Kevin Bickart, MD, PhD: Precision Medicine Approach to Chronic Traumatic Brain Injury is Underway

Kevin Bickart, MD, PhD

Most patients recover from mild traumatic brain injuries, including concussions. However, a “critical minority” experience ongoing symptoms even if there’s no observable injury on a brain scan. These chronic symptoms include headaches, dizziness, sensitivity to light, brain fog and depression or anxiety. Dr. Kevin Bickart, MD, PhD, Assistant Professor of Neurology at UCLA Health and the David Geffen School of Medicine at UCLA is an expert in traumatic brain injury and focuses his research on this critical minority. “It can be debilitating,” Dr. Bickart notes. “The studies in the field of traumatic brain injury have shown for those people who do develop chronic symptoms, they have a harder time getting back to work, back to school or to their sport.”
In chronic traumatic brain injury, patients often become worried that a trigger will activate symptoms. This is a phenomenon known as fear avoidance, where patients refrain from activities or situations that could trigger symptoms. But by avoiding working at a computer, exercising, or going outside into bright sunlight, they become more sensitive to these activities instead of developing a tolerance through gradual exposure. Dr. Bickart characterizes fear avoidance as a sort of “force multiplier” in chronic traumatic brain injury, because is s a significant symptom itself, but it can magnify other symptoms in this brain disease. A problem in developing new therapies for chronic traumatic brain injury is that each patient can be very different in their patterns of brain injury. A trial of a new treatment cannot be applied to all potential patients like a blanket, because the source of patient’s symptoms may be different within the brain. 
Dr. Bickart is developing a Precision Medicine approach to chronic traumatic brain injury, and applying this to fear avoidance. In a recently funded study from the Department of Defense, he will focus on modifying a particular brain circuit that his preliminary work shows to be overactive among people who experience fear avoidance symptoms. Dr. Bickart found that MRIs are able to detect a blood flow pattern indicating an over-active connection between the prefrontal cortex and the amygdala. These are two brain areas associated with planning and forecasting, and with emotional regulation. The amygdala is a region that generates and regulates emotions. The over-activity of this connection could be indication of a maladaptation that is preventing the brain from eliminating fears and resolving symptoms.
Dr. Bickart’s Department of Defense study will determine how non-invasive brain stimulation may improve chronic post-concussion symptoms in adults. Short, 1- to 2-minute courses of a painless magnetic pulse have the potential to relieve symptoms of mild traumatic brain injury, said Dr. Bickart. His approach will be first to identify the group of patients with the abnormal or hyper-connected prefrontal-to-amygdala connection after traumatic brain injury, and then targeting this connection. The approach may disrupt the rigidity of the circuit, which would then allow for more flexibility and adaptability, the brain could readdress previously triggering situations. That could help patients reintegrate normal activities into everyday life, which would build tolerance and improve symptoms, Dr. Bickart said. The four-year study starts in July 2023 and will use transcranial magnetic stimulation to inhibit nerve cells in the brain. TMS is currently approved by the Food and Drug Administration for some psychiatric conditions and certain types of migraine headaches.

Although the research will be conducted on civilians, the findings are relevant to the military, where mild traumatic brain injury is relatively common and occurs through similar mechanisms to civilians, such as motor vehicle accidents or physical trauma.

Dr. Bickart said the study advisory board will include UCLA Operation Mend, which provides health care to post-9/11 service members, to ensure the perspective of U.S. forces are represented.