Multimodal assessment of sensory processing dysfunction in schizophrenia

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Sensory processing deficits are a key component of schizophrenia. This project will analyze mechanisms underlying sensory processing dysfunction using a multimodal imaging approach incorporating both neurophysiological and MRl-based assessments. Neurophysiological studies will evaluate role of neuronal synchrony and oscillatory hierarchy impairments in etiology of neurocognitive dysfunction. In particular, it will test the hypothesis that impairments in non-linear stimulus amplification and in oscillatory entrainment may prevent response optimization in patients relative to controls. Four experiments are planned. The first experiment will analyze the role of oscillatory entrainment in the genesis of previously documented sensory processing deficits and object-attention dysfunction. For this experiment, hierarchical oscillatory analyses will be conducted using mathematical approaches and stimulation paradigms developed from Projects 2 and 3, respectively. The second experiment will analyze the role of spatial attention in sensory processing dysfunction, also using both standard ERP and oscillatory hierarchy analyses, and will also evaluate the role of phase reset vs. exogenous activity in ERP generation in patients and controls. Experiment 3 will evaluate spatial attention effects further using ssVEP approaches. Deficits in ERP generation will also be assessed relative to symptomatic and cognitive measures. The fourth experiment will evaluate the role of structural and functional connectivity impairments in etiology of sensory and attentional deficits using MR measures supported by Core B. DTI measures will be used to assess structural connectivity, while resting state fMRI will be used to assess functional connectivity. An underiying hypothesis is that deficits in neurophysiological processes such as non¿ linear gain and slow oscillatory function that are known to be NMDA receptor-dependent will lead to impaired entrainment of higher-frequency oscillations (e.g. delta, theta, gamma), leading to impaired ERP generation and behavior. Overall, this project will test the hypothesis that deficits in hierarchical processing within regions and structural and functional connectivity between regions lead to deficits in neurocognitive function in schizophrenia. RELEVANCE (See instructions): Schizophrenia is a major mental disorder. Neurocognitive dysfunction is a core component of schizophrenia and a major determinant of poor long-term outcome. This project will evaluate mechanisms underlying deficits in sensory processing and neurocognitive dysfunction in patients with chronic schizophrenia, in collaboration with other projects and core programs in order to develop improved methods for early detection, diagnosis and intervention.