Does 18 Hz deep TMS benefit a different subgroup of depressed patients relative to 10 Hz rTMS? The role of the individual alpha frequency

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.