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.

Highlights

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  This study investigates intrinsic whole-brain functional connectivity (FC) in PTSD and trauma-exposed controls.

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  We identify an imbalance between dysconnectivity of the cortex and hyperconnectivity of subcortical emotional and arousal response systems.

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  This disruption in intrinsic FC was more extensive than previously identified, impacting all major functional brain networks.

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  Degree of dysconnectivity in PTSD was further associated with dissociative symptoms.

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  Alterations in functional connectivity are also present in trauma-exposed controls but are less severe.