Effects of Prefrontal Theta-Burst Stimulation on Brain Function in Treatment-Resistant Depression: A Randomized Sham-Controlled Neuroimaging Study

Abstract Background Theta-burst transcranial magnetic stimulation (TBS) can quickly modulate brain activity and can be used to treat treatment-resistant depression (TRD). Whole-brain analytical research has revealed that left high-frequency PFC rTMS modulates brain activity in anterior cingulate cortex (ACC) and the fronto-cingulo-temporal circuit. We aimed to investigate whether the prefrontal TBS's antidepressant mechanisms involve these regions. Methods We designed a randomized, double-blind, sham-controlled neuroimaging study to investigate different mechanisms of TBS [i.e., continuous TBS (cTBS) and intermittent TBS (iTBS)]. This study included 56 TRD patients [67.8%: women; mean age (SD): 45.5 (10.6) years], who were randomly assigned to one of four groups [A: right prefrontal cTBS; B: left prefrontal iTBS; C: combined right prefrontal cTBS and left prefrontal iTBS; and D: sham-TBS]. We measured standard uptake values (SUV) of cerebral glucose metabolism, at rest, both before and after ten daily treatment sessions. Results Group B and Group C had more responders than Group A and Group D (χ2 = 9.161, p = 0.027). In Group A, the SUV was significantly increased in the ACC and medial PFC (mPFC) after treatment, while the SUV was decreased in the right temporal cortex (p  Conclusion Instead of observing inhibitory or facilitatory effects on the targeted prefrontal cortex, we found that the two-week prefrontal TBS protocols primarily modulated the fronto-cingulo-temporal circuit.