Abstract Details

Title Personalized Neuromodulation for Persistent Post-Concussive Symptoms: Preliminary Findings and Trial Protocol

Topic Neuro Trauma and Critical Care

Presentation(s) P2 - Poster Session 2 (11:45 AM-12:45 PM)

Poster/Presentation
Number 14-014

Objective

To investigate frontoamygdala neuromodulation as a novel mechanism and treatment target for fear avoidance in patients with persistent post-concussive symptoms (PPCS).

Background PPCS are heterogeneous, nonspecific, and subjective, making their etiology complex and difficult to target. One promising target is fear avoidance, or avoiding stimuli and activities that trigger symptoms, because it accounts for substantial variance in PPCS and relies on well-studied circuitry. Fear regulation relies on a dynamic interaction between ventromedial prefrontal cortex (vmPFC) and amygdala. This interaction is disrupted in animal and human models of traumatic brain injury (TBI) towards vmPFC and amygdala hyperconnectivity or hyperactivity concurrent with enhanced and persistent fear behavior. Here, we examined whether this circuitry could be modulated using transcranial magnetic stimulation (TMS) to the vmPFC.

Design/Methods Participants with substance use disorder underwent blinded, sham-controlled TMS to the left frontal pole (FP1) for 20 sessions using continuous theta burst stimulation (cTBS), which is traditionally inhibitory. We assessed resting-state fMRI connectivity (rsFC) between the vmPFC and medial amygdala from baseline to immediately and 1 month after treatment using repeated measures ANOVA.

Results vmPFC to medial amygdala rsFC decreased significantly in participants receiving real (N=9) but not sham (N=8) cTBS (Time-x-Treatment Interaction: F=6.78, p=0.02, Partial eta sq= 0.31). The effect persisted up to 1 month after treatment, greatest for participants who had the strongest baseline connectivity (R²=0.50, p<0.05). This effect was specific to the medial amygdala, not seen for the ventrolateral or dorsal amygdala subregions, which are functionally distinct.

Conclusions This is the first evidence that ventromedial frontoamygdala circuitry can be specifically and durably modulated noninvasively in humans. It sets the stage for our DOD-funded trial using personalized circuit-based frontoamygdala cTBS to reduce fear avoidance and persistent symptoms in patients with PPCS, but may also be transdiagnostic to any condition marked by similar fear and emotion dysregulation mechanisms.

Authors/Disclosures
Kevin Bickart, MD, PhD (UCLA) PRESENTER	Dr. Bickart has nothing to disclose.
Christopher Giza, MD, FAAN (UCLA, Depts of Pediatrics and Neurosurgery)	Dr. Giza has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Medical Network Speakers Bureau. Dr. Giza has stock in Highmark Interactive. The institution of Dr. Giza has received research support from UCLA: Brain Injury Research Center, Steve Tisch BrainSPORT Program, Easton Clinic for Brain Health. Dr. Giza has received publishing royalties from a publication relating to health care. Dr. Giza has a non-compensated relationship as a Advisory Board with Major League Soccer that is relevant to AAN interests or activities. Dr. Giza has a non-compensated relationship as a Advisory Board with National Basketball Association that is relevant to AAN interests or activities. Dr. Giza has a non-compensated relationship as a Consultant with United States Soccer Federation that is relevant to AAN interests or activities. Dr. Giza has a non-compensated relationship as a Co-founder & Advisor with Symptomwise that is relevant to AAN interests or activities.
Andrew Leuchter (UCLA)	No disclosure on file
Colleen Hanlon	No disclosure on file

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