Brain trauma among football players (and athletes in other sports such as soccer and ice hockey) may be less the result of violent collisions that cause concussions as the cumulative effect of repetitive head impacts (RHI). The discovery has lead to increased calls by experts to take steps at all levels of sports, from professional down to the youth level, to limit exposure to such repetitive trauma, while a shrinking minority (including the NCAA) continue to urge a more cautious approach until more is known.
Although scientists have long suspected that RHI caused brain damage, especially in boxers, a 2010 study of high school football players by researchers at Purdue University [1,13] was the first to identify a completely unexpected and previously unknown category of players who, though they displayed no clinically-observable signs of concussion, were found to have measurable impairment of neurocognitive function (primarily visual working memory) on computerized neurocognitive tests, as well as altered activation in neurophysiologic function on sophisticated brain imaging tests (fMRI).
Indeed, researchers found, the players with the most impaired visual memory skills were not those in who had been diagnosed with concussions but were in the group which, in the preceding week, had experienced a large number of RHI - around 150 hits - mostly in the 40 to 80 g range of linear acceleration.
Publication of the Purdue study sent shock-waves reverberating through the football world, with the findings cited by concussion experts calling on youth sports organizations to take more aggressive action to minimize exposure to RHI, including sub-concussive blows, by changing the way contact and collision sports are played and practiced, and reducing the amount of brain trauma a child incurs by limiting the number of hits they sustain in a sports season, over the course of a year, and during a career.
Pop Warner responded by instituting rule changes in 2012 designed to limit contact during practices.
In June 2013, the Pac-12 announced that it would adopt a policy limiting full-contact practices as well, although it did not state what those limits would be, only that they would be less than allowed by the NCAA. The next month, the conference announced that the limit would be two a week, the same as the Ivy League put in place before the 2011 season. No other major college football conference has followed suit, at least so far.
In July 2014, the NCAA issued new guidelines recommending that full-contact practices during the season be limited to two per week. The NCAA guidelines also recommend no more than four contact practices per week during the preseason and no more than eight of the 15 sessions during spring football.
That same month California governor Jerry Brown signed into law AB 2127, limiting middle and high school to two full-contact practices - each no more than 90 minutes long - per a week during the 30 day period before the regular season and during the regular season itself, and banning off-season contact practices completely.
Cause for concern
Since publication of the first Purdue study, similar findings about the effects of RHI, both in the short- and medium-term, have been reported by researchers [8,9,16,19,21,22,26,27,28, 29-38], with several of the studies finding changes which persisted for weeks and even months after a football season ended.
Summarizing the state of the research in 2015, a study by researchers at the University of Virginia found that, in the short term, RHI has been "linked to increased susceptibility to concussion, decreased cogntitive function, altered gray matter functional connectivity, and changes in white matter microstructure," and that, in the long term, "retired football players who have sustained high levels of subconcussive impact over their careers have been hypothesized to have an increased risk of developing neurodegenerative disorders, like amytrophic lateral sclerosis [e.g. Lou Gehrig's disease], Alzheimer's disease, Parkinson's disease, and chronic traumatic encephalopathy (CTE)."
In a 2012 study, researchers at the University of Rochester Medical Center (URMC) measured before-and-after data from the brains of a group of nine high school football and hockey players using an advanced form of imaging similar to an MRI called diffusion tensor imaging (DTI). They found subtle evidence of axonal injury at the cellular level in six athletes who had not been diagnosed with concussion but sustained RHI during the normal course of play. The abnormalities disclosed on post-season DTI scans among the players were closer to the scan of the one player with diagnosed concussion than to the normal brains in the control group. Axons, which are like cables woven throughout brain tissue, swell up when traumatic brain injury occurs.
The imaging changes also strongly correlated with the number of head hits (self-reported by the athletes in a diary), the symptoms experienced, and independent cognitive tests, said lead author Jeffrey Bazarian, M.D., M.P.H., associate professor of Emergency Medicine at URMC.
Another 2012 study  found that new learning on a sophisticated pencil-and-paper neurocognitive test declined over a single season of RHIs among college football and hockey players who did not experience concussions. The study found that the players had poorer post-season reaction time and scores on a test of visual attention and task switching, which deficits were associated with greater head impact exposures.
Using DTI imaging technique, researchers at Indiana University School of Medicine and the Geisel School of Medicine at Dartmouth College, found in a 2013 study  significant differences in brain white matter of varsity football and hockey players compared with a group of non-contact-sport athletes, with the number of times they were hit correlated with changes in the white matter. They also found that some of the athletes, none of whom suffered diagnosed concussions, didn't do as well as predicted on tests of learning and memory at the end of the season, although the study did not find "large-scale, systemic differences" in the brain scan measures, which the authors found "somewhat reassuring" and consistent with the fact that millions of athletes play contact sports for many years without developing progressive neurodegenerative disorders.[17,18]
Another 2013 study by researchers at URMC and the Cleveland Clinic  also found evidence of brain damage in college football players from RHI in the form of elevated levels of S100B, a protein in the blood usually present only in the brain. The presence of the S100B protein triggers the release by the body of antibodies which can then leak back into the brain through the damaged blood-brain barrier, where they are thought to attack brain tissue. The highest protein levels were found among players who sustained the most hits to the head during games and practices.
Using DTI, researchers at Wake Forest found in a 2014 study that a single season of high school football can produce changes in the white matter of the brain of the type previously associated with mTBI in the absence of a clinical diagnosis of concussion, and that these impact-related changes in the brain are strongly associated with a postseason change in the verbal memory composite score from baseline on the ImPACT neurocognitive test. "Taken together, these data add to the growing body of literature providing evidence that a season of play in a contact sport can show brain changes in the absence of concussion or clinical findings," they wrote.
In a research paper presented at the annual meeting of the Radiological Society of North America in December 2014 analyzing the same data,[27,28] the Wake Forest researchers found that players experiencing greater levels of RHI (heavy hitters) had more changes to specific areas of their brains compared to players with lower impact exposure (light hitters).
Most recently, a remarkable series of eight studies<31-38by Purdue scientists as part of an ongoing study of brain changes in high school football players, made a host of significant findings:
- the number of head impacts was related to substantive neurophysiological changes during the course of a football season, with all players sustaining more than 500 cumulative head impacts "flagged" for scoring more poorly on at least one component of the ImPACT neurocognitive test compared to their baseline, and/or displaying a statistically significant difference between pre- and post-season fMRI scans on 11 or more of 116 "regions of interest" in the brain;
- high magnitude hits (over 60 g's of linear force) players accrued over the course of a season were more likely to prompt abnormal biochemical/metabolic responses in regions of the brain responsible for executive and motor function, with abnormal increases in metabolites sometimes followed by metabolic decreases, all dependent on the timing, number, magnitude, and location of blows to the helmet. The findings led the researchers to conclude that, with such "diverse metabolic consequences to accumulating sub-concussive blows, such competing mechanisms could (1) lead to no noticeable differences in overall metabolic levels and (2) ultimately mask symptoms in injured athletes," and provided "further evidence for a cumulative effect of head blows on neural health."
- players who sustained more than 900 hits over the course of a season were much more likely than players hit less than 600 times in a season to be flagged by ImPACT, fMRI, or both.
- players who averaged more than 50 head impacts per week (coincidentally, the typical number of plays a high school football offense or defense ran in a game) were flagged at a rate of 83% while those who received less than 50 hits per week were only flagged 43% of the time, a threshold the researchers considered significant.
- when tested between 2 and 5 months after the football season ended, 6 out of 10 players had results which were flagged as abnormal, 11 by ImPACT, 12 by fMRI, with 3 flagged by both. The findings led the researchers to conclude that using a neurocognitive test such as ImPACT, more commonly used by clinicians in measuring the effects of concussion and assisting in making return to play decisions, in combination with fMRI, which is sensitive to more subtle changes in brain physiology that may not be exhibited in cognitive performance, may provide a better assessments of a player's brain health than either measure by itself.
- where on the helmet a player was hit most rather than the number of hits was the best predictor of changes in the brain, suggesting that a player's style of play may be particularly important in determining brain changes resulting from subconcussive impacts.
- abnormal brain activation patterns while players performed tasks involving visual working memory appeared to be related to exposure to contact: after several months of play, the players exhibited a high rate of deviation from their respective pre-season measures of brain activation, with the amount of abnormal activity increasing during the primary months of contact (August-October), only beginning to drop more than two months after the season ended (October/November), and not returning to baseline again until February-April. they said, as it suggested that, "even at sub-concussive levels of head impacts, there is neural reorganization and no true return to 'normal,' which, in turn, suggests that neural plasticity could be acting as a compensatory mechanism to keep football players asymptomatic." As Thomas Talavage, a professor of electrical and computer engineering and biomedical engineering and co-director of the Purdue MRI facility, told Purdue News, "The brain is pretty amazing at covering up a lot of changes. Some of these kids have no outward symptoms, but we can see their brains have rewired themselves to skp around the parts that are affected."
- athletes exposed to RHI exhibited significant abnormalities in the white matter of the brain during the season which increased as the season wore on, and persisted after the season. Interestingly, the data suggested that the greater number of lesser intensity collisions experienced by the members of one football team resulted in injury at the cellular level (inflammation of the axons, which are like cables woven throughout brain tissue), while a lesser number of high intensity collisions experienced by the second team may have been more injurious to the fiber structure of the brain. While the researchers said it was an "open question" whether one or the other may be of more clinical significance, the bottom line was the same: that the injury to the white matter of the brain was "slowly accumulating, with magnitude and number of events affecting the nature of the observed changes."
Changes to brain persist
Perhaps most concerning, four of the Purdue studies found that damage to the brain from RHI persisted after the football season was over, as did a 2014 study by Bazarian and his URMC colleagues  which found changes in brain white matter in a small group of college football players which persisted six months after the season was over. They found a strong correlation between the white matter changes and the number of head hits with a peak rotational acceleration exceeding 4500 rad/sec2 and the number of head hits with a peak rotational acceleration exceeding 6,000 rad/sec2, and an especially strong correlation where the number of the former exceeded 30-40 for the season, and the number of the latter exceeded 10-15 for the season. (For reference, a person nodding his head up and down as fast as possible produces a rotational acceleration of approximately 180 rads/sec2).
That six months off may not be long enough for the brains of football players to completely heal after a single season, putting them at even greater risk of head injury the next season, was concerning, said Bazarian.
"I don't want to be an alarmist, but this is something to be concerned about. At this point we don't know the implications, but there is a valid concern that six months of no-contact rest may not be enough for some players," he said. "And the reality of high school, college and professional athletics is that most players don't actually rest during the off-season. They continue to train and push themselves and prepare for the next season."
The findings of the first Purdue study alone were troubling, said Larry J. Leverenz, PhD, ATC, a Clinical Professor in the school's Department of Health and Kinesiology, shortly after the study was published, because it meant that players were:
- Escaping detection. Because they have not suffered damage to areas of the brain associated with language and auditory processing, they are unlikely to exhibit clinical signs of head injury (such as headache or dizziness), or show impairment on sideline assessment for concussion, all of which test for verbal, not visual memory, Leverenz said that "there is no way right now to identify" the group suffering sub-concussive blows to the head that may be dangerous. Hence, they will likely continue participating in football-related activities, even when changes in brain physiology are present, which studies show likely increases the risk of future neurologic injury;
- Didn't know they were injured. If working memory deficits are sufficiently small, a player may not be aware of the additional effort required to complete everyday tasks, and therefore not think to bring the problem to anyone's attention (although at least one of the players in the impaired group seemed to have figured this out, and played with better, heads-up technique the next season, reducing the number of hits he took to the forehead); and
- Facing an uncertain future. Even though the players in the original Purdue study who suffered short-term cognitive impairment from repeated sub-concussive blows exhibited results on fMRI and ImPACT tests administered before season #2 comparable to the baseline results before season #1, their return to baseline did not necessarily mean that there was 100% recovery, as several of the subsequent Purdue studies demonstrated. It is possible that the damage will only be known over the long term, years later.
Commenting at the time on the 2010 Purdue study for Sports Illustrated , Randall Benson, a neurologist at Wayne State University in Detroit, speculated that the Purdue researchers may have taken what amounted to a "real-time snapshot" of the early stages of the corrosive creep that wears away at the frontal lobe, a part of the brain involved in navigating social situations. Too much erosion and victims reach a breaking point - like former Steelers offensive lineman Terry Long, who died in 2005 from drinking antifreeze. "It's an insidious progression," Benson said, "and it's not obvious when you talk to [players]."
Four years later, Benson's speculation was echoed in eerily similar comments by Bazarian and his colleagues in the 2014 URMC study: "[i]f RHIs are related to neurodegeneration many years later, a long clinically silent period between the onset of neuronal injury and overt symptoms of dementia would not be unexpected." During this clinically silent period, however, there may be indicators of dysfunction on a cellular level, such as the elevated levels of S100B antibody found in the cerebral spinal fluid in the football players in the study, even six months after the end of the season, which he said, could "potentially herald[ ] the early stages of [chronic traumatic encephalopathy] or CTE."
"Pending confirmation in a long term longitudinal study tracking athletes prospectively for years to decades looking for manifestations of early cognitive dysfunction and dementia," writes Bazarian, "we believe our results suggest that these persistent DTI changes are likely detrimental. If borne out in future research, the long-term persistence of these [white matter] changes would mean that athletes returning to play the following season would be at risk for expanded RHI-related WM changes, undetectable by conventional assessments. Could the lack of WM recovery we observed result in cumulative WM damage with subsequent football seasons of RHI exposures? If so, could this cumulative WM damage be related to the long-term development of CTE?"
Commenting on the recent series of Purdue studies for Purdue News, Eric Nauman, a professor of mechanical engineering, basic medical sciences and biomedical engineering, and author or co-author of all 10 of the Purdue studies, said he was "particularly disturbed that when you get to the offseason, - we are looking somewhere between two and four months after the season has ended - the majority of players are still showing that they had not fully recovered."