Researchers have identified cells and circuits in a specific area of the brain that are involved in generating the subjective state called dissociation.

Dissociation has been described as the uncanny feeling that one is “outside” of one’s own body “looking in.” It is a disruption in the integrity and continuity of experience, as we perceive it, that sometimes occurs during or just after a trauma. It is a debilitating symptom, sometimes chronic, of people who suffer from post-traumatic stress disorder (PTSD), and is also experienced by some individuals who have been diagnosed with epilepsy and borderline personality disorder. Dissociation has also been reported by some who have taken psychoactive drugs including ketamine.

A team led by Karl Deisseroth, M.D., Ph.D., used several cutting-edge techniques enabling them to record and control the activity of neurons across the brain’s cortex in mice. They also recorded neural activity in the human brain, in a patient being treated for epilepsy who repeatedly experiences dissociation.

These experiments, reported in Nature, enabled them to discover a characteristic rhythm in a part of the human brain called the PMC (posteromedial cortex), which is connected to many other areas and is involved in generating awareness. The rhythm, an oscillation generated by neurons firing at 3 cycles per second (3Hz), was seen only in this part of the cortex and only when the patient being observed experienced dissociative symptoms just ahead of the onset of an epileptic seizure.

The very same 3Hz rhythm was observed in the corresponding area of the mouse brain, in animals that had been induced to display dissociative-like behavior minutes after an injection of ketamine.

Dr. Deisseroth, a member of the BBRF Scientific Council, is the 2013 BBRF Goldman-Rakic Prize winner and a 2007 and 2005 BBRF Young Investigator grantee. Among other innovations, Dr. Deisseroth and his colleagues have changed the field of neuroscience with their development of a technology called optogenetics, which employs colored laser light to experimentally manipulate the activity of individual neurons as well as entire brain circuits in animals.

The team used optogenetics in their newly reported research to test their observations linking the 3 Hz rhythm in the mouse-equivalent of the PMC with dissociation-like behavior. Using light to stimulate the neurons in this region, they observed dissociation-like behavior in mice that had not been given ketamine, thus suggesting a causal connection between the telltale rhythm and dissociation.

The mouse experiments also enabled the team to identify a specific protein called HCN1 involved in the mechanism involved in dissociation.  HCN1 forms a tiny pore-like channel in the surface of certain neurons, whose activation is involved in generating the 3Hz rhythm.  Although it is only one part of a more complex mechanism, its identification makes it a potential target for future treatments to control or prevent dissociation.

Dr. Deisseroth says that nearly three of every four individuals who experience a trauma will enter a dissociative state during the event or in the hours, days, or weeks following.  In many cases, these symptoms subside, but they can become a chronic problem, especially in those who develop PTSD.

“Our study has identified brain circuitry that plays a role in a well-defined subjective experience,” Dr. Deisseroth said. “Even beyond its medical implications, it gets at the question, ‘What is the self?’ That’s a big question in law and literature, and even for our own introspections.”

The technologies used to discover the cortical rhythm linked with dissociation highlight the value of methods that are beginning to enable scientists to experiment with circuitry involved in generating that greatest of human mysteries: the “internal representations” in our minds that give rise to our sense of self.