Elsevier

Biological Psychiatry

Volume 60, Issue 4, 15 August 2006, Pages 376-382
Biological Psychiatry

Review
Neurocircuitry Models of Posttraumatic Stress Disorder and Extinction: Human Neuroimaging Research—Past, Present, and Future

https://doi.org/10.1016/j.biopsych.2006.06.004Get rights and content

The prevailing neurocircuitry models of anxiety disorders have been amygdalocentric in form. The bases for such models have progressed from theoretical considerations, extrapolated from research in animals, to in vivo human imaging data. For example, one current model of posttraumatic stress disorder (PTSD) has been highly influenced by knowledge from rodent fear conditioning research. Given the phenomenological parallels between fear conditioning and the pathogenesis of PTSD, we have proposed that PTSD is characterized by exaggerated amygdala responses (subserving exaggerated acquisition of fear associations and expression of fear responses) and deficient frontal cortical function (mediating deficits in extinction and the capacity to suppress attention/response to trauma-related stimuli), as well as deficient hippocampal function (mediating deficits in appreciation of safe contexts and explicit learning/memory). Neuroimaging studies have yielded convergent findings in support of this model. However, to date, neuroimaging investigations of PTSD have not principally employed conditioning and extinction paradigms per se. The recent development of such imaging probes now sets the stage for directly testing hypotheses regarding the neural substrates of fear conditioning and extinction abnormalities in PTSD.

Section snippets

Neurocircuitry Model of PTSD

We have previously presented a neurocircuitry model of PTSD that emphasizes the role of the amygdala, as well as its interactions with the ventral/medial prefrontal cortex (vmPFC) and hippocampus (Rauch et al 1998). Briefly, this model hypothesizes hyperresponsivity within the amygdala to threat-related stimuli, with inadequate top-down governance over the amygdala by vmPFC (encompassing the rostral anterior cingulate cortex [rACC], medial prefrontal cortex [mPFC], subcallosal cortex [SC,

Functional Neuroimaging Findings in PTSD

An initial positron emission tomography (PET) symptom provocation study of PTSD (Rauch et al 1996) used a script-driven imagery method for inducing symptoms. For the provoked versus control conditions, increased regional cerebral blood flow (rCBF) was found within the right amygdala and rACC, as well as other anterior paralimbic regions; decreases in rCBF were observed within the left inferior frontal region (Broca’s area). Interpretations of this initial study, with regard to the

Structural and Neurochemical Imaging Findings in PTSD

To date, morphometric magnetic resonance imaging (MRI) studies of PTSD have focused on subtle between-group differences with respect to hippocampal volume. The possibility of reduced hippocampal volume and function is scientifically appealing, given that studies of chronic stress in animals have shown degenerative changes within the hippocampus associated with chronic exposure to glucocorticoids (Sapolsky et al 1990). In fact, an initial series of four studies showed smaller hippocampal volumes

Summary of PTSD Neuroimaging Research to Date

Taken together, imaging data support the current neurocircuitry model of PTSD that emphasizes the functional relationship between a triad of brain structures: the amygdala, vmPFC, and hippocampus. When exposed to reminders of traumatic events, subjects appear to recruit anterior paralimbic regions and the amygdala, while exhibiting decreased activity within other heteromodal cortical areas. In comparison with control subjects, patients with PTSD exhibit vmPFC activation of diminished magnitude

The Future of Neuroimaging Research in PTSD

Although current neurocircuitry models of PTSD are steeped in references to fear conditioning, thus far, neuroimaging studies of PTSD have yet to employ a full range of fear conditioning and extinction paradigms (Bremner et al 2005). Rather, as outlined above, neuroimaging of amygdala function in PTSD has involved reminders of the traumatic event or emotionally expressive face stimuli, rather than conditioned fear acquisition protocols. Similarly, neuroimaging studies of the vmPFC have utilized

Fear Conditioning and the Amygdala

Consistent with animal research (e.g., LeDoux 1996), several neuroimaging experiments of fear conditioning in healthy humans have likewise implicated the amygdala. Such studies have found significant correlation between rCBF changes in the right amygdala and electrodermal activity changes (Fredrikson et al 1995, Furmark et al 1997), as well as interregional correlations between amygdala and thalamus (Morris et al 1997). Several fMRI studies have also demonstrated amygdala activation during fear

Implications for Cognitive and Behavioral Therapies

The implications of extinction research for behavior therapies are detailed in other articles within this special issue (see Davis et al 2006, Hermans et al 2006, in this issue). Here, however, we wish to emphasize two points that are of particular relevance to neuroimaging. First, it remains to be determined to what degree cognitive therapies, which depend on conscious reappraisal of threatening stimuli or contexts, rely on the same neurocircuitry as behavior therapies that involve extinction

Summary and Conclusions

Animal studies of fear conditioning and extinction have provided a foundation for neurocurcuitry models of anxiety disorders in humans. Specifically, it has been hypothesized that PTSD is characterized by exaggerated amygdala responsivity and deficient top-down governance of the amygdala by vmPFC and hippocampus. Moreover, we have proposed that this regional pathophysiology in PTSD corresponds to exuberant acquisition of conditioned fear and exaggerated fear responses, as well as deficient

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