A substantial body of literature indicates that impairments in cognitive control play a central role in schizophrenia but the mechanisms underlying these deficits are still undetermined. The overarching goal of the proposed work is to understand two core components of self-control of action, response inhibition and response monitoring, in schizophrenia. The saccade countermanding paradigm provides an ideal framework for the quantification of the mechanisms of control of action by indexing one's ability to stop an initiated movement. Research on both the computational model and neurophysiology of saccade countermanding is being conducted at Vanderbilt University. Combination of work in humans and non-human primates provides unprecedented leverage on these crucial questions of the specificity of executive control dysfunction in schizophrenia as it allows the application of sophisticated models of behavior, as well as spatially and temporally precise measures of brain activity, to understanding the processes and their underlying mechanisms that are impaired and preserved in schizophrenia.
The specific aims of this project are to specify the behavioral and neural markers of response inhibition and performance monitoring deficits using the countermanding task in schizophrenia and to articulate how these two processes are related in healthy controls and patients. Deficits in performance monitoring and response inhibition in patients with schizophrenia will be examined, and the relationship between trial-by-trial reaction time adjustments based on prior responses and quantitative measures of response inhibition will be examined in healthy controls and patients with schizophrenia. To elucidate the neural basis of difficulties in control of action, the electrophysiological correlates of performance monitoring and response inhibition will be investigated in patients with schizophrenia and healthy controls.

Public Health Relevance

Implications for public health: Cognitive deficits predict functional outcome better than clinical symptoms and the remediation of cognitive deficits in schizophrenia is an urgent and important public health challenge. Thus, more specific understanding of the components of cognitive deficits has the potential to allow avenues for improved behavioral and pharmacological treatment and intervention.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Predoctoral Individual National Research Service Award (F31)
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Special Emphasis Panel (ZRG1-F12B-N (20))
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Rubio, Mercedes
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Vanderbilt University Medical Center
Schools of Arts and Sciences
United States
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Thakkar, Katharine N; Schall, Jeffrey D; Heckers, Stephan et al. (2015) Disrupted Saccadic Corollary Discharge in Schizophrenia. J Neurosci 35:9935-45
Thakkar, Katharine N; Schall, Jeffrey D; Logan, Gordon D et al. (2015) Response inhibition and response monitoring in a saccadic double-step task in schizophrenia. Brain Cogn 95:90-8
Thakkar, Katharine N; Schall, Jeffrey D; Logan, Gordon D et al. (2015) Cognitive control of gaze in bipolar disorder and schizophrenia. Psychiatry Res 225:254-62
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Thakkar, Katharine N; Park, Sohee (2012) Impaired passive maintenance and spared manipulation of internal representations in patients with schizophrenia. Schizophr Bull 38:787-95
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Thakkar, Katharine N; Schall, Jeffrey D; Boucher, Leanne et al. (2011) Response inhibition and response monitoring in a saccadic countermanding task in schizophrenia. Biol Psychiatry 69:55-62
Thakkar, Katharine N; Park, Sohee (2010) Empathy, schizotypy, and visuospatial transformations. Cogn Neuropsychiatry 15:477-500
Thakkar, Katharine N; Brugger, Peter; Park, Sohee (2009) Exploring empathic space: correlates of perspective transformation ability and biases in spatial attention. PLoS One 4:e5864