Default mode network abnormalities in posttraumatic stress disorder: A novel network-restricted topology approach

Abstract

Disruption in the default mode network (DMN) has been implicated in numerous neuropsychiatric disorders, including posttraumatic stress disorder (PTSD). However, studies have largely been limited to seed-based methods and involved inconsistent definitions of the DMN. Recent advances in neuroimaging and graph theory now permit the systematic exploration of intrinsic brain networks. In this study, we used resting-state functional magnetic resonance imaging (fMRI), diffusion MRI, and graph theoretical analyses to systematically examine the DMN connectivity and its relationship with PTSD symptom severity in a cohort of 65 combat-exposed US Veterans. We employed metrics that index overall connectivity strength, network integration (global efficiency), and network segregation (clustering coefficient). Then, we conducted a modularity and network-based statistical analysis to identify DMN regions of particular importance in PTSD. Finally, structural connectivity analyses were used to probe whether white matter abnormalities are associated with the identified functional DMN changes. We found decreased DMN functional connectivity strength to be associated with increased PTSD symptom severity. Further topological characterization suggests decreased functional integration and increased segregation in subjects with severe PTSD. Modularity analyses suggest a spared connectivity in the posterior DMN community (posterior cingulate, precuneus, angular gyrus) despite overall DMN weakened connections with increasing PTSD severity. Edge-wise network-based statistical analyses revealed a prefrontal dysconnectivity. Analysis of the diffusion networks revealed no alterations in overall strength or prefrontal structural connectivity. DMN abnormalities in patients with severe PTSD symptoms are characterized by decreased overall interconnections. On a finer scale, we found a pattern of prefrontal dysconnectivity, but increased cohesiveness in the posterior DMN community and relative sparing of connectivity in this region. The DMN measures established in this study may serve as a biomarker of disease severity and could have potential utility in developing circuit-based therapeutics.

Large‐scale white matter network reorganization in posttraumatic stress disorder

“…Further, potential effects of prior drug therapies may have influenced study findings. A modularity analysis of the functional brain network in adult PTSD revealed a spared functional connectivity in the posterior default mode network (DMN) (Akiki et al, 2018). However, this study did not exclude participants with psychiatric comorbidities and psychotropic medications.…”

“…We have previously characterized white matter networks in pediatric PTSD, showing a disrupted topological organization (Suo et al, 2017). A modularity analysis of the functional brain network in adult PTSD revealed a spared functional connectivity in the posterior default mode network (DMN) (Akiki et al, 2018). However, this study compared adult PTSD patients with nontraumatized healthy controls, making it difficult to determine whether observed effects were correlated with PTSD per se or represented a general consequence of traumatic stress exposure.…”

“…All participants had no psychiatric comorbidity and had received no prior treatment with psychiatric medications. Based on previous evidence of increased segregation in functional networks (Akiki et al, 2018;Lei et al, 2015) and increased integration of white matter networks in adult PTSD after traffic accidents trauma (Long et al, 2013), we hypothesized that similar disruptions would characterize white matter networks in adult PTSD patients. We also hypothesized that PTSD patients would show abnormal modular characterization of white matter networks, for example, in DMN.…”

PTSD and its dissociative subtype through the lens of the insula: Anterior and posterior insula resting‐state functional connectivity and its predictive validity using machine learning

“…Notably, the insula's involvement in emotion and social processing relies not only on activation of this region but also on its wider connectivity to functional neural networks (Couto et al, 2013). Here, the insula is thought to modulate two resting-state networks: (a) an anterior insula-based network that works in tandem with the anterior cingulate cortex to influence brain regions in both the default-mode network, involved in introspection, and in the central executive network, involved centrally in emotional appraisal (Akiki et al, 2018;Bressler & Menon, 2010;Cauda et al, 2011;Chen et al, 2013;Fox et al, 2005;Simmons et al, 2013); and (b) a posterior insula-based network that maintains connections with sensorimotor areas involved in environmental monitoring (e.g., pre-and postcentral gyri and the midcingulate; Deen, Pitskel, & Pelphrey, 2011;Simmons et al, 2013;Taylor, Seminowicz, & Davis, 2009). Moreover, the insula, the ventral frontoparietal areas (e.g., the inferior frontal gyrus | 3 of 23 HARRICHARAN et Al. and the temporoparietal junction), and the subcortical structures form a right-lateralized ventral attention network that is thought to mediate bottom-up attentional processes and salience processing (Corbetta, Patel, & Shulman, 2008;Frank & Sabatinelli, 2012).…”

Determining the Hierarchical Architecture of the Human Brain Using Subject-Level Clustering of Functional Networks

“…In the brain, these communities are known to represent subsystems and mediate distinct neurophysiological functions (e.g., the brain's visual subnetwork) Power et al, 2011;Cole et al, 2014). Moreover, this scale is highly sensitive to disease, where several psychiatric disorders have shown selective disruption in particular brain communities (Alexander-Bloch et al, 2012;Akiki et al, 2017Akiki et al, , 2018Menon, 2011;Cisler et al, 2016). This apparent importance has prompted interest in this line of investigation; while a vast wealth of knowledge has been gained from these efforts, several methodological pitfalls remain.…”