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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Specialized Center (P50)
Project #
5P50MH086385-05
Application #
8502372
Study Section
Special Emphasis Panel (ZMH1-ERB-F)
Project Start
Project End
Budget Start
2013-07-01
Budget End
2014-06-30
Support Year
5
Fiscal Year
2013
Total Cost
$216,522
Indirect Cost
$22,490
Name
Columbia University (N.Y.)
Department
Type
DUNS #
621889815
City
New York
State
NY
Country
United States
Zip Code
10032
Hillyard, Steven A; Störmer, Viola S; Feng, Wenfeng et al. (2016) Cross-modal orienting of visual attention. Neuropsychologia 83:170-8
Smiley, John F; Hackett, Troy A; Bleiwas, Cynthia et al. (2016) Reduced GABA neuron density in auditory cerebral cortex of subjects with major depressive disorder. J Chem Neuroanat 76:108-121
Sershen, Henry; Hashim, Audrey; Dunlop, David S et al. (2016) Modulating NMDA Receptor Function with D-Amino Acid Oxidase Inhibitors: Understanding Functional Activity in PCP-Treated Mouse Model. Neurochem Res 41:398-408
Kantrowitz, Joshua T; Hoptman, Matthew J; Leitman, David I et al. (2015) Neural Substrates of Auditory Emotion Recognition Deficits in Schizophrenia. J Neurosci 35:14909-21
Javitt, Daniel C (2015) Current and emergent treatments for symptoms and neurocognitive impairment in schizophrenia. Curr Treat Options Psychiatry 1:107-120
Haegens, Saskia; Barczak, Annamaria; Musacchia, Gabriella et al. (2015) Laminar Profile and Physiology of the α Rhythm in Primary Visual, Auditory, and Somatosensory Regions of Neocortex. J Neurosci 35:14341-52
Javitt, Daniel C; Freedman, Robert (2015) Sensory processing dysfunction in the personal experience and neuronal machinery of schizophrenia. Am J Psychiatry 172:17-31
Carrión, Ricardo E; Cornblatt, Barbara A; McLaughlin, Danielle et al. (2015) Contributions of early cortical processing and reading ability to functional status in individuals at clinical high risk for psychosis. Schizophr Res 164:1-7
Brang, David; Towle, Vernon L; Suzuki, Satoru et al. (2015) Peripheral sounds rapidly activate visual cortex: evidence from electrocorticography. J Neurophysiol 114:3023-8
Smiley, John F; Saito, Mariko; Bleiwas, Cynthia et al. (2015) Selective reduction of cerebral cortex GABA neurons in a late gestation model of fetal alcohol spectrum disorder. Alcohol 49:571-80

Showing the most recent 10 out of 81 publications