L’integrazione sensori-motoria nella Sclerosi Multipla: studio di correlazione dei parametri neurofisiologici, clinici e di neuroimaging in una coorte di pazienti affetti da forma recidivante-remittente

Introduction: Somatosensory temporal discrimination threshold (STDT) is a neurophysiological measure of sensory information processing. Through mechanisms of sensory gating, sensorimotor integration ensures continuous monitoring of sensory inflow to adjust motor plan and performance. Voluntary movement modulates STDT through the interplay between basal ganglia and thalamus in healthy controls (HC). Although it has been demonstrated that STDT is altered in patients with multiple sclerosis (MS), subcortical mechanisms of sensorimotor integration have never been explored. Aim of the study was to combine neurophysiological and magnetic resonance imaging (MRI) measures to investigate STDT modulation during movement execution in MS.  Methods: Subjects: Thirty-eight patients with relapsing-remitting MS (mean age 40,8±7,9 years), a median Expanded Disability Status Scale (EDSS) of 1.5 (range 0-3.5) and and 27 age-matched HC were recruited. Neurophysiological measures: To test STDT at the baseline we delivered couples of electric stimuli with a progressively increasing interstimulus interval. STDT was considered as the first of three consecutive intervals at which participants recognized the two stimuli as temporally separate. We then tested STDT at 0 ms, 100 ms and 200 ms after the onset of index-finger abduction. We recorded the kinematic features of the movement by using the SMART system. MRI measures: All participants underwent a 3T MRI protocol including 3D-T1 and T2-FLAIR images; we used the semi-automated software Jim (v5.0) for white matter (WM) lesions detection and FSL-FIRST for subcortical volume calculation.  For diffusion MR imaging we used DTI Fit to generate whole brain fractional anistrophy (FA) and mean diffusivity (MD). Results: Neurophysiological measures: STDT at baseline was higher in patients compared to HC( F=9.67, p=0.002) (Figure 1). During voluntary movement, the percentage time-related changes in STDT did not differ between patients and controls (p=0.06) (Figure 2) although mean movement velocity significantly decreased in patients (p=0.003) but not in HC (Figure 3). MRI measures: Subcortical volumes analysis showed that the volume of caudate nucleus was significantly decreased in patients with MS compared to HC (p=0.02). DTI parameters were altered in patients compared to HC: MD was increased in patients than HC in putamen (p=0.02), pallidum (p=0.04) and thalamus (p=0.04), while mean FA resulted decreased in patients group compared to HC in the pallidum (p=0.02). Correlations: STDT at baseline negatively correlated with thalamic volume (r=-0.38, p=0.02) and positevely correlated with EDSS scores (r=0.39, p=0.02). In patients, time-related changes in STDT (r=0.41, p=0.01) and mean velocity (r=0.42, p=0.02) positively correlated with putaminal volume (Figure 4). Lastly, we did not find any correlation between neurophysiological measures and WM lesion load.  Conclusions: Altered STDT is related to thalamic atrophy and not to WM damage in patients with MS. Although sensory gating is preserved in MS, motor performance deteriorates during the task. The relationship between putaminal volume, STDT changes and movement kinematics suggests a key role of the putamen in this integrative function. Overall, our results shed light on the role of basal ganglia in sensorimotor integration in MS and could represent the background for new multitasking rehabilitation approaches.