Prefrontal neurons and the genetics of schizophrenia.

The concept of locally specialized functions dominates research on higher brain function and its disorders. Locally special- ized functions must be complemented by processes that coordinate those functions, however, and impairment of coordinating processes may be central to some psychotic conditions. Evidence for processes that coordinate activity is provided by neurobiological and psycho- logical studies of contextual disambiguation and dynamic grouping. Mechanisms by which this important class of cognitive functions could be achieved include those long-range connections within and between cortical regions that activate synaptic channels via NMDA- receptors, and which control gain through their voltage-dependent mode of operation. An impairment of these mechanisms is central to PCP-psychosis, and the cognitive capabilities that they could provide are impaired in some forms of schizophrenia. We conclude that impaired cognitive coordination due to reduced ion flow through NMDA-channels is involved in schizophrenia, and we suggest that it may also be involved in other disorders. This perspective suggests several ways in which further research could enhance our under- standing of cognitive coordination, its neural basis, and its relevance to psychopathology.

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Convergence of biological and psychological perspectives on cognitive coordination in schizophrenia

Objective: Patients with schizophrenia consistently show performance deficits on measures of visual backward masking, but the nature of these deficits is not well understood. Performance deficits on backward masking tasks may indicate an underlying predisposition instead of the presence of illness, because deficits are present in unaffected first-degree relatives. Performance deficits in remitted patients would constitute converging support for this hypothesis. Method: Eleven patients with recent-onset schizophrenia who were in a period of no medication use during remission of psychosis were compared with a matched normal group on three visual masking conditions. These conditions included target identification tasks with a high-energy mask, a low-energy mask, and a blurred target. Results: Patients in psychotic remission showed significant deficits across all conditions. In addition, trend analyses revealed significant group differences in the shape of the masking functions: the comparison group showed an oscillating performance pattern across all masking conditions, whereas the patients did not exhibit this pattern on any condition. Conclusions: These data from patients in well-documented psychotic remission add converging support for the hypothesis that deficits on backward masking procedures are indicators of vulnerability to schizophrenia. Because visual masking procedures may reflect underlying neural oscillations of 30 to 70 Hz in the visual cortex, the pattern of results is consistent with the theory that visual masking deficits in schizophrenia stem from an underlying failure to establish cortical oscillations.

https://ajp.psychiatryonline.org/doi/pdf/10.1176/ajp.156.9.1367

Backward Masking in Unmedicated Schizophrenic Patients in Psychotic Remission: Possible Reflection of Aberrant Cortical Oscillation

Towards a quantitative characterisation of functional states of the brain: from the non-linear methodology to the global linear description.

Recent reports of functional and anatomical studies have provided evidence that aberrant neural connectivity lies at the heart of many mental disorders. Information related to neural networks has elucidated the nonlinear dynamical complexity in brain signals over a range of temporal scales. The recent advent of nonlinear analytic methods, which have served for the quantitative description of the brain signal complexity, has provided new insights into aberrant neural connectivity in many mental disorders. Although many studies have underpinned aberrant neural connectivity, findings related to complexity behavior are still inconsistent. This inconsistency might result from (i) heterogeneity in mental disorders, (ii) analytical issues, (iii) interference of typical development and aging. First, most mental disorders are heterogeneous in their clinical feature or intrinsic pathological mechanisms. Second, neurophysiologic output signals from complex brain connectivity might be characterized with multiple time scales or frequencies. Finally, age-related brain complexity changes must be considered when investigating pathological brain because typical brain complexity is not constant across generations. Future systematic studies addressing these issues will greatly expand our knowledge of neural connections and dynamics related to mental disorders.

Complexity of spontaneous brain activity in mental disorders.

Dimensional complexity reflects the number of independent variables contributing to a dynamic process. EEG epochs recorded from 12 neuroleptic-free schizophrenic patients and 11 normal control subjects were Laplacian-filtered to highlight activity specific to prefrontal and parietal areas, and dimensional complexity measures of the resulting signals were then derived. Complexity of EEG waveforms generated by schizophrenic patients was depressed relative to that of normal subjects, especially in left frontal and right parietal regions. These data suggest that complexity of underlying is also reduced.

Tsai K

Papers

Dimensional complexity of EEG waveforms in neuroleptic-free schizophrenic patients and normal control subjects