br Methods br Results Overall each participant performed

Methods
Results Overall, each participant performed 20 headers, achieving a mean force of impact of 13.1±1.9g (Table 1), with a coefficient of variance of 18%(±3%).
Discussion Following a standardized session of football heading designed to simulate routine soccer practice our data demonstrate immediate alterations in GSK2656157 electrophysiological and cognitive function compared to baseline assessments in a cohort of healthy, young soccer players. Specifically, using TMS we found a measurable increase in cortical silent period (cSP) after just 20 consecutive headers. Furthermore, in cognitive assessments, our data demonstrate evidence of decreases in measures of both short- and long-term memory immediately following heading. Notably, in this single exposure paradigm, these alterations in brain corticomotor inhibition and cognitive function appeared short-lived; the effects apparently normalizing in follow-up assessments from 24h onwards. In contrast to previous studies in athletes and patients with confirmed concussion or mild TBI (De Beaumont et al., 2007; Chistyakov et al., 2001; Bernabeu et al., 2009; Livingston et al., 2010) these novel observations demonstrate, for the first time, detectable alterations in brain function in footballers exposed to ‘routine’ head impacts not associated with clinically recognizable brain injury. The prolonged silent period of neuromuscular recruitment found in this study is a sign of increased inhibition in the motor system and is thought to reflect GABA activity (Inghilleri et al., 1993; McDonnell et al., 2006) which is the most powerful inhibitor in the motor system. Although the mechanisms behind corticomotor inhibition are not fully understood (Chen et al., 1999), increased inhibition following repeated sub-concussive head impact may reflect protective mechanisms against minor injury. What is a concern however is that such protective mechanisms could become maladaptive when stimulated repeatedly, as occurs during soccer heading practice. Albeit apparently transient, the acute increases in corticomotor inhibition following football heading could trigger a pathological process damaging brain health through the accumulative effect of sub-concussive head impact. Increased corticomotor inhibition silent period has been found to be associated with pathophysiology in brain damage suggesting a link between functional deficits and hyperactivity of cortical inhibitory interneurons (Classen et al., 1997). Further study into the dynamic metabolic processes as a direct result of soccer heading is required. When we understand the complex interplay between functional, metabolic, and structural brain changes following repeated sub-concussive head impact, we can establish the link to accumulative and long-term consequences. At present, the current findings at least suggest acute brain changes occur as a direct consequence of soccer heading. As well as increased corticomotor inhibition, parameters of memory function were altered following the heading protocol, consistent with a recent report of a relationship between memory function and history of heading in soccer (Lipton et al., 2013). Furthermore, a study of retired Australian Rules footballers found that elite players performed more poorly on the Paired Associate Learning test than amateurs (Pearce et al., 2014). Practical limitations of cognitive-based tests to detect impairment in athletes are due to reliability: in high performance sports athletes have been recognized to purposely produce low baseline performances on cognitive tests to allow them to avoid removal from play, or to reduce return to play intervals (Erdal, 2012). For completeness postural control (balance) was included as a secondary, albeit indirect, outcome measure as concussion has been shown to result in impaired balance (McCrory et al., 2013; Powers et al., 2014), yet the participants in the current study were able to maintain their balance despite an increased level of corticomotor inhibition. And while one study has shown a decrease in postural control following bouts of soccer heading (Haran et al., 2013), another study has not (Broglio et al., 2004); and now our own show no change in postural control.