Tools for Improving and Understanding Transcranial Magnetic Stimulation

Abstract

Transcranial magnetic stimulation (TMS) is a non-invasive brain stimulation technique that can modulate brain activity through a time-varying magnetic field which induces an electric field in the brain. TMS has been used extensively in research and clinical applications because of its ability to non-surgically deliver suprathreshold stimulation to the brain in a safe manner. Despite the popularity of TMS, there are still major gaps in our understanding of how TMS modulates brain activity on a fundamental neuroscience level. Therefore, the TMS mechanism of action is still under investigation. Improved stimulation technology and computational tools have promise for bridging this gap in our understanding. In my dissertation, I developed new methodologies and computational models that advance the current state-of-the-art in TMS and can assist researchers in their future investigations. First, I describe a closed-loop TMS system that can deliver the stimulation based on the instantaneous brain state. This allows researchers to investigate the role of the intrinsic neural activity on the brain’s responsiveness to TMS. To further provide insights into how TMS modulates brain activity at a large brain-scale and the neuronal level, I developed a multi-scale modeling paradigm. Computational simulations have been used extensively to estimate electric fields induced in the brain by TMS, however, their results still need to be validated. To this end, in the second study here, I utilize analytical solutions to evaluate these numerical simulations. After confirming the accuracy of the electric field models, I incorporated multi-scale modeling to further investigate how the externally induced electric fields alter the behavior of neurons and their subcellular activity. The subcellular modeling of neurons allows researchers to study the lasting effects of TMS in neurons in a sophisticated multi-scale model for the first time. In summary, the tools developed in my PhD can facilitate answering long-lasting questions about the TMS mechanism of action. This, in turn, will enable developing more effective TMS protocols/equipment which can lead to improved clinical outcomes in the treatment of psychiatric and neurological disorders with TMS.