All research in this Center is directed at testing a general hypothesis concerning the origin of the information processing deficits of schizophrenia. The hypothesis states that molecular alterations among GABA neurons give rise to abnormalities of cerebral cortical oscillatory activity and that abnormal oscillatory activity gives rise to impaired information processing. Testing this hypothesis will lead to an improved understanding of the pathophysiological mechanisms that underlie impaired information processing in schizophrenia and will thereby pave the way to the development of novel, mechanistically-based treatments. Project 3 will contribute to the attainment of the goals of the Center by characterizing cognition-related oscillatory activity in the cerebral cortex of behaving monkeys. Experiments conducted under Aim 1 will focus on gamma-band (30-80 Hz) oscillations in frontal cortex that accompany the preparation to overcome a prepotent response. Experiments conducted under Aim 2 will focus on gamma-band oscillations in occipitotemporal cortex that accompany selective visual attention. Experiments conducted under Aim 3 will focus on theta-band (4-8 Hz) oscillations in occipitotemporal cortex evoked by displays consisting of a central and a peripheral visual stimulus. In each experiment, oscillatory activity will be examined at multiple levels of spatial resolution (dural surface potential, local field potential and action potential). In each experiment, the dependence of oscillatory activity on GABA neurotransmission will be assessed by measuring the impact of locally administered agents that exert a potentiating (benzodiazepine) or blocking (GABA antagonist) effect at GABA-A receptors. In each experiment, three fundamental hypotheses will be tested: (1) that the amplitude of oscillatory activity depends on the task conditions;(2) that oscillatory activity recorded at an intracranial site is correlated with oscillatory activity recorded at the overlying cortical surface;(3) that oscillatory activity depends on GABA neurotransmission. By improving our understanding (a) of how cortical oscillatory activity recorded at the brain surface is related to intracranial oscillatory activity and (b) of how intracranial oscillatory activity depends on GABA, the results will increase our understanding of the neural mechanisms that underlie scalprecorded oscillatory activity in healthy subjects. This will form a basis for drawing inferences about the pathophysiological mechanisms that underlie abnormal cognition-related oscillatory activity in schizophrenia. An understanding of the pathophysiology will form a foundation for the development of novel mechanistically based treatments aimed at ameliorating the cognitive impairments of schizophrenia.

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National Institute of Mental Health (NIMH)
Specialized Center (P50)
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Special Emphasis Panel (ZMH1)
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University of Pittsburgh
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