A 1–3-Hz rhythm in deep posteromedial cortex underlies dissociative states in both mice and humans. In mice, precisely-dosed ketamine or phencyclidine induced this rhythm in layer 5 neurons of the retrosplenial cortex, which coupled with thalamus circuitry but uncoupled from most other brain regions. Rhythmic optogenetic activation of these neurons recapitulated dissociation-like behaviors. Local HCN1 pacemakers were required for ketamine to induce the rhythm and behavioral effects. In a patient with focal epilepsy, a similar localized rhythm in the homologous deep posteromedial cortex correlated with pre-seizure self-reported dissociation, and electrical stimulation of this region elicited dissociative experiences.
Ketamine rapidly induces altered states of consciousness, but the neural mechanisms are unclear. In a randomized, placebo-controlled study with nonclinical adults, functional neuroimaging examined brain activity during emotional tasks under placebo, low-dose (0.05 mg/kg), and high-dose (0.5 mg/kg) ketamine. Different dissociative experiences had opposing effects on right anterior insula activity: depersonalization reduced task-evoked activity by 0.39 standard deviations, while dissociative amnesia increased it by 0.32 standard deviations. These findings suggest that specific dissociative states may influence how ketamine affects brain activity, potentially informing treatment responses in depression.