Functional connectivity gradients and neurotransmitter maps among patients with mild cognitive impairment and depression symptoms

Xiaozheng Liu; Xiaojun Chen; Jinming Cheng; Fuquan Wei; Hongtao Hou; Jiapeng Li; Kun Liu; Zhongwei Guo; Zhihan Yan; Aiqin Wu

doi:10.1503/jpn.240111

Functional connectivity gradients and neurotransmitter maps among patients with mild cognitive impairment and depression symptoms

J Psychiatry Neurosci. 2025 Jan 3;50(1):E11-E20. doi: 10.1503/jpn.240111. Print 2025 Jan-Feb.

Authors

Xiaozheng Liu^#¹, Xiaojun Chen^#¹, Jinming Cheng¹, Fuquan Wei¹, Hongtao Hou¹, Jiapeng Li¹, Kun Liu¹, Zhongwei Guo², Zhihan Yan², Aiqin Wu²

Affiliations

¹ From the Second Affiliated Hospital and Yuying Children's Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China (X. Liu, Chen, K. Liu, Yan, Wu); the Wenzhou Key Laboratory of Structural and Functional Imaging, Wenzhou, Zhejiang Province, China (X. Liu, Chen, K. Liu, Yan); the Jinhua Municipal Central Hospital, Jinhua, Zhejiang 321000, China (Chen); the Hebei General Hospital, Shijiazhuang, Hebei 050050, China (Cheng); the Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang 310012, China (Wei, Hou, Li, Guo); the Zhoushan Second People's Hospital, Zhoushan, Zhejiang 316000, China (Guo).
² From the Second Affiliated Hospital and Yuying Children's Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China (X. Liu, Chen, K. Liu, Yan, Wu); the Wenzhou Key Laboratory of Structural and Functional Imaging, Wenzhou, Zhejiang Province, China (X. Liu, Chen, K. Liu, Yan); the Jinhua Municipal Central Hospital, Jinhua, Zhejiang 321000, China (Chen); the Hebei General Hospital, Shijiazhuang, Hebei 050050, China (Cheng); the Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang 310012, China (Wei, Hou, Li, Guo); the Zhoushan Second People's Hospital, Zhoushan, Zhejiang 316000, China (Guo) [email protected] [email protected] [email protected].

^# Contributed equally.

PMID: 39753307
DOI: 10.1503/jpn.240111

Abstract

Background: Both depressive symptoms and neurotransmitter changes affect the characteristics of functional brain networks in clinical patients. We sought to explore how brain functional grading is organized among patients with mild cognitive impairment and depressive symptoms (D-MCI) and whether changes in brain organization are related to neurotransmitter distribution.

Methods: Using 3 T magnetic resonance imaging (MRI) we acquired functional MRI (fMRI) data from patients with D-MCI, patients with mild cognitive impairment without depression (nD-MCI), and healthy controls. We used resting-state fMRI and diffusion embedding to examine the pattern of functional connectivity gradients. We used analysis of covariance and post hoc t tests to compare the difference in functional connectivity gradients among the 3 groups. We examined the correlation between variations in functional connectivity gradients and neurotransmitter maps using the JuSpace toolbox.

Results: We included 105 participants, including 31 patients with D-MCI, 40 patients with nD-MCI, and 34 healthy controls. Compared with healthy controls, both the nD-MCI and D-MCI groups showed abnormalities in the principal unimodal-transmodal gradient pattern. Compared with controls, the D-MCI group showed an increased secondary gradient in the default mode network. Differences in the functional connectivity gradients between the D-MCI and nD-MCI groups were significantly correlated with the distribution of 5-hydroxytryptamine receptor subtype 1A.

Limitations: The small sample size affects the generalizability of the results, and the neurotransmitter template is based on healthy participants, not patients.

Conclusion: Our results suggest that depressive symptoms cause abnormalities in the hierarchical segregation of functional brain organization among patients with MCI. Such abnormal changes may be related to the distribution of neurotransmitters.