Alterations in knee sensorimotor brain functional connectivity contributes to ACL injury in male high-school football players: a prospective neuroimaging analysis

Highlights

• Prospective brain connectivity was evaluated in male high school football players.

• Three athletes sustained complete ACL ruptures.

• Twelve healthy athletes were matched based on school, age, height, weight, and grade.

• Our sample (n = 3) of ACL-injured athletes exhibited prospective decreased connectivity.

• We discuss augmenting ACL prevention programs with sensorimotor-based training.

Abstract

Objective

This study’s purpose was to utilize a prospective dataset to examine differences in functional brain connectivity in male high school athletes who suffered an anterior cruciate ligament (ACL) injury relative to their non-injured peers.

Methods

Sixty-two male high school football players were evaluated using functional magnetic resonance imaging prior to their competitive season to evaluate resting-state functional brain connectivity. Three athletes later experienced an ACL injury and were matched to 12 teammates who did not go on to sustain an ACL injury (controls) based on school, age, height, weight, and year in school. Twenty-five knee-motor regions of interest (ROIs) were created to identify differences in connectivity between the two groups. Between-subject F and t tests were used to identify significant ROI differences using a false discovery rate correction for multiple comparisons.

Results

There was significantly less connectivity between the left secondary somatosensory cortex and the left supplementary motor area (p = 0.025), right pre-motor cortex (p = 0.026), right supplementary motor area (p = 0.026), left primary somatosensory cortex (superior division; p = 0.026), left primary somatosensory cortex (inferior division; p = 0.026), and left primary motor cortex (p = 0.048) for the ACL-injured compared to the control subjects. No other ROI-to-ROI comparisons were significantly different between the groups (all p > 0.05).

Conclusion

Our preliminary data indicate a potential sensorimotor disruption for male football players who go on to experience an ACL injury. Future studies with larger sample sizes and complementary measures of neuromuscular control are needed to support these findings.

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