Schizophrenia has traditionally been associated with deficits in high order processing involving cortical regions such as prefrontal or temporohippocampal brain regions. More recently, however, dysfunction of early stages of sensory processing have been demonstrated as well. In the auditory system, schizophrenia patients show impaired generation of mismatch negativity (MMN), an index of neurophysiological dysfunction at the level of auditory sensory cortex, along with impaired generation of auditory N1. Deficits in MMN generation correlate with deficits in performance on tests of tone matching, reflecting impaired auditory sensory memory(ASM) performance. Similar deficits have now been documented in the visual system. Thus, patients with schizophrenia show impaired ability to close fragmented images, reflecting dysfunction at the level of lateral occipital cortex (LO). In addition, amplitude of the P1 visual component is reduced over dorsal stream regions, whereas amplitudes of the ventral stream P1 and N1 components are relatively intact. Visual findings are consistent with impaired visual processing particularly within the magnocellular visual pathway and with impaired dorsal/ventral system interaction. The overall goals of the present study are to further define mechanisms of neurophysiological dysfunction within the auditory and visual systems deficits and to evaluate the degree to which a single underlying deficit (e.g., NMDA dysfunction) could account for the pattern of dysfunction observed. Finally, this project will begin to evaluate the degree to which separate deficits in auditory and visual processing lead to impairments in higher order processes.

Public Health Relevance

to public health: Schizophrenia is a severe mental disorder that affects up to 1% of the population worldwide. Deficits in cognitive function predict poor out come and continued disability. This project will analyze neural basis of cognitive dysfunction.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37MH049334-21
Application #
8223286
Study Section
Special Emphasis Panel (NSS)
Program Officer
Meinecke, Douglas L
Project Start
1993-01-01
Project End
2013-02-28
Budget Start
2012-03-01
Budget End
2013-02-28
Support Year
21
Fiscal Year
2012
Total Cost
$429,658
Indirect Cost
$146,761
Name
Nathan Kline Institute for Psychiatric Research
Department
Type
DUNS #
167204762
City
Orangeburg
State
NY
Country
United States
Zip Code
10962
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Kantrowitz, J T; Scaramello, N; Jakubovitz, A et al. (2014) Amusia and protolanguage impairments in schizophrenia. Psychol Med 44:2739-48
Van Zaen, Jerome; Murray, Micah M; Meuli, Reto A et al. (2013) Adaptive filtering methods for identifying cross-frequency couplings in human EEG. PLoS One 8:e60513
Kantrowitz, Joshua; Javitt, Daniel C (2012) Glutamatergic transmission in schizophrenia: from basic research to clinical practice. Curr Opin Psychiatry 25:96-102
Friedman, Tamara; Sehatpour, Pejman; Dias, Elisa et al. (2012) Differential relationships of mismatch negativity and visual p1 deficits to premorbid characteristics and functional outcome in schizophrenia. Biol Psychiatry 71:521-9
Gold, Rinat; Butler, Pamela; Revheim, Nadine et al. (2012) Auditory emotion recognition impairments in schizophrenia: relationship to acoustic features and cognition. Am J Psychiatry 169:424-32
Yang, L; Chen, S; Chen, C-M et al. (2012) Schizophrenia, culture and neuropsychology: sensory deficits, language impairments and social functioning in Chinese-speaking schizophrenia patients. Psychol Med 42:1485-94
Leitman, David I; Sehatpour, Pejman; Garidis, Christina et al. (2011) Preliminary Evidence of Pre-Attentive Distinctions of Frequency-Modulated Tones that Convey Affect. Front Hum Neurosci 5:96
Javitt, Daniel C; Schoepp, Darryle; Kalivas, Peter W et al. (2011) Translating glutamate: from pathophysiology to treatment. Sci Transl Med 3:102mr2
Dias, Elisa C; Butler, Pamela D; Hoptman, Matthew J et al. (2011) Early sensory contributions to contextual encoding deficits in schizophrenia. Arch Gen Psychiatry 68:654-64

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