Virtual Neurostimulation: Computer-aided transcranial magnetic stimulation (TMS) guidance and dosimetry

Transcranial magnetic stimulation (TMS) is a noninvasive treatment that uses electromagnetic pulses to stimulate nerve cells. For decades, it is attempted to use high frequency trains of TMS pulses (repetitive or rTMS) to improve symptoms of neurological or mental health disorders. Nowadays TMS is mainly used to treat depression. It has proven to be successful in helping patients who don’t respond to antidepressant medication. In 2008 the Food and Drug Administration (FDA) approved TMS for this purpose in the US, and many other countries followed, including the Netherlands where health insurances now reimburse rTMS treatment. Furthermore, TMS is used increasingly to diagnose diseases of and damage to the central and peripheral nervous system. TMS therapies, diagnostic use and research applications are plagued by poor reproducibility and suffer from the large variability in responses and outcomes. We propose that computer models of induced electric fields and initial implementations of models describing the interaction between induced currents and neuronal signaling in the stimulated tissue could help improve the efficacy of TMS treatment and aid many other applications of TMS. The work presented in thesis involves a multimodal approach validating the models that we developed for TMS-induced currents using in-vivo experiments. The focus is on comparing the predicted TMS-induced electrical field intensity and spatial distribution from numerical computer models, combined with models of electric currents and their interaction with neurons in the cortical layers, with measurable physiological responses. For this purpose, we developed a sophisticated framework capable of producing subject-specific 3D models of TMS effects. This thesis not only develops such models but also validates them empirically in several experiments mainly on human volunteers (and one on rodents), which is an effort seldom made by other groups, who mainly report modeling results without much empirical validation. The technical advances that were needed for this empirical work are also presented (chapter 6). Finally, we also present a first application of my modeling work, in the form of a miniature cooled rodent TMS coil, which was constructed based on my initial models and is useful in translational TMS research involving the treatment of stroke and is now brought to market by a company that was involved in the work presented here.