Modeling functional connectivity with learning and memory in a mouse model of Alzheimer's disease

IntroductionFunctional connectivity (FC) is a metric of how different brain regions interact with each other. Although there have been some studies correlating learning and memory with FC, there have not yet been, to date, studies that use machine learning (ML) to explain how FC changes can be used...

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Main Authors: Lindsay Fadel, Elizabeth Hipskind, Steen E. Pedersen, Jonathan Romero, Caitlyn Ortiz, Eric Shin, Md Abul Hassan Samee, Robia G. Pautler
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-04-01
Series:Frontiers in Neuroimaging
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Online Access:https://www.frontiersin.org/articles/10.3389/fnimg.2025.1558759/full
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author Lindsay Fadel
Elizabeth Hipskind
Steen E. Pedersen
Jonathan Romero
Caitlyn Ortiz
Caitlyn Ortiz
Eric Shin
Md Abul Hassan Samee
Robia G. Pautler
Robia G. Pautler
Robia G. Pautler
author_facet Lindsay Fadel
Elizabeth Hipskind
Steen E. Pedersen
Jonathan Romero
Caitlyn Ortiz
Caitlyn Ortiz
Eric Shin
Md Abul Hassan Samee
Robia G. Pautler
Robia G. Pautler
Robia G. Pautler
author_sort Lindsay Fadel
collection DOAJ
description IntroductionFunctional connectivity (FC) is a metric of how different brain regions interact with each other. Although there have been some studies correlating learning and memory with FC, there have not yet been, to date, studies that use machine learning (ML) to explain how FC changes can be used to explain behavior not only in healthy mice, but also in mouse models of Alzheimer's Disease (AD). Here, we investigated changes in FC and their relationship to learning and memory in a mouse model of AD across disease progression.MethodsWe assessed the APP/PS1 mouse model of AD and wild-type controls at 3-, 6-, and 10-months of age. Using resting state functional magnetic resonance imaging (rs-fMRI) in awake, unanesthetized mice, we assessed FC between 30 brain regions. ML models were then used to define interactions between neuroimaging readouts with learning and memory performance.ResultsIn the APP/PS1 mice, we identified a pattern of hyperconnectivity across all three time points, with 47 hyperconnected regions at 3 months, 46 at 6 months, and 84 at 10 months. Notably, FC changes were also observed in the Default Mode Network, exhibiting a loss of hyperconnectivity over time. Modeling revealed functional connections that support learning and memory performance differ between the 6- and 10-month groups.DiscussionThese ML models show potential for early disease detection by identifying connectivity patterns associated with cognitive decline. Additionally, ML may provide a means to begin to understand how FC translates into learning and memory performance.
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spelling doaj-art-d2821bd7c17a4fae8b5e2bb32eb6f4af2025-08-20T02:28:26ZengFrontiers Media S.A.Frontiers in Neuroimaging2813-11932025-04-01410.3389/fnimg.2025.15587591558759Modeling functional connectivity with learning and memory in a mouse model of Alzheimer's diseaseLindsay Fadel0Elizabeth Hipskind1Steen E. Pedersen2Jonathan Romero3Caitlyn Ortiz4Caitlyn Ortiz5Eric Shin6Md Abul Hassan Samee7Robia G. Pautler8Robia G. Pautler9Robia G. Pautler10Department of Neuroscience, Baylor College of Medicine, Houston, TX, United StatesDepartment of Neuroscience, Baylor College of Medicine, Houston, TX, United StatesDepartment of Integrative Physiology, Baylor College of Medicine, Houston, TX, United StatesSmall Animal Imaging Facility, Texas Children's Hospital, Houston, TX, United StatesDepartment of Integrative Physiology, Baylor College of Medicine, Houston, TX, United StatesSmall Animal Imaging Facility, Texas Children's Hospital, Houston, TX, United StatesDepartment of Integrative Physiology, Baylor College of Medicine, Houston, TX, United StatesDepartment of Integrative Physiology, Baylor College of Medicine, Houston, TX, United StatesDepartment of Neuroscience, Baylor College of Medicine, Houston, TX, United StatesDepartment of Integrative Physiology, Baylor College of Medicine, Houston, TX, United StatesSmall Animal Imaging Facility, Texas Children's Hospital, Houston, TX, United StatesIntroductionFunctional connectivity (FC) is a metric of how different brain regions interact with each other. Although there have been some studies correlating learning and memory with FC, there have not yet been, to date, studies that use machine learning (ML) to explain how FC changes can be used to explain behavior not only in healthy mice, but also in mouse models of Alzheimer's Disease (AD). Here, we investigated changes in FC and their relationship to learning and memory in a mouse model of AD across disease progression.MethodsWe assessed the APP/PS1 mouse model of AD and wild-type controls at 3-, 6-, and 10-months of age. Using resting state functional magnetic resonance imaging (rs-fMRI) in awake, unanesthetized mice, we assessed FC between 30 brain regions. ML models were then used to define interactions between neuroimaging readouts with learning and memory performance.ResultsIn the APP/PS1 mice, we identified a pattern of hyperconnectivity across all three time points, with 47 hyperconnected regions at 3 months, 46 at 6 months, and 84 at 10 months. Notably, FC changes were also observed in the Default Mode Network, exhibiting a loss of hyperconnectivity over time. Modeling revealed functional connections that support learning and memory performance differ between the 6- and 10-month groups.DiscussionThese ML models show potential for early disease detection by identifying connectivity patterns associated with cognitive decline. Additionally, ML may provide a means to begin to understand how FC translates into learning and memory performance.https://www.frontiersin.org/articles/10.3389/fnimg.2025.1558759/fullAlzheimer's diseasers-fMRIfunctional connectivitymodelingbehaviormouse model
spellingShingle Lindsay Fadel
Elizabeth Hipskind
Steen E. Pedersen
Jonathan Romero
Caitlyn Ortiz
Caitlyn Ortiz
Eric Shin
Md Abul Hassan Samee
Robia G. Pautler
Robia G. Pautler
Robia G. Pautler
Modeling functional connectivity with learning and memory in a mouse model of Alzheimer's disease
Frontiers in Neuroimaging
Alzheimer's disease
rs-fMRI
functional connectivity
modeling
behavior
mouse model
title Modeling functional connectivity with learning and memory in a mouse model of Alzheimer's disease
title_full Modeling functional connectivity with learning and memory in a mouse model of Alzheimer's disease
title_fullStr Modeling functional connectivity with learning and memory in a mouse model of Alzheimer's disease
title_full_unstemmed Modeling functional connectivity with learning and memory in a mouse model of Alzheimer's disease
title_short Modeling functional connectivity with learning and memory in a mouse model of Alzheimer's disease
title_sort modeling functional connectivity with learning and memory in a mouse model of alzheimer s disease
topic Alzheimer's disease
rs-fMRI
functional connectivity
modeling
behavior
mouse model
url https://www.frontiersin.org/articles/10.3389/fnimg.2025.1558759/full
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