M30 - Comprehensive analysis of longitudinal cortical morphometry patterns in collegiate contact sport athletes

Introduction: : The repetitive concussive and sub-concussive head impact (RHI) exposure associated with contact sports poses significant neurological risks to athletes. There are rising concerns of longitudinal neuropathology, predominantly chronic traumatic encephalopathy (CTE), that has increasingly been associated with contact sport participation. CTE is a neurodegenerative disease that is characterized by deposition of hyperphosphorylated tau protein clusters around small cerebral blood vessels at the depths of sulci. In early stages, the tau protein deposits are primarily observed in the frontal and temporal lobes.
Critical neurodevelopmental changes occur during adolescence and into early adulthood. Understanding how RHI exposure affects cortical development in collegiate athletes is essential for determining the long-term neurological consequences of contact sports. Furthermore, by isolating regions of interest (ROIs) previously associated with early-stage CTE, we can potentially identify preliminary pathogenetic indicators in these areas.
Acutely, previous literature has shown that RHI exposure can significantly influence cortical morphometry in athletes of all ages. However, there is no clear consensus on the direction of association between RHI exposure and cortical metrics. Additionally, there are few longitudinal studies focused on these cortical parameters, with little investigation beyond American football athletes. To address these research gaps, we investigated longitudinal cortical morphometry in women’s and men’s collegiate contact sport athletes using magnetic resonance imaging (MRI).
Primarily, we expect to see a reduction in age-related cortical thinning in contact sports athletes. In addition, we may see contact sport-related changes in cortical and subcortical volume, sulcal depth, and sulcal curvature.

Materials and

Methods: : We recruited 84 varsity collegiate contact sport athletes from men's and women's ice hockey, women's rugby, and 38 control athletes from non-contact sports without prior concussion history (H21-00400). Over 3 years, participants received pre- and post-season MRI scans coinciding with contact sports seasons. Data was acquired using a 3T MRI scanner (Philips MR7700) and a 32-channel head coil. T1-weighted images of the brain were acquired using a 3D MPRAGE sequence (FA = 8°, TE/TR = 4.3/2400 ms, TI = 950 ms, FOV 256 x 256 x 180 mm3, 0.8 mm3 isotropic resolution, CS factor 3.6).
A total of 293 scans were collected across all athletes. Cortical reconstruction and segmentation of T1-weighted images was completed using the FreeSurfer longitudinal pipeline (v.6.0). All unique base templates (n = 84) underwent multiple iterations of rigorous manual editing to improve and correct cortical boundary measurements at the pial surface. Cortical thickness and volume parcellation were conducted through FreeSurfer based on the Desikan-Killiany atlas. Seven CTE-related grey matter regions in the frontal and temporal lobes and three subcortical structures were bilaterally selected for analysis. Two linear mixed effects models were applied: a novel mass-univariate voxel-wise approach in MATLAB and an ROI-based model in R. Additionally, two analytical approaches were taken: a mixed effect analysis of cortical parameters between contact and non-contact athletes, and a within-contact athlete sub-analysis focused on independent risk factors previously shown to influence cortical morphometry. All results reported are considered significant following multiple comparisons correction (False Discovery Rate test).

Results, Conclusions, and Discussions:: Our findings demonstrate that contact sport participation was associated with differences in some morphometry parameters, and cortical morphometry can be significantly modulated by concussion history and alcohol consumption.
In voxel-wise analysis, women's rugby showed lower cortical thickness (-0.265 mm/vertex) in the right entorhinal region (94 vertices) compared with controls. Women's hockey exhibited accelerated cortical thinning (-0.185 mm/yr/vertex) across 353 vertices in four right hemisphere regions: precentral, superior frontal, superior parietal, and precuneus. In ROI analysis, men's hockey athletes displayed higher cortical thickness bilaterally in superior frontal regions (LH: 0.074 mm; RH: 0.090 mm) and left insula (0.091 mm) compared with controls, while women's rugby showed greater left amygdala volume increase over time (115.639 mm/yr). Within men's hockey, prior concussion history and severe alcohol use were associated with increased sulcal depth in the left caudal middle frontal region. Additionally, prior concussion history correlated with decreased Gaussian curvature in the temporal pole over time.
Our findings suggest that cortical morphometry alterations associated with repetitive sub-concussive and concussive head impact exposure may commence while young athletes are actively participating in contact sports. Notably, these alterations are present in the frontal and temporal lobes, two regions that are predisposed to early-stage CTE pathology. Group-level differences were observed irrespective of time, indicating that divergence in neurostructural development may originate during formative adolescent years. Despite the associations identified in our study, further investigation of the potential role in early adolescent contact sport involvement on brain morphometry needs to be investigated with prospective studies that enroll youth athletes prior to they start contact. We also identified significant modulating factors outside the main hypothesis, particularly with severe alcohol use in the men’s analysis. Additionally, there is a lack of homogeneity in cortical morphometry patterns between sexes in contact sport athletes that should be addressed in future studies with direct sex comparisons. The current findings highlight the importance of longitudinal monitoring to better understand the neuropathology associated with repetitive head impact exposure. Some morphometry parameters may be used as early biomarkers for identifying potential long-term brain changes.

Acknowledgements and/or References (Optional)::