Supplementary Material for Evaluating the Effective Connectivity of Resting State Networks

Supplementary Material for “Evaluating the effective connectivity of resting state networks using conditional Granger causality”

Wei Liaoa,†, Dante Mantinib,c,d,†, Zhiqiang Zhange, Zhengyong Pana, Huafu Chena,*, Jurong Dinga, Qiyong Gongf, Yihong Yangg

a Key Laboratory for Neuroinformation of Ministry of Education, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu 610054, PR China.

b Institute for Advanced Biomedical Technologies, G. D’Annunzio University Foundation, Chieti, Italy.

c Department of Clinical Sciences and Bio-imaging, G. D’Annunzio University, Chieti, Italy.

d Laboratory for Neuro-psychophysiology, K.U. Leuven Medical School, Leuven, Belgium.

e Department of Medical Imaging, Nanjing Jinling Hospital, Clinical School, Medical College, Nanjing University, Nanjing 210002, PR China.

f Huaxi MR Research Center (HMRRC), Department of Radiology, West China Hospital of Sichuan University, West China School of Medicine, 610041, PR China.

g Neuroimaging Research Branch, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD, USA.

†Wei Liao and Dante Mantini contribute equally to this work.

Running title: effective connectivity of resting state networks

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Supplementary Fig. 1

Components estimation from minimum description length (MDL) criteria. For our resting state fMRI data, MDL indicated 40 components.

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Supplementary Fig. 2

Net Granger causal afferent connections (Out-degree) of all RSNs. Significant differences in net Granger causal afferent connections between RSN 7 (self-referential network) and other RSNs, statistically assessed with the Mann-Whitney U test (P < 0.05, FDR-corrected for multiple comparison), are indicated with a green line. Similarly, significant differences in net Granger causal afferent between RSN 1 (DMN) and other RSNs are shown with a red line.

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Supplementary Fig. 3

Net Granger causal efferent connections (In-degree) of all RSNs. Significant differences in net Granger causal efferent connections between RSN 7 (self-referential network) and other RSNs, statistically assessed with the Mann-Whitney U test (P < 0.05, FDR-corrected for multiple comparison), are indicated with a green line. Similarly, significant differences in net Granger causal efferent between RSN 1 (DMN) and other RSNs are shown with a red line.

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Supplementary Table 1

Peak foci of the brain areas that compose the eight RSNs

Anatomical region / BA / Cluster size
Voxels L/R / MNI coordinates
L/R / Z-score
L/R
RSN 1
Medial frontal gyrus, orbital / 10,11 / 144/128 / (0,63,-6)/(3,63,-6) / 7.65/6.76
Superior frontal gyrus, medial / 10,11 / 458/341 / (0,63,12)/(3,63,12) / 6.99/6.68
Rectus / 10,11 / 43/20 / (0,60,-15)/(3,60,-15) / 6.30/5.62
Anterior cingulate gyrus / 10,11 / 144/68 / (-3,54,-3)/(3,54,12) / 4.38/4.82
Precuneus / 23,30 / 182/97 / (0,-57,15)/(3,-57,18) / 4.46/4.02
Calcarine / 17 / 63/50 / (0,-60,15)/(3,-57,12) / 4.36/4.15
Superior frontal gyrus / 9,10 / 245/122 / (-9,69,15)/(12,66,24) / 3.99/4.33
Posterior cingulate gyrus / 23,26,29 / 55/20 / (0,-54,21)/(3,-57,30) / 3.80/2.58
Cuneus / 18,23 / 36/10 / (0,-66,21)/(6,-63,21) / 3.70/2.65
Superior frontal gyrus, orbital / 11 / 36/20 / (-12,60,-6)/(9,63,-18) / 3.48/2.48
Lingual / 17,18 / 15/26 / (0,-63,9)/(3,-60,6) / 3.38/3.18
Middle temporal gyrus / 37,39 / 10/87 / (-51,-72,9)/(54,-69,21) / 1.79/2.58
Middle frontal gyrus / 8 / 26/7 / (-21,27,54)/(21,63,27) / 2.19/2.48
Middle occipital gyrus / 19,37 / 11/56 / (-51,-75,9)/(54,-69,24) / 1.66/2.44
Middle frontal gyrus / 9,45,46 / 46/249 / (-45,27,39)/(45,36,36) / -1.88/-4.40
Inferior frontal gyrus, triangular / 44,45 / NA/26 / NA/(48,30,30) / NA/-2.45
Cuneus / 18,19 / 28/26 / (-6,-84,33)/(9,-81,36) / -1.94/-1.98
Angular / 39,40 / 24/35 / (-57,-60,33)/(51,-57,42) / -1.93/-1.90
Inferior parietal gyrus / 39,40 / 10/28 / (-57,-57,36)/(51,-54,42) / -1.88/-1.90
RSN 2
Middle occipital gyrus / 7,19,39 / 341/74 / (-36,-81,39)/(39,-78,39) / 6.85/2.54
Inferior parietal gyrus / 7,40 / 172/NA / (-36,-81,42)/NA / 6.82/NA
Angular / 7,39,40 / 282/121 / (-39,-75,45)/(42,-72,48) / 6.51/2.62
Superior parietal gyrus / 7 / 84/17 / (-30,-75,54)/(36,-78,48) / 5.28/2.32
Middle temporal gyrus / 21,37,39 / 206/NA / (-48,-75,21)/NA / 4.33/NA
Superior occipital gyrus / 7,19 / 45/13 / (-24,-84,45)/(36,-78,45) / 3.78/2.35
Posterior cingulate gyrus / 23,26 / 101/23 / (-3,-42,33)/(3,-45,30) / 3.55/2.51
Median cingulate gyrus / 23 / 73/21 / (-3,-42,34)/(3,-42,33) / 3.55/2.64
Middle frontal gyrus / 8,9,44 / 347/19 / (-30,18,60)/(48,37,31) / 3.18/1.88
Precuneus / 23,30 / 198/39 / (-3,-60,21)/(3,-60,21) / 2.89/2.20
Inferior temporal gyrus / 20,37 / 140/NA / (-60,-36,-15)/NA / 2.88/NA
Superior frontal gyrus / 8,9,32 / 159/NA / (-21,30,51)/NA / 2.79/NA
Cuneus / 18,23 / 67/NA / (-3,-69,24)/NA / 2.76/NA
Calcarine fissure / 18,23 / 70/10 / (-3,-66,21)/(3,-60,18) / 2.69/2.05
Gyrus rectus / 11 / 19/NA / (-3,54,-15)/NA / 2.27/NA
Medial frontal gyrus, orbital / 11 / 12/NA / (-3,54,-15)/NA / 2.27/NA
Inferior frontal gyrus, triangular / 45,46,47 / 32/NA / (-42,42,0)/NA / 2.06/NA
Inferior frontal gyrus, orbital / 45,46,47 / 46/NA / (-42,42,-3)/NA / 2.04/NA
Middle frontal gyrus, orbital / 46,47 / 19/NA / (-42,45,-6)/NA / 2.04/NA
Superior frontal gyrus, medial / 10 / 17/24 / (0,60,12)/(3,60,12) / -2.18/-2.28
Cuneus / 19 / NA/23 / NA/(9,-87,39) / NA/-2.21
RSN 3
Middle occipital gyrus / 7,9 / NA/181 / NA/(51,-69,27) / NA/6.23
Middle temporal gyrus / 21,22,39 / NA/591 / NA/(64,-63,21) / NA/6.16
Angular gyrus / 22,39 / NA/391 / NA/(51,-69,30) / NA/6.15
Superior temporal gyrus / 22,42 / NA/61 / NA/(57,-60,21) / NA/5.68
Superior frontal gyrus / 8,9 / NA/512 / NA/(24,27,57) / NA/4.99
Middle frontal gyrus / 8,44,46 / 31/635 / (-39,27,36)/(27,36,48) / 1.90/4.27
Inferior parietal gyrus / 8,9,46 / NA/70 / NA/(54,-63,39) / NA/3.90
Supramarginal gyrus / 39,40 / NA/49 / NA/(60,-51,24) / NA/3.36
Superior frontal gyrus, medial / 8,9,32 / 35/215 / (3,51,39)/(15,33,60) / 2.01/3.27
Inferior temporal gyrus / 20,21 / NA/84 / NA/(60,-21,-18) / NA/2.72
Supplementary motor area / 6,8 / NA/19 / NA/(15,24,66) / NA/2.67
Precuneus / 23 / NA/145 / NA/(6,-57,33) / NA/2.28
Posterior cingulate gyrus / 23 / NA/12 / NA/(6,-57,30) / NA/2.28
Inferior frontal gyrus, opercular / 44,48 / NA/34 / NA/(42,24,30) / NA/2.21
Precentral gyrus / 6,9 / NA/22 / NA/(45,9,48) / NA/2.11
Median cingulate gyrus / 32 / NA/53 / NA/(6,-51,33) / NA/2.09
Inferior frontal gyrus, triangular / 44,45,48 / NA/16 / NA/(45,24,30) / NA/2.04
Anterior cingulate gyrus / 32 / NA/34 / NA/(6,51,9) / NA/1.87
Superior parietal gyrus / 7 / 140/43 / (-21,-81,51)/(27,-72,51) / -2.34/-1.93
Precuneus / 7 / 18/NA / (-12,-78,57)/NA / -2.07/NA
Superior frontal gyrus / 10,46 / 44/NA / (-24,60,24)/NA / -2.05/NA
Superior frontal gyrus, medial / 10 / 22/NA / (-6,63,30)/NA / -1.99/NA
Superior occipital gyrus / 7,19 / 33/NA / (-18,-84,48)/NA / -1.95/NA
Inferior parietal gyrus / 7,40 / 83/NA / (-36,-63,54)/NA / -1.88/NA
Angular gyrus / 7 / NA/12 / NA/(30,-69,48) / NA/-1.84
Middle frontal gyrus / 45,46 / NA/24 / NA/(51,45,18) / NA/-1.83
RSN 4
Superior occipital gyrus / 18,19 / 329/338 / (-15,-90,36)/(27,-90,30) / 3.79/4.06
Middle occipital gyrus / 19,39 / 440/378 / (-21,-93,18)/(30,-87,21) / 3.34/3.88
Cuneus / 17,18,19 / 187/230 / (-9,-93,33)/(15,-90,39) / 3.32/3.75
Inferior temporal gyrus / 19,37 / NA/99 / NA/(48,-72,-6) / NA/3.20
Inferior occipital gyrus / 18,19 / 155/168 / (-39,-84,-6)/(45,-75,-3) / 2.58/3.20
Middle temporal gyrus / 19,37 / NA/110 / NA/(48,-75,0) / NA/3.20
Superior parietal gyrus / 7 / 42/69 / (-18,-81,45)/(12,-84,48) / 2.12/2.92
Calcarine fissure / 17,18 / 171/147 / (-3,-93,12)/(9,-93,12) / 2.79/2.79
Lingual gyrus / 17,18 / 154/172 / (-6,-84,-3)/(21,-69,-15) / 2.29/2.41
Fusiform gyrus / 18,19,37 / 51/119 / (-42,-75,-15)/(45,-66,-18) / 2.25/2.39
Precuneus / 7 / NA/14 / NA/(12,-81,48) / NA/2.20
Superior frontal gyrus / 8,9 / 56/16 / (-15,39,54)/(18,36,57) / 2.11/1.78
Superior frontal gyrus, medial / 8,9 / 13/NA / (-9,42,54)/NA / 1.79/NA
Lingual gyrus / 18 / NA/11 / NA/(15,-102,-12) / NA/-2.14
Calcarine fissure / 17 / 14/16 / (3,-102,-6)/(15,-57,9) / -1.99/-1.93
RSN 5
Superior temporal gyrus / 21,22,41,42,48 / 523/713 / (-63,-24,9)/(66,-21,6) / 4.90/6.40
Middle temporal gyrus / 21,22,37,42 / 439/198 / (-63,-12,0)/(66,-33,3) / 4.43/3.95
Supramarginal gyrus / 2,4,43,48 / 76/209 / (-63,-24,15)/(66,-24,18) / 4.30/3.78
Superior temporal pole / 48 / 11/88 / (-60,3,0)/(60,3,-3) / 2.55/4.25
Rolandic operculum / 48 / 32/123 / (-60,0,3)/(63,-18,12) / 2.60/4.21
Postcentral gyrus / 1,2,3 / 56/72 / (-60,-21,15)/(63,-15,15) / 3.64/2.69
Heschl gyrus / 48 / 16/39 / (-60,-12,9)/(51,-12,3) / 2.61/3.54
Middle temporal pole / 20 / NA/29 / NA/(45,6,-33) / NA/2.59
Insula / 48 / NA/18 / NA/(45,-12,0) / NA/2.17
Calcarine fissure / 17 / 15/NA / (-3,-99,3)/NA / 1.90/NA
Precuneus / 23 / 30/NA / (-3,-57,27)/NA / 1.76/NA
Anterior cingulate gyrus / 10,11 / 80/34 / (0,36,-6)/(0,33,-3) / -3.37/-2.99
Medial frontal gyrus, orbital / 11 / 13/15 / (-3,36,-9)/(0,33,-9) / -2.43/-3.04
Superior temporal pole / 38 / 31/NA / (-39,12,-21)/NA / -2.04/NA
Superior frontal gyrus / 9 / NA/16 / NA/(18,48,48) / NA/-1.83
Superior frontal gyrus, medial / 9 / NA/16 / NA/(6,54,45) / NA/-1.80
RSN 6
Precuneus / 5 / 146/118 / (-3,-45,78)/(3,-48,78) / 4.64/4.88
Paracentral lobul / 4 / 247/198 / (-3,-39,81)/(3,-42,78) / 4.48/4.68
Postcentral gyrus / 1,2,3,4 / 315/415 / (-21,-36,81)/(24,-36,81) / 4.50/4.40
Supplementary motor area / 6 / 71/105 / (0,-21,60)/(3,-18,78) / 3.16/4.10
Precentral gyrus / 4,6 / 120/186 / (-27,-24,78)/(24,-24,81) / 3.08/3.83
Superior parietal gyrus / 5,7 / 92/119 / (-21,-45,78)/(24,-45,78) / 3.52/3.17
Median cingulate gyrus / 23 / 74/46 / (0,-27,51)/(3,-27,51) / 2.66/2.52
Superior temporal pole / 38 / NA/35 / NA/(57,15,-15) / NA/2.17
Inferior parietal gyrus / 40 / 10/NA / (-48,-42,60)/NA / 2.02/NA
Cerebelum 4,5 / 30 / 10/NA / (-3,-45,-12)/NA / 1.95/NA
Vermis 10 / - / 27 / (0,-45,-30) / -3.60
Superior frontal gyrus / 8 / NA/10 / NA/(18,27,63) / NA/-1.77
RSN 7
Gyrus rectus / 11 / 205/149 / (-3,48,-18)/(3,48,-18) / 11.3/9.57
Medial frontal gyrus, orbital / 10,11 / 181/229 / (-3,48,-15)/(3,48,-15) / 10.6/8.69
Superior frontal gyrus, orbital / 11 / 138/173 / (-9,48,-21)/(9,54,-21) / 6.91/6.84
Anterior cingulate gyrus / 24,25,32 / 145/98 / (0,42,-6)/(3,36,-9) / 6.80/5.62
Middle frontal gyrus, orbital / 10,11 / 80/45 / (-21,45,-18)/(15,51,-18) / 3.77/5.02
Superior frontal gyrus, medial / 10,11 / 41/42 / (-12,51,0)/(3,45,0) / 2.80/3.92
Olfactory cortex / 11,25 / 11/NA / (-6,30,-3)/NA / 2.93/NA
Inferior frontal gyrus, orbital / 11,47 / 39/NA / (-27,39,-18)/NA / 2.67/NA
Vermis 10 / - / 10 / (0,-48,-30) / 2.02
Vermis 3 / - / 16 / (0,-42,-12) / -2.04
RSN 8
Superior frontal gyrus, medial / 9,10,32 / 385/279 / (-3,39,33)/(3,39,36) / 4.92/4.90
Median cingulate gyrus / 24,32 / 18/99 / (-3,30,36)/(3,39,30) / 4.25/4.75
Anterior cingulate gyrus / 24,32 / 219/232 / (-3,36,27)/(3,39,27) / 4.26/4.38
Supplementary motor area / 6,8,32 / 41/53 / (-3,24,48)/(3,24,48) / 3.95/3.92
Middle frontal gyrus / 44,45,46 / NA/219 / NA/(45,27,39) / NA/2.85
Medial frontal gyrus, orbital / 10 / 18/27 / (0,51,-3)/(3,48,-3) / 2.73/2.40
Superior frontal gyrus / 32 / NA/14 / NA/(12,39,27) / NA/2.30
Inferior frontal gyrus, orbital / 47 / 16/44 / (-30,21,-18)/(33,24,-12) / 1.95/2.30
Insula / 38,47 / NA/32 / NA/(33,21,-12) / NA/2.14
Middle temporal gyrus / 20,21 / NA/21 / NA/(63,-21,-18) / NA/2.12
Inferior frontal gyrus, triangular / 44,45 / NA/15 / NA/(48,30,30) / NA/2.03
Angular gyrus / 39,40 / 39/39 / (-48,-60,33)/(48,-60,39) / 1.90/1.90
Inferior parietal gyrus / 39 / NA/15 / NA/(51,-60,39) / NA/1.78
Supramarginal gyrus / 40,48 / NA/69 / NA/(63,-33,24) / NA/-2.79
Superior temporal gyrus / 22,41,42 / 36/113 / (-60,-48,15)/(63,-33,21) / -2.00/-2.58
Middle temporal gyrus / 37,39 / 18/181 / (-60,-51,12)/(57,-66,9) / -1.89/-2..34
Middle frontal gyrus / 46 / 98/NA / (-39,42,27)/NA / -2.19/NA
Gyrus rectus / 11 / 14/NA / (0,57,-24)/NA / -1.91/NA
Rolandic operculum / 48 / 14/NA / (-57,3,6)/NA / -1.68/NA

Regions above threshold were selected, along with MNI coordinates of peak foci, as well as the Brodmann areas (BA) in which activations occur. Left and right denote the left hemisphere and right hemisphere, respectively. NA denotes not available.

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Supplementary Table 2

Mean CGCA directed influence F values ( and ) (mean ± SE across subjects) between pairs of RSNs in low frequency

Fx→y / RSN 1 / RSN 2 / RSN 3 / RSN 4 / RSN 5 / RSN 6 / RSN 7 / RSN 8
RSN 1 / – / (5.1±1.2)10-2 / (5.3±1.7)10-2 / (5.6±1.4)10-2 / (5.8±1.3)10-2 / (2.7±0.8)10-2 / (3.5±1.3)10-2 / (4.8±1.1)10-2
RSN 2 / (3.7±0.9)10-2 / – / (4.0±0.9)10-2 / (4.3±1.0)10-2 / (3.8±0.9)10-2 / (6.5±1.4)10-2
(p<0.0001) / (3.3±1.0)10-2 / (4.0±1.1)10-2
RSN 3 / (6.9±2.4)10-2
(p<0.0001) / (4.1±1.0)10-2 / – / (4.7±0.9)10-2 / (4.6±1.2)10-2 / (3.9±1.0)10-2 / (4.2±1.1)10-2 / (6.4±1.4)10-2
(p<0.0001)
RSN 4 / (4.1±0.9)10-2 / (6.1±1.1)10-2 / (3.7±0.9)10-2 / – / (3.4±1.0)10-2 / (8.7±1.3)10-2
(p<0.0001) / (3.7±0.9)10-2 / (4.5±0.6)10-2
RSN 5 / (7.1±1.4)10-2
(p<0.0001) / (6.0±1.5)10-2 / (6.8±1.7)10-2
(p<0.0001) / (8.4±1.8)10-2
(p<0.0001) / – / (19±3.2)10-2
(p<0.0001) / (5.0±1.1)10-2 / (6.1±1.3)10-2
RSN 6 / (6.0±1.4)10-2 / (5.7±1.1)10-2 / (5.5±2.0)10-2 / (10±2.2)10-2
(p<0.0001) / (12±2.1)10-2
(p<0.0001) / – / (4.5±1.2)10-2 / (4.6±1.4)10-2
RSN 7 / (6.5±1.4)10-2
(p<0.0001) / (5.1±1.2)10-2 / (6.7±1.3)10-2
(p<0.0001) / (4.9±1.1)10-2 / (6.3±1.2)10-2
(p<0.0001) / (4.3±0.9)10-2 / – / (5.4±1.2)10-2
RSN 8 / (6.8±1.4)10-2
(p<0.0001) / (6.9±1.9)10-2
(p<0.0001) / (6.7±1.5)10-2
(p<0.0001) / (5.5±1.3)10-2 / (4.8±1.0)10-2 / (5.5±1.6)10-2 / (2.7±1.1)10-2 / –

CGAC directed influence terms ( and ) (mean ± SE, between pairs of RSNs across subjects). Influences are from row RSN to column RSN. Violet boxes indicate significant directed influence at group-level (p < 0.05, FDR corrected for multiple comparison; p values are in brackets).