Advancement of deep brain stimulation could improve treatment of movement disorders

Recent discoveries by researchers at Charité – Universitätsmedizin Berlin may prove vital in improving the treatment of dystonia, a neurological movement disorder. Published in PNAS*, their findings show that very specific networks in the brain must be stimulated to alleviate the symptoms seen in different types of dystonia.

Dystonia is a rare neurological disorder, characterized by involuntary, twisted, and distorted movements and postures. People with dystonia may have a limited ability to perform activities of daily living, such as drinking, walking, and talking. In Germany, approximately 160,000 people have dystonia. The condition is subdivided into generalized dystonia, which affects the entire body, and focal dystonia, which is limited to specific parts of the body. The latter category includes cervical dystonia, which affects the neck. The underlying causes of the condition are not fully understood, but experts hypothesize that the symptoms are the result of faulty interactions between specific areas of the brain that lead to abnormal signal transmission. Depending on the form of dystonia involved, genetic defects may also play a role.

One treatment option available for patients with dystonia is a neurosurgical procedure that involves the implantation of electrodes in specific areas of the brain. Once implanted, the electrodes emit weak electrical signals that help restore normal brain function. Known as deep brain stimulation, the procedure involves the implantation of a pacemaker-like device and is often the only treatment capable of relieving symptoms.

“How precisely this stimulation should be tailored to the symptoms seen in the different types of dystonia was not clear until now,” explains study leader Prof. Dr. Andrea Kühn, Head of the Department of Neurology and Movement Disorders. of Experimental Neurology. and the Neuromodulation Section and Spokesperson of the ReTune Transregional Collaborative Research Center (SFB/Transregio TRR 295), which helped support the current study.

Prof. Kühn’s team examined a total of 80 patients who had received treatment for generalized or cervical dystonia at one of five different hospitals in Germany and Austria. After analyzing the precise positions of the electrodes, the researchers were able to generate computer models showing which brain networks were activated in each of the investigated patients. By mapping data on symptom improvements onto their network models, the researchers were able to determine which of the identified networks were crucial to treatment success.

A key finding was that the optimal target for stimulation depends on the type of dystonia being treated. This means that optimal treatment outcomes were associated with specific connections between the thalamus (the largest structure in the diencephalon or “interbrain”) and the pallidum (a pale-colored structure in the center of the basal ganglia). The basal ganglia are deep brain structures that play a role in the control of movement. In patients with cervical dystonia, the determining factor was electrical stimulation of a specific neural network that also activated the head and neck region of the primary motor cortex. As the brain’s motor command center, this area is responsible for planning and initiating movements, as well as storing movement memory. In contrast, for patients with generalized dystonia, beneficial effects were obtained through stimulation of a different network that projected to the entire primary motor cortex.

“Our study shows clear differences in the optimal stimulation sites, which correspond to the somatotopic structure of the internal pallidum. This means that the neural areas in the brain map to the areas of the body they represent,” says the study’s first author, Dr. Andreas Horn from the Department of Neurology and Experimental Neurology. He adds: “Given the dearth of alternative treatment options beyond deep brain stimulation, our findings make an important contribution to improving dystonia treatment. In the future, we may be able to more deliberately treat specific types of the disorder.”

Reference: Horn A, Reich MM, Ewert S, et al. Optimal networks and sites of deep brain stimulation for cervical versus generalized dystonia. Proceedings of the National Academy of Sciences. 2022;119(14):e2114985119. doi:10.1073/pnas.2114985119

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