Abnormalities in Functional Connectivity in Collegiate Football Athletes with and without a Concussion History: Implications and Role of Neuroactive Kynurenine Pathway Metabolites

J Neurotrauma. 2017 Feb 15;34(4):824-837. doi: 10.1089/neu.2016.4599. Epub 2016 Oct 13.

Abstract

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.

Keywords: kynurenine; mild traumatic brain injury; quinolinic acid; resting state; sport concussion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Athletic Injuries / diagnostic imaging
  • Athletic Injuries / physiopathology*
  • Brain Concussion / blood*
  • Brain Concussion / diagnostic imaging
  • Brain Concussion / physiopathology*
  • Cerebral Cortex / diagnostic imaging
  • Cerebral Cortex / physiopathology*
  • Connectome / methods*
  • Football*
  • Humans
  • Kynurenine / blood*
  • Male
  • Metabolic Networks and Pathways / physiology*
  • Quinolinic Acid / blood
  • Students
  • Universities
  • Young Adult

Substances

  • Kynurenine
  • Quinolinic Acid