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.

A comparison of the functional connectome in mild traumatic brain injury and post‐traumatic stress disorder

“…A bias towards greater perceived saliency (reflected as a hyperactive salience network) has been proposed to underlie reduced cognitive capacity (impacting the cognitive control network) and disruptions in internal mentation and sense of self (impacting the default mode brain network) in PTSD (Akiki et al, 2017 ). These findings are consistent with the clinical profile of PTSD insofar as they have been associated with emotional dysregulation, re‐experiencing and numbing or avoidance symptoms in PTSD (Breukelaar et al, 2021 ; Miller et al, 2017 ). On the other hand, chronic hyperconnectivity within hippocampal, thalamic, left frontal and temporal regions has been previously shown to be positively associated with PTSD severity (Dunkley et al, 2014 , 2018 ).…”

“…Altered whole‐brain connectivity has also been reported in PTSD. Studies have found that PTSD participants displayed hypoconnectivity among higher cortical areas and emotion regulation areas such as lateral frontal, supplementary motor area, salience network, DMN, executive control networks and between the parahippocampal and visual cortex areas (Bao et al, 2021 ; Breukelaar et al, 2021 ; Misaki et al, 2018 ; Ross & Cisler, 2020 ). A bias towards greater perceived saliency (reflected as a hyperactive salience network) has been proposed to underlie reduced cognitive capacity (impacting the cognitive control network) and disruptions in internal mentation and sense of self (impacting the default mode brain network) in PTSD (Akiki et al, 2017 ).…”

Diverse therapeutic developments for post-traumatic stress disorder (PTSD) indicate common mechanisms of memory modulation

“…Moreover, changes in brain connectivity involving frontoparietal executive control circuits have recently been reported in PTSD and have been linked to behavioural treatment responsivity, highlighting the importance of prefrontal cortex and its connectivity in PTSD (Korgaonkar, et al, 2020). Differences in the functional connectome have been found for PTSD compared to controls (Breukelaar, Bryant, & Korgaonkar, 2021), including reduced connectivity between regions part of the default mode and executive control network, whereas increased connectivity was found between regions involved in emotional and arousal response such as subcortical and limbic areas.…”

Altered Resting-State Functional Connectivity in the Anterior Versus Posterior Hippocampus in Post-traumatic Stress Disorder: The Central Role of the Anterior Hippocampus

“…The anterior insula is known to be a major hub in the SN, involved in network switching and predisposing attention to salient interoceptive sensations and exteroceptive stimuli [26]. There have been mixed findings in the literature concerning hippocampal-SN connectivity in PTSD, where some found hyperconnectivity [35, 120], others found hypoconnectivity [121], and yet others found no connectivity differences in those with PTSD, compared to controls[62]. Our analyses, incorporating separate aHipp and pHipp seeded functional connectivity, offer a resolution to these discrepant findings, as we showed increased aHipp, but not pHipp functional connectivity with the anterior insula, consistent with findings of salience detection by the anterior insula [122, 123], which becomes abnormal in PTSD [124].…”