Placebo aiTBS attenuates suicidal ideation and frontopolar cortical perfusion in major depression

The application of repetitive transcranial magnetic stimulation has been shown to rapidly decrease suicidal ideation in major depressive disorder (MDD). However, the neural working mechanisms behind this prompt attenuation of suicidal thoughts remains to be determined. Here, we examined how placebo-accelerated intermittent theta burst stimulation (aiTBS) may influence brain perfusion and suicidal thoughts using arterial spin labeling (ASL). In a randomized double-blind sham-controlled crossover trial, 45 MDD patients received aiTBS applied to the left dorsolateral prefrontal cortex (Trial registration: http://clinicaltrials.gov/show/NCT01832805). With each ASL scan measurement, suicidal ideation was assessed with the Beck Scale for Suicidal Ideation (BSI) and depression severity with the Beck Depression Inventory (BDI). Compared with active stimulation, the attenuation of suicidal ideation after 4 days of placebo aiTBS was related to significant frontopolar prefrontal perfusion decreases. These findings were unrelated to changes in depression severity scores. Although both active and sham aiTBS resulted in prompt decreases in suicidal ideation, specifically sham aiTBS significantly attenuated frontopolar perfusion in relation to reductions in BSI scores. Our findings show that in accelerated neurostimulation paradigms, placebo responses are related to perfusion decreases in brain areas associated with higher cognitive processes, resulting in suicidal ideation attenuation.