Benefits of pallidal stimulation in dystonia are linked to cerebellar volume and cortical inhibition

Abstract

Clinical benefits of pallidal deep brain stimulation (GPi DBS) in dystonia increase relatively slowly suggesting slow plastic processes in the motor network. Twenty-two patients with dystonia of various distribution and etiology treated by chronic GPi DBS and 22 healthy subjects were examined for short-latency intracortical inhibition of the motor cortex elicited by paired transcranial magnetic stimulation. The relationships between grey matter volume and intracortical inhibition considering the long-term clinical outcome and states of the GPi DBS were analysed. The acute effects of GPi DBS were associated with a shortening of the motor response whereas the grey matter of chronically treated patients with a better clinical outcome showed hypertrophy of the supplementary motor area and cerebellar vermis. In addition, the volume of the cerebellar hemispheres of patients correlated with the improvement of intracortical inhibition which was generally less effective in patients than in controls regardless of the DBS states. Importantly, good responders to GPi DBS showed a similar level of short-latency intracortical inhibition in the motor cortex as healthy controls whereas non-responders were unable to increase it. All these results support the multilevel impact of effective DBS on the motor networks in dystonia and suggest potential biomarkers of responsiveness to this treatment.

Botulinum toxin injection changes resting state cerebellar connectivity in cervical dystonia

“…The decreasing cerebro-cerebellar connectivity after treatment is in line with evidence for abnormally “increased” (i.e., less negative) connectivity in CD between the sensorimotor cortex and a cerebellar seed in vermis defined as an overlap of dystonia-related brain lesions 9 . Our findings also have to be considered in the context of previous published papers on central treatment effects in idiopathic dystonia e.g., 12 , 18 , 38 .…”

“…Further evidence for the role of the cerebellum comes from structural imaging studies. In patients with various types of dystonia chronically treated with deep brain stimulation (DBS), voxel-based morphometry revealed increased gray matter density in the cerebellar vermis, supplementary motor area (SMA) and anterior cingulate cortex, which was more profound in good responders 18 . Together with our data, this study suggests a prominent role of the cerebellum and its frontal connections in the normalization of the motor function, though the exact mechanisms in DBS and BoNT may considerably differ.…”

Task-related brain activity and functional connectivity in upper limb dystonia: a functional magnetic resonance imaging (fMRI) and functional near-infrared spectroscopy (fNIRS) study

“…5 Cerebellar modulation of the motor cortex is altered in patients with focal dystonia 10 and structural changes have been observed across several studies. [11][12][13][14] The cerebellum might influence the primary cortex responsiveness by a complex mechanism with several nodes through the cerebello-thalamo-cortical pathway, and studies suggest that, through cerebellar stimulation, it might be possible to regulate the motor excitability and plasticity. 15 Whether cerebellar abnormalities are due to compensatory changes or a cause of idiopathic dystonia demands further exploration.…”

“… 5 Cerebellar modulation of the motor cortex is altered in patients with focal dystonia 10 and structural changes have been observed across several studies. 11 – 14 …”

Analysis of Neural Activity of the Human Basal Ganglia in Dystonia: a Review

“…Dystonia affects about 1% of the population, and women are more prone to it than men [1]. Deep brain stimulation of the globus pallidus internus (GPi-DBS) is an effective treatment for pharmacoresistant dystonic syndromes, where pathophysiological mechanisms of action are not yet fully understood [2]. The age of onset is a factor in determining the phenotype of dystonia.…”