Accelerated iTBS treatment applied to the left DLPFC in depressed patients results in a rapid volume increase in the left hippocampal dentate gyrus, not driven by brain perfusion

Accelerated intermittent Theta Burst Stimulation (aiTBS) has been shown to be an effective antidepressant treatment. Although neurobiological changes shortly after this intervention have been reported, whether aiTBS results in structural brain changes must still be determined. Furthermore, it possible that rapid volumetric changes are driven by factors other than neurotrophic processes.We examined whether possible grey matter volumetric (GMV) increases after aiTBS treatment could be driven by increased brain perfusion, measured by Arterial Spin Labeling (ASL).46 treatment-resistant depressed patients were randomized to receive 20 sessions of active or sham iTBS applied to the left dorsolateral prefrontal cortex. All sessions were delivered over 4 days at 5 sessions per day (trial registration: http://clinicaltrials.gov/show/NCT01832805). Patients were scanned the day before starting stimulation and three days after aiTBS.There was a significant cluster of increased left hippocampal GMV in the dentate gyrus related to HRSD changes after active aiTBS, but not after sham stimulation. These GMV increases became more pronounced when accounting for changes in cerebral perfusion.Active, but not sham, aiTBS, resulted in acute volumetric changes in parts of the left dentate gyrus, suggesting a connection with adult neurogenesis. Furthermore, taking cerebral perfusion measurements into account impacts on detection of the GMV changes. Whether these hippocampal volumetric changes produced by active aiTBS are necessary for long-term clinical improvement remains to be determined.