Disturbed hierarchy and mediation in reward-related circuits in depression

IF 3.4 2区 医学 Q2 NEUROIMAGING Neuroimage-Clinical Pub Date : 2025-01-01 DOI:10.1016/j.nicl.2025.103739
Ruikun Yang , Junxia Chen , Suping Yue , Yue Yu , Jiamin Fan , Yuling Luo , Hui He , Mingjun Duan , Sisi Jiang , Dezhong Yao , Cheng Luo
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Abstract

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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来源期刊
Neuroimage-Clinical
Neuroimage-Clinical NEUROIMAGING-
CiteScore
7.50
自引率
4.80%
发文量
368
审稿时长
52 days
期刊介绍: NeuroImage: Clinical, a journal of diseases, disorders and syndromes involving the Nervous System, provides a vehicle for communicating important advances in the study of abnormal structure-function relationships of the human nervous system based on imaging. The focus of NeuroImage: Clinical is on defining changes to the brain associated with primary neurologic and psychiatric diseases and disorders of the nervous system as well as behavioral syndromes and developmental conditions. The main criterion for judging papers is the extent of scientific advancement in the understanding of the pathophysiologic mechanisms of diseases and disorders, in identification of functional models that link clinical signs and symptoms with brain function and in the creation of image based tools applicable to a broad range of clinical needs including diagnosis, monitoring and tracking of illness, predicting therapeutic response and development of new treatments. Papers dealing with structure and function in animal models will also be considered if they reveal mechanisms that can be readily translated to human conditions.
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