DESCRIPTION (provided by applicant): This project focuses on understanding the psychological and neural mechanisms that give rise to cognitive control. Cognitive control processes are a component of human mental function that is fundamentally important in a wide range of domains, including attention, working memory, episodic memory, and decision making. Cognitive control disruptions are thought to be a major source of functional impairment for individuals suffering from a variety of mental health disorders and neuropsychiatric diseases (e.g., schizophrenia, depression, ADHD, Parkinson's, Alzheimer's, etc). Prior research, conducted over the last decade, has suggested that there may be a core dimension of variability related to the temporal dynamics and neural circuitry of cognitive control, which is reflected in shifts between two qualitatively distinct modes of control, proactive and reactive. This work has provided a strong experimental base of findings suggesting that this variability is: a) present in healthy individuals and occurs across a range of cognitive domains, b) observable in terms of unique dynamic neural signatures, and c) likely contributing to behavioral deficits in impaired populations (e.g., healthy aging, schizophrenia). However, to date, this research has been confined to small-scale studies focusing on single tasks and using restricted participant samples. In the current proposal represents a rigorous and ambitious attempt to "scale up" this research endeavor, through a large-sample study, involving within-subject fMRI assessments in multiple cognitive control domains, a combined correlational/experimental design, extensive characterization of individual differences variation, and sophisticated psychometric and statistical data modeling. A key feature of the proposed project is its integration and synergistic relationship with the on-going Human Connectome Project (HCP), which will provide the most comprehensive characterization of normative human brain function and variation in the history of neuroscience research. Specifically, as part of the current project, a subset of HCP participants (a diverse and well-characterized sample of MZ/DZ twins) will be recruited for retesting in tasks that are specifically designed to probe and dissociate proactive and reactive control, while utilizing the same fMRI scanner, acquisition, analysis and databasing protocols of the HCP. This will enable the project to achieve tight integration and linkage with comprehensive brain connectivity and genetic data acquired through the HCP. The key goal of the project will be to test and validate the provocative hypothesis that proactive and reactive control form distinct and coherent endophenotypic constructs that provide a bridge between genetic variation, neural circuitry and dynamics, and observable behavioral profiles. Success is in this effort will have important theoretical and clinical implications, by providing a clearer understanding of the sources of normal human variation, and even more importantly, highlighting potential risk vulnerability factors for a range of mental health disorders.

PUBLIC HEALTH RELEVANCE: This project has high relevance for public health by providing critical and detailed information regarding the brain-basis of normal human variation in higher mental functions such as attention, memory, decision-making, and intelligence. Such knowledge will be critical in helping to better understand the relationship between normal functioning and mental health disorders (such as schizophrenia, depression, addiction, ADHD), as well as risk vulnerability factors that may contribute to such disorders.