Our current study results suggest that a nonlinear relationship exists between exposure to heading during the previous year, as measured by the EHQ, and both abnormal white matter microstructure and poorer neurocognitive performance on a test of memory. Notably, these findings were not significantly associated with prior concussion, yet they are consistent with findings seen in patients with TBI, as indicated in a study by Palacios et al (26). The relationships detected in this current study between heading and both imaging and cognitive outcomes provide some intriguing clues to pathophysiologic mechanisms. It is well established that most patients with mild TBI recover fully over time, indicating that intrinsic mechanisms are generally able to effect repair of low-level injury, as reviewed by Povlishok and Katz (27). Increasing heading exposure in this study, up to a threshold (β2), without associated imaging or cognitive changes, may indicate a range of exposure within which these intrinsic injury repair mechanisms are effective. The appearance of significant associations of imaging and cognitive changes with heading above the threshold, on the other hand, suggests that these repair mechanisms may be unable to keep pace with the cumulative injury that occurs beyond this degree of exposure.
One unexpected feature of our current results is the location of the brain abnormalities opposite the presumed point of heading impact on the forehead. We interpret this as analogous to the phenomenon of contrecoup injury, which occurs opposite the site of impact in contusional brain injury. Of note, the spatial extent and severity of contrecoup contusion injury is typically greater than that at the site of impact (coup injury). Thus, the chance of detecting a subtle degree of injury may in fact be greater opposite the impact location. Another consideration is that heading technique is not necessarily uniform, and variability in impact site is probably common. It is also possible that the imaging abnormalities we have detected index significant injury in general, though it is injury at other locations, too subtle to detect in this small sample, that is the specific cause of the memory changes.
We detected a lower heading threshold for imaging measures compared with the threshold for worse memory function. The imaging measures reveal pathologic changes in tissue (low FA) that would be expected to precede functional manifestations (cognition) related to tissue changes. These disparate thresholds could indicate differential lead time to the evolution of pathologic and clinical manifestations following injury, a widely recognized epidemiologic phenomenon. Virtually all subjects with exposures exceeding the threshold (β2) levels had low FA, suggesting that heading above some defined level may be generally unsafe. The important obverse of this finding is that exposure below the threshold level may be generally safe. Last, although subjects with exposure below the threshold (β2) identified in this study generally had FA and cognitive performance above the group mean, we did detect a subset of individuals with FA and cognitive function below the group mean, despite exposure well below the threshold (β2). This pattern suggests that, although exposure below a threshold may be generally safe, some individuals may be particularly sensitive to the effect of subconcussive heading and at higher risk for brain injury and adverse cognitive outcomes after even modest exposure.
The current study findings add to our understanding of the effects of heading on brain structure and function beyond the recognized role of heading as a relatively uncommon cause of concussion. Researchers in previous studies who have reported on concussion and/or cognitive impairment in soccer players at various skill levels have only addressed heading insofar as it is one of many potential causes of concussion in soccer. Additional limitations of prior studies of concussion in soccer are that they have generally not quantified subconcussive heading exposure and have not used quantitative neuroimaging. On the basis of these published studies, safety guidelines have focused on mitigating concussion caused by many potential types of impact, such as those detailed by Koutures and Gregory (8). Nonetheless, these guidelines have noted concern in regard to the independent risk of heading and note the lack of data addressing heading itself. In one recent study (13), researchers used diffusion-tensor imaging to compare a small number of elite soccer players with no history of concussion with a control group of competitive swimmers, finding low anisotropy in the soccer group and attributing the finding to heading. However, this study did not quantify exposure to heading or assess functional outcomes. To our knowledge, our current study is thus the first to quantify subconcussive heading as an exposure and to assess the association of heading with imaging evidence of brain pathologic findings and neurocognitive function.
An important limitation of this study is its cross-sectional nature, which does not allow us to specifically infer a causal relationship between heading and imaging or functional changes. Although the fits of our data to the nonlinear model used herein were highly significant, such models are most robust with large samples. Further confirmation of these findings in a larger sample is thus important. Factors that contribute heterogeneity to our sample, such as the inclusion of men and women, could be considered a limitation but also reflect the expected prevalence of soccer play among these demographics and, if at all, would be likely to dampen the strength of our associations rather than create a systematic bias. Assessing heading exposure is a complex undertaking, particularly in light of the consideration that cumulative lifetime exposure is likely most important, as suggested by our emerging understanding of long-term effects of concussive brain injury such as chronic traumatic encephalopathy. We validated and used a prior 12-month self-reporting measure for this study, considering recall over this time frame, in the context of total years of play, as a proxy for lifetime exposure. A limitation of any self-reporting measure is that the subject’s ability to recall the number of heading events over the long term is potentially subject to bias. Although heading could be quantified prospectively, such an approach would be only a partial assessment of lifetime exposure and would thus not address the role of lifetime (or even relatively recent) cumulative exposure, as players typically begin heading as children. Another limitation is that we were not able to characterize features of individual heading events, such as site of impact, velocity, rotation, and other features. It is of course likely that heading events vary greatly, but these features could only be captured with prospective use of biomechanical instrumentation. Such an approach, which was beyond the scope of this study, would, however, also be affected by the limitation on assessment of cumulative lifetime exposure described above. Our findings are based on analysis of FA and not of other diffusion parameters. We chose this approach because FA is the parameter that has been most widely studied in TBI and, particularly, in association with cognitive outcomes in TBI patients. Investigation of other diffusion measures may shed additional light on the underlying pathologic mechanisms of the effects we detect and is an area of opportunity for future study. We do not, however, expect that the basic associations we reported here would be altered.
Further research is required to confirm and characterize threshold effects and possible modifiers that are applicable to specific settings and populations. Characterizing the dose-response curve linking heading and TBI toward understanding threshold effects might facilitate safety guidelines that could help minimize the risk of adverse effects on the brain. Prospective monitoring of exposure at the team level, perhaps to be termed head counts, could identify a point at which a player’s heading should be curtailed for a specific recovery period, also to be defined through further research. Such an approach mirrors pitch counts that have mitigated upper extremity injury due to excess exposure in youth baseball (28). Further study is also warranted to identify risk factors, which could become the foundation for public health interventions designed to prevent exposure in vulnerable individuals. Were a genetic variant such as the apolipoprotein ε4 allele, or ApoE4, for example, shown to confer greater risk for heading-related TBI, individuals could be screened and those with apolipoprotein ε4 allele advised not to head. Further research is thus essential to develop evidence-based protective strategies that can ensure the future of safe soccer play.
Advances in Knowledge
• High frequency of soccer heading (>885–1800 headings per year) in otherwise healthy adult amateur players is associated with lower white matter fractional anisotropy (FA) (P < .00001) and worse memory performance (P < .00001) than in players who performed less heading.
• Heading alone is associated with both low FA and worse memory; whether players do or do not have history of one or more concussions does not explain differences in FA and memory among players (P = .38).
• The associations between heading and diminished FA, as well as between heading and memory, are nonlinear, with evidence of a threshold dose-response relationship.
Implication for Patient Care
Disclosures of Conflicts of Interest: M.L.L. No relevant conflicts of interest to disclose. N.K. No relevant conflicts of interest to disclose. M.E.Z. No relevant conflicts of interest to disclose. M.K. No relevant conflicts of interest to disclose. W.F.S. No relevant conflicts of interest to disclose. C.A.B. No relevant conflicts of interesst to disclose. R.B.L. Financial activities related to the present article: none to disclose. Financial activities not related to the present article: receives research support from the National Headache Foundation, and the Migraine Research Fund; serves on the editorial boards of Neurology and Cephalalgia and as senior advisor to Headache; has reviewed for the National Institute on Aging and National Institute of Neurological Disorders and Stroke; holds stock options in eNeura Therapeutics (a company without commercial products); serves as consultant, advisory board member, or has received honoraria from Allergan, American Headache Society, Autonomic Technologies, Boehringer-Ingelheim Pharmaceuticals, Boston Scientific, Bristol Myers Squibb, Cognimed, Colucid, Eli Lilly, eNeura Therapeutics, GlaxoSmithKline, MAP, Merck, Nautilus Neuroscience, Novartis, NuPathe, Vedanta, and Zogenix. Other relationships: none to disclose.
The authors acknowledge the essential contributions of Nina Ackerman, BA, Albert Einstein College of Medicine of Yeshiva University, Bronx, NY, to subject recruitment and assessment.