Effects of prefrontal theta-burst stimulation on brain function in treatment-resistant depression: A randomized sham-controlled neuroimaging study

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 < 0.05, FWE-corrected for multiple comparisons). In contrast, in Group B, SUV was decreased in the ACC and mPFC and increased in the bilateral temporal cortex. Group C also had increased SUV in the bilateral temporal cortices. 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.