Gradual changes in TMS-induced motor excitability are associated with excitation-inhibition balance dynamics

Single-pulse transcranial magnetic stimulation (spTMS) applied to the primary motor cortex (M1) is widely used to assess corticospinal excitability through motor evoked potentials (MEPs). While trial-by-trial variability in MEP amplitude is thought to reflect dynamic shifts in cortical excitability, implications and neural underpinnings of gradual changes in MEP amplitude over the course of a spTMS session remain unexplored. We addressed this gap by investigating the relationship between slow MEP amplitude fluctuations and shifts in electroencephalography (EEG)-derived excitation/inhibition (E/I) balance.We analyzed EEG-TMS-MEP data from 20 healthy participants, each comprising 1000-1200 trials. E/I-balance metrics, including spectral power in alpha, beta, and gamma bands, aperiodic signal components (offset and exponent), and sample entropy, were computed for 126 individual channels. Linear mixed-effects models (LMMs) for MEP trend were then applied for each channel and E/I balance metric. We selected models based on the lowest Akaike Information Criterion (AIC) scores and assessed the significance of E/I balance coefficients using t-tests.Across E/I balance metrics, we found consistent relationships between gradual changes in E/I balance and MEP amplitude in left central and frontal regions. However, spatial distribution, directionality and magnitude of these associations varied within and between E/I balance metrics. Further, our results indicated a strong positive relationship between alpha/beta power and MEP amplitude trend in areas surrounding the stimulated motor cortex. Our works substantiates the potential of EEG-derived E/I balance metrics as predictors of MEP amplitude trends, while highlighting the complexity of regional excitatory and inhibitory dynamics.