Disturbed hierarchy and mediation in reward-related circuits in depression

Backgrounds/Objective: Deep brain stimulation (DBS) has proved the viability of alleviating depression symptoms by stimulating deep reward-related nuclei. This study aims to investigate the abnormal connectivity profiles among superficial, intermediate, and deep brain regions within the reward circu...

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Main Authors: Ruikun Yang, Junxia Chen, Suping Yue, Yue Yu, Jiamin Fan, Yuling Luo, Hui He, Mingjun Duan, Sisi Jiang, Dezhong Yao, Cheng Luo
Format: Article
Language:English
Published: Elsevier 2025-01-01
Series:NeuroImage: Clinical
Online Access:http://www.sciencedirect.com/science/article/pii/S2213158225000099
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author Ruikun Yang
Junxia Chen
Suping Yue
Yue Yu
Jiamin Fan
Yuling Luo
Hui He
Mingjun Duan
Sisi Jiang
Dezhong Yao
Cheng Luo
author_facet Ruikun Yang
Junxia Chen
Suping Yue
Yue Yu
Jiamin Fan
Yuling Luo
Hui He
Mingjun Duan
Sisi Jiang
Dezhong Yao
Cheng Luo
author_sort Ruikun Yang
collection DOAJ
description Backgrounds/Objective: Deep brain stimulation (DBS) has proved the viability of alleviating depression symptoms by stimulating deep reward-related nuclei. This study aims to investigate the abnormal connectivity profiles among superficial, intermediate, and deep brain regions within the reward circuit in major depressive disorder (MDD) and therefore provides references for identifying potential superficial cortical targets for non-invasive neuromodulation. Methods: Resting-state functional magnetic resonance imaging data were collected from a cohort of depression patients (N = 52) and demographically matched healthy controls (N = 60). Utilizing existing DBS targets as seeds, we conducted step-wise functional connectivity (sFC) analyses to delineate hierarchical pathways linking to cerebral cortices. Subsequently, the mediation effects of cortical regions on the interaction within reward-related circuits were further explored by constructing mediation models. Results: In both cohorts, sFC analysis revealed two reward-related pathways from the deepest DBS targets to intermediate regions including the thalamus, insula, and anterior cingulate cortex (ACC), then to the superficial cortical cortex including medial frontal cortex, posterior default mode network (pDMN), and right dorsolateral prefrontal cortex (DLPFC). Patients exhibited reduced sFC in bilateral thalamus and medial frontal cortex in short and long steps respectively compared to healthy controls. We also discovered the disappearance of the mediation effects of superficial cortical regions on the interaction between DBS targets and intermediate regions in reward-related pathways in patients with MDD. Conclusion: Our findings support abnormal hierarchical connectivity and mediation effects in reward-related brain regions at different depth levels in MDD, which might elucidate the underlying pathophysiological mechanisms and inspire novel targets for non-invasive interventions.
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spelling doaj-art-2fb5ae38283e423184d7ce809237b4dd2025-08-20T02:06:20ZengElsevierNeuroImage: Clinical2213-15822025-01-014510373910.1016/j.nicl.2025.103739Disturbed hierarchy and mediation in reward-related circuits in depressionRuikun Yang0Junxia Chen1Suping Yue2Yue Yu3Jiamin Fan4Yuling Luo5Hui He6Mingjun Duan7Sisi Jiang8Dezhong Yao9Cheng Luo10The Clinical Hospital of Chengdu Brain Science Institute MOE Key Lab for Neuroinformation School of Life Science and Technology University of Electronic Science and Technology of China Chengdu PR ChinaThe Clinical Hospital of Chengdu Brain Science Institute MOE Key Lab for Neuroinformation School of Life Science and Technology University of Electronic Science and Technology of China Chengdu PR ChinaThe Clinical Hospital of Chengdu Brain Science Institute MOE Key Lab for Neuroinformation School of Life Science and Technology University of Electronic Science and Technology of China Chengdu PR ChinaThe Clinical Hospital of Chengdu Brain Science Institute MOE Key Lab for Neuroinformation School of Life Science and Technology University of Electronic Science and Technology of China Chengdu PR ChinaThe Clinical Hospital of Chengdu Brain Science Institute MOE Key Lab for Neuroinformation School of Life Science and Technology University of Electronic Science and Technology of China Chengdu PR ChinaThe Clinical Hospital of Chengdu Brain Science Institute MOE Key Lab for Neuroinformation School of Life Science and Technology University of Electronic Science and Technology of China Chengdu PR ChinaThe Clinical Hospital of Chengdu Brain Science Institute MOE Key Lab for Neuroinformation School of Life Science and Technology University of Electronic Science and Technology of China Chengdu PR ChinaThe Clinical Hospital of Chengdu Brain Science Institute MOE Key Lab for Neuroinformation School of Life Science and Technology University of Electronic Science and Technology of China Chengdu PR ChinaThe Clinical Hospital of Chengdu Brain Science Institute MOE Key Lab for Neuroinformation School of Life Science and Technology University of Electronic Science and Technology of China Chengdu PR China; High-Field Magnetic Resonance Brain Imaging Key Laboratory of Sichuan Province Center for Information in Medicine University of Electronic Science and Technology of China Chengdu PR ChinaThe Clinical Hospital of Chengdu Brain Science Institute MOE Key Lab for Neuroinformation School of Life Science and Technology University of Electronic Science and Technology of China Chengdu PR China; High-Field Magnetic Resonance Brain Imaging Key Laboratory of Sichuan Province Center for Information in Medicine University of Electronic Science and Technology of China Chengdu PR China; Research Unit of NeuroInformation Chinese Academy of Medical Sciences Chengdu PR ChinaThe Clinical Hospital of Chengdu Brain Science Institute MOE Key Lab for Neuroinformation School of Life Science and Technology University of Electronic Science and Technology of China Chengdu PR China; High-Field Magnetic Resonance Brain Imaging Key Laboratory of Sichuan Province Center for Information in Medicine University of Electronic Science and Technology of China Chengdu PR China; Research Unit of NeuroInformation Chinese Academy of Medical Sciences Chengdu PR China; Corresponding author at: The Clinical Hospital of Chengdu Brain Science Institute, MOE Key Lab for Neuroinformation, School of Life Science and Technology, University of Electronic Sciencea nd Technology of China, Chengdu 611731, PR China.Backgrounds/Objective: Deep brain stimulation (DBS) has proved the viability of alleviating depression symptoms by stimulating deep reward-related nuclei. This study aims to investigate the abnormal connectivity profiles among superficial, intermediate, and deep brain regions within the reward circuit in major depressive disorder (MDD) and therefore provides references for identifying potential superficial cortical targets for non-invasive neuromodulation. Methods: Resting-state functional magnetic resonance imaging data were collected from a cohort of depression patients (N = 52) and demographically matched healthy controls (N = 60). Utilizing existing DBS targets as seeds, we conducted step-wise functional connectivity (sFC) analyses to delineate hierarchical pathways linking to cerebral cortices. Subsequently, the mediation effects of cortical regions on the interaction within reward-related circuits were further explored by constructing mediation models. Results: In both cohorts, sFC analysis revealed two reward-related pathways from the deepest DBS targets to intermediate regions including the thalamus, insula, and anterior cingulate cortex (ACC), then to the superficial cortical cortex including medial frontal cortex, posterior default mode network (pDMN), and right dorsolateral prefrontal cortex (DLPFC). Patients exhibited reduced sFC in bilateral thalamus and medial frontal cortex in short and long steps respectively compared to healthy controls. We also discovered the disappearance of the mediation effects of superficial cortical regions on the interaction between DBS targets and intermediate regions in reward-related pathways in patients with MDD. Conclusion: Our findings support abnormal hierarchical connectivity and mediation effects in reward-related brain regions at different depth levels in MDD, which might elucidate the underlying pathophysiological mechanisms and inspire novel targets for non-invasive interventions.http://www.sciencedirect.com/science/article/pii/S2213158225000099
spellingShingle Ruikun Yang
Junxia Chen
Suping Yue
Yue Yu
Jiamin Fan
Yuling Luo
Hui He
Mingjun Duan
Sisi Jiang
Dezhong Yao
Cheng Luo
Disturbed hierarchy and mediation in reward-related circuits in depression
NeuroImage: Clinical
title Disturbed hierarchy and mediation in reward-related circuits in depression
title_full Disturbed hierarchy and mediation in reward-related circuits in depression
title_fullStr Disturbed hierarchy and mediation in reward-related circuits in depression
title_full_unstemmed Disturbed hierarchy and mediation in reward-related circuits in depression
title_short Disturbed hierarchy and mediation in reward-related circuits in depression
title_sort disturbed hierarchy and mediation in reward related circuits in depression
url http://www.sciencedirect.com/science/article/pii/S2213158225000099
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