We recruited 42 right-handed participants who had been exposed to criterion A traumatic events (e.g., assault, motor vehicle accidents, abuse, and witnessing serious injury/death). Of these, 21 had current PTSD and 21 never developed PTSD. Within the PTSD group, two participants were removed due to excessive movement during the scan, one participant stopped the scan before the task began, and one participant failed to respond to an adequate number (75%) of trials. Within the TENP group, two participants were excluded due to a button box malfunction, and one participant was excluded due to excessive errors (greater than 25%). A total of 17 PTSD (14 female) and 18 TENP (13 female) participants were included in the final analyses.

PTSD diagnoses were determined using the Clinician Administered PTSD Scale (CAPS) [16]. All other diagnoses were made using the Structured Clinical Interview for the DSM-IV Axis I Disorders (SCID) [2]. Participants were free of the following: contraindications to MRI (e.g., metallic implants), complicating major medical conditions such as neurological disorders, pregnancy, current use of psychotropic medications, and a history of drug/alcohol abuse in the last six months. None of the TENP participants met criteria for any psychiatric disorders. Some participants with PTSD were also diagnosed with current major depressive disorder (MDD; n=5), specific phobia (n=1), and panic disorder (n=3). Psychometric and clinical data are presented in Table 1. All participants provided written informed consent. This study was in compliance with the Helsinki Declaration and approved by the institutional review board at Partners Healthcare System, Boston, Massachusetts.

Table 1 Demographic and psychometric data Full size table

Stimuli and procedures

Stimuli consisted of black and white photographs of 10 faces (5 male), each displaying one happy and one fearful expression [19], with either the word “happy” or “afraid” superimposed on each face (Figure 1). In the Congruent condition (low-interference), the superimposed word matched the facial expression. In the Incongruent condition (high-interference), the superimposed word did not match the facial expression. In the Baseline condition, a string of Xs was superimposed on the facial expression. Presentation timing was jittered using Optseq [20]. Faces were presented for 1300 milliseconds (ms), with a 700 ms inter-stimulus interval, in a pseudorandom order such that the same identity was never presented in succession. Fearful and happy faces were presented an equal number of times for a total of 180 stimuli per run. Interleaved within the facial stimuli were 28 white fixation crosses (null trials), which were presented for either 1300 ms or 3300 ms.

Figure 1 The face on the left is an example of a Congruent trial, in which the word matched the facial expression. The face on the right is an example of an Incongruent trial, in which the word did not match the facial expression. Full size image

Participants completed four runs (6 minutes and 40 seconds each), but fMRI (and behavioral) analyses included only the first two runs to avoid decrements in anterior cingulate activation that are known to occur with extended task performance [21]. Face stimuli were displayed using MacStim Carbon 3.2.1 and projected via a Sharp Notevision6 (XG-NV6XU) LCD projector (Osaka, Japan). Participants used a button box to indicate whether faces were happy or afraid. Button assignments for “happy” and “afraid” were counterbalanced across subjects.

Image acquisition

Participants were scanned using a Symphony/Sonata 1.5T whole body high-speed imaging device, equipped for echo planar imaging (Siemens Medical Systems, Iselin, NJ) with a 3-axis gradient head coil. First, we collected an automated scout image and shimmed [22]. Next, we collected two high-resolution three-dimensional magnetization prepared rapid acquisition gradient echo (MPRAGE) sequences (TR/TE/Flip angle=2730 ms/3.39 ms/7°) with 1.33 mm slice thickness. We acquired fMRI blood-oxygen-level dependent (BOLD) signal images [23] using gradient echo T2*-weighted sequences (TR/TE/Flip angle=2000 ms/40 ms/90°) in 22 coronal slices, (thickness=7 mm, 1 mm gap), with interleaved excitation order and foot-to-head phase encoding. To allow longitudinal magnetization to reach equilibrium, four images were acquired and discarded before the start of each functional scan.

Data analysis

Behavioral analyses

Response times were averaged across correct trials within each condition. Separate 2 (Group: PTSD, TENP) × 2 (Condition: Incongruent, Congruent) analyses of variance (ANOVA) were used to analyze response time and error rate data. With regard to error rates, we examined both errors of commission (incorrect response) and errors of omission (failure to respond) in separate ANOVAs.

FMRI analyses

We performed all fMRI statistical analyses using SPM 2.0 software (Wellcome Department of Cognitive Neurology, London, UK). Functional images were slice-time and motion corrected (realigned to the first volume in the time series), co-registered to structural images, spatially normalized into a standard stereotactic space (Montreal Neurological Institute [MNI] template), and smoothed with a Gaussian filter set at 7mm full width at half maximum.

Voxelwise Incongruent vs. Congruent (IvC) contrast images were created for each participant. These contrast images were then submitted to a second-level random effects model to assess differences between groups (PTSD vs. TENP). Trials involving either errors of commission or omission were excluded from all contrasts.

Statistical parametric maps were inspected for activations in rACC and dorsal anterior cingulate cortex (dACC) that exceeded a significance threshold of p<0.001 (one-tailed), uncorrected. We included the dACC as a secondary region of interest because previous studies have shown relatively greater dACC activation in PTSD versus non-PTSD groups (e.g., [6, 14, 24, 25]). Consistent with previous research, the rACC was defined as the region superior/anterior to the corpus callosum and inferior to the cingulate sulcus, with a y coordinate greater than +30 [26]. The dACC was defined as the region superior to the corpus callosum and inferior to the cingulate sulcus, with a y coordinate between 0 and +30 [25–27]. Activations observed outside of these predefined regions of interest (ROIs) were subjected to the more conservative threshold of p<0.00001, uncorrected. Data from clusters exceeding these thresholds were extracted using MarsBaR (MRC Cognition and Brain Sciences Unit, Cambridge, United Kingdom).

Voxelwise whole brain correlations

To assess the relationship between current CAPS scores and IvC signal change in the PTSD group, we conducted the following voxelwise whole brain correlational analyses. First, we computed the IvC contrast within each participant in the PTSD group and correlated those contrast images with total CAPS scores. Because IvC activation could be related differently to different types of PTSD symptoms, we also ran correlations with CAPS-B (re-experiencing), CAPS-C (avoidance/numbing) and CAPS-D (hyper-arousal) subscale scores. We then inspected our regions of interest for significant clusters using the same p-value thresholds as described above.