A preliminary model of football-related neural stress that integrates metabolomics with transcriptomics and virtual reality
Nicole L. Vike,
Sumra Bari,
Khrystyna Stetsiv,
Alexa Walter,
Sharlene Newman,
Keisuke Kawata,
Jeffrey J. Bazarian,
Zoran Martinovich,
Eric A. Nauman,
Thomas M. Talavage,
Linda Papa,
Semyon M. Slobounov,
Hans C. Breiter
Affiliations
Nicole L. Vike
Warren Wright Adolescent Center Department of Psychiatry and Behavioral Sciences, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
Sumra Bari
Warren Wright Adolescent Center Department of Psychiatry and Behavioral Sciences, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
Khrystyna Stetsiv
Warren Wright Adolescent Center Department of Psychiatry and Behavioral Sciences, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
Alexa Walter
Department of Kinesiology, Pennsylvania State University, University Park, PA 16801, USA
Sharlene Newman
Department of Psychological and Brain Sciences, Indiana University, Bloomington, IN 47405, USA
Keisuke Kawata
Department of Kinesiology, School of Public Health-Bloomington, Indiana University, Bloomington, IN 47405, USA; Program in Neuroscience, College of Arts and Sciences, Indiana University, Bloomington, IN 47405, USA
Jeffrey J. Bazarian
Department of Emergency Medicine, University of Rochester, Rochester, NY 14627, USA
Zoran Martinovich
Warren Wright Adolescent Center Department of Psychiatry and Behavioral Sciences, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
Eric A. Nauman
Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN 47907, USA; School of Mechanical Engineering, Purdue University, West Lafayette, IN 47907, USA; Department of Basic Medical Sciences, Purdue University, West Lafayette, IN 47907, USA
Thomas M. Talavage
Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN 47907, USA; School of Electrical and Computer Engineering, Purdue University, West Lafayette, IN 47907, USA; Department of Biomedical Engineering, University of Cincinnati, Cincinnati, OH 45221, USA
Linda Papa
Department of Emergency Medicine, Orlando Regional Medical Center, Orlando, FL 32806, USA
Semyon M. Slobounov
Department of Kinesiology, Pennsylvania State University, University Park, PA 16801, USA; Corresponding author
Hans C. Breiter
Warren Wright Adolescent Center Department of Psychiatry and Behavioral Sciences, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA; Laboratory of Neuroimaging and Genetics, Department of Psychiatry, Massachusetts General Hospital and Harvard School of Medicine, Boston, MA 02114, USA; Corresponding author
Summary: Research suggests contact sports affect neurological health. This study used permutation-based mediation statistics to integrate measures of metabolomics, neuroinflammatory miRNAs, and virtual reality (VR)-based motor control to investigate multi-scale relationships across a season of collegiate American football. Fourteen significant mediations (six pre-season, eight across-season) were observed where metabolites always mediated the statistical relationship between miRNAs and VR-based motor control (pSobelperm ≤ 0.05; total effect > 50%), suggesting a hypothesis that metabolites sit in the statistical pathway between transcriptome and behavior. Three results further supported a model of chronic neuroinflammation, consistent with mitochondrial dysfunction: (1) Mediating metabolites were consistently medium-to-long chain fatty acids, (2) tricarboxylic acid cycle metabolites decreased across-season, and (3) accumulated head acceleration events statistically moderated pre-season metabolite levels to directionally model post-season metabolite levels. These preliminary findings implicate potential mitochondrial dysfunction and highlight probable peripheral blood biomarkers underlying repetitive head impacts in otherwise healthy collegiate football athletes.
