Project Summary/Abstract Multi-Level Assays of Working Memory and Psychopathology The NIMH Research Domains Criteria (RDoC) initiative aims to advance understanding of mental health through critical re-evaluation of the traditional diagnostic system and development of alternate methods for measurement of biologically valid dimensions and categories. The proposed project focuses on the RDoC Working Memory construct using a "bottom-up" strategy that first determines the validity of three neural circuits (Local Cortical, Fronto-Posterior, and Cortico-Hippocampal) using convergent measures from electroencephalography (EEG) and magnetic resonance imaging (MRI). Next the project determines the relations of these circuits to four working memory component dimensions that were specified by RDoC workshops (Storage Capacity, Goal Maintenance, Interference Control, and Long Term Memory). Finally, the project will determine how the circuit and cognitive dimensions compare to conventionally assessed symptoms and diagnostic categories in explaining real-world functional disability. The project innovates by recruiting participants in two broad groups - Care Seeking and Non-Care Seeking - to overcome the extreme-group bias affecting most previous research that has used conventional diagnostic categories as inclusion-exclusion criteria. By systematically testing the validity of associations across circuits, cognitive functions, symptoms, syndromes, and real-world disability, the project will determine how well Working Memory serves the RDoC mission, and accomplish this free of biases associated with diagnostic categories that have limited prior research.

Project Narrative/Relevance Multi-Level Assays of Working Memory and Psychopathology This project takes a novel approach to research on mental illness by studying brain functions associated with mental illness without preconceptions about the validity of the current diagnostic system, thereby eliminating biases that are introduced in most current research on psychiatric syndromes. The project identifies problems in three fundamental brain circuits using advanced magnetic resonance imaging (MRI) and electroencephalography (EEG), and links these circuits to "working memory" processes prioritized by the NIMH Research Domains Criteria initiative. The project further determines if these dimensions of brain structure and function, when compared directly with the conventionally used symptoms and diagnostic categories, do a better job of explaining real-world impact as expressed in functional disability.