Fear processing has been a primary focus of neurocognitive research in PTSD18-21 because the disorder is characterized by a pathological acquisition, expression, and persistence of learned fear. Putative irregularities in the fear circuitry of individuals with PTSD have been examined through various paradigms, and the results have basically converged.
Fear Conditioning and Extinction Paradigms
Divergent neural circuitry activations between people with PTSD and healthy controls (with or without trauma history) are commonly observed in Pavlovian conditioning paradigms,22-24 during which a neutral conditioned stimulus (CS) is paired with an aversive unconditioned stimulus (US; e.g., a shock). After several paired exposures, the CS acquires the capacity to initiate conditioned fear responses (CRs), such as freezing in rodents25 and skin conductance responses (SCR) in humans,26 in the absence of the US. However, repeated presentations of the CS, without recurrence of the US, lead to extinction, such that the CS no longer elicits the CR. If there is re-exposure to the extinguished CS in the context in which extinction occurred, “recall” of the extinction memory is manifest in a lesser CR.
PTSD is frequently conceptualized within the Pavlovian fear conditioning and extinction framework,27 in which any number of environmental stimuli become associated with a traumatizing event, and strong emotional memories are formed that are resistant to normal extinction processes. Milad et al. developed a 2-day fear conditioning and extinction paradigm that employed neuroimaging.28 In general, these studies revealed variations of activation in the amygdala, hippocampus, insula, dACC, the vmPFC, the putamen, and caudate compared with trauma-exposed control subjects who did not develop PTSD.2 29 30
Activation in the vmPFC and hippocampus is positively correlated with level of extinction recall. Specifically, when testing for level of extinction retention 24 hours after extinction learning, greater dACC activation and less vmPFC activation are seen in PTSD versus trauma-exposed controls.2 vmPFC is suggested to inhibit fear response using top-down control over the amygdala,2 and underactive vmPFC may correlate with an inability to utilize contextual memory.11 Furthermore, hypoactivation of the vmPFC has been shown to be highly correlated with symptoms severity in PTSD.6
The hyperactivation of the dACC during fear extinction retention might promote difficulty in utilizing environmental contextual stimuli in modulating fear responses in individuals with PTSD because the dACC subserves response selection in fear learning. Although the dACC was not included in many of the early neurocircuitry models of PTSD, recent studies have suggested that the dACC is hyperresponsive in PTSD.31 Of note, recently, Shvil and colleagues found that only men with PTSD, not women, tended to exhibit increased activation in the dACC when tested during extinction recall.32