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
Avissar, Michael; Xie, Shanghong; Vail, Blair et al. (2018) Meta-analysis of mismatch negativity to simple versus complex deviants in schizophrenia. Schizophr Res 191:25-34
Pobric, Gorana; Hulleman, Johan; Lavidor, Michal et al. (2018) Seeing the World as it is: Mimicking Veridical Motion Perception in Schizophrenia Using Non-invasive Brain Stimulation in Healthy Participants. Brain Topogr 31:827-837
Lee, M; Sehatpour, P; Hoptman, M J et al. (2017) Neural mechanisms of mismatch negativity dysfunction in schizophrenia. Mol Psychiatry 22:1585-1593
Tobe, Russell H; Corcoran, Cheryl M; Breland, Melissa et al. (2016) Differential profiles in auditory social cognition deficits between adults with autism and schizophrenia spectrum disorders: A preliminary analysis. J Psychiatr Res 79:21-27
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
Kantrowitz, J T; Scaramello, N; Jakubovitz, A et al. (2014) Amusia and protolanguage impairments in schizophrenia. Psychol Med 44:2739-48
Kantrowitz, J T; Hoptman, M J; Leitman, D I et al. (2014) The 5% difference: early sensory processing predicts sarcasm perception in schizophrenia and schizo-affective disorder. Psychol Med 44:25-36
Lakatos, Peter; Schroeder, Charles E; Leitman, David I et al. (2013) Predictive suppression of cortical excitability and its deficit in schizophrenia. J Neurosci 33:11692-702
Calderone, Daniel J; Hoptman, Matthew J; Martínez, Antígona et al. (2013) Contributions of low and high spatial frequency processing to impaired object recognition circuitry in schizophrenia. Cereb Cortex 23:1849-58
Kantrowitz, Joshua T; Leitman, David I; Lehrfeld, Jonathan M et al. (2013) Reduction in tonal discriminations predicts receptive emotion processing deficits in schizophrenia and schizoaffective disorder. Schizophr Bull 39:86-93

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