Impaired right inferior frontal gyrus response to contextual cues in male veterans with PTSD during response inhibition

Abstract

Background: Posttraumatic stress disorder (PTSD) is often associated with impaired fear inhibition and decreased safety cue processing; however, studies capturing the cognitive aspect of inhibition and contextual cue processing are limited. In this fMRI study, the role of contextual cues in response inhibition was investigated.

Methods: Male medication-naive war veterans with PTSD, male control veterans (combat controls) and healthy nonmilitary men (healthy controls) underwent fMRI while performing the stop-signal anticipation task (SSAT). The SSAT evokes 2 forms of response inhibition: reactive inhibition (outright stopping) and proactive inhibition (anticipation of stopping based on contextual cues).

Results: We enrolled 28 veterans with PTSD, 26 combat controls and 25 healthy controls in our study. Reduced reactive inhibition was observed in all veterans, both with and without PTSD, but not in nonmilitary controls, whereas decreased inhibition of the left pre/postcentral gyrus appeared to be specifically associated with PTSD. Impaired behavioural proactive inhibition was also specific to PTSD. Furthermore, the PTSD group showed a reduced right inferior frontal gyrus response during proactive inhibition compared with the combat control group.

Limitations: Most patients with PTSD had comorbid psychiatric disorders, but such comorbidity is common in patients with PTSD. Also, the education level (estimate of intelligence) of participants, but not of their parents, differed among the groups.

Conclusion: Our findings of reduced proactive inhibition imply that patients with PTSD show reduced contextual cue processing. These results complement previous findings on fear inhibition and demonstrate that contextual cue processing in patients with PTSD is also reduced during cognitive processes, indicating a more general deficit.

Figures

Fig. 1

Stop-signal anticipation task (SSAT). Three horizontal lines are displayed. A bar moves in 1000 ms from the bottom line to the top. The intertrial interval is also 1000 ms. The moving bar has to be stopped at the middle colored line at 800 ms. These trials are referred to as “go trials” (A). In a subpart of the trials the moving bar will stop on its own before reaching the middle colored line (stop signal). The stop response has to be withheld in these trials, and they are therefore referred to as “stop trials” (B). The colour of the middle line indicates the stop-signal probability: green 0%, yellow 17%, amber 20%, orange 25% and red 33% (C). The task consists of 414 go trials (0%, n = 234; 17%, n = 30; 20%, n = 48, 25%, n = 54; 33%, n = 48) and 60 top trials (17%, n = 6; 20%, n = 12, 25%, n = 18; 33%, n = 24). These trials were presented in pseudo-random order. The time before the stop signal appears (i.e., stop-signal delay [SSD]) was set at 550 ms, but varies in accordance with stop performance to generate a reasonably similar number of correct and incorrect trials. When stopping was successful, SSD was increased by 25 ms, making stopping more difficult. Vice versa, SSD was decreased by 25 ms each time the participant failed to stop. The SSD was adjusted for each stop-signal probability separately. For more details on the task, see the study by Zandbelt and Vink.

Fig. 2

Whole brain activation during (A) reactive inhibition (successful stop-signal versus go-signal 0% activation) and (B) proactive inhibition (parametric increase in activation as a function of stop-signal probability) in patients with posttraumatic stress disorder patients (PTSD; top panel), combat controls (CC; middle panel) and healthy controls (HC; bottom panel). The arrows point to the regions of interest (a) left pre/postcentral gyrus (b) right inferior frontal gyrus (rIFG) (c) right striatum. Significant (de)activated clusters (1-sample t tests; significance tested at cluster-defined threshold of p < 0.005, and a p < 0.05 family-wise error–corrected critical cluster size) are displayed on a standardized brain (MRIcron).