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Neural dysregulation in posttraumatic stress disorder: evidence for disrupted equilibrium between salience and default mode brain networks.

ABSTRACT: Convergent research demonstrates disrupted attention and heightened threat sensitivity in posttraumatic stress disorder (PTSD). This might be linked to aberrations in large-scale networks subserving the detection of salient stimuli (i.e., the salience network [SN]) and stimulus-independent, internally focused thought (i.e., the default mode network [DMN]).Resting-state brain activity was measured in returning veterans with and without PTSD (n = 15 in each group) and in healthy community controls (n = 15). Correlation coefficients were calculated between the time course of seed regions in key SN and DMN regions and all other voxels of the brain.Compared with control groups, participants with PTSD showed reduced functional connectivity within the DMN (between DMN seeds and other DMN regions) including the rostral anterior cingulate cortex/ventromedial prefrontal cortex (z = 3.31; p = .005, corrected) and increased connectivity within the SN (between insula seeds and other SN regions) including the amygdala (z = 3.03; p = .01, corrected). Participants with PTSD also demonstrated increased cross-network connectivity. DMN seeds exhibited elevated connectivity with SN regions including the insula (z = 3.06; p = .03, corrected), and SN seeds exhibited elevated connectivity with DMN regions including the hippocampus (z = 3.10; p = .048, corrected).During resting-state scanning, participants with PTSD showed reduced coupling within the DMN, greater coupling within the SN, and increased coupling between the DMN and the SN. Our findings suggest a relative dominance of threat-sensitive circuitry in PTSD, even in task-free conditions. Disequilibrium between large-scale networks subserving salience detection versus internally focused thought may be associated with PTSD pathophysiology.

SUBMITTER: Sripada RK

PROVIDER: S-EPMC3498527 | biostudies-literature | 2012 Nov-Dec

REPOSITORIES: biostudies-literature

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Neural dysregulation in posttraumatic stress disorder: evidence for disrupted equilibrium between salience and default mode brain networks.

Sripada Rebecca K RK King Anthony P AP Welsh Robert C RC Garfinkel Sarah N SN Wang Xin X Sripada Chandra S CS Liberzon Israel I

Psychosomatic medicine 20121031 9

<h4>Objective</h4>Convergent research demonstrates disrupted attention and heightened threat sensitivity in posttraumatic stress disorder (PTSD). This might be linked to aberrations in large-scale networks subserving the detection of salient stimuli (i.e., the salience network [SN]) and stimulus-independent, internally focused thought (i.e., the default mode network [DMN]).<h4>Methods</h4>Resting-state brain activity was measured in returning veterans with and without PTSD (n = 15 in each group) ...[more]

PMID: 23115342

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Project description:ObjectiveResting-state functional magnetic resonance imaging (rs-fMRI) studies of adult posttraumatic stress disorder (PTSD) have identified default-mode network (DMN) abnormalities, including reduced within-network connectivity and reduced anticorrelation between the DMN and task-positive network (TPN). However, no prior studies have specifically examined DMN connectivity in pediatric PTSD, which may differ due to neurodevelopmental factors.MethodA total of 29 youth with PTSD and 30 nontraumatized healthy youth of comparable age and sex completed rs-fMRI. DMN properties were examined using posterior cingulate cortex (PCC) seed-based connectivity and independent component analysis (ICA).ResultsContrary to findings in adult studies, youth with PTSD displayed increased connectivity within the DMN, including increased PCC-inferior parietal gyrus connectivity, and age-related increases in PCC-ventromedial prefrontal cortex connectivity. Strikingly, youth with PTSD also displayed greater anticorrelation between the PCC and multiple nodes within salience and attentional control networks of the TPN. ICA revealed greater anticorrelation between the entire DMN and TPN networks in youth with PTSD. Furthermore, DMN and TPN connectivity strength were positively and negatively associated, respectively, with re-experiencing symptoms of PTSD.ConclusionPediatric PTSD is characterized by heightened within-DMN connectivity, which may contribute to re-experiencing symptoms of PTSD and is consistent with the role of the DMN in autobiographical memory. At the same time, greater anticorrelation between the DMN and attentional control networks may represent compensatory mechanisms aimed at suppressing trauma-related thought, a notion supported by the inverse relationship between TPN strength and re-experiencing. These findings provide new insights into large-scale network abnormalities underlying pediatric PTSD, which could serve as biomarkers of illness and treatment response.

Project description:While chronic cocaine use is associated with abnormalities in both brain structure and function within and interactions between regions, previous studies have been limited to interrogating structure and function independently, and the detected neural differences have not been applied to independent samples to assess the clinical relevance of results. We investigated consequences of structural differences on resting-state functional connectivity in cocaine addiction and tested whether resting-state functional connectivity of the identified circuits predict relapse in an independent cohort. Subjects included 64 non-treatment-seeking cocaine users (NTSCUs) and 67 healthy control subjects and an independent treatment-completed cohort (n = 45) of cocaine-dependent individuals scanned at the end of a 30-day residential treatment programme. Differences in cortical thickness and related resting-state functional connectivity between NTSCUs and healthy control subjects were identified. Survival analysis, applying cortical thickness of the identified regions, resting-state functional connectivity of the identified circuits and clinical characteristics to the treatment cohort, was used to predict relapse. Lower cortical thickness in bilateral insula and higher thickness in bilateral temporal pole were found in NTSCUs versus healthy control subjects. Whole brain resting-state functional connectivity analyses with these four different anatomical regions as seeds revealed eight weaker circuits including within the salience network (insula seeds) and between temporal pole and elements of the default mode network in NTSCUs. Applying these circuits and clinical characteristics to the independent cocaine-dependent treatment cohort, functional connectivity between right temporal pole and medial prefrontal cortex, combined with years of education, predicted relapse status at 150 days with 88% accuracy. Deficits in the salience network suggest an impaired ability to process physiologically salient events, while abnormalities in a temporal pole-medial prefrontal cortex circuit might speak to the social-emotional functional alterations in cocaine addiction. The involvement of the temporal pole-medial prefrontal cortex circuit in a model highly predictive of relapse highlights the importance of social-emotional functions in cocaine dependence, and provides a potential underlying neural target for therapeutic interventions, and for identifying those at high risk of relapse.

Project description:Self-related processes define assorted self-relevant or social-cognitive functions that allow us to gather insight and to draw inferences related to our own mental conditions. Self-related processes are mediated by the default mode network (DMN), which, critically, shows altered functionality in individuals with posttraumatic stress disorder (PTSD). In PTSD, the midbrain periaqueductal gray (PAG) demonstrates stronger functional connectivity with the DMN [i.e., precuneus (PCN), medial prefrontal cortex (mPFC)] as compared to healthy individuals during subliminal, trauma-related stimulus processing. Here, we analyzed the directed functional connectivity between the PAG and the PCN, as well as between the PAG and the mPFC to more explicitly characterize the functional connectivity we have observed previously on the corresponding sample and paradigm. We evaluated three models varying with regard to context-dependent modulatory directions (i.e., bi-directional, bottom-up, top-down) among individuals with PTSD (n = 26) and healthy participants (n = 20), where Bayesian model selection was used to identify the most optimal model for each group. We then compared the effective connectivity strength for each parameter across the models and between our groups using Bayesian model averaging. Bi-directional models were found to be favoured across both groups. In PTSD, we revealed the PAG to show stronger excitatory effective connectivity to the PCN, as well as to the mPFC as compared to controls. In PTSD, we further demonstrated that PAG-mediated effective connectivity to the PCN, as well as to the mPFC were modulated more strongly during subliminal, trauma-related stimulus conditions as compared to controls. Clinical disturbances towards self-related processes are reported widely by participants with PTSD during trauma-related stimulus processing, where altered functional connectivity directed by the PAG to the DMN may elucidate experiential links between self- and trauma-related processing in traumatized individuals.

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Neural dysregulation in posttraumatic stress disorder: evidence for disrupted equilibrium between salience and default mode brain networks.

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Neural dysregulation in posttraumatic stress disorder: evidence for disrupted equilibrium between salience and default mode brain networks.

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