Original ResearchAlterations in knee sensorimotor brain functional connectivity contributes to ACL injury in male high-school football players: a prospective neuroimaging analysis
Introduction
Anterior cruciate ligament (ACL) injuries are debilitating knee injuries, with annual direct costs exceeding $2 billion in the United States.1 Nearly 75% of ACL injuries occur via noncontact mechanisms without direct blows to the knee,2 typically attributed to motor coordination errors resulting in tri-planar hip, knee, and ankle motion increasing strain on the ACL.3, 4, 5, 6, 7 Recent evidence indicates that ACL injury can induce central nervous system (CNS) changes in cortical electrical activity when measured by electroencephalography8, 9 and altered cortical and subcortical blood oxygen dependent level (BOLD) signal activity by means of functional magnetic resonance imaging (fMRI).10, 11, 12 While such retrospective information may help guide rehabilitation for ACL injury through brain-targeted approaches,13, 14 prospective data pertaining to the state of the CNS contributing to the initial injury could also be beneficial to prevent injury altogether. Video analyses of ACL injury illustrate that complex CNS processing, including the integration of cognitive, visual, proprioceptive, vestibular, and motor systems, are needed to avoid compromising knee positions that result in traumatic injury.15, 16 Considering that sensorimotor processing, including brain activity and connectivity, are related to overt motor control, behavioral outcomes, and changes in performance,17, 18, 19, 20, 21, 22, 23, 24 prospective CNS data related to ACL injury could supplement injury prevention efforts aimed to leverage neural processes.17, 25, 26
Limited literature exists detailing neurologic data prior to knee injury.12, 27, 28, 29 Specifically, decreased neurocognitive function,29 depressed quadriceps activation,28 and altered BOLD signal activity12 have been observed in athletes prior to an ACL injury. Neurocognitive function, however, is an indirect measure of neural function and quadriceps activation does not provide information on what part of the CNS is driving muscle inhibition. Further, the participant investigated previously12 had a prior ACL injury which may have neurologically contributed to the reported prospective second contralateral injury.
A potential complementary approach to understanding CNS function is through the examination of the temporal coherence of the BOLD signal among spatially distinct brain regions at rest (i.e., functional connectivity).30, 31 Functional connectivity reflects the degree of BOLD signal co-activation (or lack thereof) during active states,32, 33 provides stable indicators of brain function as evidenced through consistent reproducibility of network connectivity,34, 35 and has been suggested as a potential neural biomarker for therapeutic care.36 Functional connectivity is capable of distinguishing pathologies such as Alzheimer’s and Parkinson’s disease37, 38 and is sensitive to detecting neurological changes resulting from combined cognitive and motor skill training.39 Recently, a prospective functional connectivity analysis was used to identify differences between female athletes who went on to experience an ACL injury compared to matched controls.27 Connectivity between regions of the ‘knee motor network’ (i.e., active brain regions during knee movement) were evaluated and depressed functional connectivity between the left primary somatosensory cortex and the right posterior lobe of the cerebellum (Lobule XIIB) was identified in the ACL injured athletes.27 Although a specific mechanism for ACL injury related to such prospective altered connectivity was not reported,27 tasks with high spatial and temporal sensorimotor coordination demands (scenarios where ACL injury often occurs15, 16) increase sensory to cerebellar connectivity40 and such connectivity is critical for error-free movement.41 Sensory-cerebellar connectivity is also involved with timed, spatial orienting tasks,42 thus, lessened connectivity may indicate that this interactive process is disrupted, thereby hindering an athlete’s ability to maintain a safe knee position during dynamic, athletic scenarios.
While the identified connectivity alteration may provide a neural mechanistic target for interventions aimed to restore sensory-cerebellar connectivity,27 this finding was in a cohort of only female athletes and not directly generalizable to male athletes. When comparing ACL injury differences between sexes, females have an estimated 2–4 times greater incidence rate of ACL rupture compared to males,43, 44 but males still constitute a higher absolute number of ACL injuries and exhibit similar lifelong ailments, such as rapid osteoarthritis progression and prolonged disability.45, 46, 47, 48 Considering the differences underlying ACL injury risk mechanisms for males and females (e.g., hormones, laxity, etc.),49 combined with potential functional connectivity sex-differences,50, 51 we aimed to determine if neural activity may influence ACL injury risk in males. The purpose of this study was to utilize a prospective dataset to examine differences in functional brain connectivity in male high school athletes who subsequently suffered an ACL injury relative to their non-injured peers. We hypothesized that those who experienced an ACL injury would exhibit decreased functional brain connectivity of the knee motor network compared to those who did not experience a traumatic knee injury during their competitive season.27
Section snippets
Participants
Sixty-two healthy male varsity high-school football players from two large, local, private high schools enrolled in a prospective longitudinal neuroimaging study examining head impacts. All participants enrolled for one year and a subset (n = 32) enrolled for a second year, with MRI testing occurring prior to and following each football regular season. This study was approved by the institutional review board at Cincinnati Children’s Hospital Medical Center and each participant signed an
Results
The omnibus test revealed significant connectivity differences between the ACL-injured and control participants for the left secondary somatosensory cortex and all other target ROIs, F (3, 11) = 10.46, p = .037. Post-hoc analyses revealed significantly decreased connectivity between the left secondary somatosensory cortex and the left supplementary motor area (SMA), t (13) = −4.19, p = 0.025, U = 0.0, p = 0.004, right pre-motor cortex, t (13) = −3.76, p = 0.026, U = 0.0, p = 0.004, right SMA, t
Discussion
We prospectively examined the functional brain connectivity at rest in male high-school football players who went on to sustain an ACL injury compared to their non-injured counterparts. This study supports a prior investigation of ACL injury in high school female soccer players27 by corroborating a potential neural predisposition to injury, but with unique differences in this male football sample. Congruent with our hypothesis and previous findings in female high school athletes, depressed knee
Alternative explanations and limitations
The above results and discussion of depressed sensorimotor functional connectivity in athletes who experienced an ACL rupture should be interpreted with caution. First, it is interesting to note that the seed which exhibited a significant group effect in its connectivity pattern (SII) was localized to the left hemisphere (and not the right hemisphere), and the ACL-injured participants all injured their left leg. Considering some bilateral findings were present in our results (right and left
Conclusion
Preseason functional connectivity alterations in sensorimotor networks were present in our sample (n = 3) of male high school football athletes who went on to sustain ACL injuries during their competitive season. Future studies with larger sample sizes, combined with complementary prospective lower extremity kinematic and kinetic analyses, are needed to further confirm the current results. In addition, enhanced video analyses of actual injury events are warranted to better understand the
Conflicts of interest
The authors declare no conflicts of interest.
References (97)
- et al.
Robotic simulation of identical athletic-task kinematics on cadaveric limbs exhibits a lack of differences in knee mechanics between contralateral pairs
J Biomech
(2017) - et al.
The influence of internal and external tibial rotation offsets on knee joint and ligament biomechanics during simulated athletic tasks
Clin Biomech
(2018) - et al.
Does brain functional connectivity contribute to musculoskeletal injury? A preliminary prospective analysis of a neural biomarker of ACL injury risk
J Sci Med Sport
(2019) - et al.
One-year test-retest reliability of intrinsic connectivity network fMRI in older adults
NeuroImage
(2012) - et al.
Group independent component analysis reveals consistent resting-state networks across multiple sessions
Brain Res
(2008) - et al.
Incidence of anterior cruciate ligament injury and other knee ligament injuries: a national population-based study
J Sci Med Sport
(2009) - et al.
A component based noise correction method (CompCor) for BOLD and perfusion based fMRI
NeuroImage
(2007) - et al.
Lower limb sensorimotor network: issues of somatotopy and overlap
Cortex
(2007) - et al.
Topological FDR for neuroimaging
Neuroimage
(2010) - et al.
Sensorimotor integration in human primary and secondary somatosensory cortices
Brain Res
(1998)
Sexual dimorphism and asymmetries in the gray-white composition of the human cerebrum
NeuroImage
White matter microstructure in female to male transsexuals before cross-sex hormonal treatment. A diffusion tensor imaging study
J Psychiatr Res
Sex-related differences in amygdala functional connectivity during resting conditions
NeuroImage
Intrinsic functional connectivity of the periaqueductal gray, a resting fMRI study
Behav Brain Res
The acute effects of local muscle vibration frequency on peak torque, rate of torque development, and EMG activity
J Electromyogr Kinesiol
Structurofunctional resting-state networks correlate with motor function in chronic stroke
NeuroImage Clin
Effects of threat cues on attentional shifting, disengagement and response slowing in anxious individuals
Behav Res Ther
Cost effectiveness of anterior cruciate ligament reconstruction in young adults
Clin Orthop Relat Res
Mechanisms of anterior cruciate ligament injury
Orthopedics
Posterior tibial slope angle correlates with peak sagittal and frontal plane knee joint loading during robotic simulations of athletic tasks
Am J Sports Med
Knee abduction affects greater magnitude of change in ACL and MCL strains than matched internal tibial rotation in vitro
Clin Orthop Relat Res
Biomechanical measures of neuromuscular control and valgus loading of the knee predict anterior cruciate ligament injury risk in female athletes
Am J Sports Med
Altered electrocortical brain activity after ACL reconstruction during force control
J Orthop Res
Changed cortical activity after anterior cruciate ligament reconstruction in a joint position paradigm: an EEG study
Scand J Med Sci Sports
Neuroplasticity following anterior cruciate ligament injury: a framework for visual-motor training approaches in rehabilitation
J Orthop Sports Phys Ther
Neuroplasticity associated with anterior cruciate ligament reconstruction
J Orthop Sports Phys Ther
Brain activation for knee movement measured days before second anterior cruciate ligament injury: neuroimaging in musculoskeletal medicine
J Athl Train
Principles of motor learning to support neuroplasticity after ACL injury: implications for optimizing performance and reducing risk of second ACL injury
Sports Med
Central nervous system adaptation after ligamentous injury: a summary of theories, evidence, and clinical interpretation
Sports Med
Mechanisms of anterior cruciate ligament injury in basketball: video analysis of 39 cases
Am J Sports Med
Biomechanical analysis of anterior cruciate ligament injury mechanisms: three-dimensional motion reconstruction from video sequences
Scand J Med Sci Sports
Brain-behavior mechanisms for the transfer of neuromuscular training adaptions to simulated sport: initial findings from the train the brain project
J Sport Rehabil
Gait speed and gait variability are associated with different functional brain networks
Front Aging Neurosci
Functional connectivity associated with gait velocity during walking and walking-while-talking in aging: a resting-state fMRI study
Hum Brain Mapp
Brain activation associated with active and passive lower limb stepping
Front Hum Neurosci
EEG topographies provide subject-specific correlates of motor control
Sci Rep
Correlations between brain activity and components of motor learning in middle-aged adults: an fMRI study
Front Hum Neurosci
The characteristics of EEG power spectra changes after ACL rupture
PLoS One
MRI-compatible device for examining brain activation related to stepping
IEEE Trans Med Imaging
Mechanisms underlying ACL injury-prevention training: the brain-behavior relationship
J Athl Train
Neuroscience application to noncontact anterior cruciate ligament injury prevention
Sports Health
Decreased quadriceps activation measured hours prior to a noncontact anterior cruciate ligament tear
J Orthop Sports Phys Ther
The relationship between neurocognitive function and noncontact anterior cruciate ligament injuries
Am J Sports Med
Functional connectivity in the motor cortex of resting human brain using echo-planar BRI
Magn Reson Med
Functional connectivity in the resting brain: a network analysis of the default mode hypothesis
Proc Natl Acad Sci U S A
Functional connectivity and neurological recovery
Dev Psychobiol
Task vs. rest-different network configurations between the coactivation and the resting-state brain networks
Front Hum Neurosci
Reproducibility and temporal structure in weekly resting-state fMRI over a period of 3.5 years
PLoS One
Cited by (25)
Proprioceptive postural control strategies differ among non-injured athletes
2022, Neuroscience LettersCitation Excerpt :Neuromuscular flexibility may protect from injury as greater degree of movement variability reduced the risk of ACL injury after reconstruction [41]. Impaired activation and functional connectivity between the left primary and secondary somatosensory cortex and the cerebellum has also been associated with future ACL rupture [20,22,42]. As optimal postural stability requires appropriate proprioceptive reweighting [1,8,32,33], and poor balance control and inadequate hamstring recruitment are associated with an increased risk of ACL tear [16,17], further studies are needed to assess the relationship between proprioceptive strategies and injury risk.
Integrating neurocognitive challenges into injury prevention training: A clinical commentary
2021, Physical Therapy in SportCitation Excerpt :However, the common non-contact mechanism of ACL injury may not be entirely explained by mechanical factors alone, as neurocognitive deficits also contribute to injury risk (Swanik et al., 2007; Wilkerson, 2012). In addition to decreased neurocognition directly increasing injury risk, two prospective studies have identified altered sensorimotor brain functional connectivity in high school athletes who later went on to suffer an ACL injury (Diekfuss et al., 2019a, 2019b). Decreased connectivity between cortical sensory and motor regions may contribute to slower processing speeds and reaction to environmental stimuli during sport participation, further implicating neurocognitive function as an ACL injury risk factor (Diekfuss et al., 2019a, 2019b).
Integrated 3D motion analysis with functional magnetic resonance neuroimaging to identify neural correlates of lower extremity movement
2021, Journal of Neuroscience MethodsCitation Excerpt :Two common biomechanical risk factors for ACL injury are increased knee valgus in the frontal plane and decreased knee flexion in the sagittal plane during dynamic multi-joint coordinated movements such as landing and change of direction maneuvers (a ‘stiff’ movement strategy that strains the ACL) (Dingenen et al., 2015; Havens and Sigward, 2015; Hewett et al., 2005; Paterno et al., 2010). As the majority of ACL injury events are noncontact, as in occurring secondary to motor ‘coordination’ errors that regulate knee position and not direct blows or player contact, central nervous system (CNS) processing of knee position has been implicated to play a role (Bonnette et al., 2020; Diekfuss et al., 2019a, b; Grooms et al., 2015; Swanik, 2015). Accordingly, preliminary methods have emerged to discover how the CNS contributes to knee injury-risk movement mechanics to support the development of combined brain and body therapeutics for those with and without movement disorders (Armijo-Olivo, 2018; Bonnette et al., 2020; Diekfuss et al., 2020a, 2020b, 2020c, 2020d; Grooms et al., 2018; Silfies et al., 2017).
The Evolution of Neuroimaging Technologies to Evaluate Neural Activity Related to Knee Pain and Injury Risk
2024, Current Reviews in Musculoskeletal MedicineThe impact of differential knee laxity on brain activation during passive knee joint loading
2024, Journal of Orthopaedic Research