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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.

Background: Deep brain stimulation (DBS) of the globus pallidus interna is an effective tool for the treatment of dystonia with possible distant effects reaching beyond the basal ganglia network., Aim: We analyzed the cortical silent period (CoSP) to test inhibitory circuits at the cortical level, and the cutaneous silent period (CuSP) and the H-reflex to test inhibitory circuits at the spinal level., Methods: The upper limb muscles of 16 patients (9F, aged 54±(SD)16years) with generalized (N=9) and cervical (N=7) dystonia treated with DBS bilaterally were examined by the CoSP, CuSP and H-reflex in two states with random order: (i) in DBS ON and (ii) in DBS OFF condition two hours later, and compared with healthy controls., Results: While the CuSP and H-Reflex did not differ between groups and remained unaffected by DBS, the CoSP was influenced significantly in dystonia. The CoSP onset latency was shortened (p<0.05 corrected) and the CoSP duration prolonged (p<0.01 corrected) in ON versus OFF condition. This effect was especially larger in generalized or phasic type of dystonia. Compared to healthy controls, the CoSP latency and duration became shorter in patients during the OFF condition only., Conclusion: The pallidal DBS did not affect the spinal inhibitory circuitry in dystonia. However, the abnormally low cortical inhibition was normalized after DBS possibly offering more efficient suppression of aberrant dystonic movements., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Introduction Deep brain stimulation (DBS) of the globus pallidus interna (GPi) is widely used in treatment of pharmacoresistant dystonic syndromes. In our study, we analyzed functional connectivity change derived from resting state fMRI in two conditions: with the DBS chronically switched on (ON condition) and two hours after switching the DBS off (OFF condition). We used a graph theory utilizing the degree of centrality (DC) based on mapping links at the voxel level in each condition. Methods We examined 21 patients (13 women, 8 men, aged 46 ± (SD)18 years) with dystonia of various origin (14 idiopathic, 2 DYT-1, 2 PKAN, 2 with parkinsonism, 1 post-anoxic) treated with GPi DBS bilaterally (10–102 months after implantation). The clinical state of patients with generalized dystonia ( N = 13) was assessed by the Burke Fahn Marsden Dystonia Scale and patients with cervical dystonia ( N = 8) were rated by the Toronto Western Spasmodic Torticollis Rating Scale one week before surgery and on the day of the fMRI session in the ON condition. Each subject was instructed to watch a cross while lying motionless in the supine position for 10 minutes during fMRI acquisition (1.5 T, T2*-weighted gradient-echo echo-planar imaging: FA/TR/TE = 90°/3000/51 ms, 200 repetitions). Group analysis of connectivity change was based on voxel-wise comparison between the DC maps in the ON and OFF conditions and on comparison with age-matched healthy subjects and displayed with FWE correction ( P <0.05) at cluster level. Results In ON compared with OFF condition, a significant increase of DC was found in the thalamus bilaterally, in the right accumbens and subthalamus, in the upper and posterior brainstem and the left cerebellum ( Fig. 1 ). Patients in OFF condition when compared to healthy controls showed lower DC in the thalamus and putamen bilaterally, in the mesial region involving SMA, pre-SMA, middle cingulate and precuneus, as well as in the left premotor cortex and parieto-occipital cortex bilaterally ( Fig. 2 ). In the ON condition, DC was found to be lower than healthy controls only in the precuneus and left parietal cortex. Conclusions Chronic GPi DBS in patients regardless of the type and etiology of dystonia caused an increase of resting state functional connectivity in the thalamus, subthalamic nucleus and brainstem, which are the key structures where the GPi directly or indirectly projects to. This observation is in agreement with the comparison of patients with healthy controls: in OFF condition, patients showed lower connectivity in the basal ganglia and motor network, while in the ON condition, functional connectivity in these regions became similar like in the healthy subjects. Supported by the projects IGA MZ Č R NT12282-5/2011 and PRVOUK P26/LF1/4. [ABSTRACT FROM AUTHOR]