In an innovative clinical trial, a blend of brain stimulation and virtual reality exposure therapy has shown promising results for U.S. military veterans grappling with post-traumatic stress disorder (PTSD). The study, detailed in a recent publication in JAMA Psychiatry, found a significant easing of PTSD symptoms among participants undergoing this novel treatment approach.
PTSD is a condition that severely impacts individuals’ lives, characterized by symptoms such as intrusive thoughts, avoidance behaviors, heightened arousal, and mood disturbances. It’s notably prevalent and debilitating among veterans, often leading to serious health complications, substance use issues, and an increased risk of suicide.
Traditional treatments, including trauma-focused cognitive behavioral therapies and medication, are valuable, but a substantial number of patients either do not respond adequately to these treatments or are unable to tolerate the adverse effects associated with medication. Additionally, a considerable percentage of individuals undergoing psychotherapy drop out, indicating a significant gap in the effective treatment of PTSD.
Noah Philip, a professor at Brown University’s Warren Alpert Medical School, and his colleagues aimed to explore a novel approach combining two treatments: transcranial direct current stimulation (tDCS) and virtual reality exposure therapy, to potentially offer a more effective treatment option for PTSD sufferers.
“This is a different and innovative way of approaching treatment where we’re combining the best aspects of psychotherapy, neuroscience and brain stimulation to help people get better,” said Philip, who leads mental health research at the Providence V.A. Center for Neurorestoration and Neurotechnology. “There’s a lot of promise here, and that offers hope.”
The study hinged on the hypothesis that modulating the connection between amygdala and the ventromedial prefrontal cortex could enhance fear extinction, the neurobiological processes involved in learning to no longer fear a previously frightening stimulus.
The amygdala plays a crucial role in processing fear and emotional responses. It helps to encode and remember the emotional significance of events, particularly those that are threatening. The ventromedial prefrontal cortex, on the other hand, is involved in the regulation and suppression of emotional responses generated by the amygdala.
“Through exposure therapy, the brain is reprocessing the trauma, and learning that even though the traumatic experience was dangerous, the memories of the traumatic experience, as well as the thoughts and feelings that are conjured up by those memories, are not dangerous — they are safe,” said co-author Mascha van ’t Wout-Frank, an investigator at the V.A. Providence Center for Neurorestoration and Neurotechnology. “This results in a decline in conditioned fear response.”
To conduct their study, the researchers designed a double-blind, sham-controlled clinical trial involving 54 U.S. military veterans diagnosed with chronic PTSD. These individuals were recruited from the VA Providence Healthcare System over a span from April 2018 to May 2023. The inclusion criteria specified a diagnosis of chronic PTSD related to warzone experiences, assessed through the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5), and allowed for a broad range of warzone-related traumas, including both combat and non-combat experiences.
Participants of any sex or gender, aged between 18 to 65 years, were eligible, provided they had been on a stable psychiatric treatment regimen for more than 6 weeks, with no significant changes expected during the study period. Individuals were excluded if they had conditions or situations that might interfere with the study’s safety or outcomes, such as bipolar I disorder, severe traumatic brain injury, active substance use disorders (excluding nicotine and caffeine), or suicidal intentions.
The study employed a parallel-group design, randomly assigning participants to either the active treatment group, receiving real tDCS and virtual reality exposure, or the control group, receiving sham (placebo) tDCS and the same virtual reality exposure.
The tDCS involved applying a low (2 milliamp) electrical current to the ventromedial prefrontal cortex for six 25-minute sessions during the virtual reality exposure, spread over two to three weeks. The virtual reality exposure therapy comprised standardized warzone scenarios designed to incrementally expose participants to trauma-related stimuli without replicating any individual’s personal trauma.
Participants who received the active treatment reported significant reductions in PTSD symptom severity. This was measured using the PTSD Checklist for DSM-5 (PCL-5), where a clinically meaningful improvement was defined as a reduction of 10 points or more.
Such improvements were observed after just three sessions (midpoint of the treatment) and were sustained at the end of the treatment course, with effects persisting at a one-month follow-up. This indicates not only the immediate impact of the combined treatment on reducing PTSD symptoms but also its lasting benefits.
Further reinforcing the positive outcomes, participants in the active treatment group also demonstrated significant improvements in self-reported quality of life and clinician-assessed social and occupational functioning at the three-month follow-up. These findings suggest that the benefits of the treatment extend beyond alleviating PTSD symptoms, positively affecting broader aspects of participants’ lives.
While improvements in depressive symptoms were observed over time in both the active and sham treatment groups, the significant and meaningful enhancements in PTSD symptomatology and functional outcomes were specific to the active tDCS plus virtual reality exposure group.
The study also explored psychophysiological outcomes, specifically skin conductance (SC) reactivity, as a measure of physiological response to the virtual reality exposure therapy. Participants receiving active tDCS demonstrated greater habituation to the virtual reality stimuli across sessions compared to the sham group. This suggests that the active treatment enhanced the participants’ ability to physiologically adapt to the trauma-related stimuli over time, a key component of exposure therapy’s effectiveness.
Regarding safety, the combined treatment was well-tolerated by participants, with adverse effects being mild and consistent with the known safety profiles of both tDCS and virtual reality exposure therapy. This is an important consideration, as the acceptability and safety of novel treatments are crucial for their potential adoption and implementation.
While the study’s outcomes are promising, the researchers acknowledge several limitations. A notable attrition rate at follow-up assessments may impact the long-term efficacy conclusions. The interactions between this novel treatment and ongoing psychiatric medications remain uncertain.
Looking ahead, the research team aims to conduct further studies with larger participant groups, longer follow-up periods, and potentially repeated treatment sessions to understand the sustained effects and brain changes induced by this therapy. They are hopeful that these findings can pave the way for more effective, accessible PTSD treatments, especially for veterans who bear a disproportionately high burden of this challenging condition.
“This intervention imposed low participant burden, had modest technical cost, and yielded clinically meaningful improvements in an otherwise difficult-to-treat patient population. This reflects an important step forward in the use of combined brain stimulation and contextual control and underscores the innovative capability of these technologies,” the researchers concluded.
The study, “Virtual Reality and Transcranial Direct Current Stimulation for Posttraumatic Stress Disorder A Randomized Clinical Trial,” was authored by Mascha van ’t Wout-Frank, Amanda R. Arulpragasam, Christiana Faucher, Emily Aiken, M. Tracie Shea, Richard N. Jones, Benjamin D. Greenberg, and Noah S. Philip.
