This competitive renewal application requests five years of support to continue our MEG studies in schizophrenia, specifically, to address findings relating to altered sensory cortical localization, sensory memory and the role of attentional mechanisms in cortical plasticity in patients with schizophrenia. Whole-cortex MEG and 3T MRI will be used to measure the functional and structural underpinnings of primary and secondary auditory and somatosensory cortex in schizophrenia. Emerging MEG-based evidence from our and other laboratories suggests possible disturbances in sensory registration involving attentional, timing, and memory mechanisms, as well as anomalous brain asymmetry, and altered organization and localization of primary and secondary sensory cortex in schizophrenia. We will study a total of 90 subjects (50% female) including 45 subjects with schizophrenia and 45 controls. MEG recordings have been designed to selectively activate functional sources in primary and secondary auditory and somatosensory cortical areas. These structural regions will also be identified, segmented, and reconstructed from MRI images, and MEG functional sources will be superimposed upon neuroanatomy. The effects of attention on source geometry will be measured, and estimates made of echoic and haptic memory function in primary and secondary sensory cortex. Anatomical asymmetry measures including brain torque will be obtained and compared to functional asymmetry. We believe the abnormalities in the sensory cortical regions being addressed could underlie components of the fundamental cognitive disturbances, including language and executive function, accompanying schizophrenia. They imply possible cortical dis- or reorganization and impaired cortical plasticity in schizophrenia. ? ?
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