The power of context: Enhancing repetitive transcranial magnetic stimulation effects through skillful behavior.

INTRODUCTION: Non-invasive neuromodulation techniques like repetitive transcranial magnetic stimulation (rTMS) have shown promise in treating psychopathology. However, emerging evidence suggests that the brain's functional state during stimulation may significantly influence treatment outcomes. Pairing neurostimulation with cognitively engaging tasks that activate targeted neural networks could enhance neuroplasticity and improve efficacy. Emotional dysregulation is a core feature of many psychiatric disorders. To explore whether combining behavioral interventions with neuromodulation enhances outcomes, we conducted a secondary analysis examining the effects of pairing rTMS with cognitive restructuring (CR), a skill-based intervention, on emotion regulation. MATERIALS AND METHODS: Forty-three adults with high emotional dysregulation completed an fMRI task involving aversive sounds to identify individualized neurostimulation targets. During a subsequent experimental visit, participants engaged in three randomized tasks involving either passive listening or active downregulation of distress from aversive or neutral sounds. Each task was paired with one of three stimulation conditions: sham rTMS, 10 Hz rTMS targeting the emotion regulation network, or 1 Hz rTMS targeting a non-congruent network. RESULTS: Results revealed that 10 Hz rTMS combined with CR significantly reduced self-reported distress. Moreover, pairing CR with stimulation over the emotion regulation network led to lower distress and increased high-frequency heart rate variability (HF-HRV), a physiological marker of emotion regulation, compared to stimulation of a non-targeted network. CONCLUSION: These findings underscore the importance of contextual factors in neuromodulation and suggest that integrating rTMS with active cognitive strategies like CR may be a promising approach for enhancing emotion regulation in adults with psychiatric distress.