Evaluating the safety profile of connectome-based repetitive transcranial magnetic stimulation

New developments in neuro-navigation and machine learning have allowed for personalised approaches to repetitive transcranial magnetic stimulation (rTMS) to treat various neuropsychiatric disorders. One specific approach, known as the cingulum framework, identifies individualised brain parcellations from resting state fMRI based on a machine-learning algorithm. Theta burst stimulation, a more rapid form of rTMS, is then delivered for 25 sessions, 5 per day, over 5 days consecutively or spaced out over 10 days. Preliminary studies have documented this approach for various neurological and psychiatric ailments. However, the safety and tolerability of this approach are unclear.

We performed a retrospective study on 165 unique patients (202 target sets) treated with this personalised approach between January 2020 and December 2023.

Common side effects included fatigue (102/202, 50%), local muscle twitching (89/202, 43%), headaches (49/202, 23%), and discomfort (31/202, 17%), all transient. The top 10 unique parcellations commonly found in the target sets included L8av (52%), LPGs (28%), LTe1m (21%), RTe1m (18%), LPFM (17%), Ls6-8 (13%), Rs6-8 (9%), L46 (7%), L1 (6%), and L6v (6%). Fatigue was most common in target sets that contained R6v (6/6, 100%) and L8c (5/5, 100%). Muscle twitches were most common in target sets that contained RTGv (5/5, 100%) and LTGv (4/4, 100%).

These side effects were all transient and well-tolerated. No serious side effects were recorded. Results suggested that individualised, connectome-guided rTMS is safe and contain side-effect profiles similar to other TMS approaches reported in the literature.