Increased Amygdala Activation During Symptom Provocation Predicts Response to Combined Repetitive Transcranial Magnetic Stimulation and Exposure Therapy in Obsessive-Compulsive Disorder in a Randomized Controlled Trial

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) combined with exposure and response prevention is a promising treatment modality for treatment-refractory obsessive-compulsive disorder (OCD). However, not all patients respond sufficiently to this treatment. We investigated whether brain activation during a symptom provocation task could predict treatment response. METHODS: Sixty-one adults with OCD (39 female/22 male) underwent symptom provocation with OCD- and fear-related visual stimuli during functional magnetic resonance imaging prior to an 8-week combined rTMS and exposure and response prevention treatment regimen. Participants received one of the following 3 rTMS treatments as part of a randomized controlled trial: 1) 10-Hz rTMS (110% resting motor threshold) to the left dorsolateral prefrontal cortex, 2) 10-Hz rTMS (110% resting motor threshold) to the left presupplementary motor area, or 3) 10-Hz control rTMS (60% resting motor threshold) to the vertex. Multiple regression and correlation were used to examine the predictive value of task-related brain activation for treatment response in the following regions of interest: the dorsomedial prefrontal cortex, amygdala, dorsolateral prefrontal cortex, and left presupplementary motor area. RESULTS: The different treatment groups responded equally to treatment. Higher pretreatment task-related activation of the right amygdala to OCD-related stimuli showed a positive association with treatment response in all groups. Exploratory whole-brain analyses showed positive associations between activation in multiple taskrelevant regions and treatment response. Only dorsal anterior cingulate cortex activation to fear-related stimuli showed a negative association with treatment outcome. CONCLUSIONS: Higher pretreatment right amygdala activation during symptom provocation predicts better treatment response to combined rTMS and exposure and response prevention in OCD.