Altered processing of contextual information during fear extinction in PTSD: an fMRI study

Abstract

Medial prefrontal cortical areas have been hypothesized to underlie altered contextual processing in posttraumatic stress disorder (PTSD). We investigated brain signaling of contextual information in this disorder. Eighteen PTSD subjects and 16 healthy trauma-exposed subjects underwent a two-day fear conditioning and extinction paradigm. On day 1, within visual context A, a conditioned stimulus (CS) was followed 60% of the time by an electric shock (conditioning). The conditioned response was then extinguished (extinction learning) in context B. On day 2, recall of the extinction memory was tested in context B. Skin conductance response (SCR) and functional magnetic resonance imaging (fMRI) data were collected during context presentations. There were no SCR group differences in any context presentation. Concerning fMRI data, during late conditioning, when context A signaled danger, PTSD subjects showed dorsal anterior cingulate cortical (dACC) hyperactivation. During early extinction, when context B had not yet fully acquired signal value for safety, PTSD subjects still showed dACC hyperactivation. During late extinction, when context B had come to signal safety, they showed ventromedial prefrontal cortex (vmPFC) hypoactivation. During early extinction recall, when context B signaled safety, they showed both vmPFC hypoactivation and dACC hyperactivation. These findings suggest that PTSD subjects show alterations in the processing of contextual information related to danger and safety. This impairment is manifest even prior to a physiologically-measured, cue-elicited fear response, and characterized by hypoactivation in vmPFC and hyperactivation in dACC.

Figure 1

Conditioning: dACC/SFG activation during the last 16 (late) context presentations. Graph shows comparison of beta values in relation to baseline activity of the two groups (error bars indicate SEM). Numbers following x, y, and z refer to MNI coordinates. Figure shows map of brain activation at a threshold of P= 0.0001 displayed on a group averaged T1‐template. Yellow = increased activation in PTSD versus TENC subjects. Red circle indicates dACC.

Figure 2

Extinction learning: A. dACC activation during the first 16 (early) context presentations. B. vmPFC deactivation during the last 16 (late) context presentations. Same description of plots and figures as in Figure 1. Yellow = increased activation, blue = decreased activation in PTSD versus TENC subjects. Red circles indicate dACC and vmPFC.

Figure 3

Extinction recall: A. dACC activation and B. vmPFC deactivation during context presentation for the first 16 (early) context presentations. Same description of plots and figures as in Figure 1. Red circles indicate dACC and vmPFC.