Nature
September 16, 2020
Sam Vesuna, Isaac Kauvar, Ethan B Richman et al.
291 citations
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.
Nature Communications
October 19, 2023
Laura M Hack, Xue Zhang, B. Heifets et al.
20 citations
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.
Science
April 12, 2019
R. N. Moda-Sava, Mitchell H. Murdock, P. Parekh et al.
Ketamine rescues depression-like behavior in mice by reversing stress-induced loss of dendritic spines and restoring coordinated neural activity in the prefrontal cortex. Spine formation in this brain region is necessary for sustaining—but not for initially inducing—ketamine's antidepressant effects on motivated escape behavior. Optogenetically deleting newly formed spines eliminated the long-term behavioral benefits, while deleting random spines did not. The findings suggest that interventions aimed at preserving restored synapses could help maintain remission from depression.