Transcranial Temporal Interference Stimulation Enables Focal Deep Brain Neuromodulation in Humans
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Deep brain stimulation currently relies on invasive surgical procedures, limiting its widespread application for treating neurological and psychiatric disorders, but a new approach offers a non-invasive alternative. Pierre Vassiliadis, Elena Beanato, Maximilian J. Wessel, and Friedhelm C. Hummel, from institutions including École Polytechnique Fédérale de Lausanne and University Hospital Würzburg, demonstrate the potential of transcranial Temporal Interference Stimulation (tTIS) to overcome the limitations of conventional brain stimulation techniques. This method successfully delivers focused electrical stimulation to deep brain regions, such as the hippocampus and striatum, without requiring surgery, a feat previously considered impossible due to the inherent challenges of achieving both depth and precision.
The team’s work represents a significant step forward, opening new avenues for fundamental neuroscience research and the development of innovative treatments for a range of neuropsychiatric conditions, and promises to reshape our understanding of brain stimulation and its therapeutic possibilities. Researchers are actively investigating methods to improve the spatial precision of stimulation, including innovative electrode designs and stimulation patterns. A key trend involves combining NIBS with neuroimaging techniques like fMRI and EEG to monitor brain activity during stimulation and potentially guide adaptive protocols, allowing scientists to observe network-level effects and understand how NIBS influences large-scale brain circuits. The research highlights several key areas of investigation, including optimizing TI parameters such as frequency selection, electrode configuration, and waveform design. A significant focus lies on developing personalized and adaptive stimulation protocols, utilizing real-time monitoring and closed-loop systems to adjust parameters based on individual brain states. Conventional techniques struggle to selectively target deep brain regions without affecting superficial cortical areas.
The team engineered tTIS by adapting principles from peripheral nerve stimulation and validating the concept through computational modeling and animal experiments before translating it to human studies. The technique applies pairs of high-frequency alternating currents to the scalp, creating an interference pattern that generates a low-frequency envelope, proposed to selectively modulate activity in targeted deep brain regions, minimizing off-target stimulation. Experiments demonstrate the ability to reach deep brain structures without significantly affecting overlying cortical regions, a key innovation addressing the limitations of conventional non-invasive brain stimulation. This approach offers a new avenue for investigating the function of subcortical regions and developing targeted interventions for neurological and psychiatric disorders, including Alzheimer’s disease, Parkinson’s disease, and obsessive-compulsive disorder. This work demonstrates the ability to focally modulate activity in deep brain regions, such as the hippocampus and striatum, without the need for surgery. Initial validation through computational modeling and rodent studies paved the way for successful translation to human subjects. Experiments confirm the feasibility and safety of tTIS, showing it can modulate cortical regions similarly to established transcranial alternating current stimulation techniques, offering a safe technology with the potential to selectively modulate deep brain activity and induce relevant behavioral changes. Data shows tTIS can achieve focal neuronal activation in the hippocampus, without affecting the contralateral hippocampus or overlying cortex, as demonstrated in preclinical studies. Computational modeling reveals that tTIS generates electric fields with distinct characteristics compared to high-frequency carrier fields. Conventional non-invasive brain stimulation techniques struggle to reach structures deep within the brain, often requiring surgical implantation of electrodes. This team has successfully translated transcranial temporal interference stimulation (tTIS), previously validated through computational modelling and animal studies, to human participants, enabling targeted stimulation of areas like the hippocampus and striatum, opening new avenues for investigating the causal role of deep brain structures in both healthy cognitive function and neuropsychiatric disorders. By allowing researchers to perturb specific deep brain regions without the confounding effects of cortical co-activation seen in other techniques, tTIS offers a more precise tool for understanding complex neural networks. The method’s ability to spatially steer and selectively target stimulation based on timing further enhances its potential for detailed investigation. Further research is needed to fully understand the underlying mechanisms of tTIS and to optimize stimulation parameters, such as intensity and focality, promising to advance both fundamental neuroscience and the development of novel interventions for neurological and psychiatric conditions. 👉 More information 🗞 Temporal interference stimulation for deep brain neuromodulation in humans 🧠 ArXiv: https://arxiv.org/abs/2512.14359 Tags: