Cannabis: Our recent pilot clinical trial included 43 adult soccer players (Cannabis group using cannabis at least once a week for the past 6 months, n=24; non-cannabis control group, n=19). Twenty soccer headings, induced by our controlled heading model, significantly impaired ocular-motor function, but the degrees of impairments were less in the cannabis group compared to controls. The control group significantly increased its serum S100B level after heading, whereas no change was observed in the cannabis group (Kalbfell, Rettke et al. 2023 iScience). Our data suggest that chronic cannabis use may be associated with an enhancement of oculomotor functional resiliency and suppression of the neuroinflammatory response following 20 soccer headings. An R01 related to this topic was resubmitted (R01NS140417-01A1) and currently under review.

 

Ovarian hormones: In collaboration with IU Women’s Water Polo team, we uncovered that an increase in serum levels of NfL (axonal injury marker) was associated with cumulative head impact magnitude. Hormonal contraceptive use was associated with lower serum NfL and GFAP levels over time, and elevated salivary levels of progesterone were also associated with lower serum NfL levels (Huibregtse, Sweeney et al. 2023 J Neurotrauma). These results suggest that detecting increases in serum NfL may be a useful way to monitor cumulative head impact burden in women’s contact sports and that female-specific factors, such as hormonal contraceptive use and circulating progesterone levels, may be neuroprotective, warranting further investigations. An R21 (R21NS138866) related to this topic has received scores (43th percentile) and currently working on revision.

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ADHD: Our series of studies, including recent R21 study (R21NS116548), indicate that individuals with ADHD may also exhibit reduced neural resilience to repetitive subconcussive head impacts (SHI). Specifically, following 10 controlled soccer headings, ADHD participants exhibited acute declines in verbal and visual memory functions, elevations in brain-injury blood biomarkers (GFAP, UCH-L1),(Nowak, Ejima et al. 2022 J Atten Disord, Nowak, Kronenberger et al. 2023 Front Psychiatry) and reductions in metabolites associated with mitochondrial energy production. Such changes were less pronounced in non-ADHD counterparts. I recently submitted a Competitive Revision to include a cohort of ADHD individuals in the ongoing Parent R01 trial.

 

Omega-3 Fatty Acids: We received an R01 (NINDS R01NS137276) to conduct a double-blind, placebo-controlled trial to investigate whether pre-treatment with omega-3 fatty acids—specifically docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA)—enhances brain resilience to subconcussive head impacts. The study will evaluate key neurological outcomes, including brain microstructural integrity, neuronal network dynamics, neuroinflammation, autonomic dysregulation, and overall neurological function. This research represents the first attempt to elucidate the mechanistic effects of DHA+EPA pre-treatment on the neural response to subconcussive impacts in humans, offering critical insights into the specific neuroprotective benefits of these fatty acids.

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Neck strengths: A computational model using high-speed video, neuroimaging, and impact kinematics shows that higher head accelerations lead to greater brain tissue deformation. Our data and others indicate female soccer players experience higher head accelerations than males during headers, and young soccer players show greater peak rotational acceleration per header than football tackles. These biomechanical differences heighten female athletes' risk of brain injury. While neck features alone don’t determine neurological vulnerability, they amplify mechanical stress. In collaboration with Dr. Cheever at UT, I have led research on cervicogenic function in brain trauma (Cheever, Kawata et al. 2016 J Athl Train, Cheever, Howard et al. 2020 J Sport Rehabil, Cheever, McDevitt et al. 2021 Sports Med, Cheever, King et al. 2022 Chiropr Man Therap, Cheever, King et al. 2022 Clinical Journal of Sport Medicine). An R21 (R21NS138866) that is under revision includes biomechanical significance of neck features.

 

Mental health: Brain injury significantly impacts mental health, but the effects of subconcussive head impacts remain unclear. In our ongoing R01 study of adolescent football players, a single season showed no measurable changes in depression, anxiety, or psychological well-being(Kercher, Steinfeldt et al. 2023 J Adolesc Health). However, multiple seasons correlated with increased depressive symptoms. Similarly, our aging study found higher rates of depression, PTSD, and ADHD among former athletes with over 10 years of contact sports experience(Buddenbaum, Recht et al. 2024 Front Psychiatry). In a large-scale study (n=4,849), individuals with a concussion history had higher scores for panic disorder, alcohol, and cannabis use. Our analysis also revealed direct and indirect effects of concussion history on substance use, moderated by gender (Newman, Grantz et al. 2020 J Neurotrauma). These findings underscore the long-term mental health risks of repeated head impacts and the need for further research on prevention and intervention strategies.

 

Practice drill: USA Football, the national governing body over amateur football in the United States, has established the levels-of-contact system, which was developed to guide drill intensity in a 5-step incremental manner (air < bags < control < thud < live). In our high school football R01, we identified that after controlling for duration, increases in head-impact outcomes by level of contact were observed (air < bags = control < thud = live). These data support the levels-of-contact system as a practical approach to limiting head-impact exposure in tackle football. Our research was featured in many platform (with Altmeric score of 383) including praised by Dr. Sanjay Guputa at CNN.

 

Hypoxia, Fasting, & Sleep Deprivation: We examined whether subconcussive head impacts under hypoxia, fasting, or sleep deprivation would worsen neurological effects. Using our soccer heading model, we found no amplifying effects under any condition. This may be due to modest exposure levels: hypoxia simulated 15,000 feet (11.8% oxygen), fasting lasted 18 hours per day for five days, and sleep was restricted to 3 hours for one night. These conditions may not have been severe enough to induce significant changes. Our findings suggest short-term exposure to these stressors does not exacerbate subconcussive impacts, but my future plan is to explore more prolonged or extreme conditions.

 

Research Impact

Identifying potential therapeutics and comorbidity factors is crucial for preventing and treating the long-term neurological effects of brain trauma. Our research has been supported by multiple funding sources, including an R01 clinical trial on omega-3 fatty acids, an R21 study on ADHD, and several pilot grants. Additional grant proposals are under review or revision. It holds great promise for uncovering preventive strategies against brain trauma-induced neurodegeneration. Given its significance, my research in this area will continue expanding, driving new discoveries and therapeutic advancements.