Improved functional brain anomalies after personalized rTMS relative to classical rTMS and tDCS in resistant depression

Abstract

Introduction The iADAPT study - Imagery guided Anti-Depressive Adaptive Personalized TMS ( NCT02863380 ) - is a double-blind randomized cross-over study designed to assess the feasibility and efficiency of personalizing rTMS protocol, based on the functional imaging of single subjects, relative to classical rTMS and tDCS. Method Brain imaging included two kinds of ASL sequences, converted in rCBF, repeated in three different sessions, using different functional paradigms and contrasted to 38 normal controls. The tDCS protocol used an F3 anodal positioning (20 min, 2 mA). Classical rTMS used F3 positioning (3000 pulses, 120%, 10 Hz). Last personalized rTMS was designed to correct the rCBF anomalies. Thirty bilateral targets were planned to cover the reachable parts of the complex regions with abnormal perfusion. Coil positioning used a robotic neuronavigated device. In case of hypo-perfusion, targets were stimulated using the same protocol than HF-rTMS. There were 2 sessions per day for 10 days in each of the 3 conditions (personalized rTMS, classical rTMS, tDCS) Changes in brain perfusion were assessed on rCBF-ASL imaging and changes in connectivity were assessed on the BOLD signal. Results We report on the first 14 completers. Four patients had significant MRI anomalies (29%). The left prefrontal region was hypo-perfused in 8 subjects (57%), and hyper-perfused in 2 (15%). The right prefrontal region was hypo-perfused in 10 subjects (71%). Six patients remitted (43%) and further 2 of them responded (14%). Quite all remissions (5/6) occurred during or within a week post personalized rTMS. Brain imaging mimicked clinical improvement with perfusion increases in a large fronto-parietal network in the personalized condition (P Conclusion These are preliminary evidences that personalizing rTMS might improve its biological effect and clinical outcome.