Data Sheet 1_External trigeminal nerve stimulation for neuropsychiatric disorders: mechanisms, efficacy, and future directions.pdf

External trigeminal nerve stimulation (eTNS) is an emerging noninvasive neuromodulation technique that modulates brain network activity implicated in multiple neuropsychiatric disorders through the application of low-intensity electrical currents to the frontal branches of the trigeminal nerve. Based on a search of major biomedical databases, we narratively synthesize clinical and mechanistic studies of eTNS across neurological and psychiatric indications. Current clinical and neurophysiological studies suggest clinically meaningful benefits of eTNS in attention-deficit/hyperactivity disorder (ADHD) and migraine, show promising adjunctive efficacy in epilepsy, and may offer emerging therapeutic potential for conditions such as depression, anxiety, and disorders of consciousness. Although eTNS generally demonstrates a favorable safety profile, existing studies are constrained by small sample sizes, short follow-up periods, and considerable heterogeneity in stimulation parameters, and standardized clinical protocols are still lacking. Future research should prioritize multicenter randomized controlled trials, parameter optimization, and biomarker-guided personalized modulation. By integrating neurophysiological, neuroimaging, and behavioral metrics, such efforts may advance eTNS toward a precisely controlled, closed-loop neuromodulation system. This narrative review provides a concept-driven synthesis of the anatomical foundations, putative mechanisms, and clinical evidence for eTNS and outlines key directions for standardization and translational research, thereby providing a reference framework for the clinical implementation of eTNS in neuropsychiatric disorders.