Brain circuitry underlying dissociative experiences

Date:
September 16, 2020
Source:
Stanford Medicine
Summary:
Scientists identified key brain circuitry that plays a role in
the mysterious experience called dissociation, in which people
can feel disconnected from their own body and from reality.



FULL STORY ==========================================================================
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 Karl
Deisseroth, MD, PhD, professor of bioengineering and of psychiatry
and behavioral sciences, as well as a Howard Hughes Medical Institute investigator.

"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," Deisseroth
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, Deisseroth 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," Deisseroth said.

Now, in a study to be published online Sept. 16 in Nature, Deisseroth
and his colleagues at Stanford University have revealed molecular
underpinnings and brain-circuit dynamics underlying dissociation.



========================================================================== "This study has identified brain circuitry that plays a role in a
well-defined subjective experience," Deisseroth said. "Beyond its
potential medical implications, it gets at the question, 'What is the
self?' That's a big one in law and literature, and important even
for our own introspections." Deisseroth, the D. H. Chen Professor
and a practicing psychiatrist, is the study's senior author. Graduate
student Sam Vesuna and postdoctoral scholar Isaac Kauvar, PhD, share
lead authorship of the study.

The findings, which implicate a particular protein in a particular
set of cells as crucial to the feeling of dissociation, could lead to better-targeted therapies for conditions such as PTSD and other disorders
in which dissociation can happen, such as borderline personality disorder
and epilepsy.

A patient's feeling of dissociation The researchers mapped out this
brain-mind connection not only by observing the brains and behavior
of mice but also in the course of treating a patient with chronic
seizures at the Stanford Comprehensive Epilepsy Program. The patient had reported experiencing a feeling of dissociation immediately before each seizure. (Such a pre-seizure sensation is called an aura.) The patient described this aura as like being "outside the pilot's chair, looking at,
but not controlling, the gauges," Deisseroth said.



==========================================================================
The researchers recorded electric signals from the patient's cerebral
cortex and stimulated it electrically to try to determine the point
of origin of the seizures. In the process, the patient responded to
questions about how it felt.

Whenever the patient was about to have a seizure, the study's authors discovered, it was preceded not only by the dissociative aura but also by
a particular pattern of electrical activity localized within the patient's posteromedial cortex. This activity was characterized by an oscillating
signal generated by nerve cells firing in coordination at 3 hertz, or
three cycles per second. And when this region was stimulated electrically,
the patient experienced the dissociative aura without having a seizure.

The scientists probed the effects of ketamine in mice. The drug is known
to induce dissociative states in humans. Mice can't describe their
feelings. But at the right ketamine dose, they behaved in a way that
suggested they were experiencing a kind of dissociation -- a disconnect
between perception of incoming sensations and a more complex emotional
response to those sensations.

When placed on an uncomfortably warm surface, the mice indicated they
could feel the heat; they responded reflexively to it, flicking their
paws. But they acted as if they didn't care enough to do what they would ordinarily do voluntarily in such situations: lick their paws to cool
them off.

Inducing dissociative behavior with optogenetics The researchers used optogenetics, a technology enabling scientists to stimulate or inhibit
neuronal activity using light, to stimulate neurons in mice's equivalent
of a posteromedial cortex. Doing so at rhythms of 3 hertz could induce dissociative behavior in drug-free animals, the researchers found.

Further experiments showed that a particular type of protein, an ion
channel, was essential to the generation of the 3 hertz signal and to
the dissociative behavior in mice. This protein could be a potential
treatment target.


========================================================================== Story Source: Materials provided by Stanford_Medicine. Original written
by Bruce Goldman.

Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Vesuna, S., Kauvar, I.V., Richman, E. et al. Deep posteromedial
cortical
rhythm in dissociation. Nature, 2020 DOI: 10.1038/s41586-020-2731-9 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/09/200916113525.htm

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