Noninvasive neuromodulation with ultrasound? A continuum mechanics hypothesis

Deep brain stimulation and vagal nerve stimulation are therapeutically effective in treating some neurological diseases and psychiatric disorders. Optogenetic-based neurostimulation approaches are capable of activating individual synapses and yield the highest spatial control over brain circuit activity. Both electrical and light-based neurostimulation methods require intrusive procedures such as surgical implantation of electrodes or photon-emitting devices. Transcranial magnetic stimulation has also shown therapeutic effectiveness and represents a recent paradigm shift towards implementing less invasive brain stimulation methods. Magnetic-based stimulation, however, has a limited focusing capacity and lacks brain penetration power. Because ultrasound can be noninvasively transmitted through the skull to targeted deep brain circuits, it may offer alternative approaches to currently employed neuromodulation techniques. Encouraging this idea, literature spanning more than half a century indicates that ultrasound can modulate neuronal activity. In order to provide a comprehensive overview of potential mechanisms underlying the actions of ultrasound on neuronal excitability, here, I propose the continuum mechanics hypothesis of ultrasonic neuromodulation in which ultrasound produces effects on viscoelastic neurons and their surrounding fluid environments to alter membrane conductance. While further studies are required to test this hypothesis, experimental data indicate ultrasound represents a promising platform for developing future therapeutic neuromodulation approaches.