SP 8. Cortico-subcortical increase of resting state functional connectivity with GPi DBS in dystonia

Abstract

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 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 C R NT12282-5/2011 and PRVOUK P26/LF1/4.