NEURAL MECHANISMS OF ACCELERATED ITBS FOR TREATMENT- RESISTANT DEPRESSION: A DOUBLE-BLIND SHAM-CONTROLLED NEUROIMAGING STUDY

Abstract Background Intermittent theta-burst stimulation (iTBS), as an updated form of repetitive transcranial magnetic stimulation (rTMS), was effective in treating treatment-resistant depression (TRD)1,2,3. 10-Hz rTMS at left prefrontal cortex (PFC) was reported to have antidepressant effects by modulating the activities in bilateral frontal-cingulo-temporal circuit2. Although both 10-Hz rTMS and iTBS were found to be effective, iTBS (80% motor threshold, 1800 pulses) acted differently by modulating the activities in midline structures, such as cingulate cortex and precuneus. Although the clinical effects were not enhanced compared to single session of iTBS treatment per day, we recently reported that 2 uninterrupted sessions of iTBS were also effective4. However, it remains elusive whether accelerated protocols (i.e., two uninterrupted sessions per day: prolonged iTBS x 2, piTBS*2) may also be effective through modulation in the midline structures. Methods Patients with antidepressant-resistant major depressive disorder were randomly assigned and to the piTBS*2 group, rTMS*2 group (10Hz, 120% motor threshold, 3000pulses/session, 2 sessions/day), and sham treatment group. Before and after the trials, 18F-FDG PET was applied and depression severity by 17-item Hamilton Depression Rating Scale (HDRS- 17) was evaluated. Results HDRS-17 scores decreased significantly in all three groups. Voxel-based analysis revealed that the piTBS*2 group showed increased activities after treatment in the midline structures including anterior and middle cingulate cortex and precuneus. By contrast, rTMS increased the bilateral frontal and temporal lobe activities. Conclusion Accelerated iTBS modulated the metabolism in the midline structures, but the direction of modulation is opposite to the findings reported in the singles-session iTBS protocol. Findings in the rTMS*2 group were similarr with past studies. Our results suggested that neural mechanisms of iTBS was not linear and dose-dependent. References Cheng-Ta Li* et al. Efficacy of Prefrontal Theta-Burst Stimulation in Refractory Depression: A Randomized Sham-Controlled Study. Brain, 2014 Jul;137(Pt 7):2088-98. Cheng-Ta Li* et al. Effects of prefrontal theta-burst stimulation on brain function in treatment-resistant depression. Brain Stimulation. 2018;11(5):1054-1062. Cheng-Ta Li* et al. Antidepressant Efficacy of Prolonged Intermittent Theta Burst Stimulation Monotherapy for Recurrent Depression and Comparison of Methods for Coil Positioning: A Randomized, Double-Blind, Sham-controlled Study. Biological Psychiatry, Mar. 2020 Cheng-Ta Li* et al. The longer, the better ? Longer left-sided prolonged intermittent theta burst stimulation in patients with major depressive disorder. Asian J Psychiatry. 2023