’s also trying to extend this system into treating psychiatric and neurodegenerative diseases. See www.aspectms.com.

94. How to Build a Brain
KurweilAI.net is the kind of website that simply drives us crazy. It’s a challenge to find anything on it, it has an excess of unnecessary design, and it consumes a heap of time before you get anywhere on it. That said, it’s worth wandering around and thinking about some of the incidental insights raised in a few of the articles. Loosely the whole site deals with artificial intelligence and various efforts to look at intelligence and to simulate consciousness. We particularly enjoyed the section on How to Build a Brain. An article about Richard Feynman’s contribution to one project shows he could achieve sparkling insights while others got caught in the weeds—and how creative scientists were organized at Los Alamos (www.kurzweilai.net/meme/frame.html?m=3). Or see how Steve Kirsch sees “brain fingerprinting” to be the ultimate weapon against terrorism (www.kurzweilai
.net/meme/frame.html?main=/articles/art0331.html). Read “Green or Gray,” the debate as to whether this will be the century of biotechnology or nanotechnology (www.kurzweilai.
net/meme/frame.html?main=/articles/art0331.html). Probably the way to survey the articles here is to look at the author listing at www.kurzweilai.net/bios/frame.html.

93. Dr. Chudler’s Brain Jokes
Dr. Chudler has taken several days off from brain research and other weighty endeavors to construct a page of jokes and other amusing stuff for kids. You will want to learn, for instance, what the right hemisphere of the brain said to the left when they could not agree on anything. Answer: “Let’s split.” Or where neurologists stuck in Boston go for a nearby vacation. Answer: “Braintree.” You will find 71 of these morsels on his webpage at http://faculty.washington.edu/chudler/jokes.html. To look into Eric Chudler’s research interests, see http://faculty.washington.edu/chudler/research.html.

92. Brain Prosthetics Advance
Neuroscientists at Caltech have made progress in experiments with monkeys, reaching beyond the motor cortex to the ‘parietal reach region.” That is, they are now scanning for thoughts or intentions to perform some action, rather than the detailed instructions that are generated to translate thought into action. See The Wall Street Journal, July 9, 2004, p. B1. Also “Cyberkinetics … in Foxborough Massachusetts” now has FDA approval to test a device called BrainGate (based on the work of John Donoghue at Brown University), which uses “implanted electrodes to translate signals from patients’ premotor cortexes into movements of a wireless pen on a digital keypad.”

91. Autism Website for Parents
One of our readers, the parent of an autistic child, has found two websites quite useful. First, the Autism Research Institute at www.autism.com/ari. And then Arizona State’s Autism/Asperger’s Research Program at www.eas.asu.edu/~autism, which suggests a rapid increase in incidence of the disease, possibly arising from genetic complexities.

90. Stem Cells For Alzheimer’s?
There’s mixed evidence that stems cells that can morph into neurons may be helpful for Alzheimer’s, Parkinson’s, Huntington’s disease, and spinal cord injury. Trials in rats, as well as come in human beings, have sometimes resulted in improvement. But the thinking is that we are yet 10 years away from simple circuit repairs—and 30 or so for Alzheimer’s. Professor Jeffrey Macklis at Harvard Medical School and Kiminobu Sugaya at the Unversity of Central Florida report limited successes at memory repair, etc. in rats and mice. See The Wall Street Journal, “Harnessing Stem Cells to Battle Alzheimer’s Is at Least Worth a Try,” July 2, 2004, p. B1.

89. Mind Marketing Management
The Economist Technology Quarterly (June 12, 2004, p. 12), an insert in The Economist, does an acceptable job of reviewing the current estate of neuro-marketing. We had previously commented on this in Item 66. To be sure, this is still a primitive field in which you have to be chary of the practitioners: it’s a game for the big consumer marketers such as P & G and Coca Cola, which have excess bucks to throw against the wall. Apparently Gerry Zaltman of Harvard got the neuro-ball rolling towards the end of the 20th century. Brighthouse Neurostrategies Group in Atlanta ran with it, looking at consumer preferences in conjunction with Emory University, but not dealing with specific products or advertising tactics. Daimler in Germany, Ford of Europe, Lierberman Research Worldwide in Los Angeles along with Caltech, and FKF (a political advisor) have all experimented with it, even to the point of testing specific ad approaches.

88. Temple’s World (Autism)
Rigid thinking and behavior; poor eye contact and obliviousness to social cues; a fixation on subjects and objects; hypersensitivity to sound and a tendency to anxiety; lack of emotion and common sense; late speech and echolalia: these are some of the telltale signs of an autistic child. The surging incidence of autism in America baffles the medical establishment. The causes are not well understood. Bruno Bettelheim’s theories about the psychological underpinnings of autism have been discarded. The condition stems from neurological abnormalities in the brain, which show up as cognitive and sensory disorders in a child. Something as basic as forced eye contact or the presence of strangers can trigger sensory overload. Auditory processing deficiencies mean the child may have trouble understanding even the purpose of speech.

Thinking in Pictures, by Temple Grandin (Vintage, 1996), is an autism classic. This delightful, insightful book does not provide all the answers to the mysteries of autism. Rather, the autistic author illuminates the mind, behavior and outlook on the world of the autistic. As Dr. Oliver Sacks writes in his elegant foreword: “We get a glimpse of her total bewilderment about other people’s minds, her inability to decipher their expressions and intentions, along with her determination to study them, study us, our alien behaviors, scientifically and systematically, as if (in her own words) she were “an anthropologist on Mars.”

Grandin is a world-famous expert on cattle psychology and behavior. A third of all cattle and hogs in the U.S. are handled by equipment she designed. The key, she explains, is her ability to think in pictures (not words), and her ability to put herself into cattle’s heads and look at the world through their eyes. Grandin deploys superior visual spatial skills, which she describes as resembling a video library or computer graphics program in her imagination and memory (many autistics have heightened visual abilities for reasons not well understood). “A great deal of my success in working with animals,” she explains, “comes from the simple fact that I see all kinds of connections between their behavior and certain autistic behaviors … both cattle and people with autism can become very set in their habits. A change in a daily routine can cause an autistic person to have a tantrum…I have often observed that the senses of some people with autism resemble the acute senses of animals.” (Reviewed by Andrew Tanzer.)

The book provides many insights into animal behavior. Indeed, Grandin seems more comfortable with her animal friends than with homo sapiens. “Like most autistics, I don’t experience the feelings attached to personal relationships…. Teaching a person with autism the social graces is like coaching an actor for a play. Every step has to be planned…. Since I don’t have any social intuition, I rely on pure logic, like an expert computer program, to guide my behavior…. When people are responding to each other with emotion rather than intellect, I need to have long discussions with friends who can serve as translators.”

One of the Thinking in Pictures’ strangest and most fascinating chapters is “Einstein’s Second Cousin.” Grandin notes that the parents and relatives of many autistic children are intellectually gifted. There appear to be genetic links between autism and the depression, anxiety disorder and schizophrenia often found in artists, poets, and creative writers. “The genes that produce normal people with certain talents are likely to be the same genes that produce the abnormalities found at the extreme end of the same continuum.” She notes that Einstein, Wittgenstein, van Gogh and Bill Gates all show signs of autism, probably Asperger’s Syndrome (in recent weeks, Michelangelo has been added to the list of likely Asperger’s victims). In this high-functioning form of autism, Asperger’s victims display odd behavior, a childlike quality and greater interest in ideas and work than in human relations. “The genetic traits that can cause severe disabilities can also provide the giftedness and genius that has produced some of the world’s greatest art and scientific discoveries.”

87. Rats Can Now Almost Race
Mary Bartlett Bunge, at the University of Miami School of Medicine, reports that a 3-part treatment helped rats with spinal cord injuries regain 70% of their walking ability. Transplanted cells known as Schwann cells “from the peripheral nerves, where regeneration does occur … create a bridge across the damaged area of the spinal cord and promote the growth of axons, the nerve fibers that transmit messages.” Formerly, transplanted cells stopped growing too soon to restore functionality, but injections of other molecules (AMP) abetted the growth process in this case. See The Wall Street Journal, May 24, 2004, p. B5.

86. Vaccines for Parkinson’s and Other Brain Diseases
Vaccines to slow the advance of brain diseases are now being tested in animals and sometimes in human beings with occasional encouraging results. A four-year trial of a vaccine for Parkinson’s tested in mice protected about half the cells the disease normally would have killed. Wyeth and Elan are trying out one for Alzheimer’s that tries to resist build up of plaque. See The Wall Street Journal, June 15, 2004, p. D1 and D4.

85. Diabetes and Alzheimer’s Linked
A study at Chicago’s Rush University Medical Center of 824 individuals found that diabetes sufferers had a 65% greater risk of developing Alzheimer’s. The results were published in the May 2004 issue of the Archives of Neurology. Other small collateral studies have reached the same conclusion. Apparently, it is thought, reduced use of insulin present in the brain leads to the same plaque build-up often found in brains of

Alzheimer’s patients. See The Wall Street Journal, May 18, 2004, p. D4. Gradually we are discovering that Alzheimer’s is associated with the breakdown of the body’s very interconnected systems

84. Statins May Help With Alzheimer’s
“A study has found that taking statins may lower rates of Alzheimer’s.” Dr. Benjamin Wolozin, pharmacology professor at Loyola University, has found a deep correlation, having looked at 50,000 or so medical records at 3 hospitals and finding a 70% less incidence of the disease among statin takers. His results were published in The Archives of Neurology in 2000. (See The New York Times, April 13, 2004, pp. F1 and F6.) Other studies support his work, although the results of giving statins to Alzheimer’s patients come out mixed. Read about Wolozin and his work on sundry brain diseases at www.alzforum.org/abo/adv/wolozin.asp. The thought is that excess cholesterol, high blood pressure, etc. may tax the brain and create the environment in which Alzheimer’s flourishes.

83. Alzheimer’s—Beyond Plaque
“For 20 years Alzheimer’s research has been in the grip of the amyloid hypothesis. According to this idea, the disease is caused by the accumulation of sticky plaques made of beta-amyloid. Yet rat brains injected with beta-amyloid, Dr. Bishop found, suffered no more cell death than brains injected with innocuous salt water (referring to an article in The Journal of Neural Transmission by Glenda Bishop and Stephen Robinson of Australia’s Monash University).” See “Scientists World-Wide Battle a Narrow View of Alzheimer’s Cause,” The Wall Street Journal, April 16, 2004, p. A9. However, scientists with alternate theories are having a hard time getting published in prestige journals such as Science or Nature. Likewise, they are hardpressed to get funding from the National Institutes of Health for their research, since it has signed on to the now somewhat discredited plaque thesis. We ourselves know of one significant researcher who has been turned down on 11 grants over the last year. Of course, this is not the first time dominant, wrong-headed theories have impeded promising research, but it is useful to note that our highly centralized funding processes, subject as they are to narrow ideologues, are significantly flawed, not always distributing funds to the best advantage.

82. The Chemistry of Love
Scientists are beginning to study “the neurochemical pathways that regulate social attachments.” See The Economist, February 14, 2004, pp. 73-75. “Sex stimulates the release of vasopressin and oxytocin in people, as well as voles, thought the role of these hormones in the human brain is not yet well understood.” “Love, in other words, uses the neural mechanisms that are activated during the process of addiction. ‘We are literally addicted to love.’” Robert Palmer, the recently deceased performer of the immensely successful “Addicted to Love,” would feel vindicated. As he says to us, “[Y]ou think you are immune to the stuff / It’s closer to the truth that you can’t get enough / You know you’re gonna have to face it / You’re addicted to love.” See www.robertpalmer.com. He died on September 26, 2003 at age 54, probably from love.

81. Alzheimer’s Research Forum
We don’t know a lot about Alzheimer’s Research Forum, other than it is first class and started up in 1996. It’s put together by a young, exceptionally talented team of science writers around the Boston area, and we’ve used it to look into the latest research, to get profiles on researchers with whom we are conversing, etc. It’s about as good a way as you will find at reaching around in the various communities (academic, business, etc) that have an interest in conquering or managing Alzheimer’s. See www.alzforum.org/abo/
mis/default.asp.

80. Alzheimer’s Infection?
All the interesting research on Alzheimer’s suggests we may eventually discover a root cause for the disease that will probably make it preventable. But we’re not there yet. We’re currently enthused by the work on metals being pursued by Ashley Bush (see Brain Stem #72 ). But very provocative is the work of Brian Balin and a team at the Philadelphia College of Osteopathic Medicine, which claim a strong association between Alzheimer’s and Chlamydia Pneumoniae, a bacterium found to be present in the brains of many sufferers. Of course, this bacterium is very common, so the link may prove tenuous. Jeffrey Kelly of Scripps out in San Diego has found that athenols, resulting from inflammation, can lead to the plaque build up we associate with Alzheimer’s—an inflammation, of course, that could be caused by many agents. See The Economist, March 20, 2004, pp. 88-89. For a brief summary of many of the treatments under consideration for Alzheimer’s, see NeuroInvestment at http://biz.yahoo.com/iw/031208
/060825.html.

Update: PBT-2
When we first got to know Ashley Bush, he was trying to get Harvard and NIH support for his research on the connection between biologic metals and Alzheimer’s. Roughly, he thinks plaque and the metals interact to produce brain deterioration. Call it ‘rusting.’ He had to give up the ghost in Boston and return to Australia. Now a firm called Prana is trying to commercialize his ideas, believing it has a drug in development that will go right to the heart of the disease. Since we believe researchers are generally chasing down blind alleys in their pursuit of the causes and cure of the disease, we are fascinated with these developments down under. The Aussies discovered the cause of ulcers while researchers in the U.S. flailed about. Why not Alzheimer’s? So far this work has reversed the disease in mice: now for human beings. (12/12/07)

79. Stroke Drug
Of the many compounds tested against strokes, only Genentech’s Activase has made it to market, and it is rarely used for this application. The problem is that there is only a brief period in which a drug could be effective in any event. Most strokes are ischemic, caused by a clot that temporarily blocks blood flow to part of the brain. The damage spreads fast over 5 or 6 hours, unless there is a rapid intervention. Paion in Germany is working on a good clot buster. The other approach being attempted by Pfizer, Ono in Japan, and an AstraZeneca-Renovis partnership is to uncover an agent that will insulate nerve cells against damage by trapping free radicals. Cerovive, from the latter, is the most rigorously tested thus far. See Forbes, March 29, 2004, pp. 110-11. Commentators feel, however, that both approaches only amount to partial solutions and that a multifaceted attack will have to be staged on strokes as they occur.

78. Spinal Cord Cell Regeneration
Dr. Marie T. Filbin, in an interview with The New York Times (March 16, 2004, p. D3), talked about nerve cell regeneration in the case of spinal cord injuries. The axons of damaged cells may have a hard time repairing themselves partially because of myelin. “Damaged myelin actually has chemical inhibitors that can stop regeneration.” “At my laboratory, we’ve been looking at a protein, the myelin-associated glycoprotein—MAG for short—which … either stop or promote axonal growth.” The scar that later forms on a damaged nerve also seems to inhibit growth.

77. A Site for Sore Eyes
We can think of a number of reasons for visiting the website of Oliver Sacks. See http://www.oliversacks.com. As a neurologist, he has dealt with a host of brain diseases firsthand, and here you will find an extensive bibliography, audios, etc. that will lead you through an extensive literature on the afflictions he has treated. As well, this is just about as good a website as you find for any author: It not only has plentiful detail, but it is beautifully designed, right down to the typefaces. Such aesthetic care is almost universally lacking in all the sites we encounter, even those with heavy financial backing. Only the homepage, which is pretty but not intuitive, is awkward, but once you get past it, the site is a thing of beauty. This is all to say that Sacks clearly understands the link between science and art.

We are learning in all fields, from business to medicine, that understanding flows not only from quantitative data but from narratives that capture every stray fact. Stories or histories will tell us as much or more than bits of data. Again and again, it seems, those lucky enough to be fine writers often make better investigators than their colleagues. Sacks can look at neurons, but he also tells the story of patients that may reveal aspects of how a disease works. As well, he probes his own history to understand memory and other aspects of the psyche. Interestingly, his autobiographical Uncle Tungsten in draft apparently ran to some 2,000,000 words, as he dredged up every fleeting memory, although he only used 5 or 10% of all this material in the published edition. Even books about fern collecting expeditions, such as his Oaxaca Journal, occasionally delve back into his childhood, which is never far from his mind.

76. Janet Frame
It is not only neurologists and scientists who are helped by putting pen to paper. Janet Frame, of New Zealand, just died on January 29, 2004, after a trying lifetime of mental illness. Institutionalized at 21 and subject to all the dreadful treatments such as electro-shock that have been attempted with very troubled patients, she was only saved from lobotomy because her fine writing surfaced and her surgeon was moved to let well enough alone. Later she was to write Faces in the Water, clearly an autobiographical novel, at the urging of a London psychiatrist. Fortunately, her writing not only saved her from the knife, but it was also therapeutic in a way that neither analysis nor drugs could ever be. We probably never will fully understand why soulful expression plays such a part in the relief of all sorts of illness, mental and otherwise. But there are plenty of Frames around to prove that it works. See The Economist, February 14, 2004, p. 81.

75. The Forgetting—Alzheimer’s
Read transcripts from an online chat with The Forgetting author David Shenk, etc. This is a PBS production with links to other resources. See www.pbs.org/theforgetting. The show itself is a comprehensive guide to “the forgetting” disease for the layman. We find the update of news clips on Alzheimer’s quite useful. We also compliment Twin Cities Public TV for including actual transcripts instead of the meager audio clips put out my less generous stations.

74. De-Cellerated
“The most daring new theory suggests that depression is caused not only by chemical imbalances but also by the inability of the brain to grow new brain cells…. Imaging studies on depressed humans show shrinkage in their hippocampus, a brain region involved in learning, memory and emotion that is also a region where much neurogenesis occurs.”

“This theory, proposed by [Princeton neuroscientist Barry] Jacobs with collaborators at the Salk Institute, and independently by a Yale University team” is bolstered by the fact that existing treatments seem to promote brain cell production, albeit not at the rates that are necessary. Memory Pharmaceuticals in conjunction with Roche Holdings is working on a drug to nourish neurons, while Neurogen, Aventis and Neurocrine Biosciences are testing drugs that block damaging stress hormones. See Forbes, February 2, 2004, p. 139.

73. Fighting Fire with Fire
Juan Fueyo of the University of Texas has recently published work in the Journal of the National Cancer Institute indicating that viruses might be used against a brain cancer called glioma. This type of cancer has proven resistant to surgery, radiation, and chemotherapy. Modified adenoviruses are designed to infect and kill cancerous cells, but not healthy ones. Tests of the modified viruses in mice implanted with human glioma have been quite positive. See the Economist, May 10, 2003, p. 69-70.

Update: To find a variety of sites dealing with glioma, go to http://virtualtrials.com/btlinks/bookmark.cfm, a site that is dedicated to a glioma patient now deceased. Unfortunately this is an old site that has not been well maintained, so only about 20% of the links are current and working.

72. Zinc, Copper, and Alzheimer’s
The medical discoveries that make a difference seem to come entirely out of left field, not from the labs of academia or big pharma. You will remember that an Australian doctor shocked psychiatrists and internists, all of whom nurtured special theories about the roots of ulcers, tracing them to depression, stress, bad food, too much drink, and the like. He found that plentiful bacteria were the cause, and this has been borne out in 95% of all cases, even though some in the medical establishment resist this revelation and the simple treatment indicated for it, even in the present day.

Are the Australians about to do it again? Dr. Ashley Bush, out of Australia but now at the Harvard Medical School, thinks the real genesis of Alzheimer’s is “a copper and zinc buildup in the brain.... He believes the accumulated metals mix abnormally with a protein called beta amyloid in the brain, oxidizing—literally rusting—and destroying nerve cells."

Conventional researchers believe the protein clumps are the root problem whereas he believes it all starts with the copper and zinc which are mopped up by the protein. See the Wall Street Journal, December 26, 2003, pp. A1 and A8. Moreover, he is testing clioquinol, a dysentery drug, with a history of side effects, that appears to lead to a reduction in the protein deposits. When Vitamin B-12 is used with the drug, the toxic aspects seem to go away, and the drug seems to slow the development of the disease. Clearly the absence or presence of several metals and minerals has a great deal to do with many of the ailments of old age.

Update. Ashley Bush’s own summary of his research can be found on his website at http://neuro-trials1.mgh.harvard.edu/bush/synopsis. Bush believes there are a cluster of medical conditions all of which may trace back to metal deposits in the brain:

“That’s right. That’s the potential that we have here. And so we think that like the platform science here is that there are a cluster of diseases which include Alzheimer’s disease, cataracts, Parkinson’s disease and possibly also motorneurone disease, which has as one of their biochemical foundations, this rise in copper and iron that occurs as an inevitable consequence of ageing.” (Citation from Norman Swan interview, May 2003, for the Health Report. See www.abc.net.au/rn/talks/8.30/helthrpt/stories/s862208.htm.)

Update:We have long felt that researchers in the Washington-Harvard axis were focused much too narrowly in looking for the cause of Alzheimers, Parkinson's, and a litany of brain disease. Lately research is showing that affected brain cells show viral characteristics, the disease problem starting in one small part of the brain and gradually spreading to other unaffected cell areas. Now, the part of metals in brain disease, the area where Ashley Bush has long done pioneering work whch went unrecognized, is coming to the fore. "Iron and copper appear to accumulate beyond normal levels in the brains of people with these diseases and a new Australian study published Sunday shows reducing excess iron in the brain can alleviate Alzheimer's-like symptoms –at least in mice." See Wall Street Journal, January 31, 2012, pp.D1and D3. Also see Nature Medicine, 30 Januar 2012.

71. Thanks for the Memory
Someday, not yet, we may have a chip to insert in the brain to lend a little assistance to the hippocampus. “The shrinking of the hippocampus is thought to indicate early cognitive impairment that is a precursor to Alzheimer’s disease.” Dr. Theodore Berger, director of Center for Neural Engineering at USC in L.A. envisages a chip add-on that might work as well on language problems arising from strokes and memory loss growing out of epilepsy. So far the effort has only generated mathematical models replicating brain activity and some chip designs, but fabrication is yet to come. See “A Chip that Mimics Neurons, Firing Up the Memory,” New York Times, June 20, 2002, Section G, p.7 (http://query.nytimes.com/gst/fullpage.html?res=9906E3D9173FF933A15755C0A9649
C8B63&n=Top%2fNews%2fHealth%2fTopics%2fAlzheimers).

70. Consciousness
Year after year, The New Yorker’s medical coverage soars, and it is by far the best aspect of the magazine, its other articles never quite achieving the heights reached with Shawn and earlier editors. Most recently, its “The Reeve Effect, “ November 10, 2003, pp. 82-93 tells how Christopher Reeve has marvelously progressed in coming back from the paralysis inflicted by a devastating horse-riding incident. Further it shows how he is pushing the slow-moving medical community through his celebrity and his foundation (www.christopherreeve.org/christopherreeve/christopherreevemain.cfm) to try new strategies and to introduce nascent therapies in patient trials. In the face of prevailing medical opinion that he could not expect to recover movement, he has plowed ahead with therapy and achieved dramatic results. Further, he has uncovered well-founded, contrarian views in the medical community. “One was V.R. Edgerton, a neuroscientist at U.C.L.A.. Edgerton had theorized in the early eighties that the spinal cord could function independently of the brain. This was at odds with the prevailing view that the spinal cord was merely a cable connecting brain and body…. Virtually no decent scientist would study spinal-cord injury, “which was considered the ‘graveyard of neurobiology.’” “In the late eighties, Dr. Anton Wernig, a neurophysiologist at the University of Bonn” successfully demonstrated that Edgerton’s results could be reproduced in human beings. John McDonald of Washington University in St. Louis, who later supervised Reeve’s therapy, has gone on to try to duplicate the results in a wider panel of paralyzed individuals. Reeve has also been active in conversing with and encouraging scientists engaged in nerve cell growth research. This article, incidentally, was written by Jerome Groopman, who is at the Harvard Medical School and has done endless fine medical articles for The New Yorker. His interests have expanded into neurobiology. See http://www.jeromegroopman.com/bio.html.

69. Consciousness
Adam Zerman’s Consciousness: A User’s Guide has now been brought out by Yale University Press. Zerman, a neurologist at the University of Edinborough, writes now and again for the London Times and, according to reviewer William Galvin—who himself has written a book or two such, as A Brain for All Seasons —“his treatment of the disorders of knowledge is superb.” (See New York Times Book Review, September 28, 2003, p. 24.) Galvin notes that the brain, or consciousness if you like, instinctively runs ahead of the evidence, searching and finding meanings (quite often wrong) in the fragmented perceptions offered for its inspection. “We are always seeking after meaning.” Galvin also thinks two other works, Daniel Dennett’s Consciousness Explained and Antonio Damasio’s The Feeling of What Happens, also are quite enlightening about aspects of consciousness.

68. Drugs Jumpstart Learning
“New research on the sense of touch shows that learning, and the brain rewiring necessary for learning, can be significantly enhanced by drugs. The finding could help to restore touch sensation in the elderly or injured and lead to treatments for some forms of chronic pain.” Hubert Dinse at Ruhr-University Bochum led research into co-activation which accelerated with the use of amphetamines. See New Scientist.com, 3 July 2003.

67. Early Warning for Alzheimer’s
A team of researchers at Massachusetts General has successfully tested PIB (Pittsburgh compound B) on mice, and it is has proven successful in detecting Alzheimer’s. That is, it binds with the plaque in affected mice, while quickly clearly out of the systems of those that are healthy. Since Alzheimer’s seems to get its start perhaps a decade before it shows up behaviorally, PIB promises, if it works in human beings, to reveal the problem when emerging therapies can best get at it. See the Wall Street Journal, September 23, 2003, p. D7.

66. Damaged Brain Centers
“More and more … neuroscientists are saying … underachievers may suffer from neurological abnormalities affecting ‘the brain’s CEO.’ This control center, really an array of ‘executive functions,’ orchestrates resources like memory, language and attention to achieve a goal, be it a fraction of a second or five years from now.”

“But most help involves external cues and supports, to teach the stronger parts of the brain strategies to compensate. Often, Dr. Denckla said, adults with executive deficits can be relatively successful, ‘as long as there is another human being—co-author, a teacher, a wife who acts as an auxiliary frontal lobe to keep them on track.’” See the New York Times, August 26, 2003, pp. D1 and D6.

65. Allen Brain Atlas
Backed by Paul Allen, “a team of scientists has set out to pinpoint the roughly 20,000 genes responsible for building and operating the human brain.” Dr. Mark Boguski, director of Seattle’s recently founded Allen Institute for Brain Science (see www.brainatlas.org/content/press/Anncmt_News_Release_8_2003.pdf) with $100 million from Allen, and his colleagues will lead the effort. This project will look at 10,000 genes a year as opposed to the 600 to 800 tackled by the Brain Molecular Anatomy Project at the National Institute of Mental Health. See the New York Times, September 16, 2003, p. D5. If we remember rightly, Allen suffers from some neurological disorder.

64. Neuro-Marketing
We have already talked about neuro-economics, which shows how consumers often make decisions based on rules of the head rather than the commands of the efficient marketplace. Now along comes neuro-marketing, wherein pitchmen are trying to package their advertising and their products in ways that will excite one or more parts of the brain and, eureka, lead people to make buy decisions. Forbes just did a cover article “In Search of the Buy Button,” September 1, 2003, pp.62-70. “So far, researchers are figuring out which brain states facilitate product recognition and choice; they’re related to primal urges like those for power, sex and sustenance. As for brand loyalty, it turns out that memory and emotion play a big role.” “No tool gets more use than the Zamboni-size functional magnetic resonance imaging machine, which takes neural eavesdropping to a new level.” We are still at the early stages of all this neural-insight work, where the benefits companies are deriving from the effort do not really justify the rather inflated fees consultants in this area manage to charge for their work. We would, nonetheless, take a look at some of the semi-academic groups mentioned here, such as the Brain Sciences Institute at Swinburne University of Technology—www.scan.swin.edu.au/links.html—in Melbourne, Australia or the University Clinic of Ulm, Germany, which is conducing brain-imaging work for DaimlerChrysler.

63. Agitated Malingerers; Watch Out, Liars
Nick Ward and his colleagues at University College in London have discovered that the brains of malingerers work overtime avoiding work. “In those feigning … the researchers saw increased activity in brain areas associated with conscious planning—in particular the prefrontal cortex. That suggests that subjects were consciously inhibiting a motor response. These ‘malingerers’ showed the same activation of movement-preparation areas as did their ‘paralysed’ counterparts, but the conscious-planning areas then kicked in to stop the movement from being performed.” “Dr. Halligan thinks the technique represents an improvement on traditional lie-detection methods that rely on monitoring changes in the skin’s electrical resistance caused by perspiration.” See Economist, July 12, 2003, p.73.

62. Brain Builders
An article in Nature by Shawn Green and Daphne Bavelier of the University of Rochester shows that players of high-action video games gain a visual perception advantage over non-players. The complex visual field and fast-paced action lead to intense focus and fast decision-making in the players. See Economist, May 31 2003, p. 79.

61. Brain Scans for Disabilities
Brain scanning is now being used with some success to better understand a series of psychiatric disorders. At UCLA, positron emission tomography (PET) is being used with obsessive compulsive (OCD) patients to determine who will benefit from drug treatment. Using scans, brain surgeons are also implanting electrodes in abnormal brain tissue to control Parkinson’s and OCD. Magnetic resonance imaging (MRI) has found that children with ADHD often have brains that are smaller than those of healthy children. See Boston Globe, June 3, 2003.

60. Plug-Ins for the Brain
In a far-reaching article about brain bioengineering, the Economist (see The Economist Technology Quarterly, June 21, 2003, pp. 20-21) shows how we are embarking on a host of experimental efforts to implant devices in parts of the brain that are damaged. “Dr. Theodore Berger of the University of Southern California, in Los Angeles, announced early in 2003 that his group was about to begin trials with the world’s first prosthesis, an implantable hippocampus.” A team at Stanford is working on a visual prosthesis to help deal with macular degeneration, a leading cause of blindness in people over 60. Meanwhile, researchers at a couple of institutions are working on brain robots that may help control mental diseases or, for instance, actually enable the brain to once again control parts of the body (such as limbs) over which it has lost control. Infineon Technologies in Germany, with the Max Planck Institute, has a Neuro-Chip which will help scientists better understand brain function. For more on this chip, see www.hoise.com/vmw/03/articles/vmw/LV-VM-04-03-25.html.

59. ABC2
Accelerate Brain Cancer Cure was formed as a result of the untimely passing of Dan Case, a Silicon Valley financing figure, who died of brain cancer. It exists to support fast track research in this area. We, however, find its site most useful for its extensive links page, which leads you to a host of institutions, journals, etc. both in the field of cancer and of brain research. See www.abc2.org/general_links.shtml.

58. Slowing Dementia
Dementia has been regarded as untreatable, but it may be controlled if dealt with early enough. The precursor to dementia known as M.C.I., or mild cognitive impairment, takes as much as 6 years to develop into full-blown breakdown. See the New York Times, March 18, 2003, p. D5, “Oldest Old Still Show Alertness.” “Researchers are looking into using drugs to delay or prevent that conversion. Aricept, Reminyl and Exelon, which slow the progression of Alzheimer’s in the early stages, increase the activity of a brain chemical, acetylcholine. Studies are under way to see whether those medications can benefit people with M.C.I. as well, without serious side effects.” There is a tendency, says the same article, to write off the very old, thinking that dementia and their other conditions cannot be dealt with. The thinking now is that this may not be the case.

57. Morals and Brain Development
It is not until 2 that children begin to understand the meaning of right and wrong. “Dr. Kagan thinks that the timing is due to a burst of growth in the neurons that connect the two hemispheres of the brain and, in so doing, links emotions with judgements,” bringing together feelings from the right hemisphere with the knowledge of right and wrong in the left hemisphere. Moral philosophy advances in adolescence when another growth spurt takes place in the brain. See “Scientists Explore the Molding of Children’s Morals,” New York Times, March 18, 2003, pp. D5 and D8.

56. Brain Bits
To find out which individuals and institutions generated high-impact papers in neuroscience during the 1990s, take a look at this site. Provincial as we are, we did not know what a contribution the Max Planck Institute made to the field. ScienceWatch takes the volume of papers and citations to be yet another indication of the explosion of interest in and the vast growth of professionals now involved with neuroscience. See www.sciencewatch.com/jan-feb2001/sw_jan-feb2001_page1.htm.

55. Anatomy of Melancholy
As we have said elsewhere, depression and its kin will soon be our top medical complaint, outranking cancer, heart disease, and diabetes in the number of people it affects. And as we look into seriously ill people, we find that mental afflictions are all too common companions (co-morbidities) of the serious physical maladies on which we tend to focus. That means we have a looming crisis, since “the share of employers offering mental health benefits … dropped to 76 percent last year from 84 percent in 1998.” (See “Stress is Up. So Why are Mental Health Benefits Down?,” New York Times, April 20, 2003, p. BU 9.

In his Robbins lectures, given at the London School of Economics on March 3,4, and 5, 2003, Lord Layard commented that “It is a complete scandal that we spend so little on mental health. Mental illness causes half of all the measured disability in our society and, even if you add in premature death, mental illness accounts for a quarter of the total impact of disease. Yet only 12% of the NHS budget goes on it and 5% of the MRC budget. Roughly 25% of us experience serious mental illness during our lives, and about 25% experience major depression.”

All this puts in bold relief the work of Dr. Ronald C. Kessler, professor in the Department of Health Care Policy at the Harvard Medical School. We have already commented that he is doing all sorts of pathfinding work on the economic costs to business of bad health, hoping, of course, that business will spend more to deal correctly with healthcare out of self interest. But he has also authored a blizzard of papers on psychiatric epidemiological matters which you can consult at www.hcp.med.harvard.edu/ncs. From 1990 to 1998 he is judged to have produced more high impact papers than anyone else in psychiatry, some 31 in toto. You can read more about this at www.sciencewatch.com/may-june2000/sw_may-june2000_page1.htm. Mental disease, but also the sum of diseases that affect the neurological system, are so costly to the economy that we will be forced to come to grips with them in entirely new ways. As near as we can determine, basic research in the neurological area is just as badly funded as mental healthcare.

54. Brain Cancer Radiation
Allos Therapeutics (www.allos.com , NASDAQ: ALTH), outside Denver, hopes to improve brain cancer radiation enough to give patients more than the average four months to live. It has been massaging RSR13, a small molecule, with the aim of bringing more oxygen to brain tumors, hoping to make radiation more effective. Phase III investigations are now in progress at the Cleveland Clinic, with the hope of a full scale launch in late 2004. Phase II work seemed to demonstrate that RSR13 in conjunction with radiation might add 2 months of life to those afflicted. See Wall Street Journal, March 7, 2003, p. B7.

53. Let Well Enough Alone
Often disaster counseling can hurt more than it helps. There is often a rush to the psychologists to deal with PTSD—post-traumatic stress disorder. Often as not, “the human mind recovers naturally from psychological traumas by replaying events, and constructing new memories.” Only those with ongoing problems need to resort to counseling. The problem, it seems, is a surfeit of counseling may increase the possibility of enduring disorder “by making people fear that they may be mentally ill.” Apparently 20% of those in car crashes develop PTSD: most rape victims get it, and still have it after six months. See Economist, March 8, 2003, p.55.

52. Brain Museum.org
Comparative Mammalian Brain Collections is a joint effort of the University of Wisconsin, Michigan State University, the National Museum of Health and Medicine, and the National Science Foundation. This web site provides browsers with images and information from one of the world's largest collection of well-preserved, sectioned and stained brains of mammals. Viewers can see and download photographs of brains of over 100 different species of mammals (including humans) representing 17 mammalian orders. See http://brainmuseum.org.

Update: Bits of Progress
We have remarked before on both Brain Stem and Stitch in Time that we have taken some baby steps with old-fashioned substances like garlic and arsenic in the struggle against brain cancer. Now we are coming up with a few drugs. (See New York Times, May 23, 2008, p. A18.) “Avastin,” from Genentech, “is leading a pack of new drugs that look promising as treatments for brain cancer….” The revelation that Senator Ted Kennedy is afflicted with rather drastic brain cancer has heightened attention on this ailment. “Already, the brain cancer drug Temodar, a pill sold by Schering-Plough, is on track to surpass $1 billion in sales this year….” Now there are also beta tests with a cancer vaccine. “There are only about 22,000 new cases of all brain and nervous system cancers in the United States each year, only a tenth as many as lung cancers….” “The rapid death rate also limits the appeal of developing drugs.”

“Target Acquired,” Economist, May 31, 2008, p. 86, expands on some of the work on the vaccine front. Duane Mitchell at Duke University hints that vaccines may work against glioblastomas (also see our entry on use of viruses against glioblastomas). He and his colleagues have discovered cytomegalovirus in 90% of glio patients they examined, but not in healthy surrounding tissue, nor in non-malignant tumors. Exposing immune system cells to bits of the virus and subsequently injecting cells back into patients appeared to extend life of sufferers as much as six months or more. (7/30/08)

Update: Viruses for Health
“Glioblastoma is a brain tumor so fearsome that oncologists call it ‘the terminator’” (Yale Alumni Magazine, May-June 2008, p. 38). Ordinary surgery and chemo don’t work, 75 percent of patients dying within two years of diagnosis. Yale Professor Anthony van den Pol and his colleagues have “generated a virus that targets and kills glioblastoma cells while leaving surrounding healthy tissues unscathed.” “Vesicular stomatitis virus (VSV), a bug thast causes stubborn mouth sores in livestock,” has turned out to be the most likely killer. So far it has been tasted in mice with good effect. If it is proven safe, he will begin tests on human subjects. See “SystemicVesicular Stomatitis Virus Selectively Destroys Multifocus Glioma and Metastatic Carcinoma in Brain,” Journal of Neuroscience, February 2008, 1882-93. (8/27/08)

51. Too Much Reality
In the last print version of its once great newsletter, RBC Bank does a swansong in which it discusses mental health. Called “Mental Health—Today and Tomorrow,” August 2002, the issue essays on the growing amount of growing mental illness in Canadian society and the unfortunate pariah status the mentally afflicted suffer under. It notes that schizophrenia is now more common in North America than diabetes, Alzheimer’s, or multiple sclerosis, and is the leading cause of hospital use, after accidents, in Canada. “Some experts expect that over the next five years, mentally-related disability and care claims will amount to fully half the number of claims in employee health plans.” For the writer of the letter, all this recalls T.S. Eliot’s 1935 lines that “human kind / Cannot bear very much reality.” We would say humankind cannot bear any more reality. While this article focuses on discrimination against the mentally ill, the real lesson of the piece, of course, is that we are under-resourced in the psychological arena and our health plans are in no way prepared for the mental health problems ahead. To see this issue online, go to www.rbc.com/community/letter.

50. Brain Chips
“In December, researchers from Arizona Sate University showed that they could predict more than 80 percent of seizures with a computer program using chaos theory that analyzed brain waves.” “On average, warnings of impending surges occurred more than an hour before the seizure….” “Dr. Iasemidis said… ‘We envision a device that would automatically release a very low dose of an anti-epilepsy drug or an electrical signal that would block the seizure.’” New York Times, February 18, 2003, p. D5. Such devices, however, are still quite a few years away.

49. A Lobotomy Primer
This site is a really a brief primer on lobotomy to include a lobotomy hall of fame. Basically it is talking about a modern technique, dating back to the 40s, that has not worked out terribly well. But it comments on ancient brain drilling as well. Psychosurgery has gotten a little less crude now, with brain scans permitting doctors to do some things in the present day that actually make sense. We would also recommend that you take a look at the short bibliography which we find useful, including, for instance, a link to the founders of neurology. See www.epub.org.br/cm/n02/historia/psicocirg_i.htm.

48. Brain Bucks
Now it’s neuroeconomics. Apparently there are only 50 or so people in this field in the United States. What they’re looking at is how emotions work in the brain to determine whether individuals make or reject plausible investments. Paul Glimcher at New York University and Paul Zak at Claremont are pioneers in this field. One article about this in the Wall Street Journal, November 15, 2002, p.B1 is vague about the applications of this research, although we ourselves think it will profoundly affect how financial services are marketed in the future.

Update: NeuralSpeculomics
In “Mind Games,” The Economist (January 25, 2005, p. 71) reports on so-called neuro-economics. Basically, the drift here is to see how human expectations and emotions shape economic choices and, hence, determine the ups and downs of the economy when a crowd sees the future the same way, whatever the realities. Right now, America is slogging along in neutral, so we can only suppose that we’re about evenly split between those envisioning a rosy-fingered dawn and those who can sense sunset all about us. Oddly enough, we are split right down the middle political as well, probably divided between those who feel we are going forward and those who are sure we are going backwards.

Brian Knutson of Stanford has used brain scans to see how subjects think through their potential for gains and losses, and so opt in or out of a course of action. David Laibson, an economist at Harvard, finds that we behave quite differently in weighing immediate gains and losses as opposed to choosing between long term gains and losses. For the short term, apparently, we tap into our limbic region of the brain which is strongly associated with emotions. But for the long term, we use the prefrontal cortex, the reasoning and calculating seat of affairs. This nascent field of psycho-economics is still not far enough along, however, to influence economic policymaking or the way we predict future economic outcomes. (2/23/05)

47. Mental Alertness, Sir
As we did our physical exercises in basic training, the lieutenant would call out, “Class, what’s the most important thing in physical fitness?” And we’d shout back, no matter how out of breath we were, “Mental alertness, sir.” Fact is, he was right. A recent article in the Wall Street Journal (“Yogi Berra Was Right,” October 29.2001, p. B1) documents just how much the brain is involved. “Dr. Lisberger, professor of neuroscience at the University of California in San Francisco, says the performance of elite athletes—and indeed all motor skills—starts in the head.” At work, says the article, are vestibule-occular reflexes, smooth pursuit eye movements, open loop functions, spinal cord neurons, etc., which work together to speed a speedball past the shortstop into the outfield.

46. The Flexible Brain
We used to think that specific parts of the brain controlled very specific human functions. If a part went, then the function was no more: if the speech area was damaged, speech ceased. But we are now learning that the brain can adapt and rewire itself to accommodate functions in new sections of the brain when old ones give out. This has led to new therapies for everything from stroke to dyslexia. See the Wall Street Journal, October 11, 2002, pp. B1 and B4. Also consult Jeffrey M. Schwartz’s and Sharon Begley’s forthcoming book, The Mind and the Brain: Neuroplasticity and the Power of Mental Force, which was the source of their WSJ article on this topic.

45. ADHD and the Back of the Brain
Recent research shows that it’s not only the front of the brain that plays a part in attention deficit disorder. Work done at McLean Hospital in Belmont, Mass. has shown that attention deficit children who were extremely fidgety tended to have a very active vermis, an area in the back of the cerebellum. Magnetic resonance imaging was used to detect this activity. Ritalin, a common drug used with ADHD children, tended to calm down the vermis in agitated children but, on the other hand, actually excited the vermis in those who were not fidgety. Clearly the vermis acts in concert with other parts of the brain, and it will be a while before the mechanism is understood well enough to lead to effective treatment. See the Wall Street Journal, August 1, 2002, p. D3.

44. New Therapies for Brain and Spinal Cord Injuries
“Constraint-induced movement-based therapy,” early application of amphetamines after injury, and other unusual methodologies are being applied in rehabilitation centers across the world to see if speech and body movement can be restored to the afflicted. See the New York Times, August 28, 2001, p. D6. “The new rehabilitation methods try to kick-start the process of self-repair in the brain or spinal cord.”

43. Brain Cancer Centers
Very gradual progress is being reported in brain and spinal cancer research and funding. Some Duke research results are posted on the website of Duke’s Brain Tumor Center (www.cancer.duke.edu/btc), whose program found its roots in the 30s and 40s. Meanwhile the James S. McDonnell Foundation in St. Louis (www.jsmf.org) specifies that funding for this somewhat neglected area is one of its major initiatives.

Update: Surgery Plus Cancer Vaccine
We have a laundry list of comments on brain cancer. See 248, 73, and 50 on Brain Stem. Also see 177 on Stitch in Time. Henceforth, we will collect brain cancer information in this citation.

42. Memories Are Made of This
Pierre Maquet of Belgium’s Liege University seems to have shown that we deepen our memories about things we have learned during the day in the course of our REM sleep in the evening. Using positive-emission tomography scans, he found that content patterns absorbed during the day appeared to be reinforced during sleep. Apparently the question has been whether we edit or reinforce memories during the night. Reinforcement wins out. That’s why it pays to quit studying for exams at a certain point and get a good night’s sleep: you are learning while you sleep. See the Economist, June 22, 2002, p. 77.

41. The Spinal Cord Information (SCI) Super-Site
M. Ginop, a quadriplegic, has put together this fabulous site on everything you every wanted to know about the spinal cord, plus every related issue that comes to mind—from the top rehabilitation hospitals to bladder management to handling a wheelchair. As we have said many times, the best information on health issues comes from diligent sufferers determined to deal with their own conditions and rational enough to deal with the outpourings of the medical community in a selective manner. See www.sci-info-pages.com/index.html.

40. Organization for Human Brain Mapping
This group has a clunky website, so you sort of wonder how the membership can map much anything. Nonetheless, this is a critical area of brain research, because it will let us target and focus treatments for brain-related diseases and will eventually help us refine learning theory, which, at best, gives us crude insights today on how we learn and how we can expand our brainpower. See www.humanbrainmapping.org/index.html.

39. Price of Progress
The Economist deals with the “Future of Mind Control” in its May 25, 2002 issue pp. 77-79. Raising about the same questions that come up in genetic engineering, it tries to reckon with the ethics of neuroscience. What this mostly tells us is that we have made rapid strides lately on the neurogenomics front, enough so that we can now worry what the scientists may do to us. There is a certain irony at work here. The last frontier in medicine is the brain and the diseases of aging such as Alzheimer’s, Parkinson’s, stroke, and the like. Probably we will learn how to alter conduct and behavior—further undermining man’s autonomy which has been the story of the 20^th century—before we even get a grip on the diseases that justified all the research in the first place. Just as the urgent always swallows up the important, technical virtuosity shoulders aside our real goals

38. Heart and Soul
“While there has been much backing and forthing, the preponderance of evidence has indicated a strong relationship between what can be summed up as excessive emotional stress and an elevated risk of developing and dying of heart disease,” says Jane Brody in the New York Times, May 21, 2002, p. D7. In an even more penetrating personal testament, psychiatrist and physician Anna Fels tells of “Mending of Hearts and Minds,” recounting her own personal encounters with the byplay between hear t and mind. See the New York Times, May 21, 2002, p.D5. Heart attacks themselves are taken to produce depression in patients which, in turn, can induce yet other potentially fatal heart events. Meanwhile, Columbia University research, albeit in very small studies, suggests that antidepressants reduce the risk of further heart problems in those who have suffered a heart attack. See the Wall Street Journal, May 21, 2002, p. D4. The relationship of mind to body ever perplexes philosophers and researchers, yet it becomes more and more clear that the two have to be taken together in dealing with serious or chronic illness.

37. Sights and Sounds that Don't Get Heard
The Hybrid Vigor Institute (http://hybridvigor.net/human/pubs/index.html) has just published Richard Jay Solomon's As If You Were There: Matching Machine Vision to Human Vision. His research about human neurological systems shows, for instance,
that even sophisticated cameras and listening devices don't see or hear as accurately as human beings with the implication that the machines must be re-machined as we discover more.

36. Bill Clinton's Mentor?
When we are trying to make our case with someone, we always dream up a sales pitch. We don't think about the fact that people are hotwired with all sorts of resistances that throw up a brick wall to all our blandishments. Social psychologist Eric Knowles at the University of Arkansas has carved out "resistence" or "resistance," if you like, as his territory, saying it is all well and good that we do "alpha" things that try to grab people but that we have to work the "omega," using tactics to diminish their defenses. Fundamentally, the idea is that you can, by various feints, overcome resistance for a time, and it is when their defenses are down that you zero in with your big arguments to make the kill. We can only surmise that the ex-Governor of Arkansas picked up a little of this wisdom, because he got such high ratings in the face of his impossible negatives. See the Economist, May 4, 2002,pp.77-78. Also pour through Dr. Knowles homepages at http://www.uark.edu/depts/psyc/faculty/exper/knowles.htm as well as his labsite at www.uark.edu/~omega.

35. Robotic Rats
The Wall Street Journal, and many others, reported last week on Brooklyn's Downstate Medical center experiment where electrodes were implanted in rat brains and then an ordinary computer was used to guide them through obstacles. See May 2, 2002, pp. B1 and B6. In theory, the rats, with this guidance, could be used for all sorts of useful tasks. More importantly, the experiment advances “the nascent field of neural prosthetics, in which electrodes implanted in the brains of people paralyzed by stroke or amyotrophic lateral sclerosis (Lou Gehrig's disease) might allow patients to move again.”

34. Stem Cells Help Brain Repair
In another rat experiment, researchers at the Medical College of Georgia have traced the process by which stem cells leave the bone marrow and migraine to the brain to repair damaged neurons and make new neurons and blood vessels. As a consequence, the scientists are now looking for factors which would enhance the repair mechanism in stroke victims, with the view that this would be the most natural and compatible way to enhance stroke recovery. See http://www.mcg.edu/news/2002NewsRel/hillHess.html.

33. Pinpoint Brain Research
University of Texas researchers are now working on sending signals directly to specific brain cells. Particles that amount to tiny semiconductors are sent to neurons with the ability to activate processes that can, for instance, stimulate dopamine production. Practical neurotransmitters are at least a decade away. See Business Week, December 24, 2001, p. 75.

32. Eric Chudler's Neuroscience for Kids
It would have been better if he had called it grey matter or life at the top. But, nonetheless, this is a good site for kids who like teacher stuff and parents who are trying to get their kids through school projects. See http://faculty.washington.edu/chudler/neurok.html.

29. From Heart to Brain at Merck
Merck (NYSE:MRK) has long turned in fabulous results from its heart franchise -- a raft of heart drugs that now are due to go off patent. It has ramped up its brain research multifold in the last few years -- the major unexplored frontier in medicine. Merck is late to the game, since both Pfizer and Glazo already sell $4 billion in brain drugs each year. (See "Betting on the Brain," Forbes, January 7, 2002, pp. 56-59.) Since it is behind the eight ball, Merck is trying to license drugs to put more product in the marketing pipeline. Always proud of its research, the company seems to have stayed too long in the chest and not gotten to the head fast enough. It will have to make more DNA genetic purchases to get out front again.

28. The Whole Brain Atlas
See www.med.harvard.edu/AANLIB/home.html. So you want to take a trip around the brain--either normal or diseased? Here's how you get the picture.

27. Brainbusters
Years ago we learned that the most passionately held dogmas of scientists and doctors were sure to be upset sooner or later--and often sooner. In biology, back then, we learned that nerve tissue, unlike other human cells, did not regenerate. Now this wrong-headed notion is out the window. We know now that within twenty years brain-injury victims and all the people with diseases of aging--Parkinson's, Alzheimer's, etc.--may experience rejuvenation. To get up to speed, read Michael Specter's "Rethinking the Brain" in The New Yorker, July 23, 2001, pp. 42-53, which details how Fernando Nottebohm at Rockefeller University shook up our thinking by looking at the brains of canaries. And, subsequently, scientists are discovering nerve cell output in the human brain as well. Additionally, the article helps in pinpointing seminal figures in neurogenesis, such as Pasko Rakic at Yale, Elizabeth Gould at Princeton, and Fred Gage at the Salk Institute. We learn, too, that San Diego is "the capital of American brain research," surely ironic for those of us who always said the West Coast has some very bright people but they suffer from baked brains.

26. Out of Its Mind: Psychiatry in Crisis
Hobson and Leonard talk about the decline in psychiatry and the hordes of untreated patients wandering our streets. They "provide a neat summary of recent progress in brain science and the treatments it has led to." Reviewer Paul Raeburn also notes how we have moved too deeply into treatment by drugs, cutting down on psychotherapy--the other vital part of the mental-health cocktail. See Business Week, July 9, 2001, p. 18.

25. Enhancers and Inhibitors
A host of approaches are now in trial to fight Alzheimer's as well as MCI (Mild Cognitive Impairment), a precursor of Alzheimer's. One group of drugs, called ampakines, seek to boost the memory function despite the build-up of brain-clogging plaque (insoluble protein. Others stimulate growth in memory centers, and still others are trying to attack plaque with vaccines. See Business Week, June 11, 2001, pp. 94 and 96.

24a. Rabbit Redux
Theodore Berger has been slicing and dicing rabbit brain tissue and measuring its electrical outputs at his Laboratory for Neural Engineering at the University of Southern California. He completed a neuron model and then, in 1996, adapted it to speech recognition. It is this latter work that has received major funding from DARPA, NASA, and the U.S. Navy. Based on his work, he can envision a time when brain diseases can be conquered by replacing parts of the brain with, in effect, new hardware and software. See "Brainware," Forbes, April 16, 2001, p. 328.

24. Whither Schizophrenia?
Remember when we thought ulcers were due to stress, bad food, and miscellaneous other non-relevant stimulants? Then an Australian connected ulcers to bacteria. Lo and behold, physical disease, rather than environmental factors, may lie at the heart of schizophrenia. In perhaps 30% of the cases, a "retrovirus," similar to the one that causes multiple sclerosis, may cause this mental condition. See "Tracing the Cause of Schizophrenia," Business Week, April 22, 2001, p. 69.

23. Brain Sites
For the self-absorbed, here are some sites showing what our brains look like:

22. Electroshock Is Back
For a host of brain complaints (ranging from depression to epilepsy), drugs often don't work. Now, discriminating applications of electroshock are coming into play again. Medtronic's Activa device is designed for deep brain stimulation, with plausible application to tremors and Parkinson's. Cyberonics' nerve stimulation is already approved for epilepsy. A pioneer in this development is Cyberonics' co-founder and retired Temple University physiologist Jacob Zabara. See Forbes, March 5, 2001, pp. 160-62.

21. Mapping the Brain
Using the Reimann mapping theorem, put forward in 1854, researchers now think they can make flat maps of sections of the cortex, the creased surface of the brain where most information is processed. This will provide a lot more detail about brain function. See "Navigating Your Mind," Economist, January 27, 2001, p. 81.

20. Brain Scanner Passes Away
Hardly a week passes in which we don't lose another brain pioneer. Dr. Sadek Hilal, a Columbia University radiologist, was an imagery pioneer who peered deeply into the brain. Mayor Koch of New York City called him a "genius," and Hilal did things never before attempted with advanced magnetic resonance scanners and microdensitometers. See The New York Times, January 8, 2001, p.A19.

19. Brain and Spine Symposium
As we have said, somebody will eventually make a nickel off of medicine’s last frontier—the brain. Of course, the investment bankers always make money before there is money to be made. So First Union Securities will hold its Second Annual Symposium in New York City on January 18, 2000.

18. Rebuilding the Spinal Cord
See Business Week, December 11, 2000, pp.113ff. Electric charges and transplanted stem cells are now viewed as possible ways to regenerate spinal-cord functionality. A November meeting of the Society for Neuroscience in New Orleans highlighted sundry approaches to re-growing, replacing, or retraining the spinal axons.

17. Donald Reis, Brain Pioneer, Passes Away
"Dr. Reis studied the ways in which the brain relates to emotional behavior, controls blood pressure, protects against strokes and generates neurotransmitters affecting mood and behavior." See New York Times, November 4, 2000, B l9.

16. Mental Illness Start-Up
Psychiatric Genomics, Inc. of Gaithersburg, Maryland is about to close on a new round of funding from Oxford Bioscience Partners. Tapping into various genomic databases, it plans to uncover drug candidates for treatment of illnesses such as schizophrenia, depression, and bipolar disorders.

15. Nature on the Net
Nature is a great way to keep tabs on all the life sciences. Certainly this includes neuroscience developments. We suggest http://neurosci.nature.com/ where a cluster of brain insights show up on a regular basis.

14. Things You Do Not Have to Know About the Brain
Here are some things you do not have to know about the brain in case you are feeling overburdened by knowledge. “Despite accounting for just one-fiftieth of body weight, the brain burns as much as one-fifth of our daily caloric intake.” “The human eye sees everything upside-down, but the brain turns it right side up.” See www.uselessfacts.net/cgi-bin/urlssrch.cgi.

13. Brain Symposium
Cogent Neuroscience, an underwriter of our brain domain, is putting together the First Annual Symposium on Neurogenomics, April 24-26, 200l. The heavyweights will be speaking, such as Dr. Francis Collins of the National Human Genome Research Institute; Dr. Leroy Hood, Founder of Applied Biosystems; Dr. Eric Lander, Director of the Whitehead Institute; Dr. Allen Roses of Glaxo. Dr. James Watson, President, Cold Spring Harbor Laboratory will be the keynote. To learn more, see www.neurogenomics.com/symposium.

12. Causes of Autism
Individuals that suffer from autism have malformed and missing structures in the brain stem: the superior olive and facial nucleus, respectively. Several genes cause the disease, but only the right combination of these genes produces autistic conditions. For this reason, only 16 people out of 100,000 will experience the disease. (www.naar.org) Patricia M. Rodier, “ The Early Origins of Autism,” Scientific American, February 2000, p. 56.

11. Missing Bliss
New studies have shown that there is a 50% reduction in the levels of the neurotransmitter serotonin in older people. Serotonin is responsible for feelings of happiness and euphoria. Broad reduction of serotonin has been linked to increased incidence of depression. See Catherine Johnson, “Promised Land or Purgatory?” Scientific American (Quarterly Issue) 2000, p.93.

10. FDA Okays Old Drug for New Use on Stroke Victims
The FDA recently approved Activase--a drug already licensed to dissolve clots in the heart and in the artery leading to the lungs--for use on stroke victims. However, in order to have a clinical effect, treatment must occur within three hours of stroke onset. Additionally, bleeding into the brain--i.e. a hemorrhagic stroke--must first be ruled out with a computerized tomography (CT) scan before Activase can be given. Activase is manufactured with recombinant DNA technology by Genentech, Inc. See the FDA's Center for Drug Evaluation and Research website at www.fda.gov/cder/. (This entry is an update of entry # 6 below.)

9. I Am in Control
New research suggests that individuals who feel they have control over their health have an increased rate of recovery from depression. Although clinical depression stems from the imbalance of neurotransmitters in the brain, this research argues that a "patient who feels helpless may recover better if [he is] empowered, which can be as simple as educating the patient on depression." See Charlotte Brown, et al., General Hospital Psychiatry 22, 2000, pp. 242-250.

8. Drinking for the Mind
Research has already shown that moderate alcohol consumption can improve the health of the circulatory system by lowering blood pressure. However, new research shows that the same consumption can also improve the functioning of the brain. By lowering blood pressure and improving circulation, the brain is supplied with more oxygen and nutrients while at the same time removal of waste product becomes more efficient--all of which leads to better physical functioning. Additionally, in soon to be published results, researchers have found that alcohol consumption reduces the risk of Alzheimer’s disease. See Jorge A. Cervilla, et al., British Journal of Psychiatry, July 2000.

7. The Origins of Narcolepsy
Scientists have unraveled the cause of narcolepsy, a disease which causes its victims to be unable to maintain muscle control, even when conscious. Scientists have traced the condition to a degeneration of the neurons in the brain which control muscle stimulation. Apparently, a mutation in the neurons of dogs can result in symptoms of narcolepsy--hence scientists' new understanding of this disease and its origins has come from man's best friend. See Jerome M. Siegal, "Narcolepsy," Scientific American, January 2000, p. 76.

6. Possible New Drug Treatments for Stroke (See #10 above)
Every year, strokes affect 600,000 Americans and kill 100,000 of those victims. In occlusive strokes—the most common type—50% of the brain cells that die do so immediately, while the rest die in the ensuing hours, even if the blockage is removed. Scientists have discovered that this prolonged cell death results from the remaining cells attempting to repair the brain too quickly; in doing so, these healthy cells increase their energy requirement beyond the delivery capability of the locally blocked circulatory system. Scientists are developing drugs to allow the circulatory system a chance to recover and, in turn, provide the required nutrients when the brain begins to repair itself. See Robert Langreth, “Repairing the Brain,” Forbes Magazine, August 7, 2000, p.124.

5. Memory Pills
One of the biggest concerns regarding aging is the potential loss of memory. Memory occurs when cells in the brain make new connections with other cells, creating a structural network that forms the new memory. The formation of connections requires structural changes in the brain cell, which in turn require the presence of a “Memory Protein.” Scientists have discovered a method to both regulate and to stop the activity of this protein in the neurons of fruit flies. As a result, the flies with more of this protein have shown a ten-fold increase in memory formations/retention, while flies without it have shown no ability to form new memories—a promising first-step toward a human memory pill which could help maintain memory and improve the formation of new memories. See William Weed, “Smart Pills,” Discovery, June 2000, p. 82.

4. The Biochemical Workings of the Biological Clock
Scientists are beginning to unravel how the biological clock works. In humans the pineal gland in the brain releases melatonin into the circulatory system. When light hits the retina, the production of melatonin declines while the stress hormone cortisol increases, waking the body from sleep. However, studies have show that the 24-hour cycle is maintained even without a light source, sending scientists on a search for the genetic basis for the biological clock within the brain. They discovered that the elusive clock also is controlled by the actions of genes at particular times during the daily cycle. With their experiments with fruit flies--which also display a 24-hour rhythm--scientists have uncovered proteins which cycle their concentration within the cell during night and day. While as yet these same genes have not been discovered in humans, this research means that one day we might be able to fight the biological clock via drugs that affect the interactions of these proteins. See Michael W. Young, “The Tick-Tick of the Biological Clock,” Scientific American, March 2000, p. 64.

3. Pig Cells for Parkinson's
Parkinson's Disease, a loss of muscle control which afflicts 1,000,000 Americans, results from a lack of dopamine, stemming from the death of critical brain cells. Because pigs and human beings share enough similarites in anatomy and physiology, fetal pig brain cells have shown promising results when used with sufferers. See Gunjan Sinha, “On the Road of Recovery,” Popular Science, October 1999, p. 77. Web sites with additional information include the National Parkinson Foundation (www.parkinson.org) and the Parkinson’s Disease Foundation (www.pdf.org).

2. Bacteria Behind Strokes
Chlamydia pneumomiae, already linked to heart attacks, may play a part in strokes as well, by causing inflammation that leads to stroke. See "Infection Appears to Pave Way for Stroke," New York Times, July 25, 2000, p. D8. Remember when we finally discovered that bacteria lay behind heart attacks? And now we're linking obesity to viruses. Why, there just may be a cause for practically everything!

1. Pea Brain
Recent work of Dr. John Duncan in the Cognition and Brain Science Unit at the Medical Research Council in Cambridge, England shows that a small part of the human brain solves problems and does the IQ stuff. The "lateral prefrontal cortex" does most of the work--meaning that we all use just a little of the brain the do a lot. The 80/20 or 90/10 thesis seems to apply at all times. Ten or twenty percent of just about anything drives 80 or 90 percent of all results. See Natalie Angier, "Study Finds Region of Brain May Be Key Problem Solver," New York Times, July 21, 2000, p. A11.