This study aims to explore changes in resting-state functional connectivity (rsFC) between three subregions of the amygdala and the frontal pole (FP) after personalized FP neuromodulation, as a novel treatment approach for fear avoidance in patients with persistent post-concussion symptoms (PPCS).

In concussion patients, fear avoidance—avoiding symptom-triggering activities—can perpetuate PPCS. Fear avoidance relies on dynamic interactions between the amygdala and FP, which show increased resting-state fMRI (rfMRI) connectivity in patients with PPCS. Our previous research suggests this hyperconnectivity may be specific to a medial amygdala subregion rather than its more lateral and dorsal subregions, which support distinct affective functions. In this study, we investigated whether rfMRI connectivity in the medial frontoamygdala circuit could be specifically decreased using a traditionally inhibitory form of TMS called continuous theta burst stimulation (cTBS).

We present the case of a 37-year-old female with a concussion that occurred three months prior due to a car accident. She underwent 10 sessions of cTBS targeting a portion of FP with the highest rfMRI connectivity to the medial amygdala at baseline. For treatment outcome, we assessed rfMRI connectivity between the medial, lateral, and dorsal amygdala subregions and the FP target from baseline to immediately after the first treatment, last treatment, and one and two months later.

Using a target-selection algorithm, we identified a region within the left FP with the highest connectivity to the medial amygdala. After a single session of TMS, connectivity decreased and remained attenuated immediately post-treatment and for up to two months later. The effect was specific to the medial amygdala, while connectivity with the lateral and dorsal amygdala did not show significant changes.

In conclusion, after personalized cTBS to the FP, a patient with PPCS demonstrated immediate, sustained, and specific decreases in connectivity to a medial frontoamygdala circuit involved in fear avoidance.