Functional Connectivity Analysis of Brain Networks

Functional data was preprocessed using fMRIPrep^{30 (link)}; RRID:SCR_016216). Specifically, a reference volume and its skull-stripped version were generated using a custom methodology of fMRIPrep. Head-motion parameters with respect to the BOLD reference (transformation matrices, and six corresponding rotation and translation parameters) were estimated before any spatiotemporal filtering using mcflirt (FSL 5.0.9)^{36 (link)}. BOLD runs were slice-time corrected using 3dTshift from AFNI 201 602 07^{37 (link)} (RRID:SCR_005927). The BOLD reference was then co-registered to the T1w reference using bbregister (FreeSurfer) which implements boundary-based registration³⁸ . Co-registration was configured with six degrees of freedom. The BOLD time-series were resampled into standard MNI152NLin2009cAsym space. Several confounding time-series were calculated based on the preprocessed BOLD: Frame-wise displacement (FWD) was calculated from the six motion parameters and root-mean-square difference (RMSD) of the BOLD percentage signal in the consecutive volumes. Contaminated volumes were then detected and classified as outliers by the criteria FWD > 0.5 mm or RMSD > 0.3% and replaced with new volumes generated by linear interpolation of adjacent volumes. The three global signals are extracted within the cerebrospinal fluid (CSF), the white matter masks. A bandpass filter with cut-off frequencies of 0.01 and 0.09 Hz was used. Finally, the covariates corresponding to head motion (6 realignment parameters), outliers, and the BOLD time series from the subject-specific white matter and CSF masks were used in the connectivity analysis as predictors of no interest, and were removed from the BOLD functional time series using linear regression.
ROI-to-ROI connectivity analysis was performed in CONN toolbox using 11 CONN resting state network nodes composing 3 networks (Default Mode Network (DMN): medial pre-frontal cortex (MPFC), precuneus cortex (PCC), bilateral lateral parietal (LP); Salience Network (SN): anterior cingulate cortex (ACC), bilateral anterior insula (AI), rostral pre-frontal cortex (RPFC), and supramarginal gyrus (SMG); Fronto-parietal Network (FP): bilateral lateral pre-frontal cortex (LPFC) and posterior parietal cortex (PPC)^{39 (link)}. The mean BOLD time series was computed across all voxels within each ROI. Bivariate regression analyses were used to determine the linear association of the BOLD time series between each pair of regions for each subject. Both positive and negative correlations were examined. The resultant correlation coefficients were transformed into z-scores using Fisher’s transformation to satisfy normality assumptions. The within network-level FC was calculated as the average of the FCs within the networks of SN, DMN and FPN.