Research reveals brain mechanisms behind defensive responses in PTSD

Posttraumatic stress disorder (PTSD) involves defensive responses to stress or triggers. This commonly includes active responses like irritability and aggression. However, it can also include passive responses like out-of-body experiences. In a new study, Lawson Health Research Institute’s Dr. Ruth Lanius and her team have uncovered brain mechanisms behind these responses, suggesting that patients with PTSD are poised for defense even when they are at rest.

Patients with PTSD commonly respond to stress or triggers with hyperarousal symptoms, such as irritability and aggressive behavior. These are characterized by the human fight-or-flight response. However, 15-30% of PTSD patients are diagnosed with the dissociative subtype of PTSD. The dissociative subtype is characterized by passive defensive responses, such as shutting down or freezing. This also includes out-of-body experiences where patients become so overwhelmed by stress that they detach from their emotions and body.

“It’s important to understand that people with PTSD commonly respond to stress in one of two ways,” said Dr. Ruth Lanius, Scientist at Lawson Health Research Institute and Psychiatrist at London Health Sciences Centre. “They may become very activated in response to a stressor or they may shut down or freeze.”

Past research has shown that the periaqueductal gray (PAG) is one region of the brain that plays a key role in these different types of responses. One part, the dorsolateral PAG, is believed to control active defensive responses while another, the ventrolateral PAG, is believed to control passive defensive responses.

“Given past research, we wanted to better understand the brain mechanisms, or the neural circuitry, behind these two different reactions,” said Dr. Lanius, who is also professor in the Department of Psychiatry at Western University’s Schulich School of Medicine & Dentistry.

To accomplish this, Dr. Lanius and her team conducted a seven year study with three groups of participants: PTSD patients without the dissociative subtype, PTSD patients with the dissociative subtype and those without PTSD. They used fMRI (functional magnetic resonance imaging) to scan participants’ brains at either Lawson’s imaging facility, located within the Nuclear Medicine department at St. Joseph’s Hospital, or Robarts Research Institute’s Center for Functional and Metabolic Mapping.

Dr. Lanius and her team used the scans to examine the PAG and its connections to other parts of the brain (functional brain connectivity) while participants were in a resting state. This means that participants were asked to close their eyes and let their mind wander for six minutes.

Results showed that, even at rest, patients with PTSD have extensive connections between the PAG and other areas of the brain associated with defensive action. All PTSD patients had extensive connections between the dorsolateral PAG and areas of the brain linked to hyperarousal symptoms, such as the dorsal anterior cingulate and right insula. However, only patients with the dissociative subtype demonstrated greater connections between the ventrolateral PAG and brain regions associated with passive coping strategies like increased levels of out-of-body experiences, such as the temporoparietal junction.

“These are novel findings that suggest patients with PTSD may be constantly prepared for defensive response, even when they are at rest and under conditions of relative safety,” said Sherain Harricharan, first author of the study. “Taken together, these findings represent an important first step to identifying neural and behavioral targets for new therapies that address both active and passive defensive strategies in patients with a trauma-related disorder.”

The study, “"fMRI functional connectivity of the periaqueductal gray in PTSD and its dissociative subtype”, is published online in Brain and Behavior.  Dr. Lanius continues to study the neurochemistry responses behind these two different defensive responses. She is also studying how these findings can be applied to future therapies.