Ketamine-induced pleasant but not unpleasant dissociation is linked to the functional connectivity profile of the posteromedial cortex

Along with its rapid therapeutic benefits, ketamine induces transient experience of dissociation during administration. Given the suggested association between ketamine-induced dissociation and treatment response, understanding the neural correlates of dissociation would help to elucidate its therapeutic mechanism. The posteromedial cortex (PMC) has been reported to play a vital role in the experience of dissociation induced by ketamine and psychedelics. In this study, we investigated whether ketamine-induced pleasant and unpleasant dissociations can be predicted by the PMC functional connectivity (FC) profile during ketamine infusion and at baseline in thirty-five male participants who underwent ultrahigh-field MRI. Pleasant and unpleasant dissociation during infusion were assessed by the oceanic boundlessness (OB) and anxious ego dissolution (AED) scores of five dimensions of the altered state of consciousness scale (5D-ASC), respectively. Our results showed that OB scores could be predicted predominantly by the functional links between the PMC and control network regions at baseline as well as during infusion. Regions were also found in the default mode network during infusion, while more distributed regions, including limbic and somatomotor regions, were involved at baseline. AED scores could not be predicted by the PMC profile at baseline or during infusion. Our findings highlight differential brain mechanisms underlying pleasant and unpleasant dissociations, complementing the literature findings suggesting a potential role of the quality of drug-induced dissociation in treatment response. Furthermore, our findings suggest that PMC FC reconfiguration might be a shared neural correlate of dissociation induced by ketamine and psychedelics, even though their main target neurotransmitter systems differ.