Functionally-detected cognitive impairment in high school football players without clinically-diagnosed concussion

Abstract

Head trauma and concussion in football players have recently received considerable media attention. Postmortem evidence suggests that accrual of damage to the brain may occur with repeated blows to the head, even when the individual blows fail to produce clinical symptoms. There is an urgent need for improved detection and characterization of head trauma to reduce future injury risk and promote development of new therapies. In this study we examined neurological performance and health in the presence of head collision events in high school football players, using longitudinal measures of collision events (the HIT(™) System), neurocognitive testing (ImPACT(™)), and functional magnetic resonance imaging MRI (fMRI). Longitudinal assessment (including baseline) was conducted in 11 young men (ages 15-19 years) participating on the varsity and junior varsity football teams at a single high school. We expected and observed subjects in two previously described categories: (1) no clinically-diagnosed concussion and no changes in neurological behavior, and (2) clinically-diagnosed concussion with changes in neurological behavior. Additionally, we observed players in a previously undiscovered third category, who exhibited no clinically-observed symptoms associated with concussion, but who demonstrated measurable neurocognitive (primarily visual working memory) and neurophysiological (altered activation in the dorsolateral prefrontal cortex [DLPFC]) impairments. This new category was associated with significantly higher numbers of head collision events to the top-front of the head, directly above the DLPFC. The discovery of this new category suggests that more players are suffering neurological injury than are currently being detected using traditional concussion-assessment tools. These individuals are unlikely to undergo clinical evaluation, and thus may continue to participate in football-related activities, even when changes in brain physiology (and potential brain damage) are present, which will increase the risk of future neurological injury.

FIG. 1.

Summary of observed player categories, with representative functional magnetic resonance imaging (fMRI) observations. Categories are based on both clinical observation by the team physician of impairment associated with concussion (clinically-observed impairment; COI+ or COI−), and the presence or absence of significant neurocognitive impairment via ImPACT (functionally-observed impairment; FOI+ or FOI−). fMRI activations are depicted for all players using a sagittal slice through the left inferior parietal lobule (L IPL), to illustrate the presence of many changes, relative to pre-season assessment, for FOI+ players. Details of the depicted fMRI activations can be seen in Figures 2 and 3. (Bottom right) As expected, all (3/3) players who were diagnosed by the team physician as having experienced a concussion (COI+) were also found to exhibit significantly reduced ImPACT scores (FOI+), and are categorized as COI+/FOI+ (see also Fig. 2). (Top left) Half (4/8) of players brought in for assessment ostensibly for control purposes (i.e., presenting with no clinically-observable impairments, COI−) were found to be neurocognitively consistent with pre-season assessment (FOI−), and are categorized as COI−/FOI−. (Top right) The other half (4/8) of the intended control group, studied in the absence of diagnosed concussion (COI−), were found to exhibit significantly impaired ImPACT performance (FOI+), and are categorized as COI−/FOI+ (see also Fig. 3). This group represents a newly-observed category of possible neurological injury. (Bottom left) No players who were diagnosed with a concussion (COI+) were found to exhibit ImPACT scores consistent with pre-season assessments (FOI−). Color image is available at www.liebertpub.com/neu

FIG. 2.

Significant alterations in functional magnetic resonance imaging (fMRI) activation during in-season assessment were found in the left middle and superior temporal gyri (L MTG and L STG; green circles) under a MarsBaR-based (Brett et al. 2002) region-of-interest (ROI) analysis for COI+/FOI+ players, but not for COI−/FOI− players. For the COI+/FOI+ group, in-season assessments took place within 72 h of diagnosis of concussion by the team physician. fMRI activations are depicted for a contrast between 2-back and 1-back working memory tasks, with observation of greater activation for the 2-back (1-back) task indicated using the red-yellow (blue-cyan) color scale, thresholded at a statistical significance level of p < 0.05, corrected for false-discovery rate. MarsBaR ROIs were said to exhibit significant alteration if the mean t-statistic fell outside the ROI-specific 99.9% confidence interval (derived from the pre-season data for 23 players), for both the group fixed-effects mean, and in a majority of the players within the group. For the COI+/FOI+group, the L MTG and L STG were two of five ROIs that exhibited such significant alterations. Other anatomical ROIs were left middle occipital gyrus, left cerebellum 10, and right cerebellum 3. The L MTG persisted in exhibiting significant deviation in the post-season data. For the COI−/FOI− group, only the right cerebellum 3 anatomical ROI was found to exhibit significant deviation during in-season assessment. It is important to note that all players performed the working-memory task at a consistent near-ceiling level over all sessions (COI, clinically-observed impairment; FOI, functionally-observed impairment). Color image is available at www.liebertpub.com/neu

FIG. 3.

Significant alterations in functional magnetic resonance imaging (fMRI) activation during in-season assessment were found in left middle and superior frontal gyri (L MFG and L SFG; green circles) under a MarsBaR-based (Brett et al., 2002) region-of-interest (ROI) analysis for COI−/FOI+ players, but not for COI−/FOI− players. These ROIs represent much of dorsolateral prefrontal cortex (DLPFC). Coupled with observations of significantly reduced ImPACT scores, the COI−/FOI+ group represents a newly observed category of neurological injury, as these players are functionally impaired, yet do not exhibit symptoms associated with a clinical diagnosis of concussion. See Figure 2 for information regarding the depicted fMRI activations. For the COI−/FOI+ group, the L MFG and L SFG were two of eight ROIs that exhibited significant alterations in multiple in-season assessments. Other anatomical ROIs were right middle and superior frontal gyrus (R MFG and R SFG), both the right and left superior parietal lobules (R SPL and L SPL), the right pars triangularis, and the right cerebellum crus 1. Three of these ROIs (L MFG, L SFG, and R SFG) exhibited deviant activation in all in-season assessments for all COI−/FOI+ subjects. For the COI−/FOI− group, only the right cerebellum 3 anatomical ROI was found to exhibit significant deviation during in-season assessment. It is important to note that all players performed the working-memory task at a consistent near-ceiling level over all sessions (COI, clinically-observed impairment; FOI, functionally-observed impairment). Color image is available at www.liebertpub.com/neu

FIG. 4.

While peak linear acceleration was not predictive for neurological trauma, the pattern of average collision events per individual was significantly related to the concussion group as identified using neurocognitive testing (ImPACT). Each participant wore a Riddell^® Revolution^™ helmet (Riddell, Elyria, OH) outfitted with a sensor array (HIT System) to record head accelerations in practices and games once the season started (Crisco et al., 2004). Overall the COI−/FOI+ group experienced the greatest number of collision events to each region of the helmet. The COI−/FOI− group accumulated more collisions per player in each location than did the COI+/FOI+ group, suggesting that the latter group's injuries were not the result of the number of blows, but likely were due to a single or a small number of particularly deleterious collisions. (A) For collision events less than 20g, the COI−/FOI+ group experienced significantly more collision events to the side and the top-front of the helmet (p < 0.05, group-wise one-way ANOVA and Bonferroni-corrected one-tailed t-test). (B) Between 20 and 80g, the COI−/FOI+ group experienced a greater number of collision events to each region of the helmet, but the only location where it reached significance was the top-front. (C) Above 80g, the COI+/FOI+ group experienced significantly more blows to the side of the head, while the COI−/FOI+ group continued to experience a statistically greater number of blows to the top-front of the helmet (COI, clinically-observed impairment; FOI, functionally-observed impairment; ANOVA, analysis of variance).

FIG. 5.

The number of head collision events exceeding 14.4g experienced by a player was found to be inversely correlated with the fMRI contrast (2-back versus 1-back) observed during in-season assessments. All frontal regions of interest in the MarsBaR (Brett et al., 2002) were aggregated to obtain a frontal lobe region of interest (ROI), from which an average percent signal change was computed for this contrast in each of the 14 completed in-season fMRI assessments, and the corresponding pre-season assessment for the same subject. The difference between these assessments is plotted against the total number of HIT-System-reported collision events. Different symbols have been used to identify the three groups (COI−/FOI−, COI−/FOI+, and COI+/FOI+) of players, illustrating the greater number of collision events for the COI−/FOI+ group (see Fig. 4). The regression line across the 14 comparisons achieves R² = 0.46, indicating that the recent accrual of head collision events is meaningfully related to the degree of change in neurophysiological response (COI, clinically-observed impairment; FOI, functionally-observed impairment; fMRI, functional magnetic resonance imaging).