Identifying Neurophysiological Markers of Intermittent Theta Burst Stimulation in Treatment-Resistant Depression Using Transcranial Magnetic Stimulation-Electroencephalography

Rebecca Strafella; Davide Momi; Reza Zomorrodi; Jennifer Lissemore; Yoshihiro Noda; Robert Chen; Tarek K Rajji; John D Griffiths; Fidel Vila-Rodriguez; Jonathan Downar; Zafiris J Daskalakis; Daniel M Blumberger; Daphne Voineskos

doi:10.1016/j.biopsych.2023.04.011

Identifying Neurophysiological Markers of Intermittent Theta Burst Stimulation in Treatment-Resistant Depression Using Transcranial Magnetic Stimulation-Electroencephalography

Biol Psychiatry. 2023 Sep 15;94(6):454-465. doi: 10.1016/j.biopsych.2023.04.011. Epub 2023 Apr 20.

Authors

Affiliations

¹ Institute of Medical Sciences, University of Toronto, Toronto, Ontario, Canada; Temerty Centre for Therapeutic Brain Intervention, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
² Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada; Krembil Centre for Neuroinformatics, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
³ Temerty Centre for Therapeutic Brain Intervention, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
⁴ Department of Psychiatry and Behavioral Sciences, Stanford University, Palo Alto, California.
⁵ Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan.
⁶ Institute of Medical Sciences, University of Toronto, Toronto, Ontario, Canada; Krembil Research Institute, Toronto Western Hospital, University Health Network, Toronto, Ontario, Canada; Division of Neurology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
⁷ Institute of Medical Sciences, University of Toronto, Toronto, Ontario, Canada; Temerty Centre for Therapeutic Brain Intervention, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada; Toronto Dementia Research Alliance, University of Toronto, Toronto, Ontario, Canada.
⁸ Institute of Medical Sciences, University of Toronto, Toronto, Ontario, Canada; Krembil Centre for Neuroinformatics, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
⁹ Non-Invasive Neurostimulation Therapies Laboratory, Vancouver, British Columbia, Canada; Department of Psychiatry, University of British Columbia, Vancouver, British Columbia, Canada.
¹⁰ Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
¹¹ Department of Psychiatry, University of California San Diego, La Jolla, California.
¹² Institute of Medical Sciences, University of Toronto, Toronto, Ontario, Canada; Temerty Centre for Therapeutic Brain Intervention, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
¹³ Institute of Medical Sciences, University of Toronto, Toronto, Ontario, Canada; Temerty Centre for Therapeutic Brain Intervention, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada; Krembil Research Institute, Toronto Western Hospital, University Health Network, Toronto, Ontario, Canada. Electronic address: daphne.voineskos@camh.ca.

PMID: 37084864
DOI: 10.1016/j.biopsych.2023.04.011

Abstract

Background: Intermittent theta burst stimulation (iTBS) targeting the left dorsolateral prefrontal cortex is effective for treatment-resistant depression, but the effects of iTBS on neurophysiological markers remain unclear. Here, we indexed transcranial magnetic stimulation-electroencephalography (TMS-EEG) markers, specifically, the N45 and N100 amplitudes, at baseline and post-iTBS, comparing separated and contiguous iTBS schedules. TMS-EEG markers were also compared between iTBS responders and nonresponders.

Methods: TMS-EEG was analyzed from a triple-blind 1:1 randomized trial for treatment-resistant depression, comparing a separated (54-minute interval) and contiguous (0-minute interval) schedule of 2 × 600-pulse iTBS for 30 treatments. Participants underwent TMS-EEG over the left dorsolateral prefrontal cortex at baseline and posttreatment. One hundred fourteen participants had usable TMS-EEG at baseline, and 98 at posttreatment. TMS-evoked potential components (N45, N100) were examined via global mean field analysis.

Results: The N100 amplitude decreased from baseline to posttreatment, regardless of the treatment group (F_1,106 = 5.20, p = .02). There were no changes in N45 amplitude in either treatment group. In responders, the N100 amplitude decreased after iTBS (F_1,102 = 11.30, p = .001, p_corrected = .0004). Responders showed higher posttreatment N45 amplitude than nonresponders (F_1,94 = 4.11, p = .045, p_corrected = .016). Higher baseline N100 amplitude predicted lower post-iTBS depression scores (F_4,106 = 6.28, p = .00014).

Conclusions: These results provide further evidence for an association between the neurophysiological effects of iTBS and treatment efficacy in treatment-resistant depression. Future studies are needed to test the predictive potential for clinical applications of TMS-EEG markers.

Keywords: Electroencephalography; Major depressive disorder; Markers; TMS-EEG; iTBS; rTMS.

Publication types

Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Depression*
Electroencephalography
Evoked Potentials / physiology
Humans
Prefrontal Cortex / physiology
Transcranial Magnetic Stimulation* / methods