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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.

Despite high rates of prescription, little is known about the long-term consequences of stimulant medication therapy for attention-deficit hyperactivity disorder (ADHD) sufferers. Historically, the clinical use of stimulants for ADHD has been based on trial and error before optimal therapy is reached. Concurrently, scientific research on the mechanism of action of stimulants has influenced neurobiological models of ADHD, but has not always informed their prescription. Whilst the two main stimulant types (methylphenidate and dexamphetamine) have numerous similarities, they also differ (slightly) in mechanism and possibly individual response. A further issue relates to differences in cost and availability compounded by the expectation for stimulants to be effective in ameliorating a broad spectrum of ADHD-related symptoms. Thus, there is an increasing need for treating clinicians to prescribe not only the most effective drug, but also the most appropriate dose with the associated release mechanism and schedule for each ADHD patient presented. In this regard, the field is witnessing an emergence of the personalized medicine approach to ADHD, in which treatment decisions are tailored to each individual. This shift requires a new approach to research into treatment response prediction. Given the heterogeneity of ADHD, a profile of information may be required to capture the most sensitive predictors of treatment response in individuals. These profiles will also benefit from the integration of data from clinical rating scales with more direct measures of cognition and brain function. In conclusion, there is a need to establish a more robust normative framework as the baseline for treatment, as well as diagnostic decisions, and as discussed, the growth of integrated neuroscience databases will be important in this regard.

The quantified analysis of the electroencephalogram (qEEG) has enabled the extraction of additional psychophysiological information from the raw EEG, but in turn has introduced a number of distortions. This study compared Dynamic Spectral Analysis (DSA), a novel and mathematically stringent technique for the evaluation of qEEG activity with conventional power spectral analysis in subjects with both first episode and chronic schizophrenia and matched controls. Advantages of the technique in the automated processing of data, rejection of artefact, avoidance of artefact introduced by the mathematical trans-formation of the data and the identification of irregular low frequency artefactual activity "pi" are discussed in detail. Using this method, the study has confirmed past observations of increased slow wave activity in schizophrenia, and identified a decrease in peak frequency in the alpha band in the subjects with chronic schizophrenia. The two clinical groups differed in mean peak frequency in the delta band with the first episode schizophrenia subjects having a raised mean peak frequency and the subjects with chronic schizophrenia having a lowered mean peak frequency. The results suggest continued change in the EEG with illness chronicity in schizophrenia. These changes were most evident in the frequency domain emphasizing the importance of routine measurement of mean band frequencies in qEEG studies.

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 (

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...

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. 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.

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.

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.

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.

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-...

The effects of age on event-related potentials (ERPs) elicited during a two-tone discrimination (“oddball”) task were examined in 97 normal subjects aged from 17–80 years. Strong relationships were found between age and the latencies of the later ERP components N200 and P300. Furthermore the correlation between age and N200 latency at Pz was marginally higher than that of age and P300 latency. For the entire sample, the increase in P300 latency as a function of age was best described at Cz and Pz by linear regression equations. However, a segmented line model better described the P300/age relationship at Fz — the increase in P300 latency with age in subjects over 61 was five times that of subjects younger than 61 years. In this study the task required button-press identification of the targets — the significance of increased age and a delay in N200 latency is discussed with reference to the possibility of N200 latency indexing the speed of cognitive processing.

Evian Gordon,1 A John Rush,2 Donna M Palmer,3,4 Taylor A Braund,3 William Rekshan1 1Brain Resource, San Francisco, CA, USA; 2Duke-NUS, Singapore; 3Brain Resource, Sydney, NSW, Australia; 4Brain Dynamics Center, Sydney Medical School – Westmead and Westmead Millennium Institute, The University of Sydney, Sydney, NSW, Australia Purpose: To evaluate the performance of a cognitive and emotional test battery in a representative sample of depressed outpatients to inform likelihood of remission over 8 weeks of treatment with each of three common antidepressant medications. Patients and methods: Outpatients 18–65 years old with nonpsychotic major depressive disorder (17 sites) were randomized to escitalopram, sertraline or venlafaxine-XR (extended release). Participants scored ≥12 on the baseline 16-item Quick Inventory of Depressive Symptomatology – Self-Report and completed 8 weeks of treatment. The baseline test battery measured cognitive and emotional status. Exploratory multivariate logistic regression models predicting remission (16-item Quick Inventory of Depressive Symptomatology – Self-Report score ≤5 at 8 weeks) were developed independently for each medication in subgroups stratified by age, sex, or cognitive and emotional test performance. The model with the highest cross-validated accuracy determined the participant proportion in each arm for whom remission could be predicted with an accuracy ≥10% above chance. The proportion for whom a prediction could be made with very high certainty (positive predictive value and negative predictive value exceeding 80%) was calculated by incrementally increasing test battery thresholds to predict remission/non-remission. Results: The test battery, individually developed for each medication, improved identification of remitting and non-remitting participants by ≥10% beyond chance for 243 of 467 participants. The overall remission rates were escitalopram: 40.8%, sertraline: 30.3%, and venlafaxine-XR: 31.1%. Within this subset for whom prediction exceeded chance, test battery thresholds established a negative predictive value of ≥80%, which identified 40.9% of participants not remitting on escitalopram, 77.1% of participants not remitting on sertraline, and 38.7% of participants not remitting on venlafaxine-XR (all including 20% false negatives). Conclusion: The test battery identified about 50% of each medication group as being ≥10% more or less likely to remit than by chance, and identified about 38% of individuals who did not remit with ≥80% certainty. Clinicians might choose to avoid this specific medication in these particular patients. Keywords: depression, treatment selection, cognitive tests, biomarkers, treatment prediction, antidepressant medication