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
Kantrowitz, Joshua T; Nolan, Karen A; Epstein, Michael L et al. (2017) Neurophysiological Effects of Bitopertin in Schizophrenia. J Clin Psychopharmacol 37:447-451
Lee, M; Sehatpour, P; Hoptman, M J et al. (2017) Neural mechanisms of mismatch negativity dysfunction in schizophrenia. Mol Psychiatry 22:1585-1593
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
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
Kantrowitz, Joshua T; Epstein, Michael L; Beggel, Odeta et al. (2016) Neurophysiological mechanisms of cortical plasticity impairments in schizophrenia and modulation by the NMDA receptor agonist D-serine. Brain 139:3281-3295
Hillyard, Steven A; Störmer, Viola S; Feng, Wenfeng et al. (2016) Cross-modal orienting of visual attention. Neuropsychologia 83:170-178
van Atteveldt, Nienke; Musacchia, Gabriella; Zion-Golumbic, Elana et al. (2015) Complementary fMRI and EEG evidence for more efficient neural processing of rhythmic vs. unpredictably timed sounds. Front Psychol 6:1663
Javitt, Daniel C (2015) Current and emergent treatments for symptoms and neurocognitive impairment in schizophrenia. Curr Treat Options Psychiatry 1:107-120
Javitt, Daniel C (2015) Neurophysiological models for new treatment development in schizophrenia: early sensory approaches. Ann N Y Acad Sci 1344:92-104
Haegens, Saskia; Barczak, Annamaria; Musacchia, Gabriella et al. (2015) Laminar Profile and Physiology of the ? Rhythm in Primary Visual, Auditory, and Somatosensory Regions of Neocortex. J Neurosci 35:14341-52

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