Supplementary Figure 1. Resting State Networks Identified by Independent Component Analysis (ICA). Seventeen
networks were identified as valid, non-noise networks from the ICA (originally restricted to 30 components). Voxel based
statistics used, cluster corrected p < 0.05. Image left equals subject right. Networks: A. Cerebellum; B. Right Executive Control
Network (ECN); C. Primary Visual; D. Medial Sensory-Motor; E. Precuneus / Default Mode Network (DMN); F. Ventral DMN; G.
Anterior DMN; H. Visuospatial and Left ECN; I. Visuospatial (Lateral); J. Higher Visual; K. Language and Dorsal DMN; L. Lateral
Sensory-Motor; M. Salience; N. Basal Ganglia; O. Visuospatial (Medial); P. Auditory; Q. Medial Temporal Lobe.
Supplementary Figure 2. PCC-Connected aROIs for Clinical and Behavioral Associations. Regions of increased functional
connectivity (FC) to the seed PCC region, as identified by the seed-based FC analysis (light yellow), were overlaid with mask
regions from the AAL atlas (light purple) to determine anatomically defined regions of interest (aROIs, overlap, red). Mean
activity time courses were extracted from each of the 10 aROIs (red). The degree of correlation between the PCC seed time
course and aROI time courses were then used as input to assess correlations with clinical and behavioral measures. Image left
equals subject right. Results in Table 4A. A. left insula (z= 4); B. right insula (z = 6); C. right thalamus (z = 12); D. bilateral
putamen (z= 4); E. bilateral globus pallidus (z = 2); F. left dorsolateral prefrontal cortex (y = 44); G. left hippocampus (y = -6);
H. left amygdala (y = -2).
Supplementary Figure 3. Precuneus-Connected aROIs for Clinical and Behavioral Associations. Regions of increased
functional connectivity (FC) to the seed left precuneus region, as identified by the seed-based FC analysis (yellow), were
overlaid with mask regions from the AAL atlas (purple) to determine anatomically defined regions of interest (aROIs, overlap,
red). Mean activity time courses were extracted from each of the 11 aROIs (red). The degree of correlation between the left
precuneus seed time course and aROI time courses were then used as input to assess correlations with clinical and behavioral
measures. Image left equals subject right. Results in Table 4B. A. left ventromedial prefrontal cortex (x = -2); B. right
ventromedial prefrontal cortex (x = 6); C. left orbitofrontal cortex (z = -10); D. right orbitofrontal cortex (z = -8); E. right
anterior cingulate cortex (x = 4); F. left mid-cingulate cortex (z =34); G. right superior parietal lobe (x = 38); H. right inferior
parietal lobe (y = -54); I. right angular gyrus (x = 42); J. left precuneus (x = -6); K. right precuneus (x = 6).
A.
x=2
y = -30
x = -22
y = -74
z = 34
B.
R.
z = 26
Supplementary Figure 4. Results from Dual Regression Analysis with Site-Effects Regressed. Site-effects were regressed
from the dual regression analysis with each site entered as a covariate (EV) during the randomise step. Results were nearly
identical to the results from the original analysis, which did not include regression of site-effects. PCC peak voxel at 4, -30, 36.
Left precuneus peak voxel at -22, -74, 26.
Table S1. Mean Functional Connectivity Values (z-scores) for PCC and L. Precuneus Seed-Based FC Analyses - With and Without Global
Scaling
Original Analysis with Global Signal Regression
CPP HC
Interpretation
PCC
0.75 0.24
Negative connectivity (anticorrelation) in HCs; postive connectivity in patients.
L. Precuneus 0.02 1.19
Negative connectivity (anticorrelation) in HCs; nearly eliminated connectivity in patients.
Subsequent Confirmatory Analysis with NO Global Signal Regression
CPP HC
Interpretation
PCC
0.64 0.23
Negative connectivity (anticorrelation) in HCs; postive connectivity in patients.
L. Precuneus 0.21 1.23
Negative connectivity (anticorrelation) in HCs; less strong negative connectivity in patients.
Supplementary Table 1. Mean Functional Connectivity Values With and Without Global Signal Regression Mean z-score
values were extracted from each subject’s resting-state data within the masked region pertaining to the group seed-based
functional connectivity results, separately for PCC and left precuneus seeds. These values were averaged within each group
(45 patients, 45 HCs) for each seed (PCC, left precuneus) from two separate analyses: 1) the original analyses performed on
preprocessed data with global signal regression (as reported in the manuscript) and 2) a subsequent analysis performed on
preprocessed data without global signal regression. The results from the subsequent analysis without global signal regression
were nearly identical (both spatial distribution and direction of correlation values) indicating that the negative values
observed (anticorrelations) in the original analysis were valid and not due to global scaling.