A Review of Ultrasound Neuromodulation Technologies.

The invasiveness of neuromodulation technologies that require surgical implantation (e.g., electrical and optical stimulation) may limit their clinical application. Thus, alternative technologies that offer similar benefits without surgery are of paramount importance in the field of neuromodulation. Low-intensity ultrasound is an emerging modality for neural stimulation as ultrasound can be focused in deep tissues with millimeter resolution. Transcranial focused ultrasound stimulation (tFUS) has already been demonstrated in a wide range of animals and even humans at different sonication frequencies (mostly in the sub-MHz range due to the presence of the skull). This article first provides some fundamental knowledge in ultrasound, and then reviews various examples of successful tFUS experiments in animals and humans using different stimulation patterns, as well as available tFUS technologies for generating, focusing, and steering ultrasound beams in neural tissues. In particular, phased array technologies for the ultrasound stimulation application are discussed with an emphasis on the design, fabrication, and integration of ultrasound transducer arrays as well as the design and development of phased array electronics with beamformer and high-voltage driver circuitry. The challenges in tFUS, such as its underlying mechanism, indirect auditory response, and skull aberration effects, are also discussed.