Daily prefrontal closed-loop repetitive transcranial magnetic stimulation (rTMS) produces progressive EEG quasi-alpha phase entrainment in depressed adults

• Published in: Brain stimulation Vol. 15; no. 2; pp. 458 - 471
• Main Authors: Faller, Josef, Doose, Jayce, Sun, Xiaoxiao, Mclntosh, James R., Saber, Golbarg T., Lin, Yida, Teves, Joshua B., Blankenship, Aidan, Huffman, Sarah, Goldman, Robin I., George, Mark S., Brown, Truman R., Sajda, Paul
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.03.2022; Elsevier
• Subjects: Adult; Alpha Rhythm; Brain; Closed-loop neurostimulation; Depressive Disorder, Major - therapy; Electroencephalography (EEG); Humans; Inter-trial phase coherence (ITPC); Major depressive disorder (MDD); Prefrontal Cortex - physiology; Repetitive transcranial magnetic stimulation (rTMS); Transcranial Magnetic Stimulation - adverse effects; Treatment Outcome; Closed-loop neurostimulation; Electroencephalography (EEG); Repetitive transcranial magnetic stimulation (rTMS); Inter-trial phase coherence (ITPC); Major depressive disorder (MDD)
• ISSN: 1935-861X; 1876-4754; 1876-4754
• DOI: 10.1016/j.brs.2022.02.008

Transcranial magnetic stimulation (TMS) is a non-invasive neuromodulation modality that can treat depression, obsessive-compulsive disorder, or help smoking cessation. Research suggests that timing the delivery of TMS relative to an endogenous brain state may affect efficacy and short-term brain dynamics. To investigate whether, for a multi-week daily treatment of repetitive TMS (rTMS), there is an effect on brain dynamics that depends on the timing of the TMS relative to individuals’ prefrontal EEG quasi-alpha rhythm (between 6 and 13 Hz). We developed a novel closed-loop system that delivers personalized EEG-triggered rTMS to patients undergoing treatment for major depressive disorder. In a double blind study, patients received daily treatments of rTMS over a period of six weeks and were randomly assigned to either a synchronized or unsynchronized treatment group, where synchronization of rTMS was to their prefrontal EEG quasi-alpha rhythm. When rTMS is applied over the dorsal lateral prefrontal cortex (DLPFC) and synchronized to the patient's prefrontal quasi-alpha rhythm, patients develop strong phase entrainment over a period of weeks, both over the stimulation site as well as in a subset of areas distal to the stimulation site. In addition, at the end of the course of treatment, this group's entrainment phase shifts to be closer to the phase that optimally engages the distal target, namely the anterior cingulate cortex (ACC). These entrainment effects are not observed in the group that is given rTMS without initial EEG synchronization of each TMS train. The entrainment effects build over the course of days/weeks, suggesting that these effects engage neuroplastic changes which may have clinical consequences in depression or other diseases. •Major depressive disorder patients were treated with closed-loop EEG-triggered rTMS over DLPFC for six weeks.•Patients were randomized to rTMS triggered either synchronously or asynchronously timed to their quasi-alpha EEG oscillation.•Sync patients showed increased entrainment over sessions and decreased optimal phase difference for anterior cingulate.•Entrainment was observed both locally over the stimulation site and distally over the anterior cingulate.•The entrainment effects build over the course of days/weeks, suggesting that these effects engage neuroplastic changes.