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Psychophysiological theories characterize Attention Deficit Hyperactivity Disorder (ADHD) in terms of cortical hypoarousal and a lack of inhibition of irrelevant sensory input, drawing on evidence of abnormal electroencephalographic (EEG) delta-theta activity. To investigate the mechanisms underlying this disorder a biophysical model of the cortex was used to fit and replicate the EEGs from 54 ADHD adolescents and their control subjects. The EEG abnormalities in ADHD were accounted for by the model's neurophysiological parameters as follows: (i) dendritic response times were increased, (ii) intrathalamic activity involving the thalamic reticular nucleus (TRN) was increased, consistent with enhanced delta-theta activity, and (iii) intracortical activity was increased, consistent with slow wave (

It is not known how the brain and autonomic systems interact during perception of facial signals of danger. We recorded blood-oxygen-level-dependent (BOLD) activity using fMRI and simultaneous skin conductance measures of autonomic arousal in healthy subjects. Distinct response profiles were elicited for fear (enhanced arousal with amygdala activity), anger (rapid onset, slow recovery arousal responses with anterior cingulate) and disgust (delayed arousal responses with insula and basal ganglia activity). The findings suggest that fear, anger and disgust perception involves specific interactions in the neural arousal systems for emotion and motivation.

Objective: To examine the clinical profile, treatment and social functioning of a communitybased sample of young people presenting with their first episode of psychosis.Methods: Over a 2-year period, young people with their first episode of psychosis referred to early intervention services in two area mental health services in western Sydney were assessed with a battery of clinical, neuropsychological, psychophysiological and neuroanatomical measures. This paper reports the clinical results of the baseline section of the study.Results: Of the 224 referrals to the project, 94 subjects meet inclusion criteria and agreed to take part. Subjects were divided into three diagnostic groups – ‘Schizophrenia’, ‘Mood Disorders’ and ‘Mixed Psychosis’, the latter principally comprised of substance induced psychotic disorders. Subjects from the ‘Schizophrenia’ group differed significantly from the other two groups in that they had higher levels of negative symptoms and general psychopathology, and were less likely to be employed or engaged in study. They had poorer overall social functioning. Subjects with ‘Mixed Psychosis’ were similar to those from the ‘Schizophrenia’ group in that they were older and male, but they did not have the same burden of negative symptoms as the ‘Schizophrenia’ group. The ‘Mood Disorders’ group was younger, female and had overall a higher level of psychosocial functioning than the other two groups. Subjects from the ‘Mood Disorders’ group were more likely to be managed with mood stabilisers and multiple drug therapies. The use of atypical antipsychotic medication was almost universal.Conclusions: Even shortly after the time of presentation to mental health services young people with a schizophrenia spectrum diagnosis have a heavier burden of symptoms and are significantly more impaired by them than young people with other psychotic illnesses. This and their symptom profile differentiated them from young people with other psychotic disorders.

There has been consistent evidence for a lower incidence and milder course of schizophrenia in women, yet there have been very few investigations of sex differences in brain function in this disorder. This study used a new high-temporal-resolution measure of functional brain connectivity to test the prediction that female patients would show relatively greater inter- and intrahemispheric connectivity than male patients, particularly in the early stage of schizophrenia.Forty patients with chronic schizophrenia (20 women and 20 men) and 24 patients with first-episode schizophrenia (12 women and 12 men) and their respective matched comparison groups completed a conventional auditory oddball task. Phase synchronous gamma (40 Hz) activity was extracted from EEG recording during the task and time-locked to the oddball (target) stimuli.Chronic schizophrenia subjects showed a reduction in global functional connectivity (lower gamma phase synchrony) relative to their matched healthy subjects. Unexpectedly, this reduction was most apparent in female patients. By contrast, while first-episode patients showed a general reduction in the speed of frontal connectivity, the speed of global connectivity was relatively faster in female patients.This is the first study to investigate sex differences in schizophrenia that used the functional connectivity measure of gamma phase synchrony. The results suggest that in female patients with schizophrenia, additional breakdowns in brain network connectivity may develop with illness chronicity.

Cognitive models of social phobia propose that cognitive biases and fears regarding negative evaluation by others result in preferential attention to interpersonal sources of threat. These fears may account for the hypervigilance and avoidance of eye contact commonly reported by clinicians. This study provides the first objective examination of threat-related processing in social phobia. It was predicted that hyperscanning (hypervigilance) and eye avoidance would be most apparent in social phobia for overt expressions of threat. An infrared corneal reflection technique was used to record visual scanpaths in response to angry, sad, and happy vs. neutral facial expressions. Twenty-two subjects with social phobia were compared with age- and sex-matched normal controls. As predicted, social phobia subjects displayed hyperscanning, (increased scanpath length) and avoidance (reduced foveal fixations) of the eyes, particularly evident for angry faces. The results could not be explained by either medication or co-morbid depression. These findings are consistent with theories emphasising the role of information processing biases in social phobia, and show promise in the application to treatment evaluation in this disorder.

The authors investigated impaired differentiation of limbic-prefrontal systems by autonomic arousal in schizophrenia. It was predicted that paranoid patients would be distinguished by a disjunction of hyperarousal but reduced amygdala and medial prefrontal activity relative to both healthy comparison subjects and patients with nonparanoid schizophrenia.Pictures depicting facial expressions of fear were presented to 27 schizophrenia patients (13 paranoid, 14 nonparanoid) and 22 matched healthy comparison subjects in an implicit perception task to evoke limbic activity. Simultaneous functional magnetic resonance imaging and skin conductance arousal recordings were acquired during presentation of faces expressing fear or neutral emotion. Responses to fear stimuli were further examined by contrasting those that were associated with a skin conductance response ("with arousal") and those that were not ("without arousal").In the comparison subjects, arousal dissociated amygdala/medial prefrontal ("visceral") networks and hippocampus/lateral prefrontal ("context") networks for fear perception. Excessive arousal responses were elicited in the schizophrenia subjects, but there was an associated reduction in amygdala/medial prefrontal activity. This disjunction was pronounced in paranoid patients relative to both healthy subjects and nonparanoid patients. Paranoid patients also showed a relatively greater prefrontal deficit for "without-arousal" responses.This is the first study to reveal a functional disconnection in autonomic and central systems for processing threat-related signals in patients with paranoid schizophrenia. Paranoid cognition may reflect an internally generated cycle of misattribution regarding incoming fear signals due to a breakdown in the regulation of these systems.

Patterns of ocular fixation in free-viewing tasks reflect aspects of visual attention and cognition. To quantify these patterns, fixations must be identified in raw eye movement data by applying explicit spatial and temporal thresholds. A temporal threshold of 200 ms is commonly used in clinical visuocognitive research, despite having been originally derived from a study of eye movements in reading. We systematically explored temporal fixation thresholds below 200 ms, using biologically relevant (human face) and abstract (complex geometric) stimuli. Short fixations (

We used a psychophysiological marker of visual attention (the visual scanpath) to investigate the effects of atypical (risperidone) vs. typical (haloperidol) antipsychotic medication on facial emotion perception in schizophrenia (n=28) and healthy control (n=28) groups. Of the schizophrenia subjects, 15 were prescribed risperidone. Visual scanpaths to 'happy', 'sad' and 'neutral' faces were recorded using video-oculography, and concurrent emotion-recognition accuracy was assessed using multiple-option tasks. Compared to control subjects, both schizophrenia subgroups showed a restriction in visual scanning (reduced total fixation number and decreased scanpath length). Haloperidol-treated schizophrenia subjects exhibited an additional and consistent pattern of reduced attention (fixation) to salient features for neutral and happy. By contrast, risperidone-treated subjects showed a relatively greater attention to salient features for these expressions, in which they did not differ from controls. Recognition accuracy for happy and neutral showed a similar lack of impairment. These findings suggest that risperidone may play a specific role in schizophrenia in the ability to attend to salient features, and to integrate this information into an accurate percept for neutral and positive expressions in particular.

Objective: Databases bring together diverse information in neuroimaging and psychiatry. They usually aim for both size and diversity of measures. The present article outlines the potential insights from the first entirely standardized and centralized International Brain Database. Method: The database consists of data from over 1000 normal subjects (age range 6-70 years) and a growing number of age-matched patients with a psychiatric illness, acquired from seven laboratories (New York, Rhode Island, London, Holland, Adelaide, Melbourne and Sydney). It is an ‘integrative’ neuroimaging (electroencephalography (EEG), event-related potentials (ERP), structural and functional magnetic resonance imaging (sMRI, fMRI)), psychometric, demographic and genomic database. Results: The most notable relationships in normal controls thus far include (i) an association between grey matter volume and EEG alpha frequency in frontal regions; (ii) a systematic reduction with age in cortical arousal (EEG power), speed of processing (ERP components) and most aspects of cognitive function, particularly for >50 years; (iii) a greater cortical arousal in female versus male subjects, but slower speed of processing; and (iv) a dissociation between speed (greater in male subjects) and accuracy/verbal processing (greater in female subjects) for psychological tasks. There is potential to explore the specificity of findings in psychiatric disorders in this international standardized database. Conclusions: The size of this database has allowed for statistical tests of greater power than normal. The combination of size and diversity of measure has broader significance in providing a normative framework for evidence-based psychiatric research. It enables control for widespread individual differences, enhancing investigations of the sensitivity and specificity of brain findings, and the efficacy of medication in psychiatric disorders.

Background: Traditional averaging of late component Event Related Potentials (ERPs) might obscure important psychophysiological subprocesses underlying schizophrenia disturbances in cognitive functioning. One such subprocess could be the active orientation of attention to significant or novel stimuli. In this study, we used skin conductance responses (SCRs) to index orienting responses (ORs). ERP activity was examined in relation to concomitant ORs in a schizophrenia and nonpsychiatric control group. Schizophrenia responses were considered with respect to the Reality Distortion, Disorganisation and Psychomotor Poverty syndromes. Method: Forty schizophrenia and 40 age and sex matched control subjects were tested. The three schizophrenia syndromes were derived from a principal component analysis of Positive and Negative Syndrome Scale (PANSS) ratings. Auditory ERPs (N100, N200, P200, P300) were elicited using a conventional auditory oddball paradigm, and electrodermal SCR data were acquired simultaneously. Results: ERP data were sub-averaged according to the presence/absence of an OR. For both ‘with-’ and ‘without-OR’ ERPs, schizophrenia subjects as a group showed reduced N100 (associated with vigilance level) and N200 (associated with response selection) amplitude, and for with-OR responses, they showed an additional reduction in P300 (context processing). Concerning schizophrenia syndromes, Reality Distortion was related primarily to frontal disturbances (earlier N100/N200 latency and decreased P200/P300 amplitude), and Psychomotor Poverty to a generally delayed P300 latency. Similarly delayed P300 in Disorganisation was explained by medication effects. There were no associations with syndromes for without-OR ERPs. Conclusion: These results suggest that schizophrenia syndromes are dissociated with regard to both the direction and nature of speed of information processing disturbances, in relation to task-relevant information that produces active orientation.

Clinical observation suggests that social phobia is characterised by eye avoidance in social interaction, reflecting an exaggerated social sensitivity. These reports are consistent with cognitive models of social phobia that emphasize the role of interpersonal processing biases. Yet, these observations have not been verified empirically, nor has the psychophysiological basis of eye avoidance been examined. This is the first study to use an objective psychophysiological marker of visual attention (the visual scanpath) to examine directly how social phobia subjects process interpersonal (facial expression) stimuli. An infra-red corneal reflection technique was used to record visual scanpaths in response to neutral, happy and sad face stimuli in 15 subjects with social phobia, and 15 age and sex-matched normal controls. The social phobia subjects showed an avoidance of facial features, particularly the eyes, but extensive scanning of non-features, compared with the controls. These findings suggest that attentional strategies for the active avoidance of salient facial features are an important marker of interpersonal cues in social phobia. Visual scanpath evidence may, therefore, have important implications for clinical intervention.

The objective of this work is to determine whether Gamma (40 Hz) synchronous activity has disturbed patients with severe traumatic brain injury (TBI).Using a conventional auditory oddball paradigm, the extent of Gamma synchrony across multiple scalp sites in specific frequency bands as a function of time was examined in 15 patients with severe TBI and 15 age- and sex-matched controls. Averaged Gamma synchrony was analyzed using within and between group multiple analyses of variance with region (left versus right hemisphere, anterior versus posterior region) as the within factor.Compared to controls, subjects with TBI displayed significantly delayed early Gamma latency (from -150 to 150 ms) (F((1,28))=10.28, P0.003) across all sites in addition to other specific regional disturbances. For late Gamma synchrony, subjects with TBI displayed delayed Gamma latency at the left hemisphere (from 200 to 450 ms) (F((1,28))=8.71, P0.006) and posterior region (F((1,28))=9.18, P0.006) in comparison to controls.Impaired integration of spatially distributed brain activity ('40 Hz' electroencephalogram rhythms) may be an important marker of deficits of cortical network binding postulated to be abnormal in people who have survived TBI.

Background: Abnormal visual scanpaths to faces and facial expressions in schizophrenia may underlie schizophrenic subjects’ disturbed interpersonal communication. This study is the first to examine the specificity of these impairments to schizophrenia, by including an affective disorder psychiatric control group. Methods: The visual scanpath performance of 65 schizophrenia, 52 affective disordered, and 61 control subjects were compared in two experiments. In the “face recognition” experiment, subjects viewed four identifiable (non-degraded) neutral faces versus four matched non-identifiable (degraded) control faces. In the “facial affect recognition” experiment, subjects viewed positive (happy), negative (sad), and neutral (control) facial emotion stimuli. Concurrent behavioral tasks were face matching (face recognition) and expression matching (facial affect recognition), each under two multiple-choice conditions (7 or 3 options). Results: Scanpath disturbances were most apparent in schizophrenia subjects, who maintained a comparatively “restricted” scanpath style to all face stimuli. Schizophrenics subjects also showed the greatest recognition difficulties, particularly for neutral and happy faces. Scanpath parameters for affective disorder subjects differed only from the schizophrenia (but not the control) group, except for attention to facial features where they generally avoided facial features in all expressions and showed the greatest attentional problems of all groups for degraded faces. Conclusions: Our results suggest that a global restriction of visual scanpaths is specific to schizophrenic psychosis and might be a trait marker for this disorder, whereas scanpath abnormalities in affective disorder might instead reflect severe state-based (or discrete) attentional disturbances.

The purpose of this study was to examine the relationship between disturbance in event-related potentials (ERPs) and symptom clusters in posttraumatic stress disorder (PTSD). ERPs were recorded in 17 unmedicated civilian PTSD patients and 17 age- and sex-matched controls during a conventional auditory oddball task. PTSD symptom clusters (re-experiencing, active avoidance, numbing, hyperarousal) were correlated with ERP measures. The PTSD group showed ERP disturbances to target stimuli (reduced P200 and P300 and increased N200 amplitude, increased N200 and P300 latency) and reduced P200 amplitude to common stimuli compared to the control group. A significant negative correlation was found between the intensity of numbing symptoms and parietal P300 amplitude. This study replicates findings of disturbed N200 and P300 components in PTSD, reflecting impairments in stimulus discrimination and attention. The finding that numbing was associated with reduced attention processing (P300) is consistent with models positing a relationship between disordered arousal and attention in PTSD.

Advances in physics, computing, and signal processing have provided a range of computerized brain imaging technologies that facilitate examination of the brain as a dynamical system. This article provides a review of brain imaging advances and their application in neuropsychiatry. The review encompasses (1) a description of the imaging technologies used in neuropsychiatry; (2) an outline of their temporospatial complementarity; (3) application to clinical applications; and (4) suggested future directions including an "integrative neuroscience" approach to neuropsychiatry (in which theoretical models, data and information concerning mechanisms are integrated). In the absence of a unified theory of the brain, an integrated approach is presented as one means of exploring converging brain-imaging evidence in relation to neuropsychiatric disorders.

Objective: To explore the utility of cognitive measures for predicting response of children and adolescents to methylphenidate (MPH). Method: Participants from the International Study to Predict Optimized Treatment–in ADHD (iSPOT-A) completed a cognitive test battery prior to receiving 6 weeks of MPH. The responder criterion was a 25% reduction in ADHD-Rating Scale-IV scores. Receiver Operator Characteristics (ROC) classified non-responders from responders with maximal sensitivity and specificity. Results: Overall, 62% of participants responded to MPH. Response rates for ROC-identified groups ranged from 18% to 85%. Non-responders showed compromised cognition related to switching of attention, sustained attention, planning, and impulsivity. One group of responders were 10 years of age or older and had impaired switching of attention and impulsivity; a second group had enhanced switching of attention, normal or higher Continuous Performance Task (CPT) scores, and above average scores on digit span. Conclusion: Cognitive tests may provide a simple, low-cost tool for treatment planning for children and adolescents with ADHD.

Continuum models of cerebral cortex with parameters derived from physiological data, provide explanations of the cerebral rhythms, synchronous oscillation, and autonomous cortical activity in the gamma frequency range, and suggest possible mechanisms for dynamic self-organization in the brain. Dispersion relations and derivations of power spectral response for the models, show that a low frequency resonant mode and associated travelling wave solutions of the models' equations of state can account for the predominant 1/f spectral content of the electroencephalogram (EEG). Large scale activity in the alpha, beta, and gamma bands, is accounted for by thalamocortical interaction, under regulation by diffuse cortical excitation. System impulse responses can be used to model Event-Related Potentials. Further classes of local resonance may be generated by rapid negative feedbacks at active synapses. Activity in the gamma band around 40 Hz, associated with large amplitude oscillations of pulse density, appears at higher levels of cortical activation, and is unstable unless compensated by synaptic feedbacks. Control of cortical stability by synaptic feedbacks offers a partial account of the regulation of autonomous activity within the cortex. Synchronous oscillation occurs between concurrently excited cortical sites, and can be explained by analysis of wave motion radiating from each of the co-active sites. These models are suitable for the introduction of learning rules-most notably the coherent infomax rule.

Objectives : Frontal and lateralized schizophrenia disturbances were examined in terms of arousal-modulated changes in 40 Hz Gamma activity. Methods : Forty patients with schizophrenia and 40 age- and gender-matched controls were studied in a conventional auditory ERP oddball paradigm. We investigated sub-averaged Gamma activity based upon a simultaneous measure of electrodemal skin conductance response (phasic arousal) to differentiate novelty (large responses) from routinization (small or no responses). Both early Gamma (Gamma 1) and later induced Gamma (Gamma 2) activities were examined. Results : Patients with schizophrenia (compared with controls) had significantly reduced Gamma 1 amplitude in the right hemisphere for novelty processing and delayed Gamma 2 latency in the left hemisphere for both novelty and routinization. Overall, reduced Gamma 1 amplitude in patients with schizophrenia was also evident. Conclusions : These findings indicate that the normal laterality of Gamma activity is specifically disturbed in schizophrenia in response to novel, but not routine (familiar) stimuli. The distinct pattern of findings suggests a dysregulation of activation across left and right hemispheres during initial attention and preparatory phases of information processing, in particular, in patients with schizophrenia.

Abstract Duchenne de Boulogne (1862/1990) observed that authentic smiles are distinguished from posed smiles by contractions of the orbicularis oculi muscle that surrounds the eye. Hager and Ekman (1985) subsequently reported that the “Duchenne smile” is discriminated specifically by contractions at the outer corners of the eyes (“crows feet” wrinkles). Little is known of the visuo-cognitive strategies that underpin perception of the Duchenne smile. We examined ocular dynamics (pattern of eye fixations) as an overt and accessible index of these strategies (Stark & Ellis, 1981). The spatio-temporal fixation indices were number and duration of foveal fixations to the crows feet area relative to the total face area. In line with predictions, subjects (n = 58) made proportionately more fixations of longer duration to the crows feet area for smiling, compared to negative (sad) and baseline (neutral) control expressions. It is suggested that a “hardwired” response may be involved in reference to this particular anatomical marker of the genuine smile. Humans may have evolved to distinguish the Duchenne smile because of its important communicative role.

Background. Gamma electrical rhythms (at 40 cycles per second) are postulated to have an important role in relation to the “binding problem” (of how the brain integrates its diverse neuronal activity). Impaired integration of brain activity may be a core pathophysiological feature of schizophrenia. The focus of this study was the examination of within-sample relationships between three primary schizophrenic syndromes (Psychomotor Poverty, Disorganisation, and Reality Distortion) and induced Gamma activity in an auditory target detection paradigm. Method. A time series was constructed of all Gamma activity (extracted from the same data traditionally acquired for Event Related Potentials; ERPs). Data was examined in response to 40 target and 40 nontarget auditory stimuli, in 35 patients with schizophrenia and 35 age- and gender-matched normal controls. Results. Although schizophrenics as a group showed generally reduced Gamma activity, each syndrome was differentiated by a distinct pattern of Gamma disturba...

There have been a number of studies on smooth pursuit eye movement (SPEM) dysfunction in schizophrenia. However, the association between SPEM dysfunction and particular clinical symptoms remains unclear. We examined SPEM dysfunction in relation to schizophrenic symptoms using both the positive/negative dichotomy and the three-syndrome model. Subjects included 78 patients with schizophrenia and 60 healthy control subjects. SPEM performance was indexed by root mean square error. Symptom profiles were assessed using the Positive and Negative Syndrome Scale (PANSS), and the three-primary syndromes were identified by factor analysis of PANSS ratings (Psychomotor poverty: deficit negative symptoms; Disorganization: defined primarily by thought disorder; and Reality distortion: hallucinations and delusions). Compared with controls, the schizophrenia group showed significant impairment in global SPEM function. The three-syndrome approach produced more specific findings than the dichotomous model. Of the three syndromes, only the Disorganization dimension showed a significant association with increased global SPEM dysfunction. The specificity of SPEM dysfunction to Disorganization was verified in comparisons among schizophrenia subgroups and the control group. By contrast, the general domains of positive and negative symptoms were both found to be modestly associated with SPEM dysfunction. The separation of positive and negative symptoms that contribute to Disorganization from those that define Reality Distortion and Psychomotor Poverty has revealed significant new associations between SPEM and schizophrenic symptoms. These findings are interpreted in light of the proposal that the Disorganization syndrome is the central form of pathology in schizophrenia.

Electroencephalography (EEG) and Event Related Potentials (ERPs) studies in ADHD have generally been studied separately. This study examined these measures simultaneously in 54 adolescent unmedicated ADHD males and age and gender matched normal controls during an auditory oddball paradigm. Compared with controls, ADHD patients showed increased pre-stimulus EEG Theta activity and post-stimulus reduced N200 amplitude, increased P200 amplitude and delayed N200 and P300 latencies evoked to target stimuli. Moreover, Theta activity was negatively correlated with N200 amplitude and positively correlated with P200, N200 and P300 latency in ADHD. There were no correlations in the control group. Pre-stimulus preparatory state increases in Theta activity in ADHD may underlie some of the reported disturbances in information processing reflected in ADHD.

Specialised network disturbances such as abnormalities in processing faces, may be associated with functional disturbances of interpersonal communication in schizophrenia. This study focused on the temporal dimension, investigating facial processing deficits in patients with schizophrenia (and non-patient controls) in a passive event-related potential (ERP) paradigm. ERPs invoked to an angry and neutral face stimulus were recorded in 27 patients with schizophrenia and 27 age and sex matched normal controls. Patients with schizophrenia showed a significant generalised delay, and diminished P200 amplitude (primarily frontal) for both stimuli-with more widespread regions of disturbance associated with the angry face. Normal controls, on the other hand, showed relatively reduced posterior P200 amplitude for angry compared to neutral faces, and a lateralised pattern of engagement in response to both stimuli. These findings indicate suboptimal processing of neutral faces in patients with schizophrenia, further exacerbated for affect laden angry faces.

In this study, we measured traditional late components of the Event Related Potential (ERP: N 100, P 200, N 200 and P 300) in a conventional auditory oddball paradigm, but additionally and simultaneously assessed electrodermal "orienting reflexes (ORs)" in 40 patients with schizophrenia and 40 age and gender matched normal controls. The single epoch ERPs that did and did not evoke an OR, were sub-averaged separately. The control subjects (but not the patient group), revealed delayed P 300 latency in the ERP sub-averages without ORs (ERP-OR), compared with ERP sub-averages with ORs (ERP+OR). Between-group analysis showed reduced N 100, N 200 and P 300 amplitudes (as well as delayed P 300 latency) in the ERP+OR sub-average in patients with schizophrenia. In the ERP-OR sub-average, the patient group also had smaller N 100, N 200 and P 300 amplitudes, but larger P 200 amplitude (compared with normal controls). This study shows the potential to tease out physiologically based OR sub-processes, by simultaneous acquisition and analysis of ERPs and autonomic electrodermal activity. Such ERP sub-averages (based on autonomic responses) highlight that multiple processes overlap across the trial, and their delineation may elucidate more specific patterns of disturbance in schizophrenia, than traditional averaged measures.

Background. While numerous studies have found disturbances in the Event-Related Potentials (ERPs) of patients with schizophrenia linked to task relevant target stimuli (most notably a reduction in P300 amplitude), few have examined ERPs to task irrelevant non-targets. We hypothesize, from current models of dysfunction in information processing in schizophrenia, that there will be less difference between ERPs to targets and non-targets in patients with schizophrenia than in controls.Methods. EEGs were recorded for 40 subjects with schizophrenia and 40 age and sex matched controls during an auditory oddball reaction time task. ERPs to the targets and non-targets immediately preceding the targets were averaged separately.Results. There was a disturbance in ERPs to targets but also to non-targets (reduced N100 amplitude and earlier P200 latency) and the difference between target and non-target ERP components (N100 and P200 amplitude and P200 latency), was significantly reduced in the schizophrenic group compared with controls.Conclusions. These findings suggest a disturbance in processing task relevant and irrelevant stimuli, consistent with Gray's (1998) hypothesis of misattributions in the ‘match[ratio ]mismatch’ of novel (target) and familiar (non-target) sensory input compared with stored information.

Objectives: Gamma (‘40 Hz’) rhythms may play a role in the integration of sensory processing activity. Impaired temporal integration may be a key feature of the associated disturbances in schizophrenia. This is the first study to examine the time course of Gamma activity induced in response to stimuli in this disorder. Methods: Gamma activity induced in response to task-relevant and irrelevant auditory oddball stimuli was examined in 35 medicated schizophrenics and 35 age- and gender-matched normal controls. We employed a moving Welch window with short time FFT to examine the time course of Gamma amplitude. The amplitude spectrum for each time point was de-trended to eliminate any contribution of broad spectrum activity (EEG or EMG) to Gamma amplitude. Results: For targets, schizophrenics showed a significant decrease in post-stimulus Gamma response amplitude in left hemisphere and frontal sites and an increase in right hemisphere and parieto-occipital sites (P

Background. This study explored the possible impairment in inhibiting irrelevant stimuli (as reflected in the backward masking version of the forced-choice span of apprehension task) in subgroups of individuals with schizophrenia. Method. Subjects included 48 schizophrenics and 54 nonpsychiatric controls. Letter arrays were presented at three stimulus onset asynchronies (SOAs; 60, 100, 250msec) and three levels of complexity (3, 7, 11 distractor letters). Results. As a group, schizophrenics (n = 54) were impaired relative to nonpsychiatric controls (n = 48) for 7-distractor displays at 60msec and 250msec SOA. Cluster analysis of SAPS and SANS ratings produced four symptom subgroups. Opposing masking performances were found for Psychomotor Poverty (impaired for long SOAs) and Reality Distortion (enhanced at short SOAs) subgroups, whereas the Disorganisation subgroup was globally impaired, and the Episodic subgroup performed similarly overall to controls. Conclusion. The results highlight the potential impo...

Previous studies have revealed various abnormalities in late-component ERP amplitude and latency in schizophrenia, considered as a diagnostic category. The aim of this study was to investigate the within-sample associations between late-component ERPs and three primary syndromes of schizophrenia Reality Distortion, Psychomotor Poverty and Disorganisation. Subjects included 40 schizophrenics and 40 age and sex matched nonpsychiatric controls. Auditory ERPs (N100, N200, P200, P300) were elicited using an auditory oddball paradigm. Between-group analyses of target data showed reduced N100, N200 and P300 amplitude, increased P200 amplitude and delayed N200 latency in schizophrenics compared to controls. For non-target data, schizophrenics showed similarly reduced N100 amplitude and delayed N200 latency. Within-group analyses of target data showed that the three syndromes (determined by principal component analysis of PANSS ratings) were differentiated by ERP latency, but not amplitude (Disorganisation delayed left hemisphere P200 and P300 latency; Reality Distortion earlier global, midline and left hemisphere N200 latency; Psychomotor Poverty delayed posterior N100 latency). Notably, only Disorganisation showed a divergent pattern of associations with non-target ERP data: reduced P200 amplitude and delayed N100 latency.

Objective: The aim of this paper is to develop an aetiological model for borderline personality disorder. Method: The postulates of Hughlings Jackson are used to provide a preliminary explanatory framework for borderline phenomena. As a necessary background to this discussion, the findings concerning abuse in the early history of borderline personality disorder (BPD) and other conditions, notably somatisation disorder and dissociative states, are briefly reviewed. Other data, including family studies, which might have significance in the aetiology of BPD are also reviewed. Results: The hypothesis is put forward that the symptoms of BPD are due to the failure of ‘experience-dependent’ maturation of a cascade of neural networks, with prefrontal connections, which become active relatively late in development and which coordinate disparate elements of central nervous system function. These networks subserve higher psychological functions, including attentional focus and affect regulation. They also underpin the reflective function necessary to the emergence of self as the stream of consciousness, which appears at about the age of 4 years. Conclusion: Adverse developmental circumstances may produce an interrelated set of symptom clusters, with associated neural network disturbances that are amenable to investigation with psychometric and brain imaging techniques. Since these disturbances are seen as ‘experience-dependent’, they are considered reversible, at least in part.

There is substantial evidence that schizophrenics have deficits in face processing. We hypothesised that this difficulty is due to abnormalities in the visual scanning of faces. The specificity of these abnormalities to recognisable faces, the effect of task difficulty and their relationships to three primary symptom dimensions were examined. An infrared corneal reflection technique was used to record the visual scanpaths of 63 schizophrenics and 60 non-psychiatric controls while viewing non-degraded (‘recognisable’) and degraded (‘not recognisable’) faces. In the concurrent recognition task, subjects were asked to select the previously viewed face from among seven (exposure 1) or three (exposure 2) options. Both groups were unable to accurately recognise degraded faces, but schizophrenics were less accurate than controls for non-degraded faces in the more difficult task condition. Schizophrenics maintained a relatively ‘restricted’ scanpath style across both faces, but scanpath disturbances were most apparent for non-degraded faces. Analysis of fixation distribution to non-degraded faces showed that, unlike controls, schizophrenics did not concentrate their fixations on salient features. Scanpath aberrations showed only minimal associations with symptom dimensions. These results suggest that schizophrenic individuals have a specific deficit in the visual scanning of faces, that is a distinct case of a fundamental problem in complex object processing.

Background. This study compared the ability of two different models of psychopathology in schizophrenia to account for findings in the quantified electroencephalogram (qEEG) recorded from midline sites in a group of 40 subjects with schizophrenia. The first model was based on the positive and negative syndrome dichotomy, the second was a tripartite model that resembled Liddle's syndromes of psychomotor poverty, disorganization and reality distortion (Liddle, 1987a).Methods. A group of 40 subjects with predominantly chronic schizophrenia was assessed with the Positive and Negative Syndrome Scale (PANSS) prior to the acquisition of their quantified electroencephalogram. The relationship between EEG data and symptomatology was explored, initially with the PANSS positive and negative subscales and then with a tripartite model derived from a principal component analysis of the 14 positive and negative subscale items.Results. The tripartite syndrome model showed a greater concordance with the qEEG of the subjects than the dichotomous model. ‘Psychomotor poverty’ was significantly positively correlated with both delta and beta power and ‘reality distortion’ was significantly positively correlated with alpha-2 power. No significant correlations between the positive and negative syndrome dichotomy and the qEEG were observed.Conclusions. This study lends support to the factor analysis of psychopathology, and specifically the tripartite syndrome model of schizophrenia, as a step in explicating the biological dimensions of the disorder.

Studies of concurrent central, and autonomic activity using a conventional event-related potential (ERP) oddball paradigms, are considered useful in elucidating the relationship between central and autonomic responses, but the autonomic response tends to overlap. A new method was used to decompose and score overlapping skin conductance responses (SCR). This method enabled examination of dynamic relationships of phasic SCR, prestimulus electroencephalogram (EEG), and ERP to auditory target stimuli in 50 normal adults. SCR amplitude was negatively correlated to EEG and N200 amplitude. The SCR amplitude changes over time exhibited an exponential decline opposite to those of N200, alpha, and beta. All the fitted exponential functions had a time constant of 1-2 min. The findings suggest that a N200 component, active in the auditory sensory discrimination, is concomitant with the SCR. The narrow range of the time constant may provide a clue to the conjoint processes underlying central and autonomic adaptive functions.

The P3 amplitude is augmented by decrements in target-probability, increments in the number of nontargets preceding the target, and extensions of the interstimulus interval (ISI). Each of these changes prolongs the target-to-target interval (TTI) and, consequently, results attributed to these factors might, at least partially, be accounted for by the TTI. Recent research also indicates that the P3s elicited by targets in one-, two-, and three-stimuli tasks (in which the TTI remains invariant) are similar. However, the TTI has not been examined systematically in previous research. The present study had subjects listen to a randomized ISI (0.5, 1, 2, or 4 s) version of the auditory oddball task in which targets occurred after one, two, three, four, or five nontargets. Event-related potentials were analyzed based on ISI, sequential structure, and TTI. The study examined sequence and ISI effects independent of TTI effects and demonstrated that extensions of ISI affected N1 but not P3 amplitude, extensions of TTI enhanced P3 amplitude independent of sequential structure, and sequential structure failed to influence P3 amplitude when TTI was controlled.

Objective: Innovations in physics and computing technology over the past two decades have provided a powerful means of exploring the overall structure and function of the brain using a range of computerised brain imaging technologies (BITs). These technologies offer the means to elucidate the patterns of pathophysiology underlying mental illness. The aim of this paper is to explore the current status and some of the future directions in the application of BITs to psychiatry. Method: Brain imaging technologies provide unambiguous measures of brain structure (computerised tomography and magnetic resonance imaging [MRI]) and also index complementary measures of when (electroencephalography, event related potentials, magnetoencephalography) and where (functional MRI, single photon emission computed tomography, positron emission tomography) aspects of brain activity occur. Results: The structural technologies are primarily used to exclude a biological cause in cases of a suspected psychiatric disorder. The functional technologies show considerable potential to delineate subgroups of patients (that may have different treatment outcomes), and evaluate objectively the effects of treatment on the brain as a system. What is seldom emphasised in the literature are the numerous inconsistencies, the lack of specificity of findings and the simplistic interpretation of much of the data. Conclusion: Brain imaging technologies show considerable utility, but we are barely scratching the surface of this potential. Simplistic over-interpretation of results can be minimised by: replication of BIT findings, judicious combination of complementary methodologies, use of appropriate activation tasks, analysis with respect to large normative databases, control for performance, examining the data ‘beyond averaging’, delineating clinical subtypes, exploring the severity of symptoms, specificity of findings and effects of treatment in the same patients. The technological innovation of BITs still far outstrips the sophistication of their use; it is essential that the meaning and mechanisms underlying BITmeasures are always evaluated with respect to prevailing models of brain function across disciplines.

Objective : To determine whether a relationship existed across trials between evoked gamma and reaction time in a conventional cognitive ERP paradigm. Methods : Auditory oddball data in 40 normal subjects was examined. A moving Welch window and short time FFT were employed to elucidate the time course of gamma (29 to 45 Hz) activity in each single-trial target ERP. The time point with maximum total gamma amplitude (across all sites) was identified automatically, and the associated amplitude, power and latency of this peak was determined. Spearman's rank correlation was employed to examine the relationship of these measures with reaction time. Results : A highly significant and robust correlation between peak gamma latency and reaction time was found ( P =0.000001). Further frequency analysis revealed that this relationship was primarily confined to the 37 to 41 Hz band. This narrow band finding, coupled with the fact that the finding remained after exclusion of possibly EMG contaminated epochs, indicated that the effect was not due to EMG contamination. No relationship between peak gamma amplitude or power and reaction time was found. Conclusions : Peak evoked gamma latency was correlated with reaction time and seems likely to have functional significance in relation to stimulus processing.

The effects of age on late component (N100, P200, N200, and P300) event-related potentials (ERP) and reaction time (RT) were investigated in 50 normal subjects, 18 to 70 years of age. A conventional auditory oddball paradigm was employed. An equal number of subjects, as well as an equal number of males and females, were examined in each decade. There were no significant associations found between ERP amplitude and age. A significant positive correlation was found between age and N200/P300 latency. There were no significant effects of age on RT in the overall group. However, females had slower RT and decreased P200 and N200 amplitude as compared with males. Moreover, males had significant correlations between N200 latency and RT, whereas females showed significant correlations between P300 amplitude and RT. ERP/RT effects should be further explicated between gender, as well as across age.

We examined whether the amplitude decrement traditionally found for the N1 peak of the event-related potential (ERP) with repetition of auditory stimuli results from the process of habituation or from the refractory period of the neural elements underlying the N1 response. These competing accounts of the process underlying the N1 decrement with repetition differ in terms of the predicted effects of variations in stimulus repetition and interstimulus interval (ISI). These predictions were examined using a short-term habituation design with a factorial combination of stimulus repetition and ISI. Forty-five subjects received 21 stimulus trains, each consisting of seven innocuous tones, all at 1 kHz except the sixth, which was a 1.5-kHz tone. Each subject was assigned to one of three ISI conditions (either 1, 3 or 10 s). The results provide little support for the view that N1 response decrement with stimulus repetition reflects a process of habituation. The present results provide greater support for the view that this decrement is based on the separate refractory periods or recovery cycle processes of at least two neural generators contributing to activity in the N1 peak latency range.

The influence of the level of prestimulus alpha phase synchronicity on the N100 component and reaction time (RT) was examined, in target auditory oddball data from 25 normal subjects. Alpha phase synchronicity is a new measure consisting (for a given stimulus presentation) of the angular or circular variance of the alpha phase at stimulus onset across the parieto-occipital sites. The lower the angular variance, the higher the phase synchronicity (the more closely in phase the alpha activity across these sites) and vice versa. Subaveraged event-related potentials (ERPs) were formed for high and low prestimulus alpha phase synchronicity stimulus presentations. N100 amplitude was significantly greater in the high than the low phase synchronicity subaverages. In addition, RT was significantly reduced in the high prestimulus alpha phase synchronicity cases. Alpha phase synchronicity reflects an aspect of brain state that influences subsequent stimulus processing.

This paper presents a new method for the identification of individual event related potential (ERP) components in both frequency and time domains. Using the similar basis function (SBF) algorithm the method provides a time to frequency transform, representing a frequency domain equivalent of the component waveform. Notable features of the SBF algorithm are that it allows for unevenly spaced sampled functions in both the time and frequency domains, and estimates of spectral densities are obtained by numerical computation of finite Fourier integrals. Application of this method to ERP data from 20 normal subjects demonstrated a similar shape of component amplitude frequency characteristics for traditional late component waveforms (N1, P2, N2 and P3). On this basis, a low-frequency band was found where the component amplitude frequency characteristic was described by a Gaussian function, while the component phase frequency characteristic was a linear function of frequency. These relationships are interpreted as frequency domain equivalents of the component. Transformed to the time domain, they provided an analytical description of the ERP as the sum of positive- and negative-going monopolar waves. The study points to similar mechanisms underlying these component waveforms, and analytically defines dynamic properties for the components both in the frequency and time domains.

P300 Event Related Potentials components (P300a and P300b) were investigated using an auditory oddball paradigm (with a button press response to target stimuli) in 15 Parkinson's disease patients and 50 normal controls whilst simultaneously measuring electrodermal activity. Cluster analysis showed that the first 10 target stimuli generated the largest skin conductance responses. The first 10 single-trial ERP epochs were therefore analysed as an ERP sub-average for each individual. The P300a component (associated with the automatic 'Orienting Reflex') was expected to be most prevalent in this sub-average (compared with sub-averages of subsequent blocks of 10 target stimuli). Twenty-nine out of 50 normal controls (58%) elicited a P300a in the first 10 target sub-average, compared with only 2 out of 15 Parkinson's disease subjects (13%). The conventional P300b component (associated with controlled processing) was found to be significantly delayed for all sub-averages for the Parkinson's disease group when compared with controls. These preliminary findings suggest a possible dysfunction in both automatic and controlled processing in this disorder.

A number of studies have examined the average late component Event Related Potential (ERP) and Reaction Time (RT) in response to multiple target stimuli (across-trial averages). This study demonstrates within-trial differences in ERP brain function associated with relatively fast and slow RTs in 50 normal subjects. A conventional auditory oddball paradigm (with a 1 ISI) was employed. Increased ERP N100 and N200 amplitude (and decreased P200 amplitude), as well as earlier P200, N200 and P300 latency were found in the fast compared with the slow ERP subaverages. These results show the potential to elucidate temporal and spatial dynamics of brain function associated with changes in performance, in conventional "cognitive" paradigms applicable to both health and disease states.

The aim of this study was to explore elements of the maturational and cortical hypoarousal models in adolescent ADHD, by examining EEG activity in a rest eyes open condition, in 26 adolescent unmedicated ADHD males and 26 age and sex matched normal controls. ADHD adolescents were found to have increased anterior EEG absolute theta activity and reduced posterior relative beta activity compared with controls. These results lend some support to the continuation of a maturational lag and reduced cortical arousal in adolescent ADHD. These measures need to be further explored using concomitant EEG with electrodermal measures of arousal.

Alterations in mean frequency and power in the alpha band of the electroencephalogram (EEG) is thought to reflect fundamental attentional and cognitive factors. This study investigated changes in the mean alpha frequency of the quantified EEG in 21 subjects with schizophrenia, compared to an equal number of age and sex matched controls. Four standard electrophysiological paradigms (eyes closed, eyes open, habituation and oddball) were used to manipulate the level of cognitive demand required of each subject. Significant differences were found both between normal and schizophrenic groups in mean alpha frequency as well as within groups between different paradigms. Whilst a consistent linear relationship between site and paradigm was observed in controls subjects (slower frontally and slower with cognitive load), this was not observed in subjects with schizophrenia. The subjects with schizophrenia showed a loss of this linear relationship and increased mean alpha frequency frontally with cognitive load.

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Simultaneous measures of Event Related Potentials (ERP) and electrodermal activity (EDA) allow the delineation of ERPs that did, and did not, evoke an electrodermal 'Orienting Reflex' (OR). The OR is an automatic reflex invoked by novel or significant stimuli. Our group have developed a model to quantify electrodermal OR activity acquired in conventional late component ERP paradigms with short interstimulus intervals. Target late component (N100, P200, N200, P300) ERPs (acquired in an auditory oddball paradigm) and EDA was examined in 15 Parkinson's disease (PD) subjects and 50 normal controls. Single-trial target ERPs were averaged according to whether or not they elicited an electrodermal OR. Compared with controls, the PD group showed significantly decreased N100 and N200 amplitudes in the OR related ERPs ('Orienting ERPs'). These preliminary findings suggest that conventional late component ERPs can be delineated according to whether or not they evoked an OR. The 'orienting ERPs' in PD showed more significant disturbances compared with controls, than ERPs that did not evoke an OR.

Deep dyslexia is an acquired reading disorder that is characterized by the production of semantic reading errors, greater success when reading aloud concrete and highly imageable words, frequent visual and visual-semantic errors, morphological errors and very poor reading of nonwords. The right hemisphere hypothesis proposes that in deep dylsexia the patient is not reading with an impaired version of the normal left hemisphere reading system, and cannot use that system for reading at all. Instead, a different reading system, located in the right hemisphere is used. The right hemisphere hypothesis was examined in this study by investigating the amount of cortical activation in the left and right cerebral hemispheres of a deep dyslexic patient (L.H.) during visual word recognition. Three experimental tasks were devised to isolate a Visual Word Recognition process and a Spoken Word Production process and these tasks were administered to the deep dyslexic patient as well as another patient with left-...

Objective: To examine the individual and combined impact that traumatic brain injury (TBI) and heavy social use of alcohol have on electrophysiologic correlates of working memory and evaluation of task-relevant information. Design: Case-control study Setting: University hospital brain injury rehabilitation unit. Participants: Forty male volunteers divided into four groups on the basis of their history of TBI and alcohol intake. Subjects with TBI had experienced a severe closed head injury at least 1 year before testing. Main Outcome Measure: Event-related potentials (ERPs) and neuropsychometric tests. Results: Groups showed no significant differences in average age or neuropsychological tests. TBI groups did not differ in time postinjury or on severity measures. Alcohol use measures were significantly greater in the two alcohol groups. N200 latency and P300 amplitude were impaired in heavy social drinkers and in nondrinking subjects with TBI relative to controls, but were significantly impaired in subjects with TBI who were also heavy social drinkers. Conclusion: The results indicate that although alcohol use and TBI independently produce mild alterations in some aspects of late ERP components, the ERP changes are significantly greater when alcohol use and TBI are combined. This study provides evidence that heavy social drinking after TBI has a measurable impact on electrophysiologic correlates of cognition.

Late component event related potentials (ERP) and concomitant electrodermal activity (EDA) measures of the orienting reflex (OR) were undertaken in 50 normal subjects. Our group recently developed a model to quantify electrodermal activity in conventional ERP paradigms (auditory oddball) with short interstimulus intervals (ISI). The method was used to classify the presence or absence of skin conductance response following each auditory target stimulus. Using a conventional paradigm in which data is traditionally averaged, single-trial target ERPs were sorted into those with a skin conductance response OR (ERP[+OR]) and those without (ERP[-OR]) an OR, and ERP sub-averages of the two groups were derived. The ERP(+OR) showed significantly larger P300 amplitudes and relatively earlier N200 and P300 latency than those of the ERP(-OR). These findings suggest that using concomitant SCR-ERP measures, separate ERP related processes can be determined, that are complementary to the traditional average measure.

The microtubule-associated protein tau gene (MAPT) codes for a protein that plays an integral role in stabilisation of microtubules and axonal transport in neurons. As well as its role in susceptibility to neurodegeneration, previous studies have found an association between the MAPT haplotype and intracranial volume and regional grey matter volumes in healthy adults. The glycogen synthase kinase-3β gene (GSK3B) codes for a serine/threonine kinase that phosphorylates various proteins, including tau, and has also been associated with risk for neurodegenerative disorders and schizophrenia. We examined the effects of MAPT and two functional promoter polymorphisms in GSK3B (rs3755557 and rs334558) on total grey matter and intracranial volume in three independent cohorts totaling 776 neurologically healthy individuals. In vitro analyses revealed a significant effect of rs3755557 on gene expression, and altered binding of at least two transcription factors, Octamer transcription factor 1 (Oct-1) and Pre-B-cell leukemia transcription factor 1 (Pbx-1), to the GSK3B promoter. Meta-analysis across the three cohorts revealed a significant effect of rs3755557 on total grey matter volume (summary B = 0.082, 95% confidence interval = 0.037-0.128) and intracranial volume (summary B = 0.113, 95% confidence interval = 0.082-0.144). No significant effect was observed for MAPT H1/H2 diplotype or GSK3B rs334558 on total grey matter or intracranial volume. Our genetic and biochemical analyses have identified a role for GSK3B in brain development, which could have important aetiological implications for neurodegenerative and neurodevelopmental disorders.

A core feature of post-traumatic stress disorder (PTSD) is hypervigilence to threatening material. This study measured processing of threat material in PTSD with simultaneously acquired initial eye movements and electrodermal activity, following presentation of threatening and neutral words. Ten PTSD subjects and 10 controls were presented with 4 words in parafoveal range. On trials in which a threat word was present, PTSD subjects demonstrated initial eye fixations on the threat word more than controls. PTSD subjects also demonstrated more orienting responses on all trials than controls. These results suggest that processing of threat information in PTSD can be usefully investigated with convergent psychophysiological methodologies.