The goal of the parent grant is to delineate abnormalities in the development of structural and functional brain networks associated with executive dysfunction across psychiatric disorders including attention- deficit/hyperactivity disorder (ADHD) and the psychosis spectrum (PS). However, critical aspects of executive dysfunction remain unexplored. First, sex differences in executive function are substantial, and disorders with prominent executive dysfunction (such ADHD and psychosis) are more prevalent in males. Notably, the aims of the parent grant only proposed to examine executive dysfunction across males and females, and did not propose to examine how sex-specific network abnormalities relate to sex differences in executive function. Second, the parent grant focuses on the broad construct of executive function, which is composed of multiple specific cognitive domains including working memory, performance monitoring, set shifting, inhibition, and sustained attention. At present, the aims of the parent grant do not propose to identify specific links between brain networks and these component processes. In this supplement, we will fill these important gaps in the parent grant using advanced tools from network science and machine learning. To do this, we will capitalize upon an NIMH-funded longitudinal study of irritability in youth that provides highly relevant data and is nearly complete (n=200). Findings in this valuable dataset will be replicated in the parent grant as data accrues. Together, this supplement will provide novel insights regarding the network-level substrates of executive dysfunction and provide the candidate with a superb training experience in computational psychiatry. This training will position him to succeed in a top neuroscience graduate program.
Executive function is an important domain of cognition that develops rapidly during adolescence, and is impacted by multiple psychiatric disorders including ADHD and psychosis. A greater understanding of how abnormalities in brain network development produce executive dysfunction in psychiatric disorders may be critical for the development of earlier and more effective treatments. These novel clinical interventions would benefit public health by reducing disability and limiting the costs to society at large.
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