Linking Biophysical Modeling with Multimodal Brain Stimulation and Recording Technologies

Massachusetts General Hospital, Boston MA

Investigators

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Abstract

Project Summary The field of electromagnetic brain stimulation technologies is rapidly expanding. Despite the proven effi- cacy of Transcranial Magnetic Stimulation (TMS) and Transcranial Electrical Stimulation (TES) for treat- ment of neuropsychiatric conditions such as depression and obsessive-compulsive disorder, their mech- anism of action remains only partially understood. The overall challenge is that the effects of the stimu- lation take place over different spatial and temporal scales: from local neuronal circuits to global brain networks and from milliseconds to months. We have identified three major technology development chal- lenges that will be tackled to help better understand how the brain responds to the electromagnetic stimuli across multiple spatiotemporal scales. First, the currently available biophysical modeling approaches do not allow analyzing anatomically realistic neuron ensembles on the microscopic level due to computa- tional bottlenecks in the pre-existing electromagnetic solvers. Second, the stimulus delivery for TMS is mostly limited to single-channel applications where spatial shape of the “hot spot” is fixed and cannot be dynamically shaped to localize cortical functions rapidly and precisely. Third, the techniques for recording whole brain responses to electromagnetic stimuli face a trade-off between high spatial resolution achieved by concurrent TMS and functional MRI (fMRI), or high temporal resolution obtained by combin- ing TMS with electroencephalography (EEG). In Aim 1, we propose to utilize our recently developed Boundary Element Modeling (BEM) approach accelerated by Fast Multipole Method (FMM) or BEM-FMM to enable computational modeling of fully coupled complex neuronal clusters and to test the model pre- dictions with a novel combined TMS/TES experiment in humans in vivo. In Aim 2, we will continue the development of our multichannel TMS (mTMS) providing a flexible control of the stimulus shape, as well as an enhanced coil design with improved efficiency and thermal properties suitable for repetitive TMS (rTMS). In Aim 3, we will integrate our recently developed 28-channel TMS compatible RF coil array with EEG and mTMS, offering possibility to record both hemodynamic and electrophysiological responses concurrently with electronically controlled stimulation inside 3T scanner environment. We will demon- strate the capabilities of this approach by recording the responses to both voluntary and TMS-induced finger movements with high spatiotemporal resolution. The proposed technologies will guide the devel- opment of next generation precision brain stimulation approaches by providing insights into the neuronal responses across micro-, meso-, and macroscopic scales.