It's neither uncommon nor especially worrisome for people to lose themselves in a great book or a daydream. But it's disconcerting when feeling transported becomes so intense as to seem that one is literally separated from one's own mind or body.

Between 2% and 10% of the population will experience the mysterious phenomenon known as dissociation during their lifetimes, said the senior author.

"This state often manifests as the perception of being on the outside looking in at the cockpit of the plane that's your body or mind -- and what you're seeing you just don't consider to be yourself," the author said.

Nearly three of every four individuals who have experienced a traumatic event will enter a dissociative state during the event or in the hours, days and weeks that follow, the author said. For most people, these dissociative experiences subside on their own within a few weeks of the trauma. But dissociation can become chronic and highly disruptive -- for example, in post-traumatic stress disorder and other neuropsychiatric conditions.

Because no one knows what's going on inside the brain to trigger or sustain dissociation, it's hard to know how to stop it. "In order to develop treatments, and to understand the biology, we needed to know more," the author said.

Now, in a study to be published in Nature, the team has revealed molecular underpinnings and brain-circuit dynamics underlying dissociation. The authors established a dissociation-like state in mice, induced by precisely-dosed administration of ketamine or phencyclidine.

Large-scale imaging of neural activity revealed that these dissociative agents elicited a 1–3-Hz rhythm in layer 5 neurons of the retrosplenial cortex. Electrophysiological recording with four simultaneously deployed high-density probes revealed rhythmic coupling of the retrosplenial cortex with anatomically connected components of thalamus circuitry, but uncoupling from most other brain regions was observed—including a notable inverse correlation with frontally projecting thalamic nuclei.

In testing for causal significance, the authors found that rhythmic optogenetic activation of retrosplenial cortex layer 5 neurons recapitulated dissociation-like behavioural 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 behavioural effects.

In a patient with focal epilepsy, simultaneous intracranial stereoencephalography recordings from across the brain revealed a similarly localized rhythm in the homologous deep posteromedial cortex that was temporally correlated with pre-seizure self-reported dissociation, and local brief electrical stimulation of this region elicited dissociative experiences.

http://med.stanford.edu/news/all-news/2020/09/researchers-pinpoint-brain-circuitry-underlying-dissociation.html

https://www.nature.com/articles/s41586-020-2731-9