Different forms of prefrontal theta burst stimulation for executive function of medication- resistant depression: Evidence from a randomized sham-controlled study

Background: Even during symptomatic remission, many patients with medication resistant depression (MRD) still demonstrate impaired cognitive function, especially executive function (EF). Theta-burst transcranial magnetic stimulation (TBS) modulates cortical excitability and may treat MRD. Evidences from previous studies show that intermittent TBS (iTBS) produces cortical excitatory effects, while continuous TBS (cTBS) produces a reduction of cortical excitability. EF is highly dependent on prefrontal activity, but the effects of different forms of prefrontal TBS on EF remain unknown. Methods: 60 MRD patients were recruited and randomly assigned to one of four groups. Treatment was determined by the group to which an individual was assigned; A: cTBS 1800. pulses/session; B: iTBS 1800. pulses/session; C: a combination of cTBS + iTBS, 1800. pulses/session for each; and D: sham TBS. Wisconsin Card Sorting Test (WCST) for the performance of EF was evaluated before and after 10 daily treatment sessions. Results: Repeated measures ANOVA, with each WCST index at baseline and 2 weeks after TBS as within-subject factors, demonstrated that a statistically significant interaction of TBS groups (G) and antidepressant responses [(R), responses were defined as > 50% reduction of depression scores after 2-weeks TBS treatment] on the before-versus-after changes of all WCST indexes (G × R, p < 0.05). Responders in Group B, but not in the other groups, showed a significant improvement in WCST performance. Only nonresponders in Group A showed a trend for EF worsening. Conclusions: Our findings showed that left prefrontal iTBS, not right prefrontal cTBS, improved EF, and this can be independent from its antidepressant effects.