Cognition In First Onset Schizophrenia: Mapping Relationships Between Task Performance, Brain Function And Symptoms

Abstract

Functional dysconnectivity has been proposed as the cause of schizophrenia. This thesis proposes a model with increased neural synchrony in the gamma band (30-100 Hz) as the underlying physiological mechanism responsible for this dysconnectivity. The model is tested by examining cognition, electroencephalogram (EEG) gamma synchrony, and functional magnetic imagining (fMRI) functional connectivity, and their interrelationships, in participants with first onset schizophrenia (FOS) and matched controls. All responses were elicited by a standard paradigm of attention – the Continuous Performance Test (CPT). This is the first direct comparison across these units of analysis in schizophrenia using the same paradigm. FOS showed impaired CPT cognitive performance (best measured by accuracy; n=75). The modulation of gamma synchrony to task-evoked changes was reduced in FOS (n=59), in the context of generally higher intrinsic synchrony, particularly in frontal regions. FOS (n=22) showed abnormal fMRI functional connectivity, measured from a DLPFC seed, with decreased connectivity to the inferior parietal cortex and increased connectivity to the dorsal anterior cingulate cortex. These findings support a model of schizophrenia as a disorder of excessive intrinsic brain connectivity with a failure to recruit appropriate task-induced activity. However, when interrelationships were examined pair-wise (EEG-cognition, fMRI-cognition, EEG-fMRI), they were more complex than hypothesized and did not integrate well into the model. A case-series (n=15 FOS; n=13 controls) examining interactions among all three measures provided further evidence of this complexity. The results highlight the importance of integrating across different units of analysis using the same task in the same participants, as it was the relationships among measures that challenged the model. The findings undermine schizophrenia simply as a disorder of abnormal functional connectivity caused by aberrant gamma synchrony.