Exploring the Dose-Dependency of After-Effects: A Computational Model for Theta-Burst Transcranial Magnetic Stimulation

Transcranial magnetic stimulation (TMS) is a non-invasive neurostimulation and neuromodulation technique that is widely applied in brain research and clinical applications. However, the optimal parameters of neuromodulating TMS protocols describing the specific rhythms, such as number of pulses, frequency, and stimulation strength, are widely unknown. Improving previous rather limited and ad-hoc models, we aimed to investigate the dose-dependency of theta-burst stimulation (TBS) protocols with a more elaborate but still parsimonious quantitative model representing the non-linearities of the mechanisms of synaptic plasticity and metaplasticity during repetitive magnetic stimulation. Our model, which considers the interaction between facilitatory and inhibitory processes, successfully reproduced results from TBS experiments and provide testable predictions for prolonged TBS protocols. Moreover, we suggested that the activation of kinases and phosphatases could be potential candidates for later TMS modelling research. Although this model still simplifies the complex dynamics of cellular and molecular processes, it offers a starting basis for future studies to incorporate more intricate mechanisms. By further refining our understanding of the underlying mechanisms and improving the accuracy of prediction models, we can advance the efficacy and clinical application of TBS protocols in various neurological and psychiatric conditions.