Predicting Neuroplasticity Effects of Continuous Theta Burst Stimulation with Biomarkers from the Motor Evoked Potential TMS Input-Output Curve

The field of neuromodulation lacks predictors of individual differences in plasticity that influence responses to repetitive transcranial magnetic stimulation (rTMS). Continuous theta burst stimulation (cTBS), a form of rTMS known for its inhibitory effects, shows variable responses between individuals, potentially due to differences in neuroplasticity. Predicting individual cTBS effects could vastly enhance its clinical and experimental utility. This study explores whether motor evoked potential (MEP) input-output (IO) parameters measured prior to neuromodulation can predict motor cortex responses to cTBS. IO curves were sampled from healthy adults by recording MEPs over a range of single pulse TMS intensities to obtain parameters including MEP _max and S ₅₀ (midpoint intensity). Subjects later received cTBS over the same location of motor cortex and their MEPs before and after stimulation were compared. Both MEP _max and S ₅₀ predicted responses, significantly correlating (p<0.05, R ² >0.25) with individuals’ MEP changes at 10, 20, and 30 minutes after cTBS. Further, we introduced and validated an easily implementable biomarker that does not require the time-consuming sampling of full IO curve: MEP _130RMT (median of 10 MEPs at 130% RMT). MEP _130RMT was also a strong predictor of cTBS response (p<0.005, R ² >0.3). Head-to-head comparison against a previously studied genetic biomarker of rTMS responses (BDNF polymorphism) showed that IO based predictors had a superior performance in explaining more response variability. Thus, IO curves derived prior to cTBS administration can reliably predict cTBS-induced changes in cortical excitability. This work points toward an accessible strategy for tailoring stimulation procedures in both diagnostic and therapeutic applications of rTMS, and potentially boosting response rate to other brain stimulation approaches.