June 2003

In May Crossroads Institute successfully opened their latest facility in Orlando, Florida. Currently, our main clinic is still located in Phoenix, Arizona with a satellite office in Austin, Texas and now our latest addition in Orlando, Florida.

We feel with these two additional facilities we will be able to help more individual across the country and make it a bit more convenient for our families that are not on the West Coast.

Everyone is somewhere on the Neurodevelopmental Spectrum. Where are you on it .... where do you want to be?

Accelerated neurodevelopment allows us the ability to
maximize and use our intellectual, physical, and emotional strengths simultaneously, no matter where we begin on the spectrum.
When accelerating brain power, daily tasks such as working, studying, and sports become easier to do and manage. The brain is functioning at optimal levels and is able to make quick attentional shifts on demand.
This is the state of mind that peak performers call "the zone" and is accessible at will.

Very Low Lead Levels Linked With IQ Deficits, According To NEJM Study NIH/National Institute Of Environmental Health Sciences 2003-04-17 A new study suggests that lead may be harmful even at very low blood concentrations. The study, funded by the National Institute of Environmental Health Sciences of the National Institutes of Health, will appear in the April 17 edition of The New England Journal of Medicine. The five-year study found that children who have blood lead concentration lower than 10 micrograms per deciliter suffer intellectual impairment from the exposure. The researchers also discovered that the amount of impairment attributed to lead was most pronounced at lower levels. The study was carried out by researchers from Cornell University, Cincinnati Children's Hospital Medical Center, and the University of Rochester School of Medicine. An important feature of this new study is its focus on children with blood lead levels below 10 micrograms per deciliter, a threshold currently used by the Centers for Disease Control and Prevention to define an elevated lead level. Previous research has been concerned primarily with lead's effects in the 10 to 30 micrograms per deciliter range, yet the new study finds lead-related impairments at lower levels. "In this sample of children we find that most of the damage to intellectual functioning occurs at blood lead concentrations that are below 10 micrograms per deciliter," said Richard Canfield, Division of Nutritional Sciences at Cornell University and primary author on the study. The amount of impairment attributed to lead exposure was much greater than the researchers had expected. "We were surprised to find that in our study the IQ scores of children who had blood lead levels of 10 micrograms per deciliter were about 7 points lower than for children with levels of 1 microgram per deciliter," Canfield said. At the same time, the study found that an increase in blood lead from 10 to 30 micrograms per deciliter is associated with only a small additional decline in IQ. "Because most prior research focused on children with higher exposures than in our sample, we suspected that those investigators could estimate only the amount of additional damage that occurs after blood lead has reached 10 micrograms per deciliter – unaware that more damage may occur at lower levels," said Charles Henderson, Department of Human Development at Cornell. Deborah Cory-Slechta, director of the NIEHS Environmental Health Sciences Center at University of Rochester School of Medicine, said, "Our study also emphasizes the need to understand the behavioral deficits indicated by lower IQ scores." Before 1970, childhood lead poisoning was defined by a blood lead concentration greater than 60 micrograms per deciliter. Since then, the threshold used to define an elevated blood lead level declined several times, before reaching the current value of 10 micrograms per deciliter. . Under this definition, more than one in every 50 children in the United States between the ages of 1 and 5 years is adversely affected by lead, which has been linked to lowered intelligence, behavioral problems, and diminished school performance. Nearly 1 in 10 young children have a lead level above 5 micrograms per deciliter, according to CDC figures. "Our study suggests that there is no discernable threshold for the adverse effects of lead exposure and that many more children than previously estimated are affected by this toxin," said Bruce Lanphear, Cincinnati Children's Hospital and director of the hospital's Children's Environmental Health Center. "Despite a dramatic decline over the last two decades in the prevalence of children who have blood lead concentrations above 10 micrograms per deciliter, these data underscore the increasing importance of prevention." The study followed 172 children in the Rochester, N.Y., area whose blood lead was assessed at 6, 12, 18, 24, 36, 48, and 60 months, and who were tested for IQ at both 3 and 5 years of age. The researchers controlled for many other factors that contribute to a child's intellectual functioning, such as birth weight, mother's intelligence, income, education, and amount of stimulation in the home. "Any detectable effect occurring from such a widespread exposure is cause for concern," Walter J. Rogan, M.D., said. Rogan is a NIEHS researcher who has studied lead exposure in children but was not an author on the study. "Relatively small changes in the mean IQ of a large number of children will dramatically increase the proportion of children below any fixed level of concern, such as an IQ of 80, and decrease the proportion above any 'gifted' level such as 120," Rogan said. The authors of the study are Richard L. Canfield and Charles R. Henderson, Jr., Cornell University, Ithaca, N.Y.; Deborah A. Cory-Slechta, University of Rochester School of Medicine, Rochester, N.Y.; Christopher Cox, National Institute of Child Health and Human Development, NIH, DHHS, Bethesda, Md.; Todd A. Jusko, University of Washington, Seattle, Wash.; and Bruce P. Lanphear, Cincinnati Children's Hospital Medical Center. NIEHS funds centers for environmental and children's health at University of Rochester, University of Cincinnati, and University of Washington. UCLA Imaging Study Reveals How Active Empathy Charges Emotions; Physical Mimicry Of Others Jump-starts Key Brain Activity University Of California, Los Angeles, Health Sciences 2003-04-08 A child falls from his bicycle and his father winces. A bride says "I do" and the maid of honor grins from ear to ear. A mother frowns with displeasure and her infant son frowns back. UCLA neuroscientists using functional magnetic resonance imaging (fMRI) are the first to demonstrate that empathetic action, such as mirroring facial expressions, triggers far greater activity in the emotion centers of the brain than mere observation. Reporting in the April 15 edition of the peer-reviewed Proceedings of the National Academy of Science, the researchers also identified the brain's oval-shaped insula as a key to translating active imitation of others' feelings into meaningful emotion. The findings explain why humans vary in their ability to understand the pain, joy and anger of others, and how damage to this neural circuit might impair the ability to empathize with the emotions of others, as often seen in patients with autism, a socially isolating psychiatric disease. "For years scientists have observed the reflexive mimicking of a wince when someone suffers a painful injury, and the infectious nature of joy or anger," said Dr. Marco Iacoboni, a neuroscientist affiliated with the UCLA Neuropsychiatric Institute and the UCLA Brain Research Institute who led the study. "Our findings show for the first time how these reflexive facial expressions prompt our brain to heighten our empathy for the feelings of others," said Iacoboni, an associate professor-in-residence of psychiatry and biobehavioral sciences at the David Geffen School of Medicine at UCLA. "Understanding the mechanism for regulating empathy explains the continuum of empathy in humans, and also moves us closer toward identifying ways to better control our emotional responses and reverse impairment caused by brain injury, illness and age. This research is especially important for understanding core deficits in autism, such as imitation and empathic resonance." Using the resources of UCLA's Ahmanson-Lovelace Brain Mapping Center, the researchers evaluated the neural response of 11 research subjects to a series of pictures depicting six emotions -- happiness, sadness, anger, surprise, disgust and fear. The subjects observed the pictures through magnetic-compatible goggles and were asked either to imitate and internally generate the target emotion in the picture, or simply to observe. The researchers found that imitation and observation of emotions activated a largely similar network of brain activity. Within this network, composed by motor areas as well as the inferior frontal cortex, superior temporal cortex, insula and amygdala, researchers found increased activity during imitation than during observation of emotions. The cortex is the outer layer of the brain. Previous brain studies from Iacoboni's lab had discovered that the superior temporal and inferior frontal cortices are critical areas for imitation. These areas are connected to the limbic system -- the brain's emotion centers -- via the insula. Therefore, the researchers surmise the insula plays a fundamental role in regulating emotional content, perhaps acting as a critical relay in translating empathetic imitation into emotion. The study was funded by the Brain Mapping Medical Research Organization, the Brain Mapping Support Foundation, the Pierson-Lovelace Foundation, The Ahmanson Foundation, the Tamkin Foundation, the Jennifer Jones-Simon Foundation, the Capital Group Companies Charitable Foundation, the Robson Family, the Northstar Fund and the National Center for Research Resources. In addition to Iacoboni, other researchers involved in the study included Laurie Carr, now at Michigan State University, and Marie Charlotte Dubeau of the Ahmanson-Lovelace Brain Mapping Center at the UCLA Neuropsychiatric Institute; Dr. John C. Mazziotta, director of the Ahmanson-Lovelace Brain Mapping Center and professor and chair of neurology at UCLA's David Geffen School of Medicine; and Gian Luigi Lenzi of the Department of Neurological Sciences at the University "La Sapienza," in Rome, Italy. The UCLA Neuropsychiatric Institute is an interdisciplinary research and education institute devoted to the understanding of complex human behavior, including the genetic, biological, behavioral and sociocultural underpinnings of normal behavior, and the causes and consequences of neuropsychiatric disorders. In addition to conducting fundamental research, the institute faculty seeks to develop effective treatments for neurological and psychiatric disorders, improve access to mental-health services, and shape national health policy regarding neuropsychiatric disorders. The UCLA Brain Research Institute fosters and improves interdisciplinary collaborations in all aspects of neuroscience, from molecules to the mind, from the laboratory bench to the patient's bedside. This work has increasingly permitted the identification of pathogenic mechanisms and the creation of new therapeutic approaches. Copyright © 1995-2002 ScienceDaily Magazine Cocaine Use May Alter Brain Cells, Play Role In Depression NIH/National Institute On Drug Abuse 2003-03-07 A study by researchers from the University of Michigan and the Ann Arbor Veterans Affairs Medical Center suggests that chronic cocaine use may cause damage to brain cells that help produce feelings of pleasure, which may contribute, in part, to the high rates of depression reported among cocaine abusers. It is well-known that cocaine increases levels of the brain chemical dopamine, resulting in the "high" that abusers feel. Prolonged use of the drug, however, may reduce dopamine levels, making it harder for abusers to experience positive feelings. Dr. Karley Little, lead investigator, and colleagues studied samples of brain tissue obtained during autopsies of 35 long-term cocaine users and 35 non-users. They analyzed the tissue for dopamine and the protein VMAT2, which is found in dopamine transporters. Urine or serum samples were also analyzed for the presence of cocaine, opioids, antidepressants, and antipsychotic medications. A person close to each individual was interviewed about the individual's substance abuse, alcoholism, and symptoms of personality and mood disorders. Researchers found that cocaine users had lower concentrations of dopamine and VMAT2 in their brains than did non-users. Additionally, cocaine users suffering from depression had lower levels of VMAT2 than those who were not depressed. Dr. Little and colleagues were uncertain whether dopamine cells had been destroyed or just dysregulated by cocaine use, and if such changes could be reversed. These findings suggest that chronic cocaine use may cause changes in the brain that could make it harder for a person to feel a sense of pleasure. Further efforts at clarifying the detrimental effects of cocaine on brain cells may help in the development of effective treatment interventions and pharmacotherapies. This study, funded in part by the National Institute on Drug Abuse, was published in the January 2003 issue of the American Journal of Psychiatry.

Brain Reorganization Leah Ariniello, Science Writer, Society for Neuroscience For years scientists thought most brain development stopped after a "critical period" in the first few years of life. Recent research on monkeys and other animals shows that the brain continually and dynamically reorganizes itself, even in adulthood. This finding helps explain how learning occurs and may lead to ways of improving recovery from learning disabilities, stroke, and other brain disorders through drug treatments or special "brain exercises." Old brains can learn new tricks. For years, scientists believed that connections between the brain's nerve cells, or neurons, develop by early childhood and then become fixed throughout life. In the last decade, however, animal research has revealed that brain areas routinely adjust the way they process information and retain the ability to take on new functions during adulthood. The new findings: * Reveal how human experiences and physical disorders affect the brain. * Provide insights into the development of dyslexia and other learning disorders. * Offer hope of improved recovery from injury, stroke, and brain disorders through drugs or training regimens. During early development, genes prompt the brain's neurons to form trillions of connections. These connections are fine-tuned by the neurons' electrical activity: useful connections are maintained or added, while others often disappear. Early experiments showed that many brain functions have a "critical period" during which most of this fine-tuning takes place -- usually the first few years after birth. Scientists once thought that, except for areas involved with memory, brain functions are usually stable after this time. In the 1980s, researchers made a surprising discovery. When nerve impulses in one finger of a monkey were blocked, the part of the brain that previously responded to touch at that finger began over several months to respond to signals from surrounding fingers. The deprived brain regions began responding to different nerves. This helps explain "phantom pain," in which people with part of their body amputated report intense feeling in or near a missing arm or leg -- usually when a nearby region is stimulated. Scientists also found that many brain regions' functions were organized differently every time they were examined. This happened even in brain areas unaffected by experiments. Changes in organization also followed limited damage to nerves for vision and hearing. This suggested that all brain areas continually adapt to changing signals. Scientists are still uncertain whether adult brain reorganization results from formation of new connections or strengthening of existing, previously unused connections. A loss or increase of neuron activity in a certain area may let normally silent connections gain the upper hand and win more brain territory. Understanding the brain's ability to dynamically reorganize itself, even in adulthood, helps scientists understand how patients sometimes recover brain functions damaged by injury or disease. While the brain can't grow new neurons, new neuron connections can emerge with surprising speed. Even learning to read by Braille can increase the brain territory responding to fingertip stimulation. Scientists are now looking for ways of making reorganization more likely to occur. Proteins called nerve growth factors are being tested in humans to see if they prompt brain reorganization after stroke and other disorders. Since reorganization seems to be influenced by neural activity, scientists are also testing special "brain exercises" designed to help the brain remodel itself in beneficial ways. Brain reorganization may also contribute to the symptoms of some diseases or slow recovery. Since the brain adapts to underlying problems, it must re-adapt once the problems are removed. Understanding how these changes occur may lead to ways of preventing damage and speeding recovery in learning disorders, stroke, and other nervous system diseases. When nerve stimulation changes, as with amputation, the brain reorganizes. In one theory, signals from a finger and thumb of an uninjured person travel independantly to separate regions in the brain's thalamus (left). After amputation, however, neurons that formerly responded to signals from the finger respond to signals from the thumb (right). Copyright © 2003 Society for Neuroscience Receptor Found That Guides Nerve Cells To Their Final Connecting Sites Source: Salk Institute 2003-03-20 La Jolla, Calif. -- In the developing brain, nerve cells make connections with one another by extending processes, often over long distances. The growing tips of these nerve cell processes are guided to their ultimate connection sites by molecular cues in the environment. A Salk Institute research team has discovered a receptor-protein interaction that guides nerve cells along specific pathways. John Thomas, professor of molecular neurobiology, working on the fruit fly Drosophila, found that a protein called Wnt5, a member of a large family of signaling molecules, binds to a receptor called Derailed present on the surface of growing nerve cells. This binding guides the tips of these nerve cells to their final destination by preventing them from entering the wrong pathway. This mechanism appears especially important for nerve cells that extend processes across the midline to make connections on the opposite side of the nervous system, a prominent class of nerve cells also found in vertebrates. This research could have implications for understanding birth defects as well as the regeneration of nerve cells. The study is published in the March 17 edition of Nature.

AUTISM

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Autism, Vaccine Link Considered By Mark Benjamin From the Washington Politics & Policy Desk Published 5/5/2003 CHICAGO, May 5 (UPI) -- An epidemic of autism and other brain problems in American children is linked to vaccines, say doctors, activists and one member of Congress who met in Chicago over the weekend to discuss the disease. At a three-day meeting at Loyola University, researchers said growing evidence indicates that vaccines are linked to increasing rates of brain problems and that government health agencies have done little to recognize it. Autism One, a non-profit group dedicated to learning more about autism, sponsored the meeting. "There are some bureaucrats in these agencies who have really dropped the ball and are doing things that are malicious and may be criminal," said Dr. Boyd Haley, chairman of the Department of Chemistry at the University of Chicago. Boyd believes a mercury-based preservative added to vaccines during the 1990s may be a cause of autism. He said the Food and Drug Administration and the Centers for Disease Control and Prevention have failed to address the issue. Autism rates have increased 10 times since the late 1980s. The CDC says that one in 300 American children may suffer from autism. The leading theories about autism discussed in Chicago: A mercury-based preservative called thimerosal used during the 1990s plays a role. Mercury has known toxic effects and during that decade, the CDC drastically increased the recommended number of vaccines. Some children may have been exposed to 125 times the federal limit for mercury exposure. An intestinal disorder may eventually impact the brain. That disorder might start with vaccinations for measles, mumps and rubella, the first multi-dose vaccine for children to contain three live viruses. Some researchers said mercury poisoning might make the body unable to fight off the infection. Debate over a possible connection between brain problems and vaccines is hotly contested. Critics of the government blame a revolving door between pharmaceutical companies and government regulators for complicating the debate. Researchers who say there is a link claim they have been blackballed. "I hope somebody will ask the question, 'Is there collusion between the pharmaceutical companies and our health agencies?'" asked Rep. Dan Burton, R-Ind., chairman of the House Human Rights and Wellness Subcommittee. "The appearance in many cases is that there is." Vaccine manufacturers say the science does not favor a link between thimerosal in vaccines and autism. The Pharmaceutical Research and Manufacturers of America did not return calls seeking comment. But Len Lavenda, a spokesman for vaccine manufacturer Aventis Pasteur, told United Press International this spring that scientists have not proven a link between the additive and brain problems. "We think we are experiencing opposition to thimerosal for emotional reasons," Lavenda said. "This is not based on research and not based on testing." Burton has been investigating vaccines for more than four years. In Chicago he released a report on thimerosal criticizing government health agencies and vaccine manufacturers for their roles. Doctors and activists in Chicago also discussed a new study that claims to show an association between thimerosal and brain problems. The study claims to show "strong epidemiological evidence for a link between increasing mercury from thimerosal-containing childhood vaccines and neurodevelopmental disorders and heart disease." The study compares reports of speech disorders, autism and heart arrest for one vaccine that contained thimersosal to one that did not, over a 10-year period. It also uses information from manufacturers to determine how much mercury was in shots during different points during that decade. The study found reports of brain problems for vaccines that contained the additive and that the relative risk went up as more mercury was in vaccines in general. Two Silver Spring, Md., researchers performed the study, Dr. Mark Geier and his son David Geier. The study shows that "the relative risk of each of those disorders correlated with increasing doses of mercury contained in childhood vaccines." The CDC sets the national immunization schedule for children. The CDC says about thimerosal: "There are no data or evidence of any harm caused by the level of exposure that some children may have encountered in following the existing immunization schedule." The Institute of Medicine -- the government's adviser on medical issues -- said in October 2001 that the link between the preservative and autism is "biologically plausible" but that "current scientific evidence neither proves nor disproves a link." This March, the institute found "no association" between the measles, mumps and rubella vaccine and autism. In 1999, the American Academy of Pediatrics, followed by the CDC, called for the removal of thimerosal from vaccines but said there was no evidence showing it had harmed children. The CDC continues to recommend the measles, mumps and rubella vaccine. Autism, referred to by parents as a disease, usually showing up before age 2. Sometimes children who had previously appeared to interact normally will suddenly regress, become withdrawn and stop responding to their parents and the outside world. They may perform repetitive motions, like spinning or flapping their arms, scream uncontrollably and resist physical touch. Parents of children with autism at the Chicago conference said the disease has a way of isolating parents because of the time-consuming task of raising a child with autism. "I did not leave my son's side for four years," said Edmund Arranga, with Autism International Association. "It keeps people from connecting." Arranga said he estimates that 40 percent of parents of children with autism believe vaccines cause the disease. Many parents described previously normal children who appear to digress suddenly with signs of autism within days of receiving vaccinations. Those vaccinations often include measles, mumps and rubella vaccines and large doses of thimerosal. Liz Birt, an attorney with Burton's Subcommittee on Human Rights and Wellness, said that during the 1990s, the U.S. childhood vaccination schedule exposed some children to 125 times the federal limit on mercury exposure set by the Environmental Protection Agency. Birt said the CDC and the FDA have been slow to admit the damage the vaccines may have caused because key officials want to keep their jobs and vaccine manufacturers do not want the liability. "It all comes down to money," Birt said. Copyright © 2001-2003 United Press International Investigating Individual Differences in Brain Abnormalities in Autism. Salmond CH, de Haan M, Friston KJ, Gadian DG, Vargha-Khadem F. Developmental Cognitive Neuroscience Unit, Institute of Child Health, Autism is a psychiatric syndrome characterized by impairments in three domains: social interaction, communication, and restricted and repetitive behaviours and interests. Recent findings implicate the amygdala in the neurobiology of autism. In this paper, we report the results of a series of novel experimental investigations focusing on the structure and function of the amygdala in a group of children with autism. The first section attempts to determine if abnormality of the amygdala can be identified in an individual using magnetic resonance imaging in vivo. Using single-case voxel-based morphometric analyses, abnormality in the amygdala was detected in half the children with autism. Abnormalities in other regions were also found. In the second section, emotional modulation of the startle response was investigated in the group of autistic children. Surprisingly, there were no significant differences between the patterns of emotional modulation of the startle response in the autistic group compared with the controls.

Bone Marrow Generates New Neurons in Human Brains A new study strongly suggests that some cells from bone marrow can enter the human brain and generate new neurons and other types of brain cells. If researchers can find a way to control these cells and direct them to damaged areas of the brain, this finding may lead to new treatments for stroke, Parkinson's disease, and other neurological disorders. "This study shows that some kind of cell in bone marrow, most likely a stem cell, has the capacity to enter the brain and form neurons," says Eva Mezey, M.D., Ph.D., from the National Institute of Neurological Disorders and Stroke (NINDS), who led the study. Earlier work by Dr. Mezey and others has shown that bone marrow cells can enter the mouse brain and produce new neurons. However, the new study is the first to show that this phenomenon can occur in the human brain. The study was supported in part by the NINDS and appears in the January 20, 2003, online early edition of the Proceedings of the National Academy of Sciences.1 The NINDS is a component of the National Institutes of Health, which is part of the U.S. Department of Health and Human Services. In the study, Dr. Mezey and colleagues examined brain tissue taken at autopsy from four female patients - two adults and two children - who had received bone marrow transplants from male donors. The bone marrow transplants had been performed to treat leukemia and other non-neurological diseases, and the patients survived from 1 to 9 months after their transplants. The investigators searched the autopsied brain tissue for male cells, which contain a Y chromosome. The Y chromosomes in these cells served as a useful way of distinguishing donor-derived cells from those of the female transplant recipients. The researchers found cells with Y chromosomes in brain tissue from all four of the patients. Most of the bone marrow-derived cells in the brain tissue were glia (support cells) and other non-neuronal cells. However, a small number of neurons from each brain also contained Y chromosomes, showing that those cells had developed from the transplanted male bone marrow. Most of these neurons were found in the cerebral cortex - the outer layer of the brain, which is responsible for conscious thought - and in the hippocampus, a region that helps with memory and other functions. The Y chromosome-positive cells within each patient's brain appeared in clusters, rather than being randomly dispersed throughout the brain tissue. The clusters sometimes contained both neuronal and non-neuronal cells. This suggests that a single bone marrow-derived stem cell may migrate into an "area of need" within the brain and then change, or differentiate, into several other kinds of cells, Dr. Mezey says. The clusters also might result from a large number of marrow cells that are "called" to specific parts of the brain. Previous studies have suggested that stem cells can respond to signals from within the brain that guide them to damaged regions. The brain sections with the largest number of marrow-derived neurons came from the youngest of the four patients, who had her transplant at 9 months of age. That patient also survived for 9 months after the transplant - much longer than the other patients in this study. The researchers do not know if the number of marrow-derived neurons in this patient was due to her young age or to the length of time she survived after receiving the transplant. The brains of young people usually undergo more changes than those of older people, and this might have encouraged the development of new neurons, Dr. Mezey notes. However, it is also possible that new cells enter the brain at a steady rate over time, regardless of a person's age. It is possible that irradiation or other treatments that the four patients received might have increased the ability of marrow cells to enter the brain. However, other studies have suggested that bone marrow cells circulating in the blood enter the brain even in healthy subjects who have never received a bone marrow transplant, and there is no reason to think that a transplant is necessary for stem cells to enter the nervous system, Dr. Mezey says. The numbers of marrow-derived neurons identified in the human brain tissue were very low - much lower than the numbers identified in a previous mouse study, says Dr. Mezey. However, the numbers might be greater in patients who survive for longer periods after transplant, she suggests. Bone marrow contains at least two kinds of stem cells: hematopoietic stem cells, which usually differentiate into blood cells, and mesenchymal stem cells, which can differentiate into many kinds of cells in the body. The researchers do not yet know which type of cell differentiates into the neurons and other marrow-derived cells they identified in the brain. Recent studies have shown that instead of developing into new cell types, adult stem cells sometimes fuse with mature cells from existing tissues that have already undergone differentiation. The resulting cells carry four sex chromosomes (X and Y chromosomes) instead of the usual two. While Dr. Mezey and her colleagues cannot exclude the possibility that fusion accounts for their results, they looked at several hundred donor-derived cells from one of the patients and did not see doubled sex chromosomes in any of the cells they examined. Previous studies have found some cells with Y chromosomes in adult women who had not received any transplants. Researchers believe these Y cells may have come from a past pregnancy with a male fetus. However, two of the subjects in this study were children, and the male cells in those individuals could not have come from a pregnancy, says Dr. Mezey. Scientists must now determine what growth factors or other signals prompt the bone marrow cells to enter the brain and develop into neurons. This may lead to new ways of treating Parkinson’s disease or other disorders where neurons lost to disease are not normally replaced. Researchers might also be able to discover factors that can increase the number of cells entering the brain or prompt the cells to find useful targets. "These studies are very much the beginning, but scientists should start to look down this road and find out if and how we can go further," says Dr. Mezey. She cautions that it is too early to know if this finding will lead to useful treatments for neurological disorders. She and her colleagues are now planning to study brain tissue from people who survived for longer periods after receiving a bone marrow transplant in order to see if the number of marrow-derived neurons increases with time. They also plan to study mice to determine which cells in the bone marrow develop into neurons. Traumatic Brain Injury: From Model to Man R. G. M. Jacksonf1, K. M. Sales, D. P. McLaughlin and J. A. Stamford Neurotransmission Laboratory, Academic Department of Anaesthesia and Intensive Care, Barts and The London School of Medicine Brain injury is the leading cause of death in trauma patients and produces a large amount of disability. Unfortunately, it is particularly prevalent in young adults, with all the suffering and socio-economic loss this implies. It has a complex neurobiology that has been elucidated largely in animal models, but it has been more difficult to apply the knowledge gained to man, partly due to the heterogeneous nature of human brain injuries. Clinical management consists of trying to prevent and treat ongoing injury processes. This is achieved by early and excellent critical care combining management of intracranial and cerebral perfusion pressure, with drug therapy where needed. New monitoring modalities are arriving and providing new insights, but the majority have yet to prove their worth in terms of improving patient outcome. The knowledge gleaned from experimental work has also begun to have an impact, and new therapies based on control of the elucidated pathophysiology are now in development. The Evidence for Brain Injury in Whiplash Injuries M P Alexander Pain Research and Management The evidence that brain damage can occur in injuries that produce whiplash is reviewed. The clinical phenomena for the two injuries are the same. Pure whiplash injury implies no, or minimal head contact, but many patients also have head contact against a head rest or the steering wheel or windshield. The relative severity of the neck injury and the head injury distinguishes whiplash from mild closed head injury. If there is brain injury is some patients with whiplash, it, by definition, falls at the mildest end of the concussion spectrum. The relationship between these two injuries is examined. Multisensory Integration After Traumatic Brain Injury: A Reaction Time Study Between Pairings of Vision, Touch and Audition Author(s): Stefania Sarno ; Lutz-Peter Erasmus ; Berthold Lipp ; Wolfgang Schlaegel Brain Injury      Volume: 17 Number: 5 Page: 413 -- 426 Abstract: Traumatic brain injury (TBI) frequently results in deficits in attention and speed of information processing. In order to disentangle the influence of sensory-specific factors and the role of cross-modal integration from the supra-modal aspects of cognitive slowing, the present reaction time (RT) study was designed. Simple and choice RT to pairings of visual, auditory and tactile stimuli were measured in 35 TBI patients and 35 matched controls. Results proved a strong influence of sensory-specific and cross-modal factors in the RTs. The tactile modality was more difficult to integrate with the visual and the auditory modality, rather than the visual and the auditory modalities between them. TBI patients showed prolonged simple and choice RTs throughout all tasks, but their difficulty with integrating the tactile modality was disproportionately higher in comparison to controls. There Is Differential Loss of Pyramidal Cells from the Human Hippocampus with Survival after Blunt Head Injury W. L. Maxwell, PhD, DSc, K. Dhillon, BSc, L. Harper, BSc, J. Espin, BSc, T. K. MacIntosh, PhD, D. H. Smith, MD, and D. I. Graham, MBChB, PhD Journal of Neuropathology and Experimental Neurology: Vol. 62, No. 3, pp. 272–279. Abstract.The experimental literature has shown that neurons within sub-fields of the hippocampus possess differential sensitivities to cell loss after different types of insult to the brain. In humans, after blunt head injury, differential neuronal responses between sub-fields of the hippocampus up to 72 hours after injury have been documented. But, in only a small part of the literature have data for alterations in real numbers of neurons been provided. In this study the hypothesis was tested that, after severe blunt head injury in humans, the total number of neurons within a defined volume of brain tissue differed between different sub-fields of the hippocampus and between groups of patients with differing post-traumatic survivals. Stereological methods were used to measure total cross-sectional area of sub-fields of the hippocampus taken at the level of the lateral geniculate nucleus and count numbers of neurons within each of the CA1, CA2, CA3, and CA4 sub-fields of the hippocampus in patients. The patients used in this study were categorized as follows: Group 1 (early) had survived for 1 week or less; Group 2 (late) survived 6 months or longer after fatal severe head injury; and Group 3 (controls) consisted of age-matched patients that had no history of head injury or disease prior to death. There was a significant loss in cross-sectional area in sub-fields CA3 and CA4 at 1 week or less after injury and in sub-field CA1 at 6 months and greater survival. There was no change in CA2. There was loss of neurons from within a predefined volume of brain tissue in sub-fields CA1, CA3, and CA4 one week or less after injury. But there was no loss in CA2. There was continued loss of neurons from sub-fields CA1 and CA4 between 1 week and 6 months and greater survival, but there was no loss of neurons in sub-fields CA2 and CA3 within the same period. These novel data show that after human severe head injury there is first an acute loss (1 week or less survival) of pyramidal neurons in all hippocampal sub-fields except CA2. Second, there is an ongoing loss of neurons in sub-field CA1 and, most notably, in sub-field CA4, in patients surviving for more than 6 months. However, in neither group of patients is there loss of neurons from sub-field CA2. © Copyright by American Association of Neuropathologists, Inc. 2003

New Insights Into How The Nerve Connection Machinery Remodels Itself Duke University 2003-02-10 DURHAM, N.C. -- A Duke University Medical Center neurobiologist has identified key mechanisms by which the intricate "protein machines" that govern the strength of connections among neurons build and remodel themselves to adjust those connections. Such remodeling of the connections, called synapses, is central to the establishment of brain pathways during learning and memory, said the scientists. Also, malfunction of the synaptic machinery might well play a fundamental role in the pathology of neurodegenerative disorders including Parkinson's and Alzheimer's diseases. The findings were reported in the advanced online version of the March 2003 Nature Neuroscience by neurobiologist Michael Ehlers. Said Bill Thies, Ph.D., vice president, medical and scientific affairs of the Alzheimer's Association, a sponsor of the research "The discovery of the earliest events in Alzheimer's disease is very important to understanding the disease. This paper on activity-dependent synaptic organization and disorganization opens an interesting path to the earliest perturbations of Alzheimer's." The work was also supported by the National Institutes of Health and other private foundations. In the Nature Neuroscience paper, Ehlers reported extensive experiments revealing the function of a structure known as the "post-synaptic density" (PSD). The PSD is so named because it is a thickening of the membrane at the connection point between neurons, where one neuron receives biochemical signals called neurotransmitters from its neighbor. Such neurotransmitters are the means by which one neuron triggers the receiving neuron to launch a nerve impulse. "The post-synaptic density has been known for decades as a distinctive structure readily visible under an electron microscope," said Ehlers, who is an assistant professor of neurobiology. "Also, many of its protein components have been identified -- including neurotransmitter receptors, scaffolding proteins, signaling enzymes and adhesion molecules. So, it was clear that this was an important specialized machine for receiving the chemical signal from the pre-synaptic nerve cell." Also, said Ehlers, experiments by other researchers had shown that the PSD significantly alters its shape in response to the kind of neural activity that takes place during learning. They had also established that the neurotransmitter receptors in the PSD move in and out of the membrane during such remodeling. "But what past work has not shown is how the many components of this machine behave together," said Ehlers. "Our goal was to take a step back and look at patterns of protein accumulation and loss, rather than examining one molecule at a time -- to provide a molecular fingerprint if you will." The key to achieving such broad insights into PSD remodeling, said Ehlers, was to explore the gain or loss of a multitude of known PSD proteins, and not just one or two. Thus, in his experiments, Ehlers developed a "protein expression profiling" technique to isolate and measure the levels of some 30 proteins in the PSDs of cultured rat embryo neurons. This mass analysis revealed a distinct pattern of protein turnover, he said. "We found that a significant percentage of the major PSD protein components moved up and down with neural activity," he said. "And surprisingly, they didn't behave independently, but moved as groups or ensembles, with a whole set going up or down in response to activity. Even more notable was that we saw the exact mirror image pattern in behavior when neural activity was blocked." According to Ehlers, such a discovery could have a profound impact on scientists' ability to understand the structure and function of the intricately complex protein machine that is the PSD. "These findings allow us to begin making testable predictions about the functional networks of proteins in these synaptic complexes," he said. "For example, we believe that there are probably some master organizers in the PSD that recruit or organize large subsets of these proteins. Now, we can search for those master molecules." Further, "by providing a molecular fingerprint of the functional state of the synapse, we can now begin to compare patterns as the brain develops, ages, and learns, as well as in disease states such as Alzheimer's disease, or even across individuals with different experiences and environmental exposures." Another surprise, Ehlers found, was the mechanism behind the turnover of such proteins. In his experiments, Ehlers explored whether the cell's protein "garbage collection" system might be involved in the turnover. In this system, proteins targeted for destruction are tagged with a molecule called ubiquitin and transported to a shredding complex called the proteasome for destruction. Ehlers' studies revealed that this system was required for normal turnover of PSD proteins. Ehlers also showed that the ubiquitin-proteasome system affected specific metabolic pathways in the neurons that are known to be involved in the changes in synaptic connections associated with learning and memory. "The prevailing model for long-term plastic change at synapses has been that genes are switched on to make new proteins and incorporate them into the synapse," said Ehlers. "Much, much less appreciated has been the fact that proteins must also be removed from the structure. And what we found was that this highly regulated removal is a key part of the remodeling of the PSD." Also startling, said Ehlers, was the high base level of remodeling of the PSD. "I found that neurons in these cultures replace the content of this signaling machine multiple times a day," said Ehlers. "And if this recapitulates what's going in the mammalian brain, this means that synapses are completely turning over all of their constituents multiple times a day – a stunning finding." Neuroscientists have long been intrigued in how the brain changes with learning and experience, a phenomenon called plasticity. Yet, as Ehlers points out, "perhaps we need to think more closely about how connections in the brain remain stable in the face of such incredible ongoing turnover." "In fact, when I was doing these experiments, I anticipated a turnover on the order of days, so I took my first time measurement at about a day and found no protein label left in the sample. I thought the experiment had failed until I decided to do measurements at earlier time points." According to Ehlers, the new insights into the PSD his studies allow could have important implications for understanding neurodegenerative diseases including Parkinson's and Alzheimer's diseases. "Many of these diseases have as their hallmark pathology abnormal deposits in the brain, many of which show high levels of ubiquitin," he said. "For example, there are rare familial versions of Parkinson's that arises from mutations in genes that regulate the attachment of ubiquitin to proteins. So, these findings might give new insights into how such mutations affect the brain. Such findings might also shed light in the subtle pathological changes in synaptic connections that eventually give rise to Alzheimer's disease," he said. "There is an increasing appreciation of the idea that before the neurological damage from Alzheimer's disease becomes apparent, there may be subtle synaptic defects that cause only a mild cognitive decline," said Ehlers. "This study showing the central relationship between the ubiquitin system and synaptic organization gives us a research pathway to trace the possible origin of these subtle defects. And it is my hope that such basic insights will lead to therapies to remedy the defects early." Copyright © 1995-2002 ScienceDaily Magazine Compromise Is Name Of The Game In How Brain Works, Say University Of Toronto Researchers University Of Toronto 2003-03-11 The brain is constantly compromising as it pieces together information, often ignoring or downplaying small visual changes in the world that do not fit with its expectations. This process - far from being flawed - shows that the brain functions optimally, say University of Toronto researchers. "Our brains are very well designed," says Dr. Douglas Tweed, physiology professor at U of T and senior author on a paper in the March 6 issue of Nature. "The brain takes in raw data from its surroundings through sensors and interprets it, rejecting interpretations that it considers unlikely. The brain gauges the probabilities of things in real life and uses these estimates to guide our perceptions. But sometimes we can be fooled by bizarre things. "This shouldn't be seen as a flaw in the system, however," Tweed argues. "This is the way the brain works. Sensors are always flawed; they simply do not provide enough information for us to reconstruct our world. The brain must use prior knowledge to interpret our surroundings and we found that it seems to do this optimally." This research project, led by U of T post-doctoral fellow Matthias Niemeier, uses a theory presented in the 1800s by Hermann von Helmholtz, a German physiologist. Helmholtz, who stated that perception is a matter of unconscious inference, suggested that all of our senses are imperfect and those signals sent to the brain are flawed. With this flawed data, the brain is forced to guess - based on its sensor readings - what is happening in the environment. With small or unexpected changes it often guesses wrong, which is why people can be fooled by optical illusions or sleight of hand, Tweed explains. He and Niemeier conducted the research with Professor Douglas Crawford of York University. The researchers tested whether the brain's perception processes are working optimally given the flawed data it receives. They programmed a computer-simulated brain to make optimal use of sensor data and prior knowledge, giving it realistic vision and quick eye movements (also known as saccades). The researchers then measured how well it perceived events in its simulated world. The team compared these findings with those of human subjects. Subjects' heads were immobilized and a device shaped like a contact lens inserted into their eye to measure its motion and relay information back to a computer. Using a large screen, researchers conducted two experiments that tested participants' perceptions of distance and degree of change, using a white dot that "jumped" on the screen. They found that small jumps were invisible to participants; larger ones were seen but individuals underestimated how far the dot jumped. "What we found was that, in simple situations, the simulated computer brain perceived things the same way and made the same kinds of errors that human brains do, even when we programmed the computer to function optimally," says Niemeier. "When small changes occurred during a saccade, these changes were either ignored or downplayed by both the computer and the test subjects. So we concluded that the optimal solution when it comes to perceiving the outside environment is to ignore some changes." The brain knows what can and cannot realistically occur based on probability and prior knowledge, say the researchers. Eyes have quite a narrow field of high-resolution vision, something in the area of two degrees, Niemeier explains. To obtain a complete picture, a person's eyes are constantly making quick movements. These saccades - about 100,000 a day - scan our surroundings and take about 30 milliseconds each. The brain knows that an event is unlikely to happen in 30 milliseconds and either ignores or downplays small changes (also known as saccadic suppression of displacement). Only when a change is large enough does the brain notice, he says. "The brain makes the best possible use of the flawed data it gets from sensors like the eyes or ears, piecing together bits of information until a final picture is obtained, much like the process involved in solving a jigsaw puzzle," adds Tweed. "The sensors react even to unlikely or unexpected events but the brain disregards some of these signals to form one coherent picture. The brain is always compromising." The research was supported by the Canadian Institutes of Health Research and the Canada Research Chairs program. The Mind-Body Link The Journal of Neuroscience Many scientists once rejected the idea that the immune system, traditionally thought of as the prime internal defense system, worked closely with the nervous and endocrine systems to carry out its task. Such a finding would suggest that our mind could influence illness. Now an increasing amount of evidence is showing that the three systems are indeed working together. Sometimes everything seems against you. You slip on the ice. Your dog bites you. Then, only a week before finals, you catch your sister's cold. A fever and the blahs compound your feelings of ill fate. These symptoms, however, are a sign that something is on your side. The immune system. And your brain too, according to an increasing number of studies. The immune system battles countless enemies. Its wrath is unleashed on viruses, bacteria, parasites and other foreign molecules that make it past body borders and try to stake a claim. Immune defenses also combat abnormalities that arise inside the body, such as cancer cells. Many researchers once believed that the immune system was an entirely independent entity in the body. Now an increasing number of studies show that the immune system is tightly connected to the nervous system, as well as to another communication network known as the endocrine system. It appears that their three-way communication is vital for an adequate defense of the body and brain. The discovery of the strong connection is leading to: * Insight on how emotions can influence illness. * A clearer understanding of how the immune system fights foreign invaders and how disturbances in the circuit lead to disease. * Earlier diagnosis of diseases that might be influenced by communication between the systems. Starting in the 1980s researchers found evidence of strong connections between the immune, nervous and endocrine systems. First they identified direct links between nerve fibers and immune organs. More recently researchers determined that hormones of the endocrine system help the immune and nervous systems defend the body. For example, stress hormones can initiate actions in the brain and immune system in response to injury or germs. This stress response acts as an immune system regulator. It can dampen down the immune system so it doesn't go overboard. Scientists also recently discovered that immune molecules, known as cytokines, can initiate brain actions. For example, some cytokines help the body recuperate by sending messages to the brain that set off a series of sickness responses, such as fever. The high body temperature of a fever is thought to create an unfavorable environment for the foreign invaders. The immune molecules also can trigger feelings of sluggishness, sleepiness and loss of appetite. The behaviors can keep sick people out of harm's way until they feel better. Researchers found that cytokines can activate certain nerves for quick brain activation or set off actions from posts in the blood (see illustration). Scientists also discovered that some cytokines are produced directly in the brain. The increasing number of links that researchers are discovering between the immune, nervous and endocrine systems is leading them to investigate whether excess stress or too little stress can abnormally alter the immune defenses. Others are examining how defects in this intricate system possibly can lead to autoimmune disorders, in which the immune system attacks the body. In addition, scientists are continuing to map the cross-communication network to identify new ways to improve diagnosis and head off disease. For example, researchers recently found that a dramatic increase in one member of the defense team molecules can signal blood poisoning. This condition occurs when bacteria from an infected site such as a burn invades the blood stream. Diagnosis often comes too late, leading to a mortality rate as high as 51 percent. The researchers found larger than normal quantities of the defense molecule, nitric oxide, in the brains of rats soon after the onset of blood poisoning. This rise was detected in the spinal fluid. The scientists now are studying humans to see if this molecular signal will provide earlier diagnosis and treatment of the disease. Researchers found that one way immune molecules talk to the brain is through the blood. The large molecules are too big to cross from the blood to the brain but they may be able to slip across leaky junctions. Another way they get their message across is by attaching to special areas on blood vessels, called receptors, and triggering the production of molecules such as nitric oxide and prostaglandins. These molecules then directly relay messages to brain cells. Illustration by Lydia Kibiuk, Copyright © 1998 Lydia Kibiuk.

Brains In Dyslexic Children Can Be 'Rewired' To Improve Reading Skills Rutgers, The State University Of New Jersey 2003-03-05 (NEWARK) – In a scientific first, researchers have shown that the brains of dyslexic children can be "rewired" through intensive remedial training to function more like those found in normal readers. Paula Tallal, Board of Governors Professor of Neuroscience at Rutgers-Newark, and other members of a multi-university research team used brain-imaging scans of dyslexic children to demonstrate that areas of the brain critical to reading skills became activated for the first time and began to function more normally after only eight weeks of special training. In addition, other regions of the brain also lit up on the functional magnetic resonance imaging (fMRI) scans in a compensatory process that the dyslexics may have used as they learned to read more fluently. The researchers' groundbreaking findings were published Feb. 24 by the Proceedings of the National Academy of Sciences Early Edition. The other authors include faculty from Stanford and Cornell universities, the University of California's Los Angeles and San Francisco campuses, and one of the co-founders of Oakland-based Scientific Learning Corporation. Dyslexia, sometimes called "word blindness," is a disorder that affects 5 to 10 percent of Americans, and is characterized by difficulties in processing language. Usually these problems are severe enough to interfere with performance in school, but they cannot be attributed to a poor education, personal motivation, or impaired sight or hearing. The investigators, working at Stanford, extensively used Fast ForWord Language, a computer program designed by Tallal and other researchers at Scientific Learning Corporation. The program focuses on helping children become more adept at processing the rapidly changing sounds inside words. A dyslexic child may, for example, have difficulties distinguishing between letters that rhyme, such as B and D. "If you hear the sound 'ba' in 'butter' and 'da' in 'Doug,' the only way we know the difference is in the first 40 milliseconds of the onset of those sounds," Tallal explained. "The ability to extract sounds out of words is what is called phonological awareness." Words can be broken into sounds, and these sounds have to be mentally connected with letters. Although the process might seem intuitive, it is actually a learned skill, Tallal said. One portion of the study involved asking children if two letters of the alphabet rhymed, while their brains were imaged with fMRI scans. The scans of the 20 dyslexic children in the experiment – who struggled with the task – contrasted sharply with those of the 12 normal readers in the experiment's control group. The dyslexics' scans showed a lack of activity in the language-critical temporal regions of the brain. The training program, which included dyslexic children aged 8 to 12 years, was designed to help them learn to process and interpret the very rapid sequence of sounds within words and sentences by exaggerating them and slowing them down. "These are the building blocks you have to have in place before you can learn to read," Tallal said. "I think Fast ForWord is building the scaffolding for reading, and doing it based on scientific knowledge of the most efficient and effective way of helping the brain learn." The dyslexic children used the Fast ForWord Language computer program for 100 minutes a day, five days a week, as part of their regular school day. The program consisted of seven exercises adapted as computer games. In one exercise, for example, when a picture of a boy and a toy was shown, a voice from the computer asked the player to point to the boy – a step that required understanding the very brief difference in the sound of each word's first consonant. "Each child worked at his or her own level," Tallal said. The goal was to have the children process sounds correctly in words and sentences of increasing length and grammatical complexity, she added. The study's authors emphasized that continuous intervention would be necessary to make the dyslexics' improvements in reading skills stick and advance. "In light of President [George W.] Bush's legislation, 'No Child Left Behind,' which mandates that only scientifically validated applications be used for intervening with children, this program has the potential to help address the crisis we are facing in the large number of children failing to meet [educational] standards," Tallal observed. Brain Imaging Identifies A Brain Process Impaired In Dyslexia Aditi Shankardass, Roderick I. Nicolson & Angela J. Fawcett Dyslexia is a problem in learning to read and write for children of otherwise average ability, which afflicts almost 1 in 20 children. It is now strongly believed that this is caused not by the brains difficulty in processing language, but general visual and auditory information. Our research aims to isolate which brain process is impaired in dyslexics - is there a problem at the stage when information from the eye is first sent to the brain, or later, when that information is identified by the brain? This is done by measuring brain waves arising when the brain responds to the presentation of a visual stimulus. These brain waves indicate how fast the brain receives information and how quickly it analyses it. Our research suggests that the transfer of visual information to the brain is normal, but that processing within the brain is slower. More specifically, the difficulty is not at the stage at which the brain receives the visual information or the stage at which the brain responds to it, but at the intermediate stage when it makes decisions about the information, in particular, what it means and what to do with it. Such research is of the utmost importance, in that it shows how pure science can be used to understand, diagnose and ultimately relieve one of the most important and prevalent developmental disorders. Finns Point to Dyslexia:Gene Hint to Human Reading Ability. Nature 30 April 2003 HELEN PEARSON Up to 15% of people may have dyslexia. A Finnish family has given the first clear clue to a gene involved in dyslexia. Between 5 and 15% of people are dyslexic. They have problems reading, writing and spelling. Although scientists have suspected that genes are involved, they had not come up with a convincing candidate - until now. One gene is mutated in around 10% of Finnish dyslexics, compared with 2-3% in the rest of the population, Juha Kere of the University of Helsinki, Finland and his team found. "If you have the gene you become more susceptible, but you're not necessarily dyslexic," he says. Chimps, gorillas and other apes carry a slightly different form of the gene to humans, Kere told this week's Human Genome Organisation meeting in Cancún, Mexico. This implies that, during human evolution, a gene with some other function might have been adapted for processing words. Exactly what the gene, dubbed DYXC1, does is still a mystery. Kere suspects that it may switch other genes on and off in the brain. They stumbled across it in a Finnish family containing four dyslexics whose chromosomes were all severed at the same point, disrupting DYXC1. Such families are "a classical way of getting genes", says Mark Lathrop of the National Genotyping Centre in Evry near Paris, France. The discovery now has to be confirmed in other, larger populations, he says, before it can be branded a 'dyslexia gene'. This could be tricky: countries with different languages use different word tests to diagnose dyslexia. Thus many underlying brain problems, with different genetic causes, might be branded with the same name. Genetic gold-mine Small, isolated populations around the world are a gold-mine for geneticists. Because they grew from only a handful of founders, it is easier to find shared mutations involved in disease. "Most mutations happened once in history," says Tom Hudson of McGill University in Montreal, Canada. Hudson's research in a remote region of Quebec, for example, is revealing risk genes for heart disease and diabetes. And the Mediterranean island population of Sardinia is providing clues about susceptibility genes for asthma, the meeting heard. © Nature News Service / Macmillan Magazines Ltd 2003

Rare Brain Mapping Procedure Provides Unique Picture Of Two Areas Concerned With Language Processing And Production LOS ANGELES -- A unique opportunity to map and test the human brain has yielded new insights into two areas involved in producing and processing of language. Speaking at the annual meeting of the Society for Neuroscience, David Corina, an assistant professor of psychology at the University of Washington, reported on the roles of two brain regions called Broca's area and the supramarginal gyrus. The findings came from a rare case, a deaf person called S.T. who uses American Sign Language. S.T. underwent a procedure called an awake cortical stimulation mapping, which allows assessment of language and motor functions at specific sites in the brain's left hemisphere. Corina, a fluent signer, and an interdisciplinary team of UW researchers tested the subject and found that electrical stimulation of Broca's area and the supramarginal gyrus created repeated but different kinds of errors in S.T.'s ability to name objects. When Broca's area, which is located in the frontal lobe, was stimulated, S.T. had difficulty making clear hand shapes and specific movements associated with signs. Nonetheless, these sloppy signs resembled the target sign. Corina likens these errors to "mumbling" made in spoken languages. The subject made no effort to self-correct these lax or imperfect signs. Stimulation of the supramarginal gyrus, a small area in the parietal lobe, produced different kind of signing error. With stimulation, S.T. mixed up word meanings and word forms. For example, when shown a picture of a pig and asked to make the sign for it, S.T. made the sign for farm. The two signs are very similar in hand shape, movement and spatial location to the sign pig in American Sign Language, and would be distinct to skilled signer. Comparable errors in English might be saying oyster instead of lobster or plane instead of train. This type of error suggests that the supramarginal gyrus may be an area of the brain important in the selection and combining of word meanings with word forms. Another interesting difference in these language errors was that with stimulation to Broca's area, S.T. made no effort to self-correct his imprecise signing. However, with stimulation to the supramarginal gyrus, he would make successive attempt to produce the correct sign (for oyster he would sign "loyster," then "lobster"). This suggests that stimulation of Broca's area was effecting only the final output of a correctly selected word, while supramarginal gyrus stimulation was effecting the compiling of the word forms, according to Corina. Neuroscientists have long established that a region in the left hemisphere plays a role in language function. In the past decade it also has become evident that left hemis- phere specialization for language extends to deaf people who use sign languages, as well as for those who speak. However, scientists are just beginning to understand the particular contributions specific regions within the left hemisphere play in language processing. The data Corina reported on came from an awake cortical stimulation mapping performed on S.T., a 50-year-old man who was suffering from epileptic brain seizures. The mapping was done prior to an operation called a temporal lobectomy which reduces severe seizures. The mapping procedure helps the neurosurgeon plan this delicate operation. In the mapping, a small electrical current is applied to the exposed cortex of the brain of an awake patient. During electrical stimulation, the patient is asked to name objects and imitate actions. This procedure is often used on speaking people undergoing the brain surgery, but Corina's report and an in press paper, are the first detailed accounts of its effects on a deaf signer. "Although Broca's area has gotten considerable attention, its precise role in language behavior remains controversial," said Corina. "One controversy is whether Broca's areas is specialized just for speech or language in general. We have now been able to identify that Broca's area is involved in language production, not just speech production but any language spoken or signed. This is the best evidence that it is responsible for language independent of whether that language is expressed through the hands or the voice." Corina noted the surprising finding that stimulation to areas next Broca's area resulted in movements of the mouth and lips, but not the hands. "This study also strongly suggests that the supramarginal gyrus plays a critical role in blending semantic and phonetic information," he added, citing the word cat as an example. Cat has semantic features, being a "little furry critter that goes meow." It also has phonemic elements which correspond to the sound which make up the word cat --/k/ and /at/ in English -- and the hand shape and movements for a sign in American Sign Language. The supramarginal gyrus may be pulling together this kind of information, according to Corina. "Some people have wondered if the human brain has specialized areas of language production and processing," he said. "This work provides new evidence in favor of specialized areas of the brain which are unique to language processing and production. People also have asked if there is a so-called language organ. Our work suggests that there is a whole network of areas responsible for speech and language. Broca's area and the supramarginal gyrus are just two pieces of that network." The mapping procedure on S.T. lasted about 90 minutes prior to his surgery and was conducted while he was under a local anesthetic. The researchers tested a number of different left hemisphere sites for motor and language impairment by having S.T. do several tasks. He was shown pictures of 49 objects, such as a bird, chair, pig, bed and table, and asked to give the sign for each under normal conditions and while being electrically stimulated at each site. He also was asked to imitate signs and complex arm gestures. Only six sites showed any motor impairment and just two, Broca's area and the supramarginal gyrus, exhibited consistent impairments to language processing or production. Corina said basic research such as this is important because science is very interested in being able to provide people with improved communications skills. "One way to improve communications is to discover all the sub parts that are involved in language. To do this, we need to understand where and what portions of the brain are involved so we can develop better interventions to assist people," he said. "This work also has a practical application to help deaf people who, like hearing people, have seizures. The medical community needs to be aware that it can use the same standardized mapping procedures used on hearing people to identify language areas to ensure better post-operative outcomes on deaf patients. People need to realize that sign languages are real and naturally occurring human languages." Other members of the UW research team that mapped S.T.'s brain included George Ojemann and Carl Dodrill, professors of neurological surgery; James Brinkley, research associate professor of biological structure; Susan McBurney, doctoral student in linguistics, and Kevin Hinshaw, doctoral student in computer science and engineering. Note: This story has been adapted from a news release issued by University Of Washington for journalists and other members of the public. If you wish to quote from any part of this story, please credit University Of Washington as the original source. You may also wish to include the following link in any citation: http://www.sciencedaily.com/releases/1998/11/981109081831.htm Copyright © 1995-2001 ScienceDaily Magazine

Visual Attention Attuned To Grabbable Objects Dartmouth College 2003-03-17 HANOVER, NH – A Dartmouth research group has found a new and unexpected way our attention can be grabbed – by grabbable objects. Their study, which appears in the March 17 advance online issue of Nature Neuroscience, demonstrates that objects we typically associate with grasping, such as screwdrivers, forks or pens, automatically attract our visual attention, especially if these items are on a person's right-hand side. In the brain, there are two primary visual pathways, one for identifying objects (perception) and one to guide your arms and legs based on what you see (action). To better understand how these two systems may interact, the Dartmouth team studied whether visual perception, specifically peripheral visual attention, influences motor systems in the brain. "People have studied peripheral vision and how it helps perception, but nobody really talked about it in terms of helping action," says Todd C. Handy, the lead author and a research assistant professor at the Center for Cognitive Neuroscience at Dartmouth. "There are certain things that we all know attract our attention, like flashing lights and loud noises. Yet, think about how often we grab things without directly looking at them. Now here's evidence that, to help us do this, grabbable objects can literally grab our attention. There's a clear association." The researchers devised a simple test to measure this connection. They asked their subjects to look at a computer screen with two objects: one was something graspable, like a tool, the other was not graspable, like a cloud or a sailboat. After about a second, a set of horizontal bars flashed over one of the pictures. While concentrating in the center of the screen, the subjects were told to indicate whether the bars appeared on the left or right. The researchers determined where attention was focused when the bars flashed by measuring the electrical activity in the brain with an electroencephalogram (EEG). "When the bars flashed over a graspable object, the EEG response in the visual cortex was more intense," says Handy. "It shows evidence of attention being specifically drawn to those objects. Interestingly, the effect was more profound when the tool was on the right. It suggests that attention is more strongly drawn to grabbable objects when they are on our right." Handy's team then used fMRI (functional magnetic resonance imaging), a method that precisely identifies areas of brain activity, to confirm their results. They found that when the tool appeared on the right, the brain's classic motor areas responded to it. If the tool was on the left, the motor areas weren't as active. According to Handy, this indicates that when graspable items are on the right, the motor system recognizes that there is something to grab and attention is drawn automatically to that location. "People had already shown that simply viewing graspable objects activates motor areas in the brain," explains Handy. "What we didn't know was that graspable items can affect visual attention, and that it matters where these things are in visual space." The team is now trying to understand whether being right-handed or left-handed influences visual attention and motor activity. Handy's co-authors on the paper include Scott T. Grafton, professor of psychological and brain sciences and the Director of the Dartmouth Brain Imaging Center; Neha M. Shroff, Dartmouth alum from the Class of '02; Sarah Ketay, research assistant; and Michael S. Gazzaniga, Dean of the Faculty of Arts and Sciences at Dartmouth and a professor of psychological and brain sciences. This study was funded by the National Institutes of Health. Copyright © 1995-2002 ScienceDaily Magazine Altered Images for Brain Damage Patients Health Low Graphics People with visual agnosia could believe these animals are real Imagine looking at a dog - and not recognising it as a dog. What if you looked at a sheep or a cow, and didn't know what it was? And what if you looked at the pictures above - and thought the "babex" and "bunnyphant" might be real? That is the situation for some people with visual agnosia. People with the condition can have trouble recognising animals, faces or objects. This is just as valid a way of looking at [the world] - it's just different Dr Ros McCarthy, Cambridge University Now a series of films entitled "Eye See" is being planned to allow everyone to see the world as visual aphasics see it. The makers hope they will raise awareness of the condition, which affects up to one in four stroke victims. Visual agnosia is a disorder of the brain's visual processing system, and it can take lots of different forms depending on which area of the brain is damaged. Bill Alker, a spokesman for Headway, the brain injury association, said it was a rare, but recognised condition which could be caused by head injury. "It is condition characterised by an inability to recognise and identify objects or persons despite having knowledge of the characteristics of the objects or persons. "Traumatic brain injury also known as head injury can be the cause. For example as the result of an accident, damage caused specifically to the occipital or parietal lobes in the brain result in agnosia." Recognition One of the most interesting cases of visual agnosia is Philip, a man in his 40s who suffered brain damage in a car accident 24 years ago. Since then, he has not been able to recognise real animals - and hasn't been able to tell which are fake. He is also unable to recognise familiar faces - including those of close family and friends unless he is helped by hearing their voices, or recognising their clothing. Philip was a trainee draughtsman before his crash. Since it happened he has tried to take up jobs and even run his own business, but it has been difficult because he cannot recognise people. A 'bunnyphant' - a rabbit's head on an elephant's body Dr Ros McCarthy, a neuropsychologist at Cambridge University who is working with Philip, said: "He goes home and knows the woman there is probably the same one he has always lived with but is not totally sure until she speaks. "He recognises movement and voices, but not faces." She added: "Likewise he has problems identifying some animals and fruit and vegetables. He will look at a sheep, a deer or even a bear and say that they are fantastical creatures, they don't really exist. No 'memory bank' "But when I showed him a picture of a 'babex', something I had concocted which was part ibex and part baboon he said the horns were tusks and thought it might be something you shoot in Scotland. "So, I believe he had it confused with a deer. He also thought another creature, a 'bunnyphant' - a mixture of rabbit and elephant - was a real thing." The reason Philip and others with visual agnosia have these strange visual worlds is that they have lost the normal long-term "memory banks" we use when recognising visual information. However, he is able to use temporary memories to help his recognition. For example, when adverts are being run for Penguin biscuits, he can recognise the animal. Dr McCarthy said: "When there's an advertising campaign going on for Penguins, he can name penguin pictures, but he always comes up with the advertising slogan. "But once the campaign ends, it starts fading from his memory. Sometimes he sees a duck and thinks its a penguin - and he sees a penguin and thinks it might be a seal." Dr McCarthy said Philip simply did not have "a sense of familiarity" for animals. A 'babex' - a baboon with an ibex's head She added: "When he sees one of these composite animals, he thinks they are just as likely to be real as a genuine animal." But with other categories of image, he can distinguish between real and made-up images. For example, he would know that an image showing the front end of a car attached to a train carriage was not real. Other visual agnosics can have the opposite problem, and find it difficult to recognise objects. Dr McCarthy said Philip is quite unusual because he has the problem in a very uncomplicated way. Many people with agnosia may have additional difficulties in communication or in daily memory. Philip is fortunate in having a very restricted area of difficulty. She added: "He knows its his problem and he finds it quite interesting." Perception Dr McCarthy said visual agnosics cannot be "cured". "You can't change them but you can help them to cope better to recognise what the issue is, and to find ways around the problem." She said part of the reason for making the films, which will be funded with £38,000 from the Wellcome Trust, was to help people understand the condition. "I hope we can produce these films from the point of view of the affected individual, to try and convey in some sense the way that brain damage affects the way you see and interpret the world," she said. "And to show that this is just as valid a way of looking at it - it's just different."

Women with Disabilities Use Acupuncture to Heal Pacific College of Oriental Medicine New York, NY - In an effort to provide respectful, high-quality medical services for women with physical disabilities and chronic conditions, Pacific College of Oriental Medicine is teaming up with the Initiative for Women with Disabilities (IWD) Elly and Steve Hammerman Health and Wellness Center at the Hospital for Joint Diseases to offer acupuncture to its patients for pain management.  The IWD was founded in 1997 because "there was a need for women with disabilities to get gynecological care," said IWD Director Judith Goldberg. When IWD patients started asking for the addition of an acupuncture program in 2001, the New York branch of Pacific College joined forces with IWD. Now, student interns supervised by Licensed Acupuncturists from Pacific College have clinical rotations three times a week treating IWD patients for pain. Since its inception, the program has been very popular. There is currently a waiting list of 80 people for the acupuncture program. Over the course of fourteen weeks, a patient may receive as many 20 treatments. "This treatment helps me a lot with my pain," one patient said. "The people are also very caring and loving. This has helped my back pain decrease." Acupuncture has been cited by the World Health Organization to treat more than 43 conditions, including headaches and migraines, back pain, osteoarthritis, and constipation. According to a 1997 National Institutes of Health panel, "One of the advantages of acupuncture is that the incidence of adverse affects is substantially lower than that of many drugs other accepted medical procedures used for the same conditions." The IWD patients seem to agree. "My back pain seems better, less muscle spasm, and my ankle movements have improved a great deal," one IWD patient said. "I personally would refer anyone to try the natural healings of acupuncture treatment. I am feeling wonderful."

Words Get in the Way Talk is cheap, but it can tax your memory Bruce Bower Law-enforcement officials typically solicit descriptions of criminals from eyewitnesses, often just after an offense has occurred. It stands to reason that thorough accounts by those who saw what happened will help investigators round up the likeliest suspects. Eyewitnesses can then pick the criminals out of a lineup. When crime-scene interviewing had its first brush with memory research in 1990, however, the results proved disturbing. A series of laboratory studies found that memories for a mock criminal's face were much poorer among eyewitnesses who had described what the perpetrator looked like shortly after seeing him, compared with those who hadn't. WORDLESS RECALL. Eyewitnesses may remember a criminal's features more accurately if they don't immediately try to describe them. Psychologist Jonathan W. Schooler of the University of Pittsburgh, who directed the studies, dubbed this effect "verbal overshadowing of visual memories." His paper's subtitle put it more bluntly: "Some things are better left unsaid." Not among scientists, though. Discussion generated by Schooler's results ushered in a wave of research examining how eyewitnesses can find themselves, as he later quipped, "at a loss from words." Studies have confirmed that, at least under certain circumstances, verbal descriptions impair memories for faces and other hard-to-describe perceptions, such as the taste of a fine wine or the sound of a person's voice. Recent investigations, described in the December 2002 Applied Cognitive Psychology, extend what's known about verbal overshadowing and offer potential tactics for counteracting this memory-sapping effect. However, no one yet knows the full range of perceptions subject to verbal overshadowing or its implications for various eyewitness-interviewing techniques. "Verbal overshadowing is a genuine and reliable phenomenon," says psychologist Christian A. Meissner of Florida International University in Miami. "However, conclusions as to the mechanisms responsible for it appear [to be] complex and elusive." Memory shift Research into verbal-memory theft began with a staged felony. Schooler and a colleague showed volunteers a 30-second video depicting a man robbing a bank. Participants then spent 20 minutes on an unrelated task. At that point, a randomly chosen half of the group was asked to write a detailed description of the robber's face. These volunteers were encouraged to focus on each of the criminal's facial features and to use all of the allotted 5 minutes to jot down their memories. The rest spent 5 minutes tackling a second task unrelated to the video. Each participant then tried to identify the robber's face from an array of eight photographs, only one of which showed the criminal impersonator. About one-third of those who wrote a description picked out the correct face, compared with two-thirds of those who didn't. At first, Schooler suspected that errors in participants' verbal descriptions had altered the man's visual appearance in their mind's eye. This still-current theory holds that a person asked to describe a face inevitably makes errors in finding words for the ineffable quality of what another person looks like. Memory of the face then changes to accommodate the verbal depiction, which hinders the witness' later recognition of the face. Schooler has since adopted a contrasting explanation, which posits that the act of describing a face replaces unconscious perceptual operations with word-based, largely conscious thinking. Ensuing attempts to identify the face visually refer back to the verbal account, creating confusion and mistakes. An accurate perceptual memory of the face theoretically remains intact, but people have trouble dipping back into that knowledge, Schooler proposes. For instance, in a 1995 study, Schooler reported that verbal descriptions disrupted white volunteers' memories for the faces of white but not black individuals. He proposed that thanks to their extensive experience in looking at white faces, white volunteers used rapid, nonverbal perception to evaluate each such face as a unified entity. In contrast, volunteers spent more time studying individual features of the less-familiar black faces. Subsequent written descriptions were more consistent with the features that white participants remembered about the black faces than with the unified images they had stored for the white ones, Schooler concludes. Other research indicates that verbally adept individuals exhibit less memory loss after describing a same-race face than individuals with poor verbal skills do. Also, verbal overshadowing afflicts those with superior perceptual capabilities—such as skillful discernment of objects in cluttered scenes—to a greater extent than it does people with meager perceptual power. Schooler is now exploring other perceptual capabilities that respond to verbal overshadowing. For instance, verbal descriptions impede one's mental map of an area, according to Schooler and his Pittsburgh colleague Stephen M. Fiore. In their experiment, volunteers spent 12 minutes studying a map of a small town with a path connecting 16 landmarks, such as a library and a town hall. Half the test participants then wrote everything they could remember about the path's route and landmarks along the way. The rest took the time to write down some personal experiences unrelated to the map. Only those who had described the map had difficulty estimating the relative straight-line distances between pairs of landmarks. Schooler says that these as-the-crow-flies estimates required each volunteer to consult a mental image of the entire town's layout, a form of perceptual knowledge that he regards as susceptible to verbal interference. Verbal descriptions of the map didn't undermine recall of approximate lengths of winding paths between pairs of landmarks. This task called for route knowledge that volunteers could verbalize, as in "go left at the library, then take the long, curving path to reach the schoolhouse," Schooler says. Saving face Other findings also suggest that a shift from a perceptual to a verbal focus blocks a person's access to perceptual memories, even though they remain intact. In one study, conducted by Kim Finger of Claremont (Calif.) Graduate University, participants who wrote a description of a man's face after studying the face for 5 minutes suffered no memory loss if they were then nudged back into a perceptual frame of mind. To do this, Finger asked them either to solve a printed maze or to listen to 5 minutes of instrumental music. Both strategies yielded face memory equal to that of volunteers who didn't provide a written description. Face recall also benefits from a delay of as few as 24 minutes between completing a verbal description and viewing a photo lineup, according to a study conducted by Finger and her Claremont colleague Kathy Pezdek. Such interruptions erased memory lapses that characterized volunteers tested 10 minutes after writing a description of a man's face. Nearly half-hour breaks similarly refreshed the memories of people instructed to visualize the man's face, consider the thoughts and feelings they had while looking at his face, and report everything they could remember. Such tactics, now used by some police departments with crime witnesses (SN: 4/19/97, p. 246: http://www.sciencenews.org/sn_arc97/4_19_97/bob1.htm), yielded particularly poor face memories after 10-minute delays. For now, police officers should show patience after interviewing people at crime scenes, Finger suggests. Before asking them to pore over mug shots, perhaps give eyewitnesses a few minutes to listen to recorded music, which may safeguard their memories. Verbal descriptions can also interfere with "earwitness" memories, report psychologist Timothy J. Perfect of the University of Plymouth, England and his coworkers. In their study, volunteers heard a recorded voice say, "Just follow the instructions, don't press the alarm, and no one will get hurt." Compared with people who then sat quietly for 5 minutes, those given that same period to write down everything they could remember about the voice had far more difficulty identifying the same voice from among six choices. "Verbal overshadowing is an amazing phenomenon," Pezdek says. However, she notes that it's failed to turn up in some studies. Deceptive details Meissner proposes an explanation for the sometimes elusive nature of verbal overshadowing. He bases his argument on a statistical analysis, conducted with John C. Brigham of Florida State University in Tallahassee, of 15 separate investigations of verbal overshadowing in facial memory that recruited a total of 2,018 people. The pattern of results indicates that participants told to delineate every possible detail about a face, even to the point of guessing, litter their descriptions with blunders—especially if quizzed within 10 minutes of seeing the face, Meissner contends. They then try in vain to match their verbally retooled memories to what they see in a photo array or a lineup. This view contrasts with Schooler's idea that the original memory remains intact but inaccessible. In a new study, Meissner explores the memory effects of different types of instructions given to 576 college students who studied a face for 5 seconds. One group was told to describe the face in detail and to disregard any uncertainties about their memories. Five minutes later, only about a third of these students selected the previously seen face from a photo array. A second group of students was instructed to describe only what they could confidently remember, and after 5 minutes, slightly more than half recognized the face they had studied. A third group was told to describe only what they could recall with certainty about the face and also was warned not to guess. They performed as well as study participants who weren't required to provide a description. About two-thirds of both groups chose the correct face. These findings held whether volunteers tried to pick the previously seen face from an array of eight photos or viewed one photo at a time and gave a "yes" or "no" answer. Other studies, which have not controlled for the amount of detail in eyewitnesses' verbal descriptions, have generally concluded that one-at-a-time presentations of crime suspects yield more accurate recall than all-at-once inspections. Moreover, in Meissner's work, the group told to report even uncertain details in their descriptions made far more false identifications than any other group when shown photo arrays that didn't include the original face. Silent might Meissner's findings underscore the narrow scope of verbal overshadowing, contends Florida State University psychologist K. Anders Ericsson. People forced to generate strictly limited verbal accounts can still remember a considerable amount of perceptual information, he says. Ericsson and the late Herbert A. Simon developed a method, called protocol analysis, for interviewing individuals about their thought processes during and immediately after performing various tasks, such as mental arithmetic. Participants in these studies had been instructed to report orally only on what they can confidently recall and avoid making guesses. Under these conditions, the act of reporting one's thoughts out loud either during or just after performing a mental task often leads to better memory for that task, when compared with silent recall of one's thoughts or the performance of irrelevant acts in the interim, Ericsson maintains. Bare-bones interviewing practices, such as protocol analysis, avoid verbal overshadowing partly because the effect thrives on conscious deliberation about a prior act or perception, according to Schooler. The types of problems that volunteers grapple with also make a difference, he says. For instance, Schooler has reported that people who described their thoughts as they solved "insight" problems—"Aha!"-type puzzles that require the discovery of subtle ways to conceptualize, say, an ambiguous picture or a word problem—had more difficulty solving the tasks than did people who said nothing. However, describing ongoing thoughts had no effect on people's success at solving analytical problems, such as mental arithmetic. In other words, articulating one's inner thoughts disrupts intuition but not logical analysis, in Schooler's view (SN: 10/30/99, p. 282). Just as provocatively, research on verbal overshadowing challenges the popular notion among philosophers and psychologists that language lies at the core of thought. "Various forms of inexpressible knowledge may be best served by avoiding the application of language," Schooler says. He adds that Albert Einstein would have agreed. "I very rarely think in words at all," the great scientist once told an interviewer. "A thought comes, and I may try to express it in words afterwards." More often than the rest of us would like to admit, silence may indeed be golden. Limbic-Striatal Memory Systems and Drug Addiction. Robbins TW, Everitt BJ. Department of Experimental Psychology, University of Cambridge, Drug addiction can be understood as a pathological subversion of normal brain learning and memory processes strengthened by the motivational impact of drug-associated stimuli, leading to the establishment of compulsive drug-seeking habits. Such habits evolve through a cascade of complex associative processes with Pavlovian and instrumental components that may depend on the integration and coordination of output from several somewhat independent neural systems of learning and memory, each contributing to behavioral performance. Data are reviewed that help to define the influences of conditioned Pavlovian stimuli on goal-directed behavior via sign-tracking, motivational arousal, and conditioned reinforcement. Such influences are mediated via defined corticolimbic-striatal systems converging on the ventral striatum and driving habit-based learning that may depend on the dorsal striatum. These systems include separate and overlapping influences from the amygdala, hippocampus, and cingulate and medial prefrontal cortex on drug-seeking as well as drug-taking behavior, including the propensity to relapse. Copyright 2002 Elsevier Science (USA) Scientists Are Unlocking the Secrets of the Brain By BBC News Online Science Editor Dr David Whitehouse Scientists have managed to photograph what happens to the brain during learning and recalling memory. The observations detail some of the changes that occur to arrangements of nerve cells that take place when a memory is laid down. Exactly how these changes relate to the memory of specific things such as faces and events is an entirely different and as yet unknown matter. Researchers at the University of Geneva used an electron microscope to photograph the changes occurring at the connection points between two nerve cells when long-term memory is established. Looking at cross-sections of rat brains, the research team constructed three-dimensional images of minuscule nerve cell connections. In doing so, they saw that the memory process occurs in the duplication of certain connections or synapses between nerve cells. Stimulating environment The images, featured in the journal Nature, have been hailed as a breakthrough in the understanding of how the brain works. Before the change, red and white nerve cells have one connection. It has been known for some time that the brain of a young rat raised in a stimulating environment possesses a network of neurons much more complex than the brain of a rat that has been under-stimulated. But until now, the detailed effect of this stimulation on nerve cells had never been seen. Neurobiologists call the process "Long-Term Potentiation" (LTP) when a nerve cell is stimulated by a neighbouring cell and acts as if it "remembers" the stimulation. It is this change that acts as the fundamental storage for memory information. Billions of nerve cells The researchers noticed that following LTP, the nerve cell's sensitivity to its neighbour's nerve signal will be twice as strong. After the change, there are two Each of the 100 billion nerve cells in our brain can have up to 10,000 synapses with its surrounding neurons. But when a memory is formed, only a small number undergo a change. Scientists say this is why they have taken so long to capture images of the modifications associated with LTP. Nicolas Toni, a member of the University of Geneva team, says that that the synapses of a nerve cell that has been repeatedly stimulated by its neighbour undergoes a physical change. Its surface alters, forming a second contact point with other nerve cells about an hour after stimulation. It is this change that forms the basis for the chemical and connection changes to the nerve cells that act as memory storage units, he said.