Does 18 Hz deep TMS benefit a different subgroup of depressed patients relative to 10 Hz rTMS? The role of the individual alpha frequency
- PMID: 39395357
- DOI: 10.1016/j.euroneuro.2024.09.007
Does 18 Hz deep TMS benefit a different subgroup of depressed patients relative to 10 Hz rTMS? The role of the individual alpha frequency
Abstract
Both 10 Hz repetitive transcranial magnetic stimulation (rTMS) as well as 18 Hz deep TMS (dTMS) constitute effective, FDA-approved TMS treatment protocols for depression. However, not all patients experience sufficient symptom relief after either of these protocols. Biomarker-guided treatment stratification could aid in personalizing treatment and thereby enhancing improvement. An individual alpha frequency (iAF)-based EEG-biomarker, Brainmarker-I, can differentially stratify patients to depression treatments. For instance, an iAF close to 10 Hz was associated with better improvement to 10 Hz rTMS, possibly reflecting entrainment of endogenous oscillations to the stimulation frequency. Accordingly, we examined whether 18 Hz dTMS would result in better improvement in individuals whose iAF lies around 9 Hz, a harmonic frequency of 18 Hz. Curve fitting and regression analyses were conducted to assess the relation between iAF and improvement. For treatment stratification purposes, correlations with iAF-distance to 10 Hz compared 18 Hz dTMS (N = 114) to 10 Hz rTMS (N = 72). We found a robust quadratic effect, indicating that patients with an iAF around 9 Hz exhibited least symptom improvement (r2=0.126, p<.001). Improvement correlated positively with iAF-distance to 10 Hz (p=.003). A secondary analysis in 20 Hz figure-of-eight data confirmed this direction. A significant interaction of iAF-distance and stimulation frequency between 10 and 18 Hz datasets emerged (p=.026). These results question entrainment of endogenous oscillations by their harmonic frequency for 18 Hz, and suggest that 10 Hz and 18 Hz TMS target different subgroups of depression patients. This study adds to iAF stratification, augmenting Brainmarker-I with alternative TMS protocols (18 Hz/20 Hz) for patients with a slower iAF, thereby broadening clinical applicability and relevance of the biomarker.
Keywords: Biomarker; Deep TMS; Electroencephalography; Stratified psychiatry; TMS.
Copyright © 2024. Published by Elsevier B.V.
Conflict of interest statement
Declaration of competing interest Dr. Alyagon is an EEG consultant for BrainsWay Ltd. Dr. Downar has received research support from NIH, CIHR, Brain Canada, Ontario Brain Institute, the Klarman Family Foundation, the Arrell Family Foundation, and the Buchan Family Foundation, in-kind equipment support for investigator-initiated trials from MagVenture, is an advisor for BrainCheck, Arc Health Partners and Salience Neuro Health, and is a co-founder of Ampa Health. Dr. Zangen is an inventor of Deep TMS coils and has financial interest in BrainsWay Ltd. Dr. Sack is chief scientific advisor at PlatoScience Medical, scientific advisor at Alpha Brain Technologies, Founder and CEO of Neurowear Medical, Director of the International Clinical TMS Certification Course (www.tmscourse.eu), and receives equipment support from MagVenture, Magstim, and Deymed. Victoria Middleton and Aimee Halloran are employees of Salience Health. Dr. Donachie is Chief Medical Officer at Salience Health. Dr. Arns holds equity/stock in neurocare and Sama Therapeutics, serves as consultant to Synaeda, Sama Therapeutics and Roche and is named inventor on patents and intellectual property but receives no royalties. Brainclinics Foundation received equipment support from MagVenture and Deymed. All other authors report no biomedical financial interests or potential conflicts of interest.
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