Stimulation of a ventrolateral prefrontal-amygdala circuit modulates impulsivity in Borderline Personality Disorder

Impulsivity and emotion dysregulation are core symptoms of Borderline Personality Disorder (BPD) for which brain-based therapeutic options are very limited. Prior neuroimaging studies in BPD showed the implication of fronto-amygdala circuit dysfunction in BPD. This interventional crossover randomized trial study aims to test if individualized ventrolateral prefrontal cortex (VLPFC)-Amygdala circuit modulation with repetitive Transcranial Magnetic Stimulation (rTMS) can be applied to alter impulsivity and emotion dysregulation in BPD. A single session of excitatory intermittent Theta Burst Stimulation (iTBS) was administered to individualized right and/or left VLPFC targets with the strongest functional connectivity to the ipsilateral amygdala before and after the participants performed delayed discounting and emotional reactivity to social exclusion stimuli tasks utilized to objectively assess the behavioral measure of respectively, impulsivity and emotion dysregulation. Stimulation of the VLPFC-amygdala circuit was found to be practical, safe, and well-tolerated. Mixed-model linear regression analysis showed a significant positive modulatory effect of right-sided VLPFC stimulation. Simulation of the right VLPFC, but not the left or bilateral VLPFC, was associated with a significant reduction of impulsivity (χ2(2) = 7.76, p = 0.021) and showed a trend-level numeric reduction in participants' affective rating of photos with a social exclusion theme. There was also a significant association (p < 0.04) between decreases in impulsivity and emotional ratings following the right VLPFC stimulation. Based on these results, we suggest that the right VLPFC iTBS is a safe, tolerable, and promising procedure for modulating impulsivity and possibly emotional reactivity in BPD.