Ketamine-induced pleasant but not unpleasant dissociation is linked to the functional connectivity profile of the posteromedial cortex
Zumrut Duygu Sen, Nitin Sharma, Lena Vera Danyeli, Lejla Colic, Nils Opel, Tara Chand, Nooshin Javaheripour, Wen Qin, Bin Zhang, Deepti R. Bathula, Mayank Goswami, Oliver Speck, Martin Walter, Meng Li
preprint DOI: 10.31234/osf.io/eadr2
Summary
Ketamine induces both pleasant and unpleasant dissociative experiences during treatment, with pleasant dissociation being predicted by the functional connectivity of the posteromedial cortex (PMC) and control network regions. In a study involving thirty-five male participants, it was found that oceanic boundlessness scores were linked to PMC connectivity at baseline and during infusion, while anxious ego dissolution scores could not be predicted by PMC connectivity. These results suggest different brain mechanisms for pleasant and unpleasant dissociations.
Study at a glance
| Sample size | 35 |
|---|---|
| Population | male participants undergoing ultrahigh-field MRI |
| Key finding | Pleasant dissociation during ketamine infusion can be predicted by the functional connectivity profile of the PMC, while unpleasant dissociation cannot. |
Abstract
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.