Deficiency in contextual and enhanced responding in cued fear learning may contribute to the development of posttraumatic stress disorder (PTSD). We examined the responses to aversive Pavlovian conditioning with an unpredictable spatial context as conditioned stimulus compared to a predictable context. We hypothesized that the PTSD group would demonstrate less hippocampal and ventromedial prefrontal cortex (vmPFC) activation during acquisition and extinction of unpredictable contexts and an over-reactive amygdala response in the predictable contexts compared to controls.

A novel combined differential cue-context conditioning paradigm was applied using virtual reality with spatial contexts that required configural and cue processing. We assessed 20 patients with PTSD, 21 healthy trauma-exposed (TC) and 22 non-trauma-exposed (HC) participants using functional magnetic resonance imaging, skin conductance responses, and self-report measures.

During fear acquisition, patients with PTSD compared to TC showed lower activity in the hippocampi in the unpredictable and higher activity in the amygdalae in the predictable context. During fear extinction, TC compared to patients and HC showed higher brain activity in the vmPFC in the predictable context. There were no significant differences in self-report or skin conductance responses.

Our results suggest that patients with PTSD differ in brain activation from controls in regions such as the hippocampus, the amygdala, and the vmPFC in the processing of unpredictable and predictable contexts. Deficient encoding of more complex configurations might lead to a preponderance of cue-based predictions in PTSD. Exposure-based treatments need to focus on improving predictability of contextual processing and reducing enhanced cue reactivity.

We examined how individual differences in trait anxiety (TA) influence the neural responses associated with the acquisition and extinction of anticipatory anxiety elicited through a context conditioning paradigm, with particular focus on the amygdala and the subgenual anterior cingulate cortex (sgACC).

During two sessions of echo-planar functional magnetic resonance imaging (fMRI), 18 healthy volunteers completed a decision-making task with two randomly alternating 28-s to 32-s background screen colour blocks. One of the colours was associated with the presentation of an aversive noise (CTX+) and the other colour was ‘safe’ (CTX−). In the first session (Acquisition), 33% of CTX+ colour blocks were paired with noise and in the second session (Extinction) no noise was presented.

The amygdala displayed an increased response to CTX+ compared to CTX− colour blocks during the Acquisition and Extinction sessions and the ACC displayed an increased response to CTX+ compared to CTX− colour blocks during Extinction only. In addition, a greater conditioned response (CTX+ minus CTX−) was observed in the ACC when comparing the Extinction and Acquisition sessions. Correlation analyses further showed that higher levels of TA were associated with a higher conditioned response in the amygdala during Extinction as well as a greater differential conditioned response (i.e. Extinction>Acquisition) in the ACC.

Our results support the idea that individuals with high levels of anxiety-relevant traits and vulnerable to developing an anxiety disorder display a more resilient anxiety response during extinction that is characterized by hyper-responsivity in the amygdala.