Cognition-Modulated Frontal Activity in Prediction and Augmentation of Antidepressant Efficacy: A Randomized Controlled Pilot Study

Higher rostral anterior cingulate cortex (rACC) activity correlated with frontal theta power (frontal theta) is associated with better antidepressant responses. The antidepressant efficacy of repetitive transcranial magnetic stimulation (rTMS) varied widely; however, the effects of TMS might be modulated by manipulating the pretreatment neural states. Therefore, we conducted a pilot study to investigate whether manipulated frontal theta before rTMS treatment could predict and augment antidepressant responses. A computerized rACC-engaging cognitive task (RECT) was exploited continuously for 10 min to patients with major depressive disorder. In total, 36 patients were randomized to 3 groups (Group-A: RECT[active] + rTMS[active]; Group-B: RECT[sham] + rTMS[active]; Group-C: RECT[active] + rTMS[sham]). Frontal theta and whole-brain glucose uptakes were assessed. We found that the RECT-modulated increases in frontal theta correlated well with rACC glucose uptakes. The treatment responders demonstrated a significant increase in frontal theta after RECT. Post-RECT frontal theta had good sensitivity/specificity in predicting antidepressant responses to rTMS. Group-A had more reduction in total depression scores, had more responders, and was more likely to achieve remission than other groups (Group-A [41.6%] > Group-B [16.6%] > Group-C [0%], P < 0.05). A significant enhancement in the post-1st-rTMS frontal theta was observed in Group-A responders but not in Group-B responders, supporting the argument that RECT-modulated rTMS augmented rTMS efficacy. In conclusion, this study suggests that manipulating pre-rTMS neural activity could predict and augment antidepressant effects to rTMS treatment.