  Collision sports athletes experience many head acceleration events (HAEs) per
season. The effects of these subconcussive events are largely understudied
since HAEs may produce no overt symptoms, and are likely to diffusely manifest
across multiple scales of study (e.g., molecular, cellular network, and
behavior). This study integrated resting-state fMRI with metabolome,
transcriptome and computational virtual reality (VR) behavior measures to
assess the effects of exposure to HAEs on players in a collegiate American
football team. Permutation-based mediation and moderation analysis was used to
investigate relationships between network fingerprint, changes in omic measures
and VR metrics over the season. Change in an energy cycle fatty acid,
tridecenedioate, moderated the relationship between 1) miR-505 and DMN
fingerprint and 2) the relationship between DMN fingerprint and worsening VR
Balance measures (all p less than or equal to 0.05). In addition, the
similarity in DMN over the season was negatively related to cumulative number
of HAEs above 80G, and DMN fingerprint was less similar across the season in
athletes relative to age-matched non-athletes. miR-505 was also positively
related to average number of HAEs above 25G per session. It is important to
note that tridecenedioate has a double bond making it a candidate for ROS
scavenging. These findings between a candidate ROS-related metabolite,
inflammatory miRNA, altered brain imaging and diminished behavioral performance
suggests that impact athletes may experience chronic neuroinflammation. The
rigorous permutation-based mediation/moderation may provide a methodology for
investigating complex multi-scale biological data within humans alone and thus
assist study of other functional brain problems.
