Browsing by Author "Mayer, Andrew R."

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    Cumulative Effects of Prior Concussion and Primary Sport Participation on Brain Morphometry in Collegiate Athletes: A Study From the NCAA–DoD CARE Consortium
    (Frontiers, 2020-07-28) Brett, Benjamin L.; Bobholz, Samuel A.; España, Lezlie Y.; Huber, Daniel L.; Mayer, Andrew R.; Harezlak, Jaroslaw; Broglio, Steven P.; McAllister, Thomas W.; McCrea, Michael A.; Meier, Timothy B.; Investigators CARE Consortium; Psychiatry, School of Medicine
    Prior studies have reported long-term differences in brain structure (brain morphometry) as being associated with cumulative concussion and contact sport participation. There is emerging evidence to suggest that similar effects of prior concussion and contact sport participation on brain morphometry may be present in younger cohorts of active athletes. We investigated the relationship between prior concussion and primary sport participation with subcortical and cortical structures in active collegiate contact sport and non-contact sport athletes. Contact sport athletes (CS; N = 190) and matched non-contact sport athletes (NCS; N = 95) completed baseline clinical testing and participated in up to four serial neuroimaging sessions across a 6-months period. Subcortical and cortical structural metrics were derived using FreeSurfer. Linear mixed-effects (LME) models examined the effects of years of primary sport participation and prior concussion (0, 1+) on brain structure and baseline clinical variables. Athletes with prior concussion across both groups reported significantly more baseline concussion and psychological symptoms (all ps < 0.05). The relationship between years of primary sport participation and thalamic volume differed between CS and NCS (p = 0.015), driven by a significant inverse association between primary years of participation and thalamic volume in CS (p = 0.007). Additional analyses limited to CS alone showed that the relationship between years of primary sport participation and dorsal striatal volume was moderated by concussion history (p = 0.042). Finally, CS with prior concussion had larger hippocampal volumes than CS without prior concussion (p = 0.015). Years of contact sport exposure and prior concussion(s) are associated with differences in subcortical volumes in young-adult, active collegiate athletes, consistent with prior literature in retired, primarily symptomatic contact sport athletes. Longitudinal follow-up studies in these athletes are needed to determine clinical significance of current findings.
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    Increased brain age and relationships with blood-based biomarkers following concussion in younger populations
    (Springer, 2023) Mayer, Andrew R.; Meier, Timothy B.; Ling, Josef M.; Dodd, Andrew B.; Brett, Benjamin L.; Robertson‑Benta, Cidney R.; Huber, Daniel L.; Van der Horn, Harm J.; Broglio, Steven P.; McCrea, Michael A.; McAllister, Thomas; Psychiatry, School of Medicine
    Objective: Brain age is increasingly being applied to the spectrum of brain injury to define neuropathological changes in conjunction with blood-based biomarkers. However, data from the acute/sub-acute stages of concussion are lacking, especially among younger cohorts. Methods: Predicted brain age differences were independently calculated in large, prospectively recruited cohorts of pediatric concussion and matched healthy controls (total N = 446), as well as collegiate athletes with sport-related concussion and matched non-contact sport controls (total N = 184). Effects of repetitive head injury (i.e., exposure) were examined in a separate cohort of contact sport athletes (N = 82), as well as by quantifying concussion history through semi-structured interviews and years of contact sport participation. Results: Findings of increased brain age during acute and sub-acute concussion were independently replicated across both cohorts, with stronger evidence of recovery for pediatric (4 months) relative to concussed athletes (6 months). Mixed evidence existed for effects of repetitive head injury, as brain age was increased in contact sport athletes, but was not associated with concussion history or years of contact sport exposure. There was no difference in brain age between concussed and contact sport athletes. Total tau decreased immediately (~ 1.5 days) post-concussion relative to the non-contact group, whereas pro-inflammatory markers were increased in both concussed and contact sport athletes. Anti-inflammatory markers were inversely related to brain age, whereas markers of axonal injury (neurofilament light) exhibited a trend positive association. Conclusion: Current and previous findings collectively suggest that the chronicity of brain age differences may be mediated by age at injury (adults > children), with preliminary findings suggesting that exposure to contact sports may also increase brain age.
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    Longitudinal white-matter abnormalities in sports-related concussion: A diffusion MRI study
    (Wolters Kluwer, 2020-08) Wu, Yu-Chien; Harezlak, Jaroslaw; Elsaid, Nahla M. H.; Lin, Zikai; Wen, Qiuting; Mustafi, Sourajit M.; Riggen, Larry D.; Koch, Kevin M.; Nencka, Andrew S.; Meier, Timothy B.; Mayer, Andrew R.; Wang, Yang; Giza, Christopher C.; DiFiori, John P.; Guskiewicz, Kevin M.; Mihalik, Jason P.; LaConte, Stephen M.; Duma, Stefan M.; Broglio, Steven P.; Saykin, Andrew J.; McCrea, Michael A.; McAllister, Thomas W.; Radiology and Imaging Sciences, School of Medicine
    Objective To study longitudinal recovery trajectories of white matter after sports-related concussion (SRC) by performing diffusion tensor imaging (DTI) on collegiate athletes who sustained SRC. Methods Collegiate athletes (n = 219, 82 concussed athletes, 68 contact-sport controls, and 69 non–contact-sport controls) were included from the Concussion Assessment, Research and Education Consortium. The participants completed clinical assessments and DTI at 4 time points: 24 to 48 hours after injury, asymptomatic state, 7 days after return-to-play, and 6 months after injury. Tract-based spatial statistics was used to investigate group differences in DTI metrics and to identify white-matter areas with persistent abnormalities. Generalized linear mixed models were used to study longitudinal changes and associations between outcome measures and DTI metrics. Cox proportional hazards model was used to study effects of white-matter abnormalities on recovery time. Results In the white matter of concussed athletes, DTI-derived mean diffusivity was significantly higher than in the controls at 24 to 48 hours after injury and beyond the point when the concussed athletes became asymptomatic. While the extent of affected white matter decreased over time, part of the corpus callosum had persistent group differences across all the time points. Furthermore, greater elevation of mean diffusivity at acute concussion was associated with worse clinical outcome measures (i.e., Brief Symptom Inventory scores and symptom severity scores) and prolonged recovery time. No significant differences in DTI metrics were observed between the contact-sport and non–contact-sport controls. Conclusions Changes in white matter were evident after SRC at 6 months after injury but were not observed in contact-sport exposure. Furthermore, the persistent white-matter abnormalities were associated with clinical outcomes and delayed recovery time
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    Prevalence of Potentially Clinically Significant Magnetic Resonance Imaging Findings in Athletes with and without Sport-Related Concussion
    (Mary Ann Liebert, 2019-05-22) Klein, Andrew P.; Tetzlaff, Julie E.; Bonis, Joshua M.; Nelson, Lindsay D.; Mayer, Andrew R.; Huber, Daniel L.; Harezlak, Jaroslaw; Mathews, Vincent P.; Ulmer, John L.; Sinson, Grant P.; Nencka, Andrew S.; Koch, Kevin M.; Wu, Yu-Chien; Saykin, Andrew J.; DiFiori, John P.; Giza, Christopher C.; Goldman, Joshua; Guskiewicz, Kevin M.; Mihalik, Jason P.; Duma, Stefan M.; Rowson, Steven; Brooks, Alison; Broglio, Steven P.; McAllister, Thomas; McCrea, Michael A.; Meier, Timothy B.; Radiology and Imaging Sciences, School of Medicine
    Previous studies have shown that mild traumatic brain injury (mTBI) can cause abnormalities in clinically relevant magnetic resonance imaging (MRI) sequences. No large-scale study, however, has prospectively assessed this in athletes with sport-related concussion (SRC). The aim of the current study was to characterize and compare the prevalence of acute, trauma-related MRI findings and clinically significant, non-specific MRI findings in athletes with and without SRC. College and high-school athletes were prospectively enrolled and participated in scanning sessions between January 2015 through August 2017. Concussed contact sport athletes (n = 138; 14 female [F]; 19.5 ± 1.6 years) completed up to four scanning sessions after SRC. Non-concussed contact (n = 135; 15 F; 19.7 ± 1.6) and non-contact athletes (n = 96; 15 F; 20.0 ± 1.7) completed similar scanning sessions and served as controls. Board-certified neuroradiologists, blinded to SRC status, reviewed T1-weighted and T2-weighted fluid-attenuated inversion recovery and T2*-weighted and T2-weighted images for acute (i.e., injury-related) or non-acute findings that prompted recommendation for clinical follow-up. Concussed athletes were more likely to have MRI findings relative to contact (30.4% vs. 15.6%; odds ratio [OR] = 2.32; p = 0.01) and non-contact control athletes (19.8%; OR = 2.11; p = 0.04). Female athletes were more likely to have MRI findings than males (43.2% vs. 19.4%; OR = 2.62; p = 0.01). One athlete with SRC had an acute, injury-related finding; group differences were largely driven by increased rate of non-specific white matter hyperintensities in concussed athletes. This prospective, large-scale study demonstrates that <1% of SRCs are associated with acute injury findings on qualitative structural MRI, providing empirical support for clinical guidelines that do not recommend use of MRI after SRC.
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    Prospective study of the association between sport-related concussion and brain morphometry (3T-MRI) in collegiate athletes: A study from the NCAA-DOD CARE Consortium
    (BMJ, 2021) Bobholz, Samuel A.; Brett, Benjamin L.; España, Lezlie Y.; Huber, Daniel L.; Mayer, Andrew R.; Harezlak, Jaroslaw; Broglio, Steven P.; McAllister, Thomas; McCrea, Michael A.; Meier, Timothy B.; CARE Consortium Investigators; Psychiatry, School of Medicine
    Objectives: To determine the acute and early long-term associations of sport-related concussion (SRC) and subcortical and cortical structures in collegiate contact sport athletes. Methods: Athletes with a recent SRC (n=99) and matched contact (n=91) and non-contact sport controls (n=95) completed up to four neuroimaging sessions from 24 to 48 hours to 6 months postinjury. Subcortical volumes (amygdala, hippocampus, thalamus and dorsal striatum) and vertex-wise measurements of cortical thickness/volume were computed using FreeSurfer. Linear mixed-effects models examined the acute and longitudinal associations between concussion and structural metrics, controlling for intracranial volume (or mean thickness) and demographic variables (including prior concussions and sport exposure). Results: There were significant group-dependent changes in amygdala volumes across visits (p=0.041); this effect was driven by a trend for increased amygdala volume at 6 months relative to subacute visits in contact controls, with no differences in athletes with SRC. No differences were observed in any cortical metric (ie, thickness or volume) for primary or secondary analyses. Conclusion: A single SRC had minimal associations with grey matter structure across a 6-month time frame.
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    Resting-State fMRI Metrics in Acute Sport-Related Concussion and Their Association with Clinical Recovery: A Study from the NCAA-DOD CARE Consortium
    (Mary Ann Liebert, Inc., 2020-01) Meier, Timothy B.; Giraldo-Chica, Monica; España, Lezlie Y.; Mayer, Andrew R.; Harezlak, Jaroslaw; Nencka, Andrew S.; Wang, Yang; Koch, Kevin M.; Wu, Yu-Chien; Saykin, Andrew J.; Giza, Christopher C.; Goldman, Joshua; DiFiori, John P.; Guskiewicz, Kevin M.; Mihalik, Jason P.; Brooks, Alison; Broglio, Steven P.; McAllister, Thomas; McCrea, Michael A.; Radiology and Imaging Sciences, School of Medicine
    There has been a recent call for longitudinal cohort studies to track the physiological recovery of sport-related concussion (SRC) and its relationship with clinical recovery. Resting-state functional magnetic resonance imaging (rs-fMRI) has shown potential for detecting subtle changes in brain function after SRC. We investigated the effects of SRC on rs-fMRI metrics assessing local connectivity (regional homogeneity; REHO), global connectivity (average nodal strength), and the relative amplitude of slow oscillations of rs-fMRI (fractional amplitude of low-frequency fluctuations; fALFF). Athletes diagnosed with SRC (n = 92) completed visits with neuroimaging at 24-48 h post-injury (24 h), after clearance to begin the return-to-play (RTP) progression (asymptomatic), and 7 days following unrestricted RTP (post-RTP). Non-injured athletes (n = 82) completed visits yoked to the schedule of matched injured athletes and served as controls. Concussed athletes had elevated symptoms, worse neurocognitive performance, greater balance deficits, and elevated psychological symptoms at the 24-h visit relative to controls. These deficits were largely recovered by the asymptomatic visit. Concussed athletes still reported elevated psychological symptoms at the asymptomatic visit relative to controls. Concussed athletes also had elevated REHO in the right middle and superior frontal gyri at the 24-h visit that returned to normal levels by the asymptomatic visit. Additionally, REHO in these regions at 24 h predicted psychological symptoms at the asymptomatic visit in concussed athletes. Current results suggest that SRC is associated with an acute alteration in local connectivity that follows a similar time course as clinical recovery. Our results do not indicate strong evidence that concussion-related alterations in rs-fMRI persist beyond clinical recovery.