Corollary discharge (CD), originally described in the visual system but also documented in the auditory system may provide a mechanism for distinguishing self-generated from externally-generated percepts. Within the auditory system, corollary discharges from frontal lobes where speech is generated prepare the auditory cortex in the temporal lobe for recognizing that what is heard was self-generated. Thus, failure of CD has been posited to underlie certain positive symptoms of schizophrenia, including auditory hallucinations. This hypothesis is consistent with circuit-based models of brain dysfunction in schizophrenia that suggest disrupted connectivity between frontal and temporal lobes. While theoretically compelling, the role of corollary discharge in discriminating between self and externally generated speech, and its failure in schizophrenia, are not easily amenable to measurement. However, our recent studies using event related potential (ERP) responses, functional magnetic resonance imaging (fMRI) measures of regional brain activation, and measures of electroencephalographic (EEG) coherence between frontal and temporal lobes are all consistent with the hypothesis. In this competitive renewal, we will test patients with schizophrenia and matched healthy controls in a series of studies designed to: Extend earlier observations with new ERP and fMRI experiments that enhance our understanding of normal CD operation and refine neurobiologic observations of CD deficits in schizophrenia (Specific Aim 1); Relate diffusion tensor imaging (DTI) measures of microstructural integrity of white matter tracts connecting frontal and temporal lobes to ERP and fMRI indices of CD dysfunction (Specific Aim 2); Determine whether CD failure reflects state or trait features of hallucinatory behavior in schizophrenia by assessing ERP and EEG coherence measures before and after hallucinating schizophrenic patients undergo a course of repetitive trancranial magnetic stimulation (rTMS) treatment (Specific Aim 3).
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