Efficient Gaussian process-based motor hotspot hunting with concurrent optimization of TMS coil location and...

Transcranial magnetic stimulation (TMS) is a widely used non-invasive brain stimulation technique in neuroscience research and clinical applications. TMS-based motor hotspot hunting describes the process of identifying the optimal scalp location to elicit robust and reliable motor responses. It is critical to ensure reproducibility of TMS parameters, as well as to determine safe and precise stimulation intensities in both healthy participants and patients. Typically, this process targets motor responses in contralateral short hand muscles. However, hotspot hunting remains challenging due to the vast parameter space and time constraints. To address this, we present an approach that concurrently optimizes both spatial and angular TMS parameters for hotspot hunting using Gaussian processes and Bayesian optimization. We systematically evaluated five state-of-the-art acquisition functions on electromyographic TMS data from eight healthy individuals enhanced by simulated data from generative models. Our results consistently demonstrate that optimizing spatial and angular TMS parameters simultaneously enhances the efficacy and spatial precision of hotspot hunting. Furthermore, we provide mechanistic insights into the acquisition function behavior and the impact of coil rotation constraints, revealing critical limitations in current hotspot-hunting strategies. Specifically, we show that arbitrary constraints on coil rotation angle are suboptimal, as they reduce flexibility and fail to account for individual variability. We further demonstrate that acquisition functions differ in sampling strategies and performance. Functions overly emphasizing exploitation tend to converge prematurely to local optima, whereas those balancing exploration and exploitation-particularly Thompson sampling-achieve superior performance. These findings highlight the importance of acquisition function selection and the necessity of removing restrictive coil rotation constraints for effective hotspot hunting. Our work advances TMS-based hotspot identification, potentially reducing participant burden and improving safety in both research and clinical applications beyond the motor cortex.