Evidence for disrupted gray matter structural connectivity in posttraumatic stress disorder

Abstract

Posttraumatic stress disorder (PTSD) is characterized by atrophy within the prefrontal-limbic network. Graph analysis was used to investigate to what degree atrophy in PTSD is associated with impaired structural connectivity within prefrontal limbic network (restricted) and how this affects the integration of the prefrontal limbic network with the rest of the brain (whole-brain). 85 male veterans (45 PTSD neg, 40 PTSD pos) underwent volumetric MRI on a 3T MR. Subfield volumes were obtained using a manual labeling scheme and cortical thickness measurements and subcortical volumes from FreeSurfer. Regression analysis was used to identify regions with volume loss. Graph analytical Toolbox (GAT) was used for graph-analysis. PTSD pos had a thinner rostral anterior cingulate and insular cortex but no hippocampal volume loss. PTSD was characterized by decreased nodal degree (orbitofrontal, anterior cingulate) and clustering coefficients (thalamus) but increased nodal betweenness (insula, orbitofrontal) and a reduced small world index in the whole brain analysis and by orbitofrontal and insular nodes with increased nodal degree, clustering coefficient and nodal betweenness in the restricted analysis. PTSD associated atrophy in the prefrontal-limbic network results in an increased structural connectivity within that network that negatively affected its integration with the rest of the brain.

Structural covariance network centrality in maltreated youth with posttraumatic stress disorder

“…We selected the measures that would enable direct comparisons of our results with previous findings (Mueller et al, 2015; Teicher et al, 2014). Four types of centrality measures were analyzed using Brain Connectivity Toolbox (BCT (Rubinov and Sporns, 2010);): (a) degree centrality is the number of directly interconnected nodes, and reflects how much a node serves as a focal point of communication; (b) betweenness centrality is the frequency with which a node falls between pairs of other nodes on their shortest interconnecting path, and reflects the potential of a node to control communication; (c) closeness centrality, adapted from the distance function in BCT, reflects the normalized number of steps required to access every other node from a given node in a network, and reflects a node's speed to spread information throughout the network; (d) eigenvector centrality is a measure of a node's overall influence based on the idea that the importance of a node is recursively related to the importance of the nodes associated with it.…”

“…Previous research has also shown structural and functional disruptions to OFC and ACC in survivors of childhood maltreatment (Kelly et al, 2013; Lim et al, 2014; Teicher et al, 2014) and those with PTSD (Morey et al, 2016; Mueller et al, 2015; Spielberg et al, 2015). We hypothesized that maltreatment would be broadly associated with altered centrality in OFC and in the ACC, particularly children with PTSD as disruptions in these neural networks may increase their vulnerability to the disorder.…”

“…Cortical morphometric network analyses (Bassett et al, 2008; He et al, 2008; He and Evans, 2010; Lerch et al, 2006; Sporns, 2011) are based on structural inferences made between specific pairings of cortical regions that vary in tandem with respect to cortical thickness or gray matter volume (Gong et al, 2012; Lerch et al, 2006). Although the neurobiological interpretation of the covariance in cortical thickness across regions is yet unclear, it has been proposed that the correlation strength increases between regions that are concurrently affected by common factors, and decreases between regions that are differentially affected by such factors (Mueller et al, 2015). The structural covariance network method based on cortical thickness/gray matter volume is relatively insensitive to the noisy components that accompany task-based and resting-state functional magnetic resonance imaging (fMRI).…”

“…Moreover, military veterans with PTSD demonstrated decreased centrality in left orbitofrontal cortex and anterior cingulate cortices (ACC), and increased centrality in left insula and right orbitofrontal cortex (Mueller et al, 2015). However, these studies are focused on PTSD in adults, often decades after exposure to childhood maltreatment, and were not able to uncover the brain network alterations associated with acute effects of child maltreatment and subsequent PTSD.…”

“…Specifically, we predicted that these areas would show lower centrality in maltreated youth with PTSD than maltreated youth without PTSD and non-maltreated controls. Based on findings from previous studies of brain structural covariance network architecture in adults exposed to maltreatment (Teicher et al, 2014) or with PTSD (Mueller et al, 2015), we also anticipated between-group differences in insula/inferior frontal cortex (Ins/IFC) and temporal pole (TP).…”