Accelerated iTBS changes perfusion patterns in medication resistant depression

Accelerated intermittent Theta Burst Stimulation (aiTBS) is a new non-invasive brain stimulation protocol developed to rapidly treat medication resistant depression (MRD). However, to examine potential neurobiological changes only few sham-controlled studies combining pre/post treatment measures and brain imaging data are available. Consequently, with this Arterial Spin Labeling (ASL) brain imaging study, we investigated in 45 antidepressant-free MRD patients whether clinical improvement following aiTBS treatment applied to the left dorsolateral prefrontal cortex (Trial registration: http://clinicaltrials.gov/show/NCT01832805) would be associated with specific changes in brain perfusion patterns. We primarily expected frontolimbic perfusion changes following active and not sham aiTBS. Our ASL brain imaging findings showed that active aiTBS resulted in prompt perfusion increases in functionally connected brain regions such as the ventromedial prefrontal cortex and the right inferior parietal lobule. We also observed decreased perfusion in the left parahippocampal gyrus and the right posterior cerebellar lobe after active aiTBS. On the other hand, sham aiTBS resulted in right angular perfusion decreases, an area known to be involved in placebo responses. Overall, our perfusion findings indicate that active aiTBS treatment promptly affects brain regions functionally and structurally connected to the stimulated area and known to be part of deregulated brain circuits when clinically depressed. Placebo responses may be part of the clinical effects of accelerated ITS protocols. Our current results further shed light on how accelerated rTMS treatment protocols may promptly improve depressive symptoms in MRD.