3-d source localization of epileptic foci integrating EEG and MRI data.


A new approach in clinical neuropsychology to the assessment of spatial working memory

Access to secondary care for people with learning disabilities.

Amygdalar interhemispheric functional connectivity differs between the non-depressed and depressed human brain.

An investigation of sex differences in nonpsychiatric morbidity associated with PTSD.

Analyzing EEG signals using the probability estimating guarded neural classifier.

Anterior prefrontal cortex

Attention Deficit Hyperactivity Disorder in children Following Traumatic Brain Injury.

Autism and pervasive developmental disorders.

Autism as early expression of catatonia.

Auditory integration training and other sound therapies for autism spectrum disorders.

Calpain 10 gene polymorphisms and the risk of ischaemic stroke in a Polish population.

Childhood Head Injury and Metacognitive Processes in Language and Memory.

Chronicity in PTSD and predictors of the course of PTSD among primary care patients.

Clinical characteristics of magnetic resonance imaging-defined subcortical ischemic depression.

Clinical correlates of episodicity in juvenile mania.

Coupling of theta activity and glucose metabolism in the human rostral anterior cingulate cortex


Cocaine revisited.

Cognitive executive dysfunction in children with mild sleep-disordered breathing.

Cost-effectiveness of cognitive behaviour therapy for patients with CFS.

Creative innovation

Deep brain stimulation in treatment refractory OCD.

Depression as a communicable disorder.

Dichotic listening in children with focal epilepsy

Differentiating between memory and interpretation biases in socially anxious and nonanxious individuals.

Diffusion-Weighted Magnetic Resonance Imaging and Neurobiochemical Markers After Aortic Valve Replacement. Implications for Future Neuroprotective Trials?

Discourse Macrolevel Processing After Severe Pediatric Traumatic Brain Injury.

Do we still believe in the dopamine hypothesis? New data bring new evidence.

Drug and alcohol use among patients with schizophrenia and related psychoses

Dual diagnosis

Dysautonomia in CFS

Ecological Assessment of Executive Function in Traumatic Brain Injury.

Ectopic expression of the catalytic subunit of telomerase protects against brain injury resulting from ischemia and NMDA-induced neurotoxicity.

EEG changes induced by a noise generator in tinnitus patients and healthy controls.

EEG power and coherence analyses suggest altered brain function in abstinent male heroin-dependent patients.

Electrical neuroimaging based on biophysical constraints.

Emotional functioning in anorexia nervosa patients

Enabling computer decisions based on EEG input.

Evaluation of different measures of functional connectivity using a neural mass model.

Event-related functional magnetic resonance imaging of reward-related brain circuitry in children.

Executive control emerging from dynamic interactions between brain systems mediating language, working memory and attentional processes.

Excess mortality in remote symptomatic epilepsy.

Five years after traumatic brain injury

Functional neuroimaging of primary headache disorders.

Gender and age effects on outcome after pediatric traumatic brain injury.

Gender differences in the cortical EEG processing of visual emotional stimuli.

Generalized anxiety disorder and major depressive disorder comorbidity

Genetics of OCDs

Genome-wide screen for heavy alcohol consumption.

Grammaticality sensitivity in children with early focal brain injury and children with specific language impairment.

How well do measures of inhibition and other executive functions discriminate between children with ADHD and controls?

Hyperbaric Oxygen Therapy for the Treatment of Acute Cochlear Disorders and Tinnitus.

Hypothalamic hamartoma and epilepsy in children

Investigations of the human visual system using functional magnetic resonance imaging (FMRI).

Increased diaphragmatic strength and tolerance to fatigue after bilateral lung transplantation

Inspiratory flow limitation in obstructive sleep apnea patients.

Ketogenic diet, brain glutamate metabolism and seizure control.

Language development in children at risk for language impairment

Learning in children and sleep disordered breathing

Long-term survival after traumatic brain injury

Mania in six preschool children.

Mapping brain size and cortical gray matter changes in elderly depression.

Masculine Gender Role Stress


Matching the bipolar patient and the mood stabilizer.

Modeling of Longitudinal Academic Achievement Scores After Pediatric Traumatic Brain Injury.

Mood disturbances and regional cerebral metabolic abnormalities in recently abstinent methamphetamine abusers.


Moods in everyday situations; Effects of menstrual cycle, work, and personality.

Mortality following rehabilitation in the Traumatic Brain Injury Model Systems of Care.

Music, language and meaning

Non-invasive detection of ketosis and its application in refractory epilepsy.

Nonlinear and linear EEG complexity changes caused by gustatory stimuli in anorexia nervosa.

Neurobiology of Tourette's syndrome

Neurophysiology of Tourette's syndrome


New anticonvulsant medication uses in bipolar disorder.

Pharmacologic treatment of PTSD

Positron emission tomography in epileptogenic hypothalamic hamartomas.

Pediatric neurotransmitter diseases.

Premenstrual dysphoric disorder and psychiatric co-morbidity.

Prevalence of chronic pain and its impact on health-related quality of life in stroke survivors.

Productive use of the English past tense in children with focal brain injury and specific language impairment.

Prize reinforcement contingency management for treating cocaine users

Prospective Memory in Pediatric Traumatic Brain Injury

PTSD among patients with chronic pain and chronic fatigue.

Psychosocial issues for spouses of brain injury survivors.

Psychiatric aspects of patients with hypothalamic hamartoma and epilepsy.

Randomized controlled trial of Siberian ginseng for chronic fatigue.

Repetitive transcranial magnetic stimulation as treatment of poststroke depression

Research on Outcomes of Pediatric Traumatic Brain Injury

Resting EEG in offspring of male alcoholics

Right hemispheric dysfunction in a case of pure progressive aphemia

Secondary mechanisms in traumatic brain injury

Spatiotemporal brain dynamics during preparatory set shifting

Stress and dopamine

Suppression of complex visual hallucinatory experiences by occipital transcranial magnetic stimulation

Temporal organization of the brain

Temporal stability of high-frequency brain oscillations in the human EEG.

The "Mozart effect": an EEG analysis

The protective influence of spirituality and Health-as-a-Value against monthly substance use among adolescents varying in risk.

The psychological effects of traumatic brain injury on the quality of life of a group of spouses/partners.

Tinnitus as a prognostic sign in idiopathic sudden sensorineural hearing loss.

To err is autonomic

Treatment of panic disorder with agoraphobia in an anxiety disorders clinic

The role of EEGs in the treatment and prognosis of epilepsy.

Thiamine for Wernicke-Korsakoff Syndrome in people at risk from alcohol abuse.

Thought disorder and nucleus accumbens in childhood

Transcallosal resection of hypothalamic hamartomas in patients with intractable epilepsy.

Use and abuse of opioid analgesics

Virtual keyboardcontrolled by spontaneous EEG activity.

Visual p300 effects beyond symptoms in concussed college athletes.

Young adult follow-up of hyperactive children


Added 3/16/2004 ============================================================


Alcohol abuse and traumatic brain injury

CFS in Adolescents

Correlation of Quantitative EEG in Acute Ischemic Stroke With 30-Day NIHSS Score. Comparison With Diffusion and Perfusion MRI.

Coupling of radial-basis network and active contour model for multispectral brain MRI segmentation.

Drinking restraint, alcohol consumption and alcohol dependence among children of alcoholics.

Estimation of nonstationary EEG with Kalman smoother approach

Extensive medial frontal lobe damage on 'Theory of Mind' and cognition.
Patient GT (bilateral anterior cerebral artery infarction, without complications) acquired dysexecutive syndrome (poor planning and memory, tendency to confabulate) but was unimpaired in Theory of Mind.

Fluctuation of waking electroencephalogram and subjective alertness during a 25-hour sleep-deprivation episode in young and middle-aged subjects.

Functional neuroimaging of social cognition in pervasive developmental disorders


Here's Looking at You, Kid

Hippocampal and hypothalamic function after chronic stress.

Human brain wave activity during exposure to radiofrequency field emissions from mobile phones.

Hyperactivity in anorexia nervosa

Impulsivity, emotion regulation, and developmental psychopathology

Investigation of neuroanatomical differences between autism and asperger syndrome.

Is physical illness a risk factor for eating disorders in children?; A preliminary investigation.

Is there a specific polysomnographic sleep pattern in children with ADHD?

Methylphenidate treatment of ADHD secondary to traumatic brain injury

MRI of amygdala and other subcortical brain regions in adolescents with bipolar disorder.

Neural substrates underlying impulsivity.

Neuroanatomic variation in monozygotic twin pairs discordant for the narrow phenotype for autism.

Neurogenesis and neuroadaptation.

Neurometabolic functioning and neuropsychological correlates in children with ADHD-H

Nonhuman primate models to study anxiety, emotion regulation, and psychopathology.

Panic attack symptoms in a patient with left temporal lobe epilepsy.

Prefrontal responses to drug cues

Psychoactive substance consumption in eating disorders.

Psychological, nutritional, and energy expenditure differences in college females with anorexia nervosa vs. comparable-mass controls.

Quantitative EEG in Acute Ischemic Stroke With 30-Day NIHSS Score. Comparison With Diffusion and Perfusion MRI.

Rehabilitation following acquired brain injury

Recent advances in the neurobiology of schizophrenia.

Repetitive transcranial magnetic stimulation of the right dorsolateral prefrontal cortex in PTSD

Resource utilisation for neuropsychiatric disorders in developing countries

Response inhibition and disruptive behaviors

Riding out the storm

Rehabilitation following acquired brain injury

Selective Metabolic Reduction in Gray Matter Acutely following Human Traumatic Brain Injury.

Sex differences and hormonal effects in a model of preterm infant brain injury.

Structural effects and neurofunctional sequelae of developmental exposure to psychotherapeutic drugs

The consequences of uncontrolled epilepsy.

The effects of movement, relaxation, and education on the stress levels of women with subclinical levels of bulimia.

The effect of unilateral somatosensory stimulation on hemispheric asymmetries during slow wave sleep.

The nature of arousal in sleep.



B O O K N E W S_________________________________________

Cognitive Electrophysiology of Mind and Brain
by Alberto Zani, Alice Proverbio
Reviews developments in recording of bioelectric and magnetic responses of the brain.
More info:

Anxiety and Its Disorders, 2nd Ed: The Nature and Treatment of Anxiety and Panic
by David H. Barlow
Model of panic and anxiety based on recent developments in emotion theory, cognitive science, and neuroscience.
More info:

Cognitive Electrophysiology of Mind and Brain
by Alberto Zani, Alice Proverbio
Reviews developments in recording of bioelectric and magnetic responses of the brain.

More info:

Multiple Sclerosis: The Questions You Have - The Answers You Need
by Rosalind Kalb
Guide for multiple sclerosis; question-and-answer format.
More info:

Healing ADD: The Breakthrough Program That Allows You to See and Heal the 6 Types of ADD
by Daniel G. Amen

The Owner's Manual for the Brain: Everyday Applications from Mind-Brain Research
by Pierce J. Howard
A hodge-podge of research findings, followed by applications.
More info:

Clinical Neuropsychology
ISBN: 0195133676
A definitive text on all major neurobehavioral disorders of adults, including aphasia, alexia, agraphia, agnosia, apraxia, amnesic disorders, dementia, and others. A required reference.
More info:

Epilepsy and the Family: A New Guide
by Richard Lechtenberg
            Updated guide addresses personal questions patients with epilepsy may hesitate to ask their doctors (e.g. about sexuality, depression); treatment options, and other concerns.
More info:

Pediatric Traumatic Brain Injury: Proactive Intervention
by Roberta Depompei, Jean L. Blosser

Textbook on treatment of traumatic brain injury in children, emphasizing the use of intervention teams of medical personnel, educators, and families.
More info:

Clinicians' Guide to Adult ADHD: Assessment and Intervention
by Sam Goldstein, Anne Teeter Ellison
Mental health and education scholars discuss how the controversial attention-deficit syndrome affects adults as well as children.
More info:





Memory for Visuospatial Location Following Selective Hippocampal Sclerosis: The Use of Different Coordinate Systems

A. Incisa della Rocchetta , S. Samson and N. Ehrlé, M. Denos, D. Hasboun, and M. Baulac

Neuropsychology, 2004, Vol. 18, No. 1, 15–28

            This study addressed the role of the medial temporal lobe regions and, more specifically, the contribution of the human hippocampus in memory for body-centered (egocentric) and environment-centered (allocentric) spatial location. Twenty-one patients with unilateral atrophy of the hippocampus secondary to long-standing epilepsy (left, n = 7; right, n = 14) and 15 normal control participants underwent 3 tasks measuring recall of egocentric or allocentric spatial location. Patients with left hippocampal sclerosis were consistently impaired in the allocentric conditions of all 3 tasks but not in the egocentric conditions. Patients with right hippocampal sclerosis were impaired to a lesser extent and in only 2 of the 3 tasks. It was concluded that hippocampal structures are crucial for allocentric, but not egocentric, spatial memory.



Reading and Phonological Awareness in Williams Syndrome

Deny Menghini, Lorena Verucci, Stefano Vicari

Neuropsychology, 2004, Vol. 18, No. 1, 29–37

            This article describes the relationship between reading, phonological awareness abilities (PA), and intelligence in a group of 16 individuals with Williams syndrome (WS) and in a group of 16 typically developing children, matched for mental age. The individuals with WS were impaired in passage comprehension, in some areas of PA investigated (syllable deletion and rhyme detection), and in nonword reading accuracy, a measure of grapheme–phoneme conversion. This latter finding is relevant, considering that in Italy regular print-to-sound correspondence is the most practiced teaching routine in the early phases of learning to read.




Working Memory and Perseveration in Verbal Fluency

Tamiko Azuma

Neuropsychology, 2004, Vol. 18, No. 1, 69–77, ©2004 American Psychological Association

            Letter and semantic fluency tasks are often used in neuropsychological assessment and are sensitive to many conditions. Performance is assessed by correct responses and errors, including perseverations. Healthy young adults performed letter and semantic fluency tasks. One group performed these tasks in the conventional manner; 2 other groups performed them while maintaining memory loads. The memory loads consisted either of words from the same category as the fluency task or of words from a different category. The results showed little effect of memory loads on correct responses but significant effects of memory load on perseveration rates: Same-category loads resulted in higher rates, especially in letter fluency. The results are discussed in terms of frontal lobe function in verbal fluency.




Contribution of Organizational Strategy to Verbal Learning and Memory in Adults With Attention-Deficit/Hyperactivity Disorder

Robert M. Roth, Heather A. Wishart, Laura A. Flashman, Henry J. Riordan, Leighton Huey, and Andrew J. Saykin

Neuropsychology, 2004, Vol. 18, No. 1, 78–84, ©2004 American Psychological Association

            Statistical mediation modeling was used to test the hypothesis that poor use of a semantic organizational strategy contributes to verbal learning and memory deficits in adults with attention-deficit/hyperactivity disorder (ADHD). Comparison of 28 adults with ADHD and 34 healthy controls revealed lower performance by the ADHD group on tests of verbal learning and memory, sustained attention, and use of semantic organization during encoding. Mediation modeling indicated that state anxiety, but not semantic organization, significantly contributed to the prediction of both learning and delayed recall in the ADHD group. The pattern of findings suggests that decreased verbal learning and memory in adult ADHD is due in part to situational anxiety and not to poor use of organizational strategies during encoding.







Elevated False Recognition in Patients With Frontal Lobe Damage Is Neither a General Nor a Unitary Phenomenon

Mieke Verfaellie, Steven Z. Rapcsak, Margaret M. Keane, Michael P. Alexander

Neuropsychology, 2004, Vol. 18, No. 1, 94–103, ©2004 American Psychological Association

            This study examined verbal recognition memory in amnesic patients with frontal lesions (AF), nonamnesic patients with frontal lesions (NAF), and amnesic patients with medial temporal lesions (MT). To examine susceptibility to false alarms, the number of studied words drawn from various categories was varied. The AF and MT groups demonstrated reduced hits and increased false alarms. False alarms were especially elevated when item-specific recollection was strongest in control participants. The NAF group performed indistinguishably from control participants, but several patients showed excessive false alarms in the context of normal hit rates. These patients exhibited impaired monitoring and verification processes. The findings demonstrate that elevated false recognition is not characteristic of all frontal patients and may result from more than 1 underlying mechanism.




Control of Fixation and Saccades in Humans With Chronic Lesions of Oculomotor Cortex

Liana Machado and Robert D. Rafal

Neuropsychology, 2004, Vol. 18, No. 1, 115–123, ©2004 American Psychological Association

            To elucidate the dynamic interactions of cortical and subcortical oculomotor systems, the authors investigated reflexive and strategic control over fixation and saccades in patients with chronic unilateral lesions that involved either frontal or parietal cortex. They measured the effects of indicating the location of the forthcoming target and removing the fixation stimulus on the latencies of eye movements toward a peripheral visual target in 12 patients with frontal eye field (FEF) lesions, 9 patients with lesions restricted to parietal cortex, and 12 neurologically healthy controls. They found that chronic damage to FEF cortex disrupts cortico–collicular interactions, resulting in hypoactivity in the contralesional superior colliculus and a loss of strategic control over the intrinsic collicular circuits that regulate fixation.





A Lexical Stress Effect in Neglect Dyslexia

Maria Luisa Rusconi. Stefano F. Cappa, Michele Scala, Francesca Meneghello

Neuropsychology, 2004, Vol. 18, No. 1, 135–140, ©2004 American Psychological Association

            The aim of this study was to investigate the effect of word stress location in neglect dyslexia. An assessment was made of stress assignment in reading Italian words in 13 patients with neglect dyslexia and 13 matched normal individuals. The correspondence in stress location between target and neglect errors was preserved in 9 patients. Moreover, the proportion of words with stress on the penultimate syllable was about 50% and that on the antepenultimate syllable was also about 50%. This pattern is significantly different from the distribution observed in the Italian lexicon, in which the majority of polysyllabic words are stressed on the penultimate syllable. This result cannot be expected from the application of a "regularization" strategy associated with the operation of a nonlexical reading pathway. Taken together, these findings lead to the conclusion that lexical stress is part of the lexical information preserved in neglect dyslexia.



Impaired Decision Making Related to Working Memory Deficits in Individuals With Substance Addictions

Antoine Bechara, Eileen M. Martin

Neuropsychology, 2004, Vol. 18, No. 1, 152–162, ©2004 American Psychological Association

            This study examined whether individuals with substance dependence (ISDs) show impairments in working memory and whether there is a relationship between their impairments in decision making as measured by the gambling task (GT) paradigm and working memory as measured by a delayed nonmatching to sample (DNMS) task. Using the GT, 11% of healthy control participants and 61% of ISDs opted for choices with high immediate gains in spite of higher future losses. For the ISDs and controls with equal GT impairments, the ISDs performed significantly lower than controls on the DNMS task. The nonimpaired ISDs on the GT also performed significantly worse than matched controls on the DNMS task. The DNMS task deficit in ISDs was across all delay times, suggesting the deficit may lie in the "executive" process of working memory, which supports earlier findings (E. M. Martin et al., 2003). The authors suggest that the prefrontal cortex hosts multiple distinct mechanisms of decision making and inhibitory control and that ISDs may be affected in any one or combination of them.







Orthography and the Hemispheres: Visual and Linguistic Aspects of Letter Processing

Neuropsychology, 2004, Vol. 18, No. 1, 174–184, ©2004 American Psychological Association

Zohar Eviatar, Raphiq Ibrahim, Deia Ganayim

            Hebrew and Arabic are Semitic languages with a similar morphological structure and orthographies that differ in visual complexity. Two experiments explored the interaction of the characteristics of orthography and hemispheric abilities on lateralized versions of a letter-matching task (Experiment 1) and a global–local task (Experiment 2). In Experiment 1, native Hebrew readers and native Arabic readers fluent in Hebrew matched letters in the 2 orthographies. The results support the hypothesis that Arabic orthography is more difficult than Hebrew orthography for participants who can read both languages and that this difficulty has its strongest effects in the left visual field. In Experiment 2, native Arabic speakers performed a global–local letter detection task with Arabic letters with 2 types of inconsistent stimuli: different and similar. The results support the hypothesis that the right hemisphere of skilled Arabic readers cannot distinguish between similar Arabic letters, whereas the left hemisphere can.







Am J Psychiatry 161:133-138, January 2004

Association of the Dopamine D4 Receptor Gene 7-Repeat Allele With Neuropsychological Test Performance of Children With ADHD

Kate Langley, B.A. (Hons), Lucy Marshall, B.Sc. (Hons), Marianne van den Bree, Ph.D., Hollie Thomas, D.Phil., Michael Owen, F.R.C.Psych., Ph.D., F.Med.Sci., Michael O’Donovan, F.R.C.Psych., Ph.D., and Anita Thapar, M.R.C.Psych., Ph.D.

            OBJECTIVE: Association between attention deficit hyperactivity disorder (ADHD) and the 7-repeat allele of a variant (a 48bp variable number of tandem repeats) in the dopamine D4 receptor gene (DRD4) has been widely documented. A meta-analysis of 21 studies revealed evidence of significant association. In this article the authors examine whether the DRD4 7-repeat allele is associated with performance on a variety of neuropsychological tasks in children with ADHD. METHOD: The presence or absence of the 7-repeat allele was determined in 133 drug-naive children 6 to 13 years of age who fulfilled diagnostic criteria for ADHD. These children were then assessed on several neuropsychological tests known to be associated with attention, impulse control, and response inhibition (the Continuous Performance Test, Matching Familiar Figures Test, Go/No Go Task, and Stop Task). Activity levels were assessed with an actigraph. Children with and without at least one 7-repeat allele were compared with each other and with children in a previous population-based study. RESULTS: Children who had the 7-repeat allele had significantly more incorrect responses on the Matching Familiar Figures Test (16.1 versus 14.3) than children who did not have the allele. Children with the allele also had shorter mean reaction times for incorrect responses on the Matching Familiar Figures Test (846.1 versus 1103.7 msec) and on the Stop Task (116.6 versus 134.1 msec) than children without the allele. Children with the allele also displayed higher activity levels. The children with and without the allele did not differ significantly in number of ADHD symptoms when the symptoms were split into the areas of inattention and hyperactivity/impulsivity. Both groups of children with ADHD were more neuropsychologically impaired than the nonpatient comparison group. CONCLUSIONS: In children with ADHD, possession of the DRD4 7-repeat allele appears to be associated with an inaccurate, impulsive response style on neuropsychological tasks that is not explained by ADHD symptom severity.





The Monakow Concept of Diaschisis: Origins and Perspectives

Stanley Finger, MD; Peter J. Koehler, MD, PhD; Caroline Jagella, MD, PhD

Arch Neurol. 2004;61:283-288.

            The idea that damage to one part of the nervous system can have effects at a distance was popular during the 19th century. Constantin von Monakow, MD, accepted this idea and blended it with the newly formulated neuron doctrine early in the 20th century to account for ipsilateral paralyses and recovery of function. He called his theory of neural depression caused by loss of inputs to structures tied to the damaged area diaschisis. In this article, we examine the origins of diaschisis and the goals of Monakow. Credit is given to Monakow for drawing needed attention to the dynamics of the nervous system, remote lesion effects, and recovery of function, even though the fine details or specifics of his theory have had a mixed reception.




MS / Fatigue


The Relationship Between Diffuse Axonal Damage and Fatigue in Multiple Sclerosis

Maria Carmela Tartaglia, BSc, MD; Sridar Narayanan, MSc, PhD; Simon J. Francis, BSc; Antonio Carlos Santos, MD, PhD; Nicola De Stefano, MD, PhD; Yves Lapierre, MD; Douglas L. Arnold, MD

Arch Neurol. 2004;61:201-207.

            Background  Fatigue is a common and distressing symptom for patients with multiple sclerosis (MS). There is growing evidence that fatigue in MS has a central nervous system component. We hypothesized that diffuse cerebral axonal damage could be associated with fatigue and used proton magnetic resonance spectroscopy to noninvasively measure axonal damage or loss in the brains of patients with MS.

Objective  To assess the strength of the relationship between central brain N-acetylaspartate and fatigue.  Design  Data from 73 patients who had undergone proton magnetic resonance spectroscopy imaging and completed the Fatigue Severity Scale questionnaire were analyzed.  Results  The N-acetylaspartate–creatine ratio (NAA/Cr) was significantly lower in the high-fatigue groupthan the low-fatigue group (mean ± SD, 2.69 ± 0.29 and 2.99 ± 0.33, respectively. P = .003). Independent of the Kurtzke Expanded Disability Status Scale, T2 lesion volume, age, and disease duration, NAA/Cr was significantly lower in the high-fatigue group as compared with the low-fatigue group. There was a statistically significant linear correlation between the Fatigue Severity Scale scores and NAA/Cr (Spearman rank  = -0.361, P = .02).  Conclusions  The results of this study, combined with those of others, suggest that widespread axonal dysfunction is associated with fatigue in MS. Increased recruitment of cortical areas and pathways in response to brain injury may be responsible for the patient's sense that the effort required to perform actions is disproportionately high.





Infratentorial Lesions Predict Long-term Disability in Patients With Initial Findings Suggestive of Multiple Sclerosis

Arjan Minneboo, MD; Frederick Barkhof, MD; Chris H. Polman, MD; Bernard M. J. Uitdehaag, MD; Dirk L. Knol, PhD; Jonas A. Castelijns, MD

Arch Neurol. 2004;61:217-221.

            Background  The number and volume of abnormalities on baseline brain magnetic resonance images in patients with initial findings suggestive of multiple sclerosis are known to predict outcome in terms of disability. However, no long-term data exist on specific locations or types of lesions.  Objective  To assess the long-term predictive value of baseline magnetic resonance imaging parameters, including location of lesions and gadolinium-enhancing and hypointense lesions in patients with initial findings suggestive of multiple sclerosis for the occurrence of clinically relevant disability as defined by an Expanded Disability Status Scale score of 3.  Patients  After a median follow-up period of 8.7 years, the medical records of 42 patients were reviewed and assessed for time until patients received an Expanded Disability Status Scale score of 3. Magnetic resonance imaging parameters were dichotomized according to maximum accuracy and then used to calculate hazard ratios using the Cox model for proportional hazard ratios.  Results  Conversion to clinically definite multiple sclerosis was observed in 26 patients (62%), of whom 14 (54%) progressed to an Expanded Disability Status Scale score of 3. Two or more infratentorial lesions best predicted long-term disability (hazard ratio, 6.3). Gadolinium-enhancing and hypointense T1-weighted lesions did not show prognostic value.  Conclusion  Infratentorial lesions are related to long-term prognosis for patients with initial findings suggestive of multiple sclerosis and thus may help to identify patients at high risk for earlier occurrence of clinically relevant disability.




Prediction of Neuropsychological Impairment in Multiple Sclerosis: Comparison of Conventional Magnetic Resonance Imaging Measures of Atrophy and Lesion Burden

Ralph H. B. Benedict, PhD; Bianca Weinstock-Guttman, MD; Inna Fishman, MA; Jitendra Sharma, MD; Christopher W. Tjoa; Rohit Bakshi, MD

Arch Neurol. 2004;61:226-230.

            Background  Cognition and magnetic resonance imaging correlations are well established in patients with multiple sclerosis (MS), but it is unclear whether lesion burden or atrophy accounts for most of the predictive variance. These indices have been directly compared in only a few studies. No such study included measurement of the third ventricle, which was strongly predictive of neuropsychological competence in the early literature. Furthermore, few studies accounted for the influence of age, premorbid intelligence, or depression.  Objective  To determine if conventional measures of lesion burden or atrophy predict cognitive dysfunction in MS while accounting for age, premorbid intelligence, and depression.  Methods  We studied 37 patients with MS and 27 controls matched according to demographic variables. Correlations between neuropsychological tests and the following magnetic resonance imaging indices were considered: T1 hypointense lesion volume, fluid-attenuated inversion recovery hyperintense lesion volume, third ventricle width, bicaudate ratio, and brain parenchymal fraction. Regression models predicting neuropsychological performance controlled for the effects of age, premorbid intelligence, and depression. We included only those tests discriminating patients with MS from controls.  Results  In each regression model, third ventricle width was the sole magnetic resonance imaging measure retained. When this variable was removed from consideration, brain parenchymal fraction was retained in all analyses.  Conclusions  Brain atrophy accounts for more variance than lesion burden in predicting cognitive impairment in MS, and central atrophy in particular is strongly associated with neuropsychological morbidity. This finding may be explained in part by atrophy of the thalamus, a deep gray matter structure that mediates cognitive function via cortical and subcortical pathways. Enthusiasm for the clinical utility of third ventricle width is tempered by modest intraobserver and interobserver reliability.






Journal of Neurology Neurosurgery and Psychiatry 2004;75:396-400

Use and interpretation of on/off diaries in Parkinson’s disease

J Reimer, M Grabowski, O Lindvall and P Hagell ;

            Objective: To explore the use and interpretation of self reported on/off diary data for assessment of daily motor fluctuations in Parkinson’s disease.  Methods: 26 consecutive non-demented patients with fluctuating Parkinson’s disease received standardised training on how to fill out the four category CAPSIT-PD on/off diary, followed by four hours of clinical observation and four weeks of daytime on/off diaries every 30 minutes at home.  Results: Overall patient–clinician agreement in diary entries was good ( = 0.62; weighted  = 0.84). Agreement for individual diary categories was good for "off" and "on with dyskinesias" ( = 0.72), but moderate for "partial off" and "on" ( = 0.49). The overall validity of patient kept diaries was supported by expected symptom severity variability across diary categories, as assessed in the clinic. One day’s home diary data failed to predict outcomes from the full four weeks for all diary categories, and data from three days failed to yield good prediction (predefined as R2 = ~0.7) for the time spent in "off" and "partial off". Data from one week yielded good prediction (R2 = 0.74) in all instances except "partial off", which could not be well predicted even when two weeks’ home diary data were considered (R2 = 0.52).  Conclusions: The data provide support for the overall accuracy and validity of the four category CAPSIT-PD on/off diary, but suggest that a three category diary format may improve accuracy and validity. Interpretation of diary data beyond the assessed time frame should be made with caution unless diaries have been kept for sufficiently long periods.




J Neuropsychiatry Clin Neurosci 16:29-36, February 2004

Differential DSM-III Psychiatric Disorder Prevalence Profiles in Dystonia and Parkinson’s Disease

Edward C. Lauterbach, M.D., Alan Freeman, M.D. and Robert L. Vogel, Ph.D.; (E-mail).

            The authors investigated the prevalence of DIS-ascertained DSM-III psychiatric disorders occurring in 28 patients with dystonia and 28 patients with Parkinson’s Disease (PD). In patients with dystonia, lifetime prevalences of major depression (25.0%), bipolar disorder (7.1%), atypical bipolar disorder (7.1%), social phobia (17.9%), and generalized anxiety disorder (25.0%) were significantly more common than in epidemiologic catchment area (ECA) study population controls (p < 0.005). Social phobia and generalized anxiety disorder preceded dystonia (primary), while bipolar disorder developed after dystonia onset (secondary). In PD patients, the lifetime prevalence of simple phobia (35.7%, p < 0.0001) and atypical depression (21.4%) were significantly more common. Parkinson’s Disease was associated with primary simple phobia and secondary atypical depression. These findings are considered in light of previous results and in terms of the differences in pallidothalamic physiologies in dystonia and PD. These data suggest distinctive profiles of psychiatric disorders in dystonia and PD.





Journal of Intellectual Disability Research

Volume 47 Issue 8 Page 597  - November 2003

Validity of a performance assessment of activities of daily living for people with developmental disabilities

A. Kottorp, B. Bernspång & A. G. Fisher

            Background  Since clients with different types of developmental disabilities often experience difficulties in activities of daily living (ADL), it is critical that assessments of ADL are evaluated in order to ensure that one can make valid judgements based on the results of the appraisal. The purpose of the present study was to evaluate the validity of a specific performance assessment instrument, the Assessment of Motor and Process Skills (AMPS), when used by occupational therapists with clients with developmental disabilities. Unlike global ADL assessments, the AMPS is used not only to evaluate the level of ADL dependence, but also to estimate the quality of each specific action performed when a person is performing ADL tasks. Methods  Data were gathered from 1724 participants with different developmental disabilities, including intellectual disability (ID), cerebral palsy and spina bifida. Many-Facet Rasch (MFR) analysis was used to examine person-response validity, and task and item scale validity. Results  Goodness-of-fit statistics showed that the tasks and items had acceptable scale validity. The participants had acceptable person-response validity on the ADL motor scale, but had slightly lower than expected levels of person-response validity on the ADL process scale. The results indicate that clients with more severe forms of ID may have a higher proportion of different performance profiles in ADL than is expected by the MFR model of the AMPS. Since the proportion of participants who did not meet the criteria was only 3% lower than expected and in accordance with other studies, the difference may not be clinically meaningful. Otherwise, the results indicated that the AMPS is a valid tool when used with clients with developmental disabilities. Conclusions  Further research is needed to evaluate the use of the AMPS in clinical assessment and intervention planning for this group of clients.









Biol Res Nurs. 2004 Jan;5(3):168-76.

Cognitive executive dysfunction in children with mild sleep-disordered breathing.

Archbold KH, Giordani B, Ruzicka DL, Chervin RD.;

            In children, moderate or severe sleep-disordered breathing (SDB) may impair cognitive executive functions (EFs), including working memory, attention, and mental flexibility. The main objective of this study was to assess EFs in children with mild levels of SDB. Subjects for this descriptive study were 12 children (5 girls, 7 boys) aged 8.0 to 11.9 years (M = 9.0 +/- 0.85) participating in an ongoing study of the effects of adenotonsillectomy on behavior. Each subject had a nocturnal polysomnogram (PSG) and a multiple sleep latency test (MSLT). Mild SDB was considered present if the child's apnea/hypopnea index (AHI) was > or = 1 and < 10. Between MSLT nap attempts, each child completed standardized tests of EFs. The sample showed significant impairment of sustained attention and vigilance on a computerized continuous performance test. Children with low mental flexibility scores on the Children's Category Test (CCT) spent more time in stage 1 sleep (12.2% v. 9.5%, P = 0.028 on PSG) and showed a marginally higher arousal index (9.7 v. 6.5, P = 0.06 on PSG) than children with average or above-average CCT scores. AHI accounted for a significant proportion of the variance in CCT scores when 1 outlier was removed (N = 11, Rsq = 0.67, P = 0.002). Mild levels of SDB and associated sleep architecture disruptions may be associated with impairment of EFs in children.





Cognitive Neuroscience resources

Pain, fatigue, & injury resources,

B O O K N E W S_________________________________________

Cognitive Electrophysiology of Mind and Brain
by Alberto Zani, Alice Proverbio
Reviews developments in recording of bioelectric and magnetic responses of the brain.
More info:

Anxiety and Its Disorders, 2nd Ed: The Nature and Treatment of Anxiety and Panic
by David H. Barlow
Model of panic and anxiety based on recent developments in emotion theory, cognitive science, and neuroscience.
More info:

Cognitive Electrophysiology of Mind and Brain
by Alberto Zani, Alice Proverbio
Reviews developments in recording of bioelectric and magnetic responses of the brain.
More info:

Multiple Sclerosis: The Questions You Have - The Answers You Need
by Rosalind Kalb
Guide for multiple sclerosis; question-and-answer format.
More info:

Healing ADD: The Breakthrough Program That Allows You to See and Heal the 6 Types of ADD
by Daniel G. Amen

The Owner's Manual for the Brain: Everyday Applications from Mind-Brain Research
by Pierce J. Howard
A hodge-podge of research findings, followed by applications.
More info:

Clinical Neuropsychology
ISBN: 0195133676
A definitive text on all major neurobehavioral disorders of adults, including aphasia, alexia, agraphia, agnosia, apraxia, amnesic disorders, dementia, and others. A required reference.
More info:


Epilepsy and the Family: A New Guide
by Richard Lechtenberg
            Updated guide addresses personal questions patients with epilepsy may hesitate to ask their doctors (e.g. about sexuality, depression); treatment options, and other concerns.
More info:




Renee D. Goodwin, David M. Fergusson and L. John Horwood (2004)

Association between anxiety disorders and substance use disorders among young persons:
results of a 21-year longitudinal study.

Journal of Psychiatric Research, 38(3), 295-304.
            Objective: To examine the linkages between anxiety disorders and the development of substance use disorders in a birth cohort of young people studied to young adulthood. Method: Data were gathered over the course of a longitudinal study of a birth cohort of over 1000 New Zealand born young people. Over the course of the study, data were gathered on: (a) anxiety disorders and substance use disorders at ages 16-18 and 18-21; (b) a range of potential confounding factors including measures of childhood, social, and family factors. Results: Young people with anxiety disorders had odds of substance dependence that were between 1.3 and 3.9 times higher than young people without anxiety disorders. These associations were largely explained by a series of covariate factors relating to: (a) childhood and family factors; (b) prior substance dependence; (c) comorbid depression; (d) peer affiliations. After adjustment for these factors, anxiety disorder was unrelated to all measures of substance use. Conclusions: Young people with anxiety disorders are at increased risk of substance dependence. However, this association appears to be largely or wholly non causal and reflects the associations between childhood factors, prior substance dependence, comorbid depression, peer affiliations and the development of anxiety disorders.


=======================NEUROPSYCHOLOGIA in press================



Copyright © 2004 Elsevier Ltd. All rights reserved

Articles in Press - Note to users        

Dissociation between taste and tactile extinction on the tongue after right brain damage,

In Press, Corrected Proof, Available online 2 March 2004

Giovanni Berlucchi , Valentina Moro , Chiara Guerrini and Salvatore Maria Aglioti

            In patients with right brain damage (RBD) or left brain damage (LBD) and healthy subjects, tactile and three basic gustatory stimuli (sour, salty, bitter) were applied to the left or right hemitongues or to both hemitongues simultaneously. Tactile stimuli were detected and localized by verbal report, whereas gustatory stimuli were identified by pointing to the corresponding name on cards bearing the names of the three tastes. In the tactile test, 9 of 18 RBD patients showed extinction of left hemitongue stimuli, whereas the remaining RBD patients, 9 LBD patients and 14 healthy subjects detected virtually all stimuli in all conditions. In the gustatory test, healthy subjects outperformed the two brain damaged groups which nevertheless responded well above chance and did not differ from one another. Unexpectedly, the nine RBD patients with left hemitongue tactile extinction showed no gustatory extinction, since performance did not differ significantly between the two hemitongues on both unilateral and bilateral stimulations. To account for these findings, some evidence suggests that the tongue representation is bilateral in both modalities, but predominantly ipsilateral in the gustatory modality and predominantly contralateral in the tactile modality. The RBD patients with left hemitongue tactile extinction were those with more marked symptoms of left-sided extinction in the visual and auditory modalities, making it likely that their brain damage was also responsible for left lingual tactile extinction. The absence of left gustatory extinction in those patients can be attributed to the predominant channelling of left hemitongue taste inputs into the intact left hemisphere.



Head size and intelligence, learning, nutritional status and brain development: Head, IQ, learning, nutrition and brain, In Press, Corrected Proof, Available online 28 February 2004

Daniza M. Ivanovic , Boris P. Leiva , Hernán T. Pérez , Manuel G. Olivares , Nora S. Díaz , María Soledad C. Urrutia , Atilio F. Almagià , Triana D. Toro , Patricio T. Miller , Enrique O. Bosch and Cristián G. Larraín

            This multifactorial study investigates the interrelationships between head circumference (HC) and intellectual quotient (IQ), learning, nutritional status and brain development in Chilean school-age children graduating from high school, of both sexes and with high and low IQ and socio-economic strata (SES). The sample consisted of 96 right-handed healthy students (mean age 18.0±0.9 years) born at term. HC was measured both in the children and their parents and was expressed as Z-score (Z-HC). In children, IQ was determined by means of the Wechsler Intelligence Scale for Adults-Revised (WAIS-R), scholastic achievement (SA) through the standard Spanish language and mathematics tests and the academic aptitude test (AAT) score, nutritional status was assessed through anthropometric indicators, brain development was determined by magnetic resonance imaging (MRI) and SES applying the Graffar modified method. Results showed that microcephalic children (Z-HC2 S.D.) had significantly lower values mainly for brain volume (BV), parental Z-HC, IQ, SA, AAT, birth length (BL) and a significantly higher incidence of undernutrition in the first year of life compared with their macrocephalic peers (Z-HC > 2 S.D.). Multiple regression analysis revealed that BV, parental Z-HC and  were the independent variables with the greatest explanatory power for child's Z-HC variance (r2=0.727). These findings confirm the hypothesis formulated in this study: (1) independently of age, sex and SES, brain parameters, parental HC and prenatal nutritional indicators are the most important independent variables that determine HC and (2) microcephalic children present multiple disorders not only related to BV but also to IQ, SA and nutritional background.



Object–location memory impairment in patients with thermal lesions to the right or left hippocampus, In Press, Corrected Proof, Available online 28 February 2004

Katerina Stepankova , André A. Fenton , Eva Pastalkova , Miroslav Kalina and Véronique D. Bohbot

            Memory for object–location was investigated by testing subjects with small unilateral thermolesions to the medial temporal lobe using small-scale 2D (Abstract) or large-scale 3D (Real) recall conditions. Four patients with lesions of the left hippocampus (LH), 10 patients with damage to the right hippocampus (RH) and 9 matched normal controls (NC) were tested. Six task levels were presented in a pseudorandom order. During each level, subjects viewed one to six different objects on the floor of a circular curtained arena 2.90 m in diameter for 10 s. Recall was tested by marking the locations of objects on a map of the arena (Abstract recall) and then by replacing the objects in the arena (Real recall). Two component errors were studied by calculating the Location Error (LE), independent of the object identity and the configuration error by finding the best match to the presented configuration. The RH group was impaired relative to the NC for nearly all combinations of recall and error types. An impairment was observed in this group even for one object and it deepened sharply with an increasing object number. Damage to the right perirhinal or parahippocampal cortices did not add to the impairment. Deficits in the LH group were also observed, but less consistently. The data indicate that spatial memory is strongly but not exclusively lateralised to the right medial temporal lobe.



Number processing and basal ganglia dysfunction: a single case study, In Press, Corrected Proof, Available online 6 February 2004

Margarete Delazer, Frank Domahs, Aliette Lochy, Elfriede Karner, Thomas Benke and Werner Poewe

            Numerical processing has never been investigated in a case of Fahr's disease (FD) and only rarely in cases of basal ganglia dysfunction. The study describes the cognitive decline of a premorbidly high-functioning patient (medical doctor) affected by FD and his difficulties in number processing. A MRI scan revealed bilateral calcifications in the basal ganglia and a brain PET showed a massive reduction of glucose metabolism in the basal ganglia and both frontal lobes, but no other brain abnormalities. The patient's cognitive deficits included impairments in problem solving, in cognitive set shifting and in mental flexibility, as well as in verbal memory. These deficits are attributed to the disruption of the dorsolateral prefrontal circuit involving the basal ganglia. In number processing, the patient showed a severe deficit in the retrieval of multiplication facts, deficits in all tasks of numerical problem solving and in the execution of complex procedures. Importantly, he also showed a dense deficit in conceptual knowledge, which concerned all test conditions and all operations. The findings confirm the predictions of the triple code model ([Dehaene & Cohen, 1995]) in so far, as a disruption of cortico-subcortical loops involving the basal-ganglia may lead to specific deficits in fact retrieval. However, no verbal deficit, as assumed in the triple code model and reported in similar cases, could be observed. The present findings further add to current knowledge on numerical processing, showing how fronto-executive dysfunction may disrupt conceptual understanding of arithmetic. This study shows that not only parietal lesions may lead to severe deficits in conceptual understanding, but that basal ganglia lesions leading to frontal dysfunction may have a devastating effect.



Effects of attention and confidence on the hypothesized ERP correlates of recollection and familiarity, In Press, Corrected Proof, Available online 6 February 2004

Tim Curran

            Dual-process theories suggest that recognition memory is determined by two separate processes: familiarity and recollection. Experiment 1 behaviorally replicated past studies using the remember/know procedure to indicate that the amount of attention devoted to study influences both recollection and familiarity, but recollection more strongly. Experiments 1 and 2 assessed the effects of attention on two ERP components that have been hypothesized to be related to familiarity (FN400 old/new effect, 300–500 ms, anterior) and recollection (parietal old/new effect, 400–800 ms, posterior). Parietal old/new effects were reduced by divided attention, but FN400 old/new effects were not. Parietal ERPs (400–800 ms) in experiment 2 increased with confidence in recognizing old items, but not new items. These results support the hypothesis that the parietal old/new effect is related to recollection.



Striatal dopamine and learning strategy––an 123I-FP-CIT SPECT study, In Press, Corrected Proof, Available online 5 February 2004

Hans J. C. Berger, Alexander R. Cools, Martin W. I. M. Horstink, Wim J. G. Oyen, Elisabeth W. M. Verhoeven and Sieberen P. van der Werf

            Patients with Parkinson's disease (PD) have difficulty in processing learning tasks that lack external guidelines and, consequently, necessitate the subjects to generate their own problem-solving strategy. While the contribution of striatal dopaminergic deficiency to PD-specific motor symptoms is well established, its role in the PD-characteristic deviant learning style remains unclear.

            The aim of this study was to assess the relation between striatal dopamine activity as revealed by single photon emission computed tomography (SPECT) with 123I-FP-CIT, a ligand for the dopamine transporter (DaT), and type of learning strategy, as identified by the California Verbal Learning Task (CVLT) in 19 patients with probable PD. The results showed a robust inverse correlation between striatal dopamine DaT binding and the externally guided, serial learning strategy: the lower the DaT in caudate nucleus as well as in putamen, the more the patient group appeared to rely on externally structured learning. Additionally, a significant positive correlation was found between caudatal DaT activity and the internally generated, semantic learning strategy. Unlike these strategic learning characteristics, IQ equivalent and recall total score appeared to vary independently from striatal DaT availability.

            Conclusion: our findings provide direct evidence that striatal dopaminergic activity is specifically involved in the regulation of strategic learning processes.



Intact haptic priming in normal aging and Alzheimer's disease: evidence for dissociable memory systems*1, In Press, Corrected Proof, Available online 5 February 2004

Soledad Ballesteros and José Manuel Reales

            This study is the first to report complete priming in Alzheimer's disease (AD) patients and older control subjects for objects presented haptically. To investigate possible dissociations between implicit and explicit objects representations, young adults, Alzheimer's patients, and older controls performed a speeded object naming task followed by a recognition task. Similar haptic priming was exhibited by the three groups, although young adults responded faster than the two older groups. Furthermore, there was no difference in performance between the two healthy groups. On the other hand, younger and older healthy adults did not differ on explicit recognition while, as expected, AD patients were highly impaired. The double dissociation suggests that different memory systems mediate both types of memory tasks. The preservation of intact haptic priming in AD provides strong support to the idea that object implicit memory is mediated by a memory system that is different from the medial–temporal diencephalic system underlying explicit memory, which is impaired early in AD. Recent imaging and behavioral studies suggest that the implicit memory system may depend on extrastriate areas of the occipital cortex although somatosensory cortical mechanisms may also be involved.



Haptic face recognition and prosopagnosia, In Press, Corrected Proof, Available online 3 February 2004

Andrea R. Kilgour, Beatrice de Gelder and Susan J. Lederman

            Cases of cross-modal influence have been observed since the beginning of psychological science. Yet some abilities like face recognition are traditionally only investigated in the visual domain. People with normal visual face-recognition capacities identify inverted faces more poorly than upright faces. An abnormal pattern of performance with inverted faces by prosopagnosic individuals is characteristically interpreted as evidence for a deficit in configural processing essential for normal face recognition. We investigated whether such problems are unique to vision by examining face processing by hand in a prosopagnosic individual. We used the haptic equivalent of the visual-inversion paradigm to investigate haptic face recognition. If face processing is specific to vision, our participant should not show difficulty processing faces haptically and should perform with the same ease as normal controls. Instead, we show that a prosopagnosic individual cannot haptically recognize faces. Moreover, he shows similar abnormal inversion effects by hand and eye. These results suggest that face-processing deficits can be found across different input modalities. Our findings also extend the notion of configural processing to haptic face and object recognition.



Chromatic edges, surfaces and constancies in cerebral achromatopsia, In Press, Corrected Proof, Available online 24 January 2004

R. W. Kentridge, C. A. Heywood and A. Cowey

            We tested achromatopsic observer, MS, on a number of tasks to establish the extent to which he can process chromatic contour. Stimuli, specified in terms of cone-contrast, were presented in a three-choice oddity paradigm. First we show that MS is able to discriminate the magnitude of chromatic and luminance contrast, but performance is inferior to that of normal observers. Moreover, MS can discriminate isoluminant borders of different chromatic composition. These abilities are not the result of unintended luminance differences and are abolished when chromatic borders are masked by sharp luminance change. In simple displays, local cone-contrast signals can make a significant contribution to surface colour appearance in normal observers. In more complex displays, the perception of a surface's colour becomes largely independent of the local contrast to its background, via processes presumed to be similar to the edge integration and anchoring stages of Land's Retinex algorithm. We show that in simple displays the percepts of both MS and normal observers are dominated by local chromatic-contrast. But, although the percepts of normal observers change in line with the predictions of retinex theory in more complex displays, those of MS do not, remaining dominated by local contrast signals. We conclude that MS has lost the ability to perform edge integration and that this loss is closely related to his absence of colour experience.



Auditory extinction: the effect of stimulus similarity and task requirements, In Press, Corrected Proof, Available online 24 January 2004

Rebecca J. Shisler, Christopher L. Gore and Gordon C. Baylis

            Auditory extinction was examined in six patients with right hemisphere lesions, using an auditory double simultaneous stimulation task using letters spoken in male and female voices. Patients had to detect where the stimuli were located, and identify either the letter or the voice (the task-relevant dimension). Auditory extinction was greatest when the two stimuli were the same on the task-relevant dimension, paralleling previous studies of visual extinction. Furthermore, we found that errors of omission were much less frequent in the contralesional field if the patients were not required to report both identity and the location of stimuli. These results are consistent with the notion that auditory extinction may be due in part to a failure to bind together identity and location.



Developmental amnesia: a new pattern of dissociation with intact episodic memory, In Press, Corrected Proof, Available online 24 January 2004

Christine M. Temple and Paul Richardson

            A case of developmental amnesia is reported for a child, CL, of normal intelligence, who has intact episodic memory but impaired semantic memory for both semantic knowledge of facts and semantic knowledge of words, including general world knowledge, knowledge of word meanings and superordinate knowledge of words. In contrast to the deficits in semantic memory, there are no impairments in episodic memory for verbal or visual material, assessed by recall or recognition. Lexical decision was also intact, indicating impairment in semantic knowledge of vocabulary rather than absence of lexical representations. The case forms a double dissociation to the cases of Vargha-Khadem et al. [Science 277 (1997) 376; Episodic memory: new directions in research (2002) 153]; Gadian et al. [Brain 123 (2000) 499] for whom semantic memory was intact but episodic memory was impaired. This double dissociation suggests that semantic memory and episodic memory have the capacity to develop separately and supports models of modularity within memory development and a functional architecture for the developmental disorders within which there is residual normality rather than pervasive abnormality. Knowledge of arithmetical facts is also spared for CL, consistent with adult studies arguing for numeracy knowledge distinct from other semantics. Reading was characterised by difficulty with irregular words and homophones but intact reading of nonwords. CL has surface dyslexia with poor lexico-semantic reading skills but good phonological reading skills. The case was identified following screening from a population of normal schoolchildren suggesting that developmental amnesias may be more pervasive than has been recognised previously.



Effects of Alzheimer disease on memory for verbal emotional information, In Press, Corrected Proof, Available online 24 January 2004

Elizabeth A. Kensinger, Alberta Anderson, John H. Growdon and Suzanne Corkin

            In healthy young and older adults, emotional information is often better remembered than neutral information. It is an open question, however, whether emotional memory enhancement is blunted or preserved in Alzheimer disease (AD). Prior studies of emotional memory in AD have included small samples of patients. In addition, studies that failed to find an enhancement effect in AD used stimuli lacking semantic coherence (e.g. lists of unrelated words, some that were emotional and others that were neutral). To circumvent these limitations, the present study examined a large number of AD patients (N=80) and investigated whether AD patients would show better memory for a verbal description of an emotional event as compared to a neutral one. AD patients were equivalent to young and older control participants in rating the emotional descriptions for valence and arousal. Unlike the control groups, however, memory in AD patients did not benefit from the emotional narratives. We conclude that AD disrupts memory enhancement for at least some types of verbal emotional information.



On the role of the cerebellum in exploiting temporal contingencies: evidence from response times and preparatory EEG potentials in patients with cerebellar atrophy, In Press, Corrected Proof, Available online 22 January 2004

Peter Trillenberg, Rolf Verleger, Arjen Teetzmann, Edmund Wascher and Karl Wessel

            Patients with degenerative cerebellar disease were compared to healthy controls in their ability to adapt behaviour to temporal contingencies, both according to instructions and according to acquired experience. Participants had to press the cued key whenever the inside of a clock face changed its colour, which could occur when the pointer, rotating once every 4 s, was at "10 h" or at "12 h" or at "2 h". Probabilities varied between blocks at which of these three time points the colour change occurred, with participants being instructed accordingly. Response times correlated intraindividually with these instructed "a priori" probabilities in control participants only. Subjectively, at any moment, probabilities of occurrence depend on whether the imperative colour change had occurred before, thus may be better described by conditional ("a posteriori") probabilities. Indeed, when response times were correlated to a posteriori rather than a priori probabilities, correlations increased in both groups equally from their different a priori levels. The amplitudes of preparatory EEG negativity before responding tended to obey to the same relationships, suggesting that the difference between groups was not due to pure motor impairment. Thus, these data suggest that patients with cerebellar atrophy are more impaired in implementing and using task-relevant information in a top–down manner than in learning to modify task-relevant contingencies.



Priming illusory words: an ERP approach, In Press, Corrected Proof, Available online 22 January 2004

Michael Niedeggen, Martin Heil, Eva Ludowig, Bettina Rolke and Catherine L. Harris

            Repetition blindness (RB) was used to investigate whether illusory words emerge at a lexical-perceptual or a semantic-reconstructional level. Illusory words were evoked by the rapid serial visual presentation (RSVP) of two real words and a word fragment. The initial words share the same string of letters ("CREEP"–"SHEEP"), producing a free-floating word fragment ("SH"). This fragment is likely to be linked to a subsequently presented fragment ("IFT") if both combine to a meaningful word ("SHIFT"). The processing level of the illusions was probed by prime words preceding the RSVP sequence which were semantically related or unrelated to the second real word or to the illusion. Behavioural and electrophysiological correlates of the semantic priming effect were recorded in 14 subjects. Real words related to the prime were perceived more frequently, and evoked widespread N400-like effect in the event-related brain potentials (ERPs). An ERP effect of the same polarity was obtained for illusory words, however, its latency was delayed and the topographical distribution was restricted to left posterior electrode positions. These differences suggest that priming might affect real and illusory words at different levels of word processing: access to real words is facilitated at a semantic level, whereas lexical activation apparently accompanies the generation of illusory words.



The relationship of male testosterone to components of mental rotation, In Press, Corrected Proof, Available online 22 January 2004

Carole K. Hooven, Christopher F. Chabris, Peter T. Ellison and Stephen M. Kosslyn

            Studies suggest that higher levels of testosterone (T) in males contribute to their advantage over females in tests of spatial ability. However, the mechanisms that underlie the effects of T on spatial ability are not understood. We investigated the relationship of salivary T in men to performance on a computerized version of the mental rotation task (MRT) developed by [Science 171 (3972) (1971) 701]. We studied whether T is associated specifically with the ability to mentally rotate objects or with other aspects of the task. We collected hormonal and cognitive data from 27 college-age men on 2 days of testing. Subjects evaluated whether two block objects presented at different orientations were the same or different. We recorded each subject's mean response time (RT) and error rate (ER) and computed the slopes and intercepts of the functions relating performance to angular disparity. T level was negatively correlated with ER and RT; these effects arose from correlations with the intercepts but not the slopes of the rotation functions. These results suggest that T may facilitate male performance on MRTs by affecting cognitive processes unrelated to changing the orientation of imagined objects; including encoding stimuli, initiating the transformation processes, making a comparison and decision, or producing a response.



Hemispheric differences between left and right number representations: effects of conscious and unconscious priming, In Press, Corrected Proof, Available online 21 January 2004

Bert Reynvoet and Elie Ratinckx

            The contribution of each hemisphere to the generation of number representations was investigated by two lateralized priming experiments in which participants had to compare Arabic digits to a fixed standard of four. In Experiment 1, unmasked primes (Arabic digits or word numerals) were used. In Experiment 2, masked primes were presented consciously or subconsciously. In both experiments similar priming effects were found in the left (LH) and the right hemisphere (RH) when the prime was presented consciously. However, asymmetries emerged when the primes were presented subconsciously: while the priming effects of digits and word numbers were equally large in the right visual half field (RVF-LH), the influence of the word prime on the semantic and the response stage of the left visual half field (LVF-RH) was absent, indicating that a word prime was no longer processed when it was presented subconsciously in LVF-RH. We believe that the origin of the latter effect can be attributed to a failure to transfer word number primes from the RH to the LH when attentional resources are restricted.



Qualitative aspects of verbal fluency in HIV-associated dementia: a deficit in rule-guided lexical-semantic search processes?, In Press, Corrected Proof, Available online 6 January 2004

Steven Paul Woods, Emily Conover, Julie D. Rippeth, Catherine L. Carey, Raul Gonzalez, Thomas D. Marcotte, Robert K. Heaton, Igor Grant and The HIV Neurobehavioral Research Center (HNRC) Group

            HIV-associated dementia (HAD) is widely considered a "subcortical" dementia that involves a disruption of frontal-basal ganglia circuits. Deficits in verbal fluency are common in HAD; however, the cognitive underpinnings of these deficits are not well understood. To elucidate the cognitive mechanisms underlying the diminished verbal fluency output in HAD, we examined several qualitative aspects of letter fluency in 21 individuals with HAD, 51 nondemented persons with HIV infection (HIV+), and 30 healthy controls (HC) who were comparable for age, education, sex, ethnicity, and estimated premorbid verbal intelligence. The verbal fluency protocols were scored to obtain the total number of correct words, average phonemic cluster size, total number of switches between phonemic clusters, and the proportion of error responses (i.e., intrusions, perseverations, and variants). Consistent with prior research, HAD participants produced significantly fewer total correct words relative to the HC and nondemented HIV+ groups. The HAD group also demonstrated fewer switches and a higher proportion of response errors (especially intrusion errors), but no differences were observed in average cluster size. Findings are interpreted as reflecting a disruption of rule-guided lexical-semantic search strategies in HAD, perhaps mediated by prefrontal-striatal circuit dysfunction, rather than depleted lexical-semantic memory stores.



Wishful reality distortions in confabulation: a case report*1, In Press, Corrected Proof, Available online 6 January 2004

Aikaterini Fotopoulou, Mark Solms and Oliver Turnbull

            Several theories have been proposed to account for the complex cognitive mechanisms underlying the various forms and manifestations of confabulation. As regards the content of confabulations, deficit accounts explain what is lacking in the confabulations, but accounts of the positive features of the content may also be required to explain what remains. There is reason to believe that the content of confabulations is not motivationally neutral; in particular, they appear to `improve' the world experienced by the patient, making it more pleasant than the reality of the situation demands. The present study investigated the content of the confabulations of a neurological patient, ES: a 56-year-old man, who developed a striking confabulatory syndrome following removal of a meningioma in the pituitary and suprasellar region. ES's cognitive abilities were severely compromised, and he confabulated continuously and bizarrely. Raters presented with transcriptions of ES's confabulations found them to represent significantly more pleasant experiences than their corresponding, misrepresented realities. This finding suggests that confabulations include motivated (or `wishful') content. The influence of this motivational feature of confabulation must be considered in parallel with the memory and executive deficits which contribute to the mechanism of confabulation.



Spatial attention speeds discrimination without awareness in blindsight, In Press, Corrected Proof, Available online 5 January 2004

R. W. Kentridge, C. A. Heywood and L. Weiskrantz

            An intimate relationship is often assumed between visual attention and visual awareness. Using a subject, patient GY, with the neurological condition of `blindsight' we show that although attention may be a necessary precursor to visual awareness it is not a sufficient one. Using a Posner endogenous spatial cueing paradigm we showed that the time our subject needed to discriminate the orientation of a stimulus was reduced if he was cued to the location of the stimulus. This reaction-time advantage was obtained without any decrease in discrimination accuracy and cannot therefore be attributed to speed-error trade-off or differences in bias between cued and uncued locations. As a result of his condition GY was not aware of the stimuli to which processing was attentionally facilitated. Attention cannot, therefore be a sufficient condition for awareness.



One good turn deserves another: an event-related brain potential study of rotated mirror–normal letter discriminations, In Press, Corrected Proof, Available online 5 January 2004

Jeff P. Hamm, Blake W. Johnson and Michael C. Corballis

            The time to decide if a letter is normal or backwards (mirror-reversed) increases as the letter is rotated away from the upright. It is widely accepted that this increase in time reflects the mental rotation of the stimulus to the upright orientation in order to determine the mirror–normal status of the stimulus. Although response times tend to be longer for mirrored stimuli than for normal stimuli, the difference is constant across orientation. Little work has been focused on why mirror-image stimuli produce longer response times than normal stimuli. This study examines the question of whether or not mirrored stimuli are rotated in the picture plane at the same time as normal stimuli, and if so, why response times to mirrored stimuli are longer than that for normal stimuli. Both the behavioural and electrophysiological findings suggest that the mirrored stimuli are not only rotated in the picture plane, but that they are subsequently rotated to the normal view. It is this additional rotation that produces, at least in part, the delayed response times for mirror-image stimuli.






Volume 42, Issue 7, Pages 847-996 (2004)          



Volume 42, Issue 7, Pages 847-996 (2004)   




Early movement impairments in a patient recovering from optic ataxia, Pages 847-854

Alice C. Roy , Silvia Stefanini , Giovanni Pavesi and Maurizio Gentilucci

            Since Balint's first description, optic ataxia has been considered as a pure visuomotor impairment produced by a lesion of the posterior parietal cortex. Beyond general agreement on the parietal involvement in visually guided behaviour, the exact role of the dorsal posterior parietal cortex in the temporal aspects of visuomotor control remains unclear. Recent evidence has indicated a specific involvement of the parietal cortex in the on-line visual guidance of movement. Here, we report the motor performance of, GT, a patient recovering from an optic ataxia due to a right focal lesion of the dorsal posterior parietal cortex. When asked to reach and grasp, with his left contralesional hand, different sized objects, located at different positions from his body, GT showed an apparently complete recovery from optic ataxia. However, the early kinematic aspects of GTs prehension movement were not normally tuned either by intrinsic or extrinsic visual properties of objects. At variance with both an age-matched control group and a neurological patient with a right internal capsule lesion and no sign of optic ataxia, GTs latencies to peak wrist acceleration and peak velocity were not modulated by object location. A similar defective pattern was present in GTs grasping component where, despite the sparing of the classical scaling of grip aperture, object size did not modulate the peak velocity of grip aperture. These results constitute evidence that the posterior region of the dorsal parietal cortex, besides playing a role in the on-line control of movement execution may also be involved in the programming of early kinematics parameters.



Changes in brain activation during the acquisition of a new bimanual coordination task, Pages 855-867

F. Debaere , N. Wenderoth , S. Sunaert , P. Van Hecke and S. P. Swinnen

            Motor skill acquisition is associated with the development of automaticity and induces neuroplastic changes in the brain. Using functional magnetic resonance imaging (fMRI), the present study traced learning-related activation changes during the acquisition of a new complex bimanual skill, requiring a difficult spatio-temporal relationship between the limbs, i.e., cyclical flexion–extension movements of both hands with a phase offset of 90°. Subjects were scanned during initial learning and after the coordination pattern was established. Kinematics of the movements were accurately registered and showed that the new skill was acquired well. Learning-related decreases in activation were found in right dorsolateral prefrontal cortex (DLPFC), right premotor, bilateral superior parietal cortex, and left cerebellar lobule VI. Conversely, learning-related increases in activation were observed in bilateral primary motor cortex, bilateral superior temporal gyrus, bilateral cingulate motor cortex (CMC), left premotor cortex, cerebellar dentate nuclei/lobule III/IV/Crus I, putamen/globus pallidus and thalamus. Accordingly, bimanual skill learning was associated with a shift in activation among cortico-subcortical regions, providing further evidence for the existence of differential cortico-subcortical circuits preferentially involved during the early and advanced stages of learning. The observed activation changes account for the transition from highly attention-demanding task performance, involving processing of sensory information and corrective action planning, to automatic performance based on memory representations and forward control.



Receptive amusia: temporal auditory processing deficit in a professional musician following a left temporo-parietal lesion, Pages 868-877

Marie Di Pietro , Marina Laganaro , Béatrice Leemann and Armin Schnider

            This study examined the musical processing in a professional musician who suffered from amusia after a left temporo-parietal stroke. The patient showed preserved metric judgement and normal performance in all aspects of melodic processing. By contrast, he lost the ability to discriminate or reproduce rhythms. Arrhythmia was only observed in the auditory modality: discrimination of auditorily presented rhythms was severely impaired, whereas performance was normal in the visual modality. Moreover, a length effect was observed in discrimination of rhythm, while this was not the case for melody discrimination. The arrhythmia could not be explained by low-level auditory processing impairments such as interval and length discrimination and the impairment was limited to auditory input, since the patient produced correct rhythmic patterns from a musical score. Since rhythm processing was selectively disturbed in the auditory modality, the arrhythmia cannot be attributed to a impairment of supra-modal temporal processing. Rather, our findings suggest modality-specific encoding of musical temporal information. Besides, it is proposed that the processing of auditory rhythmic sequences involves a specific left hemispheric temporal buffer.



The contribution of executive processes to deceptive responding, Pages 878-901

Ray Johnson, Jr. , Jack Barnhardt and John Zhu

            We measured behavioral responses (RT) and recorded event-related brain potentials (ERPs) when participants made truthful and deceptive responses about perceived and remembered stimuli. Participants performed an old/new recognition test under three instructional conditions: Consistent Truthful, Consistent Deceptive and Random Deceptive. Compared to Consistent Truthful responses, Consistent Deceptive responses to both perceived and remembered stimuli produced the same pattern of less accurate, slower and more variable responses and larger medial frontal negativities (MFN). The MFN is thought to reflect activity in anterior cingulate cortex, a brain area involved in monitoring actions and resolving conflicting response tendencies. The Random Deceptive condition required participants to strategically monitor their long-term response patterns to accommodate a deceptive strategy. Even compared to the Consistent Deceptive condition, RTs in the Random Deceptive condition were significantly slower and more variable and MFN activity increased significantly. MFN scalp distribution results revealed the presence of three different patterns of brain activity; one each for truthful responses, deceptive responses and strategic monitoring. Thus, the data indicate that anterior cingulate cortex plays a key role in making deceptive responses.



Cognitive and motor functioning in a patient with selective infarction of the left basal ganglia: evidence for decreased non-routine response selection and performance, Pages 902-911

Angela K. Troyer , Sandra E. Black , Maria L. Armilio and Morris Moscovitch

            Focal damage to the basal ganglia is relatively rare, and little is known about the cognitive effects of damage to specific basal ganglia structures. A 28-year-old, highly educated male (patient RI) sustained a unilateral left ischemic infarction involving primarily the putamen and secondarily the head of the caudate and the anterior internal capsule. Two detailed neuropsychological assessments, at 3 and 16 months post-infarction, revealed that a majority of cognitive abilities were spared. RI's general intelligence, simple attention, concept formation, cognitive flexibility, and explicit memory were unaffected. Select cognitive abilities were affected, and these appeared to be related to direct involvement of the putamen and/or to indirect disruption of circuits between the basal ganglia and frontal lobes. Consistent with involvement of the left putamen, RI showed micrographia with his right hand. Interestingly, his micrographia was context-dependent, appearing only when verbal expression was involved (e.g., present when writing spontaneously, but not when copying sentences or when drawing). Evidence of disruption to frontal systems included variably decreased sustained attention, mildly decreased ability to generate words and to generate ideas, and significantly impaired abstraction ability in both verbal and visual modalities. Although there are several possible interpretations for these findings, this pattern of cognitive and motor functioning is consistent with neuroimaging research suggesting that the frontal/subcortical circuit between the putamen and frontal motor areas plays a role in non-routine response selection and performance.



Advance preparation of set-switches in Parkinson's disease, Pages 912-919

Petra M. J. Pollux

            Eighteen patients with Parkinson's disease (PD) and 18 healthy control subjects were presented with a switching task where stimuli elicited either one (no-conflict condition) or two (conflict condition) task-relevant stimulus-response mappings. The response stimulus interval (RSI) between trials was varied to allow investigation of the extent to which participants engaged in advanced preparation of task set. In line with previous findings, set-switching deficits of PD patients were only observed in the conflict condition. Prolonging the RSI led to a reduction of switch costs for control subjects in both the conflict and the no-conflict task, whereas this effect was attenuated for PD patients in the conflict condition. This deficit was explained in terms of a reduced ability to maintain cue-action representations active in working memory in high interference conditions, and was related to the possible role of the frontostriatal circuit in maintaining focussed attention.



Mirror asomatognosia in right lesions stroke victims, Pages 920-925

J. Paysant , J. M. Beis , L. Le Chapelain and J. M. André

            The objectives of this prospective study were: to search for mirror-induced disorders of the body image in right hemisphere stroke victims using a description task of the contralateral upper limb, to analyze their clinical features, and to discuss possible mechanisms. Sixteen consecutive patients with documented unilateral right hemisphere stroke were examined for asomatognosia at the acute phase of stroke, then at least 2 months after stroke under three test conditions: without a mirror, with a conventional mirror, with an inverted mirror. Video recordings of the tests were analyzed to assess performance. The diagnosis of asomatognosia was retained if the subject reported at least one of three sensations: limb transformation, limb strangeness, and/or limb alienation. During the acute phase, 14/16 patients presented manifestations of asomatognosia. All of these spontaneous manifestations had disappeared 2 months later, but were reactivated in 12 patients when exposed to mirror images. The mirror tests revealed four situations: no disorder (n=4), asomatognosia with both mirrors (n=5), asomatognosia with the conventional or inverted mirrors (n=1 and 5), and asomatognosia with the inverted mirror (n=1). These manifestations were designated as mirror-asomatognosia, a disorder resulting from adaptations of the procedures leading to reorganization of the internal representations of the body image. These findings suggest there are several such internal representations of the body image and that direct body image and mirror body image would be two specific ones. These clinical manifestations and their evolution over time are an expression of the progressive nature of the underlying compensatory mechanisms made possible by brain plasticity.



Inductive reasoning and implicit memory: evidence from intact and impaired memory systems, Pages 926-938

Luisa Girelli , Carlo Semenza and Margarete Delazer

            In this study, we modified a classic problem solving task, number series completion, in order to explore the contribution of implicit memory to inductive reasoning. Participants were required to complete number series sharing the same underlying algorithm (e.g., +2), differing in both constituent elements (e.g., 2 4 6 8 versus 5 7 9 11) and correct answers (e.g., 10 versus 13). In Experiment 1, reliable priming effects emerged, whether primes and targets were separated by four or ten fillers. Experiment 2 provided direct evidence that the observed facilitation arises at central stages of problem solving, namely the identification of the algorithm and its subsequent extrapolation. The observation of analogous priming effects in a severely amnesic patient strongly supports the hypothesis that the facilitation in number series completion was largely determined by implicit memory processes. These findings demonstrate that the influence of implicit processes extends to higher level cognitive domain such as induction reasoning.



Anterior asymmetrical alpha activity predicts Iowa gambling performance: distinctly but reversed, Pages 939-943

Dennis J. L. G. Schutter , Edward H. F. de Haan and Jack van Honk

            Animal research indicates that the prefrontal cortex (PFC) plays a crucial role in decision making. In concordance, deficits in decision making have been observed in human patients with damage to the PFC. Contemporary accounts of decision making suggest that emotion guides the process of decision making by ways of providing for reward–punishment contingencies. A task capable of assessing the influence of reward and punishment on decision making is the Iowa gambling task. In this task decisions become motivated by inherent punishment and reward schedules. Insensitivity for punishment together with a strong reward dependency results in risk taking, which is in the gambling task the disadvantageous strategy. Interestingly, the processing of punishment and reward is argued to be lateralized over the right and left PFC, respectively. Here we investigated whether more relative left compared to right-sided frontal brain activity (left-sided dominance) quantified as reduced alpha (8–12 Hz) activity in the electroencephalogram (EEG) would lead to a more risky, disadvantageous pattern of decision making. Contrary to what was expected, relatively more right compared to left frontal brain activity was strongly associated with the disadvantageous strategy. The results are discussed in terms of recent theoretical accounts which argue that the functional interpretation of baseline frontal alpha activity depends on the mental operation involved and does not necessarily imply inactivity.



From mental power to muscle power––gaining strength by using the mind, Pages 944-956

Vinoth K. Ranganathan , Vlodek Siemionow , Jing Z. Liu , Vinod Sahgal and Guang H. Yue

            The purposes of this project were to determine mental training-induced strength gains (without performing physical exercises) in the little finger abductor as well as in the elbow flexor muscles, which are frequently used during daily living, and to quantify cortical signals that mediate maximal voluntary contractions (MVCs) of the two muscle groups. Thirty young, healthy volunteers participated in the study. The first group (N=8) was trained to perform "mental contractions" of little finger abduction (ABD); the second group (N=8) performed mental contractions of elbow (ELB) flexion; and the third group (N=8) was not trained but participated in all measurements and served as a control group. Finally, six volunteers performed training of physical maximal finger abductions. Training lasted for 12 weeks (15 min per day, 5 days per week). At the end of training, we found that the ABD group had increased their finger abduction strength by 35% (P<0.005) and the ELB group augmented their elbow flexion strength by 13.5% (P<0.001). The physical training group increased the finger abduction strength by 53% (P<0.01). The control group showed no significant changes in strength for either finger abduction or elbow flexion tasks. The improvement in muscle strength for trained groups was accompanied by significant increases in electroencephalogram-derived cortical potential, a measure previously shown to be directly related to control of voluntary muscle contractions. We conclude that the mental training employed by this study enhances the cortical output signal, which drives the muscles to a higher activation level and increases strength.


A role for right medial prefrontal cortex in accurate feeling-of-knowing judgments: evidence from patients with lesions to frontal cortex, Pages 957-966

David M. Schnyer , Mieke Verfaellie , Michael P. Alexander , Ginette LaFleche , Lindsay Nicholls and Alfred W. Kaszniak

            The hypothesis that prefrontal cortex plays a critical role in accurate predictions of episodic memory performance was tested using the feeling-of-knowing (FOK) paradigm. Fourteen patients with a broad spectrum of damage to the frontal cortex and matched controls read sentences and later were tested for recall memory, confidence judgments, and FOK accuracy using as cues the sentences with the final word missing. While frontal patients were impaired at recall and recognition memory, they were able to make accurate confidence judgments about their recall attempts. By contrast, as a group, the patients were markedly impaired in the accuracy of their prospective FOK judgments. Lesion analysis of frontal patients with clear FOK impairment revealed an overlapping region of damage in right medial prefrontal cortex. These findings provide functional and anatomical evidence for a dissociation between recall confidence and prospective memory monitoring and are discussed in terms of familiarity and access theories of FOK predictions.



Cortical organization for receptive language functions in Chinese, English, and Spanish: a cross-linguistic MEG study, Pages 967-979

C. E. Valaki , F. Maestu , P. G. Simos , W. Zhang , A. Fernandez , C. M. Amo , T. M. Ortiz and A. C. Papanicolaou

            Chinese differs from Indo–European languages in both its written and spoken forms. Being a tonal language, tones convey lexically meaningful information. The current study examines patterns of neurophysiological activity in temporal and temporoparietal brain areas as speakers of two Indo–European languages (Spanish and English) and speakers of Mandarin–Chinese were engaged in a spoken-word recognition task that is used clinically for the presurgical determination of hemispheric dominace for receptive language functions. Brain magnetic activation profiles were obtained from 92 healthy adult volunteers: 30 monolingual native speakers of Mandarin–Chinese, 20 Spanish-speaking, and 42 native speakers of American English. Activation scans were acquired in two different whole-head MEG systems using identical testing methods. Results indicate that (a) the degree of hemispheric asymmetry in the duration of neurophysiological activity in temporal and temporoparietal regions was reduced in the Chinese group, (b) the proportion of individuals who showed bilaterally symmetric activation was significantly higher in this group, and (c) group differences in functional hemispheric asymmetry were first noted after the initial sensory processing of the word stimuli. Furthermore, group differences in the degree of hemispheric asymmetry were primarily due to greater degree of activation in the right temporoparietal region in the Chinese group, suggesting increased participation of this region in the spoken word recognition in Mandarin–Chinese.



Hippocampal adaptation to face repetition in healthy elderly and mild cognitive impairment, Pages 980-989

Sterling C. Johnson , Leslie C. Baxter , Lana Susskind-Wilder , Donald J. Connor , Marwan N. Sabbagh and Richard J. Caselli

            We examined the dynamic process of encoding novel repeating faces using functional MRI (fMRI) in non-demented elderly volunteers with and without diagnosed memory problems. We hypothesized that adaptation (repetition dependent reduction in activity) would occur in the mesial temporal lobe (MTL), and that this would be associated with cognitive status. Twenty-three right-handed volunteers were studied with an experimental encoding paradigm during fMRI scanning. Twelve participants had the diagnosis of mild cognitive impairment-amnestic type (MCI). The remaining 11 were cognitively healthy. All were diagnosed with a comprehensive neuropsychological battery and neurological evaluation prior to the study; they also received a brief cognitive battery the day of the scan. During the event-related fMRI task, participants viewed unfamiliar faces that repeated on average every 25 s with seven repetitions. The reduction in activation response as a function of repetition of unfamiliar faces was modeled in SPM99. Statistical parametric maps of adaptation slopes reflecting the decrease in activation with stimulus repetition were calculated for each participant, followed by a random-effects group analysis in which slope images were tested for significant group differences. Significant differences in adaptation slopes, with more negative slopes in the controls, were found in the medial temporal search region in the hippocampus and parahippocampal gyrus bilaterally, right more than left. Gray matter density analyses suggest the adaptation difference is not due to atrophy. Results suggest that the medial temporal response over repeated presentation is related to clinical status. Probes of incremental encoding processes over trials may be useful markers of medial temporal lobe integrity.







Ann E. Power

Slow-wave sleep, acetylcholine, and memory consolidation

PNAS published March 1, 2004, 10.1073/pnas.0400990101





PNAS Online

Venezuelan kindreds reveal that genetic and environmental factors modulate Huntington's disease age of onset

The U.S.-Venezuela Collaborative Research Project  and Nancy S. Wexler et al.

            Huntington's disease (HD) is an autosomal dominant neurodegenerative disease caused by a triplet (CAG) expansion mutation. The length of the triplet repeat is the most important factor in determining age of onset of HD, although substantial variability remains after controlling for repeat length. The Venezuelan HD kindreds encompass 18,149 individuals spanning 10 generations, 15,409 of whom are living. Of the 4,384 immortalized lymphocyte lines collected, 3,989 DNAs were genotyped for their HD alleles, representing a subset of the population at greatest genetic risk. There are 938 heterozygotes, 80 people with variably penetrant alleles, and 18 homozygotes. Analysis of the 83 kindreds that comprise the Venezuelan HD kindreds demonstrates that residual variability in age of onset has both genetic and environmental components. We created a residual age of onset phenotype from a regression analysis of the log of age of onset on repeat length. Familial correlations (correlation ± SE) were estimated for sibling (0.40 ± 0.09), parent-offspring (0.10 ± 0.11), avuncular (0.07 ± 0.11), and cousin (0.15 ± 0.10) pairs, suggesting a familial origin for the residual variance in onset. By using a variance-components approach with all available familial relationships, the additive genetic heritability of this residual age of onset trait is 38%. A model, including shared sibling environmental effects, estimated the components of additive genetic (0.37), shared environment (0.22), and nonshared environment (0.41) variances, confirming that 40% of the variance remaining in onset age is attributable to genes other than the HD gene and 60% is environmental. Finding the genes that contribute to this variation and studying the patients' environments may reveal what triggers, worsens, or betters the symptoms, leading to treatments that slow disease onset or progression.







PNAS Online

Amyloid  peptide load is correlated with increased -secretase activity in sporadic Alzheimer's disease patients

Rena Li *, Kristina Lindholm , Li-Bang Yang , Xu Yue *, Martin Citron , Riqiang Yan ¶, Thomas Beach ||, Lucia Sue ||, Marwan Sabbagh **, Huaibin Cai , Philip Wong , Donald Price , and Yong Shen 

            Edited by L. L. Iversen, University of Oxford, Oxford, United Kingdom, and approved December 5, 2003 (received for review September 19, 2002)

            Whether elevated -secretase (BACE) activity is related to plaque formation or amyloid  peptide (A) production in Alzheimer's disease (AD) brains remains inconclusive. Here, we report that we used sandwich enzyme-linked immunoabsorbent assay to quantitate various A species in the frontal cortex of AD brains homogenized in 70% formic acid. We found that most of the A species detected in rapidly autopsied brains (<3 h) with sporadic AD were A1-x and A1-42, as well as Ax-42. To establish a linkage between A levels and BACE, we examined BACE protein, mRNA expression and enzymatic activity in the same brain region of AD brains. We found that both BACE mRNA and protein expression is elevated in vivo in the frontal cortex. The elevation of BACE enzymatic activity in AD is correlated with brain A1-x and A1-42 production. To examine whether BACE elevation was due to mutations in the BACE-coding region, we sequenced the entire ORF region of the BACE gene in these same AD and nondemented patients and performed allelic association analysis. We found no mutations in the ORF of the BACE gene. Moreover, we found few changes of BACE protein and mRNA levels in Swedish mutated amyloid precursor protein-transfected cells. These findings demonstrate correlation between A loads and BACE elevation and also suggest that as a consequence, BACE elevation may lead to increased A production and enhanced deposition of amyloid plaques in sporadic AD patients.




PNAS Online


Coauthorship networks and patterns of scientific collaboration

M. E. J. Newman 


            By using data from three bibliographic databases in biology, physics, and mathematics, respectively, networks are constructed in which the nodes are scientists, and two scientists are connected if they have coauthored a paper. We use these networks to answer a broad variety of questions about collaboration patterns, such as the numbers of papers authors write, how many people they write them with, what the typical distance between scientists is through the network, and how patterns of collaboration vary between subjects and over time. We also summarize a number of recent results by other authors on coauthorship patterns.




PNAS Online


Traffic-based feedback on the web

Jonathan Aizen *, Daniel Huttenlocher *, Jon Kleinberg *, and Antal Novak *

*Department of Computer Science, Cornell University, 4130 Upson Hall, Ithaca, NY 14850; and Internet Archive, Presidio, San Francisco, CA 94129 E-mail:

            Usage data at a high-traffic web site can expose information about external events and surges in popularity that may not be accessible solely from analyses of content and link structure. We consider sites that are organized around a set of items available for purchase or download, consider, for example, an e-commerce site or collection of online research papers, and we study a simple indicator of collective user interest in an item, the batting average, defined as the fraction of visits to an item’s description that result in an acquisition of that item. We develop a stochastic model for identifying points in time at which an item’s batting average experiences significant change. In experiments with usage data from the Internet Archive, we find that such changes often occur in an abrupt, discrete fashion, and that these changes can be closely aligned with events such as the highlighting of an item on the site or the appearance of a link from an active external referrer. In this way, analyzing the dynamics of item popularity at an active web site can help characterize the impact of a range of events taking place both on and off the site.



Melissa A. Rosenkranz, Daren C. Jackson, Kim M. Dalton, Isa Dolski, Carol D. Ryff, Burt H. Singer, Daniel Muller, Ned H. Kalin, and Richard J. Davidson
Affective style and in vivo immune response: Neurobehavioral mechanisms
PNAS 2003 100: 11148-11152

            By monitoring activity levels in the human brain's prefrontal cortex, the researchers demonstrate for the first time that people who have more activity in the left side of this area also have a stronger immune response against disease. The findings, soon to be published in the online edition of the journal Proceedings of the National Academy of Sciences, pinpoint one of the mechanisms underlying the link between mental and physical well-being. Numerous scientific studies show that keeping a positive attitude can keep a person healthy, says Richard Davidson, a UW-Madison neuroscientist and senior author of the paper. But he adds that the reasons why this connection exists are poorly understood. By turning to the brain - an organ that sends signals that guide emotional response - Davidson and his group have identified one possible explanation: activity in the prefrontal cortex, a region of the brain long associated with affective style, or how a person responds emotionally to an event. Emotions play an important role in modulating bodily systems that influence our health," says Davidson. "We turned to the brain to understand the mechanisms by which the mind influences the body." While earlier studies have linked emotional and physical health, as well as brain activity and affective style, Davidson says none have established a direct link between brain activity and immune function. The latest study by the UW-Madison group demonstrates this connection. For the study, the researchers worked with 52 individuals between the ages of 57 and 60 who were recruited from the Wisconsin Longitudinal Study - a long-term study of more than 10,000 people who graduated from Wisconsin high schools in 1957. Specifically, the scientists wanted to know if people who showed more activity in the left side of the prefrontal cortex - a part of the brain associated with positive emotional responses - also showed greater immunity to the influenza virus after vaccination. To answer this question, the researchers vaccinated all the subjects against the flu virus. Before vaccination, they measured the study participants' brain activity, both at a baseline state and during emotion eliciting memory tasks. During these tasks, the participants were asked to recall two events - one that made them feel intensely happy and another that left them feeling intensely sad, fearful or angry. As the respondents focused on the emotion experienced for one minute, the researchers measured the electrical activity in both the right and left sides of the prefrontal cortex. Previous studies, notes Davidson, have shown that individuals with greater activity on the right side of this brain region tend to have a more negative affective style, which can cause these individuals to respond inappropriately to emotional events. The researchers collected these prefrontal cortex activity levels again after the subjects spent five minutes writing about the particular events. At this time, they also measured the participants' eyeblink reflex in response to sudden noises. This measure, explains Davidson, provides a convenient and objective way to measure how negatively or positively a person reacts to a stimulus. Three times in the six months following vaccination, the researchers collected serum samples from each subject to track the number of flu-fighting antibodies in the blood, which can determine immune function. Six months after being vaccinated against the flu virus, the subjects who had greater activity in the left side of the prefrontal cortex, instead of the right side, also had a greater rise in the number of antibodies for influenza, says Davidson. This study establishes that people with a pattern of brain activity that has been associated with a positive affective style are also the ones to show the best response to the flu vaccine," says the Wisconsin researcher. "It begins to suggest a mechanism for why subjects with a more positive emotional disposition may be healthier."









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Brain Images Reveal Effects Of Antidepressants


MADISON - The experiences of millions of people have proved that antidepressants work, but only with the advent of sophisticated imaging technology have scientists begun to learn exactly how the medications affect brain structures and circuits to bring relief from depression.


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Researchers at the University of Wisconsin-Madison and UW Medical School recently added important new information to the growing body of knowledge. For the first time, they used functional magnetic resonance imaging (fMRI)--technology that provides a view of the brain as it is working--to see what changes occur over time during antidepressant treatment while patients experience negative and positive emotions.


The study appears in the January issue of the American Journal of Psychiatry. UW psychology professor Richard Davidson, Ph.D., psychiatry department chair Ned Kalin, MD, research associate William Irwin and research assistant Michael Anderle were the authors. The researchers found that when they gave the antidepressant venlafaxine (Effexor(r)) to a small group of clinically depressed patients, the drug produced robust alterations in the anterior cingulate. This area of the brain has to do with focused attention and also becomes activated when people face conflicts. Unexpectedly, the changes were observed in just two weeks. "Conducting repeated brain scans in these patients allowed us to see for the first time how quickly antidepressants work on brain mechanisms," said Davidson, who also is director of the W. M. Keck Laboratory for Functional Brain Imaging and Behavior, where imaging for the study took place. He noted that the findings were surprising because patients don't usually begin noticing mood improvements until after they have been taking antidepressants for three to five weeks. The researchers also found that while the depressed patients displayed lower overall activity in the anterior cingulate than non-depressed controls, those depressed patients who showed relatively more activity before treatment responded better to the medication than those with lower pre-treatment activity. This kind of information may be extremely useful to clinicians someday, Kalin said. "We expect that physicians in the future will be able to predict which patients will be the best candidates for antidepressants simply by looking at brain scans that reveal this type of pertinent information," said Kalin, who also is director of the HealthEmotions Research Institute, where scientists concentrate on uncovering the scientific basis of linkages between emotions and health. One third of all patients treated with antidepressants do not respond to them, and of those that do, only about 50 percent get completely better, he added. Virtually all previous studies analyzing brain activity in depressed people used PET (positron emission tomography) and SPECT (single photon emission computed tomography) technology. With these imaging systems scientists were not able to obtain pictures with the same resolution as that which is now obtainable with fMRI, which provides a "working snapshot" of the brain. The Wisconsin team used fMRI's capability to capture brain activity as it occurred to record subjects' reactions as they viewed pictures designed to stimulate negative and positive emotions. "We believe that we can uncover the best indicators of treatment changes when we present research subjects these emotion challenges," said Davidson. "The pictures activate the individual circuits that underlie different kinds of emotional responses." UW emotions researchers have been using fMRIs with emotion-challenging pictures for several years in an effort to understand normal and abnormal brain responses to a range of emotions. They theorize that in depressed people, reactions to negative emotions are similar to, but more exaggerated than, reactions that non-depressed people have, and that the reactions may be more difficult to turn off. (i.e., neurosensitization!)




J Neuropsychiatry Clin Neurosci 16:29-36, February 2004

Differential DSM-III Psychiatric Disorder Prevalence Profiles in Dystonia and Parkinson’s Disease

Edward C. Lauterbach, M.D., Alan Freeman, M.D. and Robert L. Vogel, Ph.D. ; (E-mail).

            The authors investigated the prevalence of DIS-ascertained DSM-III psychiatric disorders occurring in 28 patients with dystonia and 28 patients with Parkinson’s Disease (PD). In patients with dystonia, lifetime prevalences of major depression (25.0%), bipolar disorder (7.1%), atypical bipolar disorder (7.1%), social phobia (17.9%), and generalized anxiety disorder (25.0%) were significantly more common than in epidemiologic catchment area (ECA) study population controls (p < 0.005). Social phobia and generalized anxiety disorder preceded dystonia (primary), while bipolar disorder developed after dystonia onset (secondary). In PD patients, the lifetime prevalence of simple phobia (35.7%, p < 0.0001) and atypical depression (21.4%) were significantly more common. Parkinson’s Disease was associated with primary simple phobia and secondary atypical depression. These findings are considered in light of previous results and in terms of the differences in pallidothalamic physiologies in dystonia and PD. These data suggest distinctive profiles of psychiatric disorders in dystonia and PD.



Alexithymia Correlates With the Size of the Right Anterior Cingulate.

Psychosomatic Medicine. 66(1):132-140, January/February 2004.

Gundel, Harald MD; Lopez-Sala, Anna PhD; Ceballos-Baumann, Andres O. MD, PhD; Deus, Joan PhD; Cardoner, Narcis MD; Marten-Mittag, Birgit MS; Soriano-Mas, Carles PhD, and; Pujol, Jesus MD

            Objective: The authors investigated a possible relationship between interindividual variability in anterior cingulate gyrus (ACG) morphology and alexithymia. Materials and Methods: Magnetic resonance images were obtained in 100 healthy university graduates (51 female, 49 male; mean age 25.6 y). Surface area measurements of the ACG were performed on reformatted sagittal views in both hemispheres. The Toronto Alexithymia Scale (TAS-20) and the Temperament and Character Inventory (TCI) were administered. Results: Right ACG surface area significantly correlated with TAS-20 total score in men (r = 0.37; p = 0.009) and in women (r = 0.30; p = 0.034). After controlling for three TCI subscales (harm avoidance, self-directedness, and self-transcendency), the correlation between TAS-20 total and right ACG became nonsignificant in women, but was only slightly reduced (r = 0.32; p = 0.032) in men. A linear regression model with right ACG as a dependent variable revealed brain volume, TCI-harm avoidance and TAS 20 total score as significant predictors in the total sample (explained proportion of total variation (EPTV) 37%). In men, beside brain volume, only TAS-20 total score showed a highly significant contribution (EPTV 41%), whereas in women only TCI-harm avoidance was a significant predictor (EPTV 36%). Conclusions: The authors' findings indicate that there is a significant positive relation between the size of the right ACG and alexithymia as measured with the TAS in healthy subjects. This applies especially for men whereas in women ACG size is more associated with the subscale harm avoidance of the TCI. Our findings also suggest a partial lateralization of human emotion processing, especially negative emotion.