Abstracts

Rationale: Recently, functional neuroimaging analyses demonstrated a disruption of premotor-basal ganglia circuits for the generation of interictal EEG activity in patients with Glucose transporter type I deficiency syndrome (GLUT1DS).In this work, we aim to infer the resting-state functional connectivity (fcMRI) of subcortical and cortical networks in patients with GLUT1DS, compared to healthy controls. We hypothesize that (a) GLUT1DS shows a disrupted functional connectivity of the basal-ganglia networks compared to controls; (b) the altered pattern of connectivity is different in children with respect to adults affected by this encephalopathy.    Methods: Eighteen GLUT1DS patients (10 children and 8 adults) with pathogenetic mutation in SLC2A1 gene were studied by means of Video-EEG simultaneously recorded with functional MRI (VideoEEG-fMRI). A control group of sex and age-matched healthy subjects (19 children and 17 adults) underwent the same protocol. Seed-based functional connectivity (fcMRI) was performed with SPM’s Functional Connectivity Toolbox (conn). The following seeds were selected (a) six bilateral regions of interest (ROIs) in the striatum; (b) one bilateral seed in the precuneus (PCU); (c) two bilateral ROIs in the primary visual cortex; (d) two bilateral ROIs in the primary motor cortex. Seed-based fcMRI was assessed for (a) all the GLUT1DS population versus controls; (b) children with GLUT1DS versus healthy children; (c) adults with GLUT1DS versus healthy adults; (d) children with GLUT1DS versus adults with GLUT1DS. Finally, the connectivity measures were correlated with main clinical variables. Results: Children with GLUT1DS showed increased functional connectivity between (a) the bilateral nucleus accumbens with left caudate head, left superior frontal gyrus and right putamen; (b) the bilateral dorsal caudate with left putamen, bilateral accumbens, right anterior cingulate cortex, right medial frontal gyrus; (c) the bilateral putamen, with the left lentiform nucleus, right claustrum, anterior cingulate cortex, bilateral supplementary motor area. In adults with GLUTDS, increased functional connectivity was limited to the connection between the right caudate nucleus to right thalamus and precuneus. No significant correlations were detected between seed-based functional connectivity and clinical variables.  Conclusions: FcMRI analyses show significant different pattern of connectivity in GLUT1DS patients respect to controls when the seeds were in the basal ganglia system. The increased correlations of BOLD signals involve the basal ganglia-frontal cortex networks. This pattern is consistently observed in the children, and appear attenuated in adults. Our findings reinforce the notion that GLUT1DS is a non-evolutive encephalopathy. We speculate that the abnormal synchrony between (and within) basal ganglia with specific frontal areas is the “intrinsic” substrate responsible of the appearance of movement disorder in GLUT1DS.  Funding: No funding