Resolution limit-free community detection reveals unique patterns of resting-state network connectivity in posttraumatic stress disorder: A PGC-ENIGMA PTSD Consortium investigation
Authors: Ross Marisa C. , Cisler Josh M. , Koch Saskia B.J. , Olff Miranda , Veltman Dick J. , Nawijn Laura , Frijling Jessie L. , van Zuiden Mirjam , Zhu Xi , Neria Yuval , Suarez-Jimenez Benjamin , Wager Tor , Haswell Courtney , De Bellis Michael D. , Rubright Emily Clarke , Stevens Jennifer S. , van Rooij Sanne J.H. , Fani Negar , Jovanovic Tanja , Ressler Kerry J. , Daniels Judith K. , Walter Henrik , Manthey Antje , Sierk Anika , Riha Pavel , Rektor Ivan , Davidson Richard , Nitschke Jack B. , Grupe Dan , Larson Christine , deRoon-Cassini Terri , Fitzgerald Jacklynn , Huggins Ashley , Weis Carissa , Lanius Ruth , Densmore Maria , Lebois Lauren A. M. , Kaufman Milissa L. , Baker Justin T. , Straube Thomas , Neumeister Paula , Hofmann David , Etkin Amit , Maron-Katz Adi , King Anthony , Liberzon Israel , Angstadt Michael , Herringa Ryan , Wang Xin , Chen Tian , Cotton Andrew , O’Leary Brian , Xie Hong , Disner Seth , Davenport Nicholas , Hage Wissam El , Quidé Yann , Geuze Elbert , Kennis Mitzy , Gordon Evan , May Geoffery , Nelson Steven , Jia-Richards Meilin , Bruce Steven , Veer Ilya , Waller Lea , Berg Hannah , Lissek Shmuel , Morey Rajendra A. , Sponheim Scott 
Published: June 2021

Posttraumatic stress disorder (PTSD) is a complex psychiatric condition that has generated much attention in the neuroimaging literature. A neurocircuitry model supporting fronto-limbic dysfunction as a major player in facilitating clinical symptoms of PTSD is well-characterized; however, recent literature suggests that network-based approaches may provide additional insight into neural dysfunction in PTSD. Our analysis uses resting-state neuroimaging scans of 1063 adults from the PGC-ENIGMA PTSD Consortium to investigate a network-based model of functional connectivity in PTSD. With a novel, resolution limit-free community detection approach, 16 communities corresponding to functionally meaningful networks were detected with high quality. After group-level community detection, participants were classified into three groups (PTSD, n=418, trauma-exposed controls without PTSD, n=434, and non-trauma exposed healthy controls, n=211). Individual network connectivity metrics were calculated, including whole-brain, default mode network, and central executive network participation coefficient and connectivity strength. Linear mixed effects models revealed group differences in the whole-brain, default mode, and central executive network participation coefficient and connectivity strength such that individuals with PTSD demonstrated overall greater values. We also described sex differences such that males demonstrate greater whole-brain participation coefficient vs. females and females demonstrate greater default mode network connectivity strength vs. males. Our results suggest that PTSD in adults is associated with reduced specialization and enhanced inter-module communication throughout the brain network, which may contribute to inefficient information processing and poor emotional regulation. This study presents a novel use of resolution limit-free community detection in a large PTSD sample, revealing robust differences in resting-state network topology.