EEG-based biomarkers predict individual differences in TMS-induced entrainment of intrinsic brain rhythms

Background: Entrainment (increase) and modulation (shift) of intrinsic brain oscillations via rhythmic-TMS (rhTMS) enables to either increase the amplitude of the individual peak oscillatory frequency, or experimentally slowing/accelerating this intrinsic peak oscillatory frequency by slightly shifting it. Both entrainment, and modulation of brain oscillations can lead to different measurable perceptual and cognitive changes. However, there are noticeable between-participant differences in such experimental entrainment outcomes. Objective/hypothesis: The current study aimed at explaining these inter-individual differences in entrainment/ frequency shift success. Here we hypothesize that the width and the height of the Arnold tongue, i.e., the frequency offsets that can still lead to oscillatory change, can be individually modelled via resting-state neural markers, and may explain and predict efficacy and limitation of successful rhythmic-TMS (rh-TMS) manipulation. Methods: Spectral decomposition of resting-state data was used to extract the spectral curve of alpha activity, serving as a proxy of an individual Arnold tongue. These parameters were then used as predictors of the rh-TMS outcome, when increasing alpha-amplitude (i.e., applying pulse train tuned to the individual alpha frequency, IAF), or modulating the alpha-frequency (i.e., making alpha faster or slower by stimulating at IAF +/- 1Hz frequencies). Results: Our results showed that the height of the at-rest alpha curve predicted how well the entrainment increased the intrinsic oscillatory peak frequency, with a higher at-rest spectral curve negatively predicting amplitude-enhancement during entrainment selectively during IAF-stimulation. In contrast, the wider the resting-state alpha curve, the higher the modulation effects aiming to shift the intrinsic frequency towards faster or slower rhythms. Conclusion: These results not only offer a theoretical and experimental model for explaining the variance across different rh-TMS studies reporting heterogenous rh-TMS outcomes, but also introduce a potential biomarker and corresponding evaluative tool to develop most optimal and personalized rh-TMS protocols, both in research and clinical applications.