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Most studies of gamma band synchrony in schizophrenia conclude that it is reduced, relative to what is observed in healthy people, during stimulus processing. However, these findings may, in part, be an artifact of greater absolute levels of synchrony in schizophrenia even at baseline. We examined absolute level of gamma band synchrony before and during emotionally neutral face processing in 28 patients with schizophrenia after their first episode of psychosis (FES) (20 male) and 71 controls (53 male) across a range of frequency bins, brain regions and time-bands. We also examined how absolute synchrony prior to stimulus onset related to synchrony change during stimulus processing, and how it related to symptoms. The FES group showed greater absolute gamma synchrony across all time-points in frontal and temporal regions. Baseline absolute synchrony predicted post-stimulus change in these regions in a pattern consistent with previous reports. However, synchrony change was not related to symptoms. These results support the recommendation that studies in this field should examine baseline absolute synchrony when attempting to characterize task-related gamma synchrony in schizophrenia.

Models of laterality infer distinct aspects of EEG alpha asymmetry in clinical disorders, which has been replicated for over three decades. This biomarker now requires a more fine-grained assessment of its clinical utility as a diagnostic and treatment predictive marker. Here, within the same study we assessed resting brain laterality across six clinical disorders, for which deviant laterality has been implicated as core dysfunction. These disorders were evaluated in comparison to a large normative dataset (∼1,900) from the Brain Resource International Database. EEG alpha asymmetry was assessed in the frontocentral region, for resting Eyes Closed and Eyes Open conditions. Schizophrenia was characterized by significantly greater left lateralized alpha power than controls, indicating a deficit in left frontal activity at rest, which may relate to “disconnections” across wider fronto-temporal networks. The depression group showed a trend-level tendency towards the opposite pattern of greater right-lateralized activity than controls. The remaining anxiety and behavioral disorders did not show any significant deviance in alpha asymmetry from the normative control group. However, at a non-significant level laterality for these groups was generally consistent with expected directions, suggesting a propensity towards a particular lateralization but still remaining within the normative range. Overall, the results of the current study indicate that EEG alpha asymmetry may show the most clinical utility as a biomarker for schizophrenia and depression in comparison to other clinical disorders.

Most brain related databases bring together specialized information, with a growing number that include neuroimaging measures. This article outlines the potential use and insights from the first entirely standardized and centralized database, which integrates information from neuroimaging measures (EEG, event related potential (ERP), structural/functional MRI), arousal (skin conductance responses (SCR)s, heart rate, respiration), neuropsychological and personality tests, genomics and demographics: The Brain Resource International Database. It comprises data from over 2,000 “normative” subjects and a growing number of patients with neurological and psychiatric illnesses, acquired from over 50 laboratories (in the USA, United Kingdom, Holland, South Africa, Israel and Australia), all with identical equipment and experimental procedures. Three primary goals of this database are to quantify individual differences in normative brain function, to compare an individual's performance to their database peers, and to provide a robust normative framework for clinical assessment and treatment prediction. We present three example demonstrations in relation to these goals. First, we show how consistent age differences may be quantified when large subject numbers are available, using EEG and ERP data from nearly 2,000 stringently screened normative subjects. Second, the use of a normalization technique provides a means to compare clinical subjects (50 ADHD subjects in this study) to the normative database with the effects of age and gender taken into account. Third, we show how a profile of EEG/ERP and autonomic measures potentially provides a means to predict treatment response in ADHD subjects. The example data consists of EEG under eyes open and eyes closed and ERP data for auditory oddball, working memory and Go-NoGo paradigms. Autonomic measures of skin conductance (tonic skin conductance level, SCL, and phasic skin conductance responses, SCRs) were acquired simultaneously with central EEG/ERP measures. The findings show that the power of large samples, tested using standardized protocols, allows for the quantification of individual differences that can subsequently be used to control such variation and to enhance the sensitivity and specificity of comparisons between normative and clinical groups. In terms of broader significance, the combination of size and multidimensional measures tapping the brain's core cognitive competencies, may provide a normative and evidence-based framework for individually-based assessments in “Personalized Medicine.”

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.

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.

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.

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.

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.

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This study explores SPECT measured in schizophrenic patients at rest. Left temporal lobe activity was found to be decreased with increasing positive symptom's scores scores. Medicated patients showed a reversal of this pattern underlying this positive symptom effect. Patients with a recent history of auditory hallucinations showed an atypical right temporal lobe dominance, which occurred independently of medication status. These preliminary data are suggestive of the potential utility of SPECT to elucidate symptom/medication/brain activity interrelationships in schizophrenia.

A 43 year old man with a traumatic amnesic syndrome experienced only a brief, if any, loss of consciousness following an injury to the head. Four years after this injury, his results on standard psychometric assessment were normal. Long-latency evoked response potentials results were normal, and the neurological examination and computed tomography scans were unhelpful in explaining his amnesic symptoms. He had no history of alcohol abuse, yet his neuropsychological profile was that of a Korsakoff-like amnesia with frontal lobe features. Magnetic-resonance images demonstrated evidence of extensive frontal lobe damage, while cerebral blood flow studies provided additional evidence of bilateral frontal lobe dysfunction. The case highlights the need for those giving opinions in medico-legal head trauma cases to go beyond a reliance on routine indicators, such as duration of coma, results of standard psychometric assessment and computed tomography scans, to more specialised neuropsychological evaluations and magnetic-resonance imaging scans.