Resting CMRO2 fluctuations show persistent network hyper-connectivity following exposure to sub-concussive collisions

Abstract

Exposure to head impacts may alter brain connectivity within cortical hubs such as the default-mode network (DMN). However, studies have yet to consider the confounding effects of altered resting cerebral blood flow (CBF0) and cerebrovascular reactivity (CVR) on changes in connectivity following sub-concussive impacts. Here, 23 Canadian collegiate football players were followed during a season using calibrated resting-state MRI and helmet accelerometers to examine the interplay between the neural and vascular factors that determine functional connectivity (FC). Connectivity-based analyses using blood oxygen level dependent (BOLD) and cerebral metabolic rate of oxygen consumption (CMRO2) mapping were used to study the DMN longitudinally. Network-specific decreases in CBF0 were observed one month following the season, while impaired CVR was documented at both mid-season and one month following the season, compared to pre-season baseline. Alterations in CBF0 and BOLD-based CVR throughout the season suggest that neurophysiological markers may show different susceptibility timelines following head impacts. DMN connectivity was increased throughout the season, independent of changes in cerebrovascular physiology, suggesting that alterations in FC following sub-concussive impacts are robust and independent of changes in brain hemodynamics. No significant correlations between impact kinematics and DMN connectivity changes were documented in this study. Altogether, these findings create a strong paradigm for future studies to examine the underlying neural and vascular mechanisms associated with increases in network connectivity following repeated exposure to sub-concussive collisions, in an effort to improve management of head impacts in contact sports. Keywords: Calibrated resting-state, Cerebrovascular physiology, Functional connectivity, Helmet accelerometers, Sub-concussive collisions