This research will use magnetoencephalographic (MEG) recordings to evaluate apparent abnormal left temporal lobe function in schizophrenia. We have found evidence, using NMG evoked field (EF) recording, and magnetic resonance (MR) imaging, that 50 and 100 msec latency auditory EF components are generated in the temporal planum, and demonstrate interhemispheric asymmetry in normal males, but not females. Further, male paranoid schizophrenic patients demonstrate left temporal lobe differences in EF source location and orientation, compared to normal males, but schizophrenic females do not. We now propose to develop a multichannel neuromagnetic recording capability, and using this, with MR imaging: 1) determine whether systematic alterations of attention (invoking more complex source geometry) may alter M100 parameters in the two hemispheres, whether males and females, and schizophrenic patients differ in this respect, 2) evaluate longer latency evoked field components, including the magnetic counterparts of N200 and P300 in normals and schizophrenic patients, to see if expected left hemisphere differences are found, and with MR imaging to determine their neuroanatomical source, 3) determine whether normal males and females exhibit differences in temporal lobe cortical and subcortical anatomy sufficient to account for apparent EF sex differences, 4) determine whether EF findings in schizophrenia correlate with temporal lobe neuroanatomical structure, 5) determine if NMG EF findings vary as a function of subtype of schizophrenia, 6) evaluate the role of antipsychotic medication in altering magnetic source parameters, 7) determine whether such temporal lobe EF abnormalities are specific to schizophrenia, or might be found in other psychotic disorders, and 8) study first degree adult relatives, and children of schizophrenic patients, to determine the prevalence of similar EF findings in those at genetic risk for schizophrenia, and whether such findings can be used to predict the risk of these children later developing a schizophrenic disorder. These studies will provide information on temporal lobe function and structure in schizophrenia, and should help in understanding poorly understood sex differences in this disorder. They may also permit a quantified assessment of risk. The studies additionally will permit a comprehensive evaluation of the potential value of MEG recordings in the assessment of CNS function in both normal and mentally ill subjects.
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