Default Mode Network Subsystems Are Differentially Disrupted in Posttraumatic Stress Disorder

Miller, Danielle R.; Hayes, Susan L.; Hayes, Jasmeet P.; Spielberg, Jeffrey M.; Lafleche, Ginette; Verfaellie, Mieke

doi:10.1016/j.bpsc.2016.12.006

Cited by 83 publications

(114 citation statements)

References 77 publications

(94 reference statements)

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“…Overall, consistent findings of reduced resting state functional connectivity between regions within the DMN in PTSD participants compared to controls has been emerging (Patel, Spreng, Shin, & Girard, ; Patriat, Birn, Keding, & Harringa, ; Sripada et al, ). PTSD participants with (Miler et al, ) and without mild traumatic brain injuries (Patriat et al, ; Sripada et al, ) have exhibited reduced connectivity between the hippocampus and prefrontal regions, such as the mPFC, compared to TEC (Jin et al, ; Spielberg, McGlinchey, Milberg, & Salat, ). This reduced within‐DMN connectivity may contribute to characteristic symptoms of PTSD such as intrusive memories, dissociation, or avoidance (Akiki, Averill, & Abdallah, ).…”

Section: Pavlovian Fear Learning and Memory In Post‐traumatic Stressmentioning

confidence: 99%

“…This reduced within‐DMN connectivity may contribute to characteristic symptoms of PTSD such as intrusive memories, dissociation, or avoidance (Akiki, Averill, & Abdallah, ). PTSD participants with more severe avoidance and numbing symptoms had less functional connectivity within DMN, between the hippocampus and the posterior cingulate cortex (PCC), compared to TEC (Miler et al, ).…”

Section: Pavlovian Fear Learning and Memory In Post‐traumatic Stressmentioning

confidence: 99%

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A review of hippocampal activation in post‐traumatic stress disorder

et al. 2019

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Post‐traumatic stress disorder (PTSD) is often characterized by deficits in memory encoding and retrieval and aberrant fear and extinction learning. The hippocampus plays a critical role in memory and contextual processing and has been implicated in intrinsic functional connectivity networks involved in self‐referential thought and memory‐related processes. This review focuses on hippocampal activation findings during memory and fear and extinction learning tasks, as well as resting state hippocampal connectivity in individuals with PTSD. A preponderance of functional neuroimaging studies to date, using memory, fear learning, and extinction tasks, report decreased or “controls comparable” hippocampal activation in individuals with PTSD, which is usually associated with poorer performance on the task imaged. Existing evidence thus raises the possibility that greater hippocampal recruitment in PTSD participants may be required for similar performance levels. Studies of resting state functional connectivity in PTSD predominantly report reduced within‐network connectivity in the default mode network (DMN), as well as greater coupling between the DMN and salience network (SN) via the hippocampus. Together, these findings suggest that deficient hippocampal activation in PTSD may be associated with poorer performance during memory, extinction recall, and fear renewal tasks. Furthermore, studies of resting state connectivity implicate the hippocampus in decreased within‐network DMN connectivity and greater coupling with SN regions characteristic of PTSD.

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Section: Pavlovian Fear Learning and Memory In Post‐traumatic Stressmentioning

confidence: 99%

Section: Pavlovian Fear Learning and Memory In Post‐traumatic Stressmentioning

confidence: 99%

A review of hippocampal activation in post‐traumatic stress disorder

et al. 2019

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“…Recent work by Miller et al. () suggests that PTSD is associated with specific disruptions in the medial temporal lobe subsystem of the DMN, which includes regions such as the hippocampus and ventromedial prefrontal cortex. It is possible that the absence of a bivariate association between PTSD and DMN connectivity in the current study is related to this reported specificity of DMN alterations in PTSD, which was not tested here.…”

Section: Discussionmentioning

confidence: 99%

Posttraumatic stress disorder symptom severity is associated with reduced default mode network connectivity in individuals with elevated genetic risk for psychopathology

et al. 2017

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Background Accumulating evidence suggests that posttraumatic stress disorder (PTSD) is associated with disrupted default mode network (DMN) connectivity, but findings across studies have not been uniform. Individual differences in relevant genes may account for some of the reported variability in the relationship between DMN connectivity and PTSD. In this study, we investigated this possibility using genome-wide association study (GWAS)-derived polygenic risk scores (PRSs) for relevant psychiatric traits. We hypothesized that the association between PTSD and DMN connectivity would be moderated by genetic risk for one or more psychiatric traits such that individuals with elevated polygenic risk for psychopathology and severe PTSD would exhibit disrupted DMN connectivity. Methods Participants were 156 white, non-Hispanic Veterans of the wars in Iraq and Afghanistan who were genotyped and underwent resting state functional magnetic resonance imaging and clinical assessment. PRSs for neuroticism, anxiety, major depressive disorder, and cross-disorder risk (based on five psychiatric disorders) were calculated using summary statistics from published large-scale consortia-based GWASs. Results Cross-disorder polygenic risk influenced the relationship between DMN connectivity and PTSD symptom severity such that individuals at greater genetic risk showed a significant negative association between PTSD symptom severity and connectivity between the posterior cingulate cortex and right middle temporal gyrus. Polygenic risk for neuroticism, anxiety, and major depressive disorder did not influence DMN connectivity directly or through an interaction with PTSD. Conclusions Findings illustrate the potential power of genome-wide PRSs to advance understanding of the relationship between PTSD and DMN connectivity, a putative neural endophenotype of the disorder.

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“…) and function (Miller et al . ). Therefore, we also examined the influence of PTSD and BDNF genotype to disentangle the contribution of this condition from mTBI‐related alterations in hippocampal volume.…”

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confidence: 97%

BDNF genotype is associated with hippocampal volume in mild traumatic brain injury

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et al. 2017

Genes Brain and Behavior

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The negative long-term effects of mild traumatic brain injury (mTBI) have been a growing concern in recent years, with accumulating evidence suggesting that mTBI combined with additional vulnerability factors may induce neurodegenerative-type changes in the brain. However, the factors instantiating risk for neurodegenerative disease following mTBI are unknown. This study examined the link between mTBI and brain-derived neurotrophic factor (BDNF) genotype, which has previously been shown to regulate processes involved in neurodegeneration including synaptic plasticity and facilitation of neural survival through its expression. Specifically, we examined nine BDNF single-nucleotide polymorphisms (SNPs; rs908867, rs11030094, rs6265, rs10501087, rs1157659, rs1491850, rs11030107, rs7127507 and rs12273363) previously associated with brain atrophy or memory deficits in mTBI. Participants were 165 white, non-Hispanic Iraq and Afghanistan war veterans between the ages of 19 and 58, 110 of whom had at least one mTBI in their lifetime. Results showed that the BDNF SNP rs1157659 interacted with mTBI to predict hippocampal volume. Furthermore, exploratory analysis of functional resting state data showed that rs1157659 minor allele homozygotes with a history of mTBI had reduced functional connectivity in the default mode network compared to major allele homozygotes and heterozygotes. Apolipoprotein E (APOE) was not a significant predictor of hippocampal volume or functional connectivity. These results suggest that rs1157659 minor allele homozygotes may be at greater risk for neurodegeneration after exposure to mTBI and provide further evidence for a potential role for BDNF in regulating neural processes following mTBI.

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Default Mode Network Subsystems Are Differentially Disrupted in Posttraumatic Stress Disorder

Cited by 83 publications

References 77 publications

A review of hippocampal activation in post‐traumatic stress disorder

A review of hippocampal activation in post‐traumatic stress disorder

Posttraumatic stress disorder symptom severity is associated with reduced default mode network connectivity in individuals with elevated genetic risk for psychopathology

BDNF genotype is associated with hippocampal volume in mild traumatic brain injury

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