J Appl Physiol 124: 866–876, 2018.
First published December 14, 2017; doi:10.1152/japplphysiol.00971.2017.
RESEARCH ARTICLE
Unilateral strength training leads to muscle-specific sparing effects during
opposite homologous limb immobilization
X Justin W. Andrushko, Joel L. Lanovaz, Kelsey M. Björkman, Saija A. Kontulainen,
and Jonathan P. Farthing
College of Kinesiology, University of Saskatchewan, Saskatoon, Saskatchewan, Canada
Submitted 27 October 2017; accepted in final form 11 December 2017
Andrushko JW, Lanovaz JL, Björkman KM, Kontulainen SA,
Farthing JP. Unilateral strength training leads to muscle-specific
sparing effects during opposite homologous limb immobilization. J
Appl Physiol 124: 866 – 876, 2018. First published December 14,
2017; doi:10.1152/japplphysiol.00971.2017.—Cross education (CE)
occurs after unilateral training whereby performance of the untrained
contralateral limb is enhanced. A few studies have shown that CE can
preserve or “spare” strength and size of an opposite immobilized limb,
but the specificity (i.e., trained homologous muscle and contraction
type) of these effects is unknown. The purpose was to investigate
specificity of CE “sparing” effects with immobilization. The non-
dominant forearm of 16 participants was immobilized with a cast, and
participants were randomly assigned to a resistance training (eccentric
wrist flexion, 3 times/week) or control group for 4 weeks. Pre- and
posttesting involved wrist flexors and extensors eccentric, concentric
and isometric maximal voluntary contractions (via dynamometer),
muscle thickness (via ultrasound), and forearm muscle cross-sectional
area (MCSA; via peripheral quantitative computed tomography). Only
the training group showed strength preservation across all contrac-
tions in the wrist flexors of the immobilized limb (training: ⫺2.4% vs.
control: ⫺21.6%; P ⫽ 0.04), and increased wrist flexors strength of
the nonimmobilized limb (training: 30.8% vs. control: ⫺7.4%; P ⫽
0.04). Immobilized arm MCSA was preserved for the training group
only (training: 1.3% vs. control: ⫺2.3%; P ⫽ 0.01). Muscle thickness
differed between groups for the immobilized (training: 2.8% vs.
control: ⫺3.2%; P ⫽ 0.01) and nonimmobilized wrist flexors (train-
ing: 7.1% vs. control: ⫺3.7%; P ⫽ 0.02). Strength preservation was
nonspecific to contraction type (P ⫽ 0.69, ␩2p ⫽ 0.03) yet specific to
the trained flexors muscle. These findings suggest that eccentric
training of the nonimmobilized limb can preserve size of the immo-
bilized contralateral homologous muscle and strength across multiple
contraction types.
NEW & NOTEWORTHY Unilateral strength training preserves
strength, muscle thickness, and muscle cross-sectional area in an
opposite immobilized limb. The preservation of size and strength was
confined to the trained homologous muscle group. However, strength
was preserved across multiple contraction types.
bilateral transfer; cross education; cross transfer; eccentric strength;
muscle lengthening
INTRODUCTION
Cross education (CE) of strength occurs when unilateral
strength training produces performance improvement of the
Address for reprint requests and other correspondence: J. P. Farthing,
College of Kinesiology, Univ. of Saskatchewan, 87 Campus Dr., Saskatoon,
Saskatchewan, Canada S7N 5B2 (e-mail: jon.farthing@usask.ca).
866 8750-7587/18 Copyright © 2018 the American Physiological Society
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untrained contralateral limb (7, 36). Within the last decade,
there is renewed scientific interest in CE, on account of
evidence of preserved strength and muscle size in an opposite
immobilized limb (26). The allure of an immobilization model
in CE research is that disuse causes accelerated loss in neural
drive, strength, and muscle size (10, 12, 13, 52) and the
prospect of CE to attenuate these decrements can be explored.
To date, there are just four studies that have investigated the
effects of CE in healthy participants with an immobilization
model (20, 21, 40, 45). All four studies found that a CE
intervention attenuated the strength loss in the immobilized
limb. However, three of these studies also found a sparing
effect for muscle size (20, 40, 45). The mechanisms of muscle
size preservation are currently unclear. Current theory suggests
CE is probably driven by neural mechanisms (7, 36) rather than
muscle or morphological factors.
The discrepancy in findings for muscle size preservation
between Farthing et al. (21) and the other three studies (20, 40,
45) warrants further investigation. All four studies used ultra-
sound to image muscle thickness. Although ultrasound is a
valid and reliable as a muscle size measure (8), it is not
considered a gold standard measure. Revisiting these size
sparing effects with a measure of muscle cross-sectional area
(MCSA) from peripheral quantitative computed tomography
(pQCT) is an important step to confirm or refute the previous
findings (26).
Regardless of ambiguity around sparing of muscle size, the
strength sparing effects of CE are consistent in all prior studies.
The mechanistic link, if any, between the strength and size
sparing effects of CE is unknown. One approach to explore the
link between size and strength sparing effects with CE is to
investigate specificity. While CE of strength has been shown to
be specific to the homologous muscle in the untrained con-
tralateral limb (30, 37, 56), and to the contraction type (29) and
velocity (18) used in training, the specificity of CE has never
been tested for an immobilized limb. Specificity effects are
convincing indices of the involvement of neural mechanisms
(24); therefore, the sparing effects of CE are hypothesized to
demonstrate specificity. However, specificity effects may pres-
ent differently for an immobilized limb due to inhibited move-
ment, altered corticospinal excitability (4, 15, 38, 43, 54),
muscle atrophy and altered protein synthesis (1, 42), and
potential systemic effects (26) that could contribute globally to
muscle size sparing.
The observed sparing effect of CE has implications for
improving rehabilitation of an injured or neurologically im-
paired limb (11, 39, 44), with the goal of restoring symmetry
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 MUSCLE-SPECIFIC SPARING EFFECTS DURING IMMOBILIZATION
after unilateral injury (22). The concept of using CE for its
sparing effects during rehabilitation from injury has the poten-
tial to reduce the total time of recovery, particularly if therapy
is started before atrophy and strength deprivation begin to
occur (22). Understanding the specificity of sparing effects of
CE as it pertains to the type of contraction and antagonistic
muscle pairs can inform the design of effective training pro-
grams to optimize rehabilitation and recovery from injuries.
The purpose of this study was to examine muscle contraction
type and task specificity of CE in an immobilized left forearm
after 4 wk of eccentric (ECC) wrist flexion training of the right
arm. The primary hypothesis was that the CE sparing effects on
muscle strength and size would be specific to muscle (i.e.,
homologous wrist flexors, not extensors), task (i.e., flexion, not
extension), and type [i.e., ECC strength not concentric (CON)
and isometric (ISO) strength]. The secondary hypothesis was
that unilateral ECC training would result in the sparing of
MCSA in the immobilized limb, as measure by pQCT.
METHODS
Participants
Sixteen participants from the University of Saskatchewan student
population volunteered to participate in this study (Table 1). Partici-
pants were randomly assigned to an immobilized control (n ⫽ 8) or
training group (n ⫽ 8). Participants were right handed, as determined
by a handedness questionnaire, healthy (i.e., no physical injuries or
neurological conditions), and were classified as currently untrained
(⬍6 mo resistance training experience in the previous year, where 1
mo of experience is equal to resistance training on average 3 times per
week for 4 wk). Before the beginning of the study, written informed
consent was obtained. This study conformed to the standards set by
the Declaration of Helsinki and was approved by the University of
Saskatchewan Behavioural and Biomedical Research Ethics Board.
Participant’s handedness was determined with the Waterloo Hand-
edness Questionnaire (3). The questionnaire scores participants as
either right (indicated by a positive score) or left handed (indicated by
a negative score) on a scale of ⫹20 representing strong right-
handedness to ⫺20 representing strong left-handedness. Participants
were required to be right-handed for this study because previous
literature has demonstrated greater CE of strength in right-handed
individuals when training their dominant arm (16, 19). An a priori
sample size calculation for the between-within factorial ANOVA
design with power (1-␤) ⫽ 0.95 and ␣ ⫽ 0.05 was determined using
G*Power 3.1 (23). An effect size estimate of 0.51 was calculated from
a previous CE immobilization study (16). The sample size estimate
was 16 participants (n ⫽ 8 per group) for the primary outcome
measure of torque.
Intervention and Design
All participants received a cast on their left, nondominant, forearm
for 4 wk according to our previous method (20, 21). Casts were placed
by a physician, with the intent to immobilize the wrist, hand, thumb,
and part of the fingers up to the middle phalanges. Notches were cut
out of the cast at the proximal end, large enough for placement of
electrodes for electromyography (EMG) monitoring of the wrist
Table 1. Demographics
Group/Sex Age, yr Height, cm
Training (n ⫽ 8: 1 man and 7 women) 20 ⫾ 2 170.3 ⫾ 10.1
Control (n ⫽ 8: 2 men and 6 women) 23 ⫾ 5 169.3 ⫾ 8.5
Data are means ⫾ SD. WHQ, Waterloo handedness questionnaire.
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867
flexors during training sessions. The training group underwent
strength training of the right wrist flexors three times per week while
the immobilized control group did not train and were instructed to
refrain from other forms of exercise during their participation in the
study. Training involved maximal effort ECC isokinetic contractions
performed through 80° of motion (40° flexion to 40° extension) with
a fixed rotational velocity of 1.05 rad/s on an isokinetic dynamometer
(Humac NORM; CSMi, Stoughton, MA). Strength training was pro-
gressive, commencing with two sets of eight repetitions and pro-
gressed in volume up to six sets of eight, with a taper to two sets for
the last session. A 1-min rest was given between each set. Participants
were prompted to position their immobilized limb in the same pro-
nated orientation as the training limb and to relax it during all testing
and training sessions to minimize mirror activity (30). The mirrored
positioning of the immobilized limb was important in controlling for
possible confounding effects of the orientation of the wrist and
homologous or no-homologous mirror activity during unilateral
movements (47).
Measures
Familiarization and testing sessions. All participants underwent a
familiarization session as an introduction to all strength and stimula-
tion testing measures. Following familiarization, participants returned
to the laboratory within 7 days for two separate pretesting sessions.
Two pretesting sessions were used to determine variance of measures
and to establish a stable baseline. An average of the two pretesting
sessions for each strength, muscle activation, and muscle thickness
measure was used in data analysis. Data collection occurred in two
separate laboratories. Muscle thickness and strength measures were
assessed by the primary researcher in one laboratory, while MCSA
was collected in a separate laboratory by a single researcher blinded
to group assignment. For pre- and posttesting, muscle thickness was
always measured before strength. MCSA was scheduled before all
other tests whenever possible or with a minimum of 48 h allotted for
recovery. The scheduling of MCSA measures was strategic to avoid
the potential influence of forearm muscle contractions (possible
edema) on the accuracy of the measure. After the second pretesting
session, participants received the nondominant forearm cast, initiating
the intervention period. After the 4-wk intervention, participants
returned to the laboratory for cast removal followed by posttesting.
The order of posttesting was consistent with MCSA measured imme-
diately after cast removal (5.7 ⫾ 3.4 min) followed by muscle thick-
ness and strength testing.
Peak torque. All testing and training sessions used an identical
setup and were supervised and completed on an isokinetic dynamom-
eter. Testing sessions involved maximal effort isokinetic ECC, CON,
and ISO muscle actions of the wrist flexors and extensors. The
primary outcome measure was peak torque, which was recorded for
each contraction type over three sets of one repetition separated by
30 s and used as a measure of contraction specific strength. The
highest torque value achieved over the three maximal attempts was
used as the strength value on each occasion. For each contraction type,
wrist flexors were tested first followed by wrist extensors. The order
of limb testing (left or right arm) was randomized and held constant
for each participant for every testing session. A 1-min rest was given
between each test. ECC and CON muscle actions were performed
through 80° of motion (40° flexion to 40° extension) with a fixed
rotational velocity of 1.05 rad/s, with ISO muscle actions performed
Weight, kg WHQ Training Experience, mo
77.2 ⫾ 19.2 18.3 ⫾ 2.4 2.3 ⫾ 4.1
85.7 ⫾ 22.7 17.1 ⫾ 2.5 2.9 ⫾ 4.3
868 MUSCLE-SPECIFIC SPARING EFFECTS DURING IMMOBILIZATION

with a neutral wrist (3-s MVC at 0° of flexion). ISO contractions were markers) and overhead transparency film were used to ensure accu-
assessed first, followed by ECC and CON in a randomized order. racy on repeat occasions. Muscle thickness was determined by mea-
Participants were seated in an upright position, with the elbow at 90°, suring a linear distance on the image of the muscle from the edge of
and the forearm resting on a pad with the wrist in a pronated position the subcutaneous tissue to the edge of the bone. This method has been
grasping the dynamometer handle. Participants were instructed to rest previously used in our laboratory on the wrist flexors (21); however,
their immobilized limb on their lap with the forearm in a similar in the current study this method was also applied for the wrist
pronated position to be consistent with the wrist orientation of the extensors. Thickness measures were taken at a standardized location
training limb. Verbal encouragement was provided by the same of one-third the distance between the medial epicondyle and radial
experimenter for each test. The precision error [coefficient of variation styloid for the wrist flexors and one-third the distance between the
(CV%)] of our laboratory for the left and right forearm torque lateral epicondyle and the ulna styloid for the wrist extensors. At each
measures is 5.7 and 4.9%, respectively (19). testing session, four measurements were recorded for each muscle,
Muscle cross-sectional area. Single operator (K. Björkman), with the average of the two closest measures used for comparison.
blinded to the group randomization, obtained MCSA (cm2) from both Muscle activation. EMG data were recorded during pre- and
forearms (at 65% site of radius length) using pQCT (XCT2000; posttesting and during the 1st, 7th, and 12th training sessions. During
Stratec, Medizintechnik, Germany) and our standard protocols (25). pre- and posttesting, surface EMG (Grass EMG P511 AC amplifier;
MCSA was analyzed using the BoneJ plugin (Version 1.3.11) for the Grass Technologies, Middleton, WI; amplification of 1,000, band-
open-source software ImageJ (48). We separated muscle tissue from width of 10 to 1,000 Hz; and VERMED NeuroPlus; 2.5 cm2, Ag/Ag
subcutaneous fat using a threshold of 30 mg/cm3 and from bone using chloride sensor) was used to measure muscle activity in the agonist
a threshold of 280 mg/cm3. Operator’s precision error (CV%RMS) of and antagonist (wrist flexors and extensors) muscles and in the biceps
forearm MCSA was 1.8%, between repeated measures (⬎24 h apart) brachii and triceps brachii of the trained and untrained limbs. Elec-
of another university student sample (Table 2) and comparable with trodes for the flexor carpi radialis (FCR) muscle were placed one-third
earlier reported precision (25). MCSA from pQCT is highly correlated of the distance from the medial epicondyle to the radial styloid
(r ⫽ 0.78 – 0.92) to MCSA derived from MRI (51), but it is unable to following the recommendations from Buschbacher and Prahlow (5)
differentiate specific muscles (e.g., forearm flexors from extensors). and Zehr (55). The extensor carpi radialis (ECR) electrodes were
Pre- and posttesting MCSA was assessed in both arms of each group placed on the medial side of the brachioradialis, at one-fifth (approx-
(intervention and control) to assess the changes in the immobilized imately three finger widths) of the distance from the lateral epicondyle
and nonimmobilized limb over the duration of the study. During on a line with the second metacarpal (55). The electrodes on the
pretesting, pQCT was measured within 7 days after the familiarization biceps brachii were placed one-third of the distance from the fossa
session; posttesting pQCT was measured immediately post cast re- cubit on a line between the fossa cubit and the medial acromion. The
moval. triceps brachii long head electrodes were placed at the 50% mark
Muscle thickness. Muscle thickness of the wrist flexor and extensor between the posterior crista of the acromion and the olecranon at two
muscles during the pre- and posttesting sessions was assessed to finger widths medial to the line as per surface electromyography for
investigate the specificity of muscle size sparing effects. Muscle the noninvasive assessment of muscles guidelines (27). The EMG data
thickness was assessed using ultrasound (LOGIQ e BTO8; GE collected in the upper arm (biceps brachii and triceps brachii) were
Healthcare, Milwaukee, WI). Ultrasound has previously been used in used during testing to visually monitor muscle activation in real time
our laboratory with precision errors for the left and right forearm only; no offline analysis of these data was conducted. Participants
muscles of 1.5 and 1.4%, respectively (19) and is a valid and reliable were instructed to relax the upper arm during contractions. During the
assessment of muscle thickness (6, 8, 33). The procedure involved 1st, 7th, and 12th training sessions, EMG was measured in wrist
placing a probe with transmission gel on the surface of the skin over flexors of each arm and was used to determine the level of mirror
the bulk of the muscle while the limb was at rest in neutral position. activity occurring in the immobilized nontraining limb during strength
Anthropometric measures and landmarks on the arms (using nontoxic training of the opposite wrist flexors.
Maximum electrically evoked contraction. A constant current high-
voltage stimulator (model DS7AH; Digitimer, Hertfordshire, UK) was
Table 2. Precision data for pQCT analysis of muscle used to supramaximally activate the wrist flexors and extensors during
cross-sectional area a 10% isometric MVC background contraction (34). Electrodes were
Muscle Cross-Sectional Area, cm2
manually pressed into the median nerve above the elbow, under the
belly of the short head of the biceps brachii to ensure adequate
Participant Number Measure One Measure Two Means SDpooled/Means CV%2 stimulation of the nerve. Electrodes were also manually pressed into
1 58.2 59.9 59.1 1.96 3.8 the radial nerve above the lateral epicondyle of the elbow for stimu-
2 34.7 34.6 34.6 0.25 0.1 lation of the wrist extensors. A series of control twitches (0.5-ms
3 24.3 23.7 24.0 1.83 3.4 pulses) were used to determine the milliamps (mA) current required to
4 31.2 30.0 30.6 2.72 7.4 reach maximum M wave (Mmax). Stimulations started with a low
5 43.8 44.4 44.1 1.05 1.1 current, barely detectable by the participant. The intensity was raised
6 54.6 53.9 54.2 0.81 0.7 progressively until a plateau in the M wave occurred. The milliamps
7 25.8 27.4 26.6 4.12 17.0 required to evoke a plateau in the peak-to-peak magnitude of the M
8 42.1 42.8 42.5 1.24 1.5
wave plus 20% was used to ensure Mmax was reached and was
9 44.2 45.0 44.6 1.23 1.5
10 52.1 51.1 51.6 1.30 1.7 recorded. The LabVIEW software was programmed to randomly
11 30.2 29.8 30.0 0.96 0.9 administer five stimulations, and the average of the evoked tracings
12 53.3 53.0 53.2 0.37 0.1 was used as the Mmax. M-wave data were filtered offline (MATLAB
13 22.3 22.5 22.4 0.61 0.4 2006b; MathWorks, Natick, MA) with a custom filter (band pass
14 44.9 43.9 44.4 1.65 2.7 between 100 and 250 Hz) to help remove stimulation artifact. The
15 50.9 52.6 51.7 2.35 5.5 Mmax was recorded at each testing occasion and used as a reference to
16 46.4 45.2 45.8 1.77 3.1 normalize the within session EMG data recorded during each MVC
Average 3.2 test.
CV%RMS 1.8
Data acquisition. Custom software in LabVIEW (version 8.6) was
pQCT, quantitative computed tomography; CV%RMS, precision error coef- used to obtain M waves from evoked contractions, and EMG and
ficient of variation (%root mean square). torque data during MVCs. All channels were acquired at a sampling

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 MUSCLE-SPECIFIC SPARING EFFECTS DURING IMMOBILIZATION
rate of 1,000 Hz. To determine activation amplitude of the EMG data,
the middle 1 s of the rectified burst activity from each voluntary
contraction was used to determine the mean absolute value and the
greatest amplitude recorded from the three repitions for each contrac-
tion type was used in analysis. An analog-to-digital converter (model
PCI-6034E; National Instruments, Austin, TX) was used to convert
the analog signals and display in LabVIEW.
Data Analysis
The study was a 2 ⫻ 2 ⫻ 2 ⫻ 3 ⫻ 2 factorial design [group (train-
ing, control) ⫻ arm (immobilized, nonimmobilized) ⫻ task (flexion,
extension) ⫻ type (ECC, CON, ISO) ⫻ time (pre, posttraining)].
Strength data were analyzed with a 2 ⫻ 2 ⫻ 2 ⫻ 3 ⫻ 2 factorial
ANOVA (group ⫻ arm ⫻ task ⫻ type ⫻ time) followed by further
assessment of the significant two- and three-way interactions appro-
priate for the research questions related to the contraction type and
task specificity. Strength data were also split by arm (immobilized,
nonimmobilized) and task (wrist flexion, extension) for several break-
down analyses to better understand the trained limb vs. the CE sparing
effect.
MCSA (via pQCT) was analyzed with a 2 ⫻ 2 ⫻ 2 (group ⫻
arm ⫻ time) factorial ANOVA, and muscle thickness (via ultrasound)
was analyzed with a 2 ⫻ 2 ⫻ 2 ⫻ 2 [group ⫻ arm ⫻ muscle (flexors
and extensors) ⫻ time] factorial ANOVA followed by further assess-
ment of the significant two- and three-way interactions appropriate for
the research questions related to the muscle specificity. Muscle size
data were also split by arm (immobilized, nonimmobilized) and
muscle (for muscle thickness; flexors, extensors) for several break-
down analyses to better understand the trained limb vs. the CE sparing
effect.
EMG data were analyzed with a 2 ⫻ 2 ⫻ 2 ⫻ 2 ⫻ 3 ⫻ 2 factorial
ANOVA [group ⫻ arm ⫻ muscle (agonist, antagonist) ⫻ task ⫻
type ⫻ time]. In addition, an EMG analysis of the mirror activation in
the left, immobilized arm of the training group was conducted for the
1st, 7th, and 12th training sessions. The mirror activation analysis
involved separate one-factor repeated-measures ANOVA to investi-
gate differences among sessions (1, 7, and 12), repetitions (1– 8), and
869
The significant group ⫻ task ⫻ time interaction indicates
muscle-specific CE effects to the trained homologous muscle
group (i.e., flexors) but the nonspecific CE effects for contrac-
tion type. To simplify the interpretation, data were separated by
task and arm and collapsed across contraction type. Significant
group ⫻ time interactions were observed for the left, P ⫽
0.049, ␩2p ⫽ 0.249, and right wrist flexors, P ⫽ 0.038,
␩2p ⫽ 0.272. For the right arm, wrist flexion strength changes
were significantly different between the training (30.8%) and
control (⫺7.4%) groups. For the immobilized left arm the
changes for wrist flexion strength were significantly different
between training (⫺2.4%) and control (⫺21.6%) groups.
There were no group differences for the changes in wrist
extension, but immobilized left arm extension strength signif-
icantly decreased pooled across group and contraction type
(⫺13.2%, P ⬍ 0.001, ␩2p ⫽ 0.709). See Fig. 1 and Table 3 for
detailed torque changes.
Muscle Cross-Sectional Area
A three-factor ANOVA revealed a significant interaction for
group ⫻ arm ⫻ time, F(1,14) ⫽ 7.328, P ⫽ 0.017, ␩2p ⫽ 0.344.
To breakdown the three-way interaction, data were split by arm
and separate group ⫻ time ANOVA tests were run. A signif-
icant group ⫻ time interaction was detected for the left, im-
mobilized arm only, P ⫽ 0.012, ␩2p ⫽ 0.375, indicating that the
change in MCSA for the left arm for the training group (1.3%)
was different from the change in the control group (⫺2.3%).
A †
35 *
30
Torque (Nm)

sets (1– 6). 25

Greenhouse-Geisser adjustments were used for violations of sphe- 20

ricity. Breakdown analyses followed where significant interactions
were detected. Data analysis was completed using SPSS version 24. 15

Significance was accepted at P ⬍ 0.05, and effect sizes are reported 10

as partial eta-squared (␩2p).
5
RESULTS
0
Left Right Left Right
Demographics
B Training Control

35
There were no participant dropouts during the study and
maintained 100% adherence to all 12 training sessions. One 30

participant reported having preexisting eczema in the palm of

Torque (Nm)

25
the immobilized hand, so the cast was trimmed (cut off ~1 cm
20
at the distal end of the cast) to allow for treatment of the Pre
eczema without compromising the quality of immobilization. 15 Post
Groups were similar in height, weight, training experience, and 10 ‡ ‡
handedness, P ⬎ 0.05. (Table 1).
5
Muscle Strength
0
Left Right Left Right
The five-factor interaction for strength data did not reach Training Control
significance, F(2,28) ⫽ 3.151, P ⫽ 0.058, ␩2p ⫽ 0.184; how- Fig. 1. Changes in wrist flexion (A) and wrist extension torque (Nm; B) averaged
ever, significant three-way interactions were found for across contraction types [concentric (CON), isometric (ISO), and eccentric (ECC)]
arm ⫻ type ⫻ task, F(2,28) ⫽ 3.447, P ⫽ 0.046, ␩2p ⫽ 0.198; from pre- to posttesting for each group. The left arm was immobilized during
group ⫻ task ⫻ time, F(1,14) ⫽ 5.263, P ⫽ 0.038, ␩2p ⫽ training. Data represent means ⫾ SD in Nm. *P ⫽ 0.049, significant group ⫻ time
interaction for left wrist flexion torque. †P ⫽ 0.038, significant group ⫻ time
0.273; and arm ⫻ task ⫻ time, F(1,14) ⫽ 7.027, P ⫽ 0.019, interaction for right wrist flexion torque. ‡P ⬍ 0.001, significant time main effect
␩2p ⫽ 0.334. for left wrist extension torque.

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870 MUSCLE-SPECIFIC SPARING EFFECTS DURING IMMOBILIZATION

Table 3. Strength changes for contraction type and task

50 † *
Training Control
45
Contractions (Type/Task/Arm) Pre Post Pre Post

MCSA (cm2)
ISO 40
Flexion
Left 12.5 ⫾ 5.3 12.0 ⫾ 4.0 15.0 ⫾ 6.7 11.2 ⫾ 5.3 35 Pre
Right 12.3 ⫾ 4.0 16.3 ⫾ 7.1 14.2 ⫾ 6.9 13.0 ⫾ 6.1 Post
Extension 30
Left 6.2 ⫾ 1.6 5.3 ⫾ 1.6 6.3 ⫾ 1.6 5.5 ⫾ 1.1
Right 6.9 ⫾ 1.6 7.1 ⫾ 1.8 7.2 ⫾ 1.6 7.1 ⫾ 1.2 25
CON
Flexion
20
Left 9.4 ⫾ 2.7 9.5 ⫾ 4.1 11.7 ⫾ 5.4 8.7 ⫾ 4.7 Left Right Left Right
Right 10.9 ⫾ 4.2 13.3 ⫾ 6.2 11.8 ⫾ 5.8 11.1 ⫾ 6.3 Training Control
Extension
Left 5.1 ⫾ 1.3 4.5 ⫾ 1.4 5.6 ⫾ 1.1 4.6 ⫾ 1.1 Fig. 2. Muscle cross-sectional area (MCSA; cm2) changes for the left, immo-
Right 5.5 ⫾ 1.2 5.9 ⫾ 1.1 6.3 ⫾ 1.5 6.1 ⫾ 1.2 bilized and right arms of the training and control groups from pre- to
ECC posttesting. Data represent means ⫾ SD in cm2. *P ⫽ 0.019, significant
Flexion arm ⫻ time interaction for control group only. †P ⫽ 0.012, significant
Left 14.9 ⫾ 4.7 14.7 ⫾ 4.7 17.8 ⫾ 7.6 15.0 ⫾ 5.5 group ⫻ time interaction for the left arm only.
Right 15.7 ⫾ 4.4 21.3 ⫾ 9.6 18.7 ⫾ 7.9 17.4 ⫾ 9.1
Extension
Left 8.1 ⫾ 2.4 7.5 ⫾ 2.1 8.3 ⫾ 2.2 7.1 ⫾ 1.8 ␩2p ⫽ 0.327, and left wrist flexors, P ⫽ 0.011, ␩2p ⫽ 0.405, but
Right 8.7 ⫾ 1.8 9.1 ⫾ 2.0 9.3 ⫾ 1.9 8.9 ⫾ 1.9 not for wrist extensor muscles of either limb.
Pooled Data were then split by group, and separate arm ⫻ mus-
Flexion
Left 12.3 ⫾ 5.4 12.0 ⫾ 4.6 14.8 ⫾ 5.4 11.6 ⫾ 4.6 cle ⫻ time ANOVA tests were run. A significant arm ⫻ mus-
Right 13.0 ⫾ 5.5 17.0 ⫾ 7.3 14.9 ⫾ 5.5 13.8 ⫾ 7.3 cle ⫻ time interaction was detected for the training group only,
Extension P ⫽ 0.006, ␩2p ⫽ 0.684. Further breakdown of the three-way
Left 6.5 ⫾ 1.6 5.8 ⫾ 1.5 6.7 ⫾ 1.6 5.7 ⫾ 1.2 interaction for the training group involved splitting these data
Right 7.0 ⫾ 1.5 7.3 ⫾ 1.6 7.6 ⫾ 1.6 7.3 ⫾ 1.3
Pooled by muscle (flexors, extensors), but this did not reveal any
Left 9.4 ⫾ 3.3 8.9 ⫾ 2.9 10.8 ⫾ 3.3 8.7 ⫾ 2.9 arm ⫻ time interactions.
Right 10.0 ⫾ 3.5 12.2 ⫾ 4.3 11.3 ⫾ 3.5 10.6 ⫾ 4.3 The ANOVA tests for muscle thickness revealed that the
Data are means ⫾ SD in Nm. There were no significant differences between change in the untrained, immobilized left flexors of the training
contraction type [concentric (CON), isometric (ISO), and eccentric (ECC)]. group (2.8%) was significantly different from control (⫺3.2%).
Pooled data revealed significant differences as shown in Fig. 1. The tests also revealed the change in the right flexors of the
training group (7.1%) was different from the control group
(⫺3.7%) (Fig. 3 and Table 4).
Further analysis involved splitting data by group and run-
ning separate arm ⫻ time ANOVA tests to compare between Muscle Activation
arm differences. These analyses revealed a significant
arm ⫻ time interaction for the control group only, P ⫽ 0.019, The six-factor omnibus factorial ANOVA failed to reach
␩2p ⫽ 0.566, indicating that the change in the left arm (⫺2.3%) significance, F(2,28) ⫽ 0.306, P ⫽ 0.739, ␩2p ⫽ 0.021. A signif-
was different from the change in the right arm (1.2%). For the
training group, the change in the left, immobilized arm (1.3%)
Table 4. Muscle size changes
was not significantly different from the change in the right,
trained arm (1.2%) (Fig. 2 and Table 4). Group/Arm/Measure Pre Post

Training
Muscle Thickness Left
Flexor MT 3.27 ⫾ 0.46 3.36 ⫾ 0.56
Normality assessments of the control group determined that Extensor MT 1.60 ⫾ 0.27 1.68 ⫾ 0.28
the left flexor muscle thickness raw change was skewed MCSA 31.10 ⫾ 6.95 31.52 ⫾ 6.87
(Zskew ⫽ 2.75) and kurtotic (Zkurt ⫽ 3.13). One participant was Right
removed from the analysis because it was determined that a Flexor MT 3.53 ⫾ 0.55 3.78 ⫾ 0.51
positive change in muscle thickness of 0.68 cm (20%) in the Extensor MT 1.65 ⫾ 0.33 1.69 ⫾ 0.29
MCSA 29.13 ⫾ 6.32 29.48 ⫾ 6.40
immobilized limb of a control participant was a result of Control
measurement error. After the removal of the outlier, there were Left
no violations of normality as determined by skewness Flexor MT 3.75 ⫾ 0.73 3.63 ⫾ 0.68
(Zskew ⫽ 1.14) and kurtosis (Zkurt ⫽ 0.59). Extensor MT 1.69 ⫾ 0.20 1.64 ⫾ 0.25
MCSA 35.18 ⫾ 7.23 34.38 ⫾ 8.12
A four-factor omnibus factorial ANOVA revealed a signif- Right
icant interaction for group ⫻ arm ⫻ muscle ⫻ time, F(1,13) ⫽ Flexor MT 3.74 ⫾ 0.62 3.60 ⫾ 0.53
6.037, P ⫽ 0.029, ␩2p ⫽ 0.317. To breakdown the four-way Extensor MT 1.68 ⫾ 0.14 1.72 ⫾ 0.14
interaction, data were split by arm and by muscle, and separate MCSA 34.29 ⫾ 7.71 34.66 ⫾ 7.96
group ⫻ time ANOVA tests were run. Significant group ⫻ Data are means ⫾ SD. MCSA, muscle cross-sectional area in cm2;
time interactions were found for the right, P ⫽ 0.026, MT, muscle thickness in cm.

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 MUSCLE-SPECIFIC SPARING EFFECTS DURING IMMOBILIZATION 871

A 6
† DISCUSSION

*
Muscle Thickness (cm)

The major finding of this study is that the CE sparing effects

5 of muscle strength were specific to the trained homologous
4
muscle in the contralateral limb but were not specific to
contraction type. ECC wrist flexion training of the nonimmo-
3 bilized limb preserved ECC, CON, and ISO strength in the
contralateral, immobilized wrist flexors. Importantly, this was
2
the first study to identify muscle size sparing effects of CE with
1
muscle area measures via pQCT. The current study has there-
fore replicated previously observed sparing effects of CE with
0
Left Right Left Right
a robust measure of muscle size (26). The confirmation of
muscle size and strength sparing effects across multiple mea-
B 6
Training Control
sures builds confidence in the reproducibility of CE sparing
Muscle Thickness (cm)

effects and their clinical relevance for improving recovery

5 from unilateral injury or impairment.
4
3 Pre
Post
2 improvement was ~24%, accompanied by preservation of
‡ ‡
1 average decrease in immobilized limb strength for nontraining
0
Left Right Left Right
Training Control
Fig. 3. Changes in muscle thickness for wrist flexors (A) and wrist extensors
(B) between groups. Note the observed significant effects only for the wrist
flexors. Data represent means ⫾ SD in cm. *P ⫽ 0.011, significant
group ⫻ time interaction for the left wrist flexors. †P ⫽ 0.026, significant
group ⫻ time interaction for the right wrist flexors.
icant interaction was observed for group ⫻ muscle ⫻ type ⫻
task ⫻ time, P ⫽ 0.004, ␩2p ⫽ 0.331.
To breakdown the significant interaction, data were split by
group and separate muscle ⫻ task ⫻ type ⫻ time ANOVA
tests were run. No significant interactions were observed that
included a time factor. Further breakdown involved splitting
these data by arm and examining between group differences.
No significant interactions including group or time factors were
observed for the immobilized and nonimmobilized limb (Table
5, Flexion, and Table 6, Extension).
M-wave data were stable between pre- and posttesting ses-
sions for the left wrist flexors (pre: 1.49 ⫾ 1.03 mV; post:
1.57 ⫾ 0.99 mV), left wrist extensors (pre: 1.65 ⫾ 1.07 mV;
post: 1.60 ⫾ 0.73 mV), right wrist flexors (pre: 1.60 ⫾ 0.96
mV; post: 1.49 ⫾ 1.16 mV), and right wrist extensors (pre:
1.90 ⫾ 0.95 mV; post: 2.04 ⫾ 0.89 mV).
Mirror Activity (Coactivation of the Nontraining Limb)
The mean EMG activity of the left, immobilized, wrist
flexors of the training group measured during the 1st, 7th and
12th training sessions was, on average, 5.6% of pretesting
isometric MVC. The mirror EMG activity (normalized to
baseline isometric MVC) was not significantly different among
sessions 1, 7, and 12 (range: 0.047 ⫾ 0.017 to 0.085 ⫾ 0.046),
P ⫽ 0.077, ␩2p ⫽ 0.360, among repititions 1 to 8 (range:
0.051 ⫾ 0.021 to 0.061 ⫾ 0.024), P ⫽ 0.553, ␩2p ⫽ 0.108, or
among sets 1 to 6 (range: 0.047 ⫾ 0.026 to 0.061 ⫾ 0.022),
P ⫽ 0.142, ␩2p ⫽ 0.245, during training sessions.
Muscle Strength
In prior CE sparing studies, the average trained limb strength
strength in the untrained, immobilized limb. Note that the
control groups in prior CE sparing studies averaged ~12%
across studies; therefore, the CE sparing effect can be esti-
mated as about half of the trained limb effect (20, 21, 40, 45).
As previously mentioned, the magnitude of CE of strength is
typically ~50% of the trained limb effect in studies not involv-
ing immobilization models (7). The current data merge well
with these prior studies, which, on average, report that the
immobilized limb of the training group shows no change in
strength (0.3%, NS) and a significant decline of 13.2% for the
immobilized limb of the nontraining control group (20, 21, 40,
45). The combined evidence to date suggests the strength
sparing effect of CE amounts to ~12% for arm immobilization
protocols of a 3- to 4-wk duration (20, 21, 40, 45).
Previous research has found CE to be highly specific, where
transfer effects reside primarily in the contralateral homolo-
gous muscle group, with the same velocity or joint angle used
in training of the opposite limb (18, 50, 53). A novel aspect of
the current study was the intent to investigate muscle size and
strength in the wrist flexor and extensor muscles of the trained
and contralateral, immobilized arm. CE attenuated strength
loss in the homologous immobilized wrist flexors, which is
congruent with muscle specificity of CE effects in studies
without immobilization and indicates that the mechanisms of
CE specificity are likely unaltered in the presence of immobi-
lization.
Unilateral training with ECC muscle actions results in
greater CE of strength in the contralateral homologous muscle
compared with CON or ISO muscle actions (18, 29). Horto-
bágyi et al. (29) observed a greater global training effect when
training with ECC muscle actions compared with CON, mean-
ing that both CON and ISO strength improved, albeit to a lesser
extent, in the contralateral homologous muscle from the ECC
training. In the present study, participants in the training group
attended three sessions per week of isolated ECC wrist flexion
actions, which resulted in a similar increase in strength of the
right wrist flexors across all contraction types (Fig. 1). Addi-
tionally, a preservation of strength regardless of contraction
type was apparent in the left, immobilized wrist flexors. ECC
muscle actions compared with CON and ISO are known to

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872 MUSCLE-SPECIFIC SPARING EFFECTS DURING IMMOBILIZATION

Table 5. Flexion EMG changes

Training Control

Flexion Contractions (Type/Muscle/Arm) Pre Post Pre Post

ISO
Agonist (FCR)
Left 0.214 ⫾ 0.111 0.159 ⫾ 0.080 0.210 ⫾ 0.098 0.154 ⫾ 0.066
Right 0.197 ⫾ 0.088 0.273 ⫾ 0.182 0.200 ⫾ 0.099 0.215 ⫾ 0.110
Antagonist (ECR)
Left 0.042 ⫾ 0.021 0.049 ⫾ 0.025 0.076 ⫾ 0.040 0.037 ⫾ 0.027
Right 0.037 ⫾ 0.018 0.049 ⫾ 0.016 0.062 ⫾ 0.028 0.047 ⫾ 0.028
CON
Agonist (FCR)
Left 0.188 ⫾ 0.075 0.143 ⫾ 0.100 0.181 ⫾ 0.082 0.128 ⫾ 0.057
Right 0.192 ⫾ 0.085 0.214 ⫾ 0.108 0.189 ⫾ 0.096 0.184 ⫾ 0.109
Antagonist (ECR)
Left 0.034 ⫾ 0.022 0.037 ⫾ 0.029 0.057 ⫾ 0.032 0.024 ⫾ 0.016
Right 0.029 ⫾ 0.015 0.039 ⫾ 0.013 0.049 ⫾ 0.019 0.038 ⫾ 0.029
ECC
Agonist (FCR)
Left 0.245 ⫾ 0.114 0.188 ⫾ 0.105 0.210 ⫾ 0.090 0.177 ⫾ 0.054
Right 0.249 ⫾ 0.110 0.266 ⫾ 0.193 0.200 ⫾ 0.088 0.216 ⫾ 0.099
Antagonist (ECR)
Left 0.032 ⫾ 0.012 0.057 ⫾ 0.046 0.061 ⫾ 0.036 0.029 ⫾ 0.016
Right 0.030 ⫾ 0.011 0.047 ⫾ 0.016 0.049 ⫾ 0.017 0.037 ⫾ 0.024
Pooled
Agonist (FCR)
Left 0.216 ⫾ 0.140 0.164 ⫾ 0.090 0.201 ⫾ 0.124 0.153 ⫾ 0.054
Right 0.213 ⫾ 0.128 0.251 ⫾ 0.159 0.196 ⫾ 0.132 0.205 ⫾ 0.104
Antagonist (ECR)
Left 0.036 ⫾ 0.024 0.047 ⫾ 0.034 0.064 ⫾ 0.052 0.030 ⫾ 0.020
Right 0.032 ⫾ 0.020 0.045 ⫾ 0.014 0.053 ⫾ 0.028 0.041 ⫾ 0.025
Data represent means ⫾ SD in normalized units. FCR, flexor carpi radialis; ECR, extensor carpi radialis. There were no significant differences between groups
regardless of muscle (flexors, extensors), task (flexion, extension) or contraction type (ECC, CON, ISO).

cause greater increases in intracortical facilitation and larger
decreases in intracortical inhibition (31, 32), which could
explain larger transfer effects with ECC, and may contribute to
the observed global strength sparing effect in the contralateral
homologous muscle group in the current study.
Muscle Size
Before this study, the muscle size sparing effect was only
observed using ultrasound measures of muscle thickness (20,
40, 45). The advantage of concurrent pQCT and ultrasound
imaging of muscle is the ability to compare whole MCSA and
site-specific muscle thickness (i.e., forearm flexors and exten-
sors). Verifying muscle size sparing effects with a measure of
MCSA is critical for progression in the field (26). The CE
sparing effects for muscle thickness revealed support for mus-
cle-specific effects to contralateral homologous wrist flexors
(Fig. 3); however, immobilization did not result in significant
decreases in muscle thickness for the extensors of either group.
Therefore, the site-specific nature of muscle size sparing ef-
fects for flexors vs. extensors is less convincing than for
strength. Further supporting the preservation of muscle thick-
ness was the confirmation of muscle size preservation with
pQCT-derived MCSA (Fig. 2). Since the pQCT MCSA method
cannot differentiate flexor vs. extensor muscles, and there were
no detectable changes in extensor muscle thickness, more work
is needed to confirm site-specific muscle size sparing of CE.
This study provides novel insight into possible mechanisms
of CE sparing. Currently, the dominant theories of CE effects
have proposed possible mechanisms for strength and skill
transfer effects to reside primarily in the brain (49). CE is
thought to be a neural phenomenon where changes in cortical
processes and motor engrams positively impact the neural
drive to the contralateral limb (17, 49). This is understandable
since CE effects typically do not present with evidence of
alterations in muscle volume (16, 36, 49), especially without
immobilization. There is no apparent candidate mechanism
that accounts for muscle size changes with CE in the untrained
limb, unless there is concurrent evidence of direct voluntary or
involuntary muscle activation in the nontraining limb of at least
15% of maximum, which has been shown to induce small
amounts of hypertrophy after 12 wk of training (28). Our
findings suggest activation of the resting immobilized limb
during training (~5.6% MVC) over a 4-wk period is not likely
to preserve the muscle, although it cannot be ruled out. This
presents the possibility that an alternate mechanism is involved
in CE sparing effects, which may be independently activated or
driven by the nervous system. It at least suggests the preser-
vation of muscle strength and size via CE are related but could
be driven by overlapping and independent mechanisms.
The regulation of muscle atrophy with immobilization or
disuse occurs through two primary processes; elevated muscle
protein breakdown and a decrease in muscle protein synthesis
(MPS), with a decrease in MPS found to be the leading
mechanism (46). While the mechanisms of muscle size pres-
ervation with CE are currently unknown, and a direct connec-
tion between neural contributions and the regulation of MPS
and muscle protein breakdown is not clear, it remains possible
that the unilateral ECC training of the wrist flexors in the

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 MUSCLE-SPECIFIC SPARING EFFECTS DURING IMMOBILIZATION 873
Table 6. Extension EMG changes
Training Control

Extension Contractions (Type/Muscle/Arm) Pre Post Pre Post

ISO
Agonist (ECR)
Left 0.124 ⫾ 0.025 0.118 ⫾ 0.060 0.175 ⫾ 0.065 0.128 ⫾ 0.052
Right 0.118 ⫾ 0.038 0.108 ⫾ 0.041 0.160 ⫾ 0.059 0.135 ⫾ 0.033
Antagonist (FCR)
Left 0.031 ⫾ 0.021 0.036 ⫾ 0.038 0.064 ⫾ 0.065 0.017 ⫾ 0.011
Right 0.032 ⫾ 0.020 0.051 ⫾ 0.034 0.043 ⫾ 0.029 0.033 ⫾ 0.030
CON
Agonist (ECR)
Left 0.118 ⫾ 0.028 0.097 ⫾ 0.033 0.182 ⫾ 0.074 0.118 ⫾ 0.035
Right 0.121 ⫾ 0.033 0.106 ⫾ 0.041 0.150 ⫾ 0.044 0.128 ⫾ 0.029
Antagonist (FCR)
Left 0.034 ⫾ 0.022 0.044 ⫾ 0.043 0.053 ⫾ 0.046 0.019 ⫾ 0.009
Right 0.030 ⫾ 0.020 0.036 ⫾ 0.026 0.032 ⫾ 0.018 0.032 ⫾ 0.027
ECC
Agonist (ECR)
Left 0.132 ⫾ 0.023 0.118 ⫾ 0.070 0.165 ⫾ 0.069 0.123 ⫾ 0.042
Right 0.124 ⫾ 0.037 0.092 ⫾ 0.031 0.151 ⫾ 0.053 0.130 ⫾ 0.042
Antagonist (FCR)
Left 0.037 ⫾ 0.024 0.043 ⫾ 0.032 0.061 ⫾ 0.047 0.024 ⫾ 0.021
Right 0.037 ⫾ 0.020 0.054 ⫾ 0.045 0.040 ⫾ 0.018 0.041 ⫾ 0.029
Pooled
Agonist (ECR)
Left 0.124 ⫾ 0.032 0.111 ⫾ 0.048 0.174 ⫾ 0.096 0.123 ⫾ 0.042
Right 0.121 ⫾ 0.048 0.102 ⫾ 0.034 0.153 ⫾ 0.072 0.131 ⫾ 0.034
Antagonist (FCR)
Left 0.034 ⫾ 0.032 0.041 ⫾ 0.034 0.059 ⫾ 0.076 0.020 ⫾ 0.014
Right 0.033 ⫾ 0.028 0.047 ⫾ 0.034 0.038 ⫾ 0.028 0.035 ⫾ 0.028
Data represent means ⫾ SD in normalized units. FCR, flexor carpi radialis; ECR, extensor carpi radialis. There were no significant differences between groups
regardless of muscle (flexors, extensors), task (flexion, extension) or contraction type (ECC, CON, ISO).

present study led to muscle size preservation in the contralat-
eral limb by influencing the balance of protein regulation. One
possible mechanism may be in the neural regulation of the
protein kinase B (AKT) and mammalian target of rapamycin
(mTOR) pathway (26). AKT and mTOR are important protein
complexes that play a role in the modulation of gene expres-
sion, cell development, growth, and survival and are upregu-
lated in the nervous system during cellular stress (9, 41). The
AKT and mTOR pathway is upregulated with skeletal muscle
hypertrophy and downregulated with muscle atrophy caused by
disuse (2). Investigating AKT and mTOR pathway modulation
with CE to an immobilized limb is an intriguing prospect in
understanding the muscle size sparing effects observed.
Muscle Activation and Mirror Activity
In the present study, the EMG data did not reveal significant
between groups differences for any of the tested contraction
types or tasks. The EMG data are inconclusive and further
investigation with a larger sample size is needed. Muscle
activation at levels as low as 10% one repetition maximum
have been shown to increase strength (35). Farthing et al. (21)
proposed that, although unlikely, it is possible for the CE
sparing effects observed in past literature to be attributed to
high levels (⬎10% MVC) of mirror activity during the unilat-
eral training intervention in the opposite limb, because mirror
activity was not monitored under the cast. Of the four studies
to investigate the CE sparing effects in healthy participants,
only Magnus et al. (40) monitored mirror activity during a
sling model of disuse. Both Magnus et al. (40) and the current
data show CE training produced low levels of mirror activity in
the immobilized limb. Although unlikely, it remains possible
that the reported 5.6% in the current study and the 3.1% (biceps
brachii) and 6.1% (triceps brachii) reported in the Magnus et al.
(40) study contributed at least some to the observed sparing
effects of size and strength in the immobilized limb. The
contribution of mirror activity to size and/or strength sparing
effects of CE remains unclear, but the current hypothesis that
cortical contributions are primarily responsible for the transfer
effects remains viable (49).
Clinical Relevance
The findings of this study have broad clinical implications
for rehabilitation from unilateral injury or impairment. The
data suggest that training of the nonimmobilized, or noninjured
limb, can benefit an opposite homologous immobilized or
injured limb through CE effects. Although there is already
published evidence that CE can benefit recovery from wrist
fracture (39) and facilitate affected limb strength in chronic
stroke patients (11), the current finding of muscle-specific
sparing effects in healthy volunteers suggests that targeted
training involving multiple muscles is needed to attenuate the
loss in size and strength of an opposite limb in a clinical
setting. Furthermore, the global sparing of strength across
multiple contraction types after training only ECC suggests
that more efficient strength rehabilitation programs can be
administered. Rehabilitation should focus on complete joint
symmetry by training both agonist and antagonistic pairs of
both distal and proximal muscle groups. Taken together, the

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874 MUSCLE-SPECIFIC SPARING EFFECTS DURING IMMOBILIZATION
current literature demonstrates a clear potential benefit of CE
for improving recovery from unilateral immobilization or in-
jury (20, 21, 39, 40, 45).
Study Strengths and Limitations
The study began in September (late summer) and ran
through the fall and winter semesters at the University of
Saskatchewan. The strategic timing of participant recruitment
is a likely cause for the 100% adherence to all 12 training
sessions without any participant dropouts. Another strength to
this study was that the MCSA data were collected by a
researcher who was blinded to group assignment, which in-
creases confidence in the outcome.
While mirror activation in the immobilized limb was mon-
itored during three testing sessions, the muscle activity was
only monitored in the wrist flexors. The lack of wrist extensor
monitoring is a noted limitation to this study. Another limita-
tion was the use of the wrist joint model for investigating
specificity of CE sparing effects. Although the wrist is clini-
cally relevant (39) and convenient for cast immobilization,
there are several muscles that make up the wrist flexors and
extensors, making EMG recording and muscle imaging of
these muscles difficult to conduct. Although we detected sig-
nificant effects for several of our main outcomes, the sample
size was small for the complexity of the design. Recruiting
participants for immobilization studies is difficult; therefore,
replication of these findings with larger samples is important.
Although the 4-wk immobilization period was longer than
most of the previous CE sparing literature (20, 21, 45), a longer
immobilization period would have been beneficial to increase
the severity of strength loss and atrophy in the immobilized
limb. This would provide a better estimate of clinical studies of
unilateral wrist fractures, which demonstrate much more pro-
found losses in strength and function after 4 – 6 wk of immo-
bilization (39). Immobilization due to unilateral injury may be
prescribed for durations longer than 4 wk, and to improve the
clinical relevance of these CE sparing effects, longer immobi-
lization periods are recommended for future research. Future
research would benefit from using MRI to assess specific
muscle volume adaptations to determine the specificity of the
sparing effects. Future research would also benefit from the use
of functional imaging or brain stimulation to investigate the
specificity of CE sparing effects. Using functional imaging or
brain stimulation has the potential to offer clear evidence of the
neural mechanisms contributing to the observed sparing effects
of strength and size. As mentioned, future research investigat-
ing the specificity of CE may benefit by recording EMG of
both the contralateral agonist (wrist flexors) and antagonist
(wrist extensors) muscles during training sessions to more
closely monitor the contributions of mirror activity in the
resting, immobilized limb. Finally, the sparing effects of CE
have not yet been shown in an older population, and the effects
may not be the same as shown here for young, healthy
volunteers.
Conclusion
This study provides novel insight into the specificity of CE
sparing effects in an immobilized limb. The finding that im-
mobilized limb strength was preserved across contraction types
for the contralateral homologous muscle after only training
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with ECC muscle actions confirms that immobilization does
not alter the specificity effects previously reported in nonim-
mobilization CE studies. There were no direct measures of
cortical or corticospinal activation changes or altered excitabil-
ity in the present study; therefore, no definitive conclusions can
be made from these data to support neural mechanisms (49).
However, the data suggest the possibility of an alternate
site-specific mechanism of CE sparing that can somehow offset
the effects of disuse in a homologous muscle. Although the
cause of the muscle size sparing remains unclear, its confir-
mation brings new insight into possible contributing mecha-
nisms of CE sparing effects. Regardless of the mechanisms, CE
appears to be a relevant and practical exercise modality to
attenuating the loss commonly associated with immobilization
and is viable for consideration in clinical settings such as
unilateral orthopedic or neurological injury (14, 39).
ACKNOWLEDGMENTS
We acknowledge Chris Buttinger for the contribution of applying the casts
throughout the study and all of the participants that were adherent and
dedicated to making this study a success. We also thank Dr. Tibor Hortobágyi
for providing helpful comments on an earlier version of the manuscript.
GRANTS
This research was funded by the National Sciences and Engineering
Research Council of Canada (NSERC) Discovery Grant RGPIN 2016 - 0529.
Justin Andrushko received a M.Sc. scholarship from the Canadian Institutes of
Health Research (CIHR) to carry out this research.
DISCLOSURES
No conflicts of interest, financial or otherwise, are declared by the authors.
AUTHOR CONTRIBUTIONS
J.W.A. and J.P.F. conceived and designed research; J.W.A. and K.M.B.
performed experiments; J.W.A. analyzed data; J.W.A., J.L.L., S.A.K., and
J.P.F. interpreted results of experiments; J.W.A. prepared figures; J.W.A.
drafted manuscript; J.W.A., J.L.L., K.M.B., S.A.K., and J.P.F. edited and
revised manuscript; J.W.A., J.L.L., K.M.B., S.A.K., and J.P.F. approved final
version of manuscript.
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