Our study examined the low-frequency blood-oxygen-level-dependent functional connectivity of the default network during the resting state in participants with and without PTSD. During rest in healthy controls, the activity in the PCC/precuneus was correlated with a set of regions implicated in the default network, including the mPFC, precuneus, lateral parietal cortices, inferior and middle temporal cortices, thalamus and cerebellum, replicating previous work.30–34
In contrast, in patients with PTSD, we observed correlation with the PCC/precuneus only with the right superior frontal gyrus (BA 9) and left ventrolateral thalamus, as well as within the PCC itself. Furthermore, direct group contrasts confirmed a greater positive functional connectivity of the PCC with the precuneus, mPFC and bilateral lateral parietal cortex (all areas considered to be part of the default network) among healthy controls than among patients with PTSD.1,4,30–34
We observed similar alterations in connectivity between the control and the PTSD groups for connectivity of seed regions in both the PCC/precuneus and the mPFC. The focus of the present manuscript is on the former seed region, as it has been the focus of most previous analyses of the default network in healthy individuals and because of the frequent observation of task-related differences in activity of this region between patients with PTSD and healthy controls.
Altered functional connectivity of midline cortical structures, including the PCC and the mPFC, has previously been demonstrated in patients with PTSD during emotion-relevant paradigms such as facial affect perception and trauma script–driven imagery.11–14
However, the extent to which such disturbances in functional connectivity are circumscribed to these tasks, as opposed to reflecting a more generalized disturbance that might also be observable at rest, has been thus far unknown. The present evidence suggests that PTSD is characterized by altered connectivity in a robust neural network previously associated with self-referential processing in the resting state.1,4,30–34
We also observed between-group differences in PCC connectivity between the PCC seed region and a number of regions previously associated with PTSD. In particular, patients with PTSD showed less connectivity than controls between the PCC and right amygdala, right hippocampus and right insula. This involvement of the right-hemisphere may be important given the suggestion that the early-life trauma experienced by the patients with PTSD may have interfered primarily with the development of the right hemisphere.40
Greater connectivity of the default network with the amygdala and hippocampus in healthy controls may be particularly interesting in light of the suggestion that a function of the default network is to maintain the organism in a state of readiness for expected future events.41
Moreover, functional neuroimaging studies have implicated the PCC in the assessment of self-reflection42
in addition to (and perhaps via relations with its role in) episodic memory.43
These studies suggest that the PCC may be a crucial node in the default network, linking past information with current environmental events and assessing these events with regard to their relevance to the self. Drawing on these studies, our findings may help to explain the hyper-vigilance and the hypersensitivity to trauma reminders that are central characteristics of PTSD in terms of an increased likelihood of an emotional response to environmental stimuli due to the altered connectivity between the default network and the amygdala, hippocampus and insula.
The association of the default network with self-reflection and self-monitoring also suggests that alterations in the activity of this network may be implicated in dissociative symptoms in patients with PTSD. The dorsolateral prefrontal cortex is part of a second resting state network that consists of areas associated with cognitive processing and that has previously been shown to be negatively correlated with the default network in healthy controls.30,31
In this study, however, among patients with PTSD, scores on the DES,37
which measures trait dissociation, were positively correlated with the extent of connectivity between the PCC/precuneus and a region of the right dorsolateral prefrontal cortex (BA 45/46). A study of working memory in patients with dissociative disorder showed increased activation in the left dorsolateral pre-frontal cortex, which was also associated with better working memory performance, in this patient group.29
Although the present study and the working memory study suggest that the right and the left dorsolateral prefrontal cortices, respectively, may be involved in dissociation, the specific results of the 2 studies may be task-dependent manifestations of a common underlying deficit. Moreover, these findings raise the hypothesis that dissociation may involve alterations in the relation between the default network and brain regions subserving cognitive activity.
Previous studies examining alterations of the default state in psychiatric conditions have examined autism,19
major depressive disorder15
and attention deficit hyper-activity disorder.44
These studies, together with the present study of default network alterations in PTSD, suggest that examination of the activity of this network may help to distinguish between these disorders on the basis of neuropathophysiology. Whereas all of the studies cited above report alterations in the default network associated with psychiatric disorders, there may also be alterations in resting-state connectivity unique to different disorders. In particular, we found less correlation in patients with PTSD than in healthy controls between the PCC/precuneus and the right amygdala, hippocampus and insula. All of these regions have been previously implicated in PTSD10–12
(reviewed in Lanius and colleagues,8
Nemeroff and colleagues9
), and have not shown altered relations with the default network in other psychiatric disorders.15–19
It should be emphasized, however, that this line of research is still in its early stages, and that published studies to date have used a variety of task conditions (including both rest and cognitive tasks) and different analytic techniques to probe the activity of the default network.
To our knowledge, ours is the first study to show that connectivity within the default network at rest is impaired in patients with PTSD. However, our study has certain limitations and also raises questions to be addressed in future studies of the default network. In particular, the PTSD group in our study comprised only women, and all had chronic, early-life trauma exposure. Thus, it may be that the results do not generalize to a population whose trauma exposure was a single incident or those who were adults at the time of trauma exposure. Future studies should also consider the potential effects of sex, as our results cannot be generalized to male patients with PTSD. The effects of comorbid psychiatric conditions and of physiologic and hormonal differences should be addressed in future research. In addition, like previous studies of the default network in patients with psychiatric disorders, our study included medicated patients.15,16,18
It is not yet clear how alterations in default mode connectivity observed to date have been affected by participants’ medication status, as there has not yet been a study that compares medicated and unmedicated patients for any disorder or any medication type. In our study, most patients were taking one or more medications at the time of the scan; however, all of them remained symptomatic, as evidenced by scores on the CAPS and measures of dissociation and alexithymia. Because the PTSD sample in our study included both unmedicated and medicated patients , it is less likely that the alterations in default network connectivity observed here were a result of medication status. However, future work examining the default network in PTSD and other psychiatric disorders should not only include cohorts of unmedicated patients, but also directly examine the potential impact of different psychotropic medications on resting state networks.
We should also note that studies of resting-state activity, as with other studies that do not incorporate an objective behavioural assessment of participants’ compliance with instructions (e.g., script-driven imagery), depend on the assumption that participants did engage in the required task. Finally, future research should examine the complexities of the default network in light of recent reports that suggest that although the 2 seed regions included in our study both correlate with other areas of the default network at rest, they show different patterns of anticorrelations with so-called “task-positive” brain regions and they appear to modulate activity in negatively correlated networks, rather than vice versa.45
In summary, the present evidence suggests that patients with chronic PTSD related to early-life trauma display significantly reduced functional connectivity within the default network during the resting-state. These brain regions, including the PCC, precuneus, and mPFC have been associated with self-referential processing during the resting-state. Accordingly, the present evidence is consistent with the altered forms of self-perception and consciousness accompanying more severe and chronic PTSD. Future studies will also examine whether patterns of default network activation may usefully predict persistence of PTSD symptoms or related post-traumatic symptomatology in acutely traumatized populations.46