Table 1.

Main results of studies investigating rs-FC in MS.

Authors	Study population	Main findings
Roosendaal et al., 2010	14 CIS, 31 RR-MS, 41 HCs	Increased rs-FC in several RSNs, including the DMN and sensorimotor network, in CIS compared to HCs and RR-MS. In RR-MS GM atrophy and abnormal WM diffusivity compared to HCs. No changes in CIS. rs-FC and structural MRI or clinical disability did not correlate in CIS and RR-MS.
Rocca et al., 2010	33 SP-MS (18 CI), 24 PP-MS (12 CI), 24 HCs	In SP-MS reduced activity in the DMN, in the medial prefrontal cortex and precentral gyrus, compared with HCs. In PP-MS reduced activity in the precentral gyrus and the ACC compared with HCs. In SP-MS increased ACC activity compared with PP-MS. RS activity in the ACC was reduced particularly in CI. DMN abnormalities correlated with cognitive test and DTI changes in the CC and the cingulum.
Bonavita et al., 2011	36 RR-MS (18 CI and 18 CP), 18 HCs	In RR-MS reduced DMN connectivity in the ACC, reduced in the core and increased at the periphery of the PCC. No correlations between FC changes and global atrophy or T2-LL, but association with regional GM loss. The findings were more marked in CP than CI.
Faivre et al., 2012	13 early RR-MS, 14 HCs	Increased rs-FC in several RSNs in early RR-MS compared with HCs. No correlations between RSNs connectivity and T2-LL or disease duration. Increased rs-FC in cognitive and sensorimotor networks negatively correlated with different cognitive and motor tasks and MSFC scores.
Rocca et al., 2012	85 RR-MS, 40 HCs	In RR-MS decreased rs-FC in different RSNs (salience, executive control, working memory, default mode, sensorimotor, and visual) and increased rs-FC in regions of the executive control and auditory RSNs. Decreased rs-FC was correlated with disability and T2 lesion volumes.
Tona et al., 2014	48 RR-MS, 24 HCs	In RR-MS both increased and decreased connectivity within the thalamic RSN. No significant correlation between thalamic FC and radiologic variables. Increased thalamocortical FC correlated with decreased cognitive performance.
Cruz-Gómez et al., 2014	60 RR-MS (30 CI and 30 CP), 18 HCs	Decreased rs-FC in the DMN in CI compared with CP and HCs. Decreased rs-FC in the LFPN in both CI and CP compared with HCs. Decreased rs-FC in the RFPN and salience network in CI compared with CP. BPF correlated with rs-FC in the DMN, LFPN and RFPN. T1-LL negatively correlated with rs-FC in all explored RSNs.
Louapre et al., 2014	35 RR-MS (15 CI and 20 CP), 20 HCs	In CI decreased rs-FC in DMN and ATT compared with CP. In CI decreased rs-FC particularly between the medial prefrontal cortex and the PCC, predicted by PCC atrophy. In CI higher WM LL and more severe GM atrophy in cognitive networks compared with CP. In CP increased rs-FC in ATT compared with HCs.
Zhou et al., 2014	24 RR-MS and 24 HC	The connections of paired DMN subregions showed decreased SC and increased FC in RR-MS patients. SC alterations correlated with EDSS. Decreased SC was correlated to atrophy.
Rocca et al., 2015	69 CP MS, 42 HCs	In CP MS decreased rs-FC between the hippocampi and several cortical–subcortical regions within the DMN. Reduced hippocampal rs-FC correlated with T2-LL, disease duration, depression and disability.
Sbardella et al., 2015	30 RR-MS and 24 HCs	In RR-MS decreased rs-FC in several networks (cerebellar, executive-control, medial-visual, basal ganglia and sensorimotor) and changes in inter-network correlations. CC microstructural damage correlated with FC in cerebellar and auditory networks. No correlations between rs-FC in all explored RSNs and T2-LL.
Liu et al., 2015	35 RR-MS, 35 HC	Compared to HC, the MS group showed significantly decreased FC between thalamus and several brain regions including right middle frontal and parahippocampal gyri, and the left inferior parietal lobule. Increased intra and inter-thalamic FC was observed in MS compared to HC. FC alterations were not correlated with T2-LL, thalamic volume or the presence of thalamic lesions.
Baltruschat et al., 2015	17 RR-MS, 15 HCs	In RR-MS increased FC between left posterior cingulate gyrus/precuneus, and left middle temporal gyrus and left cerebellum. In RR-MS GM bilateral atrophy in posterior cingulate gyrus/precuneus. BPF negatively correlated with FC between left posterior cingulate gyrus/precuneus and left cerebellum.
Rocca et al., 2016	214 MS patients (RR-MS and SP-MS), 55 HC	Global network properties (network degree, global efficiency, hierarchy, path length and assortativity) were abnormal in MS compared with HC and contributed to distinguish CI MS patients from HC, but not the main MS phenotypes. In MS, global and regional network properties were not correlated with T2-LL and normalized brain volume.
d'Ambrosio et al., 2017	187 MS patients (136 RR-MS, 42 SP-MS and 9 PP- MS), (122 CP and 65 CI); 94 HCs	In patients lower GM, WM and thalamic volumes compared with HCs. In patients decreased rs-FC between thalamic subregions and the caudate, cingulate cortex and cerebellum correlated with worse motor performance. Increased rs-FC with the insula correlated with better motor performance. In CI increased rs-FC between thalamic subregions and temporal areas compared with CP. No correlations between thalamic rs-FC and T2-LL.

ACC, anterior cingulate cortex; ATT, attentional network; CC, corpus callosum; CI, cognitive-impaired patients; CIS, clinically isolated syndrome; CP, cognitive-preserved patients; DMN, Default Mode Network; DTI, Diffusion Tensor Imaging; FC, functional connectivity; GM, gray matter; HCs, healthy controls; LFPN, left fronto-parietal network; LL, lesion load; MRI, Magnetic Resonance Imaging; MS, Multiple Sclerosis; MSFC, Multiple Sclerosis Functional Composite Score; PCC, posterior cingulate cortex; PP-MS, primary-progressive MS patients; RFPN, right fronto-parietal network; RR-MS, relapsing-remitting MS patients; rs-FC, resting-state Functional Connectivity; RSN, resting state network; SC, structural connectivity; SP-MS, secondary-progressive MS patients; WM, white matter.