Review
Neurocircuitry models of posttraumatic stress disorder and beyond: A meta-analysis of functional neuroimaging studies

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Abstract

Over the past two decades a relatively large number of studies have investigated the functional neuroanatomy of posttraumatic stress disorder (PTSD). However, findings are often inconsistent, thus challenging traditional neurocircuitry models of PTSD. As evidence mounts that cognition and behavior is an emergent property of interacting brain networks, the question arises whether PTSD can be understood by examining dysfunction in large-scale, spatially distributed neural networks. We used the activation likelihood estimation quantitative meta-analytic technique to synthesize findings across functional neuroimaging studies of PTSD that either used a non-trauma (N = 20) or trauma-exposed (N = 19) comparison control group. In line with neurocircuitry models, our findings support hyperactive amygdala and hypoactive medial prefrontal regions, but suggest hyperactive hippocampi. Characterization of additional regions under a triple network model showed functional alterations that largely overlapped with the salience network, central executive network, and default network. However, heterogeneity was observed within and across the neurocircuitry and triple network models, and between results based on comparisons to non-trauma and trauma-exposed control groups. Nonetheless, these results warrant further exploration of the neurocircuitry and large-scale network models in PTSD using connectivity analyses.

Highlights

► We present a meta-analysis of fMRI and PET studies on PTSD. ► Abnormalities were observed in regions of traditional neurocircuitry models of PTSD. ► Additional regions implicated roles of three large-scale neurocognitive networks. ► These networks subserve salience, central-executive, and default mode functions. ► Regions differed between findings based on non-trauma vs. trauma-exposed controls.

Section snippets

The traditional neurocircuitry model of PTSD

Abnormal patterns of brain activity have been characterized as showing greater activation (hyperactivation) or less activation (hypoactivation) in PTSD relative to a comparison control group. Alterations in regional activation are thought to underlie behavioral, cognitive, or emotional symptomatology. For instance, the widely adopted neurocircuitry model of PTSD first proposed by Rauch et al. (1998) suggests hypoactivation of the medial prefrontal cortex (encompassing the anterior cingulate

Beyond the neurocircuitry model

Others have suggested the traditional neurocircuitry model might be constrained by its focus on threat. That is, while some PTSD symptoms may stem from deficits in threat-related processing, other symptoms (e.g., emotional numbing, avoidance behaviors) are unexplained by this model (Liberzon and Garfkinkel, 2009). In their model, Liberzon and Garfkinkel (2009) emphasize the role of medial prefrontal cortex in contexualization, the process by which stimuli in varying situational contexts are

Study aims

There is a growing corpus of studies examining brain (dys)function in PTSD in relation to many behavioral domains. Yet, to our knowledge, no studies have examined the possibility that PTSD is associated with common or domain-general patterns of altered brain function. Evidence of reliable, domain-general aberrations in PTSD would set the stage for future investigations to elucidate how these global effects interact with more differentiated, domain-specific functional differences.

In this vein,

Study selection

A systematic literature search was conducted to identify neuroimaging studies of PTSD. Peer-reviewed articles published in English up to January 2011 were selected from the search results of two separate databases: MEDLINE and PsycINFO via Scholar's Portal. The literature search was conducted using the following search words: (1) keywords “post-traumatic stress disorder” <OR> “PTSD” <OR> “acute stress disorder” <OR> “trauma” AND (2) keywords “fMRI” <OR> “PET” <OR> “functional MRI” <OR>

PTSD > NTC

Reliable clusters of activity were observed in the PTSD group relative to the NTC group in a number of brain regions (Table 3a). Of relevance to the neurocircuitry model, both the left amygdala and right hippocampus demonstrated greater activation in PTSD; these structures also contribute to the salience and default networks, respectively. Additional clusters of reliable activation in the salience networks were found in the bilateral anterior insula and left putamen (Fig. 1A and B). In the

Discussion

We used quantitative ALE meta-analytic methods to synthesize findings from 36 functional neuroimaging studies of PTSD. Results revealed reliable clusters of abnormal activation in PTSD within the regions comprising the traditional neurocircuitry model (e.g. Rauch et al., 2006), as well as several additional clusters reflecting PTSD-related perturbations across the three large-scale brain networks implicated in the triple network model of psychopathology (Menon, 2011). Nonetheless, the patterns

Conclusion

In this meta-analysis, we aimed to characterize domain-general markers of neural activity reliably associated with PTSD. To this end, we used the ALE method to identify regions that reliably show altered activation in PTSD relative to two non-PTSD control groups: NTC and TEC groups. Our results generally supported the traditional neurocircuitry model of PTSD in terms of lower activation in medial prefrontal regions and hyperactivation of the amygdala, as well as abnormal activation in the

Acknowledgement

We thank Louis Lakatos for his assistance with data organization and collection.

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