Schizophrenia patients show aberrant brain dynamics associated with gestalt-perception and corollary discharge: Reflections from ERP and fMRI findings

Background Schizophrenia is a disorder of higher mental attributes, and is characterized by psychotic symptoms that are believed to involve a basic inability to make valid predictions about expected sensations and experiences. These have been reported separately while monitoring either externally generated environmental patterns (e.g. gestalt-perception) or self-generated sensory experiences (e.g. corollary-discharge). As the pathophysiology behind predictive dysfunction is better viewed as an aberration in brain’s functional synchrony, a whole brain assessment using electroencephalographic (EEG) event related potential (ERP) and functional magnetic resonance imaging (fMRI) techniques, would offer a wider perspective to brain network abnormalities in schizophrenia. Method We used our lab-developed game-based task which presents degraded two-tone images to assess gestalt-perception, and simultaneously alters the congruency between participant’s button-press response and its auditory feedback to assess corollary-discharge. In both patients with schizophrenia and age-matched healthy controls, we explored event-related changes in an EEG-ERP study (n=21 each) and whole brain functional connectivity changes in a fMRI study (patients,n=12; controls,n=16), using the same task. Results Patients showed reduced event-related EEG dynamics during both the error-prediction conditions (gestalt-perception and corollary-discharge), which include reduction in average waveforms (around N170 and N1-P2 complex, respectively) and altered theta dynamics (power and phase). Source-level EEG measures were clustered around the cingulo-insular network. fMRI functional connectivity analysis also found the abnormality in these brain regions, forming significantly weak connections with right insular/opercular cortex. Conclusions This is the first study to explore ‘thalamo-cortical dysfunction hypothesis’ in schizophrenia by integrating prediction-error-coding during perception (‘gestalt-perception’) and action (‘corollary-discharge’) using two neuroimaging modalities (EEG-ERP and fMRI). Besides adding to the knowledgebase of schizophrenia research, our novel task design and findings on theta-oscillation could benefit in the development of effective neuromodulatory therapeutic tools for patients with schizophrenia such as neurofeedback and transcranial brain stimulation.