Advanced non-invasive brain neuromodulation: a comprehensive review of electric, magnetic, ultrasonic, and optical modalities.

Non-invasive brain neuromodulation has emerged as a transformative frontier in neuroscience and clinical medicine, offering the ability to modulate neuronal excitability and network connectivity without the risks associated with surgical intervention. As the neurological and psychiatric disorders increase, the development of non-invasive technologies has accelerated and moved from basic physiological exploration to advanced therapeutic applications. This review provides a systematic analysis of the four non-invasive modalities of transcranial magnetic stimulation, transcranial electrical stimulation, transcranial ultrasound stimulation, and transcranial photobiomodulation. This review covers the principles, methods, clinical applications, and dosimetry of the four modalities as well as their current trends toward multi-modal and closed-loop systems. By integrating neuromodulation with real-time neuroimaging or electrophysiological monitoring, we can deliver personalized and state-dependent stimulation that adapts to the individual brain state. We also address the integration of deep learning and artificial intelligence in optimizing stimulation parameters to improve therapeutic efficacy. By synthesizing recent breakthroughs across diverse modalities, this review can provide a strategy for the next-generation brain neuromodulation, emphasizing higher precision, deeper penetration, and personalized clinical interventions.