The Penn Society for Psychedelic Science welcomes:
Dr. Sam Vesuna
“Deep posteromedial cortical rhythm in dissociation”
Dissociation is an altered behavioral state with unknown underlying neurophysiology but substantial basic and clinical significance—that can occur with trauma, epilepsy, or dissociative drug use—in which the integrity of experience is disrupted, and reproducible cognitive phenomena result. In this talk, I will present our recent work(1) establishing such a dissociation-like state in mice, beginning with precisely dosed ketamine or phencyclidine. Large-scale imaging of neural activity revealed that these dissociative agents elicited a 1–3 Hz rhythm in retrosplenial cortex layer-5 neurons. Electrophysiological recording with four simultaneously-deployed Neuropixel probes revealed rhythmic coupling of retrosplenial cortex and anatomically-connected anterior thalamus circuitry, but uncoupling from most other brain regions, including an inverse correlation with frontally-projecting thalamic nuclei. In testing for causal significance, rhythmic optogenetic activation of retrosplenial cortex layer-5 neurons recapitulated the dissociation-like behavioral effects. Local retrosplenial hyperpolarization-activated cyclic nucleotide-gated potassium channel 1 (HCN1) pacemakers were required for systemic ketamine to induce this rhythm and to elicit dissociation-like behavioral effects. In a patient with focal epilepsy, simultaneous intracranial stereoencephalography (stereo-EEG) recordings from across the brain revealed a similarly-localized rhythm in the homologous deep posteromedial cortex temporally correlated with pre-seizure self-reported dissociation, and local brief electrical stimulation elicited dissociative experiences. These results highlight the value of new brain-scale recording technologies; here, initial optical and electrical multiregional activity-screening guided further quantitative testing of precise causal hypotheses. More generally, integrative technologies with broad an high-resolution perspective may provide increasingly-informative experimental access to internal representations of sensations, cognitions, and actions at cellular resolution (and with region-wide or even brain-wide perspective), providing a path forward for elucidating the dynamics involved in creating complex brain and behavioral states important in health and disease.