Neural correlates of inhibition and contextual cue processing related to treatment response in PTSD

Abstract

Thirty to fifty percent of posttraumatic stress disorder (PTSD) patients do not respond to treatment. Understanding the neural mechanisms underlying treatment response could contribute to improve response rates. PTSD is often associated with decreased inhibition of fear responses in a safe environment. Importantly, the mechanism of effective treatment (psychotherapy) relies on inhibition and so-called contextual cue processing. Therefore, we investigate inhibition and contextual cue processing in the context of treatment. Forty-one male war veterans with PTSD and 22 healthy male war veterans (combat controls) were scanned twice with a 6- to 8-month interval, in which PTSD patients received treatment (psychotherapy). We distinguished treatment responders from nonresponders on the base of percentage symptom decrease. Inhibition and contextual cue processing were assessed with the stop-signal anticipation task. Behavioral and functional MRI measures were compared between PTSD patients and combat controls, and between responders and nonresponders using repeated measures analyses. PTSD patients showed behavioral and neural deficits in inhibition and contextual cue processing at both time points compared with combat controls. These deficits were unaffected by treatment; therefore, they likely represent vulnerability factors or scar aspects of PTSD. Second, responders showed increased pretreatment activation of the left inferior parietal lobe (IPL) during contextual cue processing compared with nonresponders. Moreover, left IPL activation predicted percentage symptom improvement. The IPL has an important role in contextual cue processing, and may therefore facilitate the effect of psychotherapy. Hence, increased left IPL activation may represent a potential predictive biomarker for PTSD treatment response.

Figures

Figure 1

Stop-signal anticipation task (SSAT). Three horizontal lines were displayed throughout the task. A bar moved in 1000 ms from the bottom line to the top. At 800 ms the bar reached the middle colored line and had to be stopped (Go trials, a). In a minority of the trials the bar stopped moving on its own before reaching the middle colored line, consequently, the stop response had to be withheld (stop trials, b). The color of the middle line indicated the stop-signal probability (c). For information on this task see Supplementary Materials and Methods S1 and van Rooij et al (2014); Zandbelt and Vink (2010).

Figure 2

Left inferior parietal lobe (IPL) activation in treatment responders and nonresponders. (a) Whole brain group analysis of contextual cue processing revealed a significant response group by time interaction. The significant cluster is displayed on a standardized brain (MRIcron). Left=left. (b) Mean activation levels of the left IPL plotted for each group pretreatment (T0) and posttreatment (T6). Error bars indicate the standard errors. (c) For each PTSD patient, mean left IPL activation level (T0) was plotted against percentage symptom reduction (based on decrease in CAPS score).