105:1146-1155, 2008. First published Aug 7, 2008; doi:10.1152/japplphysiol.01339.

2007 J Appl Physiol

James M. Dundon, John Cirillo and John G. Semmler
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, July 1,2009; 102(1): 413-423. J Neurophysiol
T. J. Dartnall, N. C. Rogasch, M. A. Nordstrom and J. G. Semmler
Discharge Patterns in Elbow Flexor Muscles
Eccentric Muscle Damage Has Variable Effects on Motor Unit Recruitment Thresholds and
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Low-frequency fatigue and neuromuscular performance after exercise-induced
damage to elbow exor muscles
James M. Dundon, John Cirillo, and John G. Semmler
Discipline of Physiology and Research Centre for Human Movement Control, School of Molecular and Biomedical Science,
The University of Adelaide, Adelaide, Australia
Submitted 17 December 2007; accepted in nal form 6 August 2008
Dundon JM, Cirillo J, Semmler JG. Low-frequency fatigue and
neuromuscular performance after exercise-induced damage to elbow
exor muscles. J Appl Physiol 105: 11461155, 2008. First published
August 7, 2008; doi:10.1152/japplphysiol.01339.2007.The purpose
of this study was to quantify the association between low-frequency
fatigue (LFF) and the increase in EMG and force uctuations after
eccentric exercise of elbow exor muscles. Ten subjects performed
two tasks involving voluntary isometric contractions of elbow exors:
a maximum voluntary contraction (MVC) and a constant-force task at
ve submaximal target forces (5, 10, 20, 40, 60% MVC) while EMG
was recorded from biceps and triceps brachii. A third task involved
electrical stimulation of biceps brachii at 12 frequencies (1100 Hz).
These tasks were performed before, after, and 2 h and 24 h after
concentric or eccentric exercise. MVC force declined after eccentric
exercise (34% decline) and remained depressed 24 h later (22%
decline), whereas the reduced force following concentric exercise
(32%) was recovered 2 h later. Biceps brachii EMG and force
uctuations during the submaximal voluntary contractions increased
after eccentric exercise (both 2 greater) with the greatest effect at
low forces. LFF was equivalent immediately after both types of
exercise (5060% reduction in 20:100 Hz force) with a slower
recovery following eccentric exercise. A signicant association was
found between the change in LFF and EMG (r
2
values up to 0.52),
with the strongest correlations observed at low forces (20% MVC)
and at 2 h after exercise. In contrast, there were no signicant
associations between LFF and force uctuations during voluntary or
electrically evoked contractions, suggesting that other physiological
factors located within the muscle are likely to be playing a major role
in the impaired motor performance after eccentric exercise.
motor performance; eccentric exercise; motor unit; electrical stimu-
lation
IT HAS LONG BEEN RECOGNIZED that unaccustomed eccentric
exercise, which involves the active lengthening of muscle
during tasks such as walking downhill, results in muscle
damage that can produce debilitating and long-lasting effects
on muscle function. In particular, the consequences of this
muscle damage include a shift in optimum muscle length for
force generation, a rise in passive muscle tension, and a decline
in maximum force-generating capacity of the muscle (see 26
for review). Despite the known effects on maximal contrac-
tions, recent evidence has indicated that these changes in
muscle function may inuence neuromuscular performance
during submaximal tasks. For example, several studies have
shown that eccentric exercise produces a more than propor-
tional increase in EMG at low forces, which results in an
abnormal nonlinear relation between muscle force and EMG
(31, 35). Furthermore, eccentric exercise has been shown to
result in impaired motor performance, as shown with increased
postural tremor (29) and increased isometric force uctuations
(19), particularly at low force levels (31).
Although several mechanisms are possible (see 31), one of
the most appealing explanations for an increase in EMG and
force uctuations after eccentric exercise involves an increase
in low-frequency fatigue. Low-frequency fatigue is the dispro-
portionate loss of force at low compared with high frequencies
of electrical stimulation and is induced following fatiguing
exercise (7, 15, 22), with the greatest effect after eccentric
exercise (15, 22). Low-frequency fatigue is caused by an
impairment of one or more processes of excitation-contraction
coupling (7), most likely due to a decrease in calcium release
from the sarcoplasmic reticulum (3, 36), with the prolonged
recovery after eccentric exercise possibly due to damage and
subsequent repair of the contractile machinery within the
muscle (38). Several authors have suggested that low-fre-
quency fatigue would lead to increased muscle activation (6,
11, 28), as single motor units discharging at low rates would no
longer be producing an equivalent force, necessitating the
recruitment of additional motor units and an increase in dis-
charge rate of the already active motor units to compensate for
the force loss. Although the decit in force with low-frequency
fatigue can be substantial (50% or more) and long lasting
(hours to days), the consequences of this aspect of fatigue have
not been established (14).
The purpose of this study was to quantify the association
between low-frequency fatigue and the increase in EMG and
force uctuations observed after concentric and eccentric ex-
ercise of the elbow exor muscles. To achieve this goal, we
have assessed low-frequency fatigue following electrical stim-
ulation of the biceps brachii muscle and compared it with
biceps brachii EMG and elbow exor force uctuations ob-
tained before and after concentric and eccentric exercise. On
the basis of our previous study (31), we have included an
additional measure of EMG and force uctuations obtained at
2 h after eccentric exercise, as this is likely to coincide with the
point of maximum muscle damage while allowing recovery
from metabolic fatigue (32, 34). Furthermore, in contrast to
previous studies (15, 22), we have examined low-frequency
fatigue after concentric and eccentric exercise when the im-
pairment in maximum force is equivalent under both condi-
tions. Using this protocol, we expect to nd greater low-
frequency fatigue of the biceps brachii after eccentric com-
pared with concentric exercise (15, 22). We also expect that the
Address for reprint requests and other correspondence: J. G. Semmler,
School of Molecular and Biomedical Science, The Univ. of Adelaide, Ad-
elaide, South Australia 5005, Australia (e-mail: john.semmler@adelaide.
edu.au).
The costs of publication of this article were defrayed in part by the payment
of page charges. The article must therefore be hereby marked advertisement
in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
J Appl Physiol 105: 11461155, 2008.
First published August 7, 2008; doi:10.1152/japplphysiol.01339.2007.
8750-7587/08 $8.00 Copyright 2008 the American Physiological Society http://www. jap.org 1146

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increase in low-frequency fatigue will be associated with the
increase in EMG and force uctuations following eccentric
exercise. These ndings would suggest that increased low-
frequency fatigue may contribute to the nonlinear EMG-force
relation and be detrimental to the performance of submaximal
contractions after eccentric exercise.
METHODS
Ten male subjects (age 21 0.6 yr) with no recent injury or
musculoskeletal pain in the upper limb performed two protocols
consisting of either concentric exercise (left arm) or eccentric exercise
(right arm) on separate days, separated by at least 1 wk. Subjects were
randomly assigned which protocol they performed rst. Written in-
formed consent was obtained from all subjects before the beginning of
the experiment, and all procedures were approved by the Human
Research Ethics Committee at the University of Adelaide.
Experimental Arrangement
The experimental arrangement was similar to that which has
been described in detail previously (31). Subjects were seated with
their forearm positioned vertically and supinated, with the upper
arm and forearm at a 90 angle. This allowed isometric force to be
measured in the sagittal plane. The forearm was tted with a
heat-moulded plastic cast and secured with two 1-in.-wide nylon
straps.
Electrical stimulation was applied to the biceps brachii muscle
through 5-cm
2
neurostimulation electrodes (PALS, Axelgaard
Manufacturing). The cathode was placed over the muscle belly and
the anode over the distal tendon. Force evoked from electrical
stimulation was recorded using a sensitive transducer (range 0112
N; model MLP-25, Transducer Techniques) located perpendicular
to the forearm at the level of the wrist and mounted on a custom-
ized manipulandum. Output from the force transducer was re-
corded on a digital tape recorder and displayed on an oscilloscope.
Surface EMG was recorded with bipolar electrodes (silver-silver
chloride, 4-mm diameter) placed 2 cm apart over the upper third of
biceps brachii and medial head of triceps brachii. A grounding
wrist strap acted as a common reference for all EMG recordings.
After the rst experimental session, electrodes and stimulation gel
pads were removed and their positions marked on the skin for
correct placement during the follow-up session performed 24 h
later. The EMG signals were amplied (5001,000), band-pass
ltered (high pass at 13 Hz, low pass at 1,000 Hz), and recorded on
a digital tape.
Experimental Procedures
Subjects performed three tasks, two requiring voluntary isometric
contraction of the elbow exor muscles (MVC and a constant-force
task) and a third task involving electrical stimulation of the biceps
brachii. The three tasks were performed before, immediately after, 2 h
after, and 24 h after either eccentric (right arm) or concentric exercise
(left arm). The tasks were performed 2 h after exercise as it was
expected that this would be the point of maximal muscle damage
without fatigue (34), whereas they were performed 24 h after exercise
as there is likely to be pain associated with delayed-onset muscle
soreness at this time.
MVC force. Subjects performed a 3-s ramp contraction (zero to
maximum) in the exion direction and then maintained the contrac-
tion for a further 3 s, receiving strong verbal encouragement. Subjects
performed multiple MVCs until two forces were within 5% of each
other. This task was then repeated in the extension direction. At least
1 min of recovery was provided between contractions.
Constant-force task. Submaximal isometric contractions were
performed at target forces of 5, 10, 20, 40, and 60% MVC
expressed relative to the MVC that preceded the submaximal
contraction. This was performed to normalize the target force to
the maximum force capability of the muscle at that particular time
point, with the expectation that EMG should scale linearly with
increasing force. A less sensitive force transducer (range 0670 N;
model MLP-150, Transducer Techniques) recorded force for both
the MVC and constant-force tasks. Subjects were instructed to
match a target elbow-exor force as closely as possible for 12 s
that was represented by a horizontal line located on an oscillo-
scope. The horizontal target line on the oscilloscope remained in
the same location for each target force by adjusting the gain on the
vertical axis. Constant-force tasks were randomized with 30 s
recovery between tasks.
Electrical stimulation. To determine the stimulus intensity for the
force-frequency measurements, trains of stimuli (1-s train duration,
0.1-ms stimulus duration) were delivered at 100 Hz with a Digi-
timer (Hertfordshire, UK) DS7A constant-current stimulator that
was externally triggered using an appropriate output pulse from a
digital-to-analog converter (model 1401) generated using Spike 2
(Cambridge Electronic Design, Cambridge, UK). The amplitude of
the stimulus gradually increased until a 10% MVC was achieved.
This intensity equated to 25% of the total force-generating
capacity of biceps brachii, which was determined from preliminary
experiments involving supramaximal stimulation in a previous
study using a similar protocol (30). This intensity was selected to
reduce discomfort from the electrical stimulation and to avoid
unwanted activation of the triceps brachii muscle. Previous studies
have shown that the results obtained with submaximal electrical
stimulation provide a reliable estimate of the contractile properties
of the whole muscle (7, 13). At this intensity, 12 trains of stimuli
at various frequencies (1, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100
Hz) were delivered randomly to the biceps brachii muscle with a
rest period of 10 s between stimuli. All subjects tolerated the
intensity and frequency of stimulation.
Exercise
Eccentric exercise. Subjects were seated at a bench that consisted
of an adjustable height seat and a padded support for the upper arm
that was positioned 45 degrees from the torso and their forearm held
vertically. A load was placed in the hand by the experimenter, and
subjects lowered the weight from an elbow joint angle of 45
(forearm held vertical) to full extension (135 range of motion) by
eccentrically contracting the elbow exor muscles. The load was set
to 40% of the subjects isometric MVC obtained at 90 exion (24,
25). Each eccentric contraction lasted 3 s followed by a 3-s rest and
was performed in time with a metronome. During the rest period, the
experimenter removed the load, and the subject returned his arm to the
starting position. Exercise consisted of 10 repetitions per set, and each
set was separated with a 20-s rest interval. Exercise continued until the
subjects MVC decreased by at least 30%. This was regularly assessed
on a separate testing apparatus by performing brief MVCs after every
set of 10 contractions once there were visible signs of tremor and
verbal conrmation from the subject that he was having difculty
controlling the load during the contraction. The required force reduc-
tion was achieved with 30170 contractions in all subjects.
Concentric exercise. In a separate session, subjects lifted the load
from full elbow extension to a fully exed position (135 range of
motion) over 3 s, with 3 s rest between contractions. The experimenter
removed the load following the concentric contraction, and the subject
returned the arm to a fully extended position. The load during
concentric exercise was set to 30% MVC (35). Ten repetitions were
performed followed by 20 s rest between sets. Exercise continued
until subjects MVC decreased by 30%, which required from 50 to
165 contractions for all subjects.
Muscle damage. In addition to the reduction in maximal force,
muscle damage was assessed using two other indirect indicators.
Relaxed elbow angle was measured using three landmarks of the arm:
1147 LOW-FREQUENCY FATIGUE AND NEUROMUSCULAR PERFORMANCE
J Appl Physiol VOL 105 OCTOBER 2008 www.jap.org

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the midpoint of the acromion and coracoid process, the lateral epi-
condyle of the humerus, and the midpoint of the ulnar and radius
styloid processes. These three points were marked with a permanent
ink pen to facilitate comparisons between days. With the subjects arm
hanging relaxed by his side, a goniometer was lined up to the three
points and the elbow angle was recorded. Subjects were asked to rate
their pain within the muscle using a visual analog scale (0 no pain,
10 extremely painful) during forced extension of the elbow joint,
which was performed with the experimenter slowly moving the
forearm to 180 (full extension). Relaxed elbow angle and pain were
measured before exercise and at the conclusion of each testing session
(immediately after, 2 h after, and 24 h after exercise).
Data Analysis
All recorded signals were downloaded onto a computer hard drive
using a 16-bit analog-to-digital converter (model 1401, CED) and
sampled at either 200 Hz (MVC and submaximal force) or 2,000 Hz
(EMG and electrical stimulation force). All data were analyzed ofine
using customized scripts within the Spike2 data analysis software. The
EMG from the MVC was full-wave rectied, and the average EMG
was measured during a 1-s period at the point of maximum force
production. During the constant-force task, a 10-s sample of force
during the middle of the trial was used to calculate the mean and
coefcient of variation (CV) of force, which is used to quantify force
uctuations. EMG from biceps brachii and triceps brachii was recti-
ed and averaged over a user-dened 1-s period corresponding to a
stable portion of the EMG and force record. EMG obtained during the
constant-force task was normalized to the maximum EMG obtained
during the most recent MVC to facilitate comparisons between sub-
jects and across time periods. To calculate force variability during the
electrical stimulation task, the mean force was calculated from the
middle 0.5 s of the contraction. The SD and CV of force were
quantied over the same time epoch after removing any slow drift in
force with a detrending procedure using a digital high-pass lter at
0.5 Hz.
Statistical Analysis
For MVC, maximum elbow exor force was analyzed with a
two-way ANOVA with a repeated-measures design, with one be-
tween-subject factor of exercise (eccentric, concentric) and one with-
in-subject factor of time (before, immediately after, 2 h after, and 24 h
after). For the constant-force tasks, a three-way repeated-measures
ANOVA for exercise, time, and force level (5, 10, 20, 40, and 60%
MVC) was used to compare CV of force and average EMG. A
two-way repeated-measures ANOVA for exercise and time was used
to compare 20:100 Hz force, which was used as an indicator of
low-frequency fatigue (7, 22). Correlations between changes in CV
and EMG with low-frequency fatigue were performed using simple
linear regression analysis. A two-way repeated-measures ANOVA for
exercise and time was used to compare both relaxed elbow angle and
pain. Signicant main effects in the ANOVA were analyzed using a
Fishers post hoc test that performed all possible comparisons. Sta-
tistical signicance was designated at P 0.05 for all comparisons,
and all values are reported as means SE.
RESULTS
Eccentric exercise caused a reduction in MVC by 35%
(312 14 N before exercise to 207 14 N immediately after
exercise, P 0.001), which was achieved with a mean load of
12.6 0.6 kg and required an average of 63 12 contractions.
MVC remained signicantly depressed 2 h (30%) and 24 h
after eccentric exercise (22%) despite some recovery (P
0.05; Fig. 1A). Concentric exercise also resulted in a reduction
in MVC of 35% (281 17 N before to 190 12 N
immediately after, P 0.001), which required an average of
99 12 contractions with a mean load of 8.0 0.4 kg. MVC
had recovered 2 h after (254 17 N) concentric exercise (Fig.
1A). Maximum EMG was not different between concentric and
eccentric exercise (exercise effect, P 0.14). Furthermore, the
maximum EMG at the different recording times was consistent
between the two exercise conditions (exercise time interac-
tion, P 0.99). No signicant differences were observed for
maximum triceps EMG between exercise conditions or at the
different recording times.
For other indicators of muscle damage, eccentric exercise
resulted in a decline in resting elbow angle immediately after
(10 reduction, P 0.003; Fig. 1B) and 2 h after (6, P 0.02)
eccentric exercise. The resting elbow angle had signicantly
Fig. 1. Indirect indicators of muscle damage obtained before, immediately
after, 2 h after, and 24 h after eccentric or concentric exercise. Data show
maximal voluntary contraction (MVC) force (A), resting elbow joint angle
(B), and muscle pain measured during forced extension of the elbow joint (C)
and expressed on a visual analog scale (VAS). MVC values were expressed
relative to the MVC obtained before exercise. Muscle pain following concen-
tric exercise was zero and therefore not shown. In B, open bars are eccentric
exercise, and lled bars are concentric exercise. *P 0.05 compared with
before exercise. #P 0.001 compared with concentric exercise.
1148 LOW-FREQUENCY FATIGUE AND NEUROMUSCULAR PERFORMANCE
J Appl Physiol VOL 105 OCTOBER 2008 www.jap.org

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recovered 24 h after eccentric exercise (P 0.07 compared
with before). There was no effect of concentric exercise on
relaxed elbow angle across all time points (P 0.8). Further-
more, during forced extension of the elbow joint, subjects
reported a signicant increase in pain of the biceps brachii
from 0 (no pain) before to 3 0.3 (moderate pain) 24 h after
eccentric exercise (P 0.001; Fig. 1C), which is indicative of
delayed-onset muscle soreness (22). Subjects reported no pain
following concentric exercise.
Constant-Force Task
Figure 2 shows original data for a single subject during an
electrical stimulation task and a 10% MVC constant-force task
before and after eccentric exercise. The MVC for this subject
was 347 N before, 247 N 2 h after, and 290 N 24 h after
eccentric exercise. After eccentric exercise there was a reduc-
tion in both the 20-Hz and 100-Hz force, with a greater relative
decline in force at 20 Hz. The 20:100 Hz ratio declined by
50% 2 h after (0.48 before to 0.23) eccentric exercise,
indicating an increase in low-frequency fatigue (7, 22). The
20:100 Hz force was not fully recovered 24 h after the exercise
(0.38). The constant-force trial for the same subject (Fig. 2,
bottom) shows biceps brachii and triceps brachii EMG as well
as force during a 10% MVC task. At each time point the target
force was normalized to the subjects maximum strength at that
time point, to ensure that the subject was contracting at the
same relative force. Despite this, biceps brachii EMG was 3%
of maximum EMG before exercise, 27% of maximum (8
larger) 2 h after, and 8% of maximum 24 h later. Similarly, the
CV of force during this trial was 2.7% before exercise, 4.1%
2 h after exercise, and 2.8% 24 h later.
When biceps brachii EMG was averaged over all subjects
and force levels, the EMG was signicantly greater for eccen-
tric (36.0 2.3% maximum) compared with concentric
(25.6 2.0% maximum) exercise (exercise effect, P 0.001).
The average biceps brachii EMG was greater immediately after
(33.1 3.2%, P 0.02) and 2 h after (37.4 3.4%, P
0.001) compared with before (22.6 2.4%) exercise (time
effect, P 0.001). Furthermore, the EMG was signicantly
increased immediately after (43.1 4.8%, P 0.001), 2 h
after (43.8 4.9%, P 0.001), and 24 h after (35.7 5.0%,
P 0.02) eccentric exercise when pooled for all force levels
compared with before (21.6 3.4%) exercise (exercise time
interaction, P 0.001). Figure 3 shows biceps brachii EMG at
ve different target force levels obtained before and after either
concentric (Fig. 3A) or eccentric (Fig. 3B) exercise. The largest
increase in EMG immediately after eccentric exercise was
observed at low forces (4 larger at 5% MVC, 2 larger at
60% MVC), with similar values obtained 2 h later (exercise
time force interaction, P 0.006). The EMG had signi-
cantly recovered 24 h later at low forces but remained elevated
at high forces (1.52 greater at 40 and 60% MVC). In
contrast, there were no differences in EMG observed immediately
after and 24 h after concentric exercise, although an increase in
EMG was observed at 40 and 60% MVC 2 h after concentric
exercise (P 0.05). In addition, there was increased triceps
brachii EMG (data not shown) immediately after (7.3 0.9%
maximum) and 2 h after (7.6 0.9% maximum) eccentric
Fig. 2. Data from one subject during electrical stimulation and a constant-force task at 10% MVC obtained before, 2 h after, and 24 h after eccentric exercise.
Top panel represents force produced at 20 Hz stimulation (shaded line) and 100 Hz stimulation (dark line). Bottom panel represents biceps brachii and triceps
brachii EMG and force during a constant-force task at 10% MVC.
1149 LOW-FREQUENCY FATIGUE AND NEUROMUSCULAR PERFORMANCE
J Appl Physiol VOL 105 OCTOBER 2008 www.jap.org

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exercise compared with before (5.0 0.4% maximum) exercise
(exercise time interaction, P 0.001). No change in triceps
brachii EMG was observed after concentric exercise.
The extent of force uctuations (CV of force) was measured
across a range of submaximal target force levels before and
after concentric (Fig. 3C) and eccentric exercise (Fig. 3D). The
CV of force was greater after eccentric (3.0 0.1%) compared
with concentric (2.0 0.1%) exercise (exercise effect, P
0.001). A signicant exercise time interaction (P 0.001)
and post hoc analysis showed that CV of force was larger
immediately after (3.8 0.2%), 2 h after (3.9 0.2%), and
24 h after (2.6 0.1%) eccentric exercise compared with
before exercise (1.8 0.1%; all P values 0.001). No
differences in the CV of force were observed after concentric
exercise except for a small increase immediately after (2.3
0.1%) compared with before exercise (1.9 0.1%, P 0.04).
Furthermore, there was a signicant increase in the CV of force
immediately after and 2 h after eccentric exercise at all force
levels. The increases in force uctuations were slightly larger
at low force levels (3 larger at 5% MVC, 2 larger at 60%
MVC). No signicant differences were observed in CV of
force at any target force level 24 h after eccentric exercise
compared with before exercise. The only effect on the CV of
force following concentric exercise was observed immediately
after exercise at low forces (5, 10, 20% MVC, P 0.02).
Electrical Stimulation
Peak force following electrical stimulation of the biceps
brachii was measured across a range of frequencies and ex-
pressed relative to the peak force obtained at 100 Hz (Fig. 4).
The effect of both forms of exercise was to shift the force-
frequency curve to the right (Fig. 4, A and B), indicating that a
lower force was produced at any given frequency of stimula-
tion after exercise. This effect was most pronounced at low
frequencies of stimulation when measured immediately after
both concentric and eccentric exercise. To quantify this shift in
the force-frequency curve, the ratio of 20:100 Hz peak force
was obtained as an indicator of the extent of low-frequency
fatigue (Fig. 4C), although this procedure may underestimate
the extent of low-frequency fatigue if a force plateau has not
been reached with high-frequency stimulation (see Fig. 4, A
and B). This analysis reveals that there was a signicant
decline (5060% reduction) in 20:100 Hz force immediately
after both concentric and eccentric exercise. For eccentric
exercise, the 20:100 Hz force was 0.53 0.04 before exercise
and 0.21 0.02 immediately after exercise (P 0.001),
whereas for concentric exercise it was 0.55 0.03 before and
0.26 0.02 immediately after exercise (P 0.001). No
signicant difference was observed in 20:100 Hz force be-
tween concentric and eccentric exercise when examined im-
mediately after exercise. However, there was a much faster
recovery of 20:100 Hz force after concentric compared with
eccentric exercise. At 2 h after eccentric exercise, the 20:100
Hz force was signicantly lower (55% reduction) compared
with 2 h after concentric exercise (24% reduction, P 0.001).
The 20:100 Hz force remained signicantly depressed (40%
reduction) 24 h after eccentric exercise but had recovered 24 h
after concentric exercise. Furthermore, the uctuations in force
at 20-Hz stimulation were larger in eccentric compared with
concentric exercise (exercise effect, P 0.02). Despite no
difference before exercise, the force uctuations were 3
larger immediately after and 2 larger 2 h after eccentric
compared with concentric exercise (exercise time effect,
P 0.004; Fig. 4D). No difference between exercise condi-
tions was observed at any time point with 100-Hz stimulation
(all CV values ranged from 0.40 to 0.53%).
Fig. 3. EMG and force uctuations during
voluntary contractions. Biceps brachii EMG
and elbow exor force uctuations during
constant-force tasks measured before, imme-
diately after, 2 h after, and 24 h after con-
centric (A, C) and eccentric (B, D) exercise.
CV, coefcient of variation of force. *P
0.05 immediately after and 2 h after exercise
compared with before exercise. #P 0.05
immediately after compared with before ex-
ercise. **P 0.05, 2 h after compared with
before exercise. ##P 0.05, 24 h after
compared with before exercise.
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Low-Frequency Fatigue, EMG, and Force Fluctuations
To assess the association between low-frequency fatigue and
the increase in EMG and force uctuations during voluntary
contractions, a linear correlation was performed for the change
(after before) in 20:100 Hz force compared with the change
(before after) in EMG and force uctuations (CV of force)
induced by concentric and eccentric exercise. A signicant
positive correlation indicated that an increase in low-frequency
fatigue (decrease in 20:100 Hz force) was associated with an
increase in EMG and force uctuations in individual subjects.
The data obtained immediately after exercise were excluded
from analysis, as there is likely to be a complex interaction
between several physiological factors in addition to low-fre-
quency fatigue that can inuence the EMG and force uctua-
tions. For example, greater extents of fatigue are associated
with a slowing of muscle ber conduction velocity (1) and
contractile speed (2), which are likely to inuence EMG
amplitude and force during voluntary contractions. Further-
more, alterations in muscle temperature with fatigue can also
affect muscle ber action potentials and motor unit twitch force
(9). Therefore, the relative contribution of the mechanisms
responsible for the increase in EMG and force uctuations are
likely to be most consistent when obtained 2 h and 24 h after
exercise. Furthermore, the data for concentric and eccentric
exercise were analyzed separately, because the type of exercise
performed had divergent effects on low-frequency fatigue and
neuromuscular performance, particularly at 24 h after exercise.
The association between the change in low-frequency fa-
tigue to the change in EMG and force uctuations after
eccentric exercise is shown in Table 1. Following exercise,
there were signicant associations between the change in
20:100 Hz force and the change in EMG when assessed 2 h and
24 h after exercise. The strongest associations were observed
2 h after eccentric exercise at moderate forces (r
2
range from
0.33 to 0.52 at 1040% MVC), with the highest correlation at
24 h (r
2
0.44) obtained at the 20% target force. In contrast,
there were no signicant associations between the change in
20:100 Hz force and the change in force uctuations at any
target force after eccentric exercise. For concentric exercise
(data not shown), the associations between the change in
Fig. 4. Force responses with electrical stim-
ulation. Force-frequency curves obtained be-
fore, after, 2 h after, and 24 h after concen-
tric (A) and eccentric (B) exercise. The ratio
of force produced at 20 Hz to that produced
at 100 Hz (20:100 Hz ratio) is expressed as
a percentage of that ratio obtained before
exercise (C). The CV of force at 20-Hz
stimulation was increased after eccentric but
not concentric exercise (D). *P 0.05 com-
pared with before exercise. #P 0.05, con-
centric vs. eccentric exercise. P 0.05
compared with after and 2 h after eccentric
exercise.
Table 1. Association between the change in low-frequency fatigue (20:100 Hz force) and the change in EMG and force
uctuations at each target force at 2 and 24 h after eccentric exercise
Force, %MVC
2 h After 24 h After Both
EMG CV EMG CV EMG CV
5 0.39 (NS) 0.07 (NS) 0.27 (NS) 0.18 (NS) 0.36 (0.006) 0.01 (NS)
10 0.35 (0.04) 0.001 (NS) 0.12 (NS) 0.26 (NS) 0.23 (0.03) 0.08 (NS)
20 0.52 (0.02) 0.10 (NS) 0.44 (0.04) 0.09 (NS) 0.45 (0.001) 0.15 (NS)
40 0.33 (0.01) 0.02 (NS) 0.34 (NS) 0.01 (NS) 0.34 (0.007) 0.03 (NS)
60 0.29 (NS) 0.04 (NS) 0.12 (NS) 0.31 (NS) 0.14 (NS) 0.14 (NS)
Mean 0.38 0.05 0.26 0.17 0.30 0.08
Values are the coefcient of determination (r
2
) with P values in parentheses. MVC, maximal voluntary contraction; CV, coefcient of variation of force; NS,
not statistically signicant.
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20:100 Hz force and the change in EMG (2 h, mean r
2
0.14;
24 h, mean r
2
0.25) and force uctuations (2 h, mean r
2

0.17; 24 h, mean r
2
0.11) were weak and largely nonsignif-
icant. Furthermore, we examined the association between the
change in low-frequency fatigue and force uctuations during
the 20-Hz electrical stimulation. There was no signicant
association between the change in 20:100 Hz force and the
change in CV of 20 Hz force at 2 or 24 h after exercise.
DISCUSSION
To induce muscle damage in the present study, we used an
eccentric exercise protocol that resulted in rapid changes in
relaxed elbow joint angle (increased passive tension), signi-
cant, and long-lasting declines in muscle strength, and subjec-
tive reports of increased muscle pain 24 h after the exercise
(delayed-onset muscle soreness), all characteristic signs of
muscle damage (24, 25). Using this protocol, we have con-
rmed previous reports indicating that eccentric exercise alters
the EMG-force relation and impairs motor performance during
submaximal isometric contractions (19, 31), even though the
subjects were contracting at the same relative force level before
and after exercise. We have extended these observations by
examining the association between changes in low-frequency
fatigue to the changes in EMG and force uctuations at
strategic time points after concentric and eccentric exercise.
The new ndings in this study include 1) increased biceps
brachii EMG and force uctuations 2 h after eccentric exercise,
which corresponds to the time of maximum muscle damage
without fatigue (34); 2) delayed recovery of low-frequency
fatigue after eccentric compared with concentric exercise,
despite similar initial reductions in maximum strength; and
3) a signicant positive association between the change in
low-frequency fatigue and the change in EMG after eccentric
exercise, with the greatest effects occurring at low to moderate
(1040% MVC) forces. These changes were most prominent
2 h after eccentric exercise, suggesting that these effects are
associated with neuromuscular adjustments as a result of mus-
cle damage induced by the exercise.
Increased EMG and Force Fluctuations with
Muscle Damage
In a previous study, we showed that eccentric exercise
resulted in an increase in elbow exor EMG and force uctu-
ations, with the greatest impact of the exercise apparent at low
forces (31). However, this effect was observed only in the
presence of putative muscle fatigue that occurred immediately
after the exercise and not 24 h later. In the present study, we
found that EMG and force uctuations were largest 2 h after
eccentric exercise, when there is likely to be no metabolic
fatigue (32, 34). Furthermore, in contrast to our previous study
(31), the increased EMG and force uctuations were still
elevated 24 h later, possibly because of the inclusion of
additional target forces biased toward low contraction levels.
These ndings after eccentric exercise therefore indicate that
the series of physiological and mechanical events that lead to
muscle damage alter the neural drive and impair motor perfor-
mance during submaximal isometric contractions in elbow
exor muscles for up to 24 h after exercise.
Prolonged Recovery of Low-Frequency Fatigue After
Muscle Damage
Low-frequency fatigue, originally described by Edwards
et al. (7), is characterized by a disproportionate loss of force at
low frequencies of stimulation, with a slow recovery process
(hours to days), and occurs in the absence of any metabolic
disturbance within the muscle (14). The mechanism of low-
frequency fatigue is likely to involve an impairment of one or
more of the processes associated with excitation-contraction
coupling, most likely from a diminished availability of calcium
(18), resulting in reduced calcium released per action potential
(3, 4). The sigmoidal relationship between force and intracel-
lular calcium concentration means that a small reduction in
calcium concentration will have the largest effect on force in
the steep portion of the curve (38), which is most likely to
occur when motor units are discharging action potentials be-
tween 10 and 30 Hz (see Fig. 4). Accordingly, we have
quantied low-frequency fatigue in the present study by
comparing the force responses with 20-Hz stimulation to
that of 100-Hz stimulation (15), with any decrease in the
ratio after exercise representing an increase in low-
frequency fatigue (17).
It is a commonly held view that low-frequency fatigue is
greater after eccentric compared with concentric or isometric
exercise (15, 22). However, in these often-cited studies, the
extent of metabolic fatigue (decline in maximal strength)
induced by the exercise was not equivalent under all exercise
conditions. For example, following isometric, concentric, and
eccentric exercise of the elbow exor muscles, Jones et al. (15)
showed that eccentric exercise resulted in a 50% reduction in
MVC and 20:100 Hz force that recovered slowly over the next
7 days. In contrast, there were minimal changes in MVC and
20:100 Hz force following isometric or concentric exercise. In
the present study, we have shown that when the decline in
maximal strength induced by concentric and eccentric exercise
is equivalent, the extent of low-frequency fatigue (20:100 Hz
force) is similar between the two conditions when assessed
soon (within minutes) after the exercise. Despite this, the
recovery of low-frequency fatigue following eccentric exercise
was signicantly prolonged, with a maximum difference be-
tween exercise conditions obtained 2 h after exercise. The
prolonged recovery of eccentric exercise is likely to be attrib-
uted to muscle damage induced by the stretching of active
muscle, where the eccentric exercise leads to sarcomere dis-
ruption and the opening of stretch-activated cation channels,
producing inward movement of sodium and calcium into the
sarcoplasm (40). The increase of sarcoplasmic calcium then
triggers proteolysis that is associated with muscle ber break-
down and repair (26). Therefore, the delay in the recovery of
low-frequency fatigue with eccentric exercise is likely to
reect a process of repair and regeneration with a time
course related to protein turnover, rather than metabolite
synthesis (14).
Low-Frequency fatigue and Neuromuscular Performance
Although an increase in low-frequency fatigue is a common
phenomenon after many types of exercise, it is not immediately
clear how this might inuence motor performance during
voluntary contractions. On a theoretical basis, however, low-
frequency fatigue would be expected to alter neural drive to the
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muscle during submaximal contractions, as the loss of force
from motor units discharging at low rates would require the
additional recruitment and increased discharge rate of active
motor units to compensate for the force loss (see 11, 28). In
support of this, de Ruiter et al. (6) showed that the presence of
low-frequency fatigue induced by a 50% submaximal isometric
fatiguing contraction of the quadriceps muscle was accompa-
nied by an increase in vastus lateralis motor unit discharge
rates of 4 Hz during postexercise contractions at 50% MVC.
When correlating the change in low-frequency fatigue with the
change in EMG after eccentric exercise, we found that the
amount of variability in EMG explained by low-frequency
fatigue ranged from 12 to 52%, with the strongest correlations
observed 2 h after exercise (Table 1). Furthermore, the stron-
gest correlations were observed at low to moderate forces
(540% MVC, Table 1), which are the target forces that are
likely to have a relatively large proportion of the active motor
units discharging on the steep portion of the force-frequency
curve.
The mechanisms responsible for a change in the relation
between surface EMG and force has been a topic of extensive
investigation over a number of decades. From these studies
under normal physiological conditions, it is generally accepted
that the EMG-force relation in different human muscles is
either linear, or there is a more than proportional increase in
EMG at high force levels (see 20). However, when the muscle
is damaged with eccentric exercise, there is an unusual EMG-
force relation where there is a more than proportional increase
in EMG at low forces. This type of EMG-force relation has
been observed previously in computer models of motor unit
activation and has been attributed to a narrowing of the force
range over which motor units are recruited (12). We provide
evidence that the increase in EMG at low forces is associated
with increased low-frequency fatigue after eccentric exercise,
and is a possible contributor to the abnormal EMG-force
relation when the muscle is damaged with eccentric exercise.
Although a compression of the recruitment range is a likely
consequence of low-frequency fatigue, the effect of eccentric
exercise on motor unit recruitment remains to be determined.
The ndings from the present study suggest that the occur-
rence of low-frequency fatigue may contribute to the increased
EMG that resulted in a nonlinear EMG-force relation, but only
when the muscle is damaged by eccentric exercise. There are at
least two reasons why there is increased EMG after eccentric
but not concentric exercise. First, the change in low-frequency
fatigue at 2 h after concentric exercise was less than half of
what it was after eccentric exercise, which may not be of
sufcient magnitude to inuence EMG under these experimen-
tal circumstances. Second, the greater low-frequency fatigue
after eccentric exercise is likely to be accompanied by other
neuromuscular adjustments due to muscle damage that may
accentuate the change in EMG after eccentric contractions. For
example, the damage to the muscle ber membrane could alter
the amplitude or frequency of the sarcolemmal action potential
(23), which may inuence the summation and cancellation of
the muscle ber action potentials when detected with surface
electrodes (16). Furthermore, we have recently shown that
motor unit synchronization is increased after eccentric exercise
(5), which can inuence EMG amplitude under some circum-
stances (39).
Due to the nature of the experimental techniques used to
assess low-frequency fatigue in humans, it is not possible to
directly compare the effects of muscle damage on the same
motor units that are activated with electrical stimulation and
voluntary contractions. The low-force voluntary contractions
performed in the present study recruit motor units according to
the size principle and are therefore likely to involve a high
proportion of slow-twitch motor units. In contrast, the classical
view is that peripheral electrical stimulation reverses the acti-
vation order in electrically evoked contractions and is likely to
include a higher proportion of fast-twitch motor units. This
comparison is also complicated by the nding that fast-twitch
motor units are preferentially damaged (10, 21) and display the
greatest low-frequency fatigue (27) after eccentric exercise,
although slow-twitch motor units are also affected (33). We
have attempted to account for these discrepancies by perform-
ing voluntary contractions over a range of contraction intensi-
ties (560% MVC) that presumably involve an increasing
contribution from higher-threshold motor units. We have com-
pared this with low-frequency fatigue using a procedure that
has been shown to provide a reliable indicator of whole muscle
contractile properties (13). This comparison produced the
strongest associations between the change in low-frequency
fatigue and the change in EMG after eccentric exercise at low
to moderate forces (Table 1). Because low-frequency fatigue is
largely manifested in motor units discharging at low rates, it
seems reasonable to suggest that the strongest associations
obtained at low to moderate forces are due to physiological
factors, rather than any methodological factors that may bias
the sampling to separate populations of motor units. The
weakest associations were observed at high forces, suggesting
that factors other than low-frequency fatigue may make a
greater relative contribution to the increased EMG under these
circumstances (see 31).
Several studies have attempted to examine the contribution
of low-frequency fatigue on motor performance with limited
success. In one such study, Smith and Newham (32) found that
there was no decrement in visuomotor-tracking performance of
the elbow joint with the development of low-frequency fatigue
after concentric or eccentric exercise and concluded that low-
frequency fatigue does not inuence skilled motor perfor-
mance. As eccentric exercise leads to increased force uctua-
tions and low-frequency fatigue, we have compared the change
in these dependent variables during voluntary and electrically
induced contractions in individual subjects to examine any
association between them. During voluntary contractions, it
was anticipated that low-frequency fatigue would lead to the
recruitment of larger motor units that is necessary to maintain
the required target force due to the loss of force experienced in
motor units discharging at low rates. It is the size of the last
recruited motor unit that has the greatest effect on force
uctuations, because it has the largest twitch force (according
to the size principle) and is most likely discharging at the
lowest, subtetanic rates (see 8). However, we found no asso-
ciation between the change in low-frequency fatigue and the
change in force uctuations during voluntary contractions after
eccentric exercise, indicating that the alteration in neural drive
and motor unit activity with low-frequency fatigue is not
manifested in the increased force uctuations under the exper-
imental conditions described in the present study. Furthermore,
during electrical stimulation of the muscle at 20 Hz, we
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found a substantial increase in force uctuations after ec-
centric exercise, but this was not associated with the in-
crease in low-frequency fatigue in individual subjects.
These ndings from electrical stimulation suggest that the
increased force uctuations after eccentric exercise are
largely attributed to peripheral factors that disrupt the force-
producing elements of the muscle but are not related to a
change in low-frequency fatigue.
In conclusion, we have used concentric and eccentric exer-
cise to induce low-frequency fatigue and used a regression
analysis to examine if a change in low-frequency fatigue is a
potential mechanism responsible for the altered neuromuscular
performance after eccentric exercise. Despite similar reduc-
tions in maximal strength, we found a delayed recovery of
low-frequency fatigue after eccentric exercise, which was as-
sociated with an increase in EMG during submaximal contrac-
tions. We found that the change in low-frequency fatigue after
eccentric exercise could explain up to 52% of the variability in
EMG, with the largest effects observed at low forces. We
regard this as an important association, considering that there
are several methodological factors that may act to weaken this
relation, and more direct tests are not feasible in human
subjects. We therefore suggest that eccentric contractions that
induce prolonged recovery of force at low frequencies may
contribute to increased neural drive and an abnormal EMG-
force relation during submaximal isometric contractions. In
contrast, there was no association between low-frequency fa-
tigue and increased force uctuations during voluntary or
electrically evoked contractions, suggesting that other physio-
logical factors related to the force-producing elements of the
muscle are likely to be playing a major role in the impaired
motor performance after eccentric exercise.
GRANTS
This research was supported by National Health and Medical Research
Council of Australia Grant 274307 awarded to J. G. Semmler.
REFERENCES
1. Bigland-Ritchie B, Donovan EF, Roussos CS. Conduction velocity and
EMG power spectrum changes in fatigue of sustained maximal efforts.
J Appl Physiol 51: 13001305, 1981.
2. Bigland-Ritchie B, Johansson R, Lippold OC, Woods JJ. Contractile
speed and EMG changes during fatigue of sustained maximal voluntary
contractions. J Neurophysiol 50: 313324, 1983.
3. Chin ER, Allen DG. The role of elevations in intracellular [Ca
2
] in the
development of low frequency fatigue in mouse single muscle bres.
J Physiol 491: 813824, 1996.
4. Chin ER, Balnave CD, Allen DG. Role of intracellular calcium and
metabolites in low-frequency fatigue of mouse skeletal muscle. Am J
Physiol Cell Physiol 272: C550C559, 1997.
5. Dartnall TJ, Nordstrom MA, Semmler JG. Motor unit synchronization
is increased in biceps brachii after exercise-induced damage to elbow
exor muscles. J Neurophysiol 99: 10081019, 2008.
6. de Ruiter CJ, Elzinga MJ, Verdijk PW, van Mechelen W, de Haan A.
Changes in force, surface and motor unit EMG during post-exercise
development of low frequency fatigue in vastus lateralis muscle. Eur
J Appl Physiol 94: 659669, 2005.
7. Edwards RH, Hill DK, Jones DA, Merton PA. Fatigue of long duration
in human skeletal muscle after exercise. J Physiol 272: 769778, 1977.
8. Enoka RM, Christou EA, Hunter SK, Kornatz KW, Semmler JG,
Taylor AM, Tracy BL. Mechanisms that contribute to differences in
motor performance between young and old adults. J Electromyogr Kine-
siol 13: 112, 2003.
9. Farina D, Arendt-Nielsen L, Graven-Nielsen T. Effect of temperature
on spike-triggered average torque and electrophysiological properties of
low-threshold motor units. J Appl Physiol 99: 97103, 2005.
10. Friden J, Sjostrom M, Ekblom B. Myobrillar damage following intense
eccentric exercise in man. Int J Sports Med 4: 170176, 1983.
11. Fuglevand AJ, Maceeld VG, Bigland-Ritchie B. Force-frequency and
fatigue properties of motor units in muscles that control digits of the
human hand. J Neurophysiol 81: 17181729, 1999.
12. Fuglevand AJ, Winter DA, Patla AE. Models of recruitment and rate
coding organization in motor-unit pools. J Neurophysiol 70: 24702488,
1993.
13. Hanchard NC, Williamson M, Caley RW, Cooper RG. Electrical
stimulation of human tibialis anterior: (A) contractile properties are stable
over a range of submaximal voltages; (B) high- and low-frequency fatigue
are inducible and reliably assessable at submaximal voltages. Clin Rehabil
12: 413427, 1998.
14. Jones DA. High-and low-frequency fatigue revisited. Acta Physiol Scand
156: 265270, 1996.
15. Jones DA, Newham DJ, Torgan C. Mechanical inuences on long-
lasting human muscle fatigue and delayed-onset pain. J Physiol 412:
415427, 1989.
16. Keenan KG, Farina D, Maluf KS, Merletti R, Enoka RM. Inuence of
amplitude cancellation on the simulated surface electromyogram. J Appl
Physiol 98: 120131, 2005.
17. Keeton RB, Binder-Macleod SA. Low-frequency fatigue. Phys Ther 86:
11461150, 2006.
18. Lannergren J, Westerblad H. Maximum tension and force-velocity
properties of fatigued, single Xenopus muscle bres studied by caffeine
and high K

. J Physiol 409: 473490, 1989.

19. Lavender AP, Nosaka K. Changes in uctuation of isometric force
following eccentric and concentric exercise of the elbow exors. Eur
J Appl Physiol 96: 235240, 2006.
20. Lawrence JH, De Luca CJ. Myoelectric signal versus force relationship
in different human muscles. J Appl Physiol 54: 16531659, 1983.
21. Lieber RL, Woodburn TM, Friden J. Muscle damage induced by
eccentric contractions of 25% strain. J Appl Physiol 70: 24982507, 1991.
22. Newham DJ, Mills KR, Quigley BM, Edwards RH. Pain and fatigue
after concentric and eccentric muscle contractions. Clin Sci (Lond) 64:
5562, 1983.
23. Piitulainen H, Komi P, Linnamo V, Avela J. Sarcolemmal excitability
as investigated with M-waves after eccentric exercise in humans. J
Electromyogr Kinesiol 18: 672681, 2008.
24. Prasartwuth O, Taylor JL, Gandevia SC. Maximal force, voluntary
activation and muscle soreness after eccentric damage to human elbow
exor muscles. J Physiol 567: 337348, 2005.
25. Prasartwuth O, Allen TJ, Butler JE, Gandevia SC, Taylor JL. Length-
dependent changes in voluntary activation, maximum voluntary torque
and twitch responses after eccentric damage in humans. J Physiol 571:
243252, 2006.
26. Proske U, Allen TJ. Damage to skeletal muscle from eccentric exercise.
Exerc Sport Sci Rev 33: 98104, 2005.
27. Rijkelijkhuizen JM, de Ruiter CJ, Huijing PA, de Haan A. Low-
frequency fatigue, post-tetanic potentiation and their interaction at differ-
ent muscle lengths following eccentric exercise. J Exp Biol 208: 5563,
2005.
28. Saugen E, Vollestad NK, Gibson H, Martin PA, Edwards RH. Disso-
ciation between metabolic and contractile responses during intermittent
isometric exercise in man. Exp Physiol 82: 213226, 1997.
29. Saxton JM, Clarkson PM, James R, Miles M, Westerfer M, Clark S,
Donnelly AE. Neuromuscular dysfunction following eccentric exercise.
Med Sci Sports Exerc 27: 11851193, 1995.
30. Semmler JG, Kutzscher DV, Enoka RM. Limb immobilization alters
muscle activation patterns during a fatiguing isometric contraction. Muscle
Nerve 23: 13811392, 2000.
31. Semmler JG, Tucker KJ, Allen TJ, Proske U. Eccentric exercise
increases EMG amplitude and force uctuations during submaximal con-
tractions of elbow exor muscles. J Appl Physiol 103: 979989, 2007.
32. Smith IC, Newham DJ. Fatigue and functional performance of human
biceps muscle following concentric or eccentric contractions. J Appl
Physiol 102: 207213, 2007.
33. Takekura H, Fujinami N, Nishizawa T, Ogasawara H, Kasuga N.
Eccentric exercise-induced morphological changes in the membrane sys-
tems involved in excitation-contraction coupling in rat skeletal muscle.
J Physiol 533: 571583, 2001.
34. Walsh LD, Hesse CW, Morgan DL, Proske U. Human forearm position
sense after fatigue of elbow exor muscles. J Physiol 558: 705715, 2004.
1154 LOW-FREQUENCY FATIGUE AND NEUROMUSCULAR PERFORMANCE
J Appl Physiol VOL 105 OCTOBER 2008 www.jap.org

o
n

N
o
v
e
m
b
e
r

1
5
,

2
0
0
9

j
a
p
.
p
h
y
s
i
o
l
o
g
y
.
o
r
g
D
o
w
n
l
o
a
d
e
d

f
r
o
m

35. Weerakkody N, Percival P, Morgan DL, Gregory JE, Proske U.
Matching different levels of isometric torque in elbow exor muscles after
eccentric exercise. Exp Brain Res 149: 141150, 2003.
36. Westerblad H, Duty S, Allen DG. Intracellular calcium concentration
during low-frequency fatigue in isolated single bers of mouse skeletal
muscle. J Appl Physiol 75: 382388, 1993.
37. Westerblad H, Allen DG. The effects of intracellular injections of
phosphate on intracellular calcium and force in single bres of mouse
skeletal muscle. Pugers Arch 431: 964970, 1996.
38. Westerblad H, Bruton JD, Allen DG, Lannergren J. Functional signif-
icance of Ca
2
in long-lasting fatigue of skeletal muscle. Eur J Appl
Physiol 83: 166174, 2000.
39. Yao W, Fuglevand RJ, Enoka RM. Motor-unit synchronization in-
creases EMG amplitude and decreases force steadiness of simulated
contractions. J Neurophysiol 83: 441452, 2000.
40. Yeung EW, Allen DG. Stretch-activated channels in stretch-induced
muscle damage: role in muscular dystrophy. Clin Exp Pharmacol Physiol
31: 551556, 2004.
1155 LOW-FREQUENCY FATIGUE AND NEUROMUSCULAR PERFORMANCE
J Appl Physiol VOL 105 OCTOBER 2008 www.jap.org

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