Ketamine-Induced Dissociation Does Not Increase Fronto-Limbic Functional Connectivity in Individuals with Posttraumatic Stress Disorder

Dissociation has been conceptualized as emotion overmodulation mediated by prefrontal inhibition of limbic regions. However, while observations of increased resting-state mPFC-amygdala functional connectivity in individuals with the dissociative subtype of posttraumatic stress disorder (PTSD) have supported this model, causal evidence is lacking. As dissociation can be elicited by intravenous infusion of subanesthetic ketamine (0.5 mg/kg) but not midazolam (0.045mg/kg), we used ketamine to pharmacologically manipulate dissociation and assessed effects on resting-state mPFC-amygdala functional connectivity in individuals with PTSD (N = 26). Contrary to our pre-registered predictions, ketamine did not promote a greater increase in mPFC-amygdala functional connectivity from baseline to infusion than midazolam. Instead, ketamine elicited a transient decrease of vmPFC-amygdala functional connectivity. Our findings challenge the emotion overmodulation model of dissociation and call for a more differentiated view on the neurobiological underpinning of dissociative phenomena in PTSD.