Parameter-Determined Effects: Advances in Transcranial Focused Ultrasound for Modulating Neural Excitation and Inhibition

Transcranial focused ultrasound stimulation (tFUS), an emerging non-invasive neuromodulation technique, has garnered growing attention owing to its high spatial resolution and precise targeting capability for deep brain structures. A body of evidence demonstrates that tFUS can effectively modulate neural activity in specific brain regions, inducing excitatory or inhibitory effects, and it is an important means to reshape neural functions. Ultrasound parameters are crucial in determining the transcranial ultrasound modulation effects. However, there is still controversy over which parameters can regulate neural excitability or inhibition, and there are significant differences in the parameters used in previous studies, which have limited the clinical application of transcranial ultrasound to some extent. Therefore, a systematic clarification of parameter-effect relationships is urgently needed to enable qualitative and quantitative understanding of ultrasound-induced neuromodulation, which is essential for achieving reliable and reproducible outcomes. This paper intends to review the effects of different tFUS parameters and their combinations on the excitability and inhibition of brain neural activities as well as the possible mechanisms. By integrating recent findings from both animal models and human clinical studies, we also discuss critical safety issues related to tFUS, aiming to provide a theoretical basis for future transcranial focused ultrasound modulation treatments for various neurological diseases such as stroke, Parkinson's disease, dementia, epilepsy, pain disorders, and disorders of consciousness while providing reference value for selecting tFUS treatment regimens.