Neural asynchrony underlying poor cognitive control in severe psychopathology

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 DESCRIPTION (provided by applicant): Severe mental disorders are associated with poor cognitive control that is evident in a failure to update responses for new circumstances, effectively use short-term memory, and inhibit behavioral responses. Limited goal-oriented control over cognition and behavior creates measurable difficulties in the day-to-day functioning of people with severe psychopathology. Despite accumulating evidence of a network of cortical regions underlying cognitive control functions, the dynamic interaction of brain regions that yield these functions are unknown. The overarching goal of the proposed work is to better understand the neural basis of compromised context updating, working memory, and response inhibition in severe psychopathology by detailing the strength and timing of bioelectrical oscillations within cortical regions composing the neural network underlying cognitive control. As part of this project, we will first identify cortical regions and frequencies pertinent to cognitive control. Through combined use of functional magnetic resonance imaging (fMRI) and electroencephalography (EEG) data gathered from people with severe psychopathology, their first-degree biological relatives, and healthy controls we will identify cortical sources common to context updating and response inhibition and identify bioelectrical oscillations in these brain regions instrumental to cognitive control. Second, we will test the generalization of oscillatory abnormalities to other samples of participants and other tasks (e.g., working memory) in order to fully determine common aspects of the cortical network governing cognitive control and what abnormalities exist in severe psychopathology. The broader samples will include individuals with severe mood dysregulation and psychosis. Third, we will test neural network oscillations for relevance to symptom, behavioral, and genetic elements of severe psychopathology. Specifically, we will investigate the significance of abnormal oscillatory activity during cognitiv control in severe psychopathology by examining associations with dimensions of symptomatology, additional behavioral measures of cognitive control, and polygenic predictors of risk for severe psychopathology as well as candidate genes identified as related to cognitive control and severe psychopathology. Completion of the aims will identify abnormalities in the temporal dynamics of activity within cortical regions underlying impaired cognitive control in severe psychopathology. New knowledge gained from this work will enable more effective interventions that target specific neural circuits in severe mental disorders and may involve the direct manipulation of brain activity. Project Units of Analysis: Units of analysis include circuit, physiology, behavior, genes, self-report.