Posttraumatic stress disorder (PTSD) is a prevalent and debilitating neuropsychiatric consequence of military combat, representing a significant burden for many Veterans. PTSD is also a highly heterogeneous disorder, with symptoms varying from patient to patient—complicating clinical decision-making. The diversity in symptom presentation has led to a growing interest in developing a biologically-grounded framework for neuropsychiatric disorders, where the focus is on symptoms, not diagnostic categories, and where symptoms are a consequence of dysfunctional neural circuits. Symptom-derived biomarkers can then guide precision medicine approaches by identifying the underlying symptom-specific neural circuits that are most sensitive to specific treatments. Yet, much of what we know about the circuit pathology associated with PTSD comes from comparing diagnostic groups on a single mechanism using a single neuroimaging measure. These univariate neuroimaging approaches precludes identification of the more complex relationship between neural mechanisms and PTSD symptoms. This complexity underscores the need for an integrated and multivariate approach to probe multiple neural circuit mechanisms underlying specific PTSD symptoms. The current proposal aims to address this gap by measuring the combined contribution of two critical mechanisms of PTSD: 1) the ‘top-down’ cognitive control over working memory (WM) storage, and 2) ‘bottom-up’ inhibition of fear responses during fear extinction recall. First, we posit that misallocating WM resources to task-irrelevant threat may help partially explain the trauma-related intrusive memories, and inability to extinguish fear responses that are characteristic of individuals with PTSD. To investigate this, Veterans (N=85) that have experienced a criterion-A trauma and have mild to severe levels of PTSD symptoms will complete separate measures including an affective WM task and a fear extinction recall paradigm while undergoing fMRI. The first goal of the project will be to use fMRI to test our hypothesis that Veterans with elevated PTSD symptoms unnecessarily maintain threat-distracters in WM and consequently diminishing WM capacity. The second goal will be to identify the common neural circuit underlying WM control and fear extinction recall. The primary goal of the study will be to test the hypothesis that the neural integration between WM and fear extinction recall dysfunction predicts PTSD symptom clusters. To investigate this last goal, we will use an innovative multivariate neuroimaging analytic strategy called multimodal neuroimaging fusion. Multimodal fusion analysis allows for the identification of unique and high- dimensional neural patterns among multiple neural measures and PTSD symptoms that a univariate approach would miss. This project will be one of the first studies to apply a multimodal neuroimaging fusion analysis in a Veteran PTSD population. Results from this project will lay the groundwork for es...