Integrating multi-omics with neuroimaging and behavior: A preliminary model of dysfunction in football athletes

Contact sports affect measures at multiple scales such as transcriptomics, metabolomics, brain function, and behavior, but studies have not yet studied the statistical structure of how they are integrated. This preliminary study, examining collegiate American football players, integrated across-seas...

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Main Authors: Sumra Bari, Nicole L. Vike, Khrystyna Stetsiv, Alexa Walter, Sharlene Newman, Keisuke Kawata, Jeffrey J. Bazarian, Linda Papa, Eric A. Nauman, Thomas M. Talavage, Semyon Slobounov, Hans C. Breiter
Format: Article
Language:English
Published: Elsevier 2021-09-01
Series:NeuroImage: Reports
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Online Access:http://www.sciencedirect.com/science/article/pii/S2666956021000301
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author Sumra Bari
Nicole L. Vike
Khrystyna Stetsiv
Alexa Walter
Sharlene Newman
Keisuke Kawata
Jeffrey J. Bazarian
Linda Papa
Eric A. Nauman
Thomas M. Talavage
Semyon Slobounov
Hans C. Breiter
author_facet Sumra Bari
Nicole L. Vike
Khrystyna Stetsiv
Alexa Walter
Sharlene Newman
Keisuke Kawata
Jeffrey J. Bazarian
Linda Papa
Eric A. Nauman
Thomas M. Talavage
Semyon Slobounov
Hans C. Breiter
author_sort Sumra Bari
collection DOAJ
description Contact sports affect measures at multiple scales such as transcriptomics, metabolomics, brain function, and behavior, but studies have not yet studied the statistical structure of how they are integrated. This preliminary study, examining collegiate American football players, integrated across-season changes (Δ) from transcriptomic and metabolomic variables (neuroinflammatory miRNAs and metabolites), neuroimaging (resting-state fMRI network fingerprint similarity), and virtual reality (VR)-based motor control. These findings were then assessed against head acceleration events (HAE). Using permutation-based moderation analysis (all pFperm,pβ3perm ≤0.05), we observed that (1) Δtridecenedioate, a mono-unsaturated fatty acid, interacted with ΔmiR-505 to predict default mode network (DMN) fingerprint similarity, meaning the interaction between two molecular biology measures predicted a neuroimaging measure. Further, (2) Δtridecenedioate and DMN fingerprint similarity interacted to predict motor control, indicating the interaction of a molecular and a neuroimaging measure predicted behavior. ΔmiR-505 was positively related to HAE and DMN fingerprint similarity was negatively related to HAE and reduced relative to non-athlete subjects. These multi-scale, moderating relationships between a potential ROS scavenger, neuroinflammatory miRNA, reduced brain connectivity, and diminished motor control argue that seemingly healthy athletes with frequent HAE may experience chronic neuroinflammation. This imaging-omics framework using permutation-based mediation/moderation analysis has general applicability for human-animal translational studies.
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spelling doaj-art-62e468591cab4c1fb4ebc22ca8adacdd2025-08-20T01:57:32ZengElsevierNeuroImage: Reports2666-95602021-09-011310003210.1016/j.ynirp.2021.100032Integrating multi-omics with neuroimaging and behavior: A preliminary model of dysfunction in football athletesSumra Bari0Nicole L. Vike1Khrystyna Stetsiv2Alexa Walter3Sharlene Newman4Keisuke Kawata5Jeffrey J. Bazarian6Linda Papa7Eric A. Nauman8Thomas M. Talavage9Semyon Slobounov10Hans C. Breiter11Warren Wright Adolescent Center Department of Psychiatry and Behavioral Sciences, Feinberg School of Medicine, Northwestern University, Chicago, IL, USAWarren Wright Adolescent Center Department of Psychiatry and Behavioral Sciences, Feinberg School of Medicine, Northwestern University, Chicago, IL, USAWarren Wright Adolescent Center Department of Psychiatry and Behavioral Sciences, Feinberg School of Medicine, Northwestern University, Chicago, IL, USADepartment of Kinesiology, Pennsylvania State University, University Park, PA, USADepartment of Psychological and Brain Sciences, Indiana University, Bloomington, IN, USADepartment of Kinesiology, School of Public Health-Bloomington, Indiana University, Bloomington, IN, USA; Program in Neuroscience, College of Arts and Sciences, Indiana University, Bloomington, IN, USADepartment of Emergency Medicine, University of Rochester, Rochester, NY, USADepartment of Emergency Medicine, Orlando Regional Medical Center, Orlando, FL, USAWeldon School of Biomedical Engineering, Purdue University, West Lafayette, IN, USA; School of Mechanical Engineering, Purdue University, West Lafayette, IN, USA; Department of Basic Medical Sciences, Purdue University, West Lafayette, IN, USAWeldon School of Biomedical Engineering, Purdue University, West Lafayette, IN, USA; School of Electrical and Computer Engineering, Purdue University, West Lafayette, IN, USA; Department of Biomedical Engineering, University of Cincinnati, Cincinnati, OH, USADepartment of Kinesiology, Pennsylvania State University, University Park, PA, USA; Corresponding author.Warren Wright Adolescent Center Department of Psychiatry and Behavioral Sciences, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA; Laboratory of Neuroimaging and Genetics, Department of Psychiatry, Massachusetts General Hospital and Harvard School of Medicine, Boston, MA, USA; Corresponding author. Warren Wright Adolescent Center Department of Psychiatry and Behavioral Sciences, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.Contact sports affect measures at multiple scales such as transcriptomics, metabolomics, brain function, and behavior, but studies have not yet studied the statistical structure of how they are integrated. This preliminary study, examining collegiate American football players, integrated across-season changes (Δ) from transcriptomic and metabolomic variables (neuroinflammatory miRNAs and metabolites), neuroimaging (resting-state fMRI network fingerprint similarity), and virtual reality (VR)-based motor control. These findings were then assessed against head acceleration events (HAE). Using permutation-based moderation analysis (all pFperm,pβ3perm ≤0.05), we observed that (1) Δtridecenedioate, a mono-unsaturated fatty acid, interacted with ΔmiR-505 to predict default mode network (DMN) fingerprint similarity, meaning the interaction between two molecular biology measures predicted a neuroimaging measure. Further, (2) Δtridecenedioate and DMN fingerprint similarity interacted to predict motor control, indicating the interaction of a molecular and a neuroimaging measure predicted behavior. ΔmiR-505 was positively related to HAE and DMN fingerprint similarity was negatively related to HAE and reduced relative to non-athlete subjects. These multi-scale, moderating relationships between a potential ROS scavenger, neuroinflammatory miRNA, reduced brain connectivity, and diminished motor control argue that seemingly healthy athletes with frequent HAE may experience chronic neuroinflammation. This imaging-omics framework using permutation-based mediation/moderation analysis has general applicability for human-animal translational studies.http://www.sciencedirect.com/science/article/pii/S2666956021000301TridecenedioatemiR-505rs-fMRIMotor controlHead impactsFootball
spellingShingle Sumra Bari
Nicole L. Vike
Khrystyna Stetsiv
Alexa Walter
Sharlene Newman
Keisuke Kawata
Jeffrey J. Bazarian
Linda Papa
Eric A. Nauman
Thomas M. Talavage
Semyon Slobounov
Hans C. Breiter
Integrating multi-omics with neuroimaging and behavior: A preliminary model of dysfunction in football athletes
NeuroImage: Reports
Tridecenedioate
miR-505
rs-fMRI
Motor control
Head impacts
Football
title Integrating multi-omics with neuroimaging and behavior: A preliminary model of dysfunction in football athletes
title_full Integrating multi-omics with neuroimaging and behavior: A preliminary model of dysfunction in football athletes
title_fullStr Integrating multi-omics with neuroimaging and behavior: A preliminary model of dysfunction in football athletes
title_full_unstemmed Integrating multi-omics with neuroimaging and behavior: A preliminary model of dysfunction in football athletes
title_short Integrating multi-omics with neuroimaging and behavior: A preliminary model of dysfunction in football athletes
title_sort integrating multi omics with neuroimaging and behavior a preliminary model of dysfunction in football athletes
topic Tridecenedioate
miR-505
rs-fMRI
Motor control
Head impacts
Football
url http://www.sciencedirect.com/science/article/pii/S2666956021000301
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