Reduced gray matter volume of the auditory cortex located on the supenor temporal gyrus (S I U) is the structural brain imaging abnormality most consistently identified in the cerebral cortex of subjects with schizophrenia. Functional studies of audition similarly indicate that subjects with schizophrenia have impairments in the precision of auditory sensory memory that localize to this region. Recently, we identified that among the contributors to reduced gray matter volume in the STG of subjects with schizophrenia was reduced pyramidal cell somal volume in deep layer 3 of auditory association cortex (BA42). In this R2 I application, we propose a series of initial studies to develop a body of data necessary for the proper interpretation of the current findings and upon which future studies of auditory cortex pathophysiology in subjects with schizophrenia will be built. Specifically we will test the following hypotheses: 1) Chemoarchitectonic criteria reliably parcellate human auditory cortex into regions corresponding to the core, lateral belt and parabelt regions delineated in non-human primates. 2) Auditory lateral belt and parabelt, but not core, cortex volumes are reduced in subjects with schizophrenia. 3) Reduced deep layer 3 pyramidal cell mean somal volume in subjects with schizophrenia results from a shift to smaller size of all cells and not from a change in cell number. The planned studies are novel in that they will be the first to examine changes in volume of a chemo- or cytoarchitectonically defined region in subjects with schizophrenia, and in their rigorous application of stereo logic techniques to the determination of somal volumes and absolute numbers of pyramidal cells in subjects with schizophrenia. Successful completion of these studies will: 1) Enhance the interpretation of current and future findings by placing them in the context of the rich electrophysiologic and connectional data present in monkey through delineation of human analogues of core, lateral belt and parabelt; 2) Identify a pathologic target on which to focus future investigations by determining which chemoarchitectonic regions demonstrate reduced gray matter volume; and 3) Provide a basis for the generation of specific mechanistic hypotheses by clarifying whether cell volume or number is altered. Finally, it is anticipated that the generation of mechanistic hypotheses in future studies of auditory cortex in subjects with schizophrenia will be enhanced by the applicant's ongoing, complementary studies of the neurobiology of psychosis in Alzheimer disease.
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