MedicineEngineering

Arnau Diez-Clos, Simona Losacco, A. F. Schrunder, Stéphane Emery, F. Hummel, Mahsa Shoaran, Komail M. H. Badami

2026.4.30IEEE Open Journal of Engineering in Medicine and Biology

DOI: 10.1109/ojemb.2026.3689259

Abstract

Noninvasive neuromodulation methods are promising for treating neurological diseases, but generally have limited ability to selectively target deep brain structures such as the basal ganglia or hippocampus. Transcranial temporal Interference Stimulation (tTIS) overcomes this limitation by superimposing high-frequency electric fields to create low-frequency amplitude-modulated envelopes that can preferentially target deep brain structures. This review explores the operation principles and recent advances of tTIS aimed at improving its spatial accuracy and versatility. Additionally, we analyze the key aspects of tTIS system design, including waveform generation, high-voltage-compliant output stage, and real-time charge balancing, which collectively enable safe and efficient stimulation delivery. We further discuss key challenges such as safety, standardization, and long-term efficacy, and outline future directions toward personalized tTIS.

Citation format

DIEZ-CLOS, Arnau, et al. Transcranial temporal interference stimulation: A brief review of architectures, circuits, and application challenges. IEEE Open Journal of Engineering in Medicine and Biology, 2026, 7: 180–186.