Personalized Circuit-Based Frontoamygdala Neuromodulation for Persistent Post-Concussive Symptoms
Abstract
The overall objective of the proposed project is to apply a well-studied and safe form of brain modulation to patients with chronic symptoms after concussion. These patients represent a vulnerable population in need of brain-targeted and personalized therapies. Chronic concussive symptoms can include emotional, physical, and cognitive problems, such as depression, anxiety, headache, dizziness, sensory sensitivities, and difficulties with memory and attention. These symptoms are costly and relatively common, representing a public health concern, yet there are no standard therapies. This is in part due to a limited understanding of the underlying cause of these symptoms. Most concussions do not cause a visible injury to the brain based on clinical-grade brain imaging. Using research-grade brain imaging however, we have identified an overactive brain circuit in patients who have more chronic symptoms after concussion and more severe forms of traumatic brain injury. Interestingly, this brain circuit connects the frontal lobe of the brain to a deep structure in the brain, called the amygdala, which is important for generating and regulating emotions. Our finding suggests that this brain circuit may be involved in chronic concussive symptoms. This is promising because the frontal lobe can be targeted with noninvasive brain modulation treatment. In fact, our preliminary findings show that inhibiting the frontal lobe at the midline, over the forehead, can decrease the activity of this brain circuit. Whereas these preliminary findings are promising, this target location and modulation technique have not been studied in patients with concussion. Here, we propose leveraging this prior work to apply the same brain modulation approach to patients with chronic symptoms after concussion. We will also advance this approach to personalize the brain modulation and optimize chances of modulating the intended brain circuit by mapping each individual’s brain circuits prior to treatment. The study will be conducted in patients from the University of California, Los Angeles (UCLA’s) BrainSPORT clinic who are between 18 and 65 years old who have had a mild traumatic brain injury, including concussion, and report a significant burden of symptoms between 3-12 months after their injury. Seventy-five participants will be randomly assigned to active modulation and sham modulation (or inactive in which the participant receives only a sensation of brain modulation without actual modulation) groups. We hypothesize that active brain modulation, as compared to sham modulation, will cause a decrease in activity in the brain circuit that we found to be abnormally overactive in our prior studies of patients with chronic concussive symptoms. Furthermore, we hypothesize that this personalized approach to frontal brain modulation will cause an improvement in chronic concussive symptoms in the active modulation but not sham modulation group, and that the improvements would be greatest for participants who showed the greatest decrease in activity of the targeted brain circuit. Finally, we will also have collected many other data points about each individual that would allow us to determine what individual characteristics make one more likely to respond to this type of treatment. This would be the first study to use brain circuit mapping on an individual level to treat patients with chronic concussive symptoms. It would not only have implications in this patient population but also any population that suffers from emotion regulation problems, such as in mood and anxiety disorders. Based on our analyses of treatment response, we may even be able to determine which people would be most likely to respond to this form of frontal lobe modulation prior to recommending the treatment, a key prerequisite for precision medicine. Importantly, the findings from this work would be directly relevant to military personnel because of their higher risk of incurring combined
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 28, 2022
- Source ID
- W81XWH2211056
Entities
People
- Kevin Bickart
Organizations
- United States Army
- University of California, Los Angeles