The purpose of this proposal is to investigate the difference in auditory cortical processing between schizophrenics and controls using a combination of magnetoencephalography (MEG), electroencephalography (EEG), and high-resolution magnetic resonance imaging (MRI). Using tools recently developed at the Martinos/MGH-NMR center, the proposed research will advance previous work by: (i) improving MEG/EEG localization using precise anatomic MR1 reconstructions and prior information from fMRI (ii) simultaneously measuring MEG and EEG to assess both radial and tangential neural currents (iii) applying novel wavelet-based, cortically constrained algorithms to MEG/EEG signals to quantify local and global cortical synchrony on the cortical surface. Specifically, these techniques will be applied to various types of auditory stimulation including the mismatched response and gamma-band phase synchrony of the sustained neuromagnetic auditory response. This could potentially allow for quantitative measurements of schizophrenic pathologies that are undetected behaviorally. Additionally, both the mismatch response and the gamma-band synchronization may lead to a better understanding of the cellular, especially the NMDA hypothesis of neuronal dysfunction and macroscopic mechanisms of schizophrenia. Later in the training period, other higher cognitive processes such as auditory hallucinations and thought disorders may be investigated and correlated with the anatomic and neurophysiological disorders. This proposed five-year training program combines the candidate's background in diagnostic neuroradiology, biomedical engineering, and magnetoencephalography (MEG) with the mentors' expertise in schizophrenia and multimodal imaging to investigate brain neurodynamics in schizophrenia. The broad, long-term objective is to create a non-invasive, clinical imaging tool, which is capable of diagnosing and monitoring the treatment of neurological disorders affecting information processing. The hypothesis is formulated that multiple deficits in the auditory system are responsible for altered auditory processing in schizophrenia, which are measurable with functional neuroimaging.
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