Altered large-scale functional brain organization in posttraumatic stress disorder: A comprehensive review of univariate and network-level neurocircuitry models of PTSD

Classical neural circuitry models of posttraumatic stress disorder (PTSD) are largely derived from univariate activation studies and implicate the fronto-limbic circuit as a main neural correlate of PTSD symptoms. Though well-supported by human neuroimaging literature, these models are limited in their ability to explain the widely distributed neural and behavioral deficits in PTSD. Emerging interest in the application of large-scale network methods to functional neuroimaging provides a new opportunity to overcome such limitations and conceptualize the neural circuitry of PTSD in the context of network patterns. This review aims to evaluate both the classical neural circuitry model and a new, network-based model of PTSD neural circuitry using a breadth of functional brain organization research in subjects with PTSD. Taken together, this literature suggests global patterns of reduced functional connectivity (FC) in PTSD groups as well as altered FC targets that reside disproportionately in canonical functional networks, especially the default mode network. This provides evidence for an integrative model that includes elements of both the classical models and network-based models to characterize the neural circuitry of PTSD.