Introduction: Changes of brain structure and function have been described in peripheral neuropathies. Aim of our study was to systematically investigate possible modifications of major large-scale brain networks using resting-state (RS)-fMRI in CMT1A patients. 
 
 Method: In this prospective cross-sectional study, from May-2017 to May-2019, we acquired 3T MRI brain scans of right-handed genetically confirmed CMT1A patients and age- and sex-comparable healthy controls. Patients also underwent clinical and electrophysiological examinations assessing neurological impairment. RS-fMRI data were analyzed using a seed-based approach, with thirty-two different seeds sampling the main hubs of default mode (DMN), sensorimotor (SMN), visual (VN), salience (SN), dorsal attention (DAN), frontoparietal (FPN), language (LN) and cerebellar (CN) networks. Between-group differences in terms of functional connectivity (FC) with the explored seeds were tested voxel-wise, correcting for local gray matter density to account for possible structural abnormalities, while the relationship between FC modifications and neurological impairment was investigated using robust correlation analyses. 
 
 Result: 18 CMT1A patients (34.0 ± 11.4 years; M/F: 11/7) were enrolled, along with 20 healthy controls (30.1±10.2years; M/F:11/9). In the CMT group compared to controls, we found clusters of increased FC with the visual cortex (p=0.001), SN (p<6·10-4), DAN (p<8·10-5), LN (p<7·10-4) (Figure 1), along with a single cluster of reduced FC with the visual cortex in the left lentiform nucleus (p=10-6). A significant positive correlation (r=0.655, p=0.006) emerged between neurophysiological impairment and the cluster of increased FC with right temporal language areas in the left inferior parietal lobule, along with an association between walking ability and the cluster of increased FC with the left supramarginal gyrus (SN) in the homolateral middle temporal gyrus (r=0.620, p=0.006). 
 
 Discussion & Conclusion: In conclusion, our data show evidence of diffuse functional reorganization involving multiple large-scale networks in the CMT1A brain, independent of structural modifications and partially correlating with peripheral nerve damage and functional impairment.

A RESTING-STATE fMRI STUDY INVESTIGATING FUNCTIONAL CONNECTIVITY MODIFICATIONS IN CMT1A PATIENTS