Heritability estimates on resting state fMRI data using ENIGMA analysis pipeline

Abstract

Big data initiatives such as the Enhancing NeuroImaging Genetics through Meta-Analysis consortium (ENIGMA), combine data collected by independent studies worldwide to achieve more generalizable estimates of effect sizes and more reliable and reproducible outcomes. Such efforts require harmonized image analyses protocols to extract phenotypes consistently. This harmonization is particularly challenging for resting state fMRI due to the wide variability of acquisition protocols and scanner platforms; this leads to site-to-site variance in quality, resolution and temporal signal-to-noise ratio (tSNR). An effective harmonization should provide optimal measures for data of different qualities. We developed a multi-site rsfMRI analysis pipeline to allow research groups around the world to process rsfMRI scans in a harmonized way, to extract consistent and quantitative measurements of connectivity and to perform coordinated statistical tests. We used the single-modality ENIGMA rsfMRI preprocessing pipeline based on modelfree Marchenko-Pastur PCA based denoising to verify and replicate resting state network heritability estimates. We analyzed two independent cohorts, GOBS (Genetics of Brain Structure) and HCP (the Human Connectome Project), which collected data using conventional and connectomics oriented fMRI protocols, respectively. We used seed-based connectivity and dual-regression approaches to show that the rsfMRI signal is consistently heritable across twenty major functional network measures. Heritability values of 20-40% were observed across both cohorts.

Fig. 1

Flowchart of ENIGMA rsfMRI analysis pipeline.

Fig. 2

ENIGMA EPI brain template (a) and segmented tissue classes (b–d) for gray matter, white matter and cerebrospinal fluid, respectively.

Fig.3

Resting state network template ROIs based on the BrainMap activation database and resting fMRI dataset [4]. Here, L=left, R=right, in (a) a₁=left primary and association auditory cortices, a₂=right primary and associated auditory cortices, in (b) r₁=posterior cingulate/precuneus, r₂=bilateral temporal-parietal regions and, r₃=ventromedial frontal cortex, in (c) f₁/f₂=left/right frontal area and p₁/p₂=left/right parietal area, in (d) m₁/m₃=left/right motor area and m₂=supplementary motor area, in (e) v₁=medial visual areas, v₂= occipital visual areas, and v₃=lateral visual areas, in (f) r₁=anterior cingulate cortex and r₂=bilateral medial frontal gyrus, in (g) r₁=anterior cingulate cortex and r₂/r₃=left/right insula, in (h) f₁/f₂=left/right middle frontal gyrus and p₁/p₂=left/right superior parietal lobule.