Neural changes in extinction recall following prolonged exposure treatment for PTSD: A longitudinal fMRI study

Abstract

Background: Neurobiological models of posttraumatic stress disorder (PTSD) implicate fear processing impairments in the maintenance of the disorder. Specific deficits in extinction recall, the retention of learned extinction, have been demonstrated. While deficient extinction recall, and the associated activation pattern of prefrontal and hippocampal regions, distinguishes individuals with PTSD from controls, research has not yet examined changes following treatment. We examined the behavioral and neural correlates of extinction recall before and after cognitive behavioral treatment of PTSD.

Methods: Fifty-eight participants (30 with PTSD, 28 trauma-exposed matched controls) underwent a 2-day behavioral fear conditioning, extinction, and recall paradigm during functional magnetic resonance imaging (fMRI). The same procedures were repeated 10 weeks later, after PTSD patients had completed prolonged exposure treatment. We analyzed fMRI data from 32 subjects (16 PTSD; 16 controls) and skin conductance response (SCR) data from 33 subjects (16 PTSD; 17 controls). Neural activity during extinction recall, SCR, and PTSD symptoms were compared across groups and over time.

Results: PTSD patients exhibited pre- to post-treatment reduction in rostral anterior cingulate cortex (rACC) activation during extinction recall, and increase in functional coherence between the rACC and the ventromedial prefrontal cortex (vmPFC) and subgenual anterior cingulate cortex (sgACC). Reduced PTSD symptom severity from pre- to post-treatment was significantly associated with reduced subgenual ACC and parahippocampal activation during this task. SCR during the extinction recall phase did not significantly change with treatment in the PTSD group, but change in SCR was associated with reduction in PTSD symptom severity.

Conclusions: Prolonged exposure treatment appears to alter neural activation in PTSD patients during recall of fear extinction, and change in extinction recall (measured by SCR) is associated with symptom reduction. We discuss results in the context of neural systems involved in response to affective stimuli.

Fig. 1

Participant retention throughout the study. Note: PTSD = Posttraumatic stress disorder; TE-HC = trauma exposed healthy controls; PE = prolonged exposure; SCR = skin conductance response; MRI = magnetic resonance imaging. *Differences in numbers between stages due to drop out (3 after consent, 8 after baseline assessment, 6 during treatment/wait period, and 2 did not complete end of treatment assessment). **Note: SCR and fMRI data overlap included: 11 TE-HC and 6 PTSD participants.

Fig. 2

Psychophysiological activation during extinction recall at baseline and after 10 weeks in PTSD (treated) and TE-HC groups.

Fig. 3

Change in neural activation during extinction recall following treatment among PTSD and TE-HC groups. Note: PTSD = posttraumatic stress disorder; TE-HC = trauma exposed healthy controls; rACC = rostral anterior cingulate cortex; mPFC = medial prefrontal cortex. Images represent pre-post contrasts and mean beta weights represent the average activation in the specified ROI of the entire cluster surviving the 0.005 threshold.

Fig. 4

Correlation between change in SCR and change in CAPS score. Note: SCR = skin conductance response; CS + E = extinguished conditioned stimulus; CS + U = unextinguished conditioned stimulus; CAPS = clinician administered posttraumatic symptom scale. Summary: individuals with the largest change in extinction recall SCR (CS + E − CS + U) from pre- to post-treatment showed the largest decrease in CAPS.

Fig. 5

Psychophysiological interactions during extinction recall phase between seed region with identified pre-to-post-treatment changes and additional regions of interest. Note: Seed = rostral anterior cingulate seed identified as decreasing in activation during extinction recall phase from pre-to-post-treatment; Positive coupling = marked region evinces increased activation when activation in the seed region increases during extinction recall; Negative coupling = marked region evinces reduction in activation when activation in the seed region increases during extinction recall; Pre > Post — coupling between marked areas and seed decrease from pre-to-post-treatment; Post > Pre — coupling between marked areas and seed increase from pre-to-post-treatment.