Supplementary MaterialsSupplementary Methods

Network Analysis

Both local and global network properties were studied using the MATLAB Brain

Connectivity Toolbox (Rubinov and Sporns, 2010).

Local Network Analysis

To characterize the general structure of the network in the local (nodal) level, the nodal

degree of the various ROIs was explored. The nodal degree of node i was defined,

Dnod ( i )= ∑j ≠ i∈G

e ij

Where e ij is the number of neighbors of node i.

Network density, the proportion of existing connections in the network out of all possible

connections, based on the entire network’s degree, was also calculated,

κ= 2 EN (N−1 )

Global Network Analysis

To look at the topological organization of the studied networks, six global network

metrics were explored. These included four parameters used to calculate small-worldness

– clustering coefficient C p, harmonic mean of shortest path lengths Lp, and their

normalized counterparts, γ and λ, as well as global and local efficiency parameters.

The clustering coefficient was defined according to (Watts and Strogatz, 1998), for a

given graph G with N nodes,

C p=1N ∑

i∈G

EDnod(i)(D nod ( i )−1)/2

Where Dnod(i) is the nodal degree of node i, and Ei is the number of edges in Gi, the

subgraph of i's neighbors.

The harmonic mean of the characteristic path length, chosen since most of our networks

are at least partially disconnected and therefore contain infinite paths, was defined

according to (Newman, 2003),

Lp=1

12N (N+1)

∑i ≥ jd ij

−1

Where d ij is the distance from node i to node j, and in which infinite values of d ij

contribute nothing to the sum, thus solving the disconnection issue.

The normalized counterparts of the clustering coefficient and characteristic path length (

γ=C preal /C p

rand and λ=Lpreal/Lp

rand, respectively, as in (Watts and Strogatz, 1998)), were

calculated, where the random variables represent the means of corresponding metrics

extracted from 100 matched random networks, preserving numbers of nodes, edges, and

degree distributions as the real networks (Maslov and Sneppen, 2002). A typical small-

world network should exhibit γ>1 and λ≈1.

Global and local efficiencies were defined according to (Latora and Marchiori, 2001),

Eglob=1

N (N−1) ∑i ≠ j∈G

1d ij

Eloc=1N∑

i∈GEglob(i)

Where Eglob is the global efficiency of Gi, the subgraph of i's neighbors.

Modularity, a measure of network segregation quantifying the degree to which the network may be subdivided into non-overlapping groups of ROIs which are densely interconnected within and sparsely connected without, was calculated according to (Newman, 2006).

Supplementary Figures

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HG

Figure e-1: Visual network graph theory metrics for both hemispheres over entire range of correlation thresholds (0.1-0.5; 0.05 increments). (A-B) Density; (C-D) Global efficiency; (E-F) Harmonized mean of characteristic path length; (G-H) Modularity.

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Figure e-2: small-world criteria curves (γ in blue, λ in orange). Values were calculated for each subject's visual network and averaged for each group and are presented for both hemispheres. (A-B) HC; (C-D) NMOSD; (E-F) CIS-ON; (G-H) CIS-nON. For the entire range of correlation thresholds, all networks shown γ>1 and λ≈1, suggesting small-worldness.

Healthy Controls NMOSD CIS-ON CIS-nON-motorCIS-nON-other

Healthy Controls NMOSD CIS-ON CIS-nON-motorCIS-nON-other

Healthy Controls NMOSD CIS-ON CIS-nON-motorCIS-nON-other

Healthy Controls NMOSD CIS-ON CIS-nON-motorCIS-nON-other

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D

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* * * ***

** *

Figure e-3: Motor network analysis results. (A) group degree for motor putamen; (B) group degree for IFG-PO; (C) motor network density; (D) motor network global efficiency. * represents significant difference from healthy control group. ** represents significant difference from NMOSD group.

Figure e-4: Average degree of all four subject groups for selected regions of the three region subdivisions (right hemisphere). HCs in blue, NMOSD in green, CIS-ON in red, CIS-nON in orange. (A) hMT (dorsal-lateral subdivision); (B) VO1 (ventral-temporal) subdivision; (C) FEF (parietal-frontal subdivision). * Significantly different than HC, p < 0.05 after multiple comparisons correction.

Figure e-5: Segregation and integration metrics for all four subject groups (right hemisphere). HCs in blue, NMOSD in green, CIS-ON in red, CIS-nON in orange. (A) Modularity; (B) Harmonized mean of characteristic path length; (C) Global efficiency. * significantly different than HC; ** significantly different than NMOSD, p < 0.05, after multiple comparisons correction.

Figure e-6: Motor network analysis results (left hemisphere). (A) group degree for motor putamen; (B) group degree for IFG-PO; (C) motor network density; (D) motor network global efficiency.

Supplementary Tables

Table e-1: Regions of Interest Names and Coordinates

(A) Visual Network (B) Motor Network

ROI Coordinates in MNI

(Left hemisphere; Right

hemisphere)

ROI Coordinates in MNI

(Left hemisphere;

Right hemisphere)

Ventral-Temporal M1 (precentral) -38, -32, 54; 34, -30, 54

V1v -6, -82, -3; 9, -80, -1 SMA -8, -8, 47; 8, -8, 45

V2v -10, -78, -8; 10, -76, -7 IFG PO -48, 4, 13; 46, 4, 23

V3v -18, -76, -10; 18, -72, -8 IFG PT -57, 17, 1; 48, 18, -2

hV4 -27, -77, -12; 29, -76, -11 Motor Putamen -26, -4, -4; 26, -8, -6

VO1 -27, -68, -10; 27,-65, -9 Dorsolateral Premotor Cortex -17, -28, 42; 35, -16, 44

VO2 -26, -60, -10; 26, -57, -8

PHC1 -25, -52, -9; 26, -50, -8

PHC2 -26, -42, -9; 27, -42, -10

Dorso-Lateral

V1d -8, -89, 4; 11, -87, 7

V2d -10, -91, 12; 14, -88, 15

V3d -17, -89, 15; 21, -86, 17

MST -47, -66, 8; 47, -60, 7

hMT -45, -74, 7; 48, -67, 8

LO1 -33, -83, 8; 36, -81, 9

LO2 -40, -80, 7; 42, -75, 8

V3a -18, -85, 23; 22, -82, 27

V3b -29, -84, 15; 34, -80, 17

Parietal and Frontal

IPS0 -25, -75, 31; 29, -73, 32

IPS1 -22, -69, 40; 26, -67, 40

IPS2 -20, -66, 47; 24, -63, 48

IPS3 -22, -59, 53; 24, -58, 53

IPS4 -27, -54, 52; 28, -52, 54

IPS5 -32, -47, 51; 32, -46, 54

SPL1 -9, -58, 53; 11, -54, 57

FEF -31, -2, 52; 30, -2, 52

V1 = primary visual cortex; V2 = secondary visual cortex; V3 = visual area V3; (v = ventral; d = dorsal);

hV4 = human visual region V4; VO = ventral occipital cortex; PHC = ; MST = medial superior temporal

area; hMT = human middle temporal region; LO = lateral occipital cortex; IPS = intraparietal sulcus; SPL =

superior parietal lobule; FEF = frontal eye field; M1 = primary motor cortex; SMA = supplementary motor

area; IFG = inferior frontal gyrus ; PO = pars opercularis; PT = pars triangularis.

Table e-2: mean region degrees for visual network by hemisphere (mean±SD)

Region HC NMOSD CIS-ON CIS-nONLeft Hemisphere

V1v 7.704±2.321 6.487±2.534 6.05±2.693 4.662±2.872V1d 7.185±2.273 6.061±2.704 6.011±3.185 4.524±2.854V2v 7.613±2.216 6.798±2.349 5.95±3.056 4.890±3.089V2d 7.588±2.078 6.330±2.630 6.186±2.960 5.083±2.720V3v 7.204±2.456 6.024±2.727 5.422±3.334 4.590±3.081V3d 7.640±2.082 6.270±2.740 5.817±3.062 4.614±2.939hV4 7.438±2.339 6.419±2.682 6.236±3.021 5.205±3.090VO1 7.185±2.436 5.996±2.822 5.386±3.068 5.131±3.044VO2 7.181±2.733 5.854±2.982 5.572±3.540 4.748±3.180PHC1 6.733±2.493 5.807±2.877 5.583±3.287 4.662±2.658PHC2 5.244±2.799 5.324±2.903 3.994±3.026 3.169±2.655MST 7.321±2.381 5.230±2.740 5.161±2.858 4.545±3.064hMT 7.165±2.293 5.880±2.752 5.861±2.726 4.286±2.422LO2 6.912±2.373 6.083±2.136 5.675±3.119 5.162±2.795LO1 7.377±2.328 6.489±2.432 6.003±3.069 4.869±2.652V3a 7.394±2.427 6.187±2.475 6.019±3.234 4.983±2.865V3b 7.387±2.176 5.989±3.051 5.967±3.308 3.617±2.766IPS0 7.479±2.590 6.35±3.213 5.567±2.841 4.762±3.067IPS1 7.321±2.276 5.939±2.903 4.747±2.911 4.848±2.867IPS2 6.190±2.840 5.222±2.870 5.347±2.807 3.860±2.666IPS3 5.588±2.483 5.430±2.980 4.883±2.981 4.552±2.208IPS4 5.504±2.520 4.935±2.768 4.072±2.258 4.417±2.806IPS5 5.556±2.386 4.646±2.278 4.858±2.989 3.788±2.550SPL1 5.337±2.774 5.348±2.347 3.758±2.687 3.540±2.267FEF 4.135±2.452 4.120±2.080 2.7±1.816 2.717±1.937

Right HemisphereV1v 6.719±2.496 6.115±2.724 6.158±2.941 4.145±3.048V1d 6.931±2.448 5.124±2.802 5.978±3.155 5.186±2.848V2v 7.273±2.457 6.072±2.441 6.328±2.573 5.262±2.567V2d 7.531±2.005 6.189±2.380 6.347±3.212 4.888±2.820V3v 7.377±2.273 5.724±2.711 5.825±2.727 5.388±2.788V3d 7.515±2.217 6.230±2.479 6.181±3.250 5.052±2.716hV4 6.758±2.997 5.391±2.545 5.825±2.899 4.964±3.190VO1 7.275±2.078 5.676±2.826 5.564±3.293 5.079±3.154VO2 6.919±2.475 5.796±2.676 6.347±3.296 4.693±2.783PHC1 6.496±2.553 5.735±2.637 5.858±3.241 4.600±2.917PHC2 5.331±2.918 5.200±2.547 5.092±2.650 3.729±2.887MST 6.979±2.650 5.315±3.013 4.956±3.409 4.300±3.072hMT 7.352±2.195 6.163±2.588 6.447±2.618 4.917±2.852LO2 6.958±2.273 5.913±2.673 5.714±3.282 5.202±2.944LO1 6.638±2.504 5.735±2.515 5.522±2.862 5.262±2.780

Region HC NMOSD CIS-ON CIS-nONV3a 7.387±2.456 6.124±2.642 6.219±2.781 5.388±2.957V3b 7.462±2.475 6.083±2.263 6.361±2.849 5.083±3.132IPS0 6.010±2.621 5.670±2.750 5.919±2.885 4.690±3.110IPS1 6.367±2.881 5.880±2.624 5.278±3.201 4.581±3.116IPS2 6.110±3.020 5.143±2.580 5.169±2.506 4.402±2.883IPS3 6.098±3.016 5.374±2.765 5.914±2.668 4.781±3.011IPS4 5.713±3.011 5.330±2.555 5.247±2.933 4.279±2.481IPS5 5.112±2.299 4.907±2.768 4.675±3.189 4.245±2.843SPL1 4.835±2.756 4.574±2.410 4.964±2.664 3.957±2.459FEF 4.102±2.230 4.193±2.897 3.561±2.164 2.464±2.175

V1 = primary visual cortex; V2 = secondary visual cortex; V3 = visual area V3; (v = ventral; d = dorsal); hV4 = human visual region V4; VO = ventral occipital cortex; PHC = ; MST = medial superior temporal area; hMT = human middle temporal region; LO = lateral occipital cortex; IPS = intraparietal sulcus; SPL = superior parietal lobule; FEF = frontal eye field

Table e-3: local region efficiency for visual network by hemisphere (mean±SD)

Region HC NMOSD CIS-ON CIS-nONLeft Hemisphere

V1v 0.386±0.070 0.373±0.083 0.350±0.121 0.289±0.120V1d 0.394±0.065 0.364±0.093 0.350±0.117 0.315±0.129V2v 0.394±0.067 0.378±0.061 0.352±0.113 0.298±0.127V2d 0.395±0.057 0.387±0.068 0.370±0.111 0.330±0.107V3v 0.405±0.046 0.374±0.076 0.352±0.112 0.304±0.115V3d 0.402±0.049 0.398±0.047 0.344±0.138 0.295±0.124hV4 0.389±0.064 0.358±0.083 0.357±0.105 0.321±0.106VO1 0.397±0.056 0.369±0.084 0.316±0.125 0.305±0.129VO2 0.381±0.079 0.388±0.076 0.334±0.124 0.315±0.124PHC1 0.383±0.085 0.374±0.074 0.336±0.116 0.320±0.114PHC2 0.329±0.120 0.355±0.098 0.259±0.146 0.258±0.126MST 0.391±0.052 0.365±0.090 0.317±0.121 0.284±0.114hMT 0.399±0.054 0.394±0.044 0.355±0.100 0.312±0.115LO2 0.414±0.035 0.402±0.036 0.328±0.123 0.308±0.110LO1 0.401±0.044 0.389±0.044 0.325±0.135 0.308±0.103V3a 0.409±0.039 0.396±0.050 0.339±0.120 0.308±0.115V3b 0.409±0.049 0.363±0.085 0.337±0.117 0.270±0.108IPS0 0.367±0.084 0.333±0.101 0.328±0.111 0.297±0.115IPS1 0.359±0.076 0.340±0.090 0.329±0.084 0.298±0.114IPS2 0.376±0.060 0.368±0.074 0.339±0.072 0.284±0.104IPS3 0.392±0.039 0.366±0.083 0.325±0.077 0.325±0.072IPS4 0.408±0.040 0.371±0.087 0.345±0.094 0.329±0.091IPS5 0.400±0.037 0.352±0.090 0.320±0.105 0.305±0.097SPL1 0.384±0.058 0.374±0.064 0.332±0.087 0.303±0.109FEF 0.356±0.082 0.336±0.091 0.266±0.128 0.239±0.110

Right HemisphereV1v 0.386±0.072 0.347±0.090 0.341±0.124 0.290±0.136V1d 0.382±0.057 0.355±0.099 0.344±0.117 0.324±0.124V2v 0.389±0.067 0.372±0.074 0.361±0.091 0.345±0.095V2d 0.393±0.053 0.388±0.041 0.345±0.117 0.323±0.112V3v 0.399±0.045 0.345±0.101 0.337±0.091 0.318±0.107V3d 0.397±0.052 0.374±0.063 0.342±0.137 0.327±0.104hV4 0.377±0.089 0.357±0.085 0.354±0.116 0.316±0.116VO1 0.403±0.049 0.356±0.089 0.330±0.125 0.307±0.121VO2 0.396±0.058 0.384±0.066 0.347±0.123 0.296±0.115PHC1 0.382±0.073 0.367±0.078 0.360±0.128 0.286±0.112PHC2 0.350±0.095 0.356±0.080 0.339±0.122 0.255±0.130MST 0.392±0.053 0.341±0.124 0.304±0.135 0.270±0.110hMT 0.393±0.056 0.371±0.080 0.370±0.087 0.305±0.114LO2 0.406±0.043 0.391±0.069 0.331±0.132 0.318±0.101LO1 0.415±0.040 0.390±0.059 0.322±0.127 0.335±0.096

Region HC NMOSD CIS-ON CIS-nONV3a 0.393±0.057 0.386±0.064 0.333±0.110 0.336±0.098V3b 0.377±0.068 0.367±0.065 0.351±0.111 0.306±0.116IPS0 0.348±0.094 0.342±0.095 0.341±0.093 0.288±0.114IPS1 0.343±0.094 0.345±0.084 0.331±0.090 0.295±0.130IPS2 0.355±0.094 0.380±0.054 0.351±0.092 0.296±0.123IPS3 0.391±0.051 0.384±0.038 0.350±0.080 0.314±0.101IPS4 0.400±0.042 0.371±0.072 0.349±0.093 0.342±0.095IPS5 0.397±0.046 0.367±0.072 0.353±0.092 0.319±0.095SPL1 0.381±0.093 0.385±0.071 0.352±0.091 0.293±0.105FEF 0.351±0.101 0.340±0.110 0.304±0.114 0.263±0.140

V1 = primary visual cortex; V2 = secondary visual cortex; V3 = visual area V3; (v = ventral; d = dorsal); hV4 = human visual region V4; VO = ventral occipital cortex; PHC = ; MST = medial superior temporal area; hMT = human middle temporal region; LO = lateral occipital cortex; IPS = intraparietal sulcus; SPL = superior parietal lobule; FEF = frontal eye field

e-References

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