Physical mechanisms of emerging neuromodulation modalities.

Abstract

One of the ultimate goals of neurostimulation field is to design materials, devices and systems that can simultaneously achieve safe, effective and tether-free operation. For that, understanding the working mechanisms and potential applicability of neurostimulation techniques is important to develop noninvasive, enhanced, and multi-modal control of neural activity. Here, we review direct and transduction-based neurostimulation techniques by discussing their interaction mechanisms with neurons via electrical, mechanical, and thermal means. We show how each technique targets modulation of specific ion channels (e.g. voltage-gated, mechanosensitive, heat-sensitive) by exploiting fundamental wave properties (e.g. interference) or engineering nanomaterial-based systems for efficient energy transduction. Overall, our review provides a detailed mechanistic understanding of neurostimulation techniques together with their applications to<i>in vitro, in vivo</i>, and translational studies to guide the researchers toward developing more advanced systems in terms of noninvasiveness, spatiotemporal resolution, and clinical applicability.