June 2004

CROSSROADS UPDATE

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Models of Attention John G Taylor, PhD Models of attention have a venerable history going back to Aristotle, who considered attention as a narrowing of the senses. More recently, numerous experiments have been performed to discover brain regions involved in various aspects of attention. Using global functional brain imaging techniques (PET and fMRI) various experiments have shown that moving the focus of attention is achieved by a different brain network from that involved in processing the input being attended to [1, 2]. The regions exercising control of attention movement are in parietal and prefrontal sites, while attended sites are in primary and secondary cortices in the various senses (and also in motor cortex for response). These locations have been supported by study of deficits in the speed of attention movement, as shown from studies by Posner and colleagues [3]. Attention modulates activity in the input sites, as shown both globally from fMRI data in attention paradigms [4] and by analysis of single cells in monkey early visual cortex [5]. Attention achieves its effects on earlier cortical sites by feedback, which changes the classical receptive fields of cells in anaesthetised monkeys as compared to awake animals [6]. Detailed timing analyses in humans, using EEG and fMRI methods, support the existence of attention-controlled feedback [7], as well as the general model of control arising from superior parietal sites in the fast dorsal steam to gate slower object representations in the ventral stream [8] Attention control has been found to arise by two mechanisms, one by bottom-up signals from the occurrence of unexpected and strong inputs (such as a brief flash of light), the other by top-down control from some required goal (such as by the face of a friend being searched for in a crowd). It had been thought that bottom-up signals normally achieved attention capture; it is now appreciated that top-down control is usually in charge. Involuntary attention capture by distracting inputs occurs only if they have a property that a person is using to find a target [9]. Thus there is a single control network deciding between the importance of desired (top-down) and unexpected (bottom-up) sites for attention. The lack of attention capture has been carefully investigated as has the phenomenon of inattentional blindness, in which apparently important and unexpected events just do not draw our attention to them [10, 11]. The two sorts of attention, termed exogenous for bottom-up and endogenous for top-down, have been found to possess quite different times for onset and decay: exogenous attention is rapid, and reaches its maximum effect about 100-200 msecs after cue onset in humans, and then falling away as rapidly. On the other hand endogenous attention is slower, rising gradually to a maximum only at about 300-400 msecs after cueing occurs. Attention can be divided between two modalities, such as vision and audition, but the degree of coupling of the control over attention in different modalities is still controversial [12]   Recent Models of Attention Theoretical models of attention have been produced which try to keep up with the rapid pace of experimental advance described above. These models are of two sorts. One is psychological/ functional, and leads to insights into information flow but not to quantitative comparisons with data. The other uses neural networks, and provides detailed simulations of psychological paradigms by interacting neurons in modules that may or may not be part of the psychological models. These latter models can therefore be more stringently tested. There are now numerous neural network models of attention; only outlines of a selection of them can be considered. The first psychological model [13] dissociates the overall control of attention into: alert interrupt localize disengage move engage inhibit. Evidence has been brought forward to support such a dissociation, with various modules, including the pulvinar nucleus in thalamus, as running the separate stages. A second approach [14] is based on selection of an area in visual space, using both inhibitory and excitatory mechanisms in a separate module to identify objects, and the movement of attention is then achieved by sliding down the gradient of an excitatory hill in another competitive network. A third model also uses biased competition to move attention to objects [15]. These and related models use a form of competition in a higher-level module to guide movement of attention on a lower order one. Neural network simulations of attention tasks implement this general idea. Simulation of visual search times for targets in the presence of distracters has been performed using an input module (representing early visual cortex), a higher order module where a competition determines where attention shall be focused (as in parietal lobe), and an object-coding module to represent objects learnt in the past (as in temporal cortex). A linear increase in search time with number of distracters has been observed in such simulations [16, 17]. Biasing the competition for attention by a frontal template has also been studied in a model with explicit frontal sites [18]. Finally both a salience-based approach and a synchronized oscillator method have been developed which cause object segmentation in cluttered scenes followed by attention orienting [19, 20]. An explicit engineering control framework has been introduced which fuses these approaches [21]. It uses a plant site (identified as early cortex and temporal lobe), an inverse control module (identified as in parietal lobe), a rules module (in prefrontal cortex) and an observer or forward model (with components in both parietal and prefrontal lobes).This model leads to close agreement of the dependence of response speed-up achieved by attention to a target as the cue-to-target time interval varies from 0 to 1.5 seconds. The calculated rise and fall of the exogenous attention shift benefit and the slower but steady rise of the endogenous shift benefit possess the features observed in humans mentioned earlier [22].Detailed contributions of some of the control components are still being assessed. References [1]. Hopfinger JB et al (2000) The neural mechanisms of top-down attentional control. Nat Neurosci 3:284-291. [2]. Kastner S & Ungerleider LG (2000) Mechanisms of Visual Attention in the Human Cortex. Ann Rev Neurosci 23:315-341. [3]. Posner M & Petersen SE (1990) The Attention System of the Human Brain. Ann Rev Neurosci 13:25-42. [4]. Friston KJ et al (1995) Characterizing Modulatory Interactions Between Areas V1 and V2 in Human Cortex: A New Treatment of Functional MRI Data. Hum Brain Map 2:211-234. [5]. Reynolds JH et al (1999) Competitive Mechanisms Subserve Attention in Macaque Areas V2 and V4. J Neursoci 19:1736-1753. [6]. Lamme VF & Roelfsema (2000) The distinct modes of vision offered by feed-forward and recurrent processing. Trends Neurosci 23:571-579. [7] Martinetz A et al (2001) Putting spatial attention on the map. Vis Res 41:1437-1457. [8] Vidyasagar TR (1999) A neuronal model of attentional spotlight: parietal guiding the temporal. Brain Res Revs 30:66-76. [9]. Pashler H (2001) Attention and Performance. Ann Rev Psych 52:629-51.  [10]. Mack A & Rock I (1998) Inattentional Blindness: Perception without Attention. Ch 3, pp 55-76 in visual attention, ed RD Wright. Cambridge MA: MIT Press..  [11]. Simms DJ (2000) Attentional capture and inattentional blindness. Trends Cognit Sci 4:147-155. [12]. Spence C et al (2000) Cross-modal selective attention: On the difficulty of ignoring sounds at the locus of visual attention. Proc Psychophys. 62:410-424. [13] Posner MI et al (1987) Isolating attentional systems: a cognitive-anatomical analysis. Psychobiology 15:107-121. [14] LaBerge D & Brown V (1989) Theory of Attentional Operations in Shape Identification. Psych Rev 96:101-124. [15] Desimone R & Duncan J (1995) Neural Mechanics of Selective Visual Attention. Ann Rev Neurosci 18:193-222.  [16] Mozer MC & Sitton M (1999) Computational modeling of spatial attention. Ch 9, pp 341-393 in Attention. ed H Pashler. New York: Taylor & Francis. [17] Deco G & Zihl J (1998) A Neuronal Model of Binding and Selective Attention for Visual Search. Pp 262-271 in Cognitive Neuroscience, Heinke D, Humphreys GW & Olson A (eds). London: Springer. [18] Jackson SR et al (1994) Networks of Anatomical Areas Controlling Visuospatial Attention. Neural Networks 7:925-944. [19] Lee DK, Itti L, Koch C, Braun J. (1999) Attention activates winner-take-all competition among visual filters. Nature Neurosci 2(4):375-81. [20] Fellenz W (1994) A sequential model for attentive object selection. In Proc 39th IWK Conf, Ilmenau. [21] Taylor JG (2001) Attention as a Neural Control System. pp 272-276 in Proc Int Joint Conf on Neural Networks (IJCNN’01), IEEE Cat #01CH37222C, ISBN# 0-07803-7046-5. [22] Taylor JG & Rogers M (2001) A control model of the movement of attention. Neural Networks 15: 309-326.   The Author John G Taylor Department of Mathematics, King’s College, Strand, London WC2R2LS, UK

ADD/ADHD

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The clinical role of computerized EEG in the evaluation and treatment of learning and attention disorders in children and adolescents. J Neuropsychiatry Clin Neurosci Chabot RJ, di Michele F, Prichep L, John ER. Department of Psychiatry, Brain Resarch Laboratories, New York University School of Medicine, NY, USA. bob@br14.med.nyu.edu Quantitative EEG (QEEG) can play an important role in the evaluation and treatment of children and adolescents with attention deficit and learning disorders. Children with learning disorders are a heterogeneous population with QEEG abnormality in 25% to 45% of reported cases. EEG slowing is the most common abnormal finding, and the nature of the QEEG abnormality may be related to future academic performance. Children with attention disorders are a more homogeneous population, with QEEG abnormalities in up to 80%. In this population, frontal/polar regions are most likely to show deviations from normal development, with the thalamocortical and/or septal-hippocampal pathways most likely to be disturbed. QEEG shows high sensitivity and specificity for distinguishing normal children and children with learning disorders and attention disorders from each other and may provide useful information for determining the likelihood that children with attention problems will respond to treatment with stimulant medication.

ALZHEIMER RESEARCH

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Alzheimer's Disease a Hormone Replacement Risk Factor Provided by Association of Operating Room Nurses. AORN Journal 5/22/2004 The US Food and Drug Administration has asked manufacturers of hormone replacement therapies to include Alzheimer's disease and other forms of dementia on the list of possible risk factors of these medications, according to a Feb 10, 2004, news release from Fisher Center for Alzheimer's Research Foundation at the Rockefeller University, New York. Hormone replacement therapies containing estrogen and progestin are used to treat symptoms of menopause, such as hot flashes and night sweats. It also was hoped that this therapy might help keep memory intact and ward off Alzheimer's disease in older women. A study found, however, that that this treatment does little to prevent Alzheimer's disease and may, in fact, increase the risk. Other possible risk factors for women taking these medications include heart disease, stroke, and breast cancer. Risk for developing a serious problem, such as Alzheimer's disease or cancer, appears to be small, however. Experts recommend that women discuss the risks with their physicians and, if they opt to take hormone replacement medications, that they take the lowest possible dose for the shortest possible time.

AMINO ACID NEWS

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Diseases of Aging Tied to Amino Acid Provided by New York Times Syndicate 5/18/2004 by Alice Dembner Eating a healthy, balanced diet supplemented by a multivitamin may help ward off many ailments of old age, according to an accumulating body of research on homocysteine, an amino acid produced by the body. Scientists have linked high levels of homocysteine to increased risk of heart disease, stroke, dementia and, just last week, to fractures due to osteoporosis. Studies show that people with the most homocysteine are about twice as likely to face these problems as those with the least. For once, there appears to be a quick fix. Eating more foods containing folic acid, and vitamins B-6 and B-12 -- such as a diet rich in animal protein, whole grains, fruits and leafy vegetables -- reduces homocysteine accumulation. Studies to test whether cutting homocysteine levels prevents disease are still underway, and it's not yet clear whether high homocysteine levels are the cause of disease or a byproduct. So, most doctors say it's not yet worth testing all patients' homocysteine levels, although those over 60 or with early signs of these diseases may want to ask their doctors about getting the blood test. Many say the early research suggests, however, that it's worth getting the antidotes -- through meals or a daily multivitamin. "Everybody should be getting the 'treatment,' because it's cheap and nontoxic and has other health benefits," said Dr. Meir J. Stampfer, professor of nutrition and epidemiology at the Harvard School of Public Health. "If it's beneficial even slightly, then it's a good bargain." Good lifestyle habits such as getting more exercise, quitting smoking and reducing alcohol intake, which are already linked to lowered risk of many diseases, also appear to help lower homocysteine levels, according to an analysis by Dr. Hus-Ko Kuo, a geriatric fellow at the Harvard Medical School Division on Aging and Hebrew Rehabilitation Center for Aged. So far, the evidence for the impact of homocysteine is strongest in heart disease. Numerous studies have found that high homocysteine levels are good predictors of future heart attacks, strokes and coronary-artery disease. Recently, the federal Centers for Disease Control and Prevention found a substantial drop in death rates from heart attack and stroke -- 48,000 fewer per year -- that coincided with the addition of folic acid to most grains and cereals in 1998. But two controlled studies in which multivitamins were added to the diet of patients with heart disease showed mixed results. Researchers reported a 38 percent reduction in the recurrence of blocked arteries in patients who had already had angioplasty and who took vitamins for a year. But they found no difference in the rate of second strokes among those who'd already had one stroke -- perhaps because the patients didn't lower their homocysteine levels early enough. On Alzheimer's, researchers following volunteers in the long-running Framingham Study found that those with the highest levels of homocysteine had twice the risk of developing the crippling brain illness. And last week, results from studies of the Framingham group and another in the Netherlands linked high homocysteine levels to a doubling or quadrupling of the risk of fractures in those with osteoporosis. "With each association of this kind, the potential benefit of homocysteine lowering becomes greater and tips the balance in terms of doing something rather than waiting," said Dr. Irwin H. Rosenberg, dean of the Friedman School of Nutrition Science and Policy at Tufts University. Scientists believe homocysteine is likely just one factor contributing to disease. There is also preliminary research suggesting that high homocysteine levels may be linked to depression, deterioration in abilities such as balance and dexterity, and diminution of mental skills separate from Alzheimer's. In the absence of any studies showing that lowering homocysteine directly prevents disease, scientists caution that is it still possible that the amino acid is just a bystander and something else is the culprit. Scientists are trying to remove the uncertainty with experiments currently underway, including giving folic acid and vitamins to people with early Alzheimer's to see if it helps slow the disease's progression. Such testing is difficult because there is no consensus on what level of homocysteine is harmful, or how early in life it should be lowered for optimal effect. There's a sort of national experiment going on, as well, since the government required food manufacturers to add folic acid, also known as folate, to wheat flour in 1998 to help prevent birth defects. The presence of that folic acid has halved the number of people with high homocysteine levels in the Framingham Study, bringing it to about 10 percent. But folic acid doesn't work alone on homocysteine, and with the current low-carbohydrate diet craze, many people may not even be getting enough folic acid in bread, pasta and other food made with flour. The body needs at least 400 micrograms of folic acid a day, as well as ample amounts of vitamins B-6 and B-12 to reduce homocysteine levels and for other bodily functions. Homocysteine doesn't have any known purpose in the body, according to Rosenberg, but it is an important intermediary in hundreds of chemical reactions. The amino acid is made by the body and then metabolized into other substances with the help of folic acid and the B vitamins. Scientists aren't sure how it might cause problems when it accumulates. But they believe that it damages blood vessels in the body and brain, which could cause heart disease as well as dementia. It may also be directly toxic to brain cells. In osteoporosis, scientists suggest it may weaken the connective tissue that forms the framework for bones. For seniors, people who already have already suffering heart disease and those with a family histories history of heart trouble, some doctors are beginning to test homocysteine levels. Rosenberg would like to see more testing for this group to guide their intake of folic acid and vitamins, since he suggests some people may require more than they can get in their diet or even with a multivitamin. The test, typically not covered by insurance, involves drawing blood and can cost from $20 to $200. There is also a small risk in increasing folic acid, since it can mask a vitamin B-12 deficiency, which can cause nerve damage. "The purists say you don't engage in treatment or public health interventions unless or until you've proven that those interventions have an impact," Rosenberg said. "The (American) Heart Association has taken that position. But we're not talking about transplants or expensive drugs. Why don't we make sure we have a lower homocysteine level, just like we say we're going to lower cholesterol."

BRAIN RESEARCH

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Unraveling The Secrets Of The Brain's Smallest Cells Source: University College London 2004-04-22 University College London scientists have made the first ever recordings of the brain's smallest cells at work sensing the outside world. Their findings could help unlock the secrets of the cerebellum, a key motor control centre in the brain which, when damaged, can lead to movement disorders such as ataxia and loss of balance. Paul Chadderton and colleagues at UCL's Wolfson Institute for Biomedical Research used a method called patch-clamping to measure the activity of a single granule cell in an intact brain. The findings are published in the latest issue of Nature. Granule cells are tiny. Their size – 20 times smaller than a human hair – has made it extremely difficult for scientists to study them in action. Granule cells make up the input layer of the cerebellum and receive sensory information from the body, for example when a finger touches a surface. The cerebellum is thought to act as a link between the body's senses and its movements, such as guiding the finger across a surface smoothly and efficiently. However, scientists still know very little about how the cerebellum does its job. The group's findings could ultimately help researchers understand more about movement disorders and potentially help in the development of drug treatments targeting the cerebellum, for example for sufferers of ataxia, a movement coordination problem which affects 150,000 people in the US, and dysmetria, where patients have difficulty regulating the rate, range and force of movement. The group also found that the activity of granule cells is kept in check by a 'tonic inhibition' mechanism. There is growing evidence that alcohol can boost this inhibition and thus affect cerebellar function, possibly accounting for the drunken swaying and unsteadiness often associated with inebriation. By applying the patch-clamp technique, where a cell membrane is gently sucked onto a glass pipette which records small electrical signals coming from the cell, UCL researchers were able to see the granule cell layer at work, confirming predictions made over 30 years ago by the celebrated English theoretical neuroscientist David Marr. Marr suggested that the layer uses a sparse coding scheme to represent sensory input, where the firing rate of the cells is low in order to maximize the number of different patterns of sensory input that can be represented by the cerebellum. In other words, the cells keep their activity low to ensure that they remain sensitive to every type of sensation that is being picked up. Paul Chadderton says: "We're delighted to provide the first evidence of a theory born thirty years ago, namely that activity in cerebellar granule cells is dampened to maximise the brain's capacity to represent many different sensations." "Neuroscience can now move forward with this technique, not only to better understand the brain, but ultimately to help those suffering from movement disorders. The more we understand about cell signalling, the better we can become at targeting drugs in complex parts of the brain." Paul Chadderton is a PhD student on a UCL Graduate Research Scholarship at UCL's Wolfson Institute for Biomedical Research. Event-related functional magnetic resonance imaging of reward-related brain circuitry in children and adolescents. Biol Psychiatry. 2004 Feb 15;55(4):359-66. May JC, Delgado MR, Dahl RE, Stenger VA, Ryan ND, Fiez JA, Carter CS. Department of Psychology, New York University, New York, NY, USA. BACKGROUND: Functional disturbances in reward-related brain systems are thought to play a role in the development of mood, impulse, and substance-abuse disorders. Studies in nonhuman primates have identified brain regions, including the dorsal/ventral striatum and orbital-frontal cortex, in which neural activity is modulated by reward. Recent studies in adults have concurred with these findings by observing reward-contingent blood oxygen level-dependent (BOLD) responses in these regions during functional magnetic resonance imaging (fMRI) paradigms; however, no previous studies indicate whether comparable modulations of neural activity exist in the brain reward systems of children and adolescents. METHODS: We used event-related fMRI and a behavioral paradigm modeled on previous work in adults to study brain responses to monetary gains and losses in psychiatrically healthy children and adolescents as part of a program examining the neural substrates of anxiety and depression in youth. RESULTS: Regions and time-courses of reward-related activity were similar to those observed in adults with condition-dependent BOLD changes in the ventral striatum and lateral and medial orbital-frontal cortex; specifically, these regions showed larger responses to positive than to negative feedback. CONCLUSIONS: These results provide further evidence for the value of event-related fMRI in examining reward systems of the brain, demonstrate the feasibility of this approach in children and adolescents, and establish a baseline from which to understand the pathophysiology of reward-related psychiatric disorders in youth. Fitness : Take Your Brain Out for a Walk Provided by Post-Tribune on 5/4/2004 by Kass Stone, Post-Tribune correspondent While the physiological benefits of going for a brisk hike have long been known, new research indicates exercise may be as good for your head as your heart. There's little doubt that walking is good for your health. According to the American Podiatric Medical Association, a brisk walk can burn up to 300 calories an hour and get the heart pumping. John Bobalik, coordinator of Purdue University Calumet's Fitness Center, knows a lot about the physical benefits of walking. "It helps you burn fat. It helps you build up your stamina. It's great as a stress release, whatever kind of stress you're under," he said. "It helps you regulate your blood sugar, which reduces the chances of you becoming a diabetic." But the seemingly easy task of putting one foot in front of another works for the brain as well. A recent study conducted by the University of Illinois and published in the March 2004 issue of the Proceedings of the National Academy of Sciences showed that walking, and other aerobic exercises improve the brain's ability to focus on a specific task and its mental ability to concentrate. This happens because aerobic activity allows more blood flow to the brain. The study showed that the increased blood flow affects the brain's middle front gyrus, which is responsible for focusing on specific goals, and the superior parietal area, which is responsible for concentrating of spatial attention. But walking also helps the brain in ways not related to aerobic activity. "It's a good diversion," Bobalik said. "Another benefit is that, for some people, you can go out and put the world on hold for awhile. You don't have to answer any questions, worry about a deadline. You get to think about what you want to think of. It's probably the one time of the day when your time is yours to focus on whatever you want to." Bobalik recommends beginning a regular walking regimen, accompanied at some point by a strengthening program, for anyone who has not exercised in a long time but wishes to get back into shape. "It's one of the safest exercises you can do," Bobalik said. "If you're not exercising at all, there is one thing everyone can do -- walk." And easing into exercise through walking is the right thing to do, Bobalik said. "Running, if you've been away from it for years, it's just too big of a risk for you," he said. "If your muscles and tendons and ligaments are not used to it you can hurt yourself." Living proof of the benefits of a regular walking regimen is Charlotte Routh. Routh, the secretary for PUC's dean of engineering, math and science, was dangerously obese. She weighed over 300 pounds, had developed diabetes and was taking three different kinds of medication for health problems generated by her obesity. Two years ago, Routh, 59 at the time, was confronted with the reality that her life could be cut short due to her size, and whatever remained of her life would be filled with health complications. "I was on two diabetic medications and a cholesterol medication and my blood sugar was going higher because I wasn't taking care of myself. My doctor got really frustrated with me and said 'If you don't want to get on insulin you've got to do something,' " Routh said. Following that advice from her doctor, Routh began to go on walks in her hometown of Highland. At first it was difficult, and she admitted being hesitant about exercising, but soon it became easier for Routh to go longer distances. Soon she walking 40 minutes a day every day of the week. By following this routine, and watching her food intake, she has lost 100 pounds in the past two years. As a result of her weight loss, Routh's diabetes has stabilized, her cholesterol is under control and she is off all medications. "I feel a lot better. I've got more energy and it's easier to move," Routh said. "I just got up one day and started walking. I figured I have to live it, so I'm going to do something I want to do, so I just started walking." (C) 2004 Post-Tribune. via ProQuest Information and Learning Company; All Rights Reserved

CHRONIC FATIGUE

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Neuropsychological deficits in patients with chronic fatigue syndrome. J Int Neuropsychol Soc. 2004 Feb;:278-285 Busichio K, Tiersky LA, Deluca J, Natelson BH. Chronic Fatigue Syndrome Center, Newark, New Jersey. The degree of neuropsychological dysfunction across multiple domains was examined in individuals suffering from chronic fatigue syndrome (CFS). In this descriptive study, a similar series of neuropsychological tests was administered to a group of CFS patients and healthy participants. More specifically, CFS patients (n = 141) who met the 1994 Case Definition criteria were compared to 76 healthy control participants on tests of memory, attention (concentration), speed of information processing, motor speed, and executive functioning. On the 18 measures administered, CFS patients scored 1 standard deviation below the healthy mean on nine measures and scored 2 standard deviations below the healthy mean on four of the measures. Moreover, results indicated that CFS patients were more likely than healthy controls to fail (1.6 SD below the healthy mean) at least one test in each of the following domains: attention, speed of information processing, and motor speed, but not on measures of memory and executive functioning. Finally, CFS patients demonstrated a greater total number of tests failed across domains. The effects of nutritional supplements on the symptoms of fibromyalgia and chronic fatigue syndrome. Integr Physiol Behav Sci. Dykman KD, Tone C, Ford C, Dykman RA. Mannatech Inc., Coppell Texas 75019, USA. This article reports the results of a within-subject design. Fifty subjects with a physician diagnosis of fibromyalgia (FM) and/or chronic fatigue syndrome (CFS) were interviewed using a structured interview from. Each subject was interviewed initially, and again nine months later (follow-up). Subjects had, on their own, consumed nutritional supplements including freeze-dried aloe vera gel extract; a combination of freeze-dried aloe vera gel extract and additional plant-derived saccharides; freeze-dried fruits and vegetables in combination with the saccharides; and a formulation of dioscorea complex containing the saccharides and a vitamin/mineral complex. With medical treatments, approximately 25 percent of FM patients improve, but the beneficial effects of medical treatment rarely persist more than a few months. All subjects in this study had received some form of medical treatment prior to taking the nutritional supplements, but none with enduring success. Nutritional supplements resulted in a remarkable reduction in initial symptom severity, with continued improvement in the period between initial assessment and the follow-up. Further research is needed to verify these results, specifically crossover designs in well-defined populations.

DYSLEXIA

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Physiological and anatomical evidence for a magnocellular defect in developmental dyslexia. Livingstone MS, Rosen GD, Drislane FW, Galaburda AM. Department of Neurobiology, Harvard Medical School, Boston, MA 02115. Several behavioral studies have shown that developmental dyslexics do poorly in tests requiring rapid visual processing. In primates fast, low-contrast visual information is carried by the magnocellular subdivision of the visual pathway, and slow, high-contrast information is carried by the parvocellular division. In this study, we found that dyslexic subjects showed diminished visually evoked potentials to rapid, low-contrast stimuli but normal responses to slow or high-contrast stimuli. The abnormalities in the dyslexic subjects' evoked potentials were consistent with a defect in the magnocellular pathway at the level of visual area 1 or earlier. We then compared the lateral geniculate nuclei from five dyslexic brains to five control brains and found abnormalities in the magnocellular, but not the parvocellular, layers. Studies using auditory and somatosensory tests have shown that dyslexics do poorly in these modalities only when the tests require rapid discriminations. We therefore hypothesize that many cortical systems are similarly divided into a fast and a slow subdivision and that dyslexia specifically affects the fast subdivisions.

CHINESE MEDICINE

Acupuncture Used As Infertility Therapy Provided by The Seattle Times on 4/30/2004 by Julia Sommerfeld Sara Cook, a stylish brunette with a Snow White complexion, lies face down as hair-thin needles are gently slipped into her ankles, the backs of her knees, her lower back and ears. A dull, warming sensation creeps over her as the small examination room with its sweet menthol smell fades away, as do worries about ovulation schedules, hormone shots and what's next after four failed attempts at in-vitro fertilization. Since October, Cook, 34, has been needled once a week by Seattle acupuncturist Stephanie Gianarelli in hopes of improving her chances of getting pregnant. Used for 2,500 years in traditional Chinese medicine and best known in Western circles as a New Age pain zapper, acupuncture has gained a following among women - and couples - as an infertility therapy. Some, like Cook, have left no stone unturned, combining the ancient remedy with the best that modern medicine has to offer, including fertility drugs and test-tube technology. Others eschew the expensive and emotionally draining tactics of fertility clinics and place their hopes on the head of a pin. "Western medicine uses the sledgehammer approach to infertility," says Gianarelli, who specializes in the problem. "But acupuncture coaxes the entire body into balance and better health so it's ready to conceive." Even mainstream physicians are hard-pressed to completely dismiss acupuncture, at least when used in conjunction with their high-tech methods. In fact, many of the women who slip away from their downtown offices for half-hour sessions with Gianarelli each week were referred by their infertility doctors. That's because two years ago a German study found acupuncture boosts the success rate of in-vitro fertilization (IVF), where egg and sperm meet in a laboratory dish and resulting embryos are transplanted to the womb. The study of 160 IVF patients found that women who had acupuncture right before and after the embryo transfer increased their chances of pregnancy from 26 percent to 43 percent. "It's only one study," Dr. Lori Marshall, an infertility doctor at Seattle's Virginia Mason Medical Center, cautions her patients. "But it's enough to say, 'Hey, there could be something there.' " It's also enough to persuade 20 to 30 percent of her clinic's IVF patients to go under the needle. Because acupuncture isn't likely to do any harm and, at about $60 to $100 a visit, is relatively inexpensive compared with mainstream fertility help, many women are willing to take their chances. Plus, because of a Washington state law, insurers must pay for acupuncture treatment for problems that they cover. "It used to be people just came as a last resort, after they've failed everything else. Now we're more often seeing women trying this before they go down those other roads," says Greg Bantick, academic dean at Seattle Institute of Oriental Medicine. With more patients asking if they should get needled, Dr. LaTasha Craig at the University of Washington Fertility and Endocrine Center wants to be able to provide a more definitive answer. So she's about to put the German findings to the test. Starting this summer, she plans to enroll 200 women in a trial comparing IVF plus acupuncture to IVF alone. She anticipates her biggest challenge will be recruiting enough women to agree they won't get acupuncture. After eight years of trying to get pregnant and three failed rounds of IVF, lingerie merchandiser Sara Cook and her husband, Jason, a firefighter, were willing to try anything. "I wanted to know I did everything I possibly could to make this work," she says. Although their insurance covers most of the costs of IVF, they've spent about $15,000 out of pocket. In October, to prepare for her fourth and final attempt at an embryo transfer, Cook began seeing Gianarelli once a week, with the blessing of her physician. "These patients are going down a pretty rough road. Anything that makes them feel better, I'm for," says Dr. Lee Hickok, her IVF doctor at Swedish Medical Center. Although the embryos implanted in January didn't result in pregnancy, Cook hasn't given up on acupuncture. She's considering having a surrogate carry her embryo, so she and her husband come in for weekly acupuncture sessions aimed at fortifying her eggs and his sperm. Acupuncture can do more than bolster IVF's success rate, says acupuncturist Kerong Xie, who works out of a converted house in Seattle's University District. Along with Chinese herbs, it can cure most cases of infertility, she says matter-of-factly. Needless to say, this is where acupuncturists and mainstream doctors part company. Rifling through a stack of Christmas-card photos and birth announcements from grateful patients, Xie tallies her recent successes. She estimates about 17 or 18 pregnancies since October. In traditional Chinese medicine, conditions such as infertility are fundamentally seen as blockages or imbalances in the body's "qi" (pronounced chee), a vital force or energy that flows throughout the body along channels called meridians. Xie diagnoses a patient by examining her tongue, asking a list of personal questions and taking several pulses. She then strategically sticks needles so tiny they hardly can be felt into points of the body that she says act as valves to manipulate qi, disperse it when it's blocked, stimulate it when it's stagnating and, in general, get the body's qi humming along. Treating infertility is a standard part of acupuncture training, says Steve Given, who heads the acupuncture clinic at Bastyr Center for Natural Health in Seattle. "Oriental medicine excels at identifying individual patterns of disharmony. If you lined up 100 different women with infertility, an acupuncturist could have a slightly different treatment for each of them." What's seen in Western medicine as a blocked fallopian tube is blocked or stagnating qi to Xie. "I prepare the body for pregnancy - how do you plant seeds when the dirt is very thin?" she asks. Many doctors don't know what to make of such mystical adages. "There's just no Western medical equivalent to this stuff," Hickok says. He'll grant that acupuncture may promote relaxation and reduce stress levels. At best, he could see this slightly improving a woman's chances of conceiving and, at the least, it can help patients feel better and more in control. Other doctors speculate acupuncture could increase blood flow to the uterus or boost production of endorphins, the body's feel-good chemicals that impact certain hormones. There's no scientific evidence that needling alone improves pregnancy rates, so most doctors discourage women who are having trouble getting pregnant from relying solely on acupuncture. "I would hate to see women who are 35 and up get hung up in alternative therapy that may not be all they need," says Dr. Kevin Johnson, an infertility doctor at Overlake Hospital Medical Center in Bellevue, Wash. He worries that women who could be helped with more-aggressive therapies could be squandering their final fertile years. He urges a fertility checkup before pursuing acupuncture. "A totally blocked fallopian tube won't be helped by acupuncture, nor will bad eggs," he says. And no amount of tinkering with a woman's qi is going to help if the problem is actually her partner's low sperm count. The other sticking point for Western doctors is the cornucopia of herbs that acupuncturists often prescribe to be boiled up in a pungent tea. "That's where I draw the line," Hickok says. "I tell my patients, don't take the herbs; I don't know what they do or how they'll interact with IVF drugs, and they haven't been tested for safety or purity. With acupuncture, I don't think there's a potential for harm, but there could be with the herbs." At 40, wedding photographer Janet Klinger had been trying to get pregnant for almost two years. She and her husband knew that IVF wasn't for them. "I didn't really want to go through that emotional roller coaster with the possibility of spending 20 grand and not succeeding," she says. After hearing about Xie from a pregnant client, she began visiting her twice a month. For three months, she would lie quietly, with needles scattered up her torso, along her "conception channel," and think "baby thoughts." She's now 28 weeks pregnant. "Whether it's for scientific reasons or just because I felt so relaxed and cared for, I don't know, but I totally believe she helped me get pregnant," Klinger says. Anecdotes like Klinger's don't make for strong medical evidence. Doctors are quick to point out there's no way of knowing whether she would have gotten pregnant anyway. But such accounts do make the rounds in infertility circles and among women friends. That's why, despite not advertising, Xie's nondescript clinic draws a steady stream of well-heeled women, some IVF patients, some looking for an outright miracle. ACUPUNCTURE POINTS If you are considering going under the needle, experts offer these tips: -Only visit acupuncturists licensed by the state. Look for the letters L.Ac. after their names. To verify that an acupuncturist's license is in good standing, plug the name into the state's health-provider-credential search engine at https://fortress.wa.gov/doh/hpqa1/Application/Credential-Search/profile.asp -Make sure your acupuncturist uses only single-use, sterile needles. -Visit a reproductive specialist for a conventional diagnosis first. "You'll want to rule out frank structural problems, like a scarred fallopian tube or tipped uterus," says Bastyr University's Steve Given. -If you are already seeing a fertility doctor, discuss your plans. Don't take any herbs without your physician's approval - they could interfere with fertility drugs.

QEEG/EEG/ERP

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THE SCIENTIFIC BASIS OF qEEG TESTING: The 1970's and 80's were decades of exploration and experimentation with qEEG. The American Medical EEG Association (AMEEGA) Adhoc Committee on qEEG has stated "qEEG is of clinical value now and developments suggest it will be of even greater use in the future". QEEG has well documented ability to aid in the diagnosis of mild traumatic brain injury, ADHD, learning disabilities, stroke, and epilepsy. AMEEGA emphasizes the importance of rigorous training and certification. AMEEGA's emphasis is on physician usage of qEEG. The American Psychological Association has endorsed qEEG and neurotherapy as within the venue of psychologists with appropriate training. Two national organizations, the National Registry of Neurofeedback Providers (NRNP) and the Academy of Certified Neurotherapists (ACN) were formed in 1992 for the certification of clinicians in the clinical application of qEEG and its related technology, neurofeedback. The NRNP has been disbanded at this point; many of us felt only one certification agency is necessary. The ACN has been subsumed into the larger Biofeedback Certification Institute of America (BCIA), established over 25 years ago to certify practitioners in peripheral (EMG, temperature, GSR) biofeedback techniques. John K. Nash, Ph.D., served on the Executive Council of the NRNP and was one of its founding members. Dr. Nash was one of fifteen scientists and clinicians on the NRNP Executive Council defining and promoting rigorous certification standards for clinicians who wished to utilize this powerful, but technically demanding procedure. He is also certified by the ACN and is certified as an advanced neurotherapy instructor by the major equipment manufacturer, Lexicor Medical Technology. He is now BCIA certified in EEG. Dr. Nash has conducted EEG research beginning in 1974. His expertise has been utilized by NASA in the peer review of research grants on human psychophysiology and space medicine. Operant conditioning of EEG characteristics is well documented in the scientific literature. Training to decrease slow activity and increase fast desynchronized EEG activity has been used for over 20 years to ameliorate ADHD and epilepsy. More recently EEG operant conditioning has been successfully applied to patients with mild traumatic brain injury. Reports of literally hundreds of case studies have been presented at conferences of the National Head Injury Society as long ago as 1987. Behavioral Medicine Associates, Inc. has many very satisfied patients who can testify that neurotherapy has reduced their brain injury symptoms. Memory has been improved, emotional instability has been decreased or eliminated, and executive function has been improved. These patients are very grateful to have been able to return to much more normal functioning, even years after no further recovery of function would be predicted by traditional neuropsychologists or neurologists. Patients report "I can remember numbers again." "I can see many sides of a situation now, so I don't fly off the handle anymore." "I am astonished at the change I've felt in the last two weeks, after two and a half years of living in a personal hell." A college student who dropped out with failing grades is now reporting "A" papers and average to above average grades. IF QEEG AND NEUROTHERAPY ARE SO GOOD, WHY AREN'T MORE CLINICIANS USING IT? An estimated 1000 clinicians are using neurotherapy in the U.S. Most psychologists and physicians simply have not been educated in the clinical applications of EEG biofeedback and have not read the existing research and clinical literature, in spite of the fact that applications to anxiety, epilepsy and attentional deficits date back to the 1970's. There also is simply a lack of "big money" behind this technology. Your physician gets free samples and color ads in his or her professional journals for the latest medicines. Continuing education for physicians and psychiatrists is strongly funded by drug companies. You get finely crafted TV commercials. There is currently no mechanism through which biofeedback technology promotes the accumulation of great wealth, which can then be used for lobbying, marketing and physician education. The instrumentation is expensive and requires serious study and training to use competently. Proper instrumentation has only recently become generally available. The International Society for Neuronal Regulation (iSNR) exists to promote such education. Attendance at national conferences has grown from 60 ten years ago to over five hundred this year. More clinicians are using neurotherapy each year. Certification in neurotherapy is advancing and, we believe, necessary so that insurers can choose to reimburse only certified clinicians. A Registry of neurologists, neuropsychologists, clinical psychologists, physicians, neuropsychiatrists and psychiatrists who are certified to do this work is published annually by the National Registry of Neurofeedback Providers and by the Academy of Certified Neurotherapists, recently joined with the Biofeedback Certification Institute of America. Together these organizations have approximately 600 certificants. QEEG is not intended to be a "stand alone" diagnostic or as a substitute for other medical diagnostics. It is, however, a helpful adjunct which can guide prognosis and intervention. QEEG is best used as an tool to aid in the clinical diagnosis of various dysfunctional states and not as a substitute for clinical judgment and medical opinion. The QEEG should be combined with other medical, psychological and neuropsychological data to best aid the patient. The sister technology to qEEG is called EEG biofeedback, neurofeedback or neurotherapy. The qEEG provides the "targeting" information. That is, it tells us where and under what conditions (reading, listening, math, etc.) the problem is worst. This analysis allows accurate electrode placement for feedback and suggests the tasks that should be used during therapy. Neurotherapy is EEG feedback-assisted cognitive behavior modification. It couples EEG feedback with the full range of traditional cognitive behavior therapy methods, including imaginal rehearsal, correction of maladaptive thought patterns, and rehearsal of new skills. We commonly utilize intensely activating, challenging tasks during the sessions to enhance brain activation and teach what it feels like to be focused and functional again. The EEG feedback signals the patient when their brain is in fact in a more activated state, indexed by decreased delta and theta brain wave amplitudes, and increased beta and/or alpha amplitudes. Neurotherapy is no panacea. Like any therapy, it works best with the smartest, least brain damaged patients. Patients with profound memory loss which prevents the acquisition of new learning at all are not likely to be helped. On the other hand, patients with emotional dyscontrol, impaired memory and concentration, and a good pre-morbid level of functioning are responding very, very well to the treatment. Most interestingly, good results are being achieved in patients who are 2, 3 or even 5 years post injury; these are times at which improvement cannot be attributed to "spontaneous recovery."

HEAD INJURY

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Glial and neuronal proteins in serum predict outcome after severe traumatic brain injury 2004 American Academy of Neurology P. E. Vos, MD PhD, K. J.B. Lamers, PhD, J. C.M. Hendriks, PhD, M. van Haaren, MD, T. Beems, MD, C. Zimmerman, MD, W. van Geel, H. de Reus, J. Biert, MD PhD and M. M. Verbeek, MSc PhD From the Departments of Neurology (Drs. Vos, Lamers, van Haaren, and Verbeek), Epidemiology and Biostatistics (Dr. Hendriks), Neurosurgery (Dr. Beems), Intensive Care (Dr. Zimmerman), Laboratory of Pediatrics and Neurology (W. van Geel, H. de Reus, and Dr. Verbeek) and Surgery (Dr. Biert), University Medical Centre Nijmegen, The Netherlands. Objective: To study the ability of glial (glial fibrillary acidic protein [GFAP] and S100b) and neuronal (neuron specific enolase [NSE]) protein levels in peripheral blood to predict outcome after severe traumatic brain injury. Methods: Eighty-five patients with severe traumatic brain injury (admission Glasgow Coma Score [GCS] 8) were included. Blood samples taken at the time of hospital admission were analyzed for S100b, GFAP, and NSE. Data collected included demographic and clinical variables. Outcome was assessed using the Glasgow Outcome Scale (GOS) at 6 months post injury. Results: The median serum levels of S100b, GFAP, and NSE were raised 18.3 fold (S100b), 4.6 fold (GFAP), and twofold (NSE) compared to normal reference values. S100b, GFAP, and NSE serum levels correlated significantly with the injury severity score and CT findings but not with age, sex, or GCS. S100b, GFAP, and NSE levels were significantly higher in patients who died or had a poor outcome 6 months post injury than in those who were alive or had good outcome. S100b level >1.13 µg/L was the strongest predictor of death with 100% discrimination, but GFAP (>1.5 µg/L) and NSE (>21.7 µg/L) levels also strongly predicted death (adjusted odds ratios 5.82 [for GFAP] and 3.91 [for NSE]). S100b, GFAP, and NSE all strongly predicted poor outcome (adjusted odds ratios 5.12 [S100b], 8.82 [GFAP], and 3.95 [NSE]). Conclusions: These results suggest that determination of serum levels of glial and neuronal proteins may add to the clinical assessment of the primary damage and prediction of outcome after severe traumatic brain injury. New Research Reveals Head Injury in Children has Lasting Impact New research from the University of Warwick reveals that children with even mild head injury may be at risk of long-term complications, including personality changes, emotional, behavioural and learning problems. The study published in the Journal of Neurology, Neurosurgery, and Psychiatry examined more than 500 children aged 5-15 years at head injury over a 6-year period. Parents were asked to register what changes they noticed in their child after the head injury, and what follow-up they had received from clinicians. Even after a mild head injury, one in five children had a change in personality according to their parents. Parents often described the personality change after the head injury as "like having a different child". Further, 43 percent of children with mild head injury had behavioural or learning problems that led to them being described as having a "moderate disability". Overall around 30 percent of parents believed that their child's personality had changed as a result of the initial damage. Among children with more serious head injuries, about two thirds had moderate disability, and about half experienced a major change in personality after the head injury. Dr Carol Hawley, from Warwick Business School at the University of Warwick, said: "Many children with mild injury do not receive routine follow-up after discharge home from hospital, yet a significant proportion of them do have some lasting problems which may affect their behaviour and ability to learn. This could put them at a disadvantage at school." While all of the children in the study had been treated in a hospital after having a head injury, only 30 percent of parents said that doctors at the hospital had made a follow-up appointment for their child. In fact, 161 of the 252 children with moderate disability did not receive any follow-up care. The study also suggests that there are there is inadequate provision for children with head injury, largely due to inadequate information. Teachers of only 40% of children were aware of the injury, and given the enduring nature of cognitive and behavioural problems following moderate or severe head injury, this is of concern. Dr Carol Hawley continued: "It is likely that there are considerable numbers of children in the community, and back at school, who have suffered a head injury in the past and who might have subtle but important difficulties relating to that head injury." To help identify children suffering from the lingering effects of a head injury, a research team is now working on a questionnaire that physicians could send to parents after children with head injury are sent home from the hospital. Children found to be at risk of problems could be offered a follow-up assessment. If necessary, children could be referred to an appropriate health professional, such as an educational psychologist or community paediatrician. That whack on the head could be more serious than you think By Dr. Catherine O'Connor / News Correspondent T uesday, May 18, 2004 A million and half people get one every year, some 300,000 of those from sports and recreational activities, according to the Centers for Disease Control in Washington, D.C. "It" is a concussion. But it's much more than just "having your bell rung." It's a brain injury, and it's serious. Like many injuries, a concussion -- officially, traumatic brain injury (TBI) -- comes in varying severities. Being knocked unconscious, of course, is the most severe and requires immediate medical attention. But a concussion can also cause dazed, foggy behavior with the patient still conscious. For children, adolescents and young adults who play sports, it's important for those on the sidelines -- parents, coaches, teachers, school officials and nurses -- to be extra vigilant in recognizing the injury and taking proper action when someone gets hit. Concussion is an elusive medical condition, difficult to identify, evaluate and treat. How hard was the head hit? Is the patient confused, dazed, unsteady, having vision problems or headaches or feeling unusually tired? Further, symptoms may be immediate or delayed, making recognition even harder for the health care provider and athlete. And many people never check with a doctor, often waiving it off as a "bump on the head" and simply taking a few aspirins. But the consequences of such an injury can be severe and lifelong, affecting concentration, memory, judgment, mood, strength, reaction time, coordination, balance, emotion and sensations like touch and vision. So that whack on the head is nothing to take lightly. Those suffering concussions must tell the doctor exactly what symptoms they experienced at the time of their injury and since their injury. Regardless of age, no one should return to any physical activity until cleared by a doctor. Note, too, a difference exists in recovery time between adults and youngsters. Just because the pro quarterback returns to action quickly (a dubious decision in most cases, to be sure) doesn't mean the young athlete can or should. The Massachusetts Medical Society offers a free, downloadable brochure, "Concussion: A Coaches Guide for Sideline Evaluation," that explains the symptoms of concussion and includes tests for assessing the condition and recommendations for basic treatment at the time of injury. Visit http://www.massmed.org/pages/concussion_brochure.asp. But it's more than just athletes who are at risk. CDC research indicates that males are twice as likely as females to sustain a concussion, and that people 15 to 24 and over age 75 are the two groups at highest risk. Any one of us, at any age, can get that unexpected hit on the head. The Brain Injury Association of America reports that some 5.3 million people live with disabilities from concussions. And among children up to 14, TBI results in an estimated 400,000 emergency room visits each year. Most of us are unwittingly in harm's way. Consider that the leading causes of concussion are motor vehicle and bicycle accidents, sports and recreational activities and falls and you quickly see that the potential for head injury is not just on the playing fields, but can occur during activities of daily life. The good news is that we can take some common sense, preventive steps to reduce the odds of injury. Here's what you can do: * In an automobile, always wear a seat belt, secure children in vehicles properly, put children under 12 securely in the back seat and don't drive or ride with someone who's drug- or alcohol-impaired. On motorcycles and bicycles, every one should wear helmets. * For sports and recreation, wear helmets in good condition for contact and collision games and for activities like skateboarding and inline skating. Wear shoes with good soles to reduce the likelihood of slips and falls. * At the playgrounds, check the quality of the equipment. Surfaces underneath should contain shock-absorbing materials. * In the home, use non-slip mats and grab bars in the bathrooms, remove tripping hazards, install safety gates and window guards for young children. We can't eliminate all the risks from life, but we can take precautions. And when someone does get whacked on the head, it should be a clarion call for quick, appropriate medical attention. Catherine O'Connor, M.D., is chairwoman of the Massachusetts Medical Society's Committee on Student Health and Sports Medicine, a general surgeon in private practice in Westfield and Northampton and team physician at Amherst College. Readers should use their own personal judgment when deciding to seek medical care and should consult with their own personal physician for treatment. MMS Physician Focus is provided as a public service by the Massachusetts Medical Society First Evidence That Brain Damage at Birth Can Be Reversed University College London More than 1000 children die or suffer permanent brain injury every year in the UK because of shortage of oxygen around the time of birth. Tragedy can strike without warning, and often following normal healthy pregnancies. If the baby survives major problems include severe cerebral palsy, learning difficulties and epilepsy. The problem has been known about for many years but until now no treatment has been found which can prevent or minimise the damage and the long-term consequences. A group of doctors and scientists at University College London and University College London Hospitals NHS Trust, using state of the art brain scanning techniques, has discovered that the brain damage doesn't occur immediately at the time of delivery. There is often a window of several hours before the injury becomes permanent; in other words there is a brief window of time when protective treatment might be effective. With support from medical charities SPARKS and Action Medical Research, studies at UCL, Bristol and other research centres around the world have shown that cooling the newborn brain by several degrees is highly effective in protecting brain cells. A Coolcap device for head cooling after birth has been designed and tested by a research team including Professor Wyatt at UCLH NHS Trust, Professor Gluckman from New Zealand, and Olympic Medical, a Seattle based medical technology company. Using a computerised controller, cold water is circulated through the cap, reducing brain temperature by several degrees. At the same time heating is applied to the body to prevent the central body temperature falling too low. Cooling is maintained for 72 hours and intensive care is maintained throughout the treatment. Professor John Wyatt said today that the international trial results should give hope for the parents of new-borns who might suffer a lack of oxygen at birth. "About one in every 1,000 newborn babies are at risk of death or brain damage from oxygen-deprivation during the birth process. The rate is much higher in countries with limited resources. Those who survive can be left with heartbreaking conditions such as cerebral palsy or severe intellectual impairment." The randomised study, conducted in 24 centres and involving 234 newborns, shows that the CoolCap can reduce the rate of death or severe disability. The key findings are: 18 months after birth, there was a significant reduction in severe disabilities among those treated with the CoolCap. Brain wave analysis used at birth enabled the researchers to identify those babies who had the best chance of responding to treatment. In this group, the number who died was reduced from 39% to 25% and the incidence of movement problems among those who survived was reduced by 60%. In the most severely affected babies, treatment with the CoolCap showed no benefit. Professor Wyatt said: "Further development is required before this treatment can be made generally available in major hospitals. It is vital that further trials of cooling treatment are completed to find the optimum way of providing cooling after birth." John Shanley, chief executive of SPARKS, commented: "We are delighted the groundbreaking research SPARKS has funded with UCLH and at Bristol has produced such positive results. "Our congratulations to all the research teams and Professor John Wyatt. "This is a major step forward and SPARKS is committed to continuing to raise funds to take this vital research on to the next stages and establish Europe's first baby brain protection and repair unit". Males and Females Respond Differently to Brain Injury Researchers at Children’s Hospital of Pittsburgh have found that males and females respond differently to brain injury and therefore, boys with brain injuries may require different life-saving treatments than girls. Children’s researchers found in animal models that levels of glutathione – a molecule that protects brain cells from death when deprived of oxygen – remain constant in females who have suffered an injury to the brain but drop by as much as 80 percent in males with the same injury. When glutathione levels drop, brain cells die much more quickly. Results of the study are being presented at the annual Pediatric Academic Societies meeting, held May 1-4, 2004, in San Francisco. This is the second year of five-year, $1.2 million study which is being funded by the National Institutes of Health and Children’s Hospital. “There is a built-in difference at the brain cell level between males and females, said Robert Clark, MD, an intensivist at Children’s Hospital and the principal investigator of the study. “Injured brain cells may eventually die, but they take different pathways to get there in males and females. This means that we may need to develop or use gender-specific therapies for brain injury from any cause.” The study results also suggest the possibility that boys with injuries could be treated with N-acetylcysteine (NAC), a drug already approved for use by the U.S. Food and Drug Administration, according to Dr. Clark. “NAC already is being used to treat people who have overdosed on acetaminophen because acetaminophen causes glutathione levels to drop and NAC can restore them,” Dr. Clark said. “Now that we’ve identified low glutathione levels in males with brain injuries, we can begin looking at NAC as a live-saving treatment for those injuries.” Dr. Clark said NAC potentially could be an effective treatment for any injury in a male in which the brain is deprived of oxygen, including cardiac arrest, drowning accidents and severe trauma. Children’s researchers including Dr. Clark, Hülya Bay&Mac249;r, MD, and Ericka Fink, MD, will conduct further studies to evaluate the effectiveness of NAC in reducing brain damage after an injury.

MEMORY

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RECOGNITION MEMORY: WHAT ARE THE ROLES OF THE PERIRHINAL CORTEX AND HIPPOCAMPUS? Nature Reviews Neuroscience 2, 51 -61 (2001); doi:10.1038/35049064 Malcolm W. Brown & John P. Aggleton about the authors Preface The hallmark of medial temporal lobe amnesia is a loss of episodic memory such that patients fail to remember new events that are set in an autobiographical context (an episode). A further symptom is a loss of recognition memory. The relationship between these two features has recently become contentious. Here, we focus on the central issue in this dispute — the relative contributions of the hippocampus and the perirhinal cortex to recognition memory. A resolution is vital not only for uncovering the neural substrates of these key aspects of memory, but also for understanding the processes disrupted in medial temporal lobe amnesia and the validity of animal models of this syndrome. Summary The potential roles of the hippocampus and perirhinal cortex in recognition memory (judgement of prior occurrence) are reviewed in relation to whether the evidence for a dual-process model of recognition memory is sufficient to reject the alternative, unitary model. Recent results from animal recording, immunohistochemical imaging and ablation studies are summarized in relation to this issue, and then considered in relation to findings from human studies. Most results from animal studies favour the view that recognition memory might be subdivided functionally and neuroanatomically within the temporal lobe into two main components: (1) One component is a familiarity and recency discrimination system centred on perirhinal cortex. This perirhinal system rapidly processes information about the novelty or prior occurrence of individual stimulus items. (2) The second component is a recollective system centred on the hippocampus. This hippocampal system is slower, associational and processes information concerning the prior occurrence of individual stimuli or collections of stimuli in relation to other stimuli, including, more generally, information about the prior occurrence of episodes or events. The implications of such a proposed division in humans are that selective hippocampal damage should impair episodic memory, including recollective and associative aspects of recognition memory, while sparing aspects of recognition memory based on familiarity discrimination of individual items. By contrast, selective lesions of the perirhinal and adjacent cortices should impair familiarity discrimination for individual items, but may leave recollective aspects of recognition memory relatively unimpaired. A review of human imaging and event-related potential (ERP) data indicates potential consistency with such a division, although not all studies support a qualitative as opposed to quantitative distinction. Moreover, this division remains to be clearly established in clinical lesion studies. Critical studies into the neural basis of human and animal amnesia need to be designed and interpreted in the light of the different systems that might be employed to solve recognition memory tasks. Selective neural representation of objects relevant for navigation Nature Neuroscience 7, 673 - 677 (2004) 16 May 2004 | doi:10.1038/nn1257 Gabriele Janzen1, 2 & Miranda van Turennout2 1 Max Planck Institute for Psycholinguistics, Postbus 310, 6500 AH Nijmegen, The Netherlands. 2 F.C. Donders Centre for Cognitive Neuroimaging, Box 9101, 6500 HB Nijmegen, The Netherlands. As people find their way through their environment, objects at navigationally relevant locations can serve as crucial landmarks. The parahippocampal gyrus has previously been shown to be involved in object and scene recognition. In the present study, we investigated the neural representation of navigationally relevant locations. Healthy human adults viewed a route through a virtual museum with objects placed at intersections (decision points) or at simple turns (non-decision points). Event-related functional magnetic resonance imaging (fMRI) data were acquired during subsequent recognition of the objects in isolation. Neural activity in the parahippocampal gyrus reflected the navigational relevance of an object's location in the museum. Parahippocampal responses were selectively increased for objects that occurred at decision points, independent of attentional demands. This increase occurred for forgotten as well as remembered objects, showing implicit retrieval of navigational information. The automatic storage of relevant object location in the parahippocampal gyrus provides a part of the neural mechanism underlying successful navigation.

NEUROTRANSMITTER NEWS

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Supplementation for marginal dietary selenium could have functional consequences Back to Healthy News It is possible that marginal dietary selenium and present cancer risk in the British population could be altered by increased selenium, as supplementation increases activity of selenium dependent enzymes. According to a study from England, "Much data indicate that overt selenium deficiency induces a number of pathologies in animals and humans. The effects of chronic marginal undernutrition of this element are unclear, although it has been argued that such subjects will be at increased risk of developing various cancers. "The dietary intake of selenium in the UK has fallen over the last 25 years, although no functional consequences of this have been recognized," wrote M.J. Jackson and coauthors. The researchers concluded: "Recent data demonstrate that restoration of selenium intakes in UK subjects induces biochemical effects with increased activity of selenium-dependent enzymes. Whether such biochemical changes are associated with functional changes is currently unclear and the subject of current investigation." Jackson and colleagues published the results of their research in Journal of Nutrition (Marginal dietary selenium intakes in the U.K.: Are there functional consequences? J Nutr, 2003;133(5 Suppl. 1):1557S-1559S). For additional information, contact M.J. Jackson, University of Liverpool, Dept Med, Liverpool L69 3GA, Merseyside, UK. The publisher of the Journal of Nutrition can be contacted at: American Institute Nutrition, 9650 Rockville Pike, Bethesda, MD 20814, USA. The information in this article comes under the major subject areas of Complementary and Alternative Medicine, Proteomics, Oncology, Immunology, and Diet and Nutrition. This article was prepared by Cancer Weekly editors from staff and other reports.

Researchers to create tool for diagnosing children with apraxia of speech Posted By: News-Medical in Child Health News Published: Tuesday, 27-Apr-2004 A new National Institutes of Health grant will enable Oregon Health & Science University researchers to create a tool for diagnosing children with apraxia of speech -- a neurologically based speech motor disorder. Children with apraxia of speech have great difficulty planning and producing the speech movements they need to make with their tongue, lips, jaw and velum, or soft palate, to form words. Children with apraxia of speech tend to speak less rhythmically than other children, including more even stress on syllables. It is estimated that about one-tenth of 1 percent of children in the United States may have apraxia of speech. Apraxia of speech can occur as a result of a brain injury, but in children born with apraxia, the cause is unclear. "Apraxia of speech is not very well understood or easily diagnosed," said John-Paul Hosom, Ph.D., the principal investigator of the three-year $492,000 grant from NIH's National Institute on Deafness and Other Communications Disorders, and an OGI School of Science & Engineering assistant professor of biomedical engineering. "It is especially difficult to diagnose apraxia of speech in young children because of the different rates at which young children learn language. It is suspected that many children with apraxia of speech go undiagnosed due to the lack of a diagnostic standard." Hosom, a computer scientist in OGI's Center for Spoken Language Understanding (http://www.cslu.ogi.edu), will collaborate with one of the nation's leading experts on childhood speech disorders, Lawrence Shriberg, Ph.D. Shriberg is a professor of communicative disorders at the University of Madison-Wisconsin, director of the NIH-supported Phonology Project, and co-director of The Phonology Clinic at the Waisman Center (www.waisman.wisc.edu). Shriberg, who has been working with children with apraxia of speech for more than 20 years, is interested in the nature and origin of childhood speech disorders of currently unknown origin and ways to identify diagnostic markers in hopes of developing new treatments. For the new NIH study, Hosom and Shriberg will examine the speech patterns of 3 to 8-year-olds whose speech has previously been recorded as part of Shriberg's long-term studies. "Using a computer, we're going to automatically measure certain characteristics of a child's speech and determine whether those characteristics are consistent with apraxia of speech," said Hosom. "So, for example, when a child with apraxia of speech says the word 'ladder,' the duration of the 'ae' and 'er' sounds may be nearly equal with both having strong energy, rather than just the first syllable. "We hope to develop a diagnostic tool for childhood apraxia of speech by automating existing measurements of the speech signal, developing new measurements and combining these different sources of information into a single diagnostic tool," said Hosom. No reliable guidelines currently exist to help people diagnose childhood apraxia of speech. "Improving the reliability of the factors involved in diagnosing the disease is a very important by-product of this study," said Hosom. "If we can develop an automated diagnostic tool, we can reduce the human variability that makes this such a difficult disorder to identify, and get these children into treatment as early as possible." Said Jan van Santen, Ph.D., director of OGI's Center for Spoken Language Understanding, "Paul's project is a good example of the new direction for both the Center and OGI as a whole--not just to apply existing technologies to health problems, but to invent entirely new technologies that we would have never thought of if we were not looking at health issues." Temporal processing deficits of language-learning impaired children ameliorated by training. Merzenich MM, Jenkins WM, Johnston P, Schreiner C, Miller SL, Tallal P. W. M. Keck Center for Integrative Neurosciences, University of California, San Francisco 94143-0732, USA. Children with language-based learning impairments (LLIs) have major deficits in their recognition of some rapidly successive phonetic elements and nonspeech sound stimuli. In the current study, LLI children were engaged in adaptive training exercises mounted as computer "games" designed to drive improvements in their "temporal processing" skills. With 8 to 16 hours of training during a 20-day period, LLI children improved markedly in their abilities to recognize brief and fast sequences of nonspeech and speech stimuli.