Cognitive impairments are a prominent feature of schizophrenia and the strongest predictor of functional outcome in this disabling disorder. One of the critical deficits is in context processing, which describes the ability to represent task-relevant information to guide goal-directed behavior. fMRI studies have shown that impaired context processing is associated with decreased prefrontal cortical (PFC) activations in schizophrenia. Similarly, EEG studies have found that disturbances in synchronous PFC oscillations in the gamma range (30-80 Hz) are associated with impaired context processing in schizophrenia. These parallels in the EEG and fMRI findings raise the possibility that disturbed cortical synchrony may underlie the PFC activation disturbances in fMRI studies. Disturbances in PFC gamma synchrony are also consistent with the post-mortem findings in schizophrenia of selective disturbances in fast-spiking interneurons, which are critical for sustaining gamma range synchrony. In this proposal, we aim to provide a synthesis of the above findings, hypothesizing that disturbed PFC gamma synchrony gives rise to impaired context processing in schizophrenia. We will develop a neurobiologically realistic computational model of impaired context processing task performance in schizophrenia, accounting for both impaired performance and disturbed synchrony. To inform and complement our modeling studies, EEG and fMRI studies of context processing will attempt a synthesis of previous findings demonstrating decreased PFC gamma synchrony in EEG and decreased PFC activation in fMRI with the same group of schizophrenia subjects. Establishing a neurobiologically constrained theoretical account and synthesis of empirical findings regarding context processing impairments and their neural basis will be an important step towards the long-term objective of employing biologically realistic models to facilitate novel therapeutic candidates for cognition in schizophrenia and integrated EEG-fMRI methods to evaluate their efficacy. Cognitive disturbances in schizophrenia are one of the most debilitating aspects of the disorder. One of the critical disturbances in cognition is the ability to organize appropriate responses to stimuli and events in the environment. This study seeks to attain a deep understanding of the brain mechanisms associated with such disturbances to facilitate the development of novel therapies for treating cognition in schizophrenia.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Clinical Investigator Award (CIA) (K08)
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Special Emphasis Panel (ZRG1-BBBP-M (02))
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Wynne, Debra K
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University of Pittsburgh
Schools of Medicine
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Meyer, Travis; Walker, Christopher; Cho, Raymond Y et al. (2014) Image familiarization sharpens response dynamics of neurons in inferotemporal cortex. Nat Neurosci 17:1388-94
Forster, Sarah E; Cho, Raymond Y (2014) Context specificity of post-error and post-conflict cognitive control adjustments. PLoS One 9:e90281
Meyer, Travis; Ramachandran, Suchitra; Olson, Carl R (2014) Statistical learning of serial visual transitions by neurons in monkey inferotemporal cortex. J Neurosci 34:9332-7
Richard, Annette E; Carter, Cameron S; Cohen, Jonathan D et al. (2013) Persistence, diagnostic specificity and genetic liability for context-processing deficits in schizophrenia. Schizophr Res 147:75-80
Kieffaber, Paul D; Kruschke, John K; Cho, Raymond Y et al. (2013) Dissociating stimulus-set and response-set in the context of task-set switching. J Exp Psychol Hum Percept Perform 39:700-19
Forster, Sarah E; Carter, Cameron S; Cohen, Jonathan D et al. (2011) Parametric manipulation of the conflict signal and control-state adaptation. J Cogn Neurosci 23:923-35
Kieffaber, Paul D; Cho, Raymond Y (2010) Induced cortical gamma-band oscillations reflect cognitive control elicited by implicit probability cues in the preparing-to-overcome-prepotency (POP) task. Cogn Affect Behav Neurosci 10:431-40
Takahashi, Tetsuya; Cho, Raymond Y; Mizuno, Tomoyuki et al. (2010) Antipsychotics reverse abnormal EEG complexity in drug-naive schizophrenia: a multiscale entropy analysis. Neuroimage 51:173-82
Mizuno, Tomoyuki; Takahashi, Tetsuya; Cho, Raymond Y et al. (2010) Assessment of EEG dynamical complexity in Alzheimer's disease using multiscale entropy. Clin Neurophysiol 121:1438-46
Cho, Raymond Y; Orr, Joseph M; Cohen, Jonathan D et al. (2009) Generalized signaling for control: evidence from postconflict and posterror performance adjustments. J Exp Psychol Hum Percept Perform 35:1161-77

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