Abstract
Transcranial focused ultrasound (tFUS) has emerged as a promising non-invasive neuromodulation technique for disorders of consciousness (DOC). This work critically evaluates tFUS's potential, highlighting its unique ability to precisely modulate deep brain structures, particularly the thalamus, while maintaining non-invasiveness. The mechanisms of action span multiple levels, from membrane-level ion channel modulation to network-wide changes in neural connectivity. Preclinical and early clinical studies have demonstrated tFUS's potential to improve DOC outcomes. Preliminary clinical trials in both acute and chronic DOC patients have shown encouraging results, including diagnostic category shifts, improvements in behavioral responsiveness, and alterations in thalamo-cortical connectivity. However, significant challenges remain. These include optimizing stimulation parameters, addressing variability in patient responses, and ensuring long-term safety. The current evidence base is limited, necessitating larger, more rigorous investigations. Future research should focus on multicenter randomized controlled trials to comprehensively evaluate tFUS across different DOC etiologies and chronicity. Key priorities include identifying predictive biomarkers, exploring combination therapies, and addressing ethical considerations. While tFUS shows significant promise in DOC management, further investigation is crucial to refine its application and establish its definitive clinical role.