Sensory processing deficits are a key component of schizophrenia. This project will analyze mechanisms underlying sensory processing dysfunction using a multimodal imaging approach incorporating both neurophysiological and MRl-based assessments. Neurophysiological studies will evaluate role of neuronal synchrony and oscillatory hierarchy impairments in etiology of neurocognitive dysfunction. In particular, it will test the hypothesis that impairments in non-linear stimulus amplification and in oscillatory entrainment may prevent response optimization in patients relative to controls. Four experiments are planned. The first experiment will analyze the role of oscillatory entrainment in the genesis of previously documented sensory processing deficits and object-attention dysfunction. For this experiment, hierarchical oscillatory analyses will be conducted using mathematical approaches and stimulation paradigms developed from Projects 2 and 3, respectively. The second experiment will analyze the role of spatial attention in sensory processing dysfunction, also using both standard ERP and oscillatory hierarchy analyses, and will also evaluate the role of phase reset vs. exogenous activity in ERP generation in patients and controls. Experiment 3 will evaluate spatial attention effects further using ssVEP approaches. Deficits in ERP generation will also be assessed relative to symptomatic and cognitive measures. The fourth experiment will evaluate the role of structural and functional connectivity impairments in etiology of sensory and attentional deficits using MR measures supported by Core B. DTI measures will be used to assess structural connectivity, while resting state fMRI will be used to assess functional connectivity. An underiying hypothesis is that deficits in neurophysiological processes such as non? linear gain and slow oscillatory function that are known to be NMDA receptor-dependent will lead to impaired entrainment of higher-frequency oscillations (e.g. delta, theta, gamma), leading to impaired ERP generation and behavior. Overall, this project will test the hypothesis that deficits in hierarchical processing within regions and structural and functional connectivity between regions lead to deficits in neurocognitive function 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 will evaluate mechanisms underlying deficits in sensory processing and neurocognitive dysfunction in patients with chronic schizophrenia, in collaboration with other projects and core programs in order to develop improved methods for early detection, diagnosis and intervention.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Specialized Center (P50)
Project #
5P50MH086385-05
Application #
8502371
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
$207,603
Indirect Cost
$56,805
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