A systematic review of preclinical and clinical transcranial ultrasound neuromodulation and opportunities for functional connectomics

Low-intensity transcranial ultrasound has surged forward as a non-invasive and disruptive tool for neuromodulation with applications in basic neuroscience research and the treatment of neurological and psychiatric conditions. To provide a comprehensive overview and update of preclinical and clinical transcranial low intensity ultrasound for neuromodulation and emphasize the emerging role of functional brain mapping to guide, better understand, and predict responses. A systematic review was conducted by searching the Web of Science and Scopus databases for studies on transcranial ultrasound neuromodulation, both in humans and animals. 187 relevant studies were identified and reviewed, including 116 preclinical and 71 clinical reports with subjects belonging to diverse cohorts. Milestones of ultrasound neuromodulation are described within an overview of the broader landscape. General neural readouts and outcome measures are discussed, potential confounds are noted, and the emerging use of functional magnetic resonance imaging is highlighted. Ultrasound neuromodulation has emerged as a powerful tool to study and treat a range of conditions and its combination with various neural readouts has significantly advanced this platform. In particular, the use of functional magnetic resonance imaging has yielded exciting inferences into ultrasound neuromodulation and has the potential to advance our understanding of brain function, neuromodulatory mechanisms, and ultimately clinical outcomes. It is anticipated that these preclinical and clinical trials are the first of many; that transcranial low intensity focused ultrasound, particularly in combination with functional magnetic resonance imaging, has the potential to enhance treatment for a spectrum of neurological conditions.