Three novel methods for determining motor threshold with transcranial magnetic stimulation outperform conventional procedures.

Thresholding of neural responses is central to many applications of transcranial magnetic stimulation (TMS), but the stochastic aspect of neuronal activity and motor evoked potentials (MEPs) challenges thresholding methods. We analyzed existing methods for obtaining TMS motor threshold and their variations, introduced new methods from other fields, and compared their accuracy and speed. Approach. In addition to existing relative-frequency methods, such as the five-out-of-ten method, we examined adaptive methods based on a probabilistic motor threshold model using maximum-likelihood (ML) or maximum a-posteriori (MAP) estimation. To improve the performance of these adaptive estimation methods, we explored variations in the estimation procedure and inclusion of population-level prior information. We adapted a Bayesian estimation method which iteratively incorporated information of the TMS responses into the probability density function. A family of non-parametric stochastic root-finding methods with different convergence criteria and stepping rules were explored as well. The performance of the thresholding methods was evaluated with an independent stochastic MEP model. Main Results. The conventional relative-frequency methods required a large number of stimuli, were inherently biased on the population level, and had wide error distributions for individual subjects. The parametric estimation methods obtained the thresholds much faster and their accuracy depended on the estimation method, with performance significantly improved when population-level prior information was included. Stochastic root-finding methods were comparable to adaptive estimation methods but were much simpler to implement and did not rely on a potentially inaccurate underlying estimation model. Significance. Two-parameter MAP estimation, Bayesian estimation, and stochastic root-finding methods have better error convergence compared to conventional single-parameter ML estimation, and all these methods require significantly fewer TMS pulses for accurate estimation than conventional relative-frequency methods. Stochastic root-finding appears particularly attractive due to the low computational requirements, simplicity of the algorithmic implementation, and independence from potential model flaws in the parametric estimators.