Dataset Information

Large-scale dynamic causal modeling of major depressive disorder based on resting-state functional magnetic resonance imaging.

ABSTRACT: Major depressive disorder (MDD) is a serious mental illness characterized by dysfunctional connectivity among distributed brain regions. Previous connectome studies based on functional magnetic resonance imaging (fMRI) have focused primarily on undirected functional connectivity and existing directed effective connectivity (EC) studies concerned mostly task-based fMRI and incorporated only a few brain regions. To overcome these limitations and understand whether MDD is mediated by within-network or between-network connectivities, we applied spectral dynamic causal modeling to estimate EC of a large-scale network with 27 regions of interests from four distributed functional brain networks (default mode, executive control, salience, and limbic networks), based on large sample-size resting-state fMRI consisting of 100 healthy subjects and 100 individuals with first-episode drug-naive MDD. We applied a newly developed parametric empirical Bayes (PEB) framework to test specific hypotheses. We showed that MDD altered EC both within and between high-order functional networks. Specifically, MDD is associated with reduced excitatory connectivity mainly within the default mode network (DMN), and between the default mode and salience networks. In addition, the network-averaged inhibitory EC within the DMN was found to be significantly elevated in the MDD. The coexistence of the reduced excitatory but increased inhibitory causal connections within the DMNs may underlie disrupted self-recognition and emotional control in MDD. Overall, this study emphasizes that MDD could be associated with altered causal interactions among high-order brain functional networks.

SUBMITTER: Li G

PROVIDER: S-EPMC7268036 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Large-scale dynamic causal modeling of major depressive disorder based on resting-state functional magnetic resonance imaging.

Li Guoshi G Liu Yujie Y Zheng Yanting Y Li Danian D Liang Xinyu X Chen Yaoping Y Cui Ying Y Yap Pew-Thian PT Qiu Shijun S Zhang Han H Zhang Han H Shen Dinggang D

Human brain mapping 20191105 4

Major depressive disorder (MDD) is a serious mental illness characterized by dysfunctional connectivity among distributed brain regions. Previous connectome studies based on functional magnetic resonance imaging (fMRI) have focused primarily on undirected functional connectivity and existing directed effective connectivity (EC) studies concerned mostly task-based fMRI and incorporated only a few brain regions. To overcome these limitations and understand whether MDD is mediated by within-network ...[more]

PMID: 32026598

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Project description:Major depressive disorder (MDD) often emerges during adolescence, a critical period of brain development. Recent resting-state fMRI studies of adults suggest that MDD is associated with abnormalities within and between resting-state networks (RSNs). Here we tested whether adolescent MDD is characterized by abnormalities in interactions among RSNs. Participants were 55 unmedicated adolescents diagnosed with MDD and 56 matched healthy controls. Functional connectivity was mapped using resting-state fMRI. We used the network-based statistic (NBS) to compare large-scale connectivity between groups and also compared the groups on graph metrics. We further assessed whether group differences identified using nodes defined from functionally defined RSNs were also evident when using anatomically defined nodes. In addition, we examined relations between network abnormalities and depression severity and duration. Finally, we compared intranetwork connectivity between groups and assessed the replication of previously reported MDD-related abnormalities in connectivity. The NBS indicated that, compared with controls, depressed adolescents exhibited reduced connectivity (p<0.024, corrected) between a specific set of RSNs, including components of the attention, central executive, salience, and default mode networks. The NBS did not identify group differences in network connectivity when using anatomically defined nodes. Longer duration of depression was significantly correlated with reduced connectivity in this set of network interactions (p=0.020, corrected), specifically with reduced connectivity between components of the dorsal attention network. The dorsal attention network was also characterized by reduced intranetwork connectivity in the MDD group. Finally, we replicated previously reported abnormal connectivity in individuals with MDD. In summary, adolescents with MDD show hypoconnectivity between large-scale brain networks compared with healthy controls. Given that connectivity among these networks typically increases during adolescent neurodevelopment, these results suggest that adolescent depression is associated with abnormalities in neural systems that are still developing during this critical period.

Project description:ImportanceMajor depressive disorder (MDD) has been linked to imbalanced communication among large-scale brain networks, as reflected by abnormal resting-state functional connectivity (rsFC). However, given variable methods and results across studies, identifying consistent patterns of network dysfunction in MDD has been elusive.ObjectiveTo investigate network dysfunction in MDD through a meta-analysis of rsFC studies.Data sourcesSeed-based voxelwise rsFC studies comparing individuals with MDD with healthy controls (published before June 30, 2014) were retrieved from electronic databases (PubMed, Web of Science, and EMBASE) and authors contacted for additional data.Study selectionTwenty-seven seed-based voxel-wise rsFC data sets from 25 publications (556 individuals with MDD and 518 healthy controls) were included in the meta-analysis.Data extraction and synthesisCoordinates of seed regions of interest and between-group effects were extracted. Seeds were categorized into seed-networks by their location within a priori functional networks. Multilevel kernel density analysis of between-group effects identified brain systems in which MDD was associated with hyperconnectivity (increased positive or reduced negative connectivity) or hypoconnectivity (increased negative or reduced positive connectivity) with each seed-network.ResultsMajor depressive disorder was characterized by hypoconnectivity within the frontoparietal network, a set of regions involved in cognitive control of attention and emotion regulation, and hypoconnectivity between frontoparietal systems and parietal regions of the dorsal attention network involved in attending to the external environment. Major depressive disorder was also associated with hyperconnectivity within the default network, a network believed to support internally oriented and self-referential thought, and hyperconnectivity between frontoparietal control systems and regions of the default network. Finally, the MDD groups exhibited hypoconnectivity between neural systems involved in processing emotion or salience and midline cortical regions that may mediate top-down regulation of such functions.Conclusions and relevanceReduced connectivity within frontoparietal control systems and imbalanced connectivity between control systems and networks involved in internal or external attention may reflect depressive biases toward internal thoughts at the cost of engaging with the external world. Meanwhile, altered connectivity between neural systems involved in cognitive control and those that support salience or emotion processing may relate to deficits regulating mood. These findings provide an empirical foundation for a neurocognitive model in which network dysfunction underlies core cognitive and affective abnormalities in depression.

Dataset Information

Large-scale dynamic causal modeling of major depressive disorder based on resting-state functional magnetic resonance imaging.

Publications

Large-scale dynamic causal modeling of major depressive disorder based on resting-state functional magnetic resonance imaging.

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