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The valence-arousal (W. Heller, 1993) and approach-withdrawal (R. J. Davidson, 1998a) models hypothesize that particular patterns of hemispheric brain activity are associated with specific motivational tendencies and psychopathologies. We tested several of these predictions in two groups-a posttraumatic stress disorder (PTSD) and a "supercontrol" group, selected to be maximally different from those with PTSD. Contrary to almost all hypotheses, individuals with PTSD did not differ from controls on resting electroencephalogram (EEG) asymmetry. Particular aspects of PTSD were also not related to EEG hemisphere differences. Our null findings are consistent with the few studies that have examined resting EEG asymmetries in PTSD and suggest that PTSD may be associated with different processes than psychopathologies previously examined in studies of hemispheric brain activity (e.g., major depressive disorder, panic disorder).

BACKGROUND: Although cognitive behaviour therapy (CBT) is the treatment of choice for post-traumatic stress disorder (PTSD), approximately half of patients do not respond to CBT. No studies have investigated the capacity for neural responses during fear processing to predict treatment response in PTSD.METHOD: Functional magnetic resonance imaging (fMRI) responses of the brain were examined in individuals with PTSD (n=14). fMRI was examined in response to fearful and neutral facial expressions presented rapidly in a backwards masking paradigm adapted for a 1.5 T scanner. Patients then received eight sessions of CBT that comprised education, imaginal and in vivo exposure, and cognitive therapy. Treatment response was assessed 6 months after therapy completion. RESULTS: Seven patients were treatment responders (defined as a reduction of 50% of pretreatment scores) and seven were non-responders. Poor improvement after treatment was associated with greater bilateral amygdala and ventral anterior cingulate activation in response to masked fearful faces. CONCLUSIONS: Excessive fear responses in response to fear-eliciting stimuli may be a key factor in limiting responses to CBT for PTSD. This excessive amygdala response to fear may reflect difficulty in managing anxiety reactions elicited during CBT, and this factor may limit optimal response to therapy.

Elevated body mass index (BMI) is associated with adverse neurocognitive outcome in adults, including reduced neuropsychological test performance. It is unknown whether this relationship also exists in children and adolescents. A total of 478 children and adolescents (age 6-19) without significant medical or psychiatric history provided demographic information and completed a computerized cognitive test battery. Participants were categorized using clinical criteria into underweight, normal weight, at risk for overweight and overweight groups based on age and gender. Partial correlation and MANCOVA analyses adjusting for age and intellectual function found no relationship between BMI and cognitive test performance in the full sample. However, analyses performed separately by gender showed that underweight females exhibited poorer memory performance than other female BMI groups. These findings suggest that elevated BMI is not associated with cognitive function in healthy children and adolescents, though underweight might be a risk factor for reduced memory performance in females. Further work is needed to clarify the inconsistent findings between adults and minors.

OBJECTIVE: To index the extent to which treatment response in posttraumatic stress disorder (PTSD) is predicted by rostral anterior cingulate cortex (rACC) volume. METHOD: We used structural magnetic resonance imaging in a 1.5 T scanner to examine subjects with PTSD (n = 13), traumatized control subjects (n = 13) and nontraumatized control subjects (n = 13). Subjects with PTSD then participated in 8 sessions of cognitive-behavioural therapy, after which we reassessed them for PTSD. RESULTS: According to voxel-based morphometry, treatment responders had larger rACC volume than nonresponders. Further, symptom reduction was associated with larger rACC volume. CONCLUSION: Consistent with evidence for the neural bases of extinction learning, PTSD patients with larger rACC volume may be better able to regulate fear during cognitive-behavioural therapy and thus achieve greater treatment gains.

This study investigated whether children and adolescents diagnosed with the predominantly inattentive and combined subtypes of attention deficit/hyperactivity disorder (AD/HD-in and AD/HD-com, respectively) differed on psychophysiological indices of working memory updating off- and on-stimulant medication, as compared with control subjects and each other. ERPs were recorded in AD/HD and control participants during a one-back working memory task. The N100 (discrimination), P150 (selection), N300 (memory retrieval), and P450wm (updating) components after nontarget stimuli, which served to update working memory with target identity, were assessed. Premedication abnormalities were obtained for the N300 component, delayed in the child AD/HD-com group, and attenuated in the adolescent AD/HD-in group and P450wm component for all AD/HD groups, expressed as either delayed latency and/or attenuated amplitude. ERP abnormalities were predominantly ameliorated after stimulant medication. There were no psychophysiological differences between the subtypes. A general feature of the disorder relates to a deficit in the conscious updating of working memory systems with newly relevant information (P450wm), which varies with age and subtype. Children with AD/HD-com and adolescents with AD/HD-in also exhibit abnormalities in the retrieval of relevant prior memories (N300). This study indicates that AD/HD is related to abnormalities in the capacity to modulate the content of working memory stores.

BACKGROUND: Previous studies have examined the impact of early life stress (ELS) on the gross morphometry of brain regions, including the corpus callosum. However, studies have not examined the relationship between ELS and the microstructural integrity of the brain. METHODS: In the present study we evaluated this relationship in healthy non-clinical participants using diffusion tensor imaging (DTI) and self-reported history of ELS. RESULTS: Regression analyses revealed significant reductions in fractional anisotropy (FA) within the genu of the corpus callosum among those exposed to the greatest number of early life stressors, suggesting reduced microstructural integrity associated with increased ELS. These effects were most pronounced in the genu of the corpus callosum compared to the body and splenium, and were evident for females rather than males despite no differences in total ELS exposure between the sexes. In addition, a further comparison of those participants who were exposed to no ELS vs. three or more ELS events revealed lower FA in the genu of the corpus callosum among the ELS-exposed group, with trends of FA reduction in the body and the whole corpus callosum. By contrast, there were no relationships between ELS and volumetric analysis of the CC regions. The two group did not differ significantly on measures of current depression, stress or anxiety. CONCLUSION: Our results reveal that greater exposure to ELS is associated with microstructural alterations in the white matter in the absence of significant volumetric changes. Importantly, our results indicate that exposure to ELS is associated with abnormalities on DTI despite the absence of clinically significant psychiatric symptoms. Future studies are needed to determine whether specific types of ELS are more likely to impact brain structure and function.

OBJECTIVE: This study explored the concurrent courses of the neuroanatomical and neuropsychological changes that occurred over the first 2-3 years of illness in patients with first-episode schizophrenia (FES). METHODS: Fifty-two patients with FES underwent neuropsychological testing and a structural magnetic resonance imaging (sMRI) scan within three months of their first presentation to mental health services with psychotic symptoms (time1). Patients' cognitive performance was evaluated via an extensive neuropsychological test battery, which assessed 9 cognitive domains. Of the 52 patients at time1, 32 returned 2-3 years later (time2) for follow-up neuropsychological testing, and 20 of these also underwent follow-up sMRI. MR images were preprocessed in SPM99. Grey matter volumes of patients' whole-brain, frontal lobes and temporal lobes were calculated by convolving the preprocessed images with manually-drawn binary masks. RESULTS: Patients exhibited longitudinal improvements in full-scale IQ, performance IQ and visual memory. In contrast, concurrent reductions in grey matter were observed for the whole-brain (3% reduction) and the frontal lobe (3.65% reduction). Furthermore, the extent of patients' whole-brain and frontal-lobe grey matter changes were positively correlated with longitudinal changes in verbal learning and memory. DISCUSSION: The results of this study suggest that while the early stages of schizophrenia are associated with a mild improvement in patients' overall cognitive functioning, they are also associated with progressive grey matter atrophy.

OBJECTIVE: It is increasingly recognized that cognitive assessments, unlike symptom ratings, provide a reliable predictor of functional outcome in schizophrenia. This study evaluated the utility of the 'IntegNeuro' computerized test battery for assessing cognition in first episode schizophrenia. We determined the presence of separable factors of general and social cognition, their equivalence to the consensus domains identified by the NIMH MATRICS project, and their effectiveness in predicting real world functional outcomes. METHOD: Fifty six first episode schizophrenia (FES) patients and 112 matched healthy controls were assessed on the touchscreen-based 'IntegNeuro' cognitive test battery and FES patients for social functioning (SOFAS) and quality of life (WHOQOL-BREF). RESULTS: Principal components analysis identified i) six factors corresponding to MATRICS domains of general cognition ('Information Processing Speed', 'Verbal Recall', 'Working Memory Capacity', 'Sustained Attention/Vigilance', 'Verbal Processing', 'Executive Function'), ii) an 'Emotional Intelligence' factor corresponding to the MATRICS social cognition domain, and iii) an additional 'Sensori-Motor Function' factor of general cognition and 'Negativity' factor of social cognition. Patients showed impairments relative to controls across all factors, but especially for Working Memory Capacity, followed by Verbal Memory, Sustained Attention/Vigilance and Negativity. These factors strongly predicted poorer social functioning in FES, along with poorer quality of life in psychological, social, and health satisfaction facets. CONCLUSION: The IntegNeuro battery has utility for assessing separable domains of general and social cognition in FES, which are predictive of real world outcomes. Thus, it may be appropriate for clinical application, including in multi-center trials targeting new treatments for cognition in schizophrenia.

The study aimed to identify brain functional indicators of working memory systems development between 6 and 18 years. Event-related potentials (ERPs) were recorded from 251 normally developing children to stimuli requiring the updating of working memory. Cluster analysis of event-related potential componentry divided the sample into three clusters (mean ages 9, 12 and 16 years), with ascending cluster membership independently associated with improved task performance. The clusters correspond to periods of grey matter loss and white matter increase observed in developing children, supporting the view that the clusters delineate three key qualitative stages in advancing cognitive capability during the maturation of higher brain systems function. This outcome identifies a biomarker with the potential for assessing abnormalities in the rate of brain development.

Results from recent studies suggest that chronic cigarette smoking is associated with increased white matter volume in the brain as determined by in vivo neuroimaging. We used diffusion tensor imaging to examine the microstructural integrity of the white matter in 10 chronic smokers and 10 nonsmokers. All individuals were healthy, without histories of medical or psychiatric illness. Fractional anisotropy (FA) and trace were measured in the genu, body, and splenium of the corpus callosum. FA provides a measure of directional versus nondirectional water diffusion, whereas trace provides a measure of nondirectional water diffusion. Lower FA and higher trace values are considered to reflect less brain integrity. Voxel-based morphometry was used to define volumes in each of these regions of the corpus callosum. Chronic smokers exhibited significantly higher FA in the body and whole corpus callosum and a strong trend for higher FA in the splenium compared with nonsmokers. FA did not differ between groups in the genu, and neither trace nor white matter volumes differed between groups in any of the regions of interest. When subdivided by Fagerström score (low vs. high), the low Fagerström group exhibited significantly higher FA in the body of the corpus callosum compared with the high Fagerström group and the nonsmokers. These results suggest that, among healthy adults, lower exposure to cigarette smoking is associated with increased microstructural integrity of the white matter compared with either no exposure or higher exposure. Additional studies are needed to further explore differences in white matter integrity between smokers and nonsmokers.

BACKGROUND: Frontotemporal lobar degeneration (FTLD) represents a clinically, pathologically and genetically heterogenous neurodegenerative disorder, often complicated by neurological signs such as motor neuron-related limb weakness, spasticity and paralysis, parkinsonism and gait disturbances. Linkage to chromosome 9p had been reported for pedigrees with the neurodegenerative disorder, frontotemporal lobar degeneration (FTLD) and motor neuron disease (MND). The objective in this study is to identify the genetic locus in a multi-generational Australian family with FTLD-MND. METHODS: Clinical review and standard neuropathological analysis of brain sections from affected pedigree members. Genome-wide scan using microsatellite markers and single nucleotide polymorphism fine mapping. Examination of candidate genes by direct DNA sequencing. RESULTS: Neuropathological examination revealed cytoplasmic deposition of the TDP-43 protein in three affected individuals. Moreover, we identify a family member with clinical Alzheimer's disease, and FTLD-Ubiquitin neuropathology. Genetic linkage and haplotype analyses, defined a critical region between markers D9S169 and D9S1845 on chromosome 9p21. Screening of all candidate genes within this region did not reveal any novel genetic alterations that co-segregate with disease haplotype, suggesting that one individual carrying a meiotic recombination may represent a phenocopy. Re-analysis of linkage data using the new affection status revealed a maximal two-point LOD score of 3.24 and a multipoint LOD score of 3.41 at marker D9S1817. This provides the highest reported LOD scores from a single FTLD-MND pedigree. CONCLUSION: Our reported increase in the minimal disease region should inform other researchers that the chromosome 9 locus may be more telomeric than predicted by published recombination boundaries. Moreover, the existence of a family member with clinical Alzheimer's disease, and who shares the disease haplotype, highlights the possibility that late-onset AD patients in the other linked pedigrees may be mis-classified as sporadic dementia cases.

OBJECTIVE: This study examines the utility of new measures of event-related spatio-temporal waves in the EEG as a marker of ADHD, previously shown to be closely related to the P3 ERP in an adult sample. METHODS: Wave activity in the EEG was assessed during both an auditory Oddball and a visual continuous performance task (CPT) for an ADHD group ranging in age from 6 to 18 years and comprising mostly Combined and Inattentive subtypes, and for an age and gender matched control group. RESULTS: The ADHD subjects had less wave activity at low frequencies ( approximately 1 Hz) during both tasks. For auditory Oddball targets, this effect was shown to be related to smaller P3 ERP amplitudes. During CPT, the approximately 1 Hz wave activity in the ADHD subjects was inversely related to clinical and behavioral measures of hyperactivity and impulsivity. CPT wave activity at approximately 1 Hz was seen to "normalise" following treatment with stimulant medication. CONCLUSIONS: The results identify a deficit in low frequency wave activity as a new marker for ADHD associated with levels of hyperactivity and impulsivity. SIGNIFICANCE: The marker is evident across a range of tasks and may be specific to ADHD. While lower approximately 1 Hz activity partly accounts for reduced P3 ERPs in ADHD, the effect also arises for tasks that do not elicit a P3. Deficits in behavioral inhibition are hypothesized to arise from underlying dysregulation of cortical inhibition.

An assistive technology developed for "hands free" control of electrical devices to be used by severely impaired people within their environment, relies upon using signal processing techniques for analyzing eyes closed (EC) and eyes open (EO) states in the electroencephalography (EEG) signal. Here, we apply a signal processing technique used in continuous chaotic modeling to investigate differences in the EEG time series between EC and EO states. This method is used to detect the degree of variability from a second-order difference plot, and quantifying this using a central tendency measures. The study used EEG time series of EO and EC states from 33 able-bodied and 17 spinal cord injured participants. The results found an increased EEG variability in brain activity during EC compared to EO. This increased EEG variability occurred in the O2 electrode, which overlays the primary visual cortex V1, and could be a result of the replacement of the coherent information obtained during EO by noise. A continuous measure of the variability was then used to demonstrate that this technique has the potential to be used as a switching mechanism for assistive technologies.

Assessment of neurocognitive functioning is a critical task in many clinical, educational, service, and industrial settings. We report on descriptive and validation data of a new, World-Wide-Web-based, comprehensive battery of neurocognitive functioning, WebNeuro, that can be used in both applied and research contexts. Fifty healthy control participants completed both WebNeuro, and an established non-Internet-based computerized cognitive assessment battery, IntegNeuro, that uses a touchscreen platform. Results indicated comparability across the two batteries, in terms of critical single test scores, factor analysis derived indices,overall performance scores, and sex differences. These results support the validity of WebNeuro as a neurocognitive assessment measure. Advantages of its use in applied and research settings are discussed.

Currently diagnosis and assessment of ADHD relies on clinical interview and subjective ratings. Standardized objective cognitive tests can provide additional information about ADHD and help distinguish symptom profiles. OBJECTIVE: To assess the cognition of adolescent ADHD subtypes using a standardized cognitive test battery. STUDY GROUP: Seventy-two ADHD combined subtype, 58 ADHD predominantly inattentive subtype and 130 age- and sex-matched healthy controls. METHODS: Cognitive differences between ADHD subtypes were examined according to 1. symptom dimensions (inattentive versus hyperactivity/impulsivity scores) and 2. category (ADHDcom vs. ADHDin). We examined whether cognitive performance would discriminate symptom profiles (from each other and from healthy controls), and whether these profiles could predict test performance. All subjects completed the standardized and fully computerized IntegNeuro test battery using a touch-screen protocol. These tests span the domains of sensori-motor, attention, executive function, language and memory, and have robust construct validity compared to traditional paper-and-pencil tests. The results highlighted the consistency with which performance varied across symptom profiles, irrespective of categorical or dimensional definitions. ADHDcom was primarily distinguished from ADHDin by increased errors and response variability in response inhibition and (to a lesser extent) selective attention tasks. Inattentive symptoms were more likely to predict cognitive performance and there is an indication that despite the same criteria, these symptoms may be more severe in the ADHDcom subtype. CONCLUSIONS: These findings highlight the specificity of cognitive deficits, which differentiate ADHD subtypes in adolescence. This study provides consistent evidence that accuracy and response variability in an executive function (response inhibition) task may best distinguish the common ADHD subtypes.

Although biases toward signals of fear may be an evolutionary adaptation necessary for survival, heightened biases may be maladaptive and associated with anxiety or depression. In this study, event-related potentials (ERPs) were used to examine the time course of neural responses to facial fear stimuli (versus neutral) presented overtly (for 500 msec with conscious attention) and covertly (for 10 msec with immediate masking to preclude conscious awareness) in 257 nonclinical subjects. We also examined the impact of trait anxiety and depression, assessed using psychometric ratings, on the time course of ERPs. In the total subject group, controlled biases to overtly processed fear were reflected in an enhancement of ERPs associated with structural encoding (120-220 msec) and sustained evaluation persisting from 250 msec and beyond, following a temporo-occipital to frontal topography. By contrast, covert fear processing elicited automatic biases, reflected in an enhancement of ERPs prior to structural encoding (80-180 msec) and again in the period associated with automatic orienting and emotion encoding (230-330 msec), which followed the reverse frontal to temporo-occipital topography. Higher levels of trait anxiety (in the clinical range) were distinguished by a heightened bias to covert fear (speeding of early ERPs), compared to higher depression which was associated with an opposing bias to overt fear (slowing of later ERPs). Anxiety also heightened early responses to covert fear, and depression to overt fear, with subsequent deficits in emotion encoding in each case. These findings are consistent with neural biases to signals of fear which operate automatically and during controlled processing, feasibly supported by parallel networks. Heightened automatic biases in anxiety may contribute to a cycle of hypervigilance and anxious thoughts, whereas depression may represent a "burnt out" emotional state in which evaluation of fear stimuli is prolonged only when conscious attention is allocated.

Posttraumatic Stress Disorder (PTSD) is thought to involve a dysregulation of medial prefrontal-amygdala activity in response to fear. PTSD studies, however, have been confounded by comorbid depression, which shows similar dysregulation. Amygdala and medial prefrontal activity was reduced in PTSD-depression compared to PTSD-alone samples, highlighting the need to account for comorbidity.

Models of emotion processing have commonly been formulated as dichotomies such as approach versus avoidance. These models and associated research on evolutionary adaptation, awareness, motivational arousal, and cortical-subcortical brain systems are reviewed. A continuum model of emotional-significance processing is proposed to integrate current dichotomies and reflect the highly interconnected nature of brain systems. This model highlights a spectrum from "mismatches," signifying potential danger, to "matches," signifying safety and the expectation of reward. Subcortical-cortical interactions and autonomic arousal modulation support mismatch and match processing across a temporal continuum from milliseconds (in which processing is automatic and arguably nonconscious) to tenths of a second (in which responses are facilitated and contextual evaluation commences) to minutes and hours (when memory consolidation and neural plasticity occur). Variations at distinct points along this continuum, with contributions from constitutional and genetic factors, may contribute to individual differences in emotional stability and instability in neuropsychiatric disorders.

Loss-of-function mutations in MCPH1 and ASPM are responsible for some cases of autosomal recessive primary microcephaly. Recent studies have indicated that certain common variants of these genes have been positively selected for during the evolution of modern humans. It is therefore possible that these variants may predispose to an increase in brain size in the normal human population. We genotyped the MCPH1 G37995C and ASPM A44871G polymorphisms in a cohort of 118 healthy people who had undergone structural magnetic resonance imaging analysis. We did not detect significant association of either MCPH1 G37995C or ASPM A44871G genotype with whole brain volume, cerebral cortical volume or proportion of grey matter in this cohort. Nor did we detect an association of combined MCPH1 37995C and ASPM 44871G allele dosage with these brain measurements. These results were also confirmed in an age-restricted subcohort of 94 individuals. This study suggests that phenotypes other than brain size may have been selected for in ASPM and MCPH1 variants during evolution of modern humans.

The present study employs standardized data acquired from the Brain Resource International Database to study the relationship between mobile phone usage, personality, and brain function (n = 300). Based on the frequency and duration of mobile phone usage, three groups were formed. The findings suggest a subtle slowing of brain activity related to mobile phone use that is not explained by differences in personality. These changes are still within normal physiological ranges. Better executive function in mobile phone users may reflect more focused attention, possibly associated with a cognitive training effect (i.e., frequently making phone calls in distracting places), rather than a direct effect of mobile phone use on cognition.

OBJECTIVE: While schizophrenia has long been considered a disorder of brain connectivity, few studies have investigated white matter abnormalities in patients with first-episode schizophrenia, and even fewer studies have investigated whether there is progressive white matter pathology in the disease. METHOD: The authors obtained a T1-weighted structural magnetic resonance imaging (MRI) scan on 41 patients with first-episode schizophrenia. These first-episode schizophrenia patients were analyzed relative to 47 age- and sex-matched healthy comparison subjects who also underwent an MRI scan. Of the baseline participants, 25 first-episode schizophrenia patients and 26 comparison subjects returned 2 to 3 years later for a follow-up scan. To identify regional volumetric white matter differences between the two groups at baseline, voxel-based morphometry in statistical parametric mapping-2 (SPM2) was used, while tensor-based morphometry was used to identify the longitudinal changes over the follow-up interval. RESULTS: The first-episode schizophrenia patients exhibited volumetric deficits in the white matter of the frontal and temporal lobes at baseline, as well as volumetric increases in the white matter of the frontoparietal junction bilaterally. Furthermore, these first-episode schizophrenia patients lost considerably more white matter over the follow-up interval relative to comparison subjects in the middle and inferior temporal cortex bilaterally. CONCLUSIONS: These results indicate that patients with schizophrenia exhibit white matter abnormalities at the time of their first presentation of psychotic symptoms to mental health services and that these abnormalities degenerate further over the initial years of illness. Given the role that white matter plays in neural communication, the authors suggest that these white matter abnormalities may be a cause of the dysfunctional neural connectivity that has been proposed to underlie the symptoms of schizophrenia.

Neuroimaging shows brain-functional differences due to apolipoprotein E (APOE) polymorphisms may exist decades before the increased risk period for Alzheimer's disease, but little is known about their effect on cognition and brain function in children and young adults. This study assessed 415 healthy epsilon2 and epsilon4 carriers and matched epsilon3/epsilon3 controls, spanning ages 6-65, on a range of cognitive tests. Subjects were also compared on a new dynamical measure of EEG activity during a visual working memory task using alphabetical stimuli. epsilon4 subjects had better verbal fluency compared to epsilon3, an effect that was strongest in 51-65 year-olds. No epsilon4 deficits in cognition were found. In 6-15 year-olds, there were differences in total spatio-temporal wave activity between epsilon3 and epsilon4 subjects in the theta band, approximately 200ms post-stimulus. Differences in brain function in younger epsilon4 subjects and superior verbal fluency across the entire age range suggest that the APOE epsilon4 allele is an example of antagonistic pleiotropy.

Previous studies have demonstrated strong developmental trends of white matter using in vivo neuroimaging. However, few studies have examined white matter using diffusion tensor imaging across the lifespan. In the present study we examined fractional anisotropy and volume in the corpus callosum in four groups (children, adolescents, young adults, and elderly). Results revealed a curvilinear relationship in the analysis of the fractional anisotropy values for these four groups, with fractional anisotropy values increasing in childhood and adolescence, reaching their peak in young adulthood, followed by a non-significant decline in the elderly. Volumetric analysis of corpus callosum regions revealed a similar pattern, with an increase in volume from childhood and adolescence through young adulthood, and a non-significant decrease in volume in the elderly group. These results define the microstructural development of the white matter across the lifespan. Future studies are required to examine the neurobehavioral correlates of these neuroimaging indices.

Variable contributions of state and trait to the electroencephalographic (EEG) signal affect the stability over time of EEG measures, quite apart from other experimental uncertainties. The extent of intraindividual and interindividual variability is an important factor in determining the statistical, and hence possibly clinical significance of observed differences in the EEG. This study investigates the changes in classical quantitative EEG (qEEG) measures, as well as of parameters obtained by fitting frequency spectra to an existing continuum model of brain electrical activity. These parameters may have extra variability due to model selection and fitting. Besides estimating the levels of intraindividual and interindividual variability, we determined approximate time scales for change in qEEG measures and model parameters. This provides an estimate of the recording length needed to capture a given percentage of the total intraindividual variability. Also, if more precise time scales can be obtained in future, these may aid the characterization of physiological processes underlying various EEG measures. Heterogeneity of the subject group was constrained by testing only healthy males in a narrow age range (mean = 22.3 years, sd = 2.7). Eyes-closed EEGs of 32 subjects were recorded at weekly intervals over an approximately six-week period, of which 13 subjects were followed for a year. QEEG measures, computed from Cz spectra, were powers in five frequency bands, alpha peak frequency, and spectral entropy. Of these, theta, alpha, and beta band powers were most reproducible. Of the nine model parameters obtained by fitting model predictions to experiment, the most reproducible ones quantified the total power and the time delay between cortex and thalamus. About 95% of the maximum change in spectral parameters was reached within minutes of recording time, implying that repeat recordings are not necessary to capture the bulk of the variability in EEG spectra.

There is little consensus about which objective markers should be used to assess major psychiatric disorders, and predict/evaluate treatment response for these disorders. Clinical practice relies instead on subjective signs and symptoms, such that there is a "translational gap" between research findings and clinical practice. This gap arises from: a) a lack of integrative theoretical models which provide a basis for understanding links between gene-brain-behavior mechanisms and clinical entities; b) the reliance on studying one measure at a time so that linkages between markers are their specificity are not established; and c) the lack of a definitive understanding of what constitutes normative function. Here, we draw on a standardized methodology for acquiring multiple sources of genomic, brain and behavioral data in the same subjects, to propose candidate markers of selected psychiatric disorders: depression, post-traumatic stress disorder, schizophrenia, attention-deficit/hyperactivity disorder and dementia disorders. This methodology has been used to establish a standardized international database which provides a comprehensive framework and the basis for testing hypotheses derived from an integrative theoretical model of the brain. Using this normative base, we present preliminary findings for a number of disorders in relation to the proposed markers. Establishing these objective markers will be the first step towards determining their sensitivity, specificity and treatment prediction in individual patients.

AIMS: QEEG and neuropsychological tests were used to investigate the underlying neural processes in dyslexia. METHODS: A group of dyslexic children were compared with a matched control group from the Brain Resource International Database on measures of cognition and brain function (EEG and coherence). RESULTS: The dyslexic group showed increased slow activity (Delta and Theta) in the frontal and right temporal regions of the brain. Beta-1 was specifically increased at F7. EEG coherence was increased in the frontal, central and temporal regions for all frequency bands. There was a symmetric increase in coherence for the lower frequency bands (Delta and Theta) and a specific right-temporocentral increase in coherence for the higher frequency bands (Alpha and Beta). Significant correlations were observed between subtests such as Rapid Naming Letters, Articulation, Spelling and Phoneme Deletion and EEG coherence profiles. DISCUSSION: The results support the double-deficit theory of dyslexia and demonstrate that the differences between the dyslexia and control group might reflect compensatory mechanisms. INTEGRATIVE SIGNIFICANCE: These findings point to a potential compensatory mechanism of brain function in dyslexia and helps to separate real dysfunction in dyslexia from acquired compensatory mechanisms.

Schizophrenia patients show a disconnection in amygdala-medial prefrontal cortex and autonomic arousal systems for processing fear. Concurrent functional magnetic resonance imaging [fMRI] and skin conductance recording were used to determine whether these disturbances are specific to fear, or present in response to other signals of danger. We also examined whether these disturbances distinguish a specific symptom profile. During scanning, 27 schizophrenia (13 paranoid, 14 nonparanoid) and 22 matched healthy control subjects viewed standardized facial expressions of fear, anger and disgust (versus neutral). Skin conductance responses [SCRs]were acquired simultaneously to assess phasic increases in arousal. 'With-arousal' versus 'without-arousal' responses were analysed using non-parametric methods. For controls, 'with-arousal' responses were associated with emotion-specific activity for fear (amygdala), disgust (insula) and anger (anterior cingulate), together with common medial prefrontal cortex [MPFC] engagement, as predicted. Schizophrenia patients displayed abnormally increased phasic arousal, with concomitant reductions in emotion-specific regions and MPFC. These findings may reflect a general disconnection between central and autonomic systems for processing signals of danger. This disjunction was most apparent in patients with a profile of paranoia, coupled with poor social function and insight. Heightened autonomic sensitivity to signals of fear, threat or contamination, without effective neural mechanisms for appraisal, may underlie paranoid delusions which concern threat and contamination, and associated social and interpersonal difficulties.

Previous studies have revealed significant differences in performance on nonlanguage dependent cognitive tests across international settings among younger individuals, with less pronounced differences evident among older individuals (>54 years of age). The present study examined a broad range of cognitive performance as well as electrophysiological indices of brain function in a multisite and international context. A total of 200 individuals in the United States, 233 individuals in Europe, and 829 individuals in Australia were administered a standardized computerized neuropsychological battery, and complementary electroencephalogram (EEG) recordings were completed. Results revealed no significant differences in cognitive function or electrophysiology across the three continents. Similarly, although there was a main effect for age, the interaction between age and continent was not significant in any of the omnibus analyses. These findings indicate a high degree of similarity in neurocognitive and electrophysiological function among individuals residing in developed Western cultures, consistent with a traitlike status and the high heritability of the EEG.

The relationship between handedness and cognitive function varies across studies, perhaps partly due to the many medical and psychiatric conditions with known cognitive impact. This study examined cognitive performance in 643 healthy individuals (age 5-82) who were categorized as strongly right-handed, moderately right-handed, or left/mixed-handed. Cognitive differences emerged, as left/mixed-handed individuals demonstrating superior psychomotor speed and cognitive flexibility, and strongly and moderately right-handed individuals exhibiting better time estimation skills. No interaction-among handedness, sex, and age were found. These findings indicate cognitive differences associated with handedness exist independent of medical and psychiatric confounds. Further work is needed to clarify these findings.