Hitting the Target with Non-Invasive Deep Brain Stimulation: Potential Therapy for Addiction, Depression and OCD

Neurological disorders, such as addiction, depression, and obsessive-compulsive disorder (OCD), affect millions of people worldwide and are often characterized by complex pathologies involving multiple brain regions and circuits. These conditions are notoriously difficult to treat due to the complex and poorly understood nature of brain functions and the difficulty of delivering therapies to deep brain structures without invasive procedures.

In the rapidly evolving field of neuroscience, non-invasive brain stimulation offers new hope for understanding and treating a myriad of neurological and psychiatric disorders without surgery or implants. The researchers, led by Friedhelm Hummel, Defitchech Chair of Clinical Neuroengineering at EPFL’s Faculty of Life Sciences, and postdoctoral fellow Pierre Vassiliadis, are pioneering a new approach in the field, opening up frontiers in the treatment of illnesses such as drug addiction and depression.

Their research, taking advantage of electrical stimulation by transcranial temporal interference (tTIS), specifically targets the deep regions of the brain which are the control centers of several important cognitive functions and involved in different neurological and psychiatric pathologies. The research, published in Human behaviorhighlights the interdisciplinary approach that integrates medicine, neuroscience, computer science and engineering to improve our understanding of the brain and develop potentially revolutionary therapies.

“Invasive deep brain stimulation (DBS) has already been successfully applied to the deepest neural control centers in order to curb addiction and treat Parkinson’s disease, OCD or depression,” explains Hummel. “The main difference with our approach is that it is non-invasive, meaning we use low-level electrical stimulation on the scalp to target these regions.”

The paper’s lead author, Vassiliadis, a physician with a joint doctorate, describes tTIS as using two pairs of electrodes attached to the scalp to apply weak electric fields inside the brain.

“Until now, we could not specifically target these regions with non-invasive techniques, because the low-level electric fields would stimulate all regions between the skull and deeper areas, making any treatment ineffective. This approach allows us to select to stimulate deep regions of the brain that are important in neuropsychiatric disorders,” he explains.

This innovative technique is based on the concept of temporal interference, initially explored in rodent models, and now successfully transposed to human applications by the EPFL team. In this experiment, one pair of electrodes is set to a frequency of 2,000 Hz, while another is set to 2,080 Hz. Using detailed computer models of brain structure, the electrodes are specifically positioned on the leather hair to ensure that their signals intersect in the target region.

This is when the magic of interference happens: the slight frequency disparity of 80 Hz between the two currents becomes the effective stimulation frequency within the target area. The brilliance of this method lies in its selectivity; high baseline frequencies (e.g. 2000 Hz) do not directly stimulate neuronal activity, leaving the intervening brain tissue unaffected and concentrating the effect only on the targeted region.

This latest research focuses on the human striatum, a key player in reward and reinforcement mechanisms. “We’re looking at how reinforcement learning, essentially the way we learn through rewards, can be influenced by targeting specific brain frequencies,” Vassiliadis explains. By applying stimulation to the striatum at 80 Hz, the team found that it could disrupt its normal functioning, directly affecting the learning process.

The therapeutic potential of their work is immense, particularly for pathologies such as addiction, apathy and depression, where reward mechanisms play a crucial role. “In addiction, for example, people tend to get too close to rewards. Our method could help reduce this pathological overemphasis,” underlines Vassiliadis, also a researcher at the UCLouvain Institute of Neuroscience.

Additionally, the team is exploring how different stimulation patterns can not only disrupt but also potentially improve brain function. “This first step was to prove the hypothesis that 80 Hz affected the striatum, and we did this by disrupting its functioning. Our research also shows promise in improving motor behavior and increasing activity of the striatum, especially in older adults with reduced learning abilities,” Vassiliadis said. adds.

Hummel, a neurologist by training, sees this technology as the start of a new chapter in brain stimulation, offering personalized treatment with less invasive methods. “We are investigating a non-invasive approach that would allow us to experiment and personalize deep brain stimulation treatment from the earliest stages,” he explains.

Another key advantage of tTIS is its minimal side effects. Most participants in their studies reported only mild sensations on the skin, making this a highly tolerable and patient-friendly approach.

Hummel and Vassiliadis are optimistic about the impact of their research. They envision a future in which non-invasive neuromodulation therapies could be readily available in hospitals, providing a cost-effective and broad range of treatments.