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, which is why they feature prominently in the NIMH RDoC matrix. Over the last decade, we have developed a theoretically coherent and mechanistic model, the Dual Mechanisms of Control (DMC) framework, which has the following core tenets: 1) cognitive control can operate in distinct modes, proactive and reactive; 2) these modes are associated with unique dynamic neural signatures, involving a shift between sustained and transient engagement of dorsolateral prefrontal cortex (dlPFC) and its interactions with the cingulo-opercular network (CON) and fronto-striatal circuitry; 3) they represent a core dimension of variability, present across a range of cognitive domains (i.e., indicating a psychologically coherent construct); 4) this variability is both state-related (and thus affected by task/situation and endogenous factors) and trait-related (a key component of individual variation); and 5) the variation encompasses cognitive control function in healthy young adults, but also in more extreme forms, contributes to dysfunction present in various impaired populations (e.g., schizophrenia, depression, ADHD, aging). Under a current MERIT award, we have been directly testing these core tenets of the DMC framework, through a large-scale project, which samples monozygotic (MZ) twin pairs and participants from the Human Connectome Project (HCP) and to comprehensively characterize proactive and reactive control at the behavioral, neural, and genetic levels. The current proposal takes full advantage of the extensive infrastructure we have already developed for this project to dramatically expand its scope, explanatory depth, and utility to the scientific community. Specifically, we propose a rigorous, multi-pronged study, that integrates our optimized cognitive control task battery with mindfulness skills training (MT), a longitudinal design with repeated neuroimaging assessments, comprehensive “neuro-psychometric” characterization of individual variation utilizing state-of-the-art analytic techniques, and incorporation of current best practices (i.e., following Open Science Framework [OSF] recommendations), to maximize the transparency, reproducibility, and ease of dissemination of project tools and findings. 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.