Neurobiological Correlates of Disturbed Cognitive Functions in Patients with Schizophrenia: A Simultaneous EEG + fMRI Study

Currently, there is evidence demonstrating that schizophrenia is an illness characterized by multiple deficits in fundamental cognitive processes such as attention and memory. The P300 component of the event-related potential is thought to reflect various cognitive processes including the allocation of attentional resources to incoming stimuli. Reduction of the auditory P300 amplitude is constantly found in schizophrenic patients. Besides it could be shown that the P300 amplitude correlated negatively with the severity of thought disorders. Thus, the P300 appears to be a suitable functional parameter of thought disorders in schizophrenic patients. We combined ERP and functional MRI data to examine discrepancies in brain regions involved in information processing as well as in the time course of neural generators of the event-related potential between schizophrenics and normal controls. So far the study comprises six patients with schizophrenia and six age-matched controls with no known history of neurological or psychiatric disorder. The subjects performed an auditive oddball task requiring responses to infrequent tones presented in a series of frequent tones of a different pitch. MR imaging was performed on a 1.5 T Siemens Sonata scanner (EPI sequence; 12 slices; TR/TE: 3000/53 ms). EEG signals were recorded with an amplifier that cannot be saturated by MR activity (61 channels according to the international 10/10 system; Cz reference). The EEG recordings showed the expected positive deflection about 400 ms after the presentation of infrequent stimuli in normal controls and a reduced P300 component in schizophrenics. Besides we could replicate findings of previous P300 studies revealing BOLD activations mainly in frontal, especially anterior cingulate cortex, SMA, insula, inferior and middle frontal gyrus as well as thalamus, temporal and parietal brain structures in healthy subjects [Fig. 1]. The functional MRI data of schizophrenic patients showed a reduced BOLD response in a widespread network of cerebral areas involved in task execution [Fig. 2]. There was a modest negative correlation between the extent of functional activation in the ACC/SMA region and thought disorders as well as negative symptoms (PANSS) that did not reach significance. Our findings suggest widespread abnormal brain functioning in patients with schizophrenia during information processing.