Simple Electroencephalographic Treatment-Emergent Marker Can Predict Repetitive Transcranial Magnetic Stimulation...

Prefrontal repetitive transcranial magnetic stimulation (rTMS) repeated daily for 4 to 6 weeks is used to treat major depressive disorder, but more than 50% of patients do not achieve significant response. Here we test the validity of a simple electroencephalographic (EEG) marker that predicts nonresponse to rTMS. Such a marker could potentially increase rTMS effectiveness by directing nonresponders to alternative treatments or by guiding early modification of stimulation parameters.

We retrospectively analyzed 2-channel EEG data captured in the OPT-TMS National Institute of Mental Health-sponsored, multicenter study. Cumulative Brain Engagement Index (cBEI), a measure derived from template matching that allows scoring EEG dynamics along treatment, was computed.

Six hundred sixty-five EEG recordings were analyzed. In the rTMS group, the median cBEI was found to increase in the responder group but remained unchanged in the nonresponder group. The difference between the cBEI of the groups became statistically significant by the third valid EEG sample. Within 5 samples, 91% of the responders presented with a cBEI above a preset threshold. Within 9 samples, 17% of the nonresponders had a cBEI above the threshold.

This study demonstrates the feasibility of a simple-to-capture EEG marker as a treatment-emergent marker of response to rTMS treatment of depression. In the OPT-TMS study, discontinuing treatment when the cBEI dropped below the threshold between the fifth to ninth treatment potentially could have avoided administration of 485 (63%) of 765 treatments. Because the marker can be generated online, it would be of interest to evaluate, in future studies, whether it could be used to tune treatment parameters and improve remission rates.