bilized side. These findings suggest that brief periods of
reduced use of a limb have overt consequences and thus
constitute a significant driving force of brain organization
equivalent to enhanced use.
p = 0.28, n = 36 Figure 2). In contrast, discrimination thresholds
for the immobilized index finger, but not for the healthy index
finger, were significantly higher (Figure 2) in cast-wearing
subjects, indicating a significant impairment of discrimination
abilities caused by, on average, 22 days of immobilization
(paired t test: p < 0.0001), with a side-to-side difference
between the healthy and the immobilized index finger of
0.44 6 0.43 mm (paired t test: p < 0.0001).
We also evaluated whether the side or duration of cast
*Correspondence: martin.tegenthoff@ruhr-uni-bochum.de (M.T.), hubert.
dinse@neuroinformatik.rub.de (H.R.D.)Current Biology 19, 837–842, May 26, 2009 ª2009 Elsevier Ltd All rights rese
Immobilization Impairs Tactil
and Shrinks Somatosensory
Silke Lissek,1,7 Claudia Wilimzig,2,5,7 Philipp Stude,1
Burkhard Pleger,1,6 Tobias Kalisch,2 Christoph Maier,3
So¨ren A. Peters,4 Volkmar Nicolas,4 Martin Tegenthoff,1,*
and Hubert R. Dinse2,*
1Department of Neurology
BG-Kliniken Bergmannsheil
2Neural Plasticity Lab
Institute for Neuroinformatics
Department of Theoretical Biology
3Department of Pain Treatment
BG-Kliniken Bergmannsheil
4Department of Radiology
BG-Kliniken Bergmannsheil
Ruhr University
D-44780 Bochum
Germany
5California Institute of Technology
Pasadena, CA
USA
6Max-Planck Institute for Human Cognitive and Brain Sciences
D-04103 Leipzig
Germany
Summary
Use is a major factor driving plasticity of cortical processing
and cortical maps. As demonstrated of blind Braille readers
and musicians, long-lasting and exceptional usage of the
fingers results in the development of outstanding sensori-
motor skills and in expansions of the cortical finger repre-
sentations. However, how periods of disuse affect cortical
representations and perception in humans remains elusive.
Here, we report that a few weeks of hand and arm immobili-
zation by cast wearing significantly reduced hand use and
impaired tactile acuity, associated with reduced activation
of the respective finger representations in the somatosen-
sory cortex (SI), measured by functional magnetic reso-
nance imaging. Hemodynamic responses in the SI corre-
lated positively with hand-use frequency and negatively
with discrimination thresholds, indicating that reduced acti-
vation was most prominent in subjects with severe percep-
tual impairment. We found, strikingly, compensatory effects
on the contralateral, healthy hand consisting of improved
perceptual performance compared to healthy controls.
Two to three weeks after cast removal, perceptual and
cortical changes recovered, whereas tactile acuity on the
healthy side remained superior to that on the formerly immo-7These authors contributed equally to this manuscriptrved DOI 10.1016/j.cub.2009.03.065
Report
e Perception
Cortical Maps
Results
Imaging studies provided compelling evidence that training
and enhanced use of a body part cause plastic reorganiza-
tional changes in the functional brain architecture of string
players [1], blind Braille readers [2–4], and musicians [5, 6].
These findings in humans corroborated the concept of use-
dependent plasticity, derived from animal studies [7–12], ac-
cording to which changes in cortical maps depend on the
amount of use that an individual allocates to conform to the
current requirements of environmental constraints. Here, we
address the issue of how enforced disuse, resulting from an
everyday-life situation of wearing a cast for several weeks as
a result of a hand or arm fracture, affects perceptual perfor-
mance and reorganization of the somatosensory cortex in an
otherwise intact nervous system.
We first confirmed the prevailing assumption that immobili-
zation reduces the amount of use of the immobilized hand as
compared with the healthy hand. During cast wearing, we re-
corded motion of the arms in two planes with the use of accel-
erometer sensors fixed to the wrists of both of the subject’s
arms (mean duration 3.23 6 0.82 hr [mean 6 SD]).
Healthy, right-handed, age-matched controls showed
acceleration values of 28.67 6 1.57 mG for the right hand
and 24.60 6 2.23 mG for the left hand. The side-to-side differ-
ence was 5.886 1.37 mG (paired t test: p < 0.0021). In contrast,
the group of right-handed, cast-wearing subjects showed
significantly reduced movement activity for the immobilized
hand (15.68 6 2.01 mG) in comparison to the healthy hand
(37.73 6 3.60 mG; paired t test: p < 0.0001), with a mean
side-to-side difference of 17.67 6 3.56 mG (paired t test: p <
0.0001). Accordingly, immobilization caused a significant
decrease of acceleration values in comparison to the left (t
test: p = 0.0026) and right hand of healthy controls (t test: p <
0.0001). Importantly, acceleration values for the healthy hand
of cast patients were substantially increased in comparison
to the left (t test: p = 0.0066) and right (t test: p < 0.04) hand
of control subjects (Figure 1). These data substantiate cast
patients’ less-than-normal use of their immobilized hand, sup-
porting the assumption that immobilization acts to enforce
disuse. However, the reduced use of the immobilized hand is
compensated for by a more frequent use of the other, healthy
hand (Figure 1).
To demonstrate perceptual implications of immobilization,
we assessed tactile acuity by measuring spatial two-point
discrimination thresholds on the tip of the index finger
[13–16]. For the healthy controls, we found no difference in
threshold between the right and the left fingers (paired t test:wearing affected the observed changes in discrimination. All

subjects were right handed; however, it was unclear whether it
made a difference if the dominant or the nondominant hand
was immobilized. We observed no significant differences in
the performance of the immobilized hand to either the side of
cast wearing (p = 0.9908) or the duration of cast wearing (p =
0.4727). However, performance of the healthy hand correlated
with the duration of cast wearing, both for differences to values
predicted by the control group (Pearson’s r = 20.3679, p =
0.045) and for differences to values predicted within the group
(r = 20.46, p = 0.010). Accordingly, whereas impairment in
performance was independent of side and duration, improve-
ment of the healthy hand depended on the duration of cast
wearing.
Figure 1. Differences in Hand and Arm Acceleration between Cast-Wearing
Subjects and Healthy, Age-Matched Control Subjects
A comparison between cast-wearing subjects and healthy controls revealed
a significant reduction in hand and arm acceleration of the immobile
hand (red) and a significantly enhanced frequency of use for the healthy
hand (green) in cast-wearing patients in comparison with the left and right
hand (light and dark blue) in healthy controls (paired t test: p < 0.0001 for
all conditions).
Figure 2. Effects of Immobilization on Tactile Spatial Discrimination
Tactile discrimination thresholds of the index fingers (IFs) in subjects
wearing a cast on their hand and arm (n = 31), resulting in immobilization
of the hand and finger, in comparison with age-matched controls (n = 36).
Cast-wearing subjects showed higher discrimination thresholds of their
immobilized IF in comparison with the right or left IF of age-matched controls
(paired t test: p < 0.0001). However, discrimination performance of the
Current Biology Vol 19 No 10
838healthy IF in cast-wearing subjects was better than that of age-matched
controls. Two to three weeks after cast removal, discrimination performance
of the immobilized hand’s IF recovered to the thresholds observed for the
healthy hand of cast-wearing subjects and age-matched controls.To assess long-term effects of immobilization, we retested
tactile acuity two to three weeks (18.0 6 6.8 days) after cast
removal. We found that discrimination thresholds of the immo-
bilized hand returned to normal (paired t test p < 0.0001; n = 29;
Figure 2), meaning that there was no significant difference
between the healthy and the previously immobilized hands
after cast removal (paired t test p = 0.780).
To facilitate better understanding of the recovery process,
we compared cast patients with controls for changes in
discrimination thresholds, separately for left- or right-hand
immobilization. With right-hand immobilization (n = 8), the
healthy hand showed superior tactile discrimination that per-
sisted after two weeks of cast removal (p = 0.0249), indicating
a sustained compensatory effect. This analysis confirmed
that for right-hand immobilization, the thresholds on the immo-
bilized index finger recovered to values typically found in
controls two weeks after cast removal. In contrast, for left,
nondominant hand immobilization (n = 6), the thresholds of
both the immobilized and the healthy finger recovered to
a normal performance typically found in age-matched subjects.
Given the perceptual changes after immobilization, we then
asked how immobilization affects cortical maps. To assess
possible blood-oxygen-level-dependent (BOLD) signal
changes within the somatosensory cortex after immobiliza-
tion, we performed fMRI measurements on two subpopula-
tions of 12 (4 and 8) subjects in total. Two of the subjects in
the first subgroup wore a cast on their right, and two wore
a cast on their left hand, for a mean duration of 2.3 6 0.5
(mean 6 SD) weeks (Figures 3 and 4). Tactile discrimination
thresholds of these subjects were in the same range as those
described for the entire population investigated. FMRI
measurements were performed once during cast wearing after
two weeks of immobilization. Additionally, in three of these
subjects, a second imaging session was performed two weeks
after cast removal for study of the reversibility of immobiliza-
tion-induced changes. The first imaging session revealed
that after two weeks of immobilization, the representation of
the immobilized index finger in the primary somatosensory
cortex (SI) decreased (Figures 3 and 4). Cluster size of the acti-
vation evoked by stimulation of the immobilized index finger
was distinctly smaller in comparison with the healthy control
index finger (immobilized finger: cluster-level = 3 voxels,
T score = 5.46; healthy finger: cluster level = 17 voxels,
T score = 5.64; n = 4; Figure 4).
The results of the group analysis are shown in the estimated
statistical parametric maps of the fixed-effect analysis
(Figure 4) and reveal focused SI activation in the postcentral
gyrus (n = 4). The second imaging session two weeks after
cast removal revealed no hemispheric differences in BOLD
signal extension and SI intensity (Figure 4), indicating the
reversibility of immobilization-induced cortical changes
(formerly immobilized index finger: cluster level = 23 voxels,
T score = 6.72; contralateral, healthy index finger: cluster
level = 17 voxels, T score = 5.84).
To corroborate the covariation of the behavioral and percep-
tual measures, as well as the fMRI changes, eight additional
right-handed subjects (aged 18 to 48 years), who wore a cast
on their right hand, were analyzed for quantitative indices of
the relationship between changes in BOLD signals and hand
use and tactile discrimination. We used the mean signal inten-
sity (MSI) as the statistical parameter for the quantification
of the BOLD response. During immobilization, we found sig-
nificant individual differences between the healthy and
the cast-wearing side for both parameters (mean signal