Researchers examined 193 individuals from the Vietnam Head Injury Study who suffered from penetrating traumatic brain injuries to determine if the location of shrapnel injuries in the brain affected the risk of developing PTSD. They found that damage to brain areas linked to the amygdala was related to a reduced likelihood of PTSD. The findings indicate that certain brain lesions that may help prevent PTSD correspond to a specific neural circuit involving the amygdala and the medial prefrontal cortex.
A groundbreaking study directed by scientists at Brigham and Women’s Hospital, part of the Mass General Brigham healthcare system, indicates that neurostimulation therapies targeting a specific brain network could potentially treat post-traumatic stress disorder (PTSD) in veterans. By studying 193 participants from the Vietnam Head Injury Study with penetrating traumatic brain injuries, the researchers discovered that those with damage to the amygdala—known as the brain’s fear center—were less likely to develop PTSD. These findings are published in Nature Neuroscience.
“PTSD is a genuine brain disorder that we can associate with specific brain circuits,” said Dr. Shan Siddiqi, the study’s lead author and a psychiatrist at Brigham’s Center for Brain Circuit Therapeutics, as well as an assistant professor at Harvard Medical School. “Many people wrongly believe that PTSD relates to a person’s mental strength or weakness, but it has no connection to moral character.”
Dr. Siddiqi collaborated with fellow researchers from the Brigham’s Center for Brain Circuit Therapeutics and experts from Northwestern University’s Feinberg School of Medicine, Brown University Alpert School of Medicine, and Duke University School of Medicine. He noted that earlier research has shown individuals with amygdala damage are less prone to PTSD, but the objective was to identify a potential therapeutic target for the disorder.
“The amygdala’s deep location in the brain makes it challenging to target precisely for stimulation without surgery,” Siddiqi explained.
Researchers at the Center for Brain Circuit Therapeutics have previously identified successful networks for treating depression and addiction using transcranial magnetic stimulation (TMS). Michael Fox, MD, PhD, another co-author of the Nature Neuroscience study and director of the Center, stated that they aim to apply their success in recognizing targets for conditions like PTSD.
“A major obstacle in developing brain stimulation treatments for PTSD is pinpointing the right therapeutic target,” Fox mentioned.
Fox pointed out that previous endeavors attempted to apply the same circuit used for depression; however, this approach did not yield successful results for PTSD.
“Instead of relying on a trial-and-error method to assess different targets, we utilized brain lesions to outline the circuit,” he stated.
The research team evaluated 193 veterans with penetrating traumatic brain injuries from the Vietnam Head Injury Study, with co-author Jordan Grafman, PhD, at Northwestern leading the project. They investigated whether these veterans developed PTSD two decades after the Vietnam War.
“Some veterans with shrapnel injuries developed PTSD, but many did not,” Fox reported. “In fact, these patients experienced PTSD at a lower rate than those without brain injuries.”
Fox emphasized that Grafman’s data was crucial for this study because he had mapped the precise sites of damage in each patient and their neurological implications.
The researchers then proposed that there must be a circuit that, when damaged, offers protection against PTSD. They employed their wiring diagram, known as the human connectome, to trace where brain injuries occurred and the connections of each lesion. This was contrasted with data from 180 veterans who did not have brain injuries, some of whom had PTSD while others did not. The analysis indicated that connections within the circuit were linked to the presence of PTSD. Ultimately, the team assessed whether this circuit would be a suitable target for treatment by reviewing past TMS trials for PTSD.
“Trials where stimulation targeted the identified circuit generally resulted in positive outcomes for patients,” Fox noted. “We also considered whether our findings could guide how to stimulate the targets, aiming for what we believe to be an effective treatment target for TMS.”
In one instance during the study, a patient suffering from severe PTSD requested TMS at Acacia Mental Health in California. Siddiqi was brought in to assist in formulating the treatment plan. Following a thorough informed consent process, the clinicians at Acacia used the circuit outlined in the study to treat the patient, which ultimately alleviated his symptoms.
Fox remarked that while this is only one case, it serves as an example of how the study’s results might be applied in clinical practice. However, before broader implementation, they will need to conduct a randomized controlled trial targeting the circuit to secure FDA approval.
Siddiqi acknowledged that one limitation of the study is the uncertainty regarding how treatment outcomes might be affected if a person is experiencing PTSD-related fear during treatment as opposed to being in a relaxed state. Fox added that the study involved solely veterans, leaving it unclear whether PTSD in non-veterans would connect to the same circuit.
“Although much work still needs to be done, we’ve made significant progress in identifying a therapeutic target for a condition that desperately requires better treatment options,” Fox concluded.
