Organization and timecourse of the neural mechanisms for cognitive flexibility

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DESCRIPTION (provided by applicant): The long-range goal of the proposed study is to characterize the neural mechanisms that mediate between internal goal-directed behavior and externally guided behavior. Failing to suppress environmental information when it conflicts with current goals may lead to inappropriate behaviors. For example, failing to suppress drug-related cues leads to drug seeking behavior, and is associated with relapse following treatment. Further, such failures are observed in many psychiatric and neurological disorders. However, most studies that have examined the underlying neural mechanisms of flexible, goal-directed behavior have relied on paradigms where subjects switch between tasks according to explicit cue stimuli. Therefore, these paradigms may not be able to fully capture the neural mechanisms associated with internally generated goal or task selection. As preliminary studies have suggested that control processes are recruited differentially when the task selection is explicitly instructed versus under participant control, it is important to identify the differences in the pattern of brain activation for these different modes of task selection. In two main experiments, we aim to 1) investigate the neural mechanisms underlying internally generated and externally biased task selection, and 2) examine the role of the posterior medial prefrontal cortex (pMFC), a region whose functional organization has been a topic of intense debate, in task selection. A parallel magnetic resonance imaging (MRI) and event- related brain potential (ERP) study will first be conducted that manipulates whether task selection is under experimenter or subject control (external vs. internal control) and manipulates the presence of irrelevant cues that may bias task selection (i.e., external bias on task selection). We will examine the differences in the spatial organization (MRI, DTI) and timecourse (ERP) of brain regions when task choice is externally or internally generated and under external bias or not. Finally, a functional MRI meta-analysis will be conducted to examine whether distinct subregions of the pMFC underlie separable processes of task selection, response selection, and response evaluation. By combining across multiple studies, the meta-analysis will yield sufficient statistical power to detect subtle differences in the pattern of activation for these processes. Knowledge of the neural mechanisms that govern executive control of internally vs. externally driven task selection will provide additional insight into the causes of successful and unsuccessful behavior in young adults, will help explain the mechanisms that underlie cued drug-seeking behavior in addiction (as well as disrupted cognitive flexibility observed across multiple clinical populations, and will facilitate the development of cognitive training and rehabilitation paradigms applicable to these populations.