The Knee 21 (2014) 736–742

Contents lists available at ScienceDirect

The Knee

Contributions of neural excitability and voluntary activation to

quadriceps muscle strength following anterior cruciate
ligament reconstruction
Adam S. Lepley a,⁎, Hayley M. Ericksen a, David H. Sohn b, Brian G. Pietrosimone c
a
Musculoskeletal Health and Movement Science Laboratory, Department of Kinesiology, University of Toledo, Toledo, OH, United States
b
Department of Orthopedic Surgery, University of Toledo, Toledo, OH, United States
c
Department of Exercise and Sport Science, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States

a r t i c l e i n f o a b s t r a c t

Article history: Background: Persistent quadriceps weakness is common following anterior cruciate ligament reconstruction
Received 4 September 2013 (ACLr). Alterations in spinal-reflexive excitability, corticospinal excitability and voluntary activation have been
Received in revised form 30 December 2013 hypothesized as underlying mechanisms contributing to quadriceps weakness. The aim of this study was to eval-
Accepted 10 February 2014 uate the predictive capabilities of spinal-reflexive excitability, corticospinal excitability and voluntary activation
on quadriceps strength in healthy and ACLr participants.
Keywords:
Methods: Quadriceps strength was measured using maximal voluntary isometric contractions (MVIC). Voluntary
Knee injury
Spinal-reflexive excitability
activation was quantified via the central activation ratio (CAR). Corticospinal and spinal-reflexive excitability
Corticospinal excitability were measured using active motor thresholds (AMT) and Hoffmann reflexes normalized to maximal muscle re-
Quadriceps weakness sponses (H:M), respectively. ACLr individuals were also split into high and low strength subsets based on MVIC.
Neuromuscular function Results: CAR was the only significant predictor in the healthy group. In the ACLr group, CAR and H:M significantly
predicted 47% of the variance in MVIC. ACLr individuals in the high strength subset demonstrated significantly
higher CAR and H:M than those in the low strength subset.
Conclusion: Increased quadriceps voluntary activation, spinal-reflexive excitability and corticospinal excitability
relates to increased quadriceps strength in participants following ACLr.
Clinical relevance: Rehabilitation strategies used to target neural alterations may be beneficial for the restoration
of muscle strength following ACLr.
© 2014 Elsevier B.V. All rights reserved.

1. Introduction
Anterior cruciate ligament (ACL) rupture is one of the most common
traumatic knee injuries, with upwards of 250,000 ACL ruptures occur-
ring in the United States each year [1]. Although there have been
advancements in surgical and rehabilitation techniques, quadriceps
muscle strength deficits have been reported to exceed 20% at a time of
return to activity, and can persist many years following ACL reconstruc-
tion (ACLr) [2,3]. Persistent quadriceps weakness has been linked to
decreases in physical performance [4], increased risk of re-injury [5],
and has been hypothesized to contribute to the development of post-
traumatic joint osteoarthritis [6,7]. Deficits in quadriceps strength
have been strongly associated with self-reported disability that is
⁎ Corresponding author at: Joint Injury and Muscle Inhibition Laboratory, Department
of Kinesiology, College of Health Science and Human Services, University of Toledo, Mail
Stop 119 W. Bancroft St., Toledo, OH 43606-3390, United States. Tel.: +1 989 385 0722.
E-mail address: adam.lepley@rockets.utoledo.edu (A.S. Lepley).
commonly reported in the years following ACLr [8,9], highlighting the
importance of restoring and maintaining optimal quadriceps function
in these patients with ACLr.
It is well known that both morphological and neural adaptations are
responsible for modifying muscle strength in healthy populations [10].
Knowing the underlying neural contributors to quadriceps weakness
following ACLr would be beneficial in developing future therapeutic
interventions. Morphological changes of the quadriceps musculature
following ACL injury have not been able to fully explain the extent of
quadriceps weakness that can persist long after ACLr [11,12]. However,
when morphological and neural contributions are considered together,
as measured by muscle cross sectional area and muscle voluntary acti-
vation, the combined effect has accounted for up to 85% of the variance
in muscle strength following injury [13–15]. In these investigations
[13–15], voluntary activation contributed nearly twice as much as
cross sectional area, suggesting that neural alterations play a large role
in modifying muscle strength. In addition, recent work has found chang-
es in fundamental, movement generating neural pathways following
both ACL injury and joint effusion models, further emphasizing the

http://dx.doi.org/10.1016/j.knee.2014.02.008
0968-0160/© 2014 Elsevier B.V. All rights reserved.
 A.S. Lepley et al. / The Knee 21 (2014) 736–742 737

need to understand the neural contributions to strength. Specifically, al- 2.1. Participants
terations in corticospinal excitability [16], spinal-reflexive excitability
[17] and voluntary activation [18] are proposed as mechanisms of Twenty-nine participants with a history of unilateral ACLr were re-
quadriceps weakness following ACLr. However, it is unknown how cruited from the university community and volunteered to participate
these neural excitability pathways and quadriceps voluntary activation in this study (Table 1). All ACLr participants needed to be cleared by
contribute to the persistent deficits in quadriceps strength observed an orthopedic surgeon for full participation in all activities without
following reconstruction. any restrictions. Participants with a history of knee surgeries other
Despite clinician's best efforts, standard therapeutic rehabilitation than ACLr, multiple ligament tears or any other lower extremity muscu-
following surgery has failed to restore knee function to pre-injury loskeletal injury in the previous six months were excluded. We enrolled
levels, as seen by the persistent deficits in quadriceps strength, in- an additional 29 healthy participants, who were matched to the ACLr
creased risk of re-injury and high rates of post-traumatic osteoarthri- group using gender, age, height and mass (Table 1). All healthy partici-
tis [3]. Traditional rehabilitation utilizes exercises to increase muscle pants were free of any lower extremity musculoskeletal injury in the
size, such as concentric strengthening. However, targeting neural previous six months, no history of major ligamentous or bony damage,
impairment is often overlooked in traditional rehabilitation [19], and no history of previous lower extremity surgery. All participants
and failure to directly treat the potential underlying influences of were excluded if they presented with neurological or muscular disor-
quadriceps weakness may result in unsuccessful restoration of quad- ders, a history of brain/cranial surgeries, migraines, seizures, or concus-
riceps strength [19,20]. In order for clinicians to develop new and sion in the past six months. Participants that had been prescribed
innovative rehabilitative strategies that target these underlying medication to alter nervous system function and pregnant females
mechanisms, it is imperative to understand how excitability of were also excluded. Participants were instructed not to consume
these influential neural mechanisms contributes to muscle strength caffeine on the day they were tested. Self-reported function was also re-
following ACLr. Although previous data exists to demonstrate neural corded using the International Knee Documentation Committee (IKDC)
alterations in injured populations, no investigation has been per- form, which is a reliable questionnaire to assess self-perceived overall
formed to examine the contributions of these neural measures on knee function.
muscle force production. Therefore, the purpose of this investigation
was to evaluate the ability of neural contributions, as quantified by
spinal-reflexive excitability, corticospinal excitability, and voluntary 2.2. Quadriceps strength and voluntary activation
activation, to predict quadriceps strength in both healthy partici-
pants, as well as those following ACLr. Additionally, we evaluated Maximal voluntary isometric contractions (MVIC) of the quadriceps
the relationship of these neural outcomes to muscle strength in a were used to assess quadriceps strength. Voluntary quadriceps activa-
subset of ACLr participants with high quadriceps strength and in tion was assessed using the burst superimposition technique (SIB) and
those with low quadriceps strength. quantified using the central activation ratio (CAR). Participants were
seated in a Biodex Systems III dynamometer (Biodex Medical Systems,
Shirley, NY) for both strength and voluntary activation procedures.
2. Materials and methods The knee and hip joints were positioned in 90° and 85° of flexion respec-
tively and bilateral shoulder and lap restraints were used to secure the
All main outcome measures (quadriceps strength, voluntary acti- participant into the dynamometer to limit any unwanted movement
vation, spinal-reflexive excitability, and corticospinal excitability) [24]. In addition, the distal shank of the tested limb was secured into
were performed during a single testing session on the ACLr limb of the dynamometer arm using a velcro strap. Two 7 × 13 cm Dura Stick
the ACLr group, and in a dominance matched limb of the healthy (Chattanooga Group, Hixson, TN) self-adhesive electrodes were
group. Quadriceps strength and activation were always performed positioned on the distal vastus medialis and proximal vastus lateralis
last in the order to limit potential effects on neural excitability [21]. for voluntary activation testing. A supramaximal stimulus of 125 V
In addition to the main outcome measures, activity level was was delivered to the quadriceps during voluntary activation testing
assessed using the Tegner activity level scale [22] and self-reported using a square wave stimulator (S88, GRASS telefactor, W. Warwick,
disability via the International Knee Documentation Committee RI) and a stimulation isolation unit (SIU8T, W. Warwick RI) with a
Form (IKDC) [23]. University approved informed consent forms 100 ms train of 10 stimuli, at 100 pulses per second, with a pulse
were signed prior to enrollment. duration of 0.6 ms, and a 0.01 ms pulse delay [25].
Participants were instructed to extend their knee with their arms
crossed over their chest. Warm up trials were conducted at a self-
perceived effort of 25%, 50% and 75% of their maximal effort. The partic-
Table 1 ipants were instructed that these trials did not have to be exact and
Demographics. served as a warm-up for the test trials. Next, participants performed
MVIC trials until there was no more increase in torque, ensuring each
Demographic ACLr group Healthy group
participant was able to perform a maximal effort contraction. For visual
n 29 (20 female, 9 male) 29 (20 female, 9 male)
feedback, the torque generated from the contraction was provided in
Age (years) 21.2 ± 3.7 21.5 ± 2.7 real time on a custom computer software program (Microsoft Visual
Height (cm) 170.7 ± 9.9 170.6 ± 8.9 Basic, Redmond, WA) and the participant was instructed to increase
Mass (kg) 72.9 ± 17.7 71.9 ± 12.7
Months post-ACLr 48.2 ± 35.5 –
the graph as high as possible. At least one-minute rest was given be-
IKDC index 84.2 ± 9.5 99.6 ± 1.1 tween trials. The last two MVIC trials were averaged for analysis and
Tegner activity level 5.9 ± 2.0 6.0 ± 1.4 also used for triggering an automated stimulus during muscle activation
Quadriceps MVIC/body 2.67 ± 0.76 3.13 ± 1.06 testing. An automated system was used to trigger the superimposed
mass (Nm/kg)
burst stimulation as it has been reported to improve reliability of this
Quadriceps CAR (%) 88.1 ± 12.0 95.9 ± 3.4
Quadriceps H:M 0.265 ± 0.154 0.196 ± 0.102 technique (Fig. 1) [26].
Quadriceps AMT (%) 43.9 ± 16.3 37.5 ± 12.7 Three additional MVIC trials were performed with the superimposed
Abbreviations: ACLr, anterior cruciate ligament reconstruction; IKDC, International Knee
stimulus. The CAR outcome variable was calculated using previously
Documentation Committee; CAR, central activation ratio; H:M, Hoffmann reflex normal- published methods (Fig. 1) [25]. The trial producing the highest CAR
ized to maximal muscle response; AMT, active motor threshold. value was used for analysis. CAR represents the percentage of muscle
738 A.S. Lepley et al. / The Knee 21 (2014) 736–742
Fig. 1. Depiction of torque graph seen by participant during MVIC and CAR testing. The
dashed line represents the average MVIC produced during the practice trials. The top,
solid black line represents 120% of the average MVIC. Participants were instructed to at-
tempt to reach the solid black line to ensure maximal effort. The automatic triggering sys-
tem was armed once the torque output reached the dotted line. Once the participant's
torque dropped 1 NM below their peak torque, the automated stimulus was delivered to
the quadriceps muscle. If the participant was unable to reach the dotted line during the
trial, the stimulus was never delivered and more rest was provided between trials. MVIC
values and superimposed burst torque values (SIB) were used to calculate CAR as seen
by the equation in the figure.
a participant voluntary has available to use, therefore a higher percent-
age represents higher voluntary activation levels.
2.3. Quadriceps corticospinal excitability
Active motor thresholds (AMT) were used to quantify corticospinal
excitability and obtained using transcranial magnetic stimulation
(TMS) with a double cone coil (Magstim Company, Wales, UK). Partici-
pants were positioned in the dynamometer as described during
strength testing. A lycra swim cap was placed on the participant's
head, and the optimal stimulating position was determined using previ-
ously published methods and marked on the swim cap [27]. The simu-
lator was then secured into that spot using a flexible camera mount
(Manfrotto Company, Cassola, Italy) and AMT was located, which was
defined as the lowest TMS intensity required to evoke a measureable
(N100 μV) motor evoked potential in five out of 10 trials [28]. During
AMT testing, each participant was directed to isometrically contract
the tested limb to 5% of their MVIC [29], while a magnetic stimulus
was applied to the motor cortex. Visual feedback of the torque generat-
ed from the contraction was provided in real time on the same custom
computer software program that was used during CAR testing. Partici-
pants were given rest and instructed to stop contracting between
stimuli. It is important to note that higher AMT denotes lower
corticomotor excitability, as more magnetic energy is required to
evoke a measureable response.
2.4. Quadriceps spinal-reflexive excitability
Quadriceps spinal-reflexive excitability was evaluated using the
Hoffmann reflex normalized to maximal muscle response (H:M). Partic-
ipants were positioned supine on a padded treatment plinth with their
arms comfortably placed at their side, their head in a neutral position,
and their knee slightly flexed and supported by a half bolster. Two
10 mm pre-gelled Ag/AgCl electromyography (BIOPAC Systems, Inc.,
Goleta CA, USA) electrodes were positioned 1.75 mm apart over the
muscle belly of the vastus medialis. A 2 mm shielded disc stimulating
electrode (EL2524S, BIOPAC Systems Inc.) was positioned over the fem-
oral nerve and secured with hypoallergenic tape. A 4 × 4 cm self-
adhesive electrode was placed over the ipsilateral hamstring muscles
to be used as a dispersive electrode. A 1 ms square wave stimulus was
produced with a BIOPAC stimulator module (STM100A, BIOPAC Sys-
tems, Inc.) and a 200 volt maximum stimulus adaptor (STMISOC,
BIOPAC Systems Inc.) and delivered to the femoral nerve. Stimulus in-
tensity was increased until a maximal Hoffmann reflex was found, in
which an increase in the stimulus intensity resulted in a decrease of
the peak-to-peak amplitude of the Hoffmann reflex. The stimulus inten-
sity was then increased until a maximal muscle response was elicited, in
which an increase in the stimulus intensity resulted in no further
increase in the peak-to-peak amplitude of the muscle response. The
average peak-to-peak values of three maximal Hoffmann reflexes
were normalized to the average peak-to-peak values of three maximal
muscle responses to create the H:M outcome variable [30]. Electromyo-
graphic signals were band-pass filtered from 10 to 50 Hz and collected
at 1024 Hz with a common-mode-rejection ratio of 110 dB using
AcqKnowledge 4.0 software (Biopac Systems Inc.). In this instance,
higher H:M denotes higher spinal-reflexive excitability.
3. Statistical analysis
Means and standard deviations were calculated for demographics
and all main outcome measures (Table 1). Stepwise hierarchal multiple
linear regression analyses were performed separately in the healthy and
ACLr groups to examine the amount of variance in MVIC values that
could be explained by the variance in CAR, H:M and AMT measures.
The order in which the predictor variables (CAR, H:M and AMT) were
entered into the regression model was determined by the magnitude
of individual simple Pearson product moment correlations. The total
R2 of the model, as well as the change in R2 to the model from the addi-
tion of each predictor variable, was analyzed. The correlations between
the three predictor variables (CAR, H:M and AMT) were also assessed
and the correlation coefficients (r) were classified as weak (0–0.4),
moderate (0.4–0.7) or strong (0.7–1.0) [8].
Additionally we assessed the relationship of neural contributions be-
tween ACLr participants exhibiting high and low quadriceps strength. A
value of central tendency for MVIC was used to split the ACLr group into
two subsets. Due to MVIC values being normally distributed, the
mean MVIC value of the whole ACLr group (2.67 Nm/kg) was used to
place people in the high strength (N2.67 Nm/kg) or low strength
(≤ 2.67 Nm/kg) subsets. Once ACLr participants were stratified into
either a high strength (HS) or low strength (LS) subset, two additional
linear regression analyses were performed on each subset in the same
manner. Further, independent t-tests were performed to detect differ-
ences in demographics, AMT, CAR, and H:M between the HS and LS
ACLr subsets.
All statistical analyses were performed using SPSS version 19.0 (IBM,
Armonk, New York) and level of significance was established a priori at
P ≤ 0.05.
4. Results
4.1. Healthy participants
There was a significant, moderate association between CAR and MVIC (r = 0.62, P =
0.03), while AMT had an insignificant, weak association with MVIC (r = 0.34, P = 0.55).
An insignificant, weak association was also found between H:M and MVIC (r = 0.33, P =
0.57). The multiple-regression model using CAR, AMT and H:M predicted an insignificant
16% of the variance in quadriceps strength as measured by MVIC (R2 = 0.16, P = 0.22;
MVIC = 11.55CAR + 0.004AMT − 0.53H:M − 7.99; Table 2.1).
There was an insignificant, moderate association between CAR and AMT (r = 0.46,
P = 0.26). There were insignificant, moderate associations between AMT and H:M
(r = 0.41, P = 0.35), and between CAR and H:M (r = −0.42, P = 0.34).
4.2. All ACLr participants
There was a significant, strong association between CAR and MVIC (r = 0.78,
P b 0.001), while H:M had a significant, moderate association with MVIC (r = 0.66,
P = 0.01). A significant, moderate association was found between AMT and MVIC (r =
−0.62, P = 0.03). The multiple-regression model using CAR and H:M significantly pre-
dicted 47% of the variance in quadriceps strength as measured by MVIC; adding AMT
only increased the predictive capabilities of the model by 2%. (R2 = .49, P = 0.001;
MVIC = 3.12CAR + 1.59H:M − 0.006AMT − 0.226; Table 2.2).
There was a significant, moderate association between CAR and AMT (r = −0.64,
P = 0.01). There were insignificant, moderate associations between AMT and H:M (r =
−0.40, P = 0.41), and between CAR and H:M (r = 0.44, P = 0.30).
 A.S. Lepley et al. / The Knee 21 (2014) 736–742 739

Table 2 significant differences in age, height, mass, activity level, or months post-ACLr were ob-
Regression analyses performed using voluntary muscle activation, spinal-reflexive excit- served between subsets (Table 3). However, ACLr participants in the HS subset reported
ability and corticospinal excitability and to explain variance in quadriceps strength. significantly higher levels of self-reported function as scored by the IKDC (P = 0.03).

Step Variable R2 ΔR2 P

2.1. Control group 5. Discussion

1 CAR 0.16⁎ 0.16⁎; P = 0.03 P = 0.03
2 AMT 0.16 0.001; P = 0.86 P = 0.11 Quadriceps voluntary activation, spinal-reflexive excitability and
3 H:M 0.16 0.002; P = 0.79 P = 0.22
corticospinal excitability significantly predicted nearly half (49%) of
2.2. ACLr group the variance associated with quadriceps strength in 29 individuals
1 CAR 0.37⁎ 0.37⁎; P b 0.001 P b 0.001 with ACLr, although corticospinal excitability only increased the predic-
2 H:M 0.47⁎ 0.10⁎; P = 0.02 P b 0.001
tive capabilities of the model by 2%. The individual correlations imply
3 AMT 0.49⁎ 0.02; P = 0.40 P = 0.001
that increased voluntary activation, spinal-reflexive excitability and
2.2A. High strength ACLr subset corticospinal excitability relates with increased strength. However,
1 CAR 0.21 0.21; P = 0.11 P = 0.11
this association between our neural measures and quadriceps strength
2 H:M 0.38 0.17; P = 0.12 P = 0.08
3 AMT 0.40 0.02; P = 0.62 P = 0.18 was not observed in the healthy participants, with only higher volun-
tary activation relating to higher quadriceps strength. Based on this
2.2B. Low strength ACLr subset
finding, it may be inferred that alterations in neural pathways manifests
1 CAR 0.41⁎ 0.41⁎; P = 0.007 P = 0.007
2 AMT 0.43⁎ 0.02; P = 0.53 P = 0.02
as an underlying mechanism of quadriceps weakness following injury,
3 H:M 0.43 0.003; P = 0.79 P = 0.07 although the retrospective nature of this study does not allow for an in-
Abbreviations: ACLr, anterior cruciate ligament reconstruction; CAR, central activation
ference of causation. It does, however, provide researchers with prelim-
ratio; H:M, Hoffmann reflex normalized to maximal muscle response; AMT, active inary information to help understand the origins of quadriceps
motor threshold. weakness following ACLr. Recent reviews [2,3] have highlighted the
⁎ Significance at P ≤ 0.05. magnitude and significance of quadriceps strength deficits that can
persist long after ACLr, and although previous literature suggests that al-
4.3. High strength subset terations in neural pathways exist, their contribution to quadriceps
weakness has been understudied. Absence of a universally effective
Within the HS ACLr subset, there was an insignificant, strong association between CAR
and MVIC (r = 0.70, P = 0.11). H:M had an insignificant, moderate association with MVIC therapeutic approach to restore muscle strength following ACL injury
(r = 0.66, P = 0.13). An insignificant, weak association was found between AMT and emphasizes the need for novel strategies to target underlying contribu-
MVIC (r = − 0.07, P = 0.80). The overall multiple-regression model in the HS subset tions. Knowing that the neural contributions assessed in this study have
predicted 40% of the variance in quadriceps strength as measured by MVIC, however the potential to influence quadriceps muscle strength following injury
it was insignificant (R2 = 0.40, P = 0.18; MVIC = 3.21CAR + 1.07H:M − 0.004AMT +
0.180; Table 2.2A).
allows for further investigation into the modalities proposed to target
All associations between the predictor variables were insignificant and weak (CAR and these neural pathways, such as transcutaneous electrical nerve stimula-
AMT: r = 0.13, P = 0.95; AMT and H:M: r = 0.33, P = 0.71; CAR and H:M: r = 0.21, P = tion (TENS) [31], neuromuscular electrical stimulation (NMES) [32] or
0.88). electromyographic biofeedback (EMG BF) [33]. Future research could
aim to supplement traditional rehabilitation with modalities directed
4.4. Low strength subset
at improving neural influences, and determine if changes in these
Within the LS subset, a significant association was found between CAR and MVIC (r =
pathways overtime lead to improvements in muscle strength.
0.80, P = 0.007), while H:M had an insignificant, weak association with MVIC (r = 0.35, Among our three predictor variables for the ACLr group, voluntary
P = 0.63). An insignificant, moderate association was found between AMT and MVIC quadriceps activation had the greatest contribution to quadriceps
(r = −0.62, P = 0.13). The overall multiple-regression model in the LS subset predicted strength (r = 0.78, P b 0.001). Previous investigations have shown
43% of the variance in quadriceps strength as measured by MVIC, however it was insignifi-
that quadriceps activation is related to strength in healthy [34], ACL de-
cant (R2 = .43, P = 0.07; MVIC = 2.07CAR − 0.004AMT + 0.21H:M + 0.518; Table 2.2B).
All associations between the predictor variables were insignificant and either moder- ficient [15], and OA populations [35,36], and has long been suggested as
ate (CAR and AMT: r = −0.64, P = 0.10) or weak (AMT and H:M: r = −0.37, P = 0.58; a contributor to quadriceps strength deficits following ACLr [2,18]. Addi-
CAR and H:M: r = 0.29, P = 0.75). tionally, changes in voluntary activation over the course of a therapeutic
exercise program in patients with OA have explained changes observed
4.5. Differences between high strength and low strength ACLr subsets in quadriceps strength [36], indicating that interventions that influence
ACLr participants who were allocated into the HS subset demonstrated significantly
quadriceps activation may be beneficial for increasing quadriceps
higher CAR (P = 0.04) and H:M (P = 0.03) values than those in the LS subset. No signif- strength. Physiologically this finding is logical, as reduced voluntary
icant difference was seen in AMT between the high and low strength subsets (Table 3). No activation is thought to decrease the recruitment and/or firing rate of

Table 3
Differences between high strength and low strength ACLr subsets.

Demographic High strength Low strength t P

n 13 (6 female; 7 male) 16 (14 female, 2 male)

Age (years) 21.5 ± 4.9 21.0 ± 2.5 −0.38 0.70

Height (cm) 174.2 ± 10.7 167.8 ± 8.4 −1.75 0.08
Mass (kg) 75.0 ± 17.1 71.2 ± 18.6 −0.57 0.56
Months post-ACLr 50.0 ± 39.5 46.8 ± 33.1 −0.23 0.81
IKDC index 88.5 ± 9.0 80.8 ± 8.8 −2.29 0.03⁎
Tegner activity level 6.6 ± 1.8 5.4 ± 2.0 −1.65 0.11
Quadriceps MVIC/body mass (Nm/kg) 2.67 ± 0.76 2.12 ± 0.53 −7.10 b0.001⁎
Quadriceps CAR (%) 92.7 ± 4.8 84.4 ± 14.0 −2.10 0.04⁎
Quadriceps H:M 0.331 ± 0.142 0.211 ± 0.147 −2.20 0.03⁎
Quadriceps AMT (%) 39.3 ± 11.1 47.6 ± 19.1 −1.37 0.18

Abbreviations: ACLr, anterior cruciate ligament reconstruction; IKDC, International Knee Documentation Committee; CAR, central activation ratio; H:M, Hoffmann reflex normalized to
maximal muscle response; AMT, active motor threshold.
⁎ Significance at P ≤ 0.05.
740 A.S. Lepley et al. / The Knee 21 (2014) 736–742
alpha motor neurons, thus decreasing force production of the muscula-
ture [20]. Spinal-reflexive excitability had the next highest contribution
to strength in our model, which is also reasonable considering that
quadriceps inhibition has been hypothesized to result from altered affer-
ent reflexive information that is transmitted from the injured joint [20].
This altered muscle response is considered a protective mechanism de-
signed to limit further joint damage, and likely contributes to deficits
in strength following ACLr. This is further highlighted by the insignificant
relationship found between spinal-reflexive excitability and quadriceps
strength in our healthy participants. The reduction in afferent informa-
tion from the damaged ACL mechanoreceptors may create an underlying
mechanism of quadriceps weakness, creating the significant association
between spinal-reflexive excitability and quadriceps strength.
Our entire regression model consisting of voluntary activation,
spinal-reflexive excitability and corticospinal excitability was signifi-
cant in the ACLr group; however, the predictive capabilities were only
improved by 2% when corticospinal excitability was entered into the
model. It is possible that neural deficits following injury largely reside
in the spinal cord, potentially due to the loss of afferent feedback
from mechanoreceptors as stated previously, as opposed to altered
corticospinal mechanisms. In contrast, individual correlations per-
formed prior to the regression analysis revealed a strong correlation
between corticospinal excitability and quadriceps strength in the
ACLr group (r = 0.62, P = 0.03). Insignificant contribution from
corticospinal excitability into the regression model may also be
explained by its significant relationship with voluntary activation (r =
−0.41, P = 0.01). Therefore, the insignificant contribution may be the
result of the inherent shared variance between the variables, rather
than indicating corticospinal excitability has no influence on quadriceps
strength. It is plausible that descending corticospinal pathways, which
have a direct effect on discharging motor units and initiating motor neu-
ron activity [37], have a large influence on voluntary activation deficits
following injury. Based on these current data, however, these conclu-
sions cannot be made. As movement generating neural pathways
could potentially influence voluntary activation, future research could
investigate how both corticospinal and spinal-reflexive pathways affect
voluntary muscle activation.
It is important to consider other factors not included in this model
that may contribute to muscle strength, such as the morphology of the
muscle. Previous research has demonstrated in ACL deficient [15] and
OA [13] populations that the combination of voluntary muscle activa-
tion and muscle cross sectional area can account for upwards of 85% of
the variance seen in quadriceps strength. This relationship has also
been demonstrated in the ankle musculature following malleolar frac-
tures [14]. Although muscle atrophy may be an important component
to strength loss, these studies report that neural alterations contribute
nearly twice as much as muscle atrophy does to strength deficits.
These authors propose that targeting neural factors during rehabilita-
tion periods would be beneficial for the restoration of muscle strength.
In agreement, previous investigations have demonstrated that follow-
ing two [38] to six [39] weeks of muscle unloading, a typical non-
weight bearing time frame following ACLr, strength decrements can
be better explained by neural factors as opposed to muscle size or
fiber type. In contrast, Krishnan et al. [40] found that changes in muscle
contractile properties significantly contributed to quadriceps weakness
following ACLr, indicating that peripheral adaptations in the muscle
itself can lead to deficits in muscle strength. It is known that both mor-
phological and neural adaptations are responsible for modifying muscle
strength, and these two are systematically connected [10]. Therefore,
ACLr individuals likely experience alterations in both neural (spinal-
reflexive, corticospinal excitability) and morphological (fiber size,
fiber type) characteristics of the muscle, which likely interact and
collectively explain deficits in quadriceps strength that are commonly
observed. Further investigation is warranted to understand how muscle
atrophy and fiber type distribution, in conjunction with neural compo-
nents, affect quadriceps strength following ACLr.
When the 29 ACLr participants were separated into subsets based on
quadriceps strength, the predictive capability of our neural measures to
explain quadriceps strength was diminished. No significant association
was found within the HS ACLr subset, however the combination of vol-
untary activation and corticospinal excitability significantly explained
43% of the variance in quadriceps strength in the subset with LS. Similar
to when examining all ACLr participants, entering corticospinal excit-
ability into the model added an insignificant improvement of 2%,
again, likely explained by the moderate correlation, and potential
shared variance between corticospinal excitability and voluntary activa-
tion. Lack of correlation between the neural measures and quadriceps
strength when examining the HS and LS subsets may be explained
by insufficient statistical power (HS: 1-ß = 0.49; LS: 1-ß = 0.69) as
compared to the whole ACLr group (1-ß = 0.99).
The LS subset demonstrated significantly lower levels of voluntary
activation and spinal-reflexive excitability when compared to the HS
subset. The LS ACLr individuals also presented with higher AMT's, or
lower corticospinal excitability, however this comparison was insignifi-
cant. Our HS ACLr individuals, therefore, were more activated with
higher levels of neural excitability than our LS subset, corroborating
our original conclusion that increased voluntary activation, spinal-
reflexive excitability and corticospinal excitability relates with in-
creased strength. Quadriceps activation deficits are commonly reported
following ACLr [18], and have long been suggested as a means to in-
crease strength following both ACLr [3,15,18] and in those with OA
[35,36]. Less is known regarding alterations in neural pathways, howev-
er deficits in spinal-reflexive [17] and corticospinal [16] excitability
have been demonstrated in the literature. To our knowledge, this is
the first investigation to illustrate that these neural measures, along
with voluntary activation, are associated with strength in the ACLr pop-
ulation. Our results reinforce previous recommendations [3,19] that
rehabilitation strategies used to target neural alterations would be
beneficial for the restoration of muscle strength, and help combat
the persistent nature of quadriceps weakness. Specifically, neural
alterations have been observed following acute injury [13,15] and
experimental effusions [17,20], suggesting that modalities used to tar-
get neural excitability should be incorporated early in the rehabilitation
process, prior to utilizing traditional strengthening exercises aimed at
increasing muscle size [19]. However, future research is needed to un-
derstand if manipulating neural excitability and voluntary activation
levels during therapeutic rehabilitation will result in greater strength
gains.
A secondary finding of this investigation revealed that stronger ACLr
individuals demonstrated significantly higher levels of self-reported
function than those who were weaker. This finding strengthens recent
evidence [8,9] which demonstrated that quadriceps strength is greatly
associated with self-reported function, with increased strength relating
to increased function. This further highlights the significance of under-
standing the underlying mechanisms that lead to persistent quadriceps
weakness following ACLr. Patient perceived function is of utmost
importance in clinical research; thus, knowing potential strategies by
which to correct self-reported disability is essential. An important next
step in this research is to understand how these neural factors, as well
as strength, affect movement patterns and joint forces, and their poten-
tial relationship to the development of post-traumatic OA.
As with any investigation, this study is not without limitations. There
was a wide range of months post ACLr reported (48.2 ± 35.5 months
post ACLr; range 6–134 months) and a total of 3 graft types used
(patellar tendon autograft, n = 12; hamstring tendon autograft, n =
14; and cadaver allograft, n = 3). Instead of allowing for interpretations
regarding a single surgical technique or time frame following ACLr, the
findings of this research adds a generalized understanding of an ACLr
population as a whole. A comprehensive evaluation of the neural and
morphological contributions to quadriceps strength was not used.
Previous works [16–18] that demonstrated alterations in the neural
measures chosen for this study provided the rationale for utilizing
 A.S. Lepley et al. / The Knee 21 (2014) 736–742
these measures in this model. Other neural measures, such as the
volitional wave or motor evoked potentials, as well as structural compo-
nents such as muscle cross sectional area and fiber type, may contribute
to quadriceps strength and add to the predictive capabilities of our
current model. Additionally, this research cannot speculate on the effect
neural excitability has on joint surface contact forces, joint congruency
or ligament tensions, which could be a focus of future research. Lastly,
the strategy we used to separate participants into HS and LS ACLr subsets
may be seen as a limitation. The individuals placed into the high strength
subset may not have high levels of quadriceps strength; rather they have
the highest levels of strength among the 29 ACLr participants included in
this study. As no normative values exist to determine the average level of
quadriceps strength following ACLr, and the wide range of months post
ACLr used in this investigation, we felt this to be the most appropriate
way to delineate subsets based on quadriceps strength.
6. Clinical implications
The results of the current study suggest that neural alterations in ACL
individuals contribute to quadriceps strength deficits following injury
and surgical reconstruction. Targeting neural impairment is often
overlooked in traditional rehabilitation [19], therefore modalities
proposed to target neural alterations may help in the reinstitution of
quadriceps strength. Specifically, modalities such as TENS [19,31],
NMES [32] and EMG BF [33] have been hypothesized to positively affect
spinal-reflexive and corticospinal excitability. TENS and NMES is
thought to increase excitatory signals being sent from the joint, thereby
disinhibiting the surrounding musculature, and EMG BF provides
individuals visual and auditory cues and allows them to quantify a phys-
iological event, potentially affecting strength by improving motor unit
recruitment and/or optimizing firing rates through cortically generated
mechanisms [33]. Therefore, the supplementation of these modalities
into traditional rehabilitation programs may help to maximize quadri-
ceps strength post-injury and reconstruction.
7. Conclusion
In conclusion, quadriceps voluntary activation, spinal-reflexive
excitability and corticospinal excitability significantly predicted nearly
half of the variance associated with quadriceps strength in ACLr partic-
ipants, however corticospinal excitability only increased the predictive
capabilities of the model by 2%. Stronger ACLr participants also showed
higher levels of voluntary quadriceps activation, spinal-reflexive and
corticospinal excitability, suggesting that increases in these neural mea-
sures relates with increased quadriceps strength. Voluntary activation
was the only significant predictor among the healthy group. Future
research is warranted to understand if modalities proposed to target
these neural mechanisms are beneficial in restoring and maintaining
levels of quadriceps strength following ACLr.
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