Abnormalities in Functional Connectivity in Collegiate Football Athletes with and without a Concussion History: Implications and Role of Neuroactive Kynurenine Pathway Metabolites.
There is a great need to identify potential long-term consequences of contact sport exposure and to identify molecular pathways that may be associated with these changes. We tested the hypothesis that football players with (Ath-mTBI) (n = 25) and without a concussion history (Ath) (n = 24) have altered resting state functional connectivity in regions with previously documented structural changes relative to healthy controls without football or concussion history (HC) (n = 27). As a secondary aim, we tested the hypothesis that group differences in functional connectivity are moderated by the relative ratio of neuroprotective to neurotoxic metabolites of the kynurenine pathway. Ath-mTBI had significantly increased connectivity of motor cortex to the supplementary motor area relative to Ath and HC. In contrast, both Ath-mTBI and Ath had increased connectivity between the left orbital frontal cortex and the right lateral frontal cortex, and between the left cornu ammonis areas 2 and 3/dentate gyrus (CA2-3/DG) of the hippocampus and the middle and posterior cingulate cortices, relative to HC. The relationship between the ratio of plasma concentrations of kynurenic acid to quinolinic acid (KYNA/QUIN) and left pregenual anterior cingulate cortex connectivity to multiple regions as well as KYNA/QUIN and right CA2-3/DG connectivity to multiple regions differed significantly according to football and concussion history. The results suggest that football exposure with and without concussion history can have a significant effect on intrinsic brain connectivity and implicate the kynurenine metabolic pathway as one potential moderator of functional connectivity dependent on football exposure and concussion history.
1 Department of Neurosurgery, Medical College of Wisconsin , Milwaukee, Wisconsin.|2 Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin , Milwaukee, Wisconsin.|3 Laureate Institute for Brain Research , Tulsa, Oklahoma.
Timothy B
TB
Meier
1 Department of Neurosurgery, Medical College of Wisconsin , Milwaukee, Wisconsin.|4 Department of Neurology, Medical College of Wisconsin , Milwaukee, Wisconsin.
Melissa A
MA
Lancaster
5 The Mind Research Network/Lovelace Biomedical and Environmental Research Institute , Albuquerque, New Mexico .|6 Neurology and Psychiatry Departments, University of New Mexico School of Medicine , Albuquerque, New Mexico .|7 Department of Psychology, University of New Mexico , Albuquerque, New Mexico .
Andrew R
AR
Mayer
8 Departments of Surgery and Psychiatry, University of Oklahoma College of Medicine , Tulsa, Oklahoma.|9 Department of Pharmaceutical Sciences, University of Oklahoma College of Pharmacy , Tulsa, Oklahoma.|10 Department of Biochemistry and Microbiology, Oklahoma State University Center for Health Sciences , Tulsa, Oklahoma.
T Kent
TK
Teague
3 Laureate Institute for Brain Research , Tulsa, Oklahoma.|11 Faculty of Community Medicine, The University of Tulsa , Tulsa, Oklahoma.
Jonathan
J
Savitz
D000328:Adult; D001265:Athletic Injuries / Q000000981:diagnostic imaging / Q000503:physiopathology*; D001924:Brain Concussion / Q000097:blood* / Q000000981:diagnostic imaging / Q000503:physiopathology*; D002540:Cerebral Cortex / Q000000981:diagnostic imaging / Q000503:physiopathology*; D063132:Connectome / Q000379:methods*; D005538:Football; D006801:Humans; D007737:Kynurenine / Q000097:blood*; D008297:Male; D053858:Metabolic Networks and Pathways / Q000502:physiology*; D017378:Quinolinic Acid / Q000097:blood; D013334:Students; D014495:Universities; D055815:Young Adult
D007737:Kynurenine; D017378:Quinolinic Acid
kynurenine; mild traumatic brain injury; quinolinic acid; resting state; sport concussion