Effects of subconcussive head impacts
Investigating the acute and chronic effects of subconcussive neural injuries through longitudinal studies to elucidate their cumulative impact on brain function.
The insidious effects of soccer heading were documented as early as 1972 and were referred to as “footballer’s migraine” (Matthews 1972 Br Med J). This syndrome was often characterized by persisting symptoms, abnormal brain waves, and impaired neurocognitive function in memory and attention, in players who habitually performed soccer headings. The neurological effects of acute head impacts do not necessarily lead to chronic issues, given that sufficient rest is one of the most effective remedies for the brain. However, because of the painless and asymptomatic nature of subconcussive head impacts, many athletes experience head impacts daily, increasing the risk of chronic changes.
Short-term (acute) effects of subconcussive head impacts
Short-term (acute) effects of head impacts can be captured through sensitive neurologic measures. Our research team is one of the leading groups in this topic, such that series of our studies in football players identified head impact-dependent changes in blood biomarker levels (e.g., S100B, NF-L),(Marchi, Bazarian et al. 2013 PLoS One, Puvenna, Brennan et al. 2014 PLoS One, Kawata, Rubin et al. 2017 J Neurotrauma, Rubin, Tierney et al. 2019 Brain Inj, Zonner, Ejima et al. 2019 Front Neurol) neuro-ophthalmologic measures (e.g., convergence, saccades),(Kawata, Rubin et al. 2016 JAMA Ophthalmol, Kawata, Tierney et al. 2016 Int J Sports Med, Zonner, Ejima et al. 2019 JAMA Ophthalmol, Nowak, Bevilacqua et al. 2020 JAMA Ophthalmol) and vestibular function (Hwang, Ma et al. 2017 J Neurotrauma). While data from field studies are complemented by our innovative soccer heading model.
We have conducted a series of studies using our soccer heading model. This model, coupled with a repeated measures design, allows us to isolate neurological effects of subconcussive head impacts. Varied doses (10 or 20) of soccer headings were used in the following studies involving adult soccer players (ages 18-30 y). Study 1: Remarkable elevations of serum S100B were observed after 20 acute headings with a large effect size (Cohen’s d=1.532, pre vs. 24h post-heading), indicating astrocyte activation and neuroinflammatory responses (Kalbfell, Rettke et al. 2023 iScience). Study 2: Our neurofilament data indicated that 10 headings gradually increased serum NF-L levels, with a significant time effect for the heading group at 24h post compared to pre-heading (Cohen’s d=1.898). A group difference also emerged at 24h post-heading.(Wirsching, Chen et al. 2019 J Neurotrauma) The neurofilament data have been corroborated by several other studies,(Wallace, Smirl et al. 2018 BMJ Open Sport Exerc Med, Nowak, Ejima et al. 2020 J Atten Disord) substantiating our findings that detectable levels of axonal microstructural changes occur after acute head impacts. Study 3: Our recent R21 study using diffusion tensor imaging shows that significant elevations in mean diffusivity (MD) in several white matter tracts, such as the longitudinal fasciculus after 10 soccer headings. Study 4: Our clinical assessment of neuro-ophthalmologic functions, including near point of convergence (NPC) and King-Devick (KD) test, showed significant impairments acutely after 10 soccer headings compared to those of kicking-control group (Kawata, Tierney et al. 2016 Int J Sports Med, Nowak, Bevilacqua et al. 2020 JAMA Ophthalmol). These data highlight the our novel intervention to study subconcussive effects in controlled settings and illustrate the sensitivity of the neurologic markers to provide a mechanistic understanding of cellular, molecular, and functional responses to acute head impacts.
Long-term (chronic) effects of subconcussive head impacts
Subconcussive head impacts can not only trigger acute neuronal cellular, physiologic, and functional impairments, but these changes can accumulate over time and begin to manifest in cognitive impairment (e.g., memory, attention) and psychiatric symptoms (e.g., depression, suicide ideation). Soccer and American football players and boxers with 10 to 20+ years of head impact exposure face higher risks for developing AD, dementia, and chronic traumatic encephalopathy (CTE). However, a causal relationship between subconcussive head impacts and neurodegenerative disorders can only be confirmed by a lifelong, prospective study, which has been deemed infeasible at the present time. Instead, our team has been leading the effort of 1~4 years prospective studies to provide insights into the longer-term effects of head impact exposure. For example, our ongoing R01 study has yielded that adolescent football players exhibit significant reduction in brain cortical structures, many of these regions are related to mental health wellbeing (Zuidema, Hou et al. 2024 JAMA Netw Open). Season-long exposure to tackles in American football can also increase brain-injury blood biomarkers and induce ocular-motor impairments (Zuidema, Bazarian et al. 2023 JAMA Network Open). Furthermore, our ongoing analysis begins to suggest that those who accumulate head impacts through 2 to 3 years of high school football exhibit elevated levels of neurodegenerative blood biomarkers (e.g., p-tau181, tau, Ab40/42), increased mental health symptoms, and changes in brain morphology in prefrontal cortex regions. This data in adolescent football players are substantiated by our research focusing on middle-aged adults with 10+ years of history in contact sports. This study has revealed that those who had extensive contact sports experiments exhibit accelerated cortical thinning, widespread changes in gyrification, heightened mental health symptoms, and elevated levels of cellular inflammatory markers (e.g., IL2, CCL2, CCL3). Our series of studies underscores the deleterious effects of both acute and chronic subconcussive head impacts on brain structures and functions, substantiating the need for further investigation into establishing prophylactic agents against neural injury occurring as a result of head impacts.
Since the 2010s, research on neurological health following head impacts has gained significant public attention. The impact of our research within the scientific community is evident through frequent publications in high-impact journals, securing major grants (such as NIH R01 and ISDH), and receiving invitations to present at various prestigious venues. Given the heightened awareness of this topic, our research has been widely featured in media, demonstrating its influence not only within the scientific community but also among the general public.
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