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.

253. -new- 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. -new- 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. -new- 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)

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 Ren� 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)

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 d�j� 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 d�j� 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 D�j� Vu Experience, the most comprehensive book on the topic,� thinks about 2/3 of the population experience feelings of d�j� 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 d�j� 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)

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)


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	Underwriter of Brain Stem--Cogent Neuroscience
	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. 253. -new- 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. -new- 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. -new- 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) 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 Ren� 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. �Neural Substrates of Envisioning the Future� has been published online by PNAS. (3/7/07) 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) 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.� The theory is controversial, however, since many have held that sleep buttresses the synapses, rather than getting them to pull back. (11/1/06) 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 d�j� 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 d�j� 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 D�j� Vu Experience, the most comprehensive book on the topic,� thinks about 2/3 of the population experience feelings of d�j� 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 d�j� 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) 194. Neuro-Art From �NeuroArt Exhibition and Conference Honour Cajal and Golgi� (International Brain Research Organization): Left: Molecular layer of the cerebellar cortex in a case of dementia praecox (S.R. Cajal, 1926). Right: Central nervous system of the Hirudo medicinalis (G. Retzius, 1891). One hundred years ago Santiago Ram�n y Cajal and Camillo Golgi were jointly awarded the Nobel Prize for Physiology or Medicine for their work on revealing the structure of the brain. To honour this momentous occasion the CosmoCaixa Science Museum, Barcelona, Spain is open its doors to the NeuroArt Exhibition on 25 April 2006. The exhibition is part of the continuing effort by the CosmoCaixa, Barcelona Science Museum of La Caixa Foundation, the International Brain Research Organization and the Spanish Council for Scientific Research (CSIC) to provide quality artistic and educational resources related to Neurosciences. This will be a permanent exhibition, but it will also tour other cities in Spain and around the world. The Exhibition The exhibition contains three sections: The early period, commencing with a detailed study of the nervous system, and containing contain drawings of some of the most important pioneers in neuroscience, including Cajal, Golgi, Retzius, Nissl, Dogiel and Alzheimer. The untouched nervous system, containing images such as those typically prepared for a scientific article or that are commonly used as cover illustrations in neuroscience journals. Left: Hippocampus of a Brainbow mouse (J. Livet, J. R. Sanes, J.W. Lichtman, 2006). Centre: Axonal rainbow (J. Livet, J. R. Sanes, J.W. Lichtman, 2006). Right: Adult stem cells from human brain (N. Sinai, A. Hinojosa, J.M. Garcia-Verdugo, A. Buylla, 2006). The interpreted nervous system, consisting of images modified by the authors in order to express an idea or concept more clearly. (6/14/06) 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) 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.� There is a host of research on plasticity, but this whole area of exploration is still quite controversial, and investigators still do not know how long the effects of brain training, even when effective, endure. We include other commentary on this topic in �Flexing Your Brain.� There is a great deal of evidence that supports the idea of brain plasticity, but its application to resurrecting tired, aged brains requires a more careful formulation of its possibilities and its limits. Some recent articles on plasticity are �Cell Type-Specific Structural Plasticity of Axonal Branches and Boutons in the Adult Neocortex� and �The Kv4.2 Potassium Channel Subunit is Required for Pain Plasticity.� 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.