Pallidum Theta Waves Associated With Dystonia Symptoms

In patients with the movement disorder known as dystonia, a particular pattern of brain activity is linked to both the severity of symptoms and the clinical outcomes achieved through deep brain stimulation, researchers from Charité Universitätsmedizin Berlin have shown. The findings may help to adapt treatment to individual patient needs.

Dystonia affects more than 500,000 people across Europe. Globally, it is the third most common movement disorder after Parkinson’s disease and essential tremor.

In patients with dystonia, the balance between excitatory and inhibitory neural connections, which is normally responsible for ‘normal’ movement processes, is disrupted. This results in patients experiencing involuntary movements, muscle spasms and contractions.

In the case of cervical dystonia, symptoms affect the muscles of the neck.

Stereotactic Brain Mapping

For the first time, researchers from the Movement Disorders Unit of the Department of Neurology have shown that both symptom severity and the clinical outcomes achieved through deep brain stimulation (DBS) are directly linked to theta but not beta oscillatory amplitudes and interhemispheric coherence. In these patients, oscillatory brain activity in enhanced in the theta band — rhythmic neural activity that occurs at a frequency of between 4 and 12 Hertz.

A total of 27 patients received bilateral DBS electrode implants as part of this study. Using stereotactic brain mapping technology, these were implanted into the globus pallidus internus (GPi), a region within the basal ganglia.

While the clinical effectiveness of this treatment is well documented, and GPi stimulation is known to be capable of reducing increased neuronal activity, the underlying mechanisms had previously remained unresolved. All of the patients studied exhibited the typical interplay between brain activity, previously determined symptom severity, proximity to the optimal stimulation target, and clinical outcomes.

DBS For Dystonic Symptoms

Prof. Dr. Andrea Kühn, of Charité’s Department of Neurology, leads a team of researchers committed to the study of movement disorders and the use of DBS-based treatments.

So far, her team has recorded the brain activity of more than 400 patients undergoing DBS treatment, analyzing all of the data collected for potential patterns which correlate with symptom severity and treatment outcomes.

Using LEAD-DBS, a type of software initially developed at Charité, the researchers used these data to reconstruct a 3-D-map of the oscillatory amplitudes within a virtual brain. This revealed a significant localized increase in the relevant activity pattern, which was found in the area of the brain associated with the best treatment outcomes in dystonia patients undergoing DBS.

“Our findings suggest that theta band oscillations may be responsible for dystonic symptoms, and may also explain the mechanism of action of DBS, as well as the location of the optimal stimulation target in affected patients,”

said Dr. Wolf-Julian Neumann of the Movement Disorders Unit.

“We are also currently studying the long-term effects of DBS on neuronal activity. We are one of a few centers in the world to do so, and are currently running a separate study involving 15 patients with dystonia. Our research is made possible thanks to an innovative DBS system, which continues to record brain activity after implantation,”

explained Prof. Dr. Andrea Kühn, head of the Movement Disorders Unit and Member of the Board of Directors of the NeuroCure Cluster of Excellence.

Neumann, W.-J., Horn, A., Ewert, S., Huebl, J., Brücke, C., Slentz, C., Schneider, G.-H. and Kühn, A. A.
A localized pallidal physiomarker in cervical dystonia
Ann Neurol., 82: 912–924. doi:10.1002/ana.25095

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