White matter volume and microstructural integrity are associated with fatigue in relapsing multiple sclerosis

Abstract Multiple sclerosis (MS) is a prevalent neurological disorder marked by inflammation and demyelination, with fatigue being one of the most reported and debilitating symptoms. While fatigue occurs across various neurological conditions and even in healthy individuals, the specific mechanisms...

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Main Authors: Alejandra Figueroa-Vargas, Sebastián Navarrete-Caro, Claudia Cárcamo, Ethel Ciampi, Macarena Vásquez-Torres, Bernardita Soler, Cristian Montalba, Matías Iriarte-Carter, María Paz Martínez-Molina, Patricio Carvajal-Paredes, Mariana Ayala-Ochoa, Víctor Márquez-Rodríguez, Paulo Figueroa-Taiba, Marcela Díaz-Díaz, Joaquín Herrero, Rodrigo Henríquez-Ch, Ximena Stecher, Carla Manterola, Francisco Zamorano, Pamela Guevara, Francisco Aboitiz, Pablo Billeke
Format: Article
Language:English
Published: Nature Portfolio 2025-05-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-01465-6
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author Alejandra Figueroa-Vargas
Sebastián Navarrete-Caro
Claudia Cárcamo
Ethel Ciampi
Macarena Vásquez-Torres
Bernardita Soler
Cristian Montalba
Matías Iriarte-Carter
María Paz Martínez-Molina
Patricio Carvajal-Paredes
Mariana Ayala-Ochoa
Víctor Márquez-Rodríguez
Paulo Figueroa-Taiba
Marcela Díaz-Díaz
Joaquín Herrero
Rodrigo Henríquez-Ch
Ximena Stecher
Carla Manterola
Francisco Zamorano
Pamela Guevara
Francisco Aboitiz
Pablo Billeke
author_facet Alejandra Figueroa-Vargas
Sebastián Navarrete-Caro
Claudia Cárcamo
Ethel Ciampi
Macarena Vásquez-Torres
Bernardita Soler
Cristian Montalba
Matías Iriarte-Carter
María Paz Martínez-Molina
Patricio Carvajal-Paredes
Mariana Ayala-Ochoa
Víctor Márquez-Rodríguez
Paulo Figueroa-Taiba
Marcela Díaz-Díaz
Joaquín Herrero
Rodrigo Henríquez-Ch
Ximena Stecher
Carla Manterola
Francisco Zamorano
Pamela Guevara
Francisco Aboitiz
Pablo Billeke
author_sort Alejandra Figueroa-Vargas
collection DOAJ
description Abstract Multiple sclerosis (MS) is a prevalent neurological disorder marked by inflammation and demyelination, with fatigue being one of the most reported and debilitating symptoms. While fatigue occurs across various neurological conditions and even in healthy individuals, the specific mechanisms contributing to fatigue in each context remain unclear. In this study, we conducted a cross-sectional analysis involving 32 people with relapsing MS (PwRMS) and 29 healthy controls who reported fatigue. Participants underwent MRI scans, including T1-weighted and diffusion-weighted imaging. Additionally, the Modified Fatigue Impact Scale was utilized. We employed Bayesian LASSO and Spike-and-Slab LASSO regression models to investigate the hypothesis that fatigue correlates differently with brain structures in PwRMS. Our findings revealed brain regions associated with general and cognitive fatigue. In particular, reduced white matter volume and compromised microstructural integrity in specific areas—such as the cingulate gyrus, inferior frontal gyrus, and the banks of the superior temporal sulcus—showed significant associations with fatigue scores in PwRMS. These results suggest that alterations in specific brain regions may play a critical role in the clinical manifestation of fatigue in MS. Understanding these insights could help differentiate general mechanisms of fatigue from those affecting people with relapsing MS, which may guide future therapeutic strategies.
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spelling doaj-art-3f0af3e29d494eb1bea96a00f0fe41c92025-08-20T03:53:58ZengNature PortfolioScientific Reports2045-23222025-05-0115111610.1038/s41598-025-01465-6White matter volume and microstructural integrity are associated with fatigue in relapsing multiple sclerosisAlejandra Figueroa-Vargas0Sebastián Navarrete-Caro1Claudia Cárcamo2Ethel Ciampi3Macarena Vásquez-Torres4Bernardita Soler5Cristian Montalba6Matías Iriarte-Carter7María Paz Martínez-Molina8Patricio Carvajal-Paredes9Mariana Ayala-Ochoa10Víctor Márquez-Rodríguez11Paulo Figueroa-Taiba12Marcela Díaz-Díaz13Joaquín Herrero14Rodrigo Henríquez-Ch15Ximena Stecher16Carla Manterola17Francisco Zamorano18Pamela Guevara19Francisco Aboitiz20Pablo Billeke21Laboratorio de Neurociencia Social y Neuromodulación (NeuroCICS), Centro de Investigación en Complejidad Social, Facultad de Gobierno, Universidad del DesarrolloDepartamento de Ingeniería Eléctrica, Facultad de Ingeniería, Universidad de ConcepciónPrograma de Esclerosis Múltiple, Facultad de Medicina, Pontificia Universidad Católica de ChilePrograma de Esclerosis Múltiple, Facultad de Medicina, Pontificia Universidad Católica de ChilePrograma de Esclerosis Múltiple, Facultad de Medicina, Pontificia Universidad Católica de ChilePrograma de Esclerosis Múltiple, Facultad de Medicina, Pontificia Universidad Católica de ChilePrograma de Esclerosis Múltiple, Facultad de Medicina, Pontificia Universidad Católica de ChileLaboratorio de Neurociencia Social y Neuromodulación (NeuroCICS), Centro de Investigación en Complejidad Social, Facultad de Gobierno, Universidad del DesarrolloLaboratorio de Neurociencia Social y Neuromodulación (NeuroCICS), Centro de Investigación en Complejidad Social, Facultad de Gobierno, Universidad del DesarrolloLaboratorio de Neurociencia Social y Neuromodulación (NeuroCICS), Centro de Investigación en Complejidad Social, Facultad de Gobierno, Universidad del DesarrolloLaboratorio de Neurociencia Social y Neuromodulación (NeuroCICS), Centro de Investigación en Complejidad Social, Facultad de Gobierno, Universidad del DesarrolloLaboratorio de Neurociencia Social y Neuromodulación (NeuroCICS), Centro de Investigación en Complejidad Social, Facultad de Gobierno, Universidad del DesarrolloLaboratorio de Neurociencia Social y Neuromodulación (NeuroCICS), Centro de Investigación en Complejidad Social, Facultad de Gobierno, Universidad del DesarrolloLaboratorio de Neurociencia Social y Neuromodulación (NeuroCICS), Centro de Investigación en Complejidad Social, Facultad de Gobierno, Universidad del DesarrolloLaboratorio LaNCE, Centro Interdisciplinario de Neurociencia, Facultad de Medicina, Pontificia Universidad Católica de ChileLaboratorio LaNCE, Centro Interdisciplinario de Neurociencia, Facultad de Medicina, Pontificia Universidad Católica de ChileUnidad de Imágenes Cuantitativas Avanzadas, Departamento de Imágenes, Facultad de Medicina, Clínica Alemana-Universidad del DesarrolloDepartamento de Pediatría, Facultad de Medicina, Clínica Alemana-Universidad del DesarrolloUnidad de Imágenes Cuantitativas Avanzadas, Departamento de Imágenes, Facultad de Medicina, Clínica Alemana-Universidad del DesarrolloDepartamento de Ingeniería Eléctrica, Facultad de Ingeniería, Universidad de ConcepciónLaboratorio LaNCE, Centro Interdisciplinario de Neurociencia, Facultad de Medicina, Pontificia Universidad Católica de ChileLaboratorio de Neurociencia Social y Neuromodulación (NeuroCICS), Centro de Investigación en Complejidad Social, Facultad de Gobierno, Universidad del DesarrolloAbstract Multiple sclerosis (MS) is a prevalent neurological disorder marked by inflammation and demyelination, with fatigue being one of the most reported and debilitating symptoms. While fatigue occurs across various neurological conditions and even in healthy individuals, the specific mechanisms contributing to fatigue in each context remain unclear. In this study, we conducted a cross-sectional analysis involving 32 people with relapsing MS (PwRMS) and 29 healthy controls who reported fatigue. Participants underwent MRI scans, including T1-weighted and diffusion-weighted imaging. Additionally, the Modified Fatigue Impact Scale was utilized. We employed Bayesian LASSO and Spike-and-Slab LASSO regression models to investigate the hypothesis that fatigue correlates differently with brain structures in PwRMS. Our findings revealed brain regions associated with general and cognitive fatigue. In particular, reduced white matter volume and compromised microstructural integrity in specific areas—such as the cingulate gyrus, inferior frontal gyrus, and the banks of the superior temporal sulcus—showed significant associations with fatigue scores in PwRMS. These results suggest that alterations in specific brain regions may play a critical role in the clinical manifestation of fatigue in MS. Understanding these insights could help differentiate general mechanisms of fatigue from those affecting people with relapsing MS, which may guide future therapeutic strategies.https://doi.org/10.1038/s41598-025-01465-6People with relapsing multiple sclerosis (PwRMS)FatigueInferior frontal gyrus (IFG)Frontal poleMagnetic resonance imaging (MRI)Diffusion tensor imaging (DTI)
spellingShingle Alejandra Figueroa-Vargas
Sebastián Navarrete-Caro
Claudia Cárcamo
Ethel Ciampi
Macarena Vásquez-Torres
Bernardita Soler
Cristian Montalba
Matías Iriarte-Carter
María Paz Martínez-Molina
Patricio Carvajal-Paredes
Mariana Ayala-Ochoa
Víctor Márquez-Rodríguez
Paulo Figueroa-Taiba
Marcela Díaz-Díaz
Joaquín Herrero
Rodrigo Henríquez-Ch
Ximena Stecher
Carla Manterola
Francisco Zamorano
Pamela Guevara
Francisco Aboitiz
Pablo Billeke
White matter volume and microstructural integrity are associated with fatigue in relapsing multiple sclerosis
Scientific Reports
People with relapsing multiple sclerosis (PwRMS)
Fatigue
Inferior frontal gyrus (IFG)
Frontal pole
Magnetic resonance imaging (MRI)
Diffusion tensor imaging (DTI)
title White matter volume and microstructural integrity are associated with fatigue in relapsing multiple sclerosis
title_full White matter volume and microstructural integrity are associated with fatigue in relapsing multiple sclerosis
title_fullStr White matter volume and microstructural integrity are associated with fatigue in relapsing multiple sclerosis
title_full_unstemmed White matter volume and microstructural integrity are associated with fatigue in relapsing multiple sclerosis
title_short White matter volume and microstructural integrity are associated with fatigue in relapsing multiple sclerosis
title_sort white matter volume and microstructural integrity are associated with fatigue in relapsing multiple sclerosis
topic People with relapsing multiple sclerosis (PwRMS)
Fatigue
Inferior frontal gyrus (IFG)
Frontal pole
Magnetic resonance imaging (MRI)
Diffusion tensor imaging (DTI)
url https://doi.org/10.1038/s41598-025-01465-6
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