Cerebral recruitment during information processing in healthy individuals and in schizophrenia

Recent evidence suggests that the fragmentation of mental activity that characterizes schizophrenia arises from impaired coordination of brain activity. When healthy individuals process information, rhythmic oscillations in brain electrical activity occur. We have recently shown in several studies that these oscillations are abnormal in people with schizophrenia, potentially leading to inconsistent recruitment of the brain when information is being processed. Similar, but less marked abnormalities occur in siblings who are at risk of developing the illness, suggesting that these abnormalities reflect the core brain disorder that predisposes to schizophrenia. We will record brain electrical activity while using magnetic resonance imaging (MRI) to obtain images of brain activity associated with processing of information, in patients, siblings and healthy comparison subjects. We hope this will lead to the development of a test that improves the reliability of diagnosis of schizophrenia, facilitating more efficient treatment and better outcome.

Schizophrenia is characterised by subtle but wide-ranging disruption of the processing of information, leading to serious, long-term disability in many cases. The nature of the core abnormality remains unknown. One plausible putative core abnormality is a disorder of connectivity between cerebral areas (Friston, 1999) but the nature of this postulated abnormality remains speculative.

A substantial body of evidence indicates that oscillatory electrical activity, observable in the electroencephalogram (EEG), plays a role in the recruitment of brain systems. For example, ongoing theta activity (4-8hz) contributes to variation in error related negativity (a electrical component reflecting the internal monitoring of performance errors) which in turn influences reaction time on subsequent trials and is associated with activation of cingulate cortex and other brain regions (Debener et al 2005)

Abnormalities of ERP components during information processing tasks are among the most robust reported abnormalities in schizophrenia. Recent studies demonstrate that these abnormalities are associated with reduced oscillatory activity, especially in the low frequency bands. Furthermore, fMRI performed during similar tasks reveals impaired recruitment of widespread cerebral regions. However, because of the variance in brain activity between trials and between subjects, these abnormalities have hitherto only been detected reliably in group comparisons (typically 10-20 individuals per group). To be of clinical use, measurement of abnormal brain function must be capable of detecting abnormality in individual cases. Few ERP studies or fMRI studies have focussed on the trial by trial variability in brain activity. Accounting for trial by trial variability in studying the recruitment of brain systems offers two potentially major advances: 1) it is likely that the variability is itself informative about the putative abnormality of recruitment of brain systems in schizophrenia; 2) treating trial by trial variation as variance of interest reduces residual variance, thereby increasing statistical power to detect abnormality in individual cases.

The primary aim of the project is to test the hypothesis that impaired recruitment of cerebral systems during information processing in schizophrenia is associated with impaired synchronization of low frequency oscillatory electrical activity, and that this abnormality is discernible in the majority of individual cases of the illness, and also in at least some siblings at risk. The proposed strategy will use fMRI (at 3T and 7T) and EEG to record brain activity during various information processing tasks in healthy individuals; in a cohort of patients with schizophrenia; and in siblings, focussing on examination of trial by trial variability.