Quadriceps cortical adaptations in individuals with an anterior cruciate ligament injury
Introduction
Quadriceps muscle weakness is common in people who have sustained an anterior cruciate ligament (ACL) injury or undergone ACL reconstruction (ACLR) [1], [2], [3]. There is evidence that quadriceps weakness contributes to disability [4], and potentially influences the onset and progression of post-traumatic knee osteoarthritis in these individuals [5], [6]. Understanding the causes of quadriceps muscle dysfunction is critical for developing interventions to effectively treat persistent muscle weakness following ACL injury [1], [3]. There is evidence that persistent quadriceps muscle weakness is a consequence of alterations within the central nervous system (CNS), more specifically alterations in the excitability of the primary motor cortex of the brain and associated descending pathways [7], [8], [9] contribute to persistent quadriceps muscle weakness.
The excitability of the cortex and associated pathways can be measured with transcranial magnetic stimulation (TMS) by evaluating the motor threshold, or the amplitude of the muscle response evoked by the TMS [10]. The motor threshold is defined as the minimum stimulus intensity required to elicit a muscle response (motor evoked potential; MEP) of a predefined size. A higher motor threshold is considered indicative of reduced corticomotor excitability, requiring higher levels of stimulation or neural drive to create excitation and neuronal depolarization [11].
Previous studies have demonstrated alterations in quadriceps corticomotor excitability in individuals with ACL injury [7] and ACLR [2], [12], and in individuals with chronic anterior knee pain [13]. Following ACLR, the active motor threshold of the primary motor cortex is higher in the involved versus uninvolved limb and uninjured healthy controls, indicating reduced corticomotor excitability in the involved limb [2], [12]. However, there were no changes in the MEP amplitude following ACLR indicating that although a greater stimulus is required for excitation and depolarization, the amplitude of the motor response is similar within the target muscle of individuals with an ACLR and uninjured individuals [2], [11]. The research suggests a role for the CNS in quadriceps neuromuscular dysfunction, as higher quadriceps active motor threshold (AMT) was found in conjunction with reduced voluntary muscle activation and quadriceps strength deficits in individuals with an ACLR [2].
Transcranial magnetic stimulation (TMS) during an active muscle contraction produces an interruption in voluntary electromyography (EMG) known as the cortical silent period (cSP). The cSP is mediated by both spinal and cortical mechanisms, with the latter part of the cSP (> 50 ms) mediated by inhibitory γ-aminobutyric acid receptor B (GABAB) activity in the cortex [14]. The inhibitory system within the human brain can be more specifically assessed using paired-pulse TMS.
Paired-pulse TMS utilizes a conditioning stimulus and a test stimulus at varying inter-stimulus intervals (ISI). Subthreshold conditioning stimuli will preferentially excite the interneurons, which will suppress or facilitate the subsequent MEP generated from the test stimulus depending on the duration of the ISI. Subthreshold conditioning stimulus coupled with a supra-threshold stimulus using an ISI of one to six milliseconds produces short-interval intracortical inhibition (SICI), and is thought to represent γ-aminobutyric acid receptor A (GABAA) activity [15], [16]. Alternatively, long interval intracortical inhibition (LICI) is the result of two suprathreshold stimuli at an ISI of 50 to 200 ms and is thought to represent GABAB activity [15], [16]. Intracortical inhibition has been assessed in this manner to examine changes in neuromuscular function associated with aging [17], and in clinical populations [18], [19], [20]. Physiological changes in the intracortical inhibitory circuits may be contributing to higher quadriceps AMT, and quadriceps neuromuscular dysfunction previously demonstrated in individuals with an ACL injury and ACLR [2], [7], [12]. Although SICI does not appear to differ between healthy individuals and those with knee osteoarthritis [18], intracortical inhibition has yet to be investigated in individuals with an ACL injury or ACLR.
Spatial reorganization within the CNS in terms of changes in size, shape and center of the cortical motor representation of the target muscle can occur following injury [21], [22], [23]. Although traditionally examined following neurological injury [24], cortical motor representation mapping has more recently been used in musculoskeletal injury research examining the effects of spatial reorganization on neuromuscular function. Alterations in cortical representation position and size have been found for forearm extensors in individuals with lateral elbow pain [22] and in the transversus abdominus in individuals with recurrent low back pain [23], but have yet to be investigated in relation to the quadriceps following ACL injury.
Identifying and understanding CNS adaptations contributing to quadriceps dysfunction would provide novel therapeutic targets within the motor cortex that may lead to improved quadriceps muscle function following ACL injury. Previous corticomotor excitability studies following ACL injury or reconstruction have focused primarily on evaluation of the single joint vasti muscles [2], [4], [7], [12]. However, there is value in exploring changes in rectus femoris following ACL injury as it has been shown that all portions of the quadriceps work to enable knee extension and loading control [25]. Given that the rectus femoris spans two joints, it is possible that it is under differential cortical control compared to the single joint vasti and thus may not be affected to the same extent as the vasti following ACL injury.
Therefore, the aims of this study were: 1) to examine rectus femoris corticomotor excitability and intracortical inhibition in individuals with an ACL injury compared to healthy uninjured individuals, and 2) to determine the calculated center position and area of the rectus femoris cortical motor representation following ACL injury compared to healthy uninjured individuals. We hypothesized that there would be a significant reduction in rectus femoris active motor threshold (AMT), MEP amplitude and cortical motor representation area (size) (H1), and that there would be a significant increase in intracortical inhibition (SICI, LICI and cSP) in those with an ACL injury compared to healthy uninjured individuals (H2).
Section snippets
Study design
This was a cross-sectional laboratory study examining rectus femoris corticomotor excitability, intracortical inhibition and cortical motor representation in a group of individuals with ACL injury, as well as a group of healthy control participants. All main outcome measures were collected during a single data collection session. All participants gave written informed consent, and the study was approved by the Ethics Committee of the University of Melbourne (ID: 1340551).
Participants
All ACL injured
Participant characteristics
Eighteen (n = 18) individuals with ACL injury, and 18 uninjured healthy individuals participated in the study. Participant demographics are provided in Table 1. Individuals with ACL injury had significantly lower self-reported knee function (KOOS-Pain, KOOS-ADL, KOOS-Symptoms and KOOS-QoL) and significantly higher self-reported pain compared to uninjured controls, but no other significant differences were found between groups (Table 1).
Corticomotor excitability and intracortical inhibition
There was a significant limb by group interaction (F1,32 =
Discussion
The aim of the present study was to examine rectus femoris corticomotor excitability and cortical motor representation in individuals with an isolated ACL injury, compared to healthy uninjured individuals. To our knowledge this is the first study to examine these TMS-related measures in rectus femoris. We found the duration of the cSP to be longer in the injured limb only of the ACL group, compared to the uninjured limb of the ACL group and matched limbs of the control group. Contrary to our
Conflict of interest
The authors declare that they have no conflicts of interest.
Acknowledgments
The authors wish to thank Dr. Ross Clark for the development of the custom LabVIEW programs used in this study. Adam Bryant and Kim Bennell are supported by a National Health and Medical Research Council (NHMRC R.D. Wright Biomedical Fellowship #1053521) and NHMRC Principal Research Fellowship (#1058440), respectively.
References (52)
- et al.
Neuromuscular consequences of anterior cruciate ligament njury
Clin Sports Med
(2008) - et al.
The anterior cruciate ligament deficiency as a model of brain plasticity
Med Hypotheses
(2006) - et al.
Non-invasive electrical and magnetic stimulation of the brain, spinal cord and roots: basic principles and procedures for routine clinical application. Report of an IFCN committee
Electroencephalogr Clin Neurophysiol
(1994) - et al.
A practical guide to diagnostic transcranial magnetic stimulation: report of an IFCN committee
Clin Neurophysiol
(2012) - et al.
Corticospinal and intracortical excitability of the quadriceps in active older and younger healthy adults
Arch Gerontol Geriatr
(2013) - et al.
Cortical inhibitory deficits in premanifest and early Huntington's disease
Behav Brain Res
(2016) - et al.
Changes of cortical motor area size during immobilization
Electroencephalogr Clin Neurophysiol
(1995) - et al.
Screening questionnaire before TMS: an update
Clin Neurophysiol
(2011) - et al.
Sampling, noise-reduction and amplitude estimation issues in surface electromyography
J Electromyogr Kinesiol
(2002) Assessment of chronic pain. I. Aspects of the reliability and validity of the visual analogue scale
Pain
(1983)
Transcranial magnetic stimulation mapping: a model based on spline interpolation
Brain Res Bull
Noninvasive mapping of muscle representations in human motor cortex
Electroencephalogr Clin Neurophysiol
Multiple measures of corticospinal excitability are associated with clinical features of multiple sclerosis
Behav Brain Res
Arthrogenic muscle response induced by an experimental knee joint effusion is mediated by pre- and post-synaptic spinal mechanisms
J Electromyogr Kinesiol
Muscle force steadiness in older adults before and after total knee arthroplasty
J Arthroplasty
Quadriceps neural alterations in anterior cruciate ligament reconstructed patients: a 6-month longitudinal investigation
Scand J Med Sci Sports
Quadriceps muscle weakness after anterior cruciate ligament reconstruction: a risk factor for knee osteoarthritis?
Arthritis Care Res
Quadriceps strength and corticospinal excitability as predictors of disability after anterior cruciate ligament reconstruction
J Sport Rehabil
A neuromuscular mechanism of posttraumatic osteoarthritis associated with ACL injury
Exerc Sport Sci Rev
The long-term consequence of anterior cruciate ligament and meniscus injuries osteoarthritis
Am J Sports Med
Corticomotor excitability associated with unilateral knee dysfunction secondary to anterior cruciate ligament injury
Knee Surg Sports Traumatol Arthrosc
A theoretical framework for understanding neuromuscular response to lower extremity joint injury
Sports Health
Neural excitability alterations after anterior cruciate ligament reconstruction
J Athl Train
Differential corticomotor control of a muscle adjacent to a painful joint
Neurorehabil Neural Repair
Role of intracortical mechanisms in the late part of the silent period to transcranial stimulation of the human motor cortex
Acta Neurol Scand
Interactions between inhibitory and excitatory circuits in the human motor cortex
Exp Brain Res
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