Demchenko Ilya, Tailor Ishaan, Chegini Sina, Yu Haochen, Nezhad Fatemeh Gholamali, Rueda Alice, Kever Anne, Krishnan Sridhar, Datta Abhishek, Meltzer Jed A, Graham Simon J, Schweizer Tom A, Rampersad Sumientra, Boyden Edward S, Violante Ines R, Chen Robert, Lozano Andres M, Bhat Venkat
Interventional Psychiatry Program, St. Michael's Hospital - Unity Health Toronto, 193 Yonge Street, Toronto, ON M5B 1M4, Canada.
Institute of Medical Science, Temerty Faculty of Medicine, University of Toronto, 6 Queen's Park Crescent, Toronto, ON M5S 3H2, Canada.
medRxiv. 2025 May 22:2025.05.16.25327804. doi: 10.1101/2025.05.16.25327804.
Many neurological and psychiatric disorders involve dysregulation of subcortical structures. Transcranial temporal interference stimulation (tTIS) is a novel, non-invasive method developed to selectively modulate these regions and associated neural circuits.
A systematic review was conducted to evaluate human applications of tTIS (PROSPERO ID: CRD42024559678). MEDLINE, Embase, APA PsycINFO, CENTRAL, ClinicalTrials.gov, and WHO ICTRP were searched up to December 12, 2024. Studies involving human applications of tTIS were eligible. Methodological quality was appraised using the NIH and modified Oxford Centre for Evidence-Based Medicine tools.
Forty-eight records were reviewed (20 published studies, 28 ongoing trials). Of published studies, 16 single-session and 4 multi-session studies assessed safety, mechanistic outcomes, or therapeutic effects of tTIS in 820 participants. Stimulation was most commonly delivered at beta (20 Hz) or gamma (30-130 Hz) envelope frequencies. Neuroimaging studies supported target engagement of the motor cortex, basal ganglia, and hippocampus in humans, particularly when stimulation was paired with behavioural tasks. Preliminary clinical findings in small samples demonstrated acute symptom improvements in bradykinesia and tremor within 60 minutes following a single tTIS session in Parkinson's disease and essential tremor. Reported adverse events across studies were mild (e.g., tingling, itching). Emerging trials increasingly utilize multi-session protocols (2-40 sessions) and are extending tTIS to patients with neurological and psychiatric disorders, particularly epilepsy and depression.
Phase 1 studies demonstrate that tTIS is safe, well-tolerated, and can engage deep brain targets in humans. Well-controlled Phase 2 trials are needed to assess its therapeutic potential in patient populations.
许多神经和精神疾病都涉及皮层下结构的调节异常。经颅颞叶干扰刺激（tTIS）是一种新开发的非侵入性方法，用于选择性调节这些区域及相关神经回路。
进行了一项系统评价，以评估tTIS在人体中的应用（PROSPERO注册号：CRD42024559678）。检索了截至2024年12月12日的MEDLINE、Embase、APA PsycINFO、CENTRAL、ClinicalTrials.gov和WHO ICTRP。纳入涉及tTIS在人体应用的研究。使用美国国立卫生研究院（NIH）和改良的牛津循证医学中心工具评估方法学质量。
共审查了48条记录（20项已发表研究，28项正在进行的试验）。在已发表的研究中，16项单疗程和4项多疗程研究评估了tTIS对820名参与者的安全性、机制结果或治疗效果。刺激最常以β（20Hz）或γ（30 - 130Hz）包络频率进行。神经影像学研究支持tTIS在人体中对运动皮层、基底神经节和海马体的靶向作用，特别是当刺激与行为任务配对时。小样本的初步临床研究表明，在帕金森病和特发性震颤患者中，单次tTIS治疗后60分钟内，运动迟缓及震颤的急性症状有所改善。各研究报告的不良事件均较轻微（如刺痛、瘙痒）。正在进行的试验越来越多地采用多疗程方案（2 - 40个疗程），并将tTIS扩展至神经和精神疾病患者，尤其是癫痫和抑郁症患者。
1期研究表明，tTIS在人体中是安全的、耐受性良好的，并且可以作用于深部脑靶点。需要进行严格对照的2期试验来评估其在患者群体中的治疗潜力。
