Large-Scale Functional Hyperconnectivity Patterns Characterizing Trauma-Related Dissociation: A rs-fMRI Study of PTSD and its Dissociative Subtype

Background: In 2012, a dissociative subtype of post-traumatic stress disorder (PTSD) was introduced into the DSM based on emerging clinical and neurobiological evidence of a distinct PTSD phenotype characterized by trauma-related dissociation. Ten years later, considerable research has demonstrated unique small-scale (i.e., node-based) and large-scale (i.e., network-related) functional connectivity patterns, specific to the dissociative subtype. However, the field has yet to arrive at a neurobiological framework able to account for the disparate findings across these various scales of investigation. Methods: We conducted the largest region of interest (ROI)-to-ROI analysis performed on a PTSD population to date, with a total of 132 ROIs and 197 participants, 134 of whom were diagnosed with PTSD. We implemented a whole-brain approach, comparing patterns of intra- and inter-network functional connectivity between participants with PTSD, its dissociative subtype, and non-traumatized, healthy controls. We also performed a joint factor analysis between the discovered patterns of functional connectivity and a battery of behavioural, demographic, and clinical scores. Results: Whereas participants with PTSD showed only modest differences to that of controls in temporal regions and the right frontoparietal network, participants with the dissociative subtype demonstrated widespread small-scale and large-scale functional hyperconnectivity, compared to controls. Three major joint factors were also identified, characterizing two dissociative and one PTSD symptom-linked factor. Conclusion: In the dissociative subtype, we found evidence of a general pattern of hyperconnectivity, especially among subcortical regions, sensory- and motor-related networks, and intrinsic connectivity networks, diverging from what we would expect based on a small-world organization of the brain.