Neuromodulation effects of low-intensity transcranial focused ultrasound in human, a systematic review focusing on motor and sensory functions

Background Low-intensity transcranial focused ultrasound (tFUS) has emerged as a novel non-invasive brain stimulation technique with therapeutic potential for various neurological conditions. However, its parameter-dependent bimodal neuromodulatory effects remain to be fully elucidated. Objective This study aims to review the evidence on tFUS-induced neuromodulation in humans, particularly its effects on motor and sensory functions, to identify specific stimulation parameters associated with excitatory and inhibitory outcomes, thereby informing future clinical applications. Methods A systematic review was conducted using Web of Science and PubMed, including primary interventional human studies on tFUS and neuromodulation published up to December 2024. Eligible studies comprised single-arm trials, quasi-experimental studies, and randomized controlled trials focusing on excitatory and inhibitory effects and specific ultrasound parameters. Results The findings summarize the current evidence on tFUS-induced neuromodulation of motor and sensory functions. Both excitatory and inhibitory effects were observed, particularly in the primary motor cortex, primary somatosensory cortex, thalamus, insula, and dorsal cingulate gyrus. These effects appear to be modifiable through specific stimulation parameters. Conclusions tFUS demonstrates both online/ offline excitatory/ inhibitory effects on sensory and motor brain regions under specific stimulation conditions. It holds promise as a potential therapeutic strategy for managing motor and sensory dysfunctions, such as stroke and chronic pain. However, the underlying mechanisms remain incompletely understood, necessitating further investigation.