Noninvasive stimulation technique modulates deep brain structures

In a groundbreaking study, scientists have successfully used a new noninvasive brain stimulation technique to modulate deep brain activity, leading to enhanced motor learning, especially in older adults. This finding, published in Nature Neuroscience, has significant implications for understanding brain function and could pave the way for new treatments for various brain disorders.

Before this study, scientists primarily used invasive methods or less targeted noninvasive techniques to study deep brain structures like the striatum, crucial for motor learning. These traditional methods either required surgical procedures or could not specifically target deeper brain regions without affecting the areas above them. Recognizing these limitations, researchers sought a noninvasive yet precise way to stimulate these deep-seated brain areas to better understand and potentially improve motor learning processes.

“Mental disorders impose a personal and financial burden on society, affecting patients and their families, and costing nearly 1 trillion Euros annually in the EU,” explained study author Friedhelm Hummel, who holds the Defitchech Chair of Clinical Neuroengineering at EPFL’s School of Life Sciences.

“Developing effective therapies for these diseases remains challenging due to the complexity of the brain and mental symptoms. Current treatment approaches, for example, psychotropic drugs, are not based on recent advances in neuroscience and neurotechnology, have limited efficacy, and come with side effects. A particular concern is symptoms that resist currently available treatment approaches, which occur in up to half of the patients with a major mental disorder such as schizophrenia, stroke, dementia, addiction or depression.”

“Addressing this unmet need requires a fresh perspective and innovative solutions,” Hummel said. “These disorders and the respective symptoms are represented by pathological brain network interactions with core structures of these networks deep in the brain such as the striatum or the hippocampus. Thus, these structures are potentially promising targets for interventional strategies based on neuromodulation.”

“Current neurotechnology allows us to target these areas only invasively due to limitations of current non-invasive approaches, like TMS. However, invasive approaches bare several risks of side-effects and suffer from acceptability especially in mental health disorders. Thus, it is critically important to develop novel non—invasive neurotechnologies to target specifically these deep brain regions to pave the way to novel treatment strategies for these unmet symptoms in mental health disorders.”

“The present concept of transcranial temporal interference electrical stimulation (tTIS) might allow us to address this mentioned gap and shortcomings, therefore we addressed this topic in a series of studies,” Hummel told PsyPost. “To this end, we selected as a target the striatum as it is a core area involved in the pathophysiology of and recovery from several neurological and psychiatric disorders, such as stroke, addiction, anxiety, depression or neurodegenerative disorders like the Parkinson spectrum.”

The study involved 45 healthy participants, split into two experiments. The first experiment included 15 young adults who underwent functional magnetic resonance imaging (fMRI) while performing a sequential finger tapping task. The researchers used tTIS during this task to modulate striatal activity, utilizing a sequence of electrical pulses, known as “theta burst,” to alter brain activity in their human participants.

In the second experiment, the research team included both older (average age 66 years) and younger adults (average age 26 years). They performed similar tasks under tTIS, but with longer task blocks and shorter overall training duration, to test if the technique’s effects were consistent across different ages and training protocols.

In the first experiment, the researchers found that the brain stimulation led to increased activity in the putamen, a region of the brain involved in motor learning, during the finger-tapping task. This effect was more pronounced in the putamen than in another part of the striatum, the caudate. Notably, the increased activity in the putamen was associated with improved performance in the motor task. Furthermore, they observed that the stimulation influenced the brain’s motor network, including regions such as the thalamus and supplementary motor area.

“There is now first proof of concept that deep brain structures can be neuromodulated, i.e. brain activity changed and behavior enhanced in a non-invasive fashion,” Hummel explained. “This might pave the way to completely novel interventional strategies for mental health disorders where deep brain structures, such as the striatum or the hippocampus play a core role, like in Alzheimer’s disease, stroke, traumatic brain injury, depression, addiction, anxiety or in movement disorders. Furthermore, it provides means to better understand brain functioning and especially the role of deep brain structures in humans.”

In the second experiment, the impact of brain stimulation was particularly significant among older adults. The older group showed a more substantial improvement in the motor task during brain stimulation compared to younger participants. This finding suggests that the technique could be especially beneficial for older individuals, who typically have a reduced capacity for motor learning.

“The effects we found in healthy older were surprisingly strong,” Hummel told PsyPost. “The stimulation during a short training period of less than 30 minutes led to an improvement of more than 30% compared to the placebo condition.”

However, it’s important to note some caveats. The technique’s success depended on the presence of task-related brain activity. In other words, the stimulation didn’t induce changes during rest periods. This specificity implies that the brain stimulation works best in conjunction with active learning processes. Moreover, the study primarily focused on short-term effects, and long-term impacts remain unclear.

“There are still several open questions to address in upcoming studies, such as better understanding of the underlying mechanism, personalization of the stimulation to the individual, better topographic resolution of the stimulation, biomarkers that allow to predict the treatment response, most importantly clinical translation (in this regard studies are ongoing),” Hummel said.

The study, “Noninvasive theta-burst stimulation of the human striatum enhances striatal activity and motor skill learning“, was authored by 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 M. Cassara, Melanie Steiner, Nir Grossman, Esra Neufeld, and Friedhelm C. Hummel.