Anterior Cruciate Ligament Injury {#section7-1941738115619164}
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Noncontact anterior cruciate ligament (ACL) injuries continue to be a primary prevention priority for the sports medicine community. Numerous systematic reviews and meta-analyses published in recent years have established several factors that may contribute to ACL injury risk and the effectiveness of injury prevention programs.^[@bibr34-1941738115619164],[@bibr35-1941738115619164]^ The current evidence-based prevention programs target neuromuscular control, strength, movement feedback, and balance to reduce the risk of ACL injury in sport.^[@bibr34-1941738115619164]^ However, despite a significant relative risk reduction (73.4%) when these known risk factors are targeted in training programs, noncontact injuries still occur.^[@bibr35-1941738115619164]^ The remaining injury risk may be due to the failure to consider other aspects of neuromuscular control and function that play a role in injury risk susceptibility.^[@bibr34-1941738115619164]^ The relative risk reduction with the current programs may be improved by addressing additional neurological factors implicated in the noncontact ACL injury mechanism.

The noncontact ACL injury scenario itself exemplifies key components of function that are not addressed in traditional neuromuscular training.^[@bibr22-1941738115619164],[@bibr34-1941738115619164]^ The video analysis of noncontact ACL injury incidents demonstrates external factors such as contact with a ball, another player, and/or distracted attention are involved in the majority of ACL noncontact events.^[@bibr6-1941738115619164],[@bibr19-1941738115619164],[@bibr28-1941738115619164]^ This environmental interaction, combined with the rapid nature of the injury (\<50 ms after ground contact),^[@bibr19-1941738115619164]^ may indicate that the error in motor control resulting in noncontact ACL injury is beyond the reactive capability of the central nervous system^[@bibr32-1941738115619164],[@bibr42-1941738115619164]^ and may be at least partially dependent on feedforward mechanisms involving motor planning and cognition.^[@bibr23-1941738115619164],[@bibr37-1941738115619164]^ Neurocognitive factors, specifically reaction time, processing speed, dual tasking, focus of attention, visual-motor control, and complex environmental interaction, all combine with biomechanical factors to directly contribute to feedback motor control and influence injury risk.^[@bibr7-1941738115619164],[@bibr28-1941738115619164]^ These attentional and environmental components of neuromuscular function are largely not addressed in training programs that target strengthening, proximal control, balance, and plyometric ability.^[@bibr34-1941738115619164]^

The "Neuro" in Neuromuscular Control {#section8-1941738115619164}
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The standard neuromuscular ACL injury prevention training program typically does not incorporate the neurocognitive components associated with maintaining joint-to-joint alignment while engaging in the complex athletic environment.^[@bibr19-1941738115619164],[@bibr41-1941738115619164]^ The ability to sustain motor control in the variable sport environment demands complex central nervous system (CNS) integration of a constantly changing profile of sensory inputs, including visual feedback, proprioception, and vestibular equilibrium. Biomechanical studies confirm that the incorporation of a layer of neurocognitive elements ranging from dual tasks, responding to stimuli,^[@bibr24-1941738115619164]^ anticipation,^[@bibr5-1941738115619164]^ decision making,^[@bibr20-1941738115619164]^ and programming motion relative to external targets^[@bibr10-1941738115619164]^ may degrade neuromuscular control relative to movement without such factors. Recently, examination of injury risk during ball-handling and offensive action (considered anticipatory and feedforward in nature) versus defending (considered unanticipatory and responsive in nature) demonstrated a disparity with basketball players at greater risk during defensive action.^[@bibr27-1941738115619164]^ These large-scale epidemiological data further support the possibility of increased injury risk when responding to unanticipated events or rapid visual-motor decision making is required.

Prospective evidence of depressed aspects of neurocognitive function increasing the risk of noncontact ACL injury further highlights the implications of visual-motor integration on noncontact ACL injury risk.^[@bibr36-1941738115619164]^ Specifically, reaction time, visual processing, and memory measured via a computerized concussion baseline assessment (IMPACT) were significantly lower in those that went on to experience a noncontact ACL injury than matched controls.^[@bibr36-1941738115619164]^ Visual processing speed is imperative to successful sport function whereby complex sensory and visual feedback must be handled with minimal preparation time.^[@bibr15-1941738115619164],[@bibr19-1941738115619164]^ The ability to keep the constantly changing environment (player or ball positions) in short-term visual memory also plays a vital role in feedforward motor planning during activity.^[@bibr33-1941738115619164]^ Thus, visual-motor function and reaction time may influence musculoskeletal injury risk in the ability to anticipate and prepare for high-risk situations.^[@bibr15-1941738115619164],[@bibr25-1941738115619164]^ Faster reaction time or processing speed may improve preparation for incoming perturbations while maintaining neuromuscular integrity and avoiding compromising knee positions (eg, excessive valgus). If visual-motor processing is suboptimal, this will decrease the ability to compensate for external stimuli and/or attenuate the rapid maneuvers that depend on quick visual-motor interaction.^[@bibr8-1941738115619164],[@bibr17-1941738115619164],[@bibr24-1941738115619164]^

Sex Differences in Neurocognition-Neurophysiology {#section9-1941738115619164}
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Neurological factors may also contribute to the greater relative noncontact ACL injury rate in female athletes.^[@bibr1-1941738115619164],[@bibr3-1941738115619164]^ The greater female ACL risk profile has been attributed to factors ranging from hormonal, skeletal alignment, muscular strength, neuromuscular, and biomechanical differences.^[@bibr16-1941738115619164]^ Aspects of physiology that have not been attributed to the sex disparity in injury risk, are neurocognitive and neurophysiological sex differences,^[@bibr26-1941738115619164]^ which influence motor control and visual processing interaction in the spatially complex sport environment.

Altered neuromuscular control during visual-motor environmental interaction increases injury risk and is supported by extensive biomechanical evidence.^[@bibr7-1941738115619164],[@bibr8-1941738115619164],[@bibr10-1941738115619164],[@bibr24-1941738115619164],[@bibr29-1941738115619164]^ The addition of an external target or stimulus that must be visually attended to during landing or change of direction maneuvers has a more pronounced effect on knee control related to injury risk in women compared with men.^[@bibr10-1941738115619164],[@bibr16-1941738115619164],[@bibr24-1941738115619164]^ Women also experience greater alterations in knee neuromuscular control during movement that requires responding to an anticipatory component that integrates visual processing and reaction time.^[@bibr8-1941738115619164]^ Incorporating short-term memory and online decision making also demonstrate sex-specific adaptations in the maintenance of joint-to-joint alignment during complex athletic maneuvers such as cutting or sidestepping.^[@bibr7-1941738115619164],[@bibr29-1941738115619164]^ This evidence may represent a sex disparity in visual-motor--related neurocognition contributing to knee neuromuscular control.

The sex-related disparity in neuromuscular control when spatial attention is challenged may have a neurophysiologic mechanism. Investigations into brain function and anatomy have demonstrated sex differences in nervous system function and structure^[@bibr13-1941738115619164],[@bibr14-1941738115619164]^ that may influence noncontact ACL injury risk. Diffusion tensor imaging has demonstrated that the male brain is structured to facilitate perception and coordinated action (intrahemispheric connectivity), whereas the female brain is structured to facilitate analytical and intuitive processing (interhemeispheric connectivity).^[@bibr18-1941738115619164]^ Men also tend to have a larger angular gyrus and visual cortices relative to overall brain mass.^[@bibr11-1941738115619164],[@bibr12-1941738115619164]^ The functional role of these areas are spatial and visual processing, and visuospatial performance tends to favor men.^[@bibr4-1941738115619164],[@bibr40-1941738115619164]^ This visuospatial processing functionality in men may assist in navigation through a chaotic athletic field while maintaining knee alignment and avoiding high injury--risk positions.^[@bibr28-1941738115619164]^

The sex differences in cognition, visual-motor function, and movement control are likely due to a complex and not entirely understood combination of biological, psychological, physiological, societal, and cultural factors.^[@bibr9-1941738115619164],[@bibr26-1941738115619164],[@bibr30-1941738115619164],[@bibr43-1941738115619164]^ The sex-specific visuospatial ability and brain anatomy may be due to evolutionary history for selecting men for hunting-related skills, creating a biological advantage for increased development of visuospatial abilities.^[@bibr31-1941738115619164]^ Male sex hormones, specifically testosterone, influence brain function to shift cognition away from the left hemisphere and toward the right, increasing a task- and/or spatial-oriented distribution that may improve visuospatial ability.^[@bibr9-1941738115619164],[@bibr39-1941738115619164]^ Experiential factors also play a role, for example, London taxi drivers have greater hippocampal gray matter volume consistent with their constant exposure to the complex visual-spatial problems of navigating a complex city.^[@bibr21-1941738115619164]^ Along similar lines, exposure to specific toys (construction, blocks, etc) and/or action video games has been shown to improve visuospatial skills, and men tend to engage in these activities to a much greater degree.^[@bibr2-1941738115619164],[@bibr38-1941738115619164]^ In light of the typical high spatial demands during sport and the noncontact ACL injury event, the male predisposition to improved spatial cognition^[@bibr40-1941738115619164]^ may play a role in the relatively higher rate of female noncontact ACL injury.

Conclusion {#section10-1941738115619164}
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The tools of neuroscience will continue to help uncover how the nervous system generates motor control and the mechanistic errors in motor control resulting in noncontact ACL injury. Adding neurocognitive elements to injury prevention programs may reduce motor control errors during sport when visual-spatial responsibilities are in high demand. Adding dual tasks such as memory recall, environmental stimulus (ball or partner perturbations), or direct visual perturbations can supplement interventions. Recognition of the neurological implications for maintaining neuromuscular control and injury avoidance may help to mitigate injury risk and improve intervention effectiveness.

The authors report no potential conflicts of interest in the development and publication of this article.
