Program in Neuroscience

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1) Neural synchrony and oscillations in schizophrenia spectrum disorders. Neural synchrony and oscillations may be required for efficient signaling within the nervous system. Persons with schizophrenia show poorer synchrony and altered oscillatory activity to auditory and visual stimulation, which may particularly affect cognitive processes requiring timing and integration. Electrophysiological measures of these phenomena are being studied in schizophrenia, Schizotypal Personality Disorder, relatives of persons with schizophrenia, and healthy individuals. This human data will test whether these deficits in synchronization meet key criteria for an endophenotype in the disorder, or are state indicators for clinical psychosis.

2) Rodent models of electrophysiological disturbance in schizophrenias. In the ketamine rodent model, we will test the sensitivity of these measures to acute and chronic administration of ketamine, a potent NMDA antagonist, and determine whether these are reversed by treatment with an atypical antipsychotic medication, olanzapine, or a glycine site agonist. The animal studies will therefore yield in-vivo evidence of the sensitivity of time-frequency measures to a well-validated rodent model of schizophrenia, and whether these deficits are ameliorated by anti-psychotic medications.

3) Human Connectivity Analysis: Application to Clinical Populationss. A fundamental goal in human neuroscience is to generate a three dimensional map which represents the organization of gray and white matter connectivity in the brain. This project will employ MRI tractography to map the connection architecture of the brain in healthy adults and individuals with disorders which appear to affect connectivity (schizophrenia and autism). New graph analytic computational methods developed by Olaf Sporns will be used to mathematically analyze network structure.

4) Cognitive remediation as a treatment for schizophrenias. Impairment of cognitive function is a key feature of schizophrenia which predates onset of psychotic symptoms, and persists after pharmacological treatment. Cognitive impairment contributes to the broad psychosocial disabilities observed in schizophrenia and has often been characterized as an illness trait that is refractory to pharmacological treatment. The purpose of this collaborative study is to test the effects of cognitive remediation (CR) on clinical, neurocognitive and psychosocial outcomes in schizophrenia. Primary outcome measures include tests of cognitive function and event-related potential (ERP) measures of brain function.