This experiment yielded three main findings. First, individuals with PTSD and CECs without PTSD showed significantly greater right amygdala activation during an affective face-matching task when compared to HCs without PTSD or combat exposure in the all faces minus shapes contrast, while only the PTSD group had significantly higher activation in the amygdala for the fearful-happy contrast when contrasted with the CEC and HC groups. Second, in the PTSD group, task-related amygdala activation showed a significant inverse correlation with the severity of avoidance symptoms (as measured by the CAPS). Third, in the CEC compared to the PTSD group, the amygdala showed greater functional connectivity with frontal and parietal regions. Taken together, these findings are consistent with the hypothesis that individuals with combat exposure show a generalized increased limbic activation (in other words, in the amygdala) versus controls without combat exposure; and that among combat-exposed individuals, greater connectivity between the amygdala and frontal cortex may be associated with greater resilience to the development of PTSD. Furthermore, these findings suggest that those with PTSD may attempt to 'turn down' amygdala activation through avoidance.
Increased emotional reactivity in the amygdala has been linked to depression , anxiety [49, 50], PTSD  and genetic vulnerability to psychiatric disorders [51, 52]. Using the same task that was administered in the current study, we observed similar findings in major depressive disorder [42, 43], trait anxiety  and victims of domestic violence . The amygdala has been a relatively robust measure of trauma-related reactivity, especially in studies using PET scans [41, 53–56]. However, amygdala findings have been somewhat split in the PTSD literature in fMRI studies, potentially due to avoidance or similar mechanisms associated with PTSD [9, 10] and/or the exact contrasts used in the analysis. In the current study, we found that amygdala activation was greater in the PTSD group in the fearful-happy contrast. This suggests that this contrast does have specific relevance to PTSD. However, this activation did not correlate to symptom severity. In contrast, we found that combat exposure was associated with amygdala hyperactivation irrespective of PTSD in the faces versus shape contrast. Despite similarly increased amygdala activation to face-shape processing in both combat-exposed groups in the current study; it may be that different functional mechanisms and neural networks are utilized in the PTSD and CEC groups to modulate amygdala hyperactivation. Specifically, the PTSD group may potentially use a psychological mechanism (such as avoidance) while preliminary evidence suggests that the CECs use a cognitive or neural regulatory mechanism (in other words, top-down modulation). These findings further extend previous work, showing weaker connectivity with amygdala functioning in PTSD versus HCs [19, 57], into the comparison with trauma-exposed controls. Even though amygdala activation was similar across trauma groups for when all faces were taken together, when fearful faces were separately contrasted with happy faces the PTSD group showed a significant difference with both control groups in more dorsal regions of the amygdala. These findings replicate prior data in PTSD literature [19–21, 24, 27] and suggest that PTSD individuals show a specific sensitivity to fearful faces that is not seen in trauma controls. These findings are in line with relative consistency of greater sensitivity in the amygdala with regard to aversive versus positive stimuli (such as fearful versus happy faces). The capacity to modulate the amygdala can therefore be an effective way to control affective responses to aversive stimuli.
There is strong evidence of a reciprocal relationship between activation in the medial prefrontal cortex and amygdala in PTSD in combat veterans . This work also showed that regional blood flow in the amygdala correlated positively with PTSD symptom severity while blood flow in the medial prefrontal cortex correlated negatively with PTSD symptom severity. A similar reciprocal relationship between the subgenual cingulate and amygdala has been shown in depression , as well as in normal controls where the rostral cingulate and lateral prefrontal cortex in conjunction appear to regulate the amygdala during processing of faces [59, 60]. Furthermore, animal and human data appear to converge on a model in which successful fear extinction depends on the functionality of this network . Taken together, these studies suggest that this amygdala-prefrontal cortex network may play an important role in trauma exposure such that those who experience trauma and have more robust connections between the amygdala and the prefrontal cortex are less likely to develop PTSD [11, 15, 35].
It is important to note that, although the CEC group showed greater functional connections between the amygdala and numerous regions across the brain, only the subgenual cingulate cluster was found to be more functionally connected to the amygdala in the PTSD group. In a prior study using the same task, we observed similar patterns of functional connectivity, whereby the dorsal cingulate was less functionally connected with the amygdala and the subgenual cingulate was more functionally connected with the amygdala in depressed versus non-depressed individuals . Decreased connectivity between the amygdala and the dorsal anterior cingulate cortex (ACC) has been observed in individuals with current depression relative to controls [62, 63], and connectivity increased significantly in depressed individuals following treatment . These findings are in line with evidence that altered functional activity of the amygdala and cingulate may represent a biomarker for psychiatric stress. In a separate study that investigated face processing, contrasting PTSD due to domestic violence and HCs, we found that the subgenual cingulate, in contrast to the insula, showed greater connectivity in the PTSD group . We interpret these findings as an indication of a recursive connection that further fosters, rather than regulates, regional activation. In line with this hypothesis, prior research has indicated that the subgenual/rostral cingulate is an important region for modulation of amygdala reaction [60, 64, 65]. The subgenual cingulate has specifically been outlined as being a primary area in the response to sad faces as well as being a biomarker for negative mood [49, 66–68]. Several PET and fMRI studies indicate that neural substrates such as the amygdala and subgenual cingulate, which are critical for emotion processing, are hyperactive in individuals with major depressive disorder both at rest  and during emotional tasks [69–72]. Conversely, brain structures such as the dorsal ACC and middle/superior frontal gyrus, which are involved in the cognitive control of behavior  and emotion , are hypoactive in individuals with depression both at rest  and during cognitive tasks . Anatomical studies in animal have identified efferent projections from the ACC to the amygdala . In connectivity studies in humans, the subgenual ACC showed strong connections with the amygdala and medial temporal lobe . It has been suggested that subgenual ACC activation is observed when individuals attend to their internal emotional states . Related evidence suggests that this structure is deactivated by performing difficult cognitive tasks that require an external focus of attention and prompt inhibitory control processes [79, 80]. This further suggests that the CECs are enacting a more cognitive approach to the situation than the PTSD group.
Modulatory control of behavioral-affective responses such as avoidance has been posited as an important mechanism for regulating emotional responses in individuals with PTSD in both psychological  and neural  models. Avoidance symptoms inversely correlate with brain activation in task relevant emotional processing areas  as well as in individuals with PTSD compared to non-traumatized  and traumatized controls . In addition, individuals with PTSD experiencing greater dissociative symptomology, as opposed to greater re-experiencing symptoms, showed attenuation of connectivity to a wide area of brain regions important in affective processing . Diffusion tensor imaging studies in PTSD suggest that the anatomical integrity of connecting fibers in the medial and posterior corpus may be compromised in children with PTSD with a history of childhood maltreatment . Similar reductions in posterior white matter integrity were found in the right superior longitudinal fasciculus OEF/OIF combat veterans who develop psychiatric disorders, such as major depressive disorder, after blast-related concussion . Taken together, these findings support the notion that avoidance symptoms in PTSD may be associated with reduced amygdala connectivity with frontal structures. This provides confirmatory evidence for the hypothesis that individuals with PTSD may show less neural/cognitive control and resort to increased symptom avoidance.
Other important regions of differential activation were observed in the current study. Specifically, the anterior cingulate gyrus was more active in the HCs versus the CECs as well as in CECs versus the individuals with PTSD. Also, the insula was more active in the PTSD patients versus the CECs. Several prior studies have reported anterior cingulate gyrus hypoactivity in PTSD [87–89], which has been hypothesized to relate to the degree to which those with PTSD engage in emotional tasks. This hypothesis is congruent with the current findings. Increased insula activation has also been associated with PTSD [9, 87]. This may suggest that individuals with PTSD have an impaired ability to maintain homeostasis via integration of physiological and emotional information . Our prior work indicates that those with PTSD may have greater ability to alter insula activation in the face of a changing affective environment .
This study has several notable limitations. First, while a complete structured clinical interview was completed in all individuals, six of the 24 participants did not complete the CAPS. Therefore, it was not possible to determine if the correlation with avoidance symptoms remained significant across the complete sample. Second, the task used was not, nor was it intended to be, a provocation task. Thus trauma response is not being modeled in the current design; rather, everyday emotion processing patterns are being assessed. In addition, the face versus shape contrast focuses on face-processing in addition to a fearful versus happy contrast. The fearful versus happy faces contrast was done primarily to verify that the current dataset is behaving in accordance with prior literature. The faces versus shape contrast was selected due to its robust findings as well as the importance of face-processing in daily functioning. While these two conditions are very different, the group differences in areas of affective processing areas are the primary focus of this paper. This contrast is being used to probe the social affective processing of judging facial expressions without focus on valence. Third, the results of this study require replication given the modest size of the sample. Fourth, since the initiation of this study much has been learned about the importance of comorbid head injury. Unfortunately, this was not measured or controlled for in the current study.