February 2004

A neurobiological mapping of theory of mind Ahmad Abu-Akel Brain Research Reviews, 2003, 43:1:29-40 Abstract This paper attempts, based on a review of a wide range of clinical, biobehavioral and neuroanatomical studies, to account for the various theory of mind impairments observed in psychiatric and developmental disorders in a single neurobiological model. The proposed model is composed of a representational component subserved by posterior brain regions (temporal and parietal) and an application/execution component subserved by prefrontal regions. Information processed in posterior regions is relayed through a limbic–paralimbic system, which is essential for the implementation of theory of mind processes. In addition to its clinical implications, the proposed model accounts for (1) the ability to mentalize about both the self and others, (2) the nature of the anatomic connections of the various brain regions and their functional correlates, and (3) theories pertaining to the inferencing mechanisms used during mental representation/attribution. New 'Shuttle' Mechanism Discovered by Which Nerve Cells' Connections are Altered DURHAM, N.C. -- In the process of strengthening or weakening their interconnections, brain cells use a "shuttle" system to increase or decrease the number of receptors for a key signal-transmitting chemical, a Duke University Medical Center neurobiologist has discovered. Such control of connection strength is critical to the processes of establishing preferred neural pathways, the basis of learning and memory in the brain. The discovery not only offers new insight into how the brain manages the strength of its connections, but also potential targets for drugs to treat stroke, epilepsy and neurodegenerative disease, said Michael Ehlers, assistant professor of neurobiology. In an article in the Nov. 22 edition of Neuron, Ehlers reports that neurons control their sensitivity to the neurotransmitter glutamate by removing or inserting receptors for glutamate from the "post-synaptic membrane" - the point on a neuron at which it receives neurotransmitter signals launched from a neighboring neuron. According to Ehlers, scientists have long known that one neuron triggers a nerve impulse in another by chemical communications at connections between neurons called synapses. In this process, one neuron launches a burst of chemical neurotransmitters such as glutamate from a "pre-synaptic membrane" across a gap between the cells called the synaptic cleft. When this neurotransmitter burst reaches the target neuron's post-synaptic membrane, it binds to molecular switches known as receptors, triggering the firing of a nerve impulse in the receiving neuron. In the case of glutamate, a neurotransmitter found in more than half the synapses in the brain, one key receptor is known as the AMPA receptor. "There has been some controversy over whether this strengthening or weakening involved a pre-synaptic or post-synaptic change," Ehlers said. "And one of the possibilities for post-synaptic change was a change in the AMPA receptors. While one theory was that the receptors were somehow made more active, a relatively recent idea was that a neuron's responsiveness could be regulated by changes in the number of receptors in the membrane available to bind glutamate." Strengthening of such neural connections is known as long-term potentiation (LTP), and weakening the connection is known as long-term depression (LTD), said Ehlers. While LTP and LTD represent changes in connection strength that occur rapidly, he explained, neurons also undergo slower adjustments in their connection strength. "So there are these two competing modes of neuronal plasticity, if you will," said Ehlers. "And up until now, we had little idea of the cellular or molecular relationship between these two modes." Thus, in his experiments, Ehlers sought to understand both the rapid and slower forms of connection adjustment. He based his work on recent studies by other researchers that indicated that AMPA receptors seemed to be mobile, cycling in and out of the cell membrane. To investigate these microscopic changes at nerve cell synapses, Ehlers used various tracers to follow the movement of AMPA receptors in the synaptic regions of rat neurons grown in culture. His studies revealed that, after the receptors spend some time in the post-synaptic membrane, they are drawn back into the cell in a process called endocytosis, in which they are enveloped in a bubble-like vesicle. His experiments revealed that the rate of both this endocytosis and reinsertion of receptors depended on the firing activity of the neurons. "Our studies revealed that in some cases, the receptors would recycle and return to the membrane, but if they received a different signal, they would be degraded," Ehlers said. "So, this system allows the neuron to very quickly decrease or increase the number of receptors in the membrane by controlling the rate of recycling. Also, by selectively shunting receptors either to return to the membrane or to be degraded, the neurons can more slowly regulate how many receptors they have at that synapse." According to Ehlers, his experiments show that the regulation of AMPA receptors also appears to be related to the activity of yet another glutamate receptor, called the NMDA receptor that sits close to the AMPA receptor synaptic membranes. "Interestingly, we found that activation of either AMPA receptors or NMDA receptors can both trigger the internalization of AMPA receptors," said Ehlers. "So, depending on the relative amount of activation of AMPA or NMDA receptors, the neuron can control whether or not it maintains its synapse by keeping receptors recycling back into it, or targets internalized receptors for degradation." Ehlers and his colleagues plan to continue their work by exploring the regulatory signals that govern the system of managing receptor numbers. Such studies could have important medical implications, he said. "If you could develop drugs that would, for example, augment recycling of these receptors, you might be able to prevent the weakening of synapses that occurs in neurodegenerative diseases or impaired memory states," he said. "On the other hand, drugs that shut off recycling and promote degradation would reduce receptor activity, and potentially be useful for treating epilepsy or strokes. "Current drugs for many of these disorders, which bind to receptors to block their activation, have fairly bad side effects, but controlling the number of receptors might give us a finer level of therapeutic control - allowing a continuous scale of increasing or decreasing receptor activity," Ehlers said.

ADD/ADHD

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Physicians Concerned About Ritalin Being Forced on School Children   by Lynda Kirk, MA, LPC, BCIA-C, QEEGT   "Dare to Say No to Drugs." How many times have you seen the familiar black tee shirt with the red logo on our elementary school kids? I've always smiled as I thought, "I'm so glad to see that we're about educating our kids about drugs at this crucial age." Now I shake my head in disbelief and wonder at the irony as I read the recent chilling report in the Journal of the American Medical Association (JAMA) that the use of Ritalin and other psychotropic drugs has increased two to threefold in the years 1991-1995 among 2-to-4-year-olds. The package insert for Ritalin, however, states: "Ritalin should not be used in children under 6 years, since safety and efficacy in this age group have not been established."    The JAMA article was not the first critique of Ritalin treatment for the Attention Deficit Disorder (ADHD). As early as 1973, the U.S. Congress began holding hearings on the overuse of stimulant drugs in our nation's schools. 25 years ago, there were over 200,000 children using Ritalin and other amphetamines to treat ADHD. Ironically, today in our public schools, which are being promoted as "drug-free zones," many of our students are routinely being given legal mind-altering drugs. Today's current estimates are that in excess of six million children are taking Ritalin on a daily basis. Nearly 90 percent of all Ritalin sales worldwide are in the USA.   In early May 2000, the American Academy of Pediatrics urged pediatricians and family doctors to take a more active role in correctly diagnosing attention deficit/hyperactivity disorder (ADHD) in children, and issued guidelines to help them. "ADHD is the most common neurobehavioral disorder of childhood," the Academy reported in this month's issue of the journal Pediatrics. "ADHD is also among the most prevalent chronic health conditions affecting school-aged children." The Academy also voiced concern about the lack of consistency in diagnosing ADHD as well as the potential for the overuse of prescription medication.   Although it is clear that psychotropic drugs do help some individuals with ADD, many parents are concerned about using such drugs in younger children as well as side effects over the long haul. Many are seeking effective, non-drug alternatives to treating ADHD. According to WebMD, "Neurofeedback, a technique for learning self-regulation of brain activity, is a new treatment option for individuals with ADHD. The individual learns how to suppress brain activity associated with distraction, while boosting brain activity associated with focused attention.   The way in which drug-free neurofeedback therapy works is illustrated in the true story of Laura, a bright, precocious eleven year-old. She has a house-full of pets, writes wonderful poetry, takes guitar lessons, and her daddy is teaching her to shoot skeet. Laura learns quickly and easily, but last year problems at school became serious.  She was not turning in assignments. Often her work was lost or misplaced. “I couldn’t concentrate,” Laura said. She was so distractible that staying focused long enough for her to finish her homework was an exhausting, frustrating process for both Laura and her mother.    Concern for her daughter’s well being led Laura’s mother to seek medical help for Laura’s problems. Her doctor diagnosed Laura’s condition as Attention Deficit Disorder (ADD) and prescribed the drug Ritalin to control the problem.    According to Laura’s mother, Ritalin proved to be an unsatisfactory and ineffective treatment, so Laura, her mother and her doctor decided on a course of EEG biofeedback (neurofeedback) as an alternative to the medication. Laura received her neurofeedback at the Austin Biofeedback Center, where her brain was found to produce an excess of slow frequency brain waves accompanied by low levels of fast frequency brain waves - a pattern that is typical of individuals with ADD.   According to Laura, “I was nervous at first, and I thought it felt kind of weird having them clip the things (sensors) on my ears - but it was fun!” Her twice-a-week training sessions began with the placement of delicate wire sensors, with drops of conductive gel, on her scalp and ears. The sensors were attached to an electroencephalograph (EEG) that “read” and interpreted the electrical activity of her brain and then fed this information into a computer. Software in the computer translated the brain activity into pictures and sounds that Laura could use to train her own brain.   Laura's brain learned to produce the higher levels of fast waves and lower levels of slow waves that are exhibited in a more focused brain. Some of the software even produced video games that Laura learned to play with her own brainwave patterns through the EEG, instead of using a joystick.   According to Jim Robbins' new book A Symphony in the Brain: The Evolution of the New Brain Wave Biofeedback, "Using electroencephalograms (EEGs) and computerized biofeedback equipment, neurofeedback clinicians train patients to function in brain frequencies they don't normally use. This exercise strengthens the brain and the rest of the nervous system, which in turn has powerful effects on the entire body. Proponents say the training not only helps treat medical problems from epilepsy to ADD but can also improve everything from golf scores to sleep to opera singers' voices."   Guided by the brainwave training on the computer and with coaching and encouragement from her biofeedback therapist, Laura began to make progress. As her brainwave patterns became more normalized and flexible, her organizational problems at home and at school began to disappear. Now, several months later, Laura reports that she has made straight A’s in the last two grading periods with no missing homework. “I’ve been able to keep my locker clean and my desk clean,” Laura smiles.   “Which is a miracle!” her mother interjects.    Even better, according to Laura, “Another problem was that I would have a ton of homework and we never had any time for activities. Now I get a lot of [homework] done in school. I’m a lot happier because it’s made things easier for me.”   Laura’s mom is happy too, “It has really helped all our lives-a lot! It has really made a difference in my life. I don’t have to constantly sit down with her and make sure she is doing her homework anymore!”   Lynda Kirk, MA, LPC, BCIA-C, QEEGT, is national authority on the clinical applications of biofeedback and has been in practice for over 20 years.   Austin Monthly Magazine Drugging Our Kids by William Norman Grigg Despite the dangers posed by drugs such as Ritalin, some schools are threatening parents with child abuse charges if they refuse to drug their children. Shaina Dunkle was a bright, energetic 10-year-old girl when she died in a pediatrician’s office in Bradford, Pennsylvania, in February 2001. A little more than a half-hour earlier, she had collapsed in the school library. Shaina had a history of asthma and problems with her kidneys and urinary tract, but these problems weren’t responsible for her tragic and unexpected death. A postmortem ruled that the child died from the toxic effects of Desipramine, a psychoactive drug she had been compelled to take after a school psychiatrist suggested she suffered from Attention Deficit Hyperactivity Disorder (ADHD). Shaina’s problems began while attending first grade in 1997. Like many other normal and healthy youngsters, she had problems sitting still, concentrating on classroom instructions, and listening to her teachers. In an interview with the investigative radio program Scams & Scandals, Shaina’s mother Vicky recalled that the youngster "was placed outside the classroom [and] not allowed to study with the other children." On one occasion, Shaina’s teacher, rebuking the child for having a messy desk, emptied its contents on the classroom floor and had her replace them as her classmates erupted in laughter. Old enough to feel the sting of ostracism, Shaina started to have "nightmares [and was] beginning to be afraid of going to school," Vicky related to her radio audience. Lost angel: Shaina Dunkle, adopted by her parents Steve and Vicky at birth, was a "sweet, caring, and giving" child who enjoyed dancing and sports. Like many healthy, active children, Shaina had difficulty adapting to a classroom environment. School administrators defined those difficulties as symptoms of a spurious medical condition called Attention Deficit Hyperactivity Disorder (ADHD), and compelled Shaina's parents toput her on a regimen of dangerous psychoactive drugs, including Desipramine. Shaina died in February 2001, at 10 years of age, from coronary arrest precipitated by "Desipramine toxicity." Knowing that their daughter had challenges with learning that could only be addressed on a one-to-one basis, Vicky and her husband Steve took Shaina out of class and home-schooled her for the rest of her first grade year. "I could see a definite difference in her behavior, and she was making very good progress in her studies," Vicky told THE NEW AMERICAN. As the summer of 1998 waned and children prepared to return to school, Shaina — feeling the pull of her peer group — wanted to go back. "She saw the other girls her age getting their school clothes and backpacks, and she wanted to be with them," Vicky recalled. After consulting with school officials, Vicky and Steve relented. But within the first two weeks of classes, Shaina’s problems resumed. "Shaina was behind the other children," Vicky recounted. "We wanted to have her undergo a learning support evaluation." Immediately after that evaluation — in January 1999, halfway through the school year — Shaina was placed in a learning support program. But this didn’t satisfy school officials. "In March [1999]," Vicky recalled, "we got a letter from the school psychologist telling us that Shaina was still struggling, and that she displayed all of the ‘characteristics’ of a child suffering from Attention Deficit Hyperactivity Disorder. This seemed odd to us, because Shaina wasn’t a disciplinary problem for anybody. She was an obedient child, sweet, caring, and giving. She did have a short attention span, and could be distracted fairly easily, but these are hardly abnormal traits in a child her age. And she did have challenges to overcome in her schoolwork. But the psychologist and other school officials focused on ADHD as the problem, and began pressuring us — not forcing us, but pressuring us — to have her examined and ‘medicated.’" Although they balked at the suggestion, Vicky continued, "we were beginning to believe that something must be wrong. After all, we thought, these people are the experts. They’re with these children eight hours a day. If this is what they say needs to be done, maybe we should do it." In April 1999, the Dunkles visited a physician. Forty-five minutes later they emerged with a diagnosis of ADHD and a prescription for Wellbutrin. Almost immediately the side effects became visible: Shaina began to lose weight and her disposition changed. Vicky took Shaina off the drug and took her back to the physician, who prescribed another drug called Effexor, which led to recurring bouts of insomnia. After the third visit, the second grader was put on a third drug, Desipramine, "which we were told had fewer side effects and was less likely to be abused than Ritalin," Vicky observed. At first, "Shaina seemed to respond well to the Desipramine," Vicky continued. "Her attention span got longer, her handwriting got neater. But then we got calls from the school telling us that she was relapsing. This happened several times, and each time we took her back for treatment — which meant a larger dose of Desipramine." Neither Shaina nor her parents were warned that Desipramine (which the FDA has not approved) should not be used by people suffering from kidney ailments, as Shaina did. After starting with a daily dosage of 10 milligrams, Shaina’s daily intake steadily increased to 200 milligrams by February 2001 — and her physical and behavioral problems escalated as well. Shortly before she died, "Shaina acted out in class, throwing a pencil at one student and threatening another with scissors," Vicky told THE NEW AMERICAN. "This sent up vivid red flags for her teachers, and for us, too, because Shaina was never an aggressive or violent child." In mid-February 2001, Shaina’s physician — who insisted that Desipramine wasn’t causing the side effects — ramped up the daily dose to 250 milligrams. One week later, Shaina was dead. "That morning, I gave her breakfast, French-braided her hair, and then administered her 250 milligrams of that drug," Vicky recalled to THE NEW AMERICAN. "She left at a quarter to eight, saying, ‘I’ll see you at three, Mommy.’" Three hours later Vicky got a call from the school nurse saying that Shaina had fallen and injured her cheek during what appeared to be a mild seizure. Vicky and Steve rushed to the school, collected their child, and drove her to the doctor’s office. Shaina appeared normal during the half-hour drive. As Vicky signed in with the receptionist, Shaina collapsed into a seizure. A physician rushed in to examine the child; after a moment he instructed a nurse to "call a code 99." "I’ve worked in hospitals, and I knew that ‘code 99’ referred to cardiac arrest," Vicky explained. "Shaina looked into my eyes as her life ended, and I could do nothing to save her," recalled Vicky. "It’s been two and a half years, and I relive those last few minutes every day." The coroner’s report certified that Shaina was killed by Desipramine toxicity. As her dosage increased — in response to complaints from school officials that her behavior wasn’t improving — Shaina was unable to metabolize the drug. The accumulated toxins in her bloodstream precipitated a heart attack. Vicky and Steve adopted Shaina at birth. Vicky was present in the delivery room when Shaina took her first breath and present in the pediatrician’s office when she took her last. "I believe God sent her to us to take care of," commented Vicky, "and I’ve asked God too many times to count why He took her from us." Every single night, Vicky and Steve visit a nearby cemetery to pray over Shaina’s grave. Just Say No? Boyhood a sickness? The DSMV-IV, sometimes called the bible of psychiatry, claims that a child who "fidgets," "squirms," or "has difficulty playing or engaging in leisure activities quietly" may suffer from ADHD. As any parent of young boys can attest, this would define practically any normal, healthy young male as suffering from mental illness. Steve and Vicky plausibly contend that the school officials who insisted on drugging Shaina were directly responsible for her tragic and unnecessary death. "Children go to school to be educated, not medicated," stated Vicky Dunkle. "Parents should not be pressured to drug their children." Over the past decade, the federal government has spent millions of dollars on drug prevention programs targeting school-age youth. At the insistence of the federal Office of National Drug Control Policy, counter-narcotics messages have been insinuated into youth-oriented television programs. With the help of federal subsidies, Drug Abuse Resistance Education (DARE) programs have been set up in nearly every school system across the country. But at the same time, school officials nationwide routinely insist that children said to suffer from ADHD be placed on various psychoactive drugs, particularly Ritalin — listed by the FDA as a Class II controlled substance along with opium, codeine, morphine, and cocaine. Much of the counter-narcotics propaganda generated by the Office of National Drug Control Policy focuses on the stereotypical schoolyard drug pusher, usually portrayed as a grimy adult or a bullying older youth. Anti-drug messages extol open communication between parents and children, and urge children to stand up boldly to pushers. All of this is well and good, of course. But, asks Scams & Scandals host/investigator Tai Aguirre, what if "the drug pusher happens to be your school social worker or psychologist, and they’re telling you your child either takes their drugs or they won’t be allowed in school — or, even worse, that [they’re] going to charge you, the parent, with neglect? What do you do then? Do you ‘just say no’? Can you say no?" Drug Him — or Lose Him Speaking at a congressional hearing in August 2002, Neil Bush — brother of President George W. Bush — described his own seven-year ordeal when his son Pierce was diagnosed with ADHD at age 10. "There is a systematic problem in this country, where schools are often forcing parents to turn to Ritalin," concluded Bush. "It’s obvious to me we have a crisis in this country." Many parents have discovered that refusing to drug their children may be met with child abuse or neglect charges and the loss of their parental rights. This highlights a critical difference between street-corner drug pushers and their counterparts on the government’s payroll. A private pusher can’t force children to take drugs by telling them that they will otherwise be torn from their families. In July 2000, Michael and Jill Carroll of Albany, New York, were reported to social services authorities after they took their son Kyle off Ritalin. As is the case with many other youngsters on Ritalin, Kyle displayed a loss of appetite and difficulty sleeping. When Mr. and Mrs. Carroll decided that it would be in Kyle’s best interest to stop using the drug, an official from the local school district filed a complaint with Albany County’s Department of Social Services. A family court judge ruled that the parents must continue to drug their son to avoid child abuse charges. In a story on the case, Albany’s NBC affiliate WNYT-TV reported that "Social Service workers will visit the family throughout the next year" to assure that the parents comply. This highlights another distinction between government dope-pushers and their private-sector equivalents: Private pushers are content to sell their product; they don’t thrust their way into their customers’ homes and force them to consume it. The Carrolls are hardly the first or only parents forced to dope their children under the threat of losing them. In 2000, Patricia Weathers of Millbrook, New York, was "hot-lined" by local school officials — threatened with the seizure of her son by Child Protective Services — after she took him off a drug regimen that included Ritalin, Dextrostat, and Paxil. "Mom, it makes me feelbad," complained nine-year-old Michael Mozer about the "cocktail" of drugs he was forced to take, including a varient of Ritalin called Dextrostat. Once a bright, active, friendly boy, Michael became sullen and withdrawn as the mind-altering drugs took their toll; he eventually began to have hallucinations in which "there's a person inside my head telling me to do bad things." After his mother defied the so-called experts and took Michael off drugs, she was "hot-lined" to Child Protective Services and accused of medical neglect. "When Michael was in kindergarten and first grade, his teachers told me he had behavior problems — he was easily distracted, had problems focusing, and wouldn’t sit down," Patricia told THE NEW AMERICAN. "I was told that if I didn’t ‘medicate’ him — that is, drug him — he wouldn’t learn. I was assured that the drugs were mild. I wasn’t told that they are as dangerous as cocaine, or that there were health risks and side effects. They kept calling me down to the office, wearing me down. Eventually the principal told me point-blank: ‘Counseling is too slow. Think of medicating this child or I will do everything in my power to transfer him into a special education program.’ So we started him on Ritalin just before the end of his first grade year." According to Patricia, Michael was "diagnosed" with ADHD on the basis of the Acters Profile for Boys, a widely used checklist for behavior disorders. "It basically lists stereotypical boy behaviors — untidiness, disorganization, inattentiveness — as symptoms of ADHD," she contended. School officials just "checked off the list, gave it to the pediatrician, and he put Michael on Ritalin." Significantly, Patricia observed, "I only put him on the drugs when he was going to school. He never had it on weekends, or on summer vacation. And I would never have done this if it weren’t for the coercion from the school." From Healthy to Haunted By third grade, Michael’s behavior had deteriorated dramatically. "He was eating his clothing, slobbering, and did not want to go out for recess," related Patricia. Michael was put on Dextrostat, which apparently exacerbated his problems. Rather than reconsidering the wisdom of drugging the child, school officials insisted that Michael suffered from "some other disorder" — variously described as either bi-polar disorder or "social anxiety." Paxil, an anti-anxiety drug — was added to the regimen. By this time — late 1999 — "Michael was telling me, ‘Mom, it makes me feel bad,’" Patricia told THE NEW AMERICAN. "He was having major incidents of violent behavior, hallucinating, and even hearing voices. I finally took him off the drugs in October 1999, and started doing my own research." After learning of the drugs’ side effects andhealth risks, Patricia confronted school officials in early January. "I made it very clear that we were finished with the drug route," she recalled. "The principal slammed my information down on my desk and said, ‘We have nothing left to offer Michael.’" Shortly thereafter, as Patricia prepared to fly to Texas with her son to seek specialized medical treatment, she was informed that school officials had "hot-lined" her to Child Protective Services (CPS), claiming that she was guilty of medical neglect. "[Michael’s] behavior at school is bizarre: He hears voices and appears delusional, he chews on his clothes and paper, he talks to himself and rambles when he talks," stated the child abuse complaint filed against Patricia Weathers by the local school district. A month-long investigation cleared Patricia of child abuse and "medical neglect" after evaluations by independent psychiatrists proved that Michael’s symptoms reflected state-ordered drug use, rather than parental mistreatment. "I trusted the judgment of ‘experts’ rather than my own common sense," commented Patricia to THE NEW AMERICAN. "Millions of other parents make the same mistake. If I had known about the risks and effects of those drugs, there is no way I would have allowed them to drug my son." While Patricia Weathers and her son survived both the forced drugging and the attempted child grab, six months after Michael was taken off the drugs he was found to have a heart murmur — a recognizable, if rare, side effect of drugs like Ritalin. Michael has been home-schooled for three years, and may enroll in private school this fall. "It’s wonderful," Patricia enthused. "It was difficult at first, but he’s growing and thriving now — and he loves to learn. He was socially isolated while he was on the drugs, and now he’s anxious to socialize and play sports." Fourteen-year-old Matthew Smith of Auburn Hills, Michigan, was not so fortunate. He died on March 21, 2000, after seven years of state-imposed Ritalin use. Matthew’s death certificate candidly states: "Death caused from long term use of methylphenidate [Ritalin]." Dr. Ljuba Dragovic, a pathologist who presided over Matthew’s autopsy, noted that the youngster’s heart displayed tell-tale small vessel damage from prolonged Ritalin use. (At the time of death Matthew’s heart had swollen to 402 grams — larger than that of a full-grown man, which typically weighs 350 grams.) "We were told Matt had ADHD when he was six years old," Matt’s father Larry told THE NEW AMERICAN. "We were told that the condition was a legitimate medical disorder, that he needed the Ritalin in order to deal with this objective medical condition. But we just didn’t have a good feeling about putting our boy on drugs." As Matt’s parents dragged their feet, the pressure to drug their child increased. A letter from the school social worker to Matthew’s parents complained: "We would have hoped you would have started Matthew on a trial of medication by now." At one counseling session, Larry Smith recounted to THE NEW AMERICAN, "the social worker told us we could be charged with medical or emotional neglect if we refused to take Matthew to the doctor and get him on Ritalin. My wife and I were intimidated and scared. We believed that there was a very real possibility of losing our children if we did not comply with the school’s threats." The Smiths took Matthew to see a physician in Birmingham, Michigan. On the basis of what Larry calls "a five-minute pencil twirling trick," Matthew was diagnosed as having ADHD. As the physician scribbled out a prescription for Ritalin, he "asked us to remind the school that he was not a pharmacy," recalled Larry Smith. "I can only conclude from his comment that we were not the first parents sent to him by this school." Essentially, the school system used the implied threat of kidnapping the Smiths’ children to force them to drug their oldest, which resulted in his death. A Growing Scourge Students--or future junkies? Ritalin is listed--along with cocaine--as a "Class II substance" for its narcotic properties. In many cities, including Detroit, Minneapolis-St. Paul, and Chicago, Ritalin is used as an inhalant drug, or combined with other narcotics such as cocaine and heroin. Military recruiters disqualify applicants with a history of Ritalin use. Yet millions of children in our public school system are pressured into taking Ritalin and similar dangerous drugs." Forced drugging of schoolchildren has become so common that the mainstream press — which can usually be counted on to carry water for the government school system — has taken note. USA Today for August 8, 2000, reported that "some public schools are accusing parents of child abuse when they balk at giving their kids drugs such as Ritalin, and as judges begin to agree, some parents are medicating their children for fear of having them hauled away." Advocates for the forced medication of schoolchildren diagnosed with ADHD and similar dubious maladies are unapologetic about the use of such totalitarian methods. "It’s becoming increasingly clear that this is a powerful treatment that can be life-saving for some children," insists Peter Jensen, a board member of Children and Adults with Attention Deficit Disorder (CHADD), which advocates the use of Ritalin and similar drugs. "This is going to be happening more and more," he promises. Dr. Jensen, whose high-profile advocacy earned him the sobriquet "Mr. ADHD," does believe, however, that there are a few parents whose judgement can be trusted when they refuse to drug their children. Speaking at a gathering of psychologists in December 2001, Dr. Jensen emphasized that "medication is not the only effective nor … the best treatment option for every child," reported the Monitor on Psychology. "When his own child was diagnosed with ADHD, Jensen told the audience, he and his wife opted not to use medication." © Copyright 2003 American Opinion Publishing Incorporated

ALZHEIMER'S RESEARCH

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Using vitamin E and C supplements together may reduce risk of Alzheimer disease Jan-2004 CHICAGO – Elderly persons who take individual vitamin E and C supplements together may reduce their risk of Alzheimer disease (AD), according to an article in the January issue of The Archives of Neurology, one of the JAMA/Archives journals. According to the article, the public health threat of AD will continue to grow as people live longer. Previous studies have shown that antioxidant vitamins may protect the brain against damage caused by free radicals and other reactive oxygen species – molecular byproducts of basic cellular metabolism. Neurons are especially sensitive to damage caused by free radicals, which is believed to be partially responsible for the development of AD. Incorporating antioxidants (which help to neutralize these free radicals) into the diet through food or supplementation may help protect neurons. Peter P. Zandi, Ph.D., of The Johns Hopkins University Bloomberg School of Public Health, Baltimore, and colleagues examined the relationship between antioxidant supplement use and risk of AD. The researchers assessed the prevalence of dementia and AD in 4,740 elderly (65 years or older) residents of Cache County, Utah in 1995 to 1997 and collected information about supplement use. These residents were followed-up in 1998 to 2000 for new cases of dementia or AD. The researchers identified 200 cases of AD (prevalent cases) between 1995 and 1997, and 104 new cases (incident cases) of AD during follow-up. The researchers categorized participants as vitamin E users if they reported taking an individual supplement of vitamin E or a multivitamin containing more than 400 IU (international units) of vitamin E. Vitamin C users reported taking vitamin C supplements or multivitamins containing at least 500 micrograms of ascorbic acid. Individuals were classified as multivitamin users if they reported taking multivitamins containing lower doses of vitamin E or C. The researchers found the greatest reduction in both prevalence and incidence of AD in participants who used individual vitamin E and C supplements in combination, with or without an additional multivitamin. "Use of vitamin E and C (ascorbic acid) supplements in combination reduced AD prevalence [by about 78 percent] and incidence [by about 64 percent]," the authors write. The researchers also found "no appreciable association with the use of vitamin C alone, vitamin E alone, or vitamin C and multivitamins in combination," and prevalence of AD. "The current… recommended daily allowance for vitamin E is 22 IU (15 micrograms), and for vitamin C (ascorbic acid), 75 to 90 micrograms," the researchers write. "Multivitamin preparations typically contain these approximate quantities of both vitamins E and C (more vitamin C in some instances), while individual supplements typically contain doses up to 1,000 IU of vitamin E and 500 to 1,000 micrograms or more of vitamin C (ascorbic acid). Our findings suggest that vitamins E and C may offer protection against AD when taken together in the higher doses available from individual supplements." Variety of Factors May Contribute to Memory Loss and "Senior Moments" Duke University Medical Center Frustrating incidents of forgetfulness seem to occur more often as people age. Throughout the day people often forget little things: "Where did I leave my keys? Who was it I was supposed to call? What does this scribbled yellow note mean, anyway?" As people age, these sorts of memory lapses or "senior moments" can become commonplace, and many in the baby boom generation simply chalk it up to advancing years. But Heidi White, M.D., assistant professor of geriatric medicine at Duke University Medical Center, says age isn't the only factor in memory loss. "If people are noticing changes in their memory and thinking, they really should mention it to their doctor," White says. "Sometimes, there are simple things that can be investigated to find an answer to why that may be happening." White says among the possible causes for cognitive decline are medications -- especially sedatives, which can dull the mind; alcohol, which interferes with sleep; depression, which affects concentration; and hearing or vision impairment. "Simple things like having your hearing and vision checked are another way of just making sure we're not shutting out aspects of the world around us that can help to keep us vital and active," she says. White adds that regular exercise for both the body and the brain helps to optimize cognitive function. "I think common sense would tell us that it's important to pursue physical exercise and that it's also important to stay active cognitively," White says.

AUTISM NEWS

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Abnormal brain lateralization in high-functioning autism. J Autism Dev Disord. 2003 Oct;33(5):539-43. Escalante-Mead PR, Minshew NJ, Sweeney JA. University of Illinois at Chicago, Chicago, IL 60612, USA. Disturbances in lateral preference in autism are of interest because of their potential to shed light on brain maturational processes in this disorder. Forty-seven autistic individuals with a history of disordered early language development and 22 autistic individuals with normal early language acquisition were matched with 112 healthy individuals and compared on a standardized measure of lateral preference, the Edinburgh Handedness Inventory. Autistic individuals with a history of early language disturbance showed more atypical cerebral dominance than both healthy participants and autistic individuals with normal early language skills. The data indicated maturational disturbances in establishing lateral preference rather than increased rates of left handedness. Atypical establishment of cerebral dominance may be one cause of disordered language development in autism. Phase 3 Study Of Secretin For Autism Fails To Meet Dual Primary Endpoints 1/5/2004 Source: Repligen Corporation Repligen Corporation announced today that its Phase 3 clinical trial in autism of RG1068, synthetic human secretin, failed to meet the study's dual primary endpoints, improvements in social interaction as measured by the Autism Diagnostic Observation Schedule ("ADOS") and the parental Clinical Global Impression of Change ("CGI"). The Phase 3 study had a higher placebo effect than was observed in the Phase 2 study and neither endpoint showed a significant treatment effect in the entire group. A prospectively defined subset analysis of the higher functioning patients (n=68) showed a statistically significant improvement of RG1068 versus placebo on ADOS but not on the CGI. This finding may indicate that measuring a response to RG1068 is more difficult in patients with lower levels of cognitive function. A preliminary review of the safety data showed no clinically meaningful differences between RG1068 and placebo in side effects and there were no serious adverse events observed in the Phase 3 trial. This study was a double-blind, placebo-controlled, clinical trial which evaluated 132 children aged 2 years 8 months to 4 years 11 months with moderate to severe symptoms of autism. Each patient was comprehensively evaluated at baseline, received six injections of RG1068 or a placebo over 18 weeks and was then reevaluated for improvements in the symptoms of autism. The primary endpoints were improvements in reciprocal social interaction as measured by ADOS, which is performed by a trained psychologist, and the parental CGI. The trial was carried out at 15 medical centers in the United States. "We would like to thank the patients, their parents and the clinicians for their participation and support in this study," stated Walter C. Herlihy, President and Chief Executive Officer of Repligen. "We have developed an extensive preclinical and clinical data set which supports the use of secretin in the treatment of other neuropsychiatric diseases and we plan to continue our efforts to develop secretin for schizophrenia. Future development in autism will be dependent on a thorough evaluation of the Phase 3 data and discussions with the Food and Drug Administration." Gastrin-releasing peptide receptor (GRPR) locus in Japanese subjects with autism Tetsuya Maruia, b, Ohiko Hashimotoa, Eiji Nanbac, Chieko Katoa, Mamoru Tochigia, d, Tadashi Umekagea, Nobumasa Katoa and Tsukasa Sasaki, , a, e a Department of Psychiatry, Graduate School of Medicine, University of Tokyo, Tokyo, Japan b Tsurugaoka Hospital, Tokyo, Japan c Gene Research Center, Tottori University,, Yonago, Japan d Haryugaoka Hospital, Fukushima, Japan e Health Service Center, University of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo, Japan May 2003. Abstract Gastrin-releasing peptide receptor (GRPR) gene is considered a candidate locus for infantile autism for several reasons. The present study investigated two polymorphic sites (C/450/T and C/661/T) in the second exon of the GRPR gene in Japanese patients with autism (DSM-IV) and healthy subjects. The two polymorphic sites were at high linkage disequilirium, consistent with a previous study in a North American population. The C450–C661 allele, which was observed in one-third of the chromosomes from the North American subjects, was less frequent (6–7%) in the Japanese subjects, suggesting a large ethnic difference in the frequency of the polymorphism. The allele frequencies and genotype distributions were not significantly different between the patients and controls. However, further studies are required to exclude the GRPR locus as a candidate locus for autism, considering the low frequency of the polymorphism in the Japanese subjects.   Parents of Children with Autism Turn to Medical Alternatives Health Behavior News Service NEWSWISE Life News (Social and Behavioral Sciences), 08-Jan-2004 -- One in three children recently diagnosed with autism received complementary or alternative medicine treatments and 9 percent used a potentially harmful type, according to a new study of patients in Philadelphia. Latino children were more likely to use complementary and alternative medicine compared to other groupings, according to Susan E. Levy, M.D., and colleagues, while those with additional, non-autistic disorders or deficits in thinking, learning and memory were less likely to do so. "The goal of many of these treatments is most likely not to treat autism per se, but rather to address some of the associated problems faced by these children," she says. The researchers studied 284 patients at The Children's Hospital of Philadelphia. Their work appears in the December issue of the Journal of Developmental and Behavioral Pediatrics. There is no cure for autism, but experts conclude that the best way to improve symptoms makes use of intensive behavioral and educational methods, says Levy, director of the hospital's Regional Autism Center. Nevertheless, parents of some autistic children may choose to try other sources of treatment in hopes of alleviating symptoms of the condition. Levy and colleagues divide these nontraditional treatments into four categories. First, there are unproven but harmless biological treatments that have no basis in medical theory (like vitamin B6, gastrointestinal medications or antifungal agents). Another group includes unproven but harmless treatments with some theoretical basis (like vitamin C, gluten-free diets or hormones). A third category includes unproven, potentially harmful treatments (such as chelation, antibiotics, high-dose vitamin A, immunoglobin or withholding immunizations). The final group consists of nonbiological treatments (including animal therapy, auditory integration training and others). Latinos were seven times more likely to try one of these approaches. However, the small number of Latinos in the study (nine) may have partially accounted for the disproportionate results, Levy says. In any case, she says, "Latino" may be too broad a term to have useful meaning. She cautions that differing national origins and levels of adaptation to American culture may produce varying results with a group commonly combined as Latino. Nevertheless, the apparently increased use of complementary or alternative practices may reflect important cultural issues concerning autism. The researchers also noticed reduced use of complementary and alternative medicine among patients with additional diagnoses, including both medical ailments and mental retardation. Use of potentially harmful complementary and alternative medicine was found in significant levels among those who had seen a health-care provider about the diagnosis before coming to the regional autism center. There was some evidence that patients who had to wait longer for an appointment at the center -- often for months -- were also were more likely to use riskier alternatives. "Longer wait times for an appointment and the older average age of those who had seen previous providers may have been associated with greater frustration among the parents of these children, leading to use of complementary and alternative medicine with higher associated risks," Levy said. Use of complementary and alternative medicine should not be dismissed out of hand, she says, and she suggests ways that physicians can creatively engage parents regarding their beliefs about autism and how to treat it. "If parents believe that clinicians do not respect their beliefs and decisions or are unwilling to negotiate around the use of additional treatment strategies," she concludes, "these strategies may become alternative rather than complementary."

BRAIN INJURY

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Building Brainpower: Neurobiofeedback helps tame the storm for brain injury patients THE FLINT JOURNAL FIRST EDITION Monday, January 19, 2004 By Ron Krueger JOURNAL STAFF WRITER QUICK FACTS The cells in an infant brain are like open grassland. As the child learns, is stimulated and exposed to the world, the grassland begins to sprout thicker grasses, then small shrubs and trees that are separated from each other. The trees grow closer larger and closer and branches multiply. Finally, there is a rich, dense canopy of connected neurons, teeming with life. The richer the canopy, the more connections there are among the trees, the more fertile the habitat. -- From A Symphony in the Brain' by Jim Robbins Darren sits in a small, darkened room with sensors connected to his scalp. Before him is a video monitor showing four frequency bars that dance up and down. The bars reflect the electrical activity on the right and left sides of the 16-year-old's brain. (Darren is not the youth's real name. The family asked that his name not be used.) Technician Don Deering instructs the Shiawassee County teen to relax and focus. "I want him to remain alert but clear his mind," Deering says. The goal of the exercise is to help the young man's brain work better in the aftermath of a brain injury suffered in a September 2002 fall. The technique is called neurofeedback, neurobiofeedback or EEG biofeedback. By instantaneously "feeding back" a person's brainwave activity, it is believed she or he can improve the efficiency of the brain. Darren's mother says it is working. "I was really scared when they said they wanted to hook his head to some computer," she said. "But I can't say enough good about this therapy. It has given me my son back." When Darren was injured, doctors told his mother he had suffered a mild brain injury and to watch for symptoms. "He called me from school one day and told me to come pick him up," she says. "He couldn't remember his locker combination or where he was supposed to go. He was totally confused." Over the next months, she says she watched him deteriorate further. He suffered headaches, blurred vision, was tense and slept for long periods. "He slept all the time, then he didn't sleep at all. He was a mess." The scientific basis of neurofeedback is the electrical activity of the brain. Author Jim Robbins calls it a "constant electrical storm," but it is little more than a whisper in terms of voltage and thus hard to measure. The first known measurements were made by German psychiatrist Hans Berger in the 1920s. He placed leads on the head of his teenage son and connected them to a pen trained on a piece of moving paper. Berger hooked up all kinds of people to his primitive electroencephalogram - or EEG. He connected his 14-year-old daughter and watched the pen jumped when he asked her to divide 196 by 7, says Robbins in "A Symphony in the Brain" . Further research showed the human brain operates between 1 and 40 hertz. A hertz is the number of cycles per second. The higher the hertz, the faster the brain wave. Wave activity was broken up into five ranges. A person sleeping normally registers 4 hertz and below. In a drowsy state, the range is 4 to 8. The expected range for someone who is relaxed but focused is 8 to 12. For someone who is relaxed but thinking, it is 12-15 and for active thinking, it is 15-18. Nineteen and above indicates excitement. These ranges have been given Greek letter names: delta and theta for low activity, alpha for relaxed focus, beta for active thinking and high beta for excitement. Later research turned up the 12-15 range ("active thinking") when sensors were attached to the so-called sensorimotor regions - the parts of the brain responsible for voluntary movement and processing information from the skin, muscles, joints and organs. Darren and his family learned about neurofeedback through Neal Alpiner, an M.D. specializing in rehabilitation. Most of his patients have brain injuries. Alpiner last year founded the Neurohealth Institute with offices in the Hurley Eastside Clinic, 2700 Robert T. Longway Blvd. The institute consists of three small rooms for neurofeedback and one each for innovative vision and auditory therapies. He contracted with Deering to perform the feedback therapy. Deering, a Ph.D. candidate in psychology, works with James White Jr., a Ph.D. psychologist, at the Michigan Institute for Neurofeedback in Troy. White has been working in neurofeedback for more than a decade. Alpiner says neurofeedback is no longer experimental, although some in the health insurance industry and medical establishment still think that. "Are physical and occupational therapy experimental? Is speech therapy experimental?" Alpiner asks. "We use them not because there are lots of expensive studies to prove they work. We just know they work. It's the same with neurofeedback. Any program that is serious about brain injury rehabilitation has to offer it." Darren's headaches and nausea are forms of biofeedback. His brain is telling him something is wrong. The stethoscope a physician uses to checks a person's heart and lungs is a biofeedback instrument. Sophisticated neurofeedback equipment and software, operated by a trained technician, allows the patient to suppress inappropriate low-frequency waves and increase the desirable beta action. How one does this isn't simple to explain. "It's an unconscious process that adults usually try to make conscious," Deering said. "It all has to do with getting that feedback and reacting to it." It is no mystery why brainwave activity in a traumatized brain will be disrupted. The effects will show themselves in an EEG, just as the physical damage will show up in a CT scan or MRI. But why do abnormal brainwaves occur where there is no visible damage? This is not precisely known, but neurofeedback experts readily share theories based on their observations. Robbins says it has to do with the "disregulated" brain. Genetics, birth trauma and a long list of environmental factors - poor diet, toxic metals in the body, overwork, an unhealthy home environment - can stress the brain into hyper- or underactivity or just plain instability, he writes. He reports that two neurotherapists, Susan and Siegfried Othmar, insist that the myriad of brain-related diagnoses - from bipolar disorder, addictions and immune dysfuction to panic attacks, epilepsy and migraines - can be traced to these three kinds of brainwave dysfunction. Robbins says research backs the effectiveness of neurofeedback in treating ADD/ADHD, epilepsy, depression and mild brain injuries. It is being used to treat many other conditions with anecdotal evidence of benefits, he adds. Research into Alzheimer's and dementia supports the thesis that maintaining an active, healthy lifestyle and using one's head - taking classes, learning new skills, even doing crossword puzzles - keeps a brain healthy. Darren, in his sessions, gets feedback two ways. The dancing bars on the screen will glow red when his brainwaves are in the desirable range and gray when they hang in the slow delta-theta range. As long as his waves remain in the active area, a tone is heard. When they slip, the tone stops. With their lower boredom threshhold, younger children need more stimulation. Ten-year-old Nicole Gay of Davison knows her active waves are in charge when a little man pushing a wheelbarrow full of gold keeps moving up the mountain. Rob Smith of Clio, 26, an automotive engineer with a severe brain injury, listens to soothing music while watching the screen. When he starts to lose focus, the music stops. Patients in time become more adept at maintaining appropriate levels, so Deering adjusts the parameters to challenge them. He also will move the sensors around on the scalp to reach different areas of the brain. "With neurofeedback, the brain eventually takes over and maintains the proper levels. If a patient slips, we always can do a tune-up, so to speak, to get them back where they belong." Those patients whom Alpiner thinks might be candidates for neurofeedback first go to Deering's Troy office for a quantitative EEG. This is an in-depth brain "mapping" procedure that tells the therapist which areas of the brain show the greatest wave abnormalities. This test is far more sophisticated than the rudimentary EEG used to determine whether individuals are susceptible to seizures, Deering said. A "QEEG" is not cheap. Deering's clinic charges $980 for one. A neurotherapy session is billed at $125 per half-hour. There is no treatment to repair damaged parts of the brain. But neurofeedback can make the healthy areas function more efficiently, Deering said. Neurofeedback has strengthened the 70 percent of Darren's brain that is undamaged enough after six months that most symptoms have subsided. "His memory has improved, he sleeps, his mood is much better and he has very few headaches," said Darren's mother. "This has done wonders." For Rob Smith, whose injury is much more severe, the changes are more subtle, but no less encouraging to his mother, Sharon. "The neurofeedback has brought him back from someone who was pretty much unresponsive. He smiles at jokes and has his way of teasing. This means a lot to us." It is a treatment once dismissed as the domain of New Age charlatans. Much of the criticism has fallen away as the technology has improved. But there is a reservoir of resistance stemming from the fact that most brain research has been based on brain chemistry, writes Robbins in his book. "Modern neuroscience is concerned almost entirely with the cellular level, with an emphasis on drugs to alter chemical flows in the brain," Robbins writes. Neurofeedback also has suffered because it was nurtured by psychologists rather than traditional medicine, he adds. James White, Deering's partner, says experience and research will determine more precisely which ailments can be most effectively be treated with neurofeedback. "The tradition of prescribing drugs and things like physical therapy and psychotherapy are limited," he said. "Drugs have side effects, some disorders aren't helped by drugs and drugs wear off. "Traditional therapies are like chipping away around the edges of a problem. Neurofeedback goes directly to the source of the problem and of opportunity to fix it. "Neurofeedback empowers the patient to rehabilitate himself. That's the really exciting thing." Language and memory profiles of adolescents with traumatic brain injury Author(s): Catherine Moran ; Gail Gillon Source: Brain Injury      Volume: 18 Number: 3 Page: 273 -- 288 Abstract: The performance of adolescents who suffered a traumatic brain injury in childhood, on language comprehension tasks with varying working memory demands, was examined. It was hypothesized that adolescents with a traumatic brain injury would perform more poorly than their non-injured peers, particularly on those tasks with high working memory demands. A case study design allowed for both group and intra-participant comparisons. A battery of language comprehension and working memory tasks was administered to six adolescents aged 12-16 years. Their performance was compared with six individually age-matched peers with typical development and to the normative data of the standardized tests. Intra-participant performance was examined by comparing results across language tasks that varied in working memory demands. Analysis revealed that individuals with traumatic brain injury performed poorly compared with their age-matched peers. However, the pattern of listening comprehension impairment differed across individuals and marked variability within the comprehension profiles for some individuals with traumatic brain injury was evident. Language comprehension tasks with high working memory demands generally posed the most difficulty for individuals with traumatic brain injury. © Taylor & Francis Ltd Attentional control and slowness of information processing after severe traumatic brain injury Author(s): Marcos Ríos ; José A. Periáñez ; Juan M. Muñoz-Céspedes Source: Brain Injury      Volume: 18 Number: 3 Page: 257 -- 272 Abstract: Attention is a basic cognitive function and a prerequisite for other cognitive processes and is frequently impaired after traumatic brain injury. In the present study, 29 severe traumatic brain injury patients and 30 control subjects completed a battery of three neuropsychological tests of attention (WCST, TMT, Stroop). The aim was to clarify the attentional mechanisms underlying tests performance and to explore the types of attentional impairment after severe traumatic brain injury. Significant differences were found between the control and clinical groups in almost all measures. However, some of these differences disappeared when the speed of information processing was controlled using covariance analysis. In addition, a factor analysis revealed a four-factor solution explaining 89.6% of the variance in the data, i.e. cognitive flexibility, speed of processing, interference and working memory. This result supports the view of at least four different subprocesses of attentional control underlie test performance and allows one to differentiate between high- and low-level processes. The implications for neuropsychological assessment and rehabilitation are discussed. © Taylor & Francis Ltd Working memory deficits after traumatic brain injury Author(s): Thomas W. Mcallister ; Laura A. Flashman ; Molly B. Sparling ; Andrew J. Saykin Source: Brain Injury      Volume: 18 Number: 4 Page: 331 -- 350 Abstract: Primary objective: To review the neural circuitry and neurochemistry of working memory and outline the evidence for working memory deficits after traumatic brain injury, and the evidence for the use of catecholaminergic agents in the amelioration of these deficits. Current knowledge gaps and research needs are identified. Main outcomes and results: Impairments in working memory are a core component of the cognitive deficits associated with traumatic brain injury. Recent progress in understanding the neural circuitry and neurochemistry of working memory suggests that catecholamines play a central role in the activation and regulation of working memory and thus lays a framework in which to consider the use of catecholaminergic agents (dopaminergic and alpha-2 adrenergic agonists) in the treatment of specific cognitive deficits after traumatic brain injury. Conclusions: The combined methods of cognitive neuroscience, functional brain imaging and neuropharmacology are proposed as an excellent method for studying working memory deficits. A strong rationale exists for the targeted use of catecholaminergic agonists in the treatment of working memory deficits after traumatic brain injury.

BRAIN RESEARCH

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Encoding Predicted Outcome and Acquired Value in Orbitofrontal Cortex during Cue Sampling Depends upon Input from Basolateral Amygdala Geoffrey Schoenbaum, Barry Setlow, Michael P. Saddoris and Michela Gallagher Neuron, 2003, 39:5:855-867 Abstract Certain goal-directed behaviors depend critically upon interactions between orbitofrontal cortex (OFC) and basolateral amygdala (ABL). Here we describe direct neurophysiological evidence of this cooperative function. We recorded from OFC in intact and ABL-lesioned rats learning odor discrimination problems. As rats learned these problems, we found that lesioned rats exhibited marked changes in the information represented in OFC during odor cue sampling. Lesioned rats had fewer cue-selective neurons in OFC after learning; the cue-selective population in lesioned rats did not include neurons that were also responsive in anticipation of the predicted outcome; and the cue-activated representations that remained in lesioned rats were less associative and more often bound to cue identity. The results provide a neural substrate for representing acquired value and features of the predicted outcome during cue sampling, disruption of which could account for deficits in goal-directed behavior after damage to this system. Emotional Participation in Decision Making Vincente M. Simon University of Valencia Psychology in Spain, Vol 2 No 1, 100-107 Emotional participation in decision-making. The results of recent neurophysiological and neuropsychological research make it necessary to take into account the participation of emotions in decision processes. The amygdala, which has revealed itself as a structure capable of assigning emotional meaning to environmental stimuli (assessment) gives rise to a series of reactions that include motor, autonomic, endocrine and central nervous system adaptations (emotional expression). All of these changes also feed back on the brain, producing what is known as emotional experience or feelings. Neuropsychological research has also shown the importance of the prefrontal cortex in decision-making, demonstrating the close cooperation of the emotional limbic mechanisms with the anticipatory and planning functions of the prefrontal cortex (Damasio's somatic marker hypothesis is presented). Neurobiology is thus confirming what Pascal intuitively expressed when he wrote that the heart has reasons that reason ignores. The necessity to make decisions, often as difficult as that which tormented Hamlet, immortalised in Shakespeare's famous monologue, is not exclusive to human beings. All living creatures that possess a repertoire of diverse behaviours have to choose between several possibilities; as the complexity of the organism increases, the farther up the evolutionary scale we go, so decision-making acquires more and more complexity and difficulty, and this for several reasons. On the one hand, because more highly evolved brains are capable of discerning with far more precision the subtle environmental differences relevant to survival; on the other, because the repertoire of available behaviours in these organisms becomes progressively wider. A further reason is because the most phylogenetically recent brains are not only able to react to present environmental conditions, but, having developed the capacity to elaborate models of future circumstances (models that include the consequences of their own behaviour), they need to take into account a wide range of projected possibilities. Thus, all living organisms that possess a nervous system have had to devote a portion of their neurons to the delicate task of making the decisions that are necessary for survival. And it is here that emotions enter the scene. Allow me, for the moment, to present emotions as an essential part of the nervous mechanism responsible for designing appropriate responses to the environmental stimuli that are of relevance for survival. They are probably the most crucial part of that mechanism, the most decisive part, in all senses of the word. Below, I shall try to explain why I make such a statement, and I shall briefly present the neurophysiological findings that justify it. THE AMYGDALA: ITS FUNCTION IN EMOTIONAL ASSESSMENT The nervous structures related to emotional mechanisms, as they are found in current mammals and in man, made their appearance on the face of the earth about 250 million years ago, at the time of the last reptiles and the first mammals (MacLean, 1993). It was not until last century, however, when human beings began to devote attention to such a fundamental part of their anatomy. The famous French neurologist Paul Broca (1878) gave the name limbic lobe (limbic means of the edge, frontier or margin) to the part of the brain that surrounds the brain stem under the neocortical layer. Due to the abundant connections of the limbic lobe with the sense of smell, the function initially assigned to this structure was an olfactory one, so that it was given the name rhinencephalon. However, the limbic lobe was not associated with emotional life until much later. In 1937 Papez presented a hypothesis linking it with the hypothalamus and with emotional expression, describing an anatomical circuit which since then has become known as the Papez Circuit (Papez, 1937). Some years later, MacLean enlarged the structures of the Papez Circuit (including the amygdala and giving great importance to the hippocampus) and called the structure the limbic system (MacLean, 1949), a name that survives to this day. Currently, the concept of the limbic system is under review, since, on the one hand, there is disagreement over which specific structures should be included in the concept and, on the other hand, not all of the so-called limbic areas participate in the genesis of the emotions. Without any doubt, the anatomical structure most clearly related to emotion is, from our current perspective, the amygdala (LeDoux, 1992). We shall now, therefore, focus our attention on the amygdala and its meaning. The amygdala is a small nervous structure, no bigger than an almond, situated at the heart of the temporal lobe (one in each temporal lobe, two in total), and which has abundant connections with a great variety of brain areas. It is the most important component of a network of structures that process emotional information. The function of this structure, as we understand it today, consists in assigning emotional significance to environmental stimuli, whatever their sensory modality. Put more simply,