Childhood Trauma and Functional Connectivity between Amygdala and Medial Prefrontal Cortex: A Dynamic Functional Connectivity and Large-Scale Network Perspective.

Josh M. Cisler

doi:10.3389/fnsys.2017.00029

Abstract

Altered functional connectivity (FC) between the medial prefrontal cortex (mPFC) and amygdala is widely implicated as a neural mechanism explaining risk for psychopathology among those exposed to early life trauma. Nonetheless, contemporary neuroimaging research has shifted toward large-scale network models of brain function, and it is not clear how this common bi-nodal finding fits into larger-scale network models. Here, using dynamic functional connectivity (DFC) approaches combined with large-scale network analyses, the larger role of bi-nodal FC between mPFC and amygdala among a sample of adolescent girls is investigated. The sample was comprised of 30 healthy control girls and 26 girls exposed to either physical or sexual assault who underwent a resting-state scan during 3T MRI. DFC using a sliding window approach was used to create weighted, undirected, graphs from the resting-state data following parcellation with a 215 regions-of-interest (ROI) atlas. Using a priori ROI, the predicted finding of lessor FC between mPFC and amygdala as a function of early life trauma was replicated in this sample. By contrast, early life trauma was associated with greater large-scale network modularity. Using a dynamic FC approach, it is also demonstrated that within-subject variability in this bi-nodal FC closely tracks within-subject fluctuations in large-scale network patterns, including connectivity between a limbic and default mode network (in which the amygdala and mPFC nodes belong, respectively) as well as overall modular organization. These results suggest that bi-nodal FC, such as amygdala-mPFC FC, may generally reflect larger-scale network patterns. Future research is necessary to understand whether these associations between nodal FC and large-scale network organization better reflect top-down processes (larger-scale network organization drives bi-nodal FC) or bottom-up processes (bi-nodal FC drives larger-scale network organization) and the related impact of early life trauma.

Highlights

A central role for the functional connectivity (FC) between the amygdala and medial prefrontal cortex is ubiquitous in neurocircuitry models of trauma and PTSD (Rauch et al, 2006; Pitman et al, 2012; Admon et al, 2013)
The purpose of the current study is to examine this common finding of altered amygdala-medial prefrontal cortex (mPFC) connectivity among those exposed to early life trauma within the context of largescale network models of human brain function
The commonly reported finding and predicted observation based on neurocircuitry models of trauma and PTSD of weakened static FC between amygdala-mPFC and childhood trauma (Rauch et al, 2006; Burghy et al, 2012; Herringa et al, 2013) was replicated in the current sample, such that the median FC between the amygdala and mPFC across the time windows was negatively correlated with the continuous emotional abuse subscale of the Childhood Trauma Questionnaire (CTQ), as has been previously reported (Dannlowski et al, FIGURE 5 | (Top) Histograms depicting the group-level distributions of the within-subject relationships between the caudate-mPFC FC and the limbic-default mode network (DMN) FC and the caudate-mPFC FC with modularity Q-values. (Bottom) Comparisons in the corresponding indices between the assaulted and control participants

Summary

Introduction

A central role for the functional connectivity (FC) between the amygdala and medial prefrontal cortex (mPFC) is ubiquitous in neurocircuitry models of trauma and PTSD (Rauch et al, 2006; Pitman et al, 2012; Admon et al, 2013). Weakened FC between these nodes is conceptualized as weakened top-down control of the amygdala by the mPFC and is theorized to mediate over-expression of negative affectivity and under-expression of emotion regulation (e.g., implicit emotion regulation, fear extinction learning, etc) among individuals with PTSD (Rauch et al, 2006; Patel et al, 2012; Pitman et al, 2012) Consistent with these models’ predictions, there is consistent data suggesting that altered amygdala-mPFC FC at rest scales with degree of early life trauma and predicts internalizing symptoms and cortisol levels (Burghy et al, 2012; Herringa et al, 2013; Pagliaccio et al, 2015). Greater values reflect networks with more cleanly segregated modules From this perspective, the intriguing question regarding amygdala-mPFC FC is whether degree of connection between these nodes belonging to different modules only reflects larger modular organization patterns of the network. Perhaps the weaker amygdala-mPFC observed among those exposed to early life trauma reflects greater overall modularity

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Conclusion