Study suggests using neurostimulation therapies on specific brain circuit could treat PTSD

A study led by researchers at Brigham and Women’s Hospital evaluated 193 participants in the Vietnam Traumatic Brain Injury Study. The team found that people with injuries to their amygdala, the fear center of the brain, were less likely to develop post-traumatic stress disorder. Their findings are published in Neuroscience of nature.

“This is a very real brain disease, and we can localize it to certain brain circuits,” said corresponding author Shan Siddiqi, MD, a psychiatrist at Brigham’s Center for Brain Circuit Therapeutics and assistant professor of psychiatry at Harvard Medical School.

“Unfortunately, people sometimes think that PTSD is related to a person’s mental strength or weakness, but it has nothing to do with moral character.”

Siddiqi collaborated with other researchers at Brigham’s Center for Brain Circuit Therapeutics, as well as researchers at Northwestern University Feinberg School of Medicine, Brown University Alpert School of Medicine and Duke University School of Medicine. He said previous studies have shown that people with amygdala damage are less likely to suffer from PTSD, but the team wanted to find a therapeutic target for the condition.

“The amygdala is located deep in the brain, making it difficult to reach it precisely with any stimulation modality without resorting to surgery,” Siddiqi said.

Researchers at the Center for Brain Circuit Therapeutics have previously discovered networks that can successfully treat depression and drug addiction using transcranial magnetic stimulation (TMS). Michael Fox, MD, PhD, co-author of the study Neuroscience of Nature Dr. Dmitry Kumar, author and director of the Center for Brain Circuit Therapeutics, said they hope to build on their success by identifying targets for conditions such as PTSD.

“One of the big challenges in developing a brain stimulation treatment for PTSD is identifying the right therapeutic target,” Fox said.

Fox said previous trials have attempted to use the same circuit his team derived for depression, but that target failed in trials for PTSD.

“Rather than continuing with a trial-and-error approach of testing different targets, we turned to brain lesions to map the circuit,” he said.

The team looked at 193 patients with penetrating traumatic brain injuries from the Vietnam Traumatic Brain Injury Study, led by co-author Jordan Grafman, Ph.D., of Northwestern University. They looked at whether these veterans developed post-traumatic stress disorder 20 years after the Vietnam War.

“Some of these veterans who were hit in the head with shrapnel developed PTSD, but many of them did not,” Fox said. “In fact, the patients developed PTSD less than other veterans who did not have brain injuries.”

Fox said the data Grafman collected was critical to this study because he mapped the exact location of the damage in each patient and what the neurological effects of that damage were.

The researchers then hypothesized that there must be a circuit that, when damaged, protects against PTSD. They used their wiring diagram, the human connectome, to map out where brain damage had occurred and where each injury connected.

They then compared the data to 180 veterans who did not have brain injuries, some of whom had PTSD and some of whom did not. They found that connectivity within the circuit correlated with whether or not they had PTSD. Finally, the team examined whether this circuit might be a good treatment target by reviewing previous trials using TMS for PTSD.

“The trials in which stimulation reached the circuit we identified were generally the ones that had good outcomes in patients,” Fox said. “We also looked at whether our results could inform how to stimulate the targets, which allowed us to identify what we think is a therapeutic target for TMS treatment.”

During the study, a patient suffering from severe PTSD requested TMS from Acacia Mental Health in California, and Siddiqi was consulted to help plan the treatment. After a careful informed consent process, Acacia clinicians used the circuit discovered in the study to treat the patient, improving his symptoms.

Fox said that while this is just one patient, the case illustrates how the study’s results could translate to a clinical setting. Before they can expand it to a larger population, they’ll need to conduct a randomized controlled trial targeting the circuit to get FDA approval.

One limitation of the study, Siddiqi said, is that they don’t yet know how treatment outcomes might change if a person is in a PTSD-induced fear state at the time of treatment versus relaxation. Fox added that the study only looked at veterans, so they’re not sure if PTSD in non-veterans maps to the same circuit.

“While there is still work to be done, we have taken an important step in identifying a therapeutic target for a disease in patients who desperately need better treatments,” Fox said.