Sensory processing deficits are a key component of schizophrenia. This Project utilizes a primate model to investigate mechanisms underlying cognitive function and dysfunction. We and others have recently demonstrated that neuronal oscillations are essential components or """"""""Instruments"""""""" of brain operation, and that neural oscillatory rhythms are organized In a hierarchical fashion, with theta band amplitude coupled to delta oscillation phase, and gamma band amplitude coupled to theta oscillation phase. While this hierarchical organization is evident when the system Is at """"""""rest,"""""""" it is also dynamic, and clearly modifiable by active cognitive operations such as attention. Hierarchical cross frequency coupling permits optimization of sensory processing and mediates effects of attention both across and within sensory systems. This project will Investigate mechanisms underlying oscillatory entrainment using Intracranial recordings in monkeys trained to perform both intermodal and intramodal attention tasks. One monkey will be studied per year. Monkeys will be Implanted to permit Intracranial recording and training on appropriate behavioral tasks. Recordings will then be obtained from sensory cortex In response to attended vs. unattended stimuli and mechanisms of attentional modulation of sensory processing will be assessed. Principal analyses will be conducted In the frequency domain, with special emphasis on the mechanistic roles of oscillatory phase manipulation and cross-frequency coupling in attentional modulation of sensory processing. Finally, effects of NMDA antagonists will be evaluated on local processes underlying attentional modulation using focal intracortical Infusion techniques, permitting assessment of the degree to which NMDA manipulations reproduce patterns of dysfunction observed In schizophrenia.

Public Health Relevance

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 is part of a Center application to determine brain mechanisms underlying neurocognitive dysfunction In schizophrenia with particular emphasis on sensory processing dysfunction. This project will study basic sensory processing mechanisms in primate models in order to assist in development of new biological assessment and Intervention approaches In schizophrenia.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Specialized Center (P50)
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Special Emphasis Panel (ZMH1-ERB-F)
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Columbia University (N.Y.)
New York
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