Mechanisms and Applications of Transcranial Ultrasound Stimulation in Neurological Disorders and Psychiatric Conditions.

Abstract

Transcranial ultrasound stimulation (TUS) is an emerging non-invasive neuromodulation strategy with high spatial precision and the ability to target both cortical and deep brain regions. This review summarizes recent progress in low-intensity, non-thermal TUS in representative neurological and psychiatric disorders, including Parkinson's disease, Alzheimer's disease, epilepsy, ischemic stroke, depression, anxiety disorders, and schizophrenia. Current preclinical evidence suggests that TUS may alleviate disease-related pathological and functional abnormalities by regulating neurotransmitter release, enhancing neurotrophic factor expression, promoting synaptic plasticity, modulating neural oscillations and circuit connectivity, improving cerebral blood flow, suppressing neuroinflammation and oxidative stress, and facilitating blood-brain barrier opening when combined with microbubbles. These biological effects may act across molecular, cellular, synaptic, circuit, and system levels, ultimately contributing to improvements in motor, cognitive, and emotional dysfunction. This review also discusses the marked heterogeneity of acoustic parameters in preclinical and clinical studies, as well as current evidence on safety. With further standardization of stimulation parameters, deeper mechanistic understanding, and stronger clinical evidence, TUS may develop into a safe, precise, and clinically translatable neuromodulation strategy.