Table 3.
RS-fMRI studies in MND patients.
| Study | Subjects (mean age, years) | Disease duration (months) | ALSFRS-R score | Analysis methods | Main findings in MND patients compared to HCs | Other findings |
|---|---|---|---|---|---|---|
| Mohammadi (38) | 20 ALS (55), 9 LMN affection (58), 20 HCs (57) | 14 | 40 | ICA | 1. DMN: less activation in ventral ACC, PCC and bilateral inferior parietal cortex. 2. SMN: less activation in PMC | – |
| Jelsone-Swain (39) | 20 ALS (58.3), 20 HCs (57.5) | 17.3 | 39.6 | Graph theory | 1. Overall systemic decrease in FC between right and left motor cortices in patients with limb-onset. 2. Pronounced disconnection between dorsal ROI pairs of M1 | Dorsal ROI connectivity strength was negatively correlated with hand strength disparity |
| Verstraete (40) | 12 ALS (48.7), 12 HCs (49.6) | 14.3 | 39.5 | Graph theory, combined with DTI and SBM | Overall functional organization of motor network was unchanged | The FC level of motor network was correlated with disease progression rate in ALS patients |
| Filippi (41) | 18 ALS (not given), 15 HCs (not given) | NA | NA | ICA, combined with VBM | 1. Dysfunction of resting state connectivity of SMN. 2. Decreased average percentage signal change of resting state fluctuations in bilateral primary sensorimotor cortex and cerebellum, SMA, left inferior frontal gyrus and inferior parietal lobule | – |
| Douaud (42) | 25 ALS (59), 15 HCs (53) | 44 | 34 | Tractography-derived FC analysis, combined with DTI | Increase of FC in primary sensorimotor cortex and PMC, anterior and motor cingulate areas, frontal and central operculum, and thalamus | 1. Regions of increased FC corresponded with decreased structural connectivity by DTI. 2. Increased FC linked to faster progression rate |
| Agosta (43) | 26 ALS (63), 15 HCs (66) | 20 | 36 | SRFC, combined with DTI | 1. Increased FC between left primary sensorimotor cortex (ROI) and the right cingulated cortex, parahippocampal gyrus, and cerebellum-crus?. 2. No right primary sensorimotor cortex FC changes were found | 1. Patients with no CST abnormalities by DTI had more widespread increased FC to left primary sensorimotor cortex. 2. There was a positive correlations between ALSFRS-R score and increased FC |
| Tedeschi (44) | 20 ALS (60.7), 20 HCs (62.1) | 1–168 | 34.2 | ICA, combined with VBM | 1. SMN: suppressed RS-fMRI fluctuations in bilateral M1. 2. R-FPN: suppressed RS-fMRI fluctuations in superior frontal gyrus and supramarginal gyrus. 3. DMN showed no significant group difference | 1. DMN (specifically PCC) and R-FPN network showed a significant age-by-disease interaction. 2. The volume of gray matter adjacent to regions of reduced FC was decreased |
| Luo (45) | 20 ALS (45.3), 20 HCs (47.1) | 15.2 | 31.9 | ALFF, combined with VBM | After gray matter correction: 1. increased ALFF in middle frontal lobe and right inferior frontal gyrus. 2. decreased ALFF in visual cortex, fusiform gyrus and right postcentral gyrus | Disease duration was positively correlated with mean ALFF in left middle frontal gyrus, while rate of disease progression was negatively correlated with it |
| Tietz (46) | 40 ALS (not given), 40 HCs (age matched) | NA | NA | ICA | Increased DMN in frontal and temporal regions | – |
| Machts (2012 and 2013) (47, 48) | 81 ALS (not given), 68 HCs (not given) | NA | NA | SRFC and fALFF | 1. SRFC: increased FC of right M1 (ROI) with SMA, precentral and postcentral gyrus; decreased FC of right M1 with PCC, frontal pole, lateral parietal cortex and inferior temporal cortex; No significant differences were found for FC with left M1. 2. fALFF: higher fALFF in right M1 and lower fALFF in PMC | 1. FC of both M1 toward contralateral precentral gyri correlated positively with patients’ disease severity as well as fALFF in bilateral PMC. 2. There was an inverse correlation between patients’ ALSFRS-R scores and fALFF in cerebellum |
| Zhou (49) | 12 ALS (49.5), 12 HCs (age matched) | 14.2 | 35.8 | Graph theory | 18 key nodes were chosen to compare within-motor network FC, ALS patients showed altered pairwise FC in 11 node pairs, both decreased and increased | Increased FC between bilateral superior parietal lobule and right anterior inferior cerebellum related to more severe disease |
| Fekete (50) | 40 MND (36 ALS, 4 PLS, 55), 30 HCs (50) | 51 | 34 | SRFC and complex network analysis | 1. SRFC: widespread FC alterations in motor network, including regions not obviously clinically affected, such as cerebellum and basal ganglia. 2. Complex network analysis: (1) reduced connectivity of both cortical and subcortical motor areas with non-motor areas, (2) reduced subcortical–cortical motor connectivity and (3) increased connectivity within subcortical motor networks | – |
| Agosta (51) | 20 ALS (61), 15 HCs (63) | 29 | 33 | ICA | 1. DMN: enhanced connectivity of left precuneus, decreased connectivity of right inferior orbitofrontal gyrus. 2. R-FPN: increased connectivity of right angular gyrus, decreased connectivity of left anterior insula/inferior frontal cortex. 3. L-FPN: increased connectivity of left inferior parietal lobule and left middle cingulum. 4. No change was found in EXN and SLN connectivity | Enhanced parietal connectivity was associated with clinical and cognitive deficits of the patients |
| Casseb (52) | 30 ALS (not given), 24 HCs (not given) | NA | NA | SRFC | BA 4 as ROI, there were no significant results | – |
| Agosta (53) | 24 PLS (62.8), 26 HCs (63.5) | 102 | 36.7 | Tractography-derived FC analysis, combined with DTI | 1. SMN: increased FC in bilateral precentral and postcentral gyri. 2. Frontal network: increased FC in bilateral ACC and superior medial frontal gyrus, left SMA, and right insula. 3. L-FPN: increased FC in left middle orbitofrontal, inferior frontal, and superior temporal gyri. 4. No FC difference was found in DMN and R-FPN | 1. Increased FC within SMN was associated with lower ALSFRS-R scores and more rapid disease progression rate. 2. Increased FC within frontal network was associated with executive dysfunction. 3. Higher FC correlated with greater structural damage to network-specific white matter tracts |
| Roll (54) | 36 ALS (not given), 34 HCs (not given) | NA | NA | SRFC, combined with DTI | Increased FC in all networks except reference network | Disease patterns observed by DTI correlated with increased FC in intrinsic networks |
| Loewe (55) | 64 ALS (not given), 38 HCs (age matched) | NA | NA | Graph theory | 1. Increased connectivity in mostly short-range connections within frontal, parietal, occipital, and temporal regions. 2. Decreased FC in motor-related areas include bilateral pre- and postcentral gyrus; decreased temporo-occipital connectivity spread from medial and inferior temporal lobes up to middle occipital lobes | – |
| Heimrath (56) | 9 ALS (57.3), 11 HCs (67.5) | 60.2 (since diagnosis) | 31.7 | Complex network analysis, combined with DTI | Increased FC in parahippocampal and parietal areas of DMN | Increased FC was correlated with pronounced cognitive deficits |
| Schmidt (57) | 64 ALS (56.9), 27 HCs (57.7) | 16.5 | 40 | Complex Network Analysis, combined with fiber assignment by continuous tracking | 1. Most structurally affected connections overlap with most functionally impaired connections.2.Direct connections of motor cortex are both structurally and functionally more affected than connections at greater topological distance from the motor cortex | |
| Zhou (58) | 12 ALS (49.5), 12 HCs (age matched) | 14.2 | 35.8 | ReHo | 1. Higher ReHo in S1 (left postcentral gyrus), PMC (right middle frontal gyrus), and sensory association cortex (including bilateral inferior parietal lobule). 2. Lower ReHo in M1 and PMC (right precentral gyrus/superior frontal gyrus), PMC (including left SMA, left precentral gyrus, right superior frontal gyrus), and S1 (right postcentral gyrus) | 1. Decreased ReHo in right S1/M1/superior frontal gyrus was correlated with lower ALSFRS-R scores.2.ReHo in left S1 and inferior parietal cortex was negatively correlated with disease duration. 3. Increased ReHo in left S1 corresponds to fast disease progression rate |
| Zhou (59) | 20 ALS (56.9), 20 HCs (57.7) | 16.2 | 35.4 | VMHC and SRFC, combined with DTI | 1. VMHC: higher VMHC coefficients in SMA, superior frontal gyrus and middle occipital gyrus, lower VMHV coefficients in M1, S1, inferior parietal lobule, cuneus/precuneus and ACC. 2. Significant FC alterations were detected in M1 and frontal/temporal/occipital bole using SRFC based on regions showing abnormal VMHC coefficients | There was a significant positive correlation between VMHC coefficients of M1 and ALSFRS-R scores |
| Meoded (60) | 16 PLS (59.7), 14 HCs (51.6) | 104 | 35.8 | Graph theory, combined with probabilistic fiber tracking | 12 regions with increased FC with a predominance of cerebrocerebellar connections, strongest between cerebellum and cortical motor areas and between cerebellum and frontal and temporal cortex | Fiber tracking detected no difference in connections between regions with increased FC |
| Trojsi (61) | 15 ALS (61.8), 15 bvFTD (61.5), 15 HCs (62.7) | 24 | 35.6 | ICA, combined with DTI and VBM | Decreased RS-fMRI signals within SMN (M1), DMN (PCC), R-FPN (right supramarginal gyrus), EXN (left middle frontal cortex), SLN (medial prefrontal cortex and insula) | ALS and bvFTD share common RS-fMRI connectivity patterns, but differ in DMN, with RS-fMRI signals in PCC enhanced in bvFTD and suppressed in ALS |
| Buchanan (62) | 30 ALS (58.3), 30 HCs (58.5) | 24 | 38.8 | Complex network analysis, combined with TBSS | Impaired motor-frontal-subcortical subnetwork involving 4 nodes within M1 (bilateral precentral and paracentral), left superior frontal, left-posterior cingulate and 4 subcortical areas (bilateral pallidum, left thalamus, left caudate) | 1. impaired network connections correlated with disease progression rate. 2. Affected network corresponded to impairment of white matter tracts identified by TBSS |
ACC, anterior cingulate cortex; ALFF, amplitude of low-frequency fluctuation; ALS, amyotrophic lateral sclerosis; ALSFRS-R, revised ALS functional rating scale; bvFTD, behavioral variant frontotemporal dementia; DLPFC, dorsolateral prefrontal cortex; DMN, default-mode network; DTI, diffusion tensor imaging; EXN, executive network; fALFF, fractional ALFF; FC, functional connectivity; FPN, frontoparietal network; HC, healthy control; ICA, independent component analysis; L-FPN, left FPN; M1, primary motor cortex; MND, motor neuron disease; NA, not available; PCC, posterior cingulate cortex; PMA, premotor cortex; PLS, primary lateral sclerosis; ReHo, regional homogeneity; R-FPN, right FPN; ROI, region of interest; RS-fMRI, resting state-fMRI; S1, primary sensor cortex; SBM, surface-based morpometry; SLN, salience network; SMA, supplementary motor area; SMN, sensorimotor network; SRFC, seed region-based FC; TBBS, tract-based spatial statistics; VBM, voxel-based morphometry; VMHC, voxel-mirrored homotopic connectivity.