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Introduction: Research investigating LAS and CAI has essentially focused on local adaptations. Recently, growing evidence is supporting the hypothesis neural plasticity occurs at both the spinal and cortical levels following (repeated) ligamentous ankle injury. These alterations might explain persisting dysfunctions, an increased injury risk, and the increased probability of developing CAI. This systematic review synthesizes the literature on brain plasticity following LAS and CAI. Methods: Studies eligible for this systematic review investigated the brain with direct outcomes measures in patients with LAS or CAI. The following electronic databases were used for the systematic search from their conception to 19/10/2021: Pubmed, Web of Science, Embase, Scopus, PEDro, The Cochrane Central Registry for Controlled Trials (CENTRAL) and SPORTDiscus. Three authors independently screened 1227 articles from 7 databases using a two-staged process to include 16 studies. The quality assessment tool for observationaland cross-sectional studies was used for the risk of bias assessment. The authors extracted and summarised relevant outcomes from each study in table 1. Results: Patients with LAS showed lower superior cerebellar peduncles (white matter microstructure) compared with healthy controls. CAI populations displayed an increased sensitivity of intermediate inhibitory neurons and a decreased sensitivity of excitatory neurons in the corticospinal pathway. They also found more variability in cortical activation in the superior parietal lobe, pre-and postcentral gyrus and the supplementary motor area with lower corticomotor excitability in several lower limb muscles in patients with CAI. Conclusion: Whilst these findings may support the hypothesis of brain plasticity in patients with ligamentous ankle injuries, all studies were retrospective in nature and most used different measurement methods which makes direct comparisons difficult and limits the strength of evidence of this review. Future research should focus on the understanding of the underlying neurophysiological mechanisms. Correspondence e-mail: alexandre.maricot@vub.be

Functional performance tests are utilized by clinicians and researchers to compile injury risk profiles, monitor rehabilitation progress and to inform a criteria-based and safe return to sport decision-making approach. Functional performance tests are measurements that evaluate an athlete’s current functional ability. Although literature documents a significant association between some functional performance test outcomes and an increased injury risk, these tests should be interpreted in a more complex, athlete centered approach of sports injuries. In a comprehensive athlete centered approach, functional performance tests should also approximate the athletic context. This highlights the need to continuously develop functional performance tests and evaluate different interactions that arise within the athletic context. Interestingly, the current functional performance test approach neglect the relevance of fatigue and adaptability. Adaptability is defined as the athlete’s ability to modify responses under a broad spectrum of conditions. Fatigue is a multidimensional phenomenon and includes both central and peripheral fatigue mechanisms as well as physical and mental fatigue constructs. The goal of the present dissertation is to gain more insight in how fatigue interacts with functional performance tests, injury risk and adaptability. In our first study (chapter two) we provide a systematic literature review to identify the existing body of evidence on the interaction between acute physical fatigue and prospectively determined injury risk factors for lower extremity injuries. The body of evidence is scarce and of low quality, with no evidence that acute fatigue increases the non-contact ACL, ITBFS or generic lower extremity injury risk profiles. Only limited evidence was found for the statement that acute fatigue negatively affects the lateral ankle sprain, patellofemoral pain syndrome or hamstring injury risk profiles. In chapter three, we describe the systematic development and test protocol of the reactive balance test. The reactive balance test is a neurocognitive single-leg balance test that integrates environmental perception, decision making and reaction time. The outcomes are accuracy and visuomotor response time. The reactive balance test is a functional performance test that allows clinicians to score an athlete’s adaptability. Consequently, we performed two randomized cross-over studies to explore the effect of mental fatigue (chapter four) and acute physical fatigue (chapter five) with four functional performance tests, including three traditional functional performance tests, the Y-balance test, the countermovement jump test, the single leg hop test and the neurocognitive reactive balance test. The results presented in chapter four illustrate that mental fatigue does not affect outcomes of the included traditional functional performance tests, but does impair accuracy in the reactive balance test. Following a 90 minute 100% incongruent Stroop task, participants accuracy significantly decreased in the reactive balance test. Mental fatigue can negatively affect adaptability. The results presented in chapter five illustrate that acute physical fatigue can cause divergent fatigue responses in functional performance test outcomes. While the countermovement jump and Y balance test performance remained unaffected, single leg hop distance significantly decreased following a 30 second all-out sprint effort (Modified Wingate procedure). Acute physical fatigue also impairs accuracy in the reactive balance test and can also negatively affect adaptability. This thesis highlights that acute physical fatigue interacts with functional performance tests, but comprises large intra- and interindividual differences. Clinicians should be aware of this interaction and a paradigm shift is needed towards evaluating individual fatigue responses. Moreover, neurocognitive functional performance test can complement the current use of functional performance tests. For future research, more teamwork is needed to merge insights from fatigue and injury prevention experts. Additionally, evaluating individual fatigue responses might expose patterns that are masked in current data monitoring strategies and group-level analyses. Prospective research is needed to explore the added value of neurocognitive functional performance tests.

Functional performance tests are utilized by clinicians and researchers to compile injury risk profiles, monitor rehabilitation progress and to inform a criteria-based and safe return to sport decision-making approach. Functional performance tests are measurements that evaluate an athlete’s current functional ability. Although literature documents a significant association between some functional performance test outcomes and an increased injury risk, these tests should be interpreted in a more complex, athlete centered approach of sports injuries. In a comprehensive athlete centered approach, functional performance tests should also approximate the athletic context. This highlights the need to continuously develop functional performance tests and evaluate different interactions that arise within the athletic context. Interestingly, the current functional performance test approach neglect the relevance of fatigue and adaptability. Adaptability is defined as the athlete’s ability to modify responses under a broad spectrum of conditions. Fatigue is a multidimensional phenomenon and includes both central and peripheral fatigue mechanisms as well as physical and mental fatigue constructs. The goal of the present dissertation is to gain more insight in how fatigue interacts with functional performance tests, injury risk and adaptability. In our first study (chapter two) we provide a systematic literature review to identify the existing body of evidence on the interaction between acute physical fatigue and prospectively determined injury risk factors for lower extremity injuries. The body of evidence is scarce and of low quality, with no evidence that acute fatigue increases the non-contact ACL, ITBFS or generic lower extremity injury risk profiles. Only limited evidence was found for the statement that acute fatigue negatively affects the lateral ankle sprain, patellofemoral pain syndrome or hamstring injury risk profiles. In chapter three, we describe the systematic development and test protocol of the reactive balance test. The reactive balance test is a neurocognitive single-leg balance test that integrates environmental perception, decision making and reaction time. The outcomes are accuracy and visuomotor response time. The reactive balance test is a functional performance test that allows clinicians to score an athlete’s adaptability. Consequently, we performed two randomized cross-over studies to explore the effect of mental fatigue (chapter four) and acute physical fatigue (chapter five) with four functional performance tests, including three traditional functional performance tests, the Y-balance test, the countermovement jump test, the single leg hop test and the neurocognitive reactive balance test. The results presented in chapter four illustrate that mental fatigue does not affect outcomes of the included traditional functional performance tests, but does impair accuracy in the reactive balance test. Following a 90 minute 100% incongruent Stroop task, participants accuracy significantly decreased in the reactive balance test. Mental fatigue can negatively affect adaptability. The results presented in chapter five illustrate that acute physical fatigue can cause divergent fatigue responses in functional performance test outcomes. While the countermovement jump and Y balance test performance remained unaffected, single leg hop distance significantly decreased following a 30 second all-out sprint effort (Modified Wingate procedure). Acute physical fatigue also impairs accuracy in the reactive balance test and can also negatively affect adaptability. This thesis highlights that acute physical fatigue interacts with functional performance tests, but comprises large intra- and interindividual differences. Clinicians should be aware of this interaction and a paradigm shift is needed towards evaluating individual fatigue responses. Moreover, neurocognitive functional performance test can complement the current use of functional performance tests. For future research, more teamwork is needed to merge insights from fatigue and injury prevention experts. Additionally, evaluating individual fatigue responses might expose patterns that are masked in current data monitoring strategies and group-level analyses. Prospective research is needed to explore the added value of neurocognitive functional performance tests.

After lower extremity injury, only half of the injured athletes return to their pre-injury sports level. Even though functional performance tests are often used to make return to sport decisions, it is unknown whether functional performance is associated with return to performance after such injuries. The aim of this systematic review was to identify, critically appraise, and analyze studies that investigated the association of functional performance tests with return to performance after lower extremity injuries in athletes participating in high-impact sports. MEDLINE, Embase, Web of Science, and CINAHL were systematically searched for relevant studies. Articles were independently screened by two authors and data were obtained from each included study using a data extraction form. Two authors independently scored methodological quality using the Quality In Prognosis Studies tool. A qualitative best evidence synthesis was conducted. Eight studies reported the association of functional performance with return to performance after lower extremity injuries, involving 1,246 athletes after anterior or posterior cruciate ligament reconstruction. No studies were found on the association of functional performance with return to performance for lower extremity injuries other than after anterior or posterior cruciate ligament reconstruction. All included studies had a high risk of bias. Two studies found significant but small associations for selected hop tests after anterior cruciate ligament reconstruction. Low evidence of association between functional performance and return to performance was present after anterior cruciate ligament reconstruction for the triple hop for distance, the 6-meter timed hop, the side hop in female athletes, and for the combination of the single and crossover hop for distance. In athletes after posterior cruciate ligament reconstruction, the vertical jump showed a significant but small association with return to performance. There is no high-quality evidence that functional performance is associated with return to performance after lower extremity injuries in athletes practicing high-impact sports. Low quality evidence suggests small associations after anterior and posterior cruciate ligament reconstruction. No evidence exists for lower extremity injuries other than after anterior or posterior cruciate ligament reconstruction. Therefore, research on functional performance associated with return to performance is recommended in high-quality prospective cohort studies including athletes with any type of lower extremity injury.