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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08MH080329-05
Application #
8217178
Study Section
Special Emphasis Panel (ZRG1-BBBP-M (02))
Program Officer
Wynne, Debra K
Project Start
2008-05-01
Project End
2014-01-31
Budget Start
2012-02-01
Budget End
2014-01-31
Support Year
5
Fiscal Year
2012
Total Cost
$171,514
Indirect Cost
$12,705
Name
University of Pittsburgh
Department
Psychiatry
Type
Schools of Medicine
DUNS #
004514360
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Ramachandran, Suchitra; Meyer, Travis; Olson, Carl R (2016) Prediction suppression in monkey inferotemporal cortex depends on the conditional probability between images. J Neurophysiol 115:355-62
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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

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