Non-invasive deep brain stimulation enhances motor learning

Mohesh Mohan/EPFL

Using a new, non-invasive brain-stimulation technique, scientists at EPFL show that it is possible to enhance the activity of deep brain structures and improve motor learning. The research opens up new ways for noninvasive treatments of brain disorders.

Video: The Hummel lab showed improvements of motor learning in older adults by noninvasive neuromodulation of a deep brain region (striatum). This is the first time in humans that deep brain structures were successfully and focally reached non-invasively. Credit: Mohesh Mohan

A growing number of neurological treatments are beginning to rely on neuromodulation, a technique that uses targeted electrical stimulation or chemical agents to change the activity of specific neurological sites in the brain and body in general. Stimulating the brain for neuromodulation is also crucial for advancing our understanding of how it works. By directly influencing neuronal activity and circuits, researchers can investigate causal relationships between brain activity and behavior and unveil the mysteries of neuroplasticity, learning and memory in the context of various neurological and psychiatric disorders.

Technologies for non-invasive deep-brain stimulation promise novel therapeutic interventions for core neurological and psychiatric disorders like stroke, dementia, and traumatic brain injury. But even though deep brain structures are important for treating these disorders, traditional non-invasive brain stimulation methods can’t reach them without affecting the entire overlying cortex. This means that targeting core deep brain structures for interventional purposes is currently limited only to invasive techniques.

Now, scientists led by Friedhelm Hummel, who holds the Defitchech Chair of Clinical Neuroengineering atEPFL’s School of Life Sciences have implemented a novel technique called “transcranial temporal interference electrical stimulation” (tTIS) for non-invasive neuromodulation in humans to successfully target deep structures and enhance motor skill learning in healthy older subjects. The research is published in Nature Neuroscience by first authors Maximilian J. Wessel and Elena Beanato.

The scientists combined computational modeling, fMRI studies, and behavioral evaluations, to show, for the first time, that tTIS can specifically modulate an area deep within the brain called the striatum, which is a central processing hub of motor control and learning. Unlike other deep neuromodulation techniques, tTIS was able to reach the striatum without the need for invasive procedures.

“We focused on learning, as it is critical for continuously acquiring skills during life and for recovering from motor disabilities,” say Wessel and Beanato.

The scientists applied bursts of electrical pulses in a specific pattern (“theta burst”) to modulate brain activity in human subjects. This pattern has been shown to induce changes in neural excitability and neuroplastic properties with large potential as an application for cognitive enhancement and neurorehabilitation.

The theta-burst tTIS revealed increased activity in the striatum and its associated motor network. Interestingly, healthy older participants, whose natural learning skills are typically lower than younger individuals, showed a larger effect of the stimulation with a more pronounced enhancement in motor performance. This suggests that tTIS could especially improve learning in populations with impaired motor functions.

“It is the first time, in humans, that the possibility to neuromodulate non-invasively and focally the striatum and enhance respective behavior is demonstrated,” says Hummel.

The non-invasive nature of tTIS and its ability to selectively modulate deep brain structures without affecting the overlying cortex or other functional areas make it an exciting new tool in neuroscience research. It also lays the foundation for innovative non-invasive treatment strategies for brain disorders where deep striatal structures play a key role, such as dementia, addiction, or stroke.

Other contributors
University Hospital Würzburg, Université Catholique de Louvain, ETH Zurich, Neuroscience Center Zurich, University of Surrey, Sion Hospital (Switzerland), Imperial College London, IT’IS Foundation, University of Geneva Medical School, UK Dementia Research Institute


Defitech Foundation
Bertarelli Foundation (Catalyst program)
Novartis Research Foundation (FreeNovation)
Wyss Center for Bio and Neuroengineering
PHRT (ETH Domain)
University Hospital of Würzburg (IZKF)


Maximilian J. Wessel, Elena Beanato, Traian Popa, Fabienne Windel, Pierre Vassiliadis, Pauline Menoud, Valeriia Beliaeva, Ines R. Violante, Hedjoudje Abderrahmane, Patrycja Dzialecka, Chang-Hyun Park, Pablo Maceira-Elvira, Takuya Morishita, Antonino Cassara, Melanie Steiner, Nir Grossman, Esra Neufeld, Friedhelm C. Hummel. Noninvasive theta burst stimulation of the human striatum enhances striatal activity and motor skill learning. Nature Neuroscience 19 October 2023. DOI: 10.1038/s41593-023-01457-7