Evidence map›Paper›PMID 42105177›Full record

ArticleJournal of molecular neuroscience : MN2026

Dynamic Triangulation of Resting-State Networks and CSF Metabolites Reveals Bidirectional Causal Pathways in Multiple Sclerosis: A Mendelian Randomization Analysis.

Junyu Chen, Jianlin Li, Liuxin Ran, Kunyi Li, Yang Xie

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Article in Journal of molecular neuroscience : MN, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

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4 · The record

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PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors.

Junyu Chen *Southwest Medical University, Luzhou, Sichuan, China.
Jianlin Li *Department of Radiology, The Third People's Hospital of Chengdu, Chengdu, Sichuan, China.
Liuxin RanSouthwest Medical University, Luzhou, Sichuan, China.
Kunyi LiSchool of Clinical Medicine, Chengdu Medical College, Chengdu, Sichuan, China. lky19911@163.com.
Yang XieDepartment of Neurology, The Affiliated Hospital of Southwest Medical University, No. 25 TaiPing St, Jiangyang District, Luzhou, Sichuan, 646000, PR China. xy114330@163.com.

Funding

Affiliated Hospital of Southwest Medical University 2024LCYXZX53
6 · The paper itself

Abstract

Emotional disorders associated with multiple sclerosis (MS) are key drivers of disease progression. Recently, resting-state functional magnetic resonance imaging (rs-fMRI) and cerebrospinal fluid (CSF) metabolites have been found to play a crucial role in elucidating this process, but the causal relationship between them remains to be clarified. Exploring underlying mechanisms is critical for developing targeted therapies, especially combined multidimensional neuromodulation. This study employed bidirectional two-sample Mendelian randomization (MR) analysis to investigate the causal relationships between 191 rs-fMRI phenotypes and MS, while also exploring the mediating role of 338 CSF metabolites. Forward MR analysis revealed that enhanced functional connectivity in networks such as the saliency and visual networks (pheno56, pheno461, pheno624, pheno932, pheno1183) is related to an elevated risk of MS, whereas enhanced functional connectivity in the motor and attention networks (pheno2, pheno681, pheno705, pheno1322, pheno1696) is linked to a reduced risk of MS. Reverse MR analysis demonstrates that MS exhibits a positive correlation with four of these phenotypes (pheno74, pheno606, pheno767, and pheno1013), and a negative correlation with one phenotype (pheno286). Furthermore, five CSF metabolites-N-formylanthranilic acid, N6-methyllysine, succinimide, methyl glucopyranoside(alpha+beta), and hypoxanthine-were identified as key mediators in the MS process acting through resting-state brain functional networks. The study establishes causal rs-fMRI signatures affecting MS susceptibility and progression, and identifies critical CSF metabolites mediating MS effects via functional networks. These findings not only provide novel intervention targets for MS and related emotional disorders but also lay a theoretical foundation for the development of multidimensional therapeutic strategies leveraging neuromodulation techniques.

Indexed as

Multiple SclerosisHumansMagnetic Resonance ImagingMendelian Randomization AnalysisBrain resting-state functional activitiesCerebrospinal fluid metabolitesMendelian randomizationMultidimensional neuromodulationMultiple sclerosis

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.