October 2003

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.

Train the brain: Neurofeedback teaches some to control their brain waves Neapolitan News Tuesday, July 8, 2003 By BETH FRANCIS, Lindsay Clark is a believer. So is Sherry Stewart. Clark, a 21-year-old Bonita Springs resident, said her neurofeedback sessions have greatly reduced her anxiety and panic attacks. Lindsay Clark, 21, relaxes her mind while hooked to an electroencephalograph for neurofeedback treatments at the Biofeedback Center of Florida in Bonita Springs. Clark has been receiving neurofeedback, or EEG biofeedback, for six months and says the treatments have greatly improved her anxiety and panic attacks. Photo by: Lexey Swall/Naples News Staff "I was a basket case when I first came in here," said Clark, an English major at Florida Gulf Coast University. "I'd feel claustrophobic and nauseous. I was afraid of going places and I wasn't doing well in school. Now I'm so much better. I'm not afraid to go out anymore, and I made all A's and a B on my report card." Stewart, a North Fort Myers interior designer, said the therapy, which changes brain wave activity, has greatly improved her two sons' symptoms from attention-deficit disorder. "It has definitely been amazing," she said. "Before we started the neurofeedback, I was at my wit's end. It's really helped my sons to calm down and focus. There are no more temper tantrums and my younger son really improved in school." Neurofeedback, also called EEG Biofeedback, is used to train the brain to produce more desirable brain waves and fewer undesirable brain waves. The technology is still new, but it is emerging as a way to treat everything from attention-deficit disorder, migraines, anxiety, depression, head injuries, and sleep disorders. JoAnn Blumenthal, a Bonita Springs licensed mental health counselor who operates the Biofeedback Center of Florida, has been performing neurofeedback for four years. Clark goes twice a week for neurofeedback treatments with Blumenthal. During a recent visit, she sat patiently as Blumenthal attached electrodes to her earlobes and the top of her head. The electrodes don't hurt and are attached with a paste. The electrodes are connected to a computer, which measures brain wave activity with an electroencephalograph (EEG). The computer monitor displays different colored boxes, which represent different types of brain waves. As Clark successfully changed the sizes of the boxes, an image on the screen of her flying through the Grand Canyon moved faster and faster. The computer also made a beeping noise as she successfully changed the size of the boxes, and thus her brain waves. The therapy is like a video game you play with your brain. Your brain serves as the control instead of buttons or a toggle stick. As the brain gets the feedback that it is successfully changing brain waves, the new brain wave patterns become ingrained over time, said Siegfried Othmer of the EEG Institute in Los Angeles, which offers training courses in neurofeedback. "It's like behavior modification for the brain," Othmer said. But how does a person will his brain to produce certain patterns? Clark said when she's trying to reduce the size of the blue box, she repeats the word "blue" to herself over and over. "You can't direct it or force it," Othmer said. "All you can do is wish it." Othmer likened the therapy to learning how to ride a bike. When you start to fall, that is your feedback that you need to you correct your balance. With neurofeedback, moving faster through the Grand Canyon and the beeping of the computer is the feedback that you are successfully changing your brain activity. Over time the repetition causes the brain wave to stay in place. "It's like riding a bike. Once you learn how, you don't forget," he said. "You're giving the brain a new skill." Andrew Stewart, 14, of Cape Coral classified himself as an unusually angry and impatient teenager until he began neurofeedback therapy two months ago. "I have improved concentration and better anger management," Stewart said during one of his weekly visits to the Biofeedback Center of Florida in Bonita Springs. Blumenthal said she thinks of the therapy as a way of training the brain. "You get auditory and visual rewards from the computer, so that over time you are conditioning the brain," Blumenthal said. For most clients, it takes 20 to 40 sessions for the therapy to hold. Some clients take home the equipment to continue doing the therapy at home. It isn't cheap, either. Blumenthal charges $100 per session. And insurance reimbursement is spotty, as the procedure is still considered experimental. In some cases, if the patient also is coming in for supplemental psychotherapy, insurance will cover it, she said. When looking for someone to perform neurofeedback, the most important thing to assess is experience, Othmer said. You might also ask if the person is certified by the Biofeedback Certification Institute of America and a member in the Association for Applied Psychophysiology and Biofeedback. "Certification is certainly a good thing, but it's not essential," Othmer said. "The most important thing is that a person be trained and experienced and that they take continuing education because this is an evolving field." For her part, Clark said she can't really explain how she changes the size of those boxes on the computer screen. All she knows it that she leaves Blumenthal's office relaxed and in charge of her emotions. "I still have a ways to go to achieve it on my own, but I've come a long way," she said. Copyright © 2003 Naples Daily News. All rights reserved. Published in Naples, Florida. A Scripps newspaper.   New Studies on Children And Pesticides Published:2003 The very young are particularly vulnerable to environmental toxins, which can disrupt the development of their rapidly developing nervous, hormonal and respiratory systems, says Philip J. Landrigan, M.D., director of the Center for Children's Health and the Environment (CCHE) at Mount Sinai School of Medicine in New York City. Two new studies underscore the need to protect pregnant women and young children from pesticides. * A study of 162 Northern California children ranging from O to 14 years, published in the September 2002 Environmental Health Perspectives (EHP), found that "exposure to household pesticides is associated with an elevated risk of childhood leukemia," according to authors Xiaomei Ma et al. of Berkeley and Stanford. Exposures prenatally through the age of three carried the highest risk. * Preschoolers fed conventional diets had approximately six times higher levels of metabolized organophosphate pesticides in their bodies than children fed organic diets, according to a study at the University of Washington that will appear in a forthcoming EHP. Authors Cynthia Curl et al. found that "consumption of organic fruits, vegetables and juice can reduce children's exposure levels from above to below the U.S. Environmental Protection Agency's current guidelines. . . ."

Age-related decline of intranasal trigeminal sensitivity: is it a peripheral event? Johannes Frasnelli and Thomas Hummel, Smell and Taste Clinic, Department of Otorhinolaryngology, University of Dresden Medical School, Fetscherstr. 74, 01307, Dresden, Germany Accepted 16 July 2003.  Abstract Compared to younger subjects, older people have a reduced sensitivity of the intranasal trigeminal system which responds to irritation of the nasal cavity. It is unclear whether the cause of this difference relates to age-dependent changes in the periphery of the system. The aim of the present study was the comparison of intranasal trigeminal thresholds assessed through electrophysiological measurements in eight young (four women, four men; mean age 25 years) and eight older subjects (four women, four men; mean age 62 years). The negative mucosa potential (NMP), a peripheral correlate of trigeminal activation, was recorded from the nasal mucosa in response to stimulation with varying concentrations of the mixed olfactory/trigeminal stimulants menthol and linalool. Thresholds were estimated as the strongest concentration which did not elicit a NMP response. Older subjects were found to have higher thresholds for menthol when compared to younger subjects. Furthermore, an explorative analysis indicated that the increase of response amplitudes to increasing stimulus concentrations was shallower in older subjects. These findings indicate that age related loss of intranasal trigeminal sensitivity seems to take place, at least to some degree, in the periphery of the intranasal trigeminal system. Limits on theory of mind use in adults Boaz Keysar, Shuhong Lin and Dale J. Barr Cognition, 2003, 89:1:25-41 Abstract By 6 years, children have a sophisticated adult-like theory of mind that enables them not only to understand the actions of social agents in terms of underlying mental states, but also to distinguish between their own mental states and those of others. Despite this, we argue that even adults do not reliably use this sophisticated ability for the very purpose for which it is designed, to interpret the actions of others. In Experiment 1, a person who played the role of ''director'' in a communication game instructed a participant to move certain objects around in a grid. Before receiving instructions, participants hid an object in a bag, such that they but not the director would know its identity. Occasionally, the descriptions that the director used to refer to a mutually-visible object more closely matched the identity of the object hidden in the bag. Although they clearly knew that the director did not know the identity of the hidden object, they often took it as the referent of the director's description, sometimes even attempting to comply with the instruction by actually moving the bag itself. In Experiment 2 this occurred even when the participants believed that the director had a false belief about the identity of the hidden object, i.e. that she thought that a different object was in the bag. These results show a stark dissociation between an ability to reflectively distinguish one's own beliefs from others', and the routine deployment of this ability in interpreting the actions of others. We propose that this dissociation indicates that important elements of the adult's theory of mind are not fully incorporated into the human comprehension system. Combining transcranial magnetic stimulation and functional imaging in cognitive brain research: possibilities and limitations Alexander T. Sack and David E.J. Linden Brain Research Reviews, April 2003; Abstract Transcranial magnetic stimulation (TMS) is a widely used tool for the non-invasive study of basic neurophysiological processes and the relationship between brain and behavior. We review the physical and physiological background of TMS and discuss the large body of perceptual and cognitive studies, mainly in the visual domain, that have been performed with TMS in the past 15 years. We compare TMS with other neurophysiological and neuropsychological research tools and propose that TMS, compared with the classical neuropsychological lesion studies, can make its own unique contribution. As the main focus of this review, we describe the different approaches of combining TMS with functional neuroimaging techniques. We also discuss important shortcomings of TMS, especially the limited knowledge concerning its physiological effects, which often make the interpretation of TMS results ambiguous. We conclude with a critical analysis of the resulting conceptual and methodological limitations that the investigation of functional brain–behavior relationships still has to face. We argue that while some of the methodological limitations of TMS applied alone can be overcome by combination with functional neuroimaging, others will persist until its physical and physiological effects can be controlled.

ALZHEIMER'S RESEARCH

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Vitamin hope for Alzheimer patients Researchers at Ohio State University found that after a year of treatment with vitamin E and the cholinesterase inhibitor donepezil, people with Alzheimer's disease performed much better on tests of cognitive ability than did people who had not taken either substance. "There were notable cognitive differences even after three years of combined therapy," said Dr David Beversdorf, the study's senior author and an assistant professor of neurology at the university. "It slowed down the cognitive decline that characterises the disease." Lead author Dr Emily Klatte, and colleagues, studied 40 patients with Alzheimer's disease who took daily doses of both vitamin E and donepezil. The participants also took a cognitive abilities test each year during the three-year study. Their annual test scores were compared to the scores of Alzheimer's patients who took the same kind of test prior to 1996 - before donepezil and similar drugs were available, and also before vitamin E was touted as possibly having a role in disease prevention and progression. The decline in cognitive test scores of patients who had not taken either agent was three times greater after a year than the decline in scores of the patients taking the combined therapy, the researchers found. For the retrospective study, the researchers reviewed the medical charts of 40 patients with mild to moderate Alzheimer's disease who had taken a minimum of 1,000 U (about 670 mg) of vitamin E in supplement form and at least 5 mg of donepezil daily for at least a year. The patients had also been given the mini-mental state examination (MMSE) - a test of cognition used to assess dementia in Alzheimer's patients. The researchers compared the MMSE scores of the people who took the dual treatment to the test scores of Alzheimer's patients listed in the Consortium to Establish a Registry for Alzheimer's disease (CERAD) database - a database that includes information on Alzheimer's patients prior to 1996. All of the subjects taking vitamin E and donepezil were given the MMSE at the beginning of the study, and again a year later. Thirty-eight subjects were tested after two years of treatment, and 22 participants were re-tested after the third year of treatment. The researchers compared these scores to subjects in the CERAD database who had taken the MMSE test for three continuous years. After the first year, the decline in test scores of the CERAD group was nearly three times higher than the decline in scores of the treated group. By the study's third year, the decline in test scores of the CERAD patients was nearly one-and-a-half times higher than the decline in scores of the comparable treated group.   Continuing Research on Fish Could Help Reduce Alzheimer's A promising study has revealed that eating fish might significantly reduce the risk of Alzheimer's disease in older people. Considering that as many as 10 percent of people over the age of 65 and 50 percent of those over 85 suffer from the disease, this is very good news. The study found that people 65 and older had a 60 percent lower risk of Alzheimer's disease when they ate fish once a week. The meals were as simple as fish sticks and tuna sandwiches. What's not clear is whether the participants in the study had eaten fish most of their lives or what other dietary habits might have influenced the results. What is clear, however, is the results have given researchers a very significant place from which to expand their study. It's believed that omega-3 fatty acids are important for brain development, and fish is a great source of omega-3. The fatty acid also has been associated with a reduced risk of heart disease and breast cancer. People who want to start fighting Alzheimer's early on, however - particularly women - should be careful about fish selections. Other studies show a high level of mercury in fish such as tuna can lead to neurological problems in developing fetuses. It's important for people to discuss with their doctors what the benefits and risks are and for researchers to continue this important work.

PREEMIE AND NEWBORN NEWS

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Factors predictive of seizures and neurologic outcome in perinatal depression Barbara Caravale, Federico Allemand and Mark H. Libenson Pediatric Neurology, 2003, 29:1:18-25 To identify which early clinical variables are predictive of outcome in newborns with perinatal depression, we prospectively examined newborns with persistently abnormal neurologic examinations at 48 hours and (1) arterial pH 7.15, (2) 5-minute Apgar 5, (3) requirement for positive pressure ventilation in the delivery room, or (4) fetal heart rate monitoring abnormalities. Eighty-four such infants completed neurodevelopmental assessment at 1 year. Five-minute Apgar (P = 0.0064), arterial pH (P = 0.0065) and base excess (P = 0.0003), neonatal encephalopathy grade at 48 hours and 7 days (both P = 0.0001), EEG at 48 hours and 7 days (both P = 0.0001), cranial ultrasound (US) at 48 hours (P = 0.0013) and 7 days (P = 0.0002), and the occurrence of neonatal seizures (P = 0.0001) all correlated significantly with developmental outcome, whereas fetal heart rate monitoring, mode of delivery, and presence of the non-neurologic hypoxic-ischemic encephalopathy syndrome did not. In the multivariate analysis, a combination of the 48-hour EEG and 48-hour cranial ultrasound provided the best model to predict developmental outcome, and a point system to predict developmental outcome based on these two variables is proposed.

BRAIN PLASTICITY

Radio National with Brain Plasticity Summary: Research from Germany has shown that the adult brain is almost as malleable and plastic as a child's. Research from Germany is showing that virtuoso violin playing can make the brain too smart for its own good, but also that the adult brain is almost as malleable and plastic as the child's. The way people learn to play the violin has shown that the adult brain is far more adaptable than many experts have thought in the past, and the researchers from the University of Konstanz have extended their findings to Braille readers. Brain plasticity means the ability of the nervous system to adapt to changed circumstances, to find new ways of learning, sometimes after an injury or a stroke, but more commonly when you want to acquire a skill for, say, a hobby or even a new job. One of the scientists who's worked on this and how our brains respond to environmental demands, is psychologist, Professor Thomas Elbert. Thomas Elbert: Twenty years ago people thought that the structure of the brain develops during childhood and once that organisation in the brain has been developed that there is very little room for changes and for plastic alterations. Now we know that there is enormous capacity. Norman Swan: Now you, earlier on, in exploring this idea that the adult brain is still very plastic, you looked at violin players. Thomas Elbert: Well, violin players use the left hand and their fingers to finger the strings, and they do so several hours a day, and these fingertips get stimulated, and what we see there is that the representation of the left-hand fingers and the right hemisphere of the brain -- Norman Swan: I should explain here that the opposite side of the brain dictates the movements and perceives sensation from the actual side of the body where the movement or sensation occurs - it crosses over. Thomas Elbert: Right, exactly. It crosses over, so in many string players the hand representation in the brain gets enlarged. So the brain assigns more tissue, more neural elements to the processing of these fingers. Norman Swan: And that's compared to non-string players, obviously. Thomas Elbert: That's compared to non-string players and also compared to the right-hand in these musicians, because the right-hand moves the bow and there's much less finger movement and much less stimulation of the fingertips involved. Norman Swan: So the fingertip representation on the right side of the brain is just much, much larger than the one on the left? Thomas Elbert: Exactly. And what we see is that if you start early in childhood playing the instrument, then this change is greater. But what is really now amazing and interesting and fantastic is that also if adult people start playing the instrument, they also change their representation, not to the extent as we see it when you start early playing the instrument, but it still occurs in adulthood. Norman Swan: What's the technology that you use to measure this? Because in the old days there was a famous Canadian neurosurgeon who, when he just happened to be operating on the brains of his patients, he would measure with electrodes physically, and get them to move their hands. Presumably you're not doing this with violin players? Thomas Elbert: No, we didn't find anyone who would allow us to open their skull, you know! So as neural elements function electrically, and with every electric process, every electric current has a magnetic field which is induced by the electric current, and we can detect this magnetic radiation. Norman Swan: Tell me about the study you did with people who read using Braille. Thomas Elbert: Yes, we have investigated several Braille readers, and there are those who used just one finger and others use several fingers at a time. And those who read Braille for several hours a day, and use several fingers simultaneously, instead of having several separate representations of the different fingertips develops a kind of merged, giant large finger, or a large representation of all the fingers simultaneously in the brain. So to speak a super highway of information from the fingertips to the centres of the brain where all that information is merged and so these people perceive at the same time, all the information from the different fingertips. On the other hand, they are no more able then to determine where the information comes from. I think normal people have a little bit the same kind of fusion and disorder representation of their toes, because they stimulate the toes simultaneously usually in the shoes and we do not develop separate representation of the toes. Whereas with the fingers we develop separate representations in the brain. Norman Swan: So what's happening then with Braille readers who use three fingers, is it that three fingers act as one? And I notice from your research that if you in fact touch their fingers... in other words if my finger or your fingers were to be touched, we would know which finger's being touched. But in fact blind Braille readers who use three fingers, they're not sure which finger's being touched of those three fingers. Thomas Elbert: Correct. If I do that with your toes, it's the same thing. If I touch your toes, your middle toes, you will not be able to tell me which one has been touched. Whether you believe it or not, you can try this. The same thing happens with these brain readers. Only those who use several fingers with the reading at the time, then the information fuses and merges in the brain, and then of course they're no more able to tell where the information at a given location comes from. Norman Swan: With one-fingered Braille readers? What happens with them? Thomas Elbert: They don't have this 'fused' representation of the fingers, but actually the finger used for Braille reading, this finger has an enlarged representation. Norman Swan: So it becomes a super finger. Thomas Elbert: It becomes a large finger, yes. Norman Swan: Are three-fingered Braille readers better Braille readers than one-fingered Braille readers? Thomas Elbert: It seems to be so, yes. They seem to be faster. Norman Swan: Going back to the original reason for doing the experiment in terms of whether the adult brain is plastic, most of these people would have learnt to read Braille as children. What about people who learn to read Braille as adults? Thomas Elbert: We basically see the same thing. Again, the amount of adaptation is smaller than compared to the ones who start as children, particularly before the age of ten. But we still see very significant changes, and a rough estimate is that the plasticity is about half as large as an adult but still it's clearly there. Norman Swan: So what are the implications of these findings? Thomas Elbert: Well first of all it's very interesting from a basic point of view, but we also hope to apply this information to certain types of disorders. For example, in the musicians, if they are virtuosos, then they can move their fingers very quickly, very fast, and it's like a simultaneous input to the fingers, and the brain's integration time may then think that there's simultaneous input to two fingers at a time and as a consequence these people may no more be able to move fingers so quickly. This order is called focal dystonia of the hand, and then like a hand-cramp may develop and this is of course very fatal for a musician. Norman Swan: So you have a violin player in whom not only are his or her fingers being 'read' in the brain as one, but in fact they start in a physical sense, in a 'muscle sense', to act as one. Thomas Elbert: Exactly. Norman Swan: How do you fix this up? Thomas Elbert: We know that the synchronous input basically causes such problems, and these people of course first think it's maybe a peripheral problem, problems of the muscles, so that they can no more move the fingers separately, whereas in fact it is the brain representations that meld together. And we just then have a training schedule that stimulates the fingers and there they have to move the fingers in a certain very defined manner in order to separate these brain regions again. Norman Swan: Mind boggling research there, so to speak. Thomas Elbert is Professor of Psychology at the University of Konstanz in Germany. Plastic-adaptive properties of cortical areas Hubert R. Dinse and Gerd Böhmer Hubert R. Dinse, PhD Institute for Neuroinformatics, Dept. Theoretical Biology Research Group Experimental Neurobiology Ruhr-University Bochum, ND Bochum, Germany Hubert.dinse@neuroinformatik.ruhr-uni-bochum.de Gerd Böhmer, PhD Institute of Physiology and Pathophysiology Gutenberg-University D-55099 Mainz, Germany May 2002 This chapter summarizes recent findings about plastic changes in adult early sensory and motor cortices. We discuss mechanisms leading to enduring changes of synaptic efficacy and of neural response behaviour in terms of receptive fields and cortical representational maps, with special emphasis on behavioural and perceptual consequences of cortical reorganizations, after peripheral lesion or injury, differential use and training. Given the assumption that the presence of plasticadaptive abilities are a prerequisite for coping successfully with an ever-changing environment, we focus on comparative aspects, evaluating apparent similarities and dissimilarities emerging across different modalities. Most of the material reviewed is from animal studies that allow the study of adaptations and underlying mechanisms induced under a large variety of natural and laboratory conditions, at all levels from channels and synapses, to groups of neurones and cortical maps. Owing to the recent development of non-invasive imaging technologies, it has become possible to explore the significance of cortical plasticity for humans, occurring in “every-daylife”. Massive and enduring reorganizations are present for all areas and modalities discussed, corroborating the view that cortical maps and response properties are in a permanent state of use-dependent fluctuation. We discuss various mechanisms controlling synaptic plasticity, the role of input statistics and attention, the top-down modulation of plastic changes, the “negative”, (maladaptive) consequences of cortical reorganization, and the coding and decoding of adaptational processes. Despite the convincing evidence for profound reorganizational changes in all areas, specifically for injury-related plasticity, there exist also clear modality-specific differences, an observation holding at both the cellular and the systemic level. Differences include magnitude of changes, readiness of induceability and specificity of neural parameters that are affected. While reorganization of somatosensory and auditory cortex appears to follow comparable rules and constraints, adult visual cortex plasticity shows a number of particularities, indicating that visual cortical maps might be more difficult to change. We discuss a number of possible explanations based on different levels of abstraction. Among these are differences in control mechanisms of synaptic plasticity, the limiting character of complex topological maps, and the possible limitations of the metaphor of “use”, as a driving force of adult plasticity.

AUDITORY/PROCESSING NEWS

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Changes in spontaneous neural activity immediately after an acoustic trauma: implications for neural correlates of tinnitus A. J. Noreñaa and J. J. Eggermont, , b a Department of Physiology and Biophysics, Neuroscience Research Group, University of Calgary, 2500 University Drive N.W., Calgary, AB, Canada T2N 1N4 b Department of Psychology, Neuroscience Research Group, University of Calgary, 2500 University Drive N.W., Calgary, AB, Canada T2N 1N4 September 2003. Abstract Changes in spontaneous activity, recorded over 15-min periods before, immediately after and within hours after an acute acoustic trauma, were studied in primary auditory cortex of ketamine-anesthetized cats. We focused on the spontaneous firing rate (SFR), the peak cross-correlation coefficient () and burst-firing activity. Multi-units (MUs) were grouped according to characteristic frequency (CF): MUs with a CF below the trauma-tone frequency (TF) were labeled as Be, those with a CF within 1 octave above the TF were labeled as Ab1 and those with a CF more than 1 octave above the TF were labeled as Ab2. Immediately after the trauma, the SFR was not significantly changed. The percentage of time that neurons were bursting, the mean burst duration, the number of spikes per burst and the mean inter-spike interval in a burst were enhanced. was locally increased in the Ab1-Ab2 and Ab2-Ab2 groups. A few hours post trauma, the SFR was increased in the Be and Ab2 groups, whereas burst-firing returned to pre-exposure levels. Moreover, was elevated in the Be-Ab2, Ab1-Ab2 and Ab2-Ab2 groups; this increase was significantly correlated to the changes in SFR. The results are discussed in the context of a neural correlate of tinnitus. Binaural interaction in the human auditory cortex revealed by neuromagnetic frequency tagging: no effect of stimulus intensity Ken-ichi Kaneko, , a, b, Nobuya Fujikib and Riitta Haria, c a Brain Research Unit, Low Temperature Laboratory, Helsinki University of Technology, b Department of Otolaryngology – Head and Neck Surgery, Kyoto University Graduate School of Medicine, c Division of Clinical Neurophysiology, Helsinki University Central Hospital, FIN-00290, Helsinki, Finland September 2003. Abstract Frequency tagging of magnetoencephalographic signals was recently introduced as a new tool to study binaural interaction in the human auditory cortex [Fujiki et al., J. Neurosci. 22 (2002) RC205]. As the method has potential value for assessing brain plasticity in patients with unilateral hearing deficits, we studied binaural interaction in 10 healthy adults at different intensity levels. Cortical steady-state fields were measured with a 306-channel whole-scalp neuromagnetometer to amplitude-modulated sounds (carrier frequency 1 kHz), presented monaurally or binaurally at 45, 60 and 75 dB SL. The modulation frequencies were 39.1 Hz for the right ear and 41.1 Hz for the left. During binaural stimulation, the ipsilateral responses were suppressed more than the contralateral ones in both hemispheres, and the hemispheric balance shifted towards the contralateral hemisphere for inputs from both ears. The patterns of binaural interaction were similar at all three stimulus intensities. These data could be useful in examining patients who suffer from auditory disorders as well as in revealing basic mechanism of human auditory processing. The emotional ear in stress K.C. Horner Neuroscience and Biobehavioral Reviews, 2003, 27:5:437-446 June 2003; Abstract Stress of some kind is encountered everyday and release of stress hormones is essential for adaptation to change. Stress can be physical (pain, noise exposure, etc.), psychological (apprehension to impending events, acoustic conditioning, etc.) or due to homeostatic disturbance (hunger, blood pressure, inner ear pressure, etc.). Persistent elevated levels of stress hormones can lead to disease states. The aim of the present review is to bring together data describing morphological or functional evidence for hormones of stress within the inner ear. The present review describes possible multiple interactions between the sympathetic and the complex feed-back neuroendocrine systems which interact with the immune system and so could contribute to various inner ear dysfunctions such as tinnitus, vertigo, hearing losses. Since there is a rapidly expanding list of genes specifically expressed within the inner ear this clearly allows for possible genomic and non-genomic local action of steroid hormones. Since stress can be encountered at any time throughout the life-time, the effects might be manifested starting from in-utero. These are avenues of research which remain relatively unexplored which merit further consideration. Progress in this domain could lead towards integration of stress concept into the overall clinical management of various inner ear pathologies.

NEUROTRANSMITTER NEWS

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Developmental pharmacodynamics: implications for child and adolescent psychopharmacology Normand Carrey, MD; Stan Kutcher, MD J Psychiatry Neurosci 1998;23(5):274ú6 Department of Psychiatry, Dalhousie University, Halifax, Nova Scotia Developmental pharmacodynamics is the study of neurofunctional capabilities, how these develop during the life span and how this development affects responses to psychotropic agents. It is well recognized that various neuroanatomical regions and neurotransmitter systems develop at different rates and mature at different times.1 Our understanding of these developments is derived from studies that have investigated neurotransmitters, receptors, second messengers, glial cells, hormones and nerve trophic factors; this growing body of knowledge is integral to our improved understanding and treatment of child and adolescent psychiatric disorders. This commentary will limit itself to the role 2 neurotransmitters, serotonin (5-HT) and dopamine, and their receptors, play in development. The serotonergic system provides an excellent example of how the interplay of neurotransmitters, receptors and glial cells reciprocally affects development. 5-HT was described as a potential "developmental signal" by Lauder as early as 19832 when he postulated that 5-HT played a different role in the immature brain than in the mature one. Prenatal depletion of 5-HT with p-chlorophenylalanine (PCPA) delays the onset of neurogenesis in 5-HT target regions,3 whereas 5-HT stimulation with 5-methoxytryptamine produces dose-dependent effects on neurite outgrowth.4 5-HT can thus be conceptualized as playing a dual role in development: autoregulation of the serotonergic neurons themselves and development of target tissues.5 Another example of the teratogenic effects on developing neural fields induced by blocking 5-HT involves feeding pregnant mother rats ethanol, resulting in a significant decrease in 5-HT innervation of the cortex and brain stem of their pups. This effect can be prevented by pretreatment with buspirone.6 Serotonergic neuroreceptors acquire different developmental functions as the organism matures; there are regional and receptor subtype specificities, the functions of which change during maturation. Serotonergic receptors in rats attain peak levels in fetal or early postnatal life and then decrease to adult levels.7 For some receptor subtypes, the highest number of receptors occurs during brain development when properly functioning synapses are not yet present. The 5-HT1C receptor may play a role in the regulation of cell division whereas the 5-HT1A type may regulate differentiation. During development, the 5-HT1A receptor is transiently expressed in high numbers and is often expressed in regions from which it is absent in the adult brain.8 The 5-HT1A receptor subtype has been thought to play a critical role in both neuronal and glial cell growth through trophic effects of nerve growth factors. Whitaker-Azmitia and Azmitia9 have shown that astroglial cells promote immature neuron growth through the secretion of S-100, a nerve growth factor, but the effect is mediated through 5-HT1A receptors on brain astroglial cells. As serotonergic neurons mature, the level of S-100 decreases, as does the number of 5-HT1A receptors on astroglia. Drugs that act as agonists to the 5-HT1A receptor, such as 8-hydroxy-di-propylaminotetralin (8-OH-DPAT), promote astroglial cell maturity. Studies of rodents have demonstrated the functional effects of these developmental changes. Teicher and Baldessarini1 observed that acute administration of imipramine to the adult rat produces sedation, whereas this is not shown until 4 weeks of age in the younger rat due to the delayed development of a serotonin-mediated inhibitory response. Similarly, McCracken and Poland10 found that in prepubertal rats the prolactin response to a serotonin agonist was not enhanced by pretreatment with amitriptyline, whereas in adult rats the prolactin response was enhanced. They suggested that immature organisms may lack the full capacity to upregulate a 5-HT-receptor-coupled response. These ontogenetic differences in the development of this monoamine system may help explain the documented differences in clinical response to antidepressants and placebo in studies comparing children and adolescents to adults. A similar developmentally sensitive role has also been documented for the dopamine receptor. The highest numbers of both D1 and D2 receptors occur in the immature brain in rats, baboons and humans.7 D2 receptors are transiently expressed in the frontal cortex of the immature rat but are absent in the adult brain. Dopamine receptors, like neuronal cell number, synapses and dendritic processes, undergo pruning as part of the developmental process. However, if receptors are blocked neonatally or are deprived of stimulation, permanent changes in binding or compensatory receptor expression may occur in adults, such as is demonstrated when neonates are treated with neuroleptics or are lesioned with 6-hydroxydopamine.11 Additionally, the D1 receptor has been localized on growth cones, the tips of the growing nerve terminal, suggesting a role in influencing neuronal differentiation and maturation. In rodent models, animals exposed to neuroleptics demonstrate developmentally specific differences in behavioural expression. For example, before rats are weaned (21 days and younger), they are very sensitive to the motor (bradykinetic) and sedative effects of neuroleptics, whereas periadolescent rats (28 to 38 days) display very strong cataleptic reactions. This parallels children's susceptibility to extrapyramidal side effects of dopamine blockade. The incidence of drug-induced dystonias and bradykinetic reactions diminishes strikingly with maturation from ages 10 to 19 years to adulthood,12 whereas neuroleptic-induced akathisia is less common in children. Neuroleptic-withdrawal dyskinesias are more common in children.13 This simplistic overview belies the complexity not only of each neurotransmitter system, but also of the multiple interactions possible between these systems during development. One neurotransmitter may have multiple effects on different systems during development. Liu and Lauder14 have shown that 5-HT, through regional effects on either raphe glia or mesencephalic glia, promote nerve growth factors affecting the maturity of serotonergic neurons or tyrosine hydroxylase neurons, respectively. Alternatively, D1 receptors have been shown to inhibit growth cone motility in serotonergic terminals; for example, if rat pups are treated prenatally with a D1 agonist, they will have greatly reduced serotonin uptake sites as adults. Knowledge of neuroreceptor development has profound implications for our understanding of child and adolescent psychiatric disorders and the possible salutary or deleterious effect of psychotropics on brain development. For example, Andersen and colleagues15 have shown that D1 and D2 receptors are first overproduced and then pruned to a greater extent in the striatum of male rats than of female rats. Dopamine receptors reach their peak at day 40 and then decrease dramatically by day 60, the period of time corresponding to puberty in the rat. From this observation, Andersen and her group have speculated that the onset, gender disparity and adolescent alterations in the clinical picture that occur in attention-deficit/hyperactivity disorder and Tourette's syndrome may stem from disregulation of receptor density development. They also found a profound reduction in 5-HT turnover in the nucleus accumbens during the peripubertal period. Again, they propose that the disinhibition, aggression and mood lability of adolescence may be due to alterations in serotonergic transmission. Many of the long-term effects of psychotropics on human developmental pharmacodynamics are not known. Based on animal data, which have shown that the blockade of neurotransmitters in the developing brain may result in a permanent downregulation of that receptor system, Vitiello and Jensen16 speculated that even a temporary blockade could result in a permanently underdeveloped system. In contrast, if psychotropic compounds can arrest the degeneration of specific brain functioning postulated to underlie such illnesses as schizophrenia, these treatments may have preventive effects. As child and adolescent psychiatrists stride toward earlier identification of childhood depression, psychosis, anxiety and obsessive-compulsive disorders, the intuitive logic of prescribing to children psychotropic drugs known to be effective in adults without knowledge of their relation to neurodevelopment should be tempered by careful clinical research. This research should be based on "bottom up" rather than "top down" strategies, in which the development of psychopharmacologic interventions is informed by an understanding of the ontogeny of the central nervous system.

AUTISM

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The Autism Bombshell ; Worrying Rise in Childhood Cases Sparks New MMR Fears A DISTURBING picture of the true extent of childhood autism in Scotland has emerged. Official figures revealed that 2,204 children were registered with the condition in 2002, a massive increase on the previous year's figure of 1,515. Among primary school children, 1,158 were recorded as having autism last year, nearly double the number in 2001. Campaigners claimed the numbers were 'just the tip of the iceberg' and raised serious questions about the safety of the MMR triple vaccine, which has been linked by some experts with increased incidence of the condition in young children. Bill Welsh, spokesman for Action Against Autism, said: 'We know that autism is on the rise and yet they constantly tell us it is down to increases in reporting, or changes to the goalposts. 'As far as I am concerned, cases are going up and we are not being told why.' Officials said yesterday that the worrying rise had been caused because schools were now recording a group of children with mild forms of autism who had not been counted in previous years. These were children who had been given an 'individualised educational programme' by schools as a result of their special needs. Previously, only children with more serious forms of autism had been counted. A Scottish Executive spokesman said: ' This accounts for the increase. By including the children on individual education programmes, we get a clearer picture.' But the explanation cut little ice with campaigners, who believe the Executive is deliberately muddying the picture in order to avoid a mass panic about the MMR jab. They have long claimed the combined mumps, measles and rubella injection is linked to both autism and bowel problems such as Crohn's disease. The fears date back to research in the late 1990s in which a link was drawn between the rise of autism and the use of the MMR triple jab, which was introduced in 1988. Medical opinion is divided and the Executive commissioned its own study into the issue as uptake of MMR slumped. Last year, new evidence suggested a link between the mumps, measles and rubella vaccine and autism when scientists reported finding a strong association between the vaccine and an immune system reaction that is thought to play a role in autism. The team, led by Dr Vijendra Singh, analysed blood samples from 125 autistic children and 92 children who did not have the disorder. In 75 of the autistic children they found antibodies showing an abnormal reaction to the measles component of the MMR vaccine. Nine out of ten of those children were also positive for antibodies thought to be involved in autism. Dr Singh has suggested that an abnormal immune response may be the root cause of many cases of autism. However, the Government's Chief Medical Officer and the British Medical Association both insist there is a wealth of scientific evidence that the triple jab is the safest way to protect children. The latest Executive figures reignite the debate and mean that previous statistics on the scale of the disorder are probably wild underestimates. Opposition parties said the much higher figures should trigger more research into why autism is on the rise. SNP health spokesman Shona Robison said: 'It is very important that we get more analysis of these figures and we need to know how and MMR but these figures back up the calls for more research to be done.' Miss Robison added: 'Until we have found out for sure what the causes of autism are, then people will continue to speculate.' David Davidson, health spokesman for the Scottish Tories, said: 'What we are finding from carers and families is that cases of autism are going unrecorded and more research needs to be done into its causes. The responsibility is with the Executive.' Health chiefs have repeatedly attempted to reassure parents about MMR. Scotland's Chief Medical Officer, Dr Mac Armstrong, has consistently stressed the importance of childhood immunisation. He has said: 'Immunisation in early childhood is still the safest and most effective way of protecting all children, and the wider community, against the risks of serious infectious diseases.' However, parents are deciding against the MMR jab in unprecedented numbers. Recent figures show that about one in eight Scottish two-year- olds are no longer given the jab. Parents are deciding that the risk of their children contracting measles, mumps or rubella is less than any sideeffects from the jab, while others opt to pay for single injections, which are not currently available on the NHS. Doctors fear it is only a matter of time before an epidemic of measles takes hold among the unprotected population while many concerned parents say that single jabs should be available free on the NHS.

EEG/ERP

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The diagnostic value of sensory evoked potentials in pediatric Wilson disease Pediatric Neurology     July 2003 Yu-Shan Hsu, Yang-Chyuan Chang, Wang-Tso Lee, Yen-Hsuan Ni, Hong-Yuan Hsu and Mei-Hwei Chang Abstract We studied the sensory evoked potentials in pediatric Wilson disease to verify their subclinical neurologic involvement and to elucidate the role of cirrhosis in abnormal evoked potentials in non-neurologic Wilson disease. Thirty children (17 male, 13 female), diagnosed with Wilson disease before 18 years, were enrolled. The mean age during studies was 15.8 ± 6.3 years, and disease duration since diagnosis was 3.0 ± 3.3 years. In 12 neurologic Wilson disease cases, there were prolonged interpeak latencies of brainstem auditory evoked potentials III-V, I-V, somatosensory evoked potentials N13-N20 (P < 0.01 vs controls and non-neurologic cases), and P100 latency (P < 0.01 vs controls). All 12 patients had at least one abnormal evoked potential, including 91.7% brainstem auditory, 58.3% somatosensory, and 25% visual evoked potentials. In 18 non-neurologic Wilson disease cases, there were still prolonged interpeak latencies for brainstem auditory evoked potentials I-V and somatosensory evoked potentials N13-N20 (P < 0.05 vs controls), with 27.8% of them having at least one abnormal evoked potential, including 16.6% brainstem auditory, 5.6% somatosensory, and 11.1% visual evoked potentials. In those with non-neurologic Wilson disease, there were no significant differences in all the evoked potential parameters between the cirrhotic and non-cirrhotic patients.

When anger becomes unrecognizable September 2003 by Helen Dell Research into how people recognize emotion has identified a brain region that seems to be involved in the perception of anger. It could be part of an extended circuit of specialized emotion-response areas, suggest the investigators. There are a limited number of emotional facial expressions that are recognized by cultures throughout the world - the so-called universal emotions of sadness, disgust, fear, anger and happiness. "The fact that they are universally recognized suggests some element of 'genetic homogeneity'," said Andy Calder, research scientist at the MRC Cognition and Brain Sciences Unit in Cambridge, UK. That is, all human brains may have an innate ability to recognize these emotions laid down by the genes. "It seems that some emotions have a certain degree of prominence because of their life-preserving properties," said Calder. It's important to be disgusted by contaminated food, for example. Calder previously worked on identifying brain areas involved in perception of fear and disgust. He hypothesized that there may also be brain areas specialized in the perception of the other major emotions. He decided to look at a region of the brain called the ventral striatum, and the system of dopamine-responsive neurons that feeds into it. "There's a lot of work tying dopamine to the aggressive response in animals and showing that lesions to the ventral striatum in animals disrupt aggressive responses," explained Calder. He and his colleagues studied people with very specific damage to the brain in the ventral striatum - usually as a result of stroke or other illness. By showing how subjects categorized pictures of the universal facial expressions, the researchers found that these people had a deficit in recognizing angry faces. "We think this region might represent an area involved in the recognition of anger," concluded Calder. Emotional stimuli are rarely as obvious as his pictures, he notes, they are usually more subtle or mixed together. "It is important the information is communicated among the different systems and perhaps feeds into one single system at one point in order to make a decision about how you should react to an emotional stimulus." Calder's team predict that that the brain regions associated with fear, disgust and anger probably form an extended circuit of intercommunication, with certain structures being disproportionately involved in processing particular emotions. The findings intrigue Mary Phillips of The Institute of Psychiatry in London. Phillips uses functional brain imaging to study emotion processing. "It does suggest that the anger that we learn and the aggression that we learn to recognise is more 'hard-wired' than we had previously realized." But the ventral striatum is not specifically geared to the perception of anger, she says. It plays a role in emotional behavior and responses to emotional stimuli, so the situation is complicated. For instance, the ventral striatum is involved in processing pleasure and reward, she notes, which begs the question why aren't the people with lesions in this area particularly bad at recognizing happy faces? She agrees that the ventral striatum and other regions in the brain are probably working together. Perhaps if one area gets knocked out, then the system doesn't work so well, she suggests. And then emotions that are more difficult to recognize may be ignored or misinterpreted. "If you ask people what the easiest expression to recognise is, they say happy, and they are also quite good at recognizing fear. Anger is a bit lower down, it is a bit more difficult to recognize," said Phillips. So, she suggests, perhaps anger is the first to go when the emotion-recognition system is disrupted.   The cognitive neuroscience of category learning Szabolcs Kéri Brain Research Reviews, June 2003; Abstract Recently, a multidisciplinary approach has provided new insights into the mechanisms of category learning. In this article, results from theoretical modeling, experimental psychology, clinical neuropsychology, functional neuroimaging, and single-cell studies are reviewed. Although the results are not conclusive, some general principles have emerged. Areas localized in the sensory neocortex are responsible for the perceptual representation of category exemplars, whereas lateral and anterior prefrontal structures are necessary for the encoding of category boundaries and abstract rules. The prefrontal cortex may influence categorical representation in the sensory neocortex via top-down control. The neostriatum is important in stimulus–response mapping, and the orbitofrontal cortex/ventral striatum are related to stimulus–reward associations accompanying category learning. Many category learning tasks can be performed implicitly. In conclusion, category learning paradigms provide a unique opportunity to investigate cognitive processes such as perception, memory, and attention in a systematic and interactive manner. Category learning tasks are suitable for mapping damaged brain systems in clinical populations. Studying spontaneous EEG activity with fMRI A. Salek-Haddadi, K.J. Friston, L. Lemieux and D.R. Fish Brain Research Reviews, April 2003; Abstract The multifaceted technological challenge of acquiring simultaneous EEG-correlated fMRI data has now been met and the potential exists for mapping electrophysiological activity with unprecedented spatio-temporal resolution. Work has already begun on studying a host of spontaneous EEG phenomena ranging from alpha rhythm and sleep patterns to epileptiform discharges and seizures, with far reaching clinical implications. However, the transformation of EEG data into linear models suitable for voxel-based statistical hypothesis testing is central to the endeavour. This in turn is predicated upon a number of assumptions regarding the manner in which the generators of EEG phenomena may engender changes in the blood oxygen level dependent (BOLD) signal. Furthermore, important limitations are posed by a set of considerations quite unique to 'paradigmless fMRI'. Here, these issues are assembled and explored to provide an overview of progress made and unresolved questions, with an emphasis on applications in epilepsy. Genetics of human prefrontal function Georg Winterer and David Goldman Brain Research Reviews, 2003, 43:1:134-163 Abstract Evolution of the prefrontal cortex was an essential precursor to civilization. During the past decade, it became increasingly obvious that human prefrontal function is under substantial genetic control. In particular, heritability studies of frontal lobe-related neuropsychological function, electrophysiology and neuroimaging have greatly improved our insight. Moreover, the first genes that are relevant for prefrontal function such as catechol-O-methyltransferase (COMT) are currently discovered. In this review, we summarize the present knowledge on the genetics of human prefrontal function. For historical reasons, we discuss the genetics of prefrontal function within the broader concept of general cognitive ability (intelligence). Special emphasis is also given to methodological concerns that need to be addressed when conducting research on the genetics of prefrontal function in humans.

Plasticity in children's language after stroke: age at injury and lesion effects Sandra Bond Chapman, Jeffrey E. Max, Jacquelyn F. Gamino, Jenny H. McGlothlin and Starr N. Cliff Pediatric Neurology, 2003, 29:1:34-41 Abstract Studies of children with stroke indicate remarkable recovery of language after some initial delay. However, complex language abilities as measured by discourse (connected language) may be required to detect the full impact of stroke on subsequent cognitive-linguistic development. This study examined discourse ability in children with stroke as compared with orthopedic controls, age-at-injury, and lesion effects. Discourse between two groups of children was compared [stroke (n = 17) vs orthopedic control (n = 17)]. The stroke group was subdivided into early age at stroke (<1 year) and late age at stroke (>1 year). The discourse samples were analyzed along two dimensions: language and information structure. Results revealed that the stroke group performed at significantly lower levels than the orthopedic control group across discourse measures. The most important finding was a poorer outcome for early age at stroke as compared with later age at stroke. These findings alter the widespread belief of optimistic language outcomes after childhood stroke. Interestingly, no site or size-of-lesion effects, common to adult stroke, were identified. These findings identify poor long-term outcome with early brain insults at stages far removed from the onset of injury. The implication is that childhood stroke management should be revised to provide protracted follow-up and treatment.

Sensitive vision University of Kentucky College of Medicine 7 July 2003 by Laura Nelson Smells affect vision, say researchers who have shown that olfactory input influences visual sensitivity in the zebrafish. The phenomenon, which appears to help fish find mates, provides one explanation for the presence of linking pathways between the retina and different sensory systems. Nerves that connect two parts of the central nervous system, called efferent or centrifugal fibers, exist in many species, including crustaceans, reptiles, birds, and mammals, and have been studied since the end of the 19th Century. But researchers have so far failed to establish a role for these structures. "The zebrafish nose and eye [study] is the first to show functional integration," said physiologist Lei Li at the University of Kentucky College of Medicine, who led the study, and has shown that dopamine is the neurotransmitter responsible. "This has wide implications for other species," he said. Li used amino acids as olfactory stimuli and assessed visual sensitivity in zebrafish by measuring the threshold of light intensity that was required for the fish to escape from a threatening shadow in a circular tank. Li predicts that the olfactory signals improve zebrafish vision in the very early morning when visual sensitivity is low due to circadian control - this is the time when the animals are sexually active. "Pheromones make them alert," said Li. "Signals are sent back to the eyes." The retinal cells themselves have circadian controls in them, but the brain, via efferent pathways, also controls day and night variation. These circadian 'clocks' may decrease visual sensitivity at the times when vision is not required, Li says. A growing body of work investigates the existence of similar mechanisms elsewhere in the animal kingdom. Work at Harvard University by professor John Dowling has shown that efferent pathways are present in birds. But there are few efferent fibers linking to the retina in mammals, says Dowling, persuading him that the mechanism does not extend that far. "I don't believe that they play an important role in mammals," he said. It is a view that fails to meet with the approval of David Marshak, professor of neurobiology and anatomy at the University of Texas. Marshak wonders what discourages researchers from working on mammals. Fewer efferent neurons in mammals does not indicate less control, he says, because each neuron has an effect on a larger area of the retina. Marshak has studied the phenomenon in monkeys, and his data reveal that there are efferent fibers, containing the neurotransmitter histamine, that link the hypothalamus to the retina. When he applies histamine to these fibers, the activity of retinal neurons is affected. He suggests that the histaminergic neurons adapt the retina for the time of day, because the histamine appears to cause the retinal cells to be less sensitive to light. Marshak hypothesizes that changes in the histaminergic centrifugal axons may affect the development of diabetic retinopathy. Other efferent pathways with different neurotransmitters may also play important roles in retinal control, he predicts. Indeed, some such pathways have been observed, such as a serotoninergic pathway from the brain's raphe nucleus to the retina, which was found in mice by Dom Miceli at the University of Quebec. "The system is there for sure," said Miceli, although he has yet to establish its function. Miceli's studies of efferent pathways in birds have been more rewarding. From these experiments, he says, it is clear that the brain differentiates between stimuli, processing some before others. Data like these surprise Robert Barlow, professor of ophthalmology and neuroscience at Upstate Medical University in Syracuse, New York. Barlow began studying brain-regulated circadian rhythms in the horseshoe crab in the 1980s. He discovered that the crab's retinal sensitivity increases up to a million times at night to compensate for lower light intensity, a feat accomplished by around ten thousand efferent nerve fibers in the brain, which synapse on the retina. "Somehow the brain is taking information from the outside world, sending information to the eye and making it more sensitive," said Barlow. "The nervous system decides what to emphasize and what not to emphasize - that intrigues me."   Optic ataxia as a deficit specific to the on-line control of actions Neuroscience and Biobehavioral Reviews     Scott Glover August 2003 Abstract Optic ataxia is characterized by inaccuracies in body movements under visual control, and is a common consequence of damage to the posterior parietal lobes in humans. It is argued here that optic ataxia can be characterized as a deficit in the visual on-line guidance of actions, with action planning remaining relatively intact. This contrasts with the common view of optic ataxia as representing a deficit in the transformations that take place between visual inputs and motor outputs. Evidence in support of the planning-control view comes from the pattern of spared and disrupted behaviors in patients with optic ataxia. It is shown that spared behaviors are those that emphasize planning, whereas disrupted behaviors are those that emphasize control. In particular, recent studies have highlighted the inability of a patient with optic ataxia to make on-line adjustments to targets that change position during the movement. Taken in sum, the data from patients with optic ataxia is more consistent with the planning-control interpretation of optic ataxia than with the visuomotor transformation interpretation. Electrophysiological correlates of purely temporal figure–ground segregation Farid I. Kandil and Manfred Fahle Vision Research, 2003, 43:24:2583-2589 Abstract Inhomogenous displays, in contrast to homogenous ones, evoke a specific potential in the VEP (tsVEP) which appears across different classical visual stimulus dimensions defining figure–ground segregation, such as luminance, orientation, (first-order) motion, and stereoscopic depth. This negative potential has a peak latency of about 200–300 ms and a peak amplitude of about -3 to -10 µV [Doc. Ophthalmol. 95 (1998) 335]. Previously, we demonstrated that human subjects reliably segregate figure from ground, even in the absence of the classical cues, leaving time of change as the only cue for segregation. The results of the present study demonstrate that also purely temporally defined checkerboards evoke a tsVEP resembling the motion-defined tsVEP regarding polarity (negative), latency (two peaks at 180 and 270 ms, respectively), amplitude of the first negativity (-5.6 µV), and overall form of its components. Visual categorization and the inferior temporal cortex Natasha Sigala Behavioural Brain Research     September 2003 Abstract We investigated the effects of categorization on the representation of stimulus features in combined psychophysical–electrophysiological experiments. We used parameterized line drawings of faces and fish as stimuli, and we varied the relevance of the different features for the categorization task. The psychophysical and electrophysiological data support an exemplar-based framework for visual object recognition. We recorded from visual neurons in the anterior inferior temporal (IT) cortex of macaque monkeys, while they were performing a categorization task. The visual neurons did not respond selectively to one stimulus set, or to one category. The majority of the anterior IT feature selective neurons were tuned for features that were diagnostic for the categorization task. We argue that this fine-tuning of the neurons reflects the perceptual sensitization to the diagnostic features.

Clinical research on treating senile dementia by combining acupuncture with acupoint-injection by Chen Y. Acupuncture and Electro-Therapeutics Research, 1992, 17(2):61-73. (UI: 92351825) UCLA Biomed W1 AC999T Abstract: Combining acupuncture with acupoint-injection of aceglutamidi has been used in treating 38 cases of senile dementia. Our experiment showed that the therapy is effective for the cases of multi-infarct dementia, the rate of success being 42.85% and of improvement 42.865, the total efficacy rate being 85.71%. The rating was based on the revised Hasegawa Dementia Scale and the Functional Activity Questionnaire. In addition, it has been observed that the component of high density lipid-cholesterone increased significantly after treatment. Composite acupuncture treatment of mental retardation in children. Journal of Traditional Chinese Medicine, 1995 Mar, 15(1):34-7. (UI: 95302779) Pub type: Clinical Trial; Joural Article; Randoized Controlled Trial. Abstract: 128 children of mental retardation were diagnosed in accordance with the diagnostic standards proposed by WHO in 1985. The patients were treated compositely with acupuncture, auriculo-acupoint pellet pressure and herbal plasters on acupoints, bringing about improved mental developments in intelligence quotient (IQ) and social adaptation behaviour (SAB), as evidenced by recognized intelligence tests for children.   Effect of acupuncture on intestinal motion and sero-enzyme activity in perioperation Chung Hsi i Chieh Ho Tsa Chih Chinese Journal of Modern Developments in Traditional Medicine, Abstract: The authors study on abdominal surgical patients (39 cases) who were randomly divided into the acupuncture and control group. In the acupuncture group, the needle inserted into Zusanli (St.36) and Sanyinjiao (Sp. 6) points at 12-24 h after operation and observed the time of the first excretion through anus. Sero-enzyme activity of GPT, GOT and gamma-GT determined before operation and at 1, 3, 5, 7 days after operation. The results showed that the time of excretion in the acupuncture group (57.78 +/- 23.94 h) was obviously faster than the control one (86.14 +/- 20.43 h), P less than 0.001). It suggested that acupuncture has the effect of promoting intestinal motion. After operation sero-enzyme activity was raised 2-3 times than before. It showed that the surgical trauma directly or indirectly impair cells to release enzyme into blood, but the time of reversing to normal level of sero-enzyme activity in the acupuncture group was obviously faster. There is possibility that acupuncture has the effect of regulating reactivity of organism on trauma and promoting the repair of damaged cell. Traditional Chinese Medicine and Pulse Diagnosis In San Francisco Health Planning: Implications For a Pacific Rim City by Richard Kass University of California, Berkeley Copyright, (c) April 1990 Abstract The purpose of this dissertation was twofold: 1) to provide background material on the Asian American culture and dual health care system in San Francisco; 2) to examine how Traditional Chinese pulse diagnosis (a renowned ancient diagnostic technique) can be used to help integrate the dual health care system in San Francisco. The overarching vision for the project is a culturally responsive health care system in San Francisco which effectively controls the spread of chronic disease. Data collection was carried out at On Lok Senior Health Services in San Francisco. Ten subjects were examined by two Traditional Chinese physicians; one using a Traditional hand palpation method and the other using a computer assisted pulse detection device. The physicians examined the pulse of the same 10 subjects and attempted to: 1) obtain the same pulse readings on a given subject (a test of the reliability of pulse diagnosis); 2) match subjects with their corresponding medical files on the basis of pulse analysis alone (a test of the validity of pulse diagnosis). Three precautions against experimenter bias were observed: 1) the subjects sat behind a screen with only the diagnostically relevant area of their wrists visible to the two physicians (a special glove was worn); 2) no contact was allowed between the two examining physicians at any time during the study; 3) the pulse examination schedule was altered in the middle of the day in order to avoid any detectable patterns. In the general and individual pulse assessment sections the physicians achieved a significant p<.0001 reliability finding. 463 matches out of a possible 660 matches (70%) were achieved in the individual pulse section (p< .0001 for 463 or more matches). Other findings suggested that there may be some validity to Traditional Chinese pulse diagnosis; one of the physicians was able to achieve a significant result (p<.047) for six correct subject/medical file matches when 1st, 2nd, & 3rd choices were taken into account. However, this conclusion must be tempered in light of a serious methodological problem which may have influenced the results. Traditional Chinese physicians use palpation to differentiate 31 pulse patterns at 18 positions on the right and left wrists. This delicate technique reportedly provides: 1. A genuine early diagnosis of functional disorders which, if left untreated, eventually will produce degenerative or malignant organic changes; 2. The specific and comprehensive, all-inclusive determination of all factors having a bearing on complex pathological processes (at the roots of chronic or constitutional diseases); 3. Specific and comprehensive and direct appreciation of the immediate effects of any applied drug or therapeutic measure or agent (indispensable for the immediate follow-up of any therapeutic measure, as well as in the assaying of new drugs). (Porkert, 1983). Traditional Chinese pulse diagnosis is the single most important technique in Traditional Chinese medical diagnosis (Broffman & McCulloch, 1986). One problem with Traditional Chinese pulse diagnosis in the United Sates is that it tends to be unreliable; rarely will two physicians come up with identical pulse assessments for a given patient. This circumstance has: 1) discouraged physicians from performing comprehensive pulse examinations on their patients jeopardizing treatment success); 2) increased skepticism toward Traditional Chinese medicine (pulse diagnosis and other aspects of Traditional Chinese medicine are suspected of being invalid); 3) been a barrier to the scholarly investigation of Traditional Chinese medicine (clinical trials which are not based on accurate and comprehensive pulse diagnoses are inconclusive). Advocates of Traditional pulse diagnosis contend that the problem lies in the application of the technique and not with the technique itself. They argue that: 1) pulse diagnosis is extremely difficult to learn (few physicians have the tactile acuity to detect subtle variations at three levels of palpation pressure); 2) few physicians are willing to devote the necessary time to master the technique (5-10 years of supervision is often needed). Several electronic devices have been developed which reportedly achieve more accurate measurements of energy at acupuncture points and meridians as well as make such technology more accessible to physicians (Laub, 1983; Lee, & Wei, 1983; Broffman & McCulloch, 1986; Tiller, 1982). These devices and their associated techniques have not become an accepted part of conventional medicine for three major reasons: l) the techniques are often unreliable (Kenyon, 1984); 2) no body of scholarly research exists demonstrating their effectiveness; 3) the metaphysical theory upon which these devices are based is untenable to most Western health professionals. Although several recent studies have supported the efficacy of this technology (Tsuei, Lehman, Lam, & Zhu, 1984; Sullivan, Eggleston, Martinoff, & Kroening, 1984), none have appeared in major medical journals. An evaluation of both traditional and electronic pulse-taking techniques was undertaken in this dissertation research. The aim was to: 1) assess the validity of Traditional Chinese pulse diagnosis; 2) determine if electronic devices can be used to increase the accessibility (with respect to requisite training) of this diagnostic method; 3) assess whether Traditional Chinese pulse diagnosis can be used to help integrate the dual health care system in San Francisco. Significant positive results would place Traditional Chinese medicine on a stronger scientific footing and suggest a greater role for Traditional Chinese medicine in the orthodox medical system in San Francisco. Investigation of Traditional Chinese Pulse Diagnosis Subjects Ten subjects from On Lok Senior Health Services in San Francisco participated in this study of Traditional Chinese pulse diagnosis. These subjects were recruited on the basis of the contents of their medical file at this center; a medical file was considered appropriate for the study if it: 1) did not contain references to physical or physiological conditions at the pulse examination area that might constitute a confounding variable; 2) did refer to such conditions at the pulse examination, but these conditions could be controlled for. Of particular concern was any medical file reference (direct or indirect) to: pulse beat abnormalities, the consistency of the radial artery (e.g.; hypertension), the physical condition of the area surrounding the wrist area (e.g.; an overweight individual has fatter wrists), abnormal shaking at the wrist area (e.g.; some manifestations of Parkinson's Disease), the sex of an individual (e.g.; women generally have smaller wrist bones). The aim was to eliminate or obscure unfair clues that could positively influence the physicians' attempt to correctly match anonymous medical files with subjects on the basis of pulse analysis alone. The following selection criteria were ultimately used to select the subjects: all subjects were female; 1. age and weight differences between subjects were minimized (the mean age was 80.5 years old); 2. no subject suffered from skin problems at the wrist area; 3. all subjects had a history of hypertension; 4. all subjects were free of pulse beat abnormalities, 5. all subjects were free of shaking syndromes at the wrist area; 6. each subject suffered from a unique set of disease conditions (so as to enable the physicians to distinguish one subject from another); 7. all subjects were Asian Americans. Materials and Equipment Medical files at On Lok Senior Health Services in San Francisco (see Appendix E) contain comprehensive medical information on every client who visits the center. These files are updated regularly (usually on a daily basis) and are considered an accurate and comprehensive account of what disease conditions plague On Lok clients at any given time. The files were used in this investigation to verify the health condition of each subject at the time of his/her pulse examination. The following bits of information were deleted from each file in order to avoid any confounding variables: name, age, height, weight, pulse rate, and blood pressure information. An electronic pulse-taking device developed by Dr. Laub (1983), working in conjunction with Dr. Broffman and Dr. McCulloch (1986) was used by one of the two Traditional Chinese. physicians taking part in the study. This device detects radial artery pulse signals at the same 18 positions palpated by Chinese physicians thousands of years ago. Pulse images are digitized by the device and written to disk as a computer file. Each image can then be printed out (see Appendix D), matched with one of the 31 recognized pulse patterns in Traditional Chinese medicine (Porkert, 1983), and used for diagnostic purposes. General Pulse Section The first section (general pulse section) assesses the radial artery pulse as it appears at three spatial locations (inch, gate, and foot) and three depth locations (superficial, middle, and deep) in the left and right wrist area. This assessment is general in nature and does not separate out unique characteristics of the pulse at the various spatial and depth locations. A total of eleven pulse categories are considered in this section. Each category is associated with two qualitative dimensions: 1) depth: floating or deep (a floating pulse is found in the upper region of a pulse position while a deep pulse is found in the bottom region); 2) intensity: strong or weak (a strong pulse refers to a forceful beat while a weak pulse refers to a delicate beat); 3) amplitude: big or small (a big pulse refers to a large stroke while a small pulse refers to a short stroke); 4) frequency: fast or slow (a fast pulse refers to frequent beats while a slow pulse refers to infrequent beats); 5) rhythm: rhythmic or arrhythmic (a rhythmic pulse refers to uniform cycles of the pulse while an arrhythmic pulse refers to irregular cycles); 6) length: long or short (a long pulse has a wide base while a short pulse has a thin base); 7) type: yang or yin (a yang pulse is characterized by an expanded pulse while a yin pulse is characterized by a deflated pulse); 8) temperature: hot or cold (a hot pulse is associated with an energetic pulse rate while a cold pulse is associated with a lethargic pulse rate); 9) quantity: shih or cold (a shih pulse contains a large amount of energy while a cold pulse contains a small amount of energy); 10) texture: hard or soft (a hard pulse is characterized by a pointed top while a soft pulse is characterized by a round top); 11) width: wide or thin (a wide pulse has a large peak while a thin pulse has a narrow peak). Sub Pulse Type Section Section two (sub pulse section) provides for a more detailed analysis of four of the eleven pulse categories in section one (depth, intensity, amplitude, and frequency). Depending on what decisions were made in this prior section, each physician chooses from among the pertinent "Sub 1" and "Sub 2" qualitative dimensions described below: 1) For floating pulses: simple, flooding, or none (sub 1) and soft, bowstring hollow, leathery, or none (sub 2) 2) For deep pulses: simple, hidden, or none (sub 1) and weak, prison, or none (sub 2) 3) For either strong or weak pulses: full, feeble, thready, or none (sub 1) and slippery or none (sub 2) 4) For either big or small pulses: long, short, or none (sub 1) 5) For slow pulses: simple or none (sub 1) and knotted or none (sub 2) For fast pulses: simple or none (sub 1) and rapid, agitated, or none (sub 2) Individual Pulse Section The third section of Pulse Assessment Form A (individual pulse section) describes the pulse as it is found at each of the three spatial locations (inch, gate, and foot) at the left and right wrist area. The same eleven pulse categories are used to analyze these six spatial locations. The various depth location findings (superficial, middle, and deep) at each spatial location are taken into account in this assessment: 1) depth: floating or deep; 2) intensity: strong or weak; 3) amplitude: big or small; 4) frequency: fast or slow; 5) rhythm: rhythmic or arrhythmic; 6) length: long or short; 7) type: yang or yin; 8) temperature: hot or cold; 9) quantity: shih or cold; 10) texture: hard or soft; 11) width: wide or thin Procedure In August of 1988 data collection for the pulse analysis component of the study was completed at On Lok Senior Health Services in San Francisco. Ten subjects were examined by two Traditional Chinese physicians; one using the Traditional hand palpation method and the other using a computer assisted electronic device. The two Traditional Chinese physicians were selected on the basis of their extensive experience using this form of diagnosis and the fact that one of them (Dr. McCulloch) used an electronic method of pulse diagnosis (Broffman & McCulloch, 1986). The two physicians examined the pulse of the same 10 subjects and attempted to: 1) obtain the same pulse readings on a given subject (a test of the reliability of pulse diagnosis); 2) correctly match subjects with their corresponding medical files on the basis of pulse analysis alone (a test of the validity of pulse diagnosis). The two Traditional Chinese physicians administered their respective pulse examinations over the course of a single day in a specially prepared room at On Lok Senior Health Services. Three precautions against experimenter bias were observed: 1) the subjects sat behind a screen with only the diagnostically relevant area of their wrists visible to the two physicians (a special glove was worn) 2) no contact was allowed between the two examining physicians at any time during the study; 3) the pulse examination schedule was altered in the middle of the day in order to avoid any detectable patterns. All pulse examinations were timed by the research assistant. The matching of the ten medical files to the two sets of pulse profiles (one traditional set and one electronic set) occurred after all pulse examinations had been completed. The physicians were given as much time as needed to fill in the two assessment forms, and were allowed to consult any resource materials. The assessment process took each physician approximately two hours. Data Analysis Reliability of Pulse Diagnosis The following hypotheses were constructed to test the extent of correlation (reliability) between Traditional pulse readings and electronic pulse readings: H(0) = matches between Traditional pulse readings and electronic pulse readings are the result of chance alone; there is no evidence to suggest that Traditional Chinese pulse-taking is reliable. H(1) = matches between Traditional pulse readings and electronic pulse readings are not the result of chance alone; there is evidence to suggest that Traditional Chinese pulse-taking is reliable. An exact correspondence between how Dr. Broffman evaluated a given pulse category for a given subject and how Dr. McCulloch evaluated the same category was considered a match in all three sections of Assessment Form A. The normal approximation to the binomial (Parzen, 1960, p. 239) was employed to determine whether the results obtained (or more extreme results) were better than chance alone would normally produce. The probability of at least x matches is the sum of the binomial probabilities [x + (x + 1) + (x + 2) ...] which can be approximated by a normal distribution. A probability value of <.05 was considered significant. The percentage of correct matches in all three sections were calculated as an additional way to assess the reliability of the two methods of pulse analysis. The results for the three sections were as follows: 87 matches of a possible 110 matches, 24 (79% of possible matches) were achieved in the general pulse assessment section. The probability of this result or more extreme results occurring by chance alone is p< .0001. In the sub pulse section: 4 out of 5 possible matches (80% of possible matches) were achieved in the depth/sub 1 category (p=.023 for 4 or more matches); 1 out of 4 possible matches (25% of possible matches) were achieved in the depth/sub 2 category (p=.52 for 1 or more matches); 2 out of 7 possible matches (29% of possible matches) were achieved in the intensity/sub 1 category (p=.56 for two or more matches); 1 out of 2 possible matches (50% of possible matches) were achieved in the intensity/sub 2 category (p=.75 for one or more matches); 2 out of 7 possible matches (29% of possible matches) were achieved in the amplitude/sub 1 category (p=.74 for two or more matches), 7 out of 7 possible matches (100% of possible matches) were achieved in the frequency/sub 1 category (p=.0078), and 7 out of 7 possible matches (100% of possible matches) were achieved in the frequency/sub 2 category (p=.0002). 463 matches out of a possible 660 matches (70%) were achieved in the individual pulse section (p< .0001 for 463 or more matches). Validity of Pulse Diagnosis Western medical theory contends that palpation of the radial artery pulse at the right and left wrist areas can not reveal diagnostic information about the stomach, lungs, pancreas, gall bladder, etc. as claimed by Traditional Chinese physicians. The following hypotheses were constructed to test this contention: H0 = correct matches between medical files and pulse profiles are the result of chance alone; there is no evidence to suggest that Traditional Chinese diagnosis is valid. H1 = correct matches between medical files and pulse profiles are not the result of chance alone; there is evidence to suggest that Traditional Chinese diagnosis is valid. Pulse/medical file matching results were considered significant in this study if the probability of occurrence by chance alone was <.05. The results were as follows: Dr. Broffman used the hand palpation method to achieve two correct 1st choices (p= .264 for two or more 1st choice matches to occur by chance alone), one correct 2nd choice (p= .322 for three or more 1st & 2nd choice matches to occur by chance alone), and three correct 3rd choices (p=.047 for six or more 1st, 2nd, & 3rd choices to occur by chance alone). Dr. McCulloch used a computer assisted electronic device to achieve two correct 1st choices (p= .264 for two or more 1st choice matches to occur by chance alone). Discussion Introduction Several methodological approaches were considered in this investigation of Traditional Chinese pulse diagnosis; a design in which: 1) both Traditional Chinese physicians used hand palpation methods; 2) both Traditional Chinese physicians used electronic pulse detection methods; 3) one physician used the hand palpation method and the other used the electronic pulse detection method. The first two alternatives were rejected in favor of the third for two major reasons: 1) testing an electronic device was an essential part of this research 25 2) only one experienced electronic device operator was available in the San Francisco Bay area. It should be noted that the results achieved for the chosen approach (palpation/electronic) do not necessarily suggest what levels of validity and reliability would have been achieved had one of the other two approaches mentioned above (palpation/palpation; electronic/electronic) been used in the study. In other words, a low reliability finding in this investigation would not rule out the possibility that a high level of reliability could have been achieved if the electronic/electronic approach had been used. Lack of reliability in this investigation could be explained in any of the following eight ways: 1) electronic assessments of the pulse are accurate but hand palpation assessments are not as a consequence of improper palpation technique; 2) electronic assessments of the pulse are accurate but hand palpation assessments are not as a consequence of faulty interpretation of pulse findings; 3) hand palpation assessments of the pulse are accurate but electronic assessments are not as a consequence of improper sensor placement; 4) hand palpation assessments of the pulse are accurate but electronic assessments are not as a consequence of faulty equipment; 5) hand palpation assessments of the pulse are accurate but electronic assessments are not as a consequence of faulty interpretation of pulse findings; 6) both electronic and hand palpation assessments are inaccurate as a consequence of improper measurement techniques; 7) both electronic and hand palpation assessments are inaccurate as a consequence of faulty interpretation of pulse findings; 8) both electronic and hand palpation assessments are inaccurate as a consequence of pulse diagnosis being nothing more than an artifact; A high level of reliability in the chosen palpation/electronic approach, however, does suggest that a high level of reliability would have been achieved if the electronic/electronic approach had been used. Significant Results In both the first section (general pulse) and third section (individual pulse) of Pulse Assessment Form A the physicians achieved a significant p<.OO01 result (79% and 70% of possible matches respectively). These sections dealt with: depth, intensity, amplitude, frequency, rhythm, length, type, temperature, quantity, texture, and width measurements of the pulse. In section two (sub pulse section) a significant p=.023 result (80% of possible matches) was obtained in the depth/sub 1 pulse category; a significant p=.0078 result (100% of possible matches) was obtained in the frequency/sub 1 pulse category; and a significant p=.0002 result (100% of possible matches) was obtained in the frequency/sub 2 pulse category. No significant findings were obtained in the remaining four categories (depth/sub 2, intensity/sub 1, intensity/sub 2, amplitude/sub 1), which represented 25%, 29%, 50%, and 29% of possible matches respectively. The above findings suggest that pulse diagnosis reliability goes down as more subtle levels of distinction are attempted. Other results suggest that there may be some validity to Traditional Chinese pulse diagnosis; in the pulse/medical file matching effort Dr. Broffman was able to achieve a statistically significant result (p<.047) for six or more correct 1st, 2nd, & 3rd choices. However, this conclusion must be tempered in light of the fact that a methodological problem was encountered which may have influenced the results. One subject with Alzheimer's Dementia behaved in a way that may have confounded the results of the subject/medical file matching effort. This subject was observed to "mumble to herself" (suggesting a mental condition) and forcefully wiggle her arms (suggesting resistance) on numerous occasions during the examination process. These two bits of information could have been used as additional clues in the matching selections made by the two physicians (a person with a mental condition such as Alzheimer's Dementia would be more likely to mumble and/or be resistant to the examination procedure than a person without this condition). It must be pointed out that although this additional information was available to the two physicians, there is no evidence that they took the information into account in their selection process. The fact that both Dr. Broffman and Dr. McCulloch achieved correct 1st choice matches on this subject could be purely coincidental and have nothing to do with a confounding variable. A second analysis was made in which the subject in question was not factored into the results. The highest probability under these circumstances was p<.l5. It also questionable whether the use of second and third choice selections in the determination of statistical significance is a viable methodological approach. The fact that a statistically significant result was obtained only after second and third choice selections were taken into account may indicate an inherent lack of precision in Traditional Chinese pulse diagnosis that limits its clinical usefulness. An alternative explanation links this seeming diagnostic imprecision to incomplete symptom recording in On Lok medical files rather than any inherent weakness in Traditional Chinese pulse diagnosis. Often symptoms that are useless from a Western medical point of view can be the key that unlocks a diagnosis in Traditional Chinese medicine. For example, chronic canker sores helps in the diagnosis of a heart condition in Traditional Chinese medicine. Minor symptoms such as this could very well be left out of Western oriented On Lok medical files; thus putting the Traditional Chinese physicians at a distinct disadvantage in their matching efforts. If more minor symptoms had been recorded in On Lok medical files the two physicians may have achieved better results. (Note: A one out of three correct rate is not deemed acceptable by most physicians (Western as well as alternative practitioners) and patients, suggesting that only first choice selections should be included in a test of pulse diagnosis validity.) The physicians may also have fared better if they been Western-trained physicians in addition to being experts in Traditional Chinese medicine. Neither their prior training nor currently available resource books afforded them much help in accurately translating Western disease conditions into Traditional Chinese nomenclature; a process which was vital to the achievement of good results. The fact that the physicians did not have extensive experience diagnosing very old individuals (the mean age of the subjects was 80.5) who suffered from so many acute and chronic disease conditions may have been another impediment to their success. It also should be noted that Traditional Chinese physicians typically cross-check pulse diagnosis findings with other physical indicators in the body such as the tongue. When contradictory findings are found at any of these other sites the pulse profile is reexamined and any errors are corrected. This recovery process could render Traditional Chinese pulse diagnosis a useful diagnostic method even if the technique and/or its implementation is less than perfect. Had the physicians been allowed to look at each patient's tongue as well as examine her pulse they may have achieved better results. Conclusion More investigation of Traditional Chinese pulse diagnosis is needed before any definitive statement can be made about the reliability and validity associated with its use. Although the results of this preliminary investigation suggest that there may be some scientific basis for this ancient technique, its reliability needs to be substantially improved in key areas of the diagnostic process. As discussed earlier, it is unclear whether low reliability findings in this study are the result of operator error, faulty equipment, or improper interpretation of pulse findings. One of the key findings in this investigation was that the complex nature of traditional hand palpation virtually rules out its effective use by Western physicians in San Francisco; accurate pulse assessments by individuals who have only a superficial training in Traditional Chinese diagnostic techniques is not a realistic objective. The electronic pulse-taking device, however, does appear to hold great promise even though it did not successfully demonstrate its diagnostic capabilities in the test of pulse diagnosis validity. The positive results achieved in the general and individual sections of Pulse Assessment Form A (the test of reliability) suggest that further refinements in this technique could eventually lead to an effective and easy to use tool for pulse diagnosis in a more integrated dual health care system in San Francisco. Although pulse diagnosis basics (i.e.; hard versus soft pulse) can be learned in a relatively short period of time, the detection and interpretation of more subtle pulse forms are needed in order to perform an accurate and comprehensive diagnosis. The fact that that the electronic device is interfaced with a PC computer holds open the possibility that a partially or completely automated system of interpreting pulse patterns (according to the thirty recognized wave forms in Traditional Chinese medicine) c