The functional connectome in posttraumatic stress disorder

Abstract

Background: Previous fMRI studies of posttraumatic stress disorder (PTSD) have investigated region-specific alterations in intrinsic connectivity but connectome-wide changes in connectivity are yet to be characterized. Understanding the neurobiology of this is important to develop novel treatment interventions for PTSD. This study aims to identify connectome-wide disruptions in PTSD to provide a more comprehensive analysis of nseural networks in this disorder.

Methods: A functional MRI scan was completed by 138 individuals (67 PTSD and 71 non-trauma-exposed healthy controls [HC]). For every individual, inter-regional intrinsic functional connectivity was estimated between 436 brain regions, comprising intra and inter-network connectivity of eight large-scale brain networks. Group-wise differences between PTSD and HC were investigated using network-based statistics at a family-wise error rate of p < 0.05. Significant network differences were then further investigated in 27 individuals with trauma exposure but no PTSD [TC]).

Results: Compared to HC, PTSD displayed lower intrinsic functional connectivity in a network of 203 connections between 420 regions within and between mid-posterior default mode, central executive, limbic, visual and somatomotor regions. Additionally, PTSD displayed higher connectivity across a network of 50 connections from thalamic and limbic to sensory and default-mode regions. Connectivity in TC in both these networks was intermediate and significantly different to PTSD and HC.

Conclusion: A large-scale imbalance between hypoconnectivity of higher-order cortical networks and hyperconnectivity of emotional and arousal response systems seems to occur on a sliding scale from trauma exposure to clinical manifestation as PTSD. Novel interventions that target this systemic functional imbalance could provide potential mitigation of PTSD.

Keywords: Connectome; Functional connectivity; Network; Neuropathology; Posttraumatic stress disorder; fMRI.

Fig. 1

Differences in connectivity in PTSD compared to HC identified with network-based statistics. For HC > PTSD, a network comprised of 203 regions and 420 edges (connections) was identified (p < 0.001, FWE-corrected) (A–C). For PTSD > HC a network comprised of 34 regions and 50 edges (connections) was identified (D–F). A & D) all significant nodes and edges of HC > PTSD subnetwork visualized on the surface of the brain (created using BrainNet viewer) B & E) a heatmap of the mean t-statistic of significantly different connections within and between the eight primary functional networks. Larger circle size and darker colour represent greater mean t-statistic of connections (larger difference in HC and PTSD connectivity). Networks are ordered based on their overall contribution to the difference in connectivity between PTSD and HC. C & F) Shows the difference in mean connectivity across all significant regions between groups. PTSD – Posttraumatic Stress Disorder, HC – Healthy Controls.

Fig. 2

Correlation between PTSD network connectivity and BDI, CADSS and CAPS, controlling for age and sex. Lower dissociation score is associated with greater connectivity in HC > PTSD network only. PTSD – Posttraumatic Stress Disorder, BDI – Beck's Depression Inventory, CADSS – Clinician Administered Dissociative States Scale, CAPS – Clinician Administered PTSD Scale.

Fig. 3

Comparison between TC, HC and PTSD connectivity in significant networks. Connectivity for significant networks was extracted from TC subgroup and compared post-hoc with HC and PTSD. One-way ANOVA showed all three groups to have significantly difference connectivity for both networks (p < 0.001). Post-hoc tests found that TC participants mean connectivity values were in between and significantly difference from HC and PTSD groups for both networks. For the HC > PTSD Networks in a) PTSD < TC: p = 0.0366 & HC > TC: p < 0.001. For the PTSD > HC Network in b) PTSD > TC: p = 0.038 & HC < TC: p = 0.046). PTSD – Posttraumatic Stress Disorder, TC – Trauma-exposed Control, HC – Healthy Control. Significance levels are denoted as **** for p < 0.001 and * for p < 0.05.