Mansourinezhad Paria, Mestrom R M C, Klooster Deborah C W, Sprengers Mathieu, Boon Paul A J M, Paulides Maarten M
Eindhoven University of Technology, De Rondom 70, Eindhoven, Eindhoven, 5612 AP, NETHERLANDS.
Ghent University, Ufo-building, Campus Ufo, Sint-Pietersnieuwstraat 33, Ghent, Flanders, 9000, BELGIUM.
J Neural Eng. 2025 Sep 9. doi: 10.1088/1741-2552/ae0524.
Transcranial temporal interference stimulation (tTIS) has recently emerged as a non-invasive neuromodulation method aimed at reaching deeper brain regions than conventional techniques. However, many questions about its effects remain, requiring further experimental studies. This review consolidates the experimental literature on tTIS's effects in the human brain, clarifies existing evidence, identifies knowledge gaps, and proposes future research directions to evaluate its potential. A systematic literature search was performed in PubMed, Web of Science, and Scopus for studies published up to January 27, 2025. Eligible studies applied tTIS to the human brain and examined its effects on neural, behavioral, and clinical outcomes. Of 127 publications screened, 18 met the inclusion criteria. Studies were analyzed for design, stimulation target, parameters, control conditions, and outcome measures. Included studies exhibited low bias or minor concerns using the Cochrane RoB2 and ROBINS-I tools. Ten studies targeted cortical regions (motor, occipito-parietal, fronto-parietal), and eight probed subcortical sites (striatum, hippocampus, globus pallidus, caudate). Motor-cortex tTIS enhanced motor-network connectivity, though the effect was similar to that of tDCS. Beta-band stimulation envelopes (20 Hz) promoted learning-related plasticity, while gamma-band envelopes (70 Hz) yielded immediate performance improvements. Occipito-parietal tTIS did not modulate alpha power. Preliminary deep-target findings are promising: 5 Hz hippocampal tTIS improved episodic recall, 100 Hz striatal tTIS enhanced motor learning in older adults, and 100 Hz hippocampal-entorhinal tTIS aided spatial navigation. Two fMRI studies confirmed network-specific modulation, although one raised concerns about using a fixed montage between individuals. Clinical evidence remains limited, with two Parkinson's pilots and one epilepsy study showing short-term benefits. Overall, tTIS shows potential to modulate human brain activity and behaviour. However, current evidence is preliminary and predominantly focused on cortical rather than deep targets. Larger, well-controlled studies are needed to reliably determine whether tTIS can effectively engage subcortical structures and provide meaningful clinical benefits.
经颅颞叶干扰刺激（tTIS）最近已成为一种非侵入性神经调节方法，旨在比传统技术更深入地到达脑区。然而，关于其效果仍有许多问题，需要进一步的实验研究。本综述整合了关于tTIS对人脑影响的实验文献，阐明现有证据，识别知识空白，并提出未来研究方向以评估其潜力。在PubMed、科学网和Scopus中进行了系统的文献检索，以查找截至2025年1月27日发表的研究。符合条件的研究将tTIS应用于人脑，并检查其对神经、行为和临床结果的影响。在筛选的127篇出版物中，18篇符合纳入标准。对研究的设计、刺激靶点、参数、对照条件和结果测量进行了分析。使用Cochrane RoB2和ROBINS-I工具分析的纳入研究显示偏倚较低或仅有轻微问题。十项研究针对皮质区域（运动、枕顶叶、额顶叶），八项研究探索了皮质下部位（纹状体、海马体、苍白球、尾状核）。运动皮质tTIS增强了运动网络连接性，尽管其效果与经颅直流电刺激（tDCS）相似。β波段刺激包络（20赫兹）促进了与学习相关的可塑性，而γ波段包络（70赫兹）使即时表现得到改善。枕顶叶tTIS未调节α波功率。初步的深部靶点研究结果很有前景：5赫兹海马体tTIS改善了情景记忆，100赫兹纹状体tTIS增强了老年人的运动学习能力，100赫兹海马体-内嗅皮质tTIS有助于空间导航。两项功能磁共振成像（fMRI）研究证实了网络特异性调节，尽管其中一项研究对在个体之间使用固定电极排列提出了担忧。临床证据仍然有限，两项帕金森病试点研究和一项癫痫研究显示了短期益处。总体而言，tTIS显示出调节人脑活动和行为的潜力。然而，目前的证据是初步的，且主要集中在皮质而非深部靶点。需要进行更大规模、严格控制的研究，以可靠地确定tTIS是否能有效作用于皮质下结构并提供有意义的临床益处。
