Posttraumatic stress disorder (PTSD) is characterized by disturbances in concentration and memory1
that have been linked to underlying alterations in working memory performance compared with both healthy controls with no exposure to trauma2
and healthy controls with trauma exposure.3–5
In a recent article, data were presented that indicate abnormal recruitment of network regions involved in working memory updating during a simple working memory maintenance task in patients with PTSD.6
Subtraction analyses of these data supported the notion that attending to simple working memory tasks, like those requiring only maintenance, demand a greater effort in PTSD patients than in healthy controls; this possibly explains the concentration problems described in the DSM-IV diagnostic criteria for PTSD. Studies also have connected PTSD symptomatology with diminished connectivity of the default mode network during rest.7,8
Because the ability to effortlessly switch between concentration on a task and an idling state during rest may be implicated in both these alterations, we undertook a functional magnetic resonance imaging (fMRI) study with a block design and a comparatively short fixation condition to study the underlying functional connectivity of areas in the default mode network during a low-demand fixation condition and a complex task.
Whereas a previous neuroimaging study showed evidence of attenuated connectivity during the resting state among default mode network regions in PTSD patients during a relatively long resting-state condition,7
modulations in connectivity due to task-induced switching between default mode networks and central-executive and salience networks have yet to be studied. To examine the effects of working memory load on connectivity in these networks, we used psychophysiologic interaction analyses to examine connectivity with seed regions in the medial prefrontal cortex (mPFC) and the posterior cingulate cortex (PCC) in patients with severe, chronic PTSD and matched, healthy controls.
Recent neuroimaging studies have lead to the hypothesis that rest is characterized by an organized baseline level of activity that is attenuated during goal-oriented mental activity. It has been hypothesized that the brain maintains this “default mode” in the absence of cognitive demands,9–11
possibly to facilitate a state of readiness to respond to environmental changes.12
Other authors have linked default mode network activity to self-referential processing because key regions like the posterior cingulate PCC and mPFC have been shown to subserve introspective mental imagery, self-reflection and self-awareness.13–16
A recent meta-analysis17
identified various areas as components of the default mode network, such as the PCC, anterior cingulate cortex (ACC), middle temporal gyrus and mPFC. The stability of the default mode network across the lifespan18–20
as well as across different states (light sedation21
), wakefulness and early stages of sleep22
has been shown, and the functional connectivity was matched by a computational model with high fidelity.23
Tasks that activate the executive network have been consistently shown to evoke decreased activation (deactivation) in the default mode network. McKiernan and colleagues24
showed that task-related deactivation increased with task difficulty. Two previous studies25,26
examined the connectivity of the default mode network during very demanding cognitive tasks and found significantly diminished functional connectivity within the default mode network under high working memory load.
Different groups have recently discussed the notion that the default mode network might comprise different subsystems.16,27
Uddin and colleagues28
revealed considerable differences by analyzing the anticorrelations of seed regions in the mPFC and PCC, suggesting that the activity of distinct nodes of the default mode network may differentially modulate activity in task-positive networks. They suggest that future research should therefore distinguish between these network components and analyze their connectivity separately.
Alterations in default mode network connectivity have emerged as possible markers for psychiatric disorders such as schizophrenia,29
In PTSD, altered functional connectivity in default mode network regions has been shown using emotion-relevant paradigms such as facial affect perception and trauma script–driven imagery.34–36
A recent study carried out by our group analyzed functional connectivity of seed regions in the PCC and the mPFC separately during rest in PTSD patients and healthy controls.7
Direct comparison between groups showed significantly reduced connectivity among default mode network areas in the PTSD group. The PTSD group still showed some, although diminished, connectivity between the PCC seed region and the right superior frontal gyrus (Brodmann area [BA] 9) and left thalamus; however, connectivity of the mPFC seed region was strictly limited to adjunct areas in the mPFC. A prospective study in a group of acutely traumatized patients8
showed that resting-state connectivity of the PCC with the right amygdala predicts future PTSD symptoms, suggesting that the integrity of the default mode network is compromised in PTSD and that the extent of these deficits reflects clinical measures of PTSD. To extend our knowledge about the specificity of these alterations, experimental paradigms that manipulate the activity of the default mode network are needed.
In this study, we investigated the relation between the task-negative default mode network and task-positive networks involved in switching to working memory updating. It has been suggested that there are 2 differentiable task-positive networks: a “salience network” that includes the dorsal ACC and the orbitofrontal-insular cortices, and an “executive-control network” that connects the dorsolateral frontal cortex with the parietal cortex.37,38
Converging evidence for the executive system stems from studies describing the same network structures across a variety of executive-type tasks.39–43
The salience network, which encompasses the frontoinsular circuit and the anterior cingulate, is uniquely positioned to initiate the control of signals that activate the central-executive network.38,44–47
It has been linked to monitoring task performance48
and the modulation of arousal during cognitively demanding tasks.49
These networks mediate higher-order control and likely facilitate the disengagement of systems that are not task-relevant, including the default mode network.46,50
Recent studies have therefore emphasized the salience and executive networks as being critically involved in switching from an idling state into a task-oriented state.38,45,51,52
Therefore, we hypothesized that the relative engagement of these networks is central to the differences in the ability of PTSD patients to engage and disengage from tasks.
We sought to determine whether connectivity with the default mode network nodes differs significantly within the 2 groups between working memory task and the control condition and whether connectivity alterations between groups emerge when comparing the working memory task with the control condition in PTSD patients and healthy controls.
Based on recent publications indicating that the default mode network might exhibit more internal differentiation than generally assumed,28
it seemed plausible that the connectivity patterns for the 2 seed regions would also differ between the PTSD group and the control group. We therefore hypothesized that during the working memory task, both seed regions would show greater connectivity with areas of networks involved in attending to the task (such as the salience network and the executive network) in healthy controls than in PTSD patients.