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Background: Post-traumatic stress disorder (PTSD) is triggered by distinct events and is therefore amenable to studies of its early pathogenesis. Longitudinal studies during the year that follows trauma exposure revealed typical symptom trajectories leading to either recovery or protracted PTSD. Thezneurobehavioral correlates of early PTSD symptoms’ trajectories have not been longitudinally explored. Objective: To present the rationale and design of a longitudinal study exploring the relationship between evolving PTSD symptoms and co-occurring cognitive functioning and structural and functional brain imaging parameters. Method: Adult civilians consecutively admitted to a general hospital emergency room (ER) for traumatic injury will be screened for early PTSD symptoms suggestive of chronic PTSD risk, and consecutively evaluated 1, 6 and 14 months following the traumatic event. Consecutive assessments will include structured clinical interviews for PTSD and comorbid disorders, self-reported depression and anxiety symptoms, a web-based assessment of cognitive domains previously linked with PTSD (e.g., memory, executive functions, cognitive flexibility), high-resolution structural MRI of both grey and white matter, functional resting-state connectivity, and fMRI tasks examining emotional reactivity and regulation, as well as motivation processing and sensitivity to risk and reward. Data analyses will explore putative cognitive predictors of non-remitting PTSD, and brain structural and functional correlates of PTSD persistence or recovery. Conclusion: This work will longitudinally document patterns of brain structures, connectivity, and functioning, predictive of (or associated with) emerging PTSD during the critical first year of after the traumatic event. It will thereby inform our understanding of the disorder’s pathogenesis and underlying neuropathology. Challenges to longitudinal MRI studies of recent survivors, and methodological choices used to optimize the study’s design are discussed.