brain neck proprioception and spatial orientation in ......33–82 years, mean 59 6 15.1 (sd); mean...
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doi:10.1093/brain/awh291 Brain (2004), 127, 2764–2778
Neck proprioception and spatial orientation incervical dystonia
Marco Bove,1 Giampaolo Brichetto,2 Giovanni Abbruzzese,2 Roberta Marchese2 and Marco Schieppati3
Correspondence to: Professor Marco Schieppati, Centro
Studi Attivita Motorie (CSAM), Fondazione Salvatore
Maugeri (IRCCS), Via Ferrata 8, 27100 Pavia, Italy
E-mail: [email protected] and [email protected]
1Department of Experimental Medicine, Section of Human
Physiology, 2Department of Neurological Sciences,
Movement Disorder Unit, University of Genoa and3Department of Experimental Medicine, Section of Human
Physiology, University of Pavia, and Human Movement
Laboratory (CSAM), Fondazione Salvatore Maugeri
(IRCCS), Scientific Institute of Pavia, Italy
SummaryNeck muscle vibration is known to influence body orienta-
tion and posture during locomotion and stance in normal
subjects. To verify the hypothesis that neck proprioceptive
input can be misinterpreted in patients with cervical dys-
tonia (CD), lateral continuous vibration was applied to the
sternocleidomastoid muscle during both stepping-in-place
and quiet stance, with eyes closed. The orienting responses
of CD patients were compared with those of normal sub-jects. Vibration effects on body orientation during step-
ping and stance were apparently different from normal,
since no effects were seen when all patients’ data collapsed
were analysed. However, while some patients did not
respond to vibratory stimuli regardless of the vibrated
side, others had a ‘good’ side, the stimulation of which
produced effects on body orientation similar to those
observed in normal subjects. Homogeneous groupswithin the patient population were identified, based on
the vibration-induced responses under stepping condi-
tions. The different orienting or postural responses
observed in CD patients were correlated with disease-
related features such as spontaneous head position, max-
imum range of voluntary head yaw, presence or absence of
a botulinum toxin treatment and disease duration. Our
data suggest that, in CD patients, the reference system
used in the control of body orientation in space is eitherrefractory to the lateralized proprioceptive neck input or
modified such that the input from both sides produces an
orientation shift in the same sense. This would depend on
the pathogenesis of the disease or on an adaptive process
connected to the head abnormal posture. It seems that this
refractoriness spreads to both sides of the neck with the
advancement of the disease, thereby possibly entraining a
progressive shift from a reference system based on thehead to a more reliable egocentric reference.
Keywords: cervical dystonia; neck muscle vibration; neck proprioception; quiet stance; stepping-in-place;
spatial orientation
Abbreviations: BTX = botulinum toxin; C = control condition; CD = cervical dystonia; CFP = centre of foot pressure;
CCW = counter-clockwise; CW = clockwise; SCM = sternocleidomastoid; Vl = vibration to the left side of the neck;
Vr = vibration to the right side of the neck.
Received February 23, 2004. Revised July 23, 2004. Accepted July 25, 2004. Advanced Access publication September 8, 2004
IntroductionProprioceptive input from the neck muscles plays an import-
ant role in the definition of the reference system for the control
of posture and locomotion. Cohen (1961) pointed to the
weight of neck proprioceptive inputs in the control of body
orientation and motor coordination in monkeys. In humans,
several studies led to the notion that neck afferent input plays
a significant role in the control of posture (Brandt, 1996) and
that disturbances to the neck musculature can provoke dizzi-
ness or unsteadiness, the so-called ‘cervico-genic dizziness’
(Brandt and Bronstein, 2001). Hlavacka and Njiokiktjien
(1985) and Fransson et al. (2000) showed an influence of
active and passive neck torsion on the direction of galvani-
cally induced postural responses, an effect expected on the
basis of the convergence of neck and labyrinth input onto
Brain Vol. 127 No. 12 # Guarantors of Brain 2004; all rights reserved
brainstem nuclei (Pompeiano et al., 1991) and vestibular neur-
ons (Anastasopoulos and Mergner, 1982). Recently, a pro-
longed contraction of dorsal neck muscles has been shown
to alter balance control through a mechanism connected to
fatigue-induced afferent inflow (Schieppati et al., 2003).
Proprioception is often studied by means of muscle
vibration, since this is an adequate stimulus for selectively
activating the spindle receptor, thereby inducing a vibration
frequency-entrained excitation of the primary endings and a
train of action potentials in the large diameter afferent fibres
(Burke et al., 1976a; Roll and Vedel, 1982; Matthews, 1988).
Lund (1980) showed that neck muscle vibration had obvious
effects on standing posture. Vibration has also been applied to
various body muscles under various behavioural conditions,
including postural and locomotor tasks (Courtine et al.,
2001). Lateral neck muscle vibration, in the absence of
vision, produces undershoot of target and deviation of the
trajectory during gait (Bove et al., 2001) and body rotation
during stepping (Bove et al., 2002); under both conditions,
the deviation is opposite to the vibration side. Ivanenko et al.
(1999, 2000) showed that when the head is horizontally
turned or the eyes are laterally rotated, vibration of dorsal
neck muscles during stepping-in-place causes stepping in
the direction of the naso-occipital axis or of the gaze,
respectively. Ledin et al. (2003) found that head tilt on
the sagittal plane, but not head rotation, produces changes
in the postural sway induced by leg muscle vibration in
standing subjects, thus confirming previous findings (Kogler
et al., 2000) on the absence of major effects of head torsion
on postural control.
The above effects can hardly be interpreted in terms of
simple reflex effects. Goodwin et al. (1972) originally
described proprioceptive illusions induced by muscle
vibration. It was shown later that neck muscle vibration elicits
apparent motion of a stationary visual target and deviation of
the perceived ‘straight ahead’, possibly by producing a change
in the egocentric body-centred coordinate system (Biguer
et al., 1988; Taylor and McCloskey, 1991; Karnath et al.,
1994). In standing subjects, neck muscle vibration induces
body tilt and increased sway, suggesting that posture is
organized with respect to a ‘body schema’, to the construction
of which neck input contributes together with eye and skeletal
muscle (Eklund, 1972; Roll et al., 1989; Gurfinkel et al., 1995;
Ivanenko et al., 1999; Kavounoudias et al., 1999). In ‘neglect’
patients, neck muscle vibration can compensate the horizontal
displacement of the sagittal midplane (Karnath et al., 1993;
Karnath, 1994). Bottini et al. (2001) have shown recently that
signals from the neck muscles and from the labyrinth
converge onto several areas of the cortex, including the
temporo-parietal junction, the insular and retroinsular cortex
and the secondary somatosensory area, and proposed the
notion that these areas contribute to the egocentric
representation of space.
Idiopathic cervical dystonia (CD) is the most common
adult-onset focal dystonia and is defined as head rotation
caused by an abnormal involuntary neck muscle contraction
(Nutt et al., 1988; Jankovic et al., 1991). Recently, the
existence of a pathogenetic role for sensory feedback in
dystonia has been discussed (Hallet, 1995; Abbruzzese
and Berardelli, 2003; Tinazzi et al., 2003). Sensory input
may be abnormal and trigger focal dystonia, or its defective
‘gating’ may cause an input–output mismatch in specific
motor programmes. Several observations strongly support
the idea that sensorimotor integration is impaired in focal
dystonia (Abbruzzese et al., 2001; Munchau et al., 2001;
Siggelkow et al., 2002). Moreover, dorsal neck input in the
context of whole-body postural control and spatial
orientation seems to be relatively ignored in CD patients
(Lekhel et al., 1997). These notions are consistent
with results obtained in these patients by means of psycho-
physical studies of spatial orientation (Anastasopoulus et al.,
1997a,b).
However, the matter is still controversial. A population of
dystonic patients has been shown to exhibit altered postural
control, and to improve their stance control after botulinum
toxin (BTX) injection that normalized neck muscle activity
(Wober et al., 1999). Other studies described a great variab-
ility in the capacity of CD patients to estimate their head and
trunk direction; nonetheless, these patients appeared to estim-
ate head and trunk displacements correctly in ego-centric and
space-centric spatial orientation tasks (Anastasopoulos et al.,
2003). The aim of the present study was to shed further light
on the effect of neck muscle proprioception in CD patients, by
using an experimental protocol recently developed, where
neck muscle vibration is used to modify the reference system
for spatial orientation during a dynamic, locomotor task (Bove
et al., 2001). In particular, we report here the effects of lateral
neck muscle vibration on body orientation during an extended
stepping-in-place task without visual information. Such sti-
mulation induces in normal subjects a clear-cut body rotation
to the side opposite to the vibrated side (Bove et al., 2002). We
argued that lateral neck vibration during stepping would be
a sensible enough protocol for answering the question of
whether the proprioceptive neck input is ignored in CD
patients in the context of spatial orientation, in which case
no effect of vibration should be observed, or whether the neck
input is centrally integrated in an abnormal way, in which case
anomalous responses would be obtained. Stepping-in-place
was used rather than linear locomotion, since stepping exhi-
bits several key characteristics of locomotion (Lyon and
Day, 1997), in addition to allowing prolonged periods of
locomotor-like activity to be recorded by means of a
movement analysis system. The stepping-in-place paradigm
has also been used extensively in the evaluation of patients
with vestibular disorders (Norre et al., 1989; Bonanni and
Newton, 1998), since the early observations by Fukuda
(1959) of body rotation during stepping in normal subjects
and vestibular patients.
In this work, the neck vibration was also administered to the
same CD patients during quiet stance.
The orienting and postural responses of CD patients and
normal subjects were therefore analysed and compared, in
Proprioception and orientation in dystonia 2765
order to understand whether, in CD patients: (i) a long-term
neck vibration affected body orientation during stepping as in
normal subjects; and (ii) vibration administered during quiet
stance produced effects coherent to those observed during
stepping. The responses were correlated with disease-related
features such as spontaneous head position, maximum range
of voluntary head yaw, presence or absence of a BTX treat-
ment and disease duration.
Material and methodsSubjectsTwelve CD patients [four men and eight women, age range
33–82 years, mean 59 6 15.1 (SD); mean disease duration
9.4 6 5.5 years] and 12 normal subjects (seven men and five
women, age range 31–76 years, mean 51 6 15.5) volunteered for
these experiments. All subjects gave their informed consent for the
study, which was approved by the local ethics committee, and the
study conformed to the Declaration of Helsinki. Normal subjects had
no history of neurological diseases or signs or symptoms of cervical
diseases or trauma. On clinical examination, subjects and patients
showed no vestibular deficits or discrepancies between right and left
lower limbs that can affect veering of locomotion (Boyadjian et al.,
1999). In CD patients, both the amplitude of head deviation from the
primary position (spontaneous head position) and the maximum
range of the voluntary head rotation (yaw) were measured during
quiet upright stance. These and other features are summarized in
Table 1. Of the 12 patients studied, seven had received type A
botulinum toxin (BTX-A) injections. The BTX-A treatment ranged
between 10 and 40 BTX-A injections [mean 19 6 11.3 (SD)] admi-
nistered in several sessions. In most cases, the injected neck muscles
were the sternocleidomastoid (SCM) controlateral to the head rota-
tion, and one of the ipsilateral dorsal muscles. During the BTX-A
treatment, the injections scheme was modified in some patients as a
function of the head posture changes. Two patients had received
BTX-A injections in both SCM muscles, and one had only the
left dorsal muscles injected. All these patients were evaluated at
least 3 months after the last injections. The remaining five patients,
candidate for receiving for the first time BTX treatment, were eval-
uated before the injection.
ProcedureWhen they first came to the laboratory, subjects and patients prac-
tised stepping-in-place, with eyes open and closed, for �30 s before
recording. For the experimental session, they were instructed to start
stepping-in-place at their own preferred pace, on a verbal go signal
until they were told to stop after 60 s. This was done under both
control (C, no vibration) and vibration (V) conditions, in which case
they were told not to react to the applied stimulation; in particular,
there was no instruction to keep any pre-set facing direction or any
definite head or body position. The CD patients were free to maintain
their spontaneous head position during stepping. In different trials,
vibration was delivered randomly to the right (Vr) and left side (Vl)
of the neck. All subjects and patients easily succeeded in the
stepping-in-place task in all trials and, within each trial, for the entire
epoch of acquisition (1 min). The room was dim lit and the subjects
kept their eyes closed during stepping. Under all conditions, the onset
of acquisition of the kinematics signal started �3 s after the verbal go
signal for stepping onset. By this time, subjects and patients had
already performed at least one or two complete stepping cycles.
For V, the vibrator was set on concurrently with the onset of the
acquisition. The vibrator and the acquisition were shut off 60 s later,
at the end of the trial. Two trials were performed randomly for each
C, Vr and Vl condition (six trials in total). The entire session lasted
�60 min, including rest periods. After the session, subjects were
asked specifically about head tilt or rotation illusions: under no
circumstances did normal subjects or CD patients report explicit
sensations of head turning or tilting on the trunk in response to
the vibration. This is not contradictory to the finding reported in
the study of Taylor and McCloskey (1991), where dorsal neck vibra-
tion rarely produced illusions of head movement. We did not check,
Table 1 Clinical features of the CD patients
Patientno.
Sex Age(years)
Duration(years)
Type ofcervicaldystonia
Associatedsigns
Treatment andSCM muscleinjected
Head deviation(�) ( + , R; �, L)
Max head voluntaryrotation (�)
to R to L Total
1 F 45 11 Rotatocollis (R) Head tremor BTX-A, R/L 8.5 32.6 59.0 91.62 M 82 13 Rotatocollis (R) – BTX-A, L 7.5 41.3 57.7 993 F 62 4 Rotatocollis (L) – BTX-A, R �25.8 22.3 37.6 59.94 F 33 11 Rotatocollis (L) – – �24.7 78.3 33.5 111.85 F 55 3 Rotatocollis (L) – – �6.5 22.0 27.4 49.46 M 47 13 Rotatocollis (L) – BTX-A, R; AC �14.4 50.0 53.1 103.17 M 63 6 Rotatocollis (L) Head tremor;
right arm dystoniaBTX-A, R/L; AC �23.2 71.1 11.9 83
8 F 42 2 Rotato- andlaterocollis (L)
– – �15.2 72.0 51.1 123.1
9 F 76 6 Rotatocollis (R) – BTX-A, L 44.5 5.2 90.7 95.910 F 70 9 Rotatocollis (L) Head tremor;
upper limbs tremor– �19.8 52.3 1.1 53.4
11 F 74 21 Laterocollis (R) Head tremor – 29.6 16.3 96.9 113.212 M 55 14 Retro- and
rotatocollis (R)– BTX-A 8.3 39.9 47.8 87.7
R = right; L = left; BTX-A = botulinum toxin type A; AC = anticholinergics; SCM = sternocleidomastoid.
2766 M. Bove et al.
however, whether vibration produced errors in the execution of
movements pointing at a specific spot in the head.
In a separate session, three of the normal subjects performed addi-
tional stepping-in-place trials, in C and V conditions, with the head
deliberately kept rotated �20�, first on the right and then on the left
side. Five other naıve subjects (two men and three women, age range
24–40 years, mean 29.6 6 6.2), who did not participate in the main
experiment, were also recruited for this experiment. This was done to
check, first, any effects of static head yaw on body rotation during
stepping under control condition and, secondly, possible differences
in the effects of neck muscle vibration on stepping orientation
when the head was in the primary position versus rotated to an
extent comparable with the spontaneous position of the head in
many CD patients. These subjects repeated three trials for each
condition.
All normal subjects and CD patients who participated in the
stepping-in-place sessions also stood upright on a dynamometric plat-
form, on the same day, after a rest period of at least 10 min (see below).
StimulationA DC motor with an eccentric on the shaft, embedded in a plastic
tube (Dynatronic, France), produced 5 N peak-to-peak vibrations at
90 Hz. The vibrator was applied on each side of the neck (left and
right sides were vibrated separately) by means of an elastic strap that
passed around the neck. The vibrated spot was the belly of the SCM
muscle, �40% of its length below its insertion on the mastoid
(�5–6 cm from the mastoid apex), with the cylinder axis about
normal to the direction of muscle. The vibrator was put in place
at the beginning of the experiment and kept in place throughout the
session. In order to evaluate the propagation of the vibration to
the temporal bone, which could possibly induce activation of the
labyrinthine receptors, in three normal subjects we used two identical
accelerometers (TSD109, BIOPAC Systems Inc., Santa Barbara,
CA), one fixed to the vibrator located on the muscle, the other placed
on the ipsilateral mastoid bone. The amplitude of the main peak in the
power spectrum of the vibration signal recorded at the mastoid bone
was, on average, <1% (0.66 6 0.03%) of the signal measured at the
muscle. This finding indicates a negligible propagation of the
mechanical wave to the labyrinth, and strongly lessens the likelihood
of vestibulum-mediated vibration effects.
KinematicsBody movements were recorded by an optoelectronic motion
analysis system (ProReflex, Qualisys AB, Sweden). Four infrared
cameras were located around the experimental field, identifying a
space of �2.5 3 2.5 3 2.5 m. The reflective markers were attached
to the skin on the forehead, vertex of the head, left and right acromion
and on the right lateral femur epicondyle. Two markers on the floor
identified a fixed reference axis. The markers’ position was sampled
at a frequency of 100 Hz. The following parameters were computed
for each trial and under each condition (C, Vr and Vl). (i) Step cycle
frequency. The recording of the vertical displacement of the knee
versus time was subjected to a fast Fourier analysis and the value
of the main peak was taken as the mean value of step frequency.
(ii) Body displacement. The first and last 100 samples (=1 s) of the
vertex marker at the beginning and the end of each trial were aver-
aged in order to obtain a mean position of the head during the first and
last stepping cycles and minimize the error connected with head
oscillation. The averaged initial position was then subtracted from
the averaged final position to obtain the final body displacement. (iii)
Body rotation. This was represented by the changes in the angle
defined by the shoulder axis and the fixed reference axis. The first
and last 100 samples of this angle value (recorded at the beginning
and the end of each trial) were averaged. The initial mean position
was then subtracted from the final mean position. In normal subjects,
the body rotation was �0 in the control condition, and could become
negative or positive when the neck was vibrated on the right or left
side of the neck, respectively (Bove et al., 2002). Negative values
indicate a counter-clockwise (CCW), and positive values a clockwise
(CW) rotation. (iv) Head–shoulder angle (yaw). This was the mean
angle between head antero-posterior axis and shoulder medio-lateral
axis evaluated during stepping-in-place.
Stabilometric recordingThe sampling frequency of the force exerted on three strain gauges of
a dynamometric platform (Medicapteurs, Toulouse, France) was set
at 10 Hz. The subjects were asked to stand still with their eyes closed,
their bare feet on a patterned surface at an angle of 30�, with their heels
separated by 10 cm, and their arms kept at their sides. Each trial lasted
51.2 s, regardless of the condition tested. The vibration was applied
to the same spot and side as in the stepping-in-place sessions. The
antero-posterior and medio-lateral displacement of the centre of foot
pressure (CFP) was measured: (i) during the stance trials without
vibration (C); (ii) during Vr; and (iii) during Vl. The trials
were spaced by at least 3 min, during which subjects were allowed
to move across the laboratory in order to allow recovery from
possible long-lasting effects of vibration (Wierzbicka et al., 1998)
and from the effects of repetition of stance trials (Tarantola
et al., 1997).
Statistical analysisThe effects of vibration on stepping frequency, body displacement,
body rotation, head–shoulder angle and displacement of CFP were
assessed by means of an analysis of variance (ANOVA) for each
subject in each experimental condition. Homogeneity of data var-
iances was evaluated by means of the Bartlett’s test. Comparisons
within groups or between groups (normal subjects or CD patients as
independent variables) were performed by means of a one-way or
two-way repeated measure ANOVA, respectively, where the depen-
dent variables were the three different experimental conditions (C,
Vr and Vl). When repeated measure ANOVA gave a significant (P <
0.05) result, the post hoc Newman–Keuls test was employed to assess
differences among C and V conditions for both the stepping-in-place
and quiet stance protocol.
Linear regression analysis was used to evaluate, in CD patients, the
possible relationship between head yaw angle and CFP mean position
in the sagittal and frontal plane during quiet stance, or between head
yaw angle and body rotation angle during stepping-in-place.
ResultsStepping-in-place
Stepping frequencyIn CD patients, a lower and marginally significant stepping
frequency with respect to normal subjects was observed
Proprioception and orientation in dystonia 2767
within all the experimental conditions (normal subjects, C,
0.93 6 0.02 Hz; Vr, 0.9 6 0.019 Hz; Vl, 0.9 6 0.018 Hz; CD
patients,C,0.7560.07Hz;Vr,0.7660.08Hz;Vl,0.7760.08Hz;
means6SE)[two-wayrepeatedmeasureANOVA,F(2,44) = 4.1;
P= 0.05]. Neck muscle vibration (V) administered during step-
ping did not modify the stepping frequency with respect to C, in
either normal subjects or CD patients [two-way repeated
measure ANOVA, F(2,22) = 0.275; P = 0.76].
Body displacement
The effect of the vibration on the capacity of subjects and
patients to step on the spot was evaluated by the distance
between their final and initial body positions. The mean dis-
tance from the starting position is indicated in Fig. 1A (normal
subjects) and B (CD patients) by the length of the dashed lines
radiating from the origin of the polar plots.
In normal subjects, under C, Vr and Vl conditions, there was
an average body displacement of 58.26 37.6, 59.36 29.4 and
52.5 6 22.8 cm (SD), respectively. This body displacement
was usually oriented forward under the control condition. The
displacement was instead directed to the left or to the right
when the vibration was applied to the right and left side of the
neck, respectively (Fig. 1A). Regardless of the actual direction
of the stepping, the final distance attained during vibration did
not show significant changes with respect to the control
condition (Vr versus C, P = 0.88; Vl versus C, P = 0.45).
In CD patients, the average body displacement was 94.9 6
51.9, 83 6 42.8 and 74.2 6 44.7 cm (SD), in C, Vr and Vl
conditions, respectively (Fig. 1B). The difference in the body
displacement between normal subjects and patients, all con-
ditions pooled, was only marginally significant [two-way
repeated measure ANOVA, F(1,22) = 4.27; P = 0.051].
A marginally significant difference across conditions was
present for the CD patients [two-way repeated measure
ANOVA, F(2,44) = 3.16; P = 0.052]. In fact, the body dis-
placement in both V conditions was lower than that observed
in the control condition, but only in the Vl condition was the
difference significant (P = 0.02).
Body rotation
Normal subjects and patients could rotate slightly on
their vertical axis during stepping-in-place under control
conditions. In the normal subjects, a slow yet continuous
body rotation was the main and consistent effect of the lateral
Fig. 1 (A and B) Polar graph representations of the effects of lateral neck vibration on body rotation and displacement duringstepping-in-place in normal subjects and CD patients. Dashed lines represent the mean angular value of body rotation; solid lines representthe 95% confidence interval (CI) of the mean value, evaluated across all subjects under the different experimental conditions. The lengthof the lines represents the main final distance of body displacement. Normal subjects exhibited only a slight body rotation under the control(C) condition. During vibration (V), there was a systematic rotation, in all subjects, in the direction opposite to the vibrated side. CDpatients showed an ample scatter of non-systematic body rotations under the control condition, leading to a mean value not different fromthat found in the normal subjects. During vibration, the mean body rotations were smaller in the patients than in the normal subjects,but the 95% CIs were about twice those obtained for the normal subjects. The final displacements were larger in the patients than in thenormal subjects. (C and D) The histogram bars represent the mean head yaw value (6SE) during 60 s of stepping-in-place in the threeexperimental conditions across all subjects. On average, in both normal subjects and CD patients, no significant vibration-induced headrotation was observed. However, the variability of the head yaw was much higher in the CD patients than in normal subjects.
2768 M. Bove et al.
neck vibration. In the patients, the rotation during stepping
was less consistent (see below). The mean rotation values
attained by the populations of normal subjects and of CD
patients at the end of the stepping trial are represented by
the angular coordinate of the dashed lines radiating from the
origin of the polar plots in Fig. 1A (normal subjects) and B
(CD patients).
Normal subjects exhibited no major rotation under control
condition, as indicated by the mean value, very close to 0�
(1.2� CCW, dashed black line), and by the small data variance,
as indicated by the two 95% confidence limits (continuous
black lines) (see Fig. 1A). Under vibration conditions, there
was a systematic rotation, in the direction opposite to the
vibrated side. In the figure, the scatter of the rotations induced
by right and left vibrations are indicated by the sectors
between the continuous dark grey and light grey lines, respect-
ively, which correspond to the two confidence limits. On
average, the rotation was �53� CCW and 68� CW with
respect to the initial body position, for vibration applied to
the right and left neck side, respectively. These values were
significantly different from the negligible rotations observed
under the control condition [two-way repeated measure
ANOVA, F(2,44) = 29.06; P < 0.005 for Vr, and P <
0.0001 for Vl]. The distribution of the rotation data around
the population mean value was similar across the two vibra-
tion conditions (Bartlett’s test: P = 0.34).
CD patients exhibited a much smaller consistency in body
rotation than normal subjects under control conditions, in
spite of their average orientation being similar to that of
normal subjects (Fig. 1B). The average final position of
the population was rotated by only a few degrees (7.8�
CW) with respect to the initial position. However, the scatter
of the rotation data was much larger across the patients’
population, as indicated by the broad sector comprised
between the 95% confidence intervals, and the variance of
the data obtained under control conditions proved to be
different between normal subjects and CD patients (Bartlett’s
test: P < 0.001).
CD patients as a population showed no significant differ-
ence in body rotation between vibration and control condi-
tions (Vr versus C, P = 0.09; Vl versus C, P = 0.56). The
amplitude of the confidence interval was similar under control
and vibration conditions, but was about twice that observed
for the normal subjects (under any conditions). The variance
of the data recorded under the C and V conditions proved to be
different between normal subjects and patients (Bartlett’s test,
C, P < 0.01; Vr, P < 0.01; Vl, P < 0.01). This scatter, however,
was more of a population result rather than the expression of
inconsistencies within patients’ performances. To show this,
the absolute differences between the rotations of the two trials
performed by each patient under each condition were aver-
aged and compared in the two populations: no significant
difference between normal subjects and CD patients was
observed in this value [two-way repeated measure
ANOVA, F(2,44) = 1.17; P = 0.32], indicating a similar
variability in each of the subjects of the two groups.
Therefore, the responses to vibration of the individual CD
patients were reproducible, as were those in the normal sub-
jects, in spite of their responses being sometimes very differ-
ent in absolute terms from those of normal subjects. In fact, in
the normal subjects, the confidence interval of the responses
to each vibration condition covered only one quadrant of the
polar diagram. Conversely, in the CD patients, the range
between the confidence intervals of the rotations under
each vibration condition partly overlapped around zero.
This is the outcome of a non-systematic response pattern to
vibration across the whole group of CD patients: CCW and
CW responses alike could occur in fact for the same neck
vibration side in different patients.
The mean position of the head on the vertical axis with
respect to the body sagittal plane was evaluated in normal
subjects and CD patients during the stepping-in-place under
all conditions. Under control conditions, normal subjects had
a mean head yaw angle of �0.08 6 0.9� (SE) (Fig. 1C), while
in the patients this mean angle reached �3.8 6 3.9� (Fig. 1D).
Interestingly enough, the mean head yaw angle during the
stepping trials underwent no significant vibration-induced
changes across any condition. This was true for both the
normal subject group [one-way ANOVA, F(2,22) = 0.006;
P = 0.99] (Fig. 1C) and the patient group [one-way ANOVA,
F(2,22) = 1.14; P = 0.34] (Fig. 1D).
Patient groups according to their responsesTo better describe the responses to neck vibration in CD
patients, data were analysed in each single patient, in order
to extract potential features common to other patients of the
same population, and possibly identify homogeneous sub-
groups. The mean body rotations under vibration conditions
are shown in Fig. 2A, for each patient. Figure 2B depicts the
same data for the normal subjects population, and allows a
comparison of the vibration effects on body rotation in the
two groups. Dashed lines are the limits of the 95% confidence
interval of the body rotations evaluated within all the CD
patients (Fig. 2A) and normal subjects (Fig. 2B) under control
conditions. The interval thus identified is considered, for each
group, as the zone where the neck vibration effects on the body
rotation are non-significant. The bars are the mean rotation
values calculated from the two trials accomplished during
vibration of the same side. Across normal subjects, the ampli-
tude and sign of the vibration-induced rotations were very con-
sistent: all subjects rotated CW on Vr and CCW on Vl. Across
the patients, vibration induced two main patterns. (i) The
responses to vibration applied to both the right and the left
side lay inside the confidence interval. Five of the 12 patients
(subjects2,3,4,6and11)had thiskind of response. Henceforth,
these patients are indicated asbelonging toagroup ‘insensitive’
to vibration stimuli (INS group). (ii) The body rotations in
response to vibration were significantly different from those
observed under control conditions (and congruent with the
responses observed in the normal subjects) when one side of
the neck was vibrated, but they were either non-significant
Proprioception and orientation in dystonia 2769
or were incongruent when the other side of the neck was
vibrated, since the body rotated in the ‘wrong’ direction
compared with normal subjects’ rotation. Hence, there was
in this group one ‘sensitive’ side and one ‘insensitive’ or
‘wrong’ side (note, however, that the wrong rotations never
exceeded the correct response on contralateral stimulation).
Seven patients showed this pattern, and were divided in turn
into two subgroups related to the neck side, the vibration of
which induced the ‘correct’ response (the RIGHT group con-
sisted of subjects 8, 9 and 12; the LEFT group consisted of
subjects 1, 5, 7 and 10).
Figure 3A, B and C summarizes the mean responses to
lateral neck vibration of INS, RIGHT and LEFT groups,
respectively. As expected, the INS group (Fig. 3A) showed
no significant rotation under vibration or control conditions
[one-way repeated measure ANOVA, F(2,8) = 1.95; P = 0.2],
while the RIGHT (Fig. 3B) and LEFT (Fig. 3C) groups were
selectively and significantly sensitive to vibration [one-way
repeated measure ANOVA: RIGHT group, F(2,4)= 10.44; P <
0.05; LEFT group, F(2,6) = 6.13; P < 0.05]. The mean RIGHT
group response to right vibration was a CCW rotation of
�111� (Vr versus C, P < 0.05), while left vibration induced
no significant effects. Conversely, the LEFT group rotated
CW �83� for vibration to the left side (Vl versus C, P <
0.05), and no significant rotation was induced by right
side vibration. Interestingly, the variability of the vibration-
induced body rotations within each of these groups, in
spite of the small number of patients, was of the same
magnitude as that in the normal subjects population.
Head–shoulder angle (yaw) versus bodyrotation angleThe spontaneous head yaw mean angles ranged between 3 and
50� in the CD patients. We tested the hypothesis that the head
positioncouldaffect thevibration-inducedbodyrotation. Since
it is known (Leis et al., 1992; Lekhel et al., 1997; Karnath et al.,
2000) that neck muscle vibration can produce sizeable effects
on head yaw in CD patients, we recorded head yaw relative to
trunk during vibration. The plot in Fig. 4 shows, for each pati-
ent, the mean head yaw during Vr and Vl (ordinate) versus the
spontaneous head yaw. Across the patients, there were no
major vibration-induced changes, as indicated by the data
points clustering close to the identity line. There were non-
negligible effects in some patients, but the effects were appar-
ently not side specific in this population. Moreover, there was
apparently no difference in the vibration-induced effects on
head yaw among the three patient groups, as defined above
(INS, RIGHT and LEFT), since the data of the patients belong-
ing to these groups formed no clear clusters in the scatterplot.
The possible effect of the head posture on the body orienta-
tion during stepping-in-place was then analysed across indi-
vidual patients stepping under both control and vibration
conditions. All individual trials from all the patients were
segregated in Fig. 5, which shows the scatter graphs of
body rotation angles against head yaws, for C (Fig. 5A),
Vr (Fig. 5B) and Vl (Fig. 5C) conditions. No significant rela-
tionships between head–shoulder angle and body rotation
angle were found either in C or V conditions (C, P = 0.26;
Vr, P = 0.12; Vl, P = 0.095). Similar results were found in
normal subjects (C, P = 0.61; Vr, P = 0.59; Vl, P = 0.59), as
already shown in Bove et al. (2002).
Head deliberately rotated in normal subjectsEight normal subjects stepped with eyes closed with the head
rotated to either side to an extent similar to that found in the
Fig. 2 Effects of vibration on body rotation for each CD patient(A) and normal subject (B). The bars are the mean values of thetwo trials performed by each patient and subject. The rotationeffects are separated for the vibration side. Dashed lines representthe upper and lower limits of the 95% confidence interval of themean evaluated across all subjects in the control condition. Theinterval thus identified is considered as the zone where the neckvibration effects on the body rotation are non-significant. In (A),the circles at the top of the bar pairs indicate CD patientsbelonging to the RIGHT (open symbols) or LEFT group (filledsymbols). The other CD patients belong to the INS group.
2770 M. Bove et al.
patients (Fig. 6A). Under the control condition, no or non-
systematic body rotations were observed, across subjects or
trials (Fig. 6B). The mean head–shoulder yaw angles were
(mean 6 SE): head in primary position, 0.68 6 1.17�; left
rotation, �28.74 6 3.11�; right rotation, 22.83 6 2.64�. These
head positions were also broadly maintained during vibration.
The vibrations, on either the right or the left side, induced
significant and systematic CCW and CW body rotations,
respectively (Fig. 6B) [two-way repeated measure
ANOVA, F(2,42) = 91.28; P < 0.001]. The analysis also
confirmed that head position did not affect the vibration-
induced body rotation [two-way repeated measure
ANOVA, interaction effect, F(4,42) = 0.96; P = 0.44]. The
deliberate head rotation did not significantly affect the abso-
lute value of the responses to vibration compared with those
observed with the head in the primary position (post hoc, left
rotation in both Vr and Vl, P > 0.1; right rotation in both Vr
and Vl, P > 0.1). To assess whether the variability of the body
rotation angles during stepping was affected by the head pos-
ture (possibly producing a scatter in the data comparable with
that seen in the CD patients), the data obtained in these trials
with the head deliberately rotated were compared with those
obtained in the population of normal subjects stepping with
the head in the primary position, illustrated in Fig. 1A. The
homogeneity of variances between these two sets of data was
confirmed by the Bartlett’s test (P = 0.19).
Upright stance
Antero-posterior CFP positionUnder control conditions, CD patients were inclined forward,
on average, somewhat more than normal subjects (Fig. 7).
Their CFP lay significantly ahead with respect to that of
normal subjects [two-way repeated measure ANOVA,
F(1,22) = 12.96; P = 0.0015]. Across the patients, there
was no relationship between the spontaneous head yaw
angle and the CFP position in the sagittal plane (F = 0.33;
P = 0.58). Vibration exerted no significant effect on the
antero-posterior position of the CFP in either normal subjects
Fig. 3 Effects of vibration on body rotation. Average values of thethree patient groups. (A) The INS group showed no significanteffects on body rotation during vibration on either neck side.(B) The RIGHT group was sensitive to vibration administered tothe right side of the neck. Left side vibration induced a small andnon-significant response toward the ‘wrong’ side with respect tothat observed for the same condition in normal subjects. (C) TheLEFT group was sensitive to vibration when vibration wasadministered to the left side of the neck, while right side vibrationinduced a response similar to that observed in the controlcondition.
Fig. 4 Mean head yaw during vibration as a function ofspontaneous head position during stance. Each patient enters thegraph with two data points for each value of the abscissa. Thesetwo data points represent the mean head yaw during vibration(white for Vr condition, grey for Vl condition). In turn, each valueon the ordinate results from the mean of two equal-conditiontrials. In general, there were no major vibration-induced effects onhead position across the patients, as indicated by the data pointsclustering close to the identity line. There were non-negligibleeffects in some patients, but these effects were apparently not sidespecific. The patient groups are identified with different symbols.There is apparently no difference in the vibration-inducedeffects on head yaw among the three groups.
Proprioception and orientation in dystonia 2771
(squares) or in CD patients (circles) [two-way repeated
measure ANOVA, F(2,44) = 2.91; P = 0.07].
Medio-lateral CFP positionUnder control conditions, the medio-lateral CFP position
was not different between normal subjects and CD patients
(Fig. 7). As for the antero-posterior plane, there was no
significant regression between spontaneous head yaw
angle and CFP position in the frontal plane (F = 0.085;
P = 0.78).
Lateral neck muscle vibration induced in the normal sub-
jects a significant CFP displacement in the frontal plane with
respect to C (Fig. 7), the amplitude of which was in turn
compatible with published data (Bove et al., 2001). In particu-
lar, Vr induced a shift to the left and Vl to the right. In the
CD patients, vibration had a much weaker effect on medio-
lateral displacement of CFP. Two-way repeated measure
ANOVA showed an effect of group (normal subjects versus
CD) and an interaction between groups and conditions.
In particular, significant differences in the medio-lateral
CFP displacements induced by vibration were observed
between normal subjects and CD patients [F(2,44) = 11.71;
P < 0.001]. Post hoc test showed a significant side-related
effect of vibration in normal subjects (P < 0.001), but no effect
in CD (P = 0.11). Therefore, on average, the patients had a
smaller sensitivity to vibratory stimuli than normal subjects
under quiet stance as well as under stepping-in-place
condition.
Effects of vibration during stance in thepatients’ groupsThe patients’ CFP was re-analysed based on the separation in
the three groups defined on the basis of the findings collected
with the stepping-in-place protocol, and the postural
responses to neck vibration of the three groups compared
separately. Figure 8A, B and C shows the mean postural
responses to lateral neck vibration of the INS, RIGHT and
LEFT groups, respectively. The INS group did not show
significant differences in medio-lateral CFP displacement
during either Vl or Vr conditions [one-way repeated measure
ANOVA, F(2,8) = 2.58; P = 0.137]. However, during V
conditions, a significant backward displacement of the CFP
along the sagittal plane with respect to C was observed [one-
way repeated measure ANOVA, F(2,8) = 4.79; P = 0.043]. In
the RIGHT group, neither Vl nor Vr evoked significant
antero-posterior displacements during vibration (one-way
repeated measure ANOVA, F(2,4) = 1.79; P = 0.28]. How-
ever, vibration produced a significant medio-lateral displace-
ment with respect to the control condition (one-way repeated
measure ANOVA, F(2,4) = 7.61; P = 0.043]. This
displacement (a mean shift to the left on the frontal plane
of�12 mm) was significant only for Vr (P < 0.05). In contrast,
Vl induced only a slight and non-significant medio-lateral
displacement with respect to C (P = 0.093) in the ‘wrong’
direction (to the left), compared with the response observed in
the normal subjects group under the same condition (Fig. 7).
In the LEFT group, no significant vibration effects on CFP
displacement on the sagittal plane were observed [one-way
repeated measure ANOVA, F(2,6) = 0.69; P = 0.54]. How-
ever, in this group, the CFP position in the frontal plane was
significantly sensitive to Vl [one-way repeated measure
ANOVA, F(2,6) = 4.62; P = 0.046]: a displacement to the
Fig. 5 Head yaw angles versus body rotation angles under C (A),Vr (B) and Vl (C) conditions. All trials of all CD patients arecollapsed. Negative head yaw angles correspond to head deviationto the left, positive correspond to head deviation to the right.Negative body rotation angles refer to counter-clockwise bodyrotation, while positive angles refer to clockwise rotation. Therewas no significant relationship between head–shoulder angle andbody rotation in any of the three experimental conditions.
2772 M. Bove et al.
right of �15 mm was induced by Vl, while Vr did not exert
any influence on CFP medio-lateral displacement (P = 0.99).
DiscussionStepping-in-placeLateralized neck muscle vibration, applied during stepping-
in-place with the eyes closed, is known to induce clear-cut
body rotation and a moderate displacement from the starting
position in normal young subjects. The rotation is invariably
toward the side opposite to the vibrated site, i.e. CW on left
and CCW on right side vibration, respectively, and the dis-
placement is in the forward direction (Bove et al., 2002). The
normal subjects recruited in the present study, who repres-
ented a population age-matched to the CD patients, repro-
duced the same patterns of body displacement observed in
the young subjects under control conditions and in response
to vibration.
Forward displacementThe CD patients showed significant differences from normal
subjects in their body progression during stepping-in-place,
under control conditions. Forward body displacement was
almost twice as large as that observed in normal subjects.
The body therefore moved with a relatively higher velocity
than in normal subjects, since the trial duration was constant.
It is worth noting that the stepping frequency of CD patients
was significantly lower than that of normal subjects, thus
patients take ‘longer steps’ than normals. The significantly
lower stepping frequency in CD patients would be in keeping
with the occurrence in these patients of ‘parkinsonian symp-
toms’ such as bradikynesia (Couch, 1976). The increased step
length should not be taken as a contradiction, since we do not
deal here with true locomotion, and the ‘high’ velocities were
in the order of 1 m/min. These incongruities may rather
Fig. 6 Neck vibration effects on the body rotation, in eight normalsubjects, during stepping-in-place with the head positioned in theprimary position or voluntarily rotated to either side. Thehistogram bars are separated into three groups, according to thecondition (C, control; Vr, vibration right; Vl, vibration left).(A) The left bar of each group refers to the head in the primaryposition, the middle bar to the head rotated to the right, and theright to the head rotated to the left. In (B), the body rotation anglesare shown for each of the head positions corresponding to thevalues reported in A. Under control conditions, there were no ornon-systematic body rotations across subjects and trials. Therewere significant body rotations when the neck vibration wasapplied to the right (Vr) or left (Vl) side. Systematic counter-clockwise and clockwise body rotations for vibration to the rightand left side, respectively, were observed. For all conditions, nosignificant effects of head position on rotatory responses tovibration were observed.
Fig. 7 Postural responses to lateral neck muscle vibration in thenormal subjects (NS, squares) and in all the CD patients (circles)are represented by the medio-lateral and antero-posterior shift ofthe centre of foot pressure (CFP) during quiet stance. Grandaverages of all subjects and trials are shown, separately for eachcondition (C, Vr and Vl). Normal subjects showed significantmedio-lateral displacements of the CFP towards the side oppositeto vibration. The position of the CFP in the CD patients wassignificantly advanced with respect to that of normal subjects(P < 0.01), but showed no significant change on right or leftvibration in either the frontal or sagittal plane.
Proprioception and orientation in dystonia 2773
indicate for CD patients a greater difficulty than normal sub-
jects to step ‘in place’ without visual information.
Vibration of the SCM muscle did not modify forward
displacement in normal stepping subjects, but in CD patients
it reduced the distance reached. Ivanenko et al. (2000) showed
that, during stepping-in-place, dorsal neck vibration produced
in normal subjects an involuntary forward stepping, which has
been explained as the consequence of an illusion of forward
movement of the head or forward sway (Lund, 1980; Lekhel
et al., 1997) to which the appropriate response is to step
forward. In our case, the vibration was not acting on dorsal
muscles; indeed, normal subjects did not increase their pro-
gression rate. It is curious nonetheless that CD patients
reduced their progression with vibration, while a forward
progression might perhaps have been expected as an effect
of diffusion of the vibration to the dorsal muscles, not least
because of the abnormal head position.
Body rotationThe CD patients exhibited a much smaller consistency in body
rotation than normal subjects under control conditions, as
proved by a significant difference between the data variances,
in spite of their average orientation being similar to that of
normal subjects. The effects of the neck muscle vibration on
body rotation during stepping were also different from nor-
mal, since when the collapsed data from all patients were
analysed, there was no effect of vibration on body rotation.
In fact, no significant difference in the average body rotation
during vibration, either on the left or on the right side, was
detected with respect to their average rotation under control
conditions. This could have been the outcome of a smaller
sensitivity to vibration in CD patients or of a ‘wrong’, abnor-
mal response to lateral neck vibration, or both. However, one
of the reasons for the lack of a systematic vibration-induced
body rotation in CD patients proved to be the ample variability
in the body rotation across subjects, under both vibration and
control conditions. This was in fact reflected in a confidence
interval of the population data that was about twice as large as
and significantly different from that observed for the normal
subjects, under any condition.
CD patients’ groupsThis analysis of the responses of each patient gave the pos-
sibility to extract potential common features and to identify
homogeneous groups within the population of CD patients. In
fact, it soon appeared that there were patients who did not
rotate, regardless of the vibrated side, or patients who had a
‘good’ side, the stimulation of which produced effects on
body rotation similar to those observed in normal subjects.
It also appeared that no CD patient exhibited a fully normal
response (CW on Vl and CCW on Vr); rather, patients were
refractory to vibration on either or both sides of the neck. In
those with one good side, the contralateral side could be
refractory or exhibit the same response observed on the vibra-
tion of the good side, as if the CNS could produce one and the
same type of rotatory response on receiving the propriocep-
tive input from either side of the neck. CD patients could then
Fig. 8 CD patients under quiet stance condition. Postural responsesto lateral neck muscle vibration of the INS, RIGHT and LEFTgroups. (A) In the INS group, vibration induced no effect on bodydisplacement in the frontal plane, while it induced a significantbackward displacement in the sagittal plane with respect to control.(B) The RIGHT group patients were sensitive to vibrationadministered to the right side of the neck. Left side vibration induceda slight and non-significant medio-lateral displacement with respectto control in the ‘wrong’ direction, compared with the responseobserved in the INS group under the same condition (see Fig. 5).(C) The LEFT group was sensitive to vibration administered to theleft side of the neck. Postural responses similar to those observed inthe control condition were obtained when vibration wasadministered on the right side of the neck.
2774 M. Bove et al.
be classified into three groups, according to their complete
(INS) or partial (RIGHT or LEFT) sensitivity.
Head abnormal posture is unrelated toabnormal body orientation response to vibrationduring stepping-in-placeA concern was represented by the possibility that the spontan-
eous head abnormal posture of CD patients would ‘deter-
mine’ the body rotation induced by the lateralized neck
vibration, either because of the ongoing asymmetrical ‘nat-
ural’ input possibly being able to modify the orientation of
stepping or because during vibration it could counteract in
some way the effect of the asymmetrical neck muscle pro-
prioceptive input. A further concern was represented by the
possibility that lateral neck muscle vibration would produce
head-on-shoulder rotation in both normal subjects and
patients, in turn possibly affecting the orientation of the
body during stepping. Neck muscle vibration in fact has
been reported to induce involuntary movements of the head
in some patients (Lekhel et al., 1997; Karnath et al., 2000). A
still further concern was that the changes in muscle length or
contraction level or in passive or active stiffness of the
vibrated muscles, due to the head posture, could modify
the mechanical effect of the vibratory stimulus (Burke
et al., 1976b).
However, during the stepping trials, no significant changes
in the head primary position were observed on lateralized
neck vibration in normal subjects. In the control experiments
on normal subjects, with the head deliberately turned, with or
without vibration, no significant relationship between head
yaw angle and body rotation angle was observed across sub-
jects and conditions, as already reported in Bove et al. (2002).
The spontaneous head position (yaw) did show some
vibration-induced changes in a few CD patients; however,
no significant relationships between head yaw and body rotation
angle during stepping-in-place across all the patients and
conditions (control and vibration) were observed. Further,
it might be noted that these relationships were characterized
by a similar slope, to underscore again a general lack of
dependence of spatial orientation effects on head postural
response to vibration of CD patients.
In spite of the variability across subjects, the absence of
significant body rotation when the head was deliberately
turned, in the normal subjects under both no vibration and
vibration conditions, points to the irrelevance of the natural
asymmetric neck input on the body rotation during the step-
ping trial. This result would be taken as evidence against the
possible influence of the muscle stiffness on the vibration-
induced afferent volley, because if stiffness or contraction had
conditioned the efficacy of the vibration, the spindle input
from the vibrated muscle would be expected to change
depending on the muscle being active and shortened or
being passive and lengthened during the head rotations.
In the treated patients studied here, the single dose of the
BTX was within the range commonly used in CD treatment
(between 15 and 100 IU). Further, the behaviour of the groups
did not differ with respect to the spontaneous head position,
BTX treatment and maximum range of voluntary head yaw
(Fig. 9). Interestingly, the spontaneous angular head deviation
with respect to the primary position (Stell et al., 1988; Tsui
et al., 1996) was not correlated with the degree of maximal
voluntary rotation of the head in any of the three groups. All
these features suggest that the absent or limited insensitivity to
vibration was not directly related to the disease effects on the
neck torsion (see below). In addition, CD patients who had
never received the BTX treatment showed the same responses
as the other patients. Moreover, treated and untreated patients
were distributed in the different CD groups and they shared
the same mean features for both spontaneous head position
and maximum head rotation angle of the other patients. This
would exclude the possibility that the observed ‘insensitivity’
was caused by the BTX injections, through its effects on
spindle afferent activity as seen in rat (Filippi et al., 1993;
Rosales, 1996) and humans (Priori et al., 1995; Naumann and
Reiners, 1997; Gilio et al., 2000). We do not know whether
larger doses or a longer period of BTX-A treatment could
affect the spindle’s transduction properties, or whether long-
term effects of the BTX could induce any effect on spindle
sensitivity. However, we observed that the two patients who
received several BTX-A injections on both SCM muscles
showed only a partial insensitivity to vibratory stimuli,
while other patients treated only on one neck side fall within
the INS group.
Quiet stanceUnder this condition, lateral neck vibration produces a medio-
lateral body displacement, opposite to the side of the vibration
Fig. 9 Maximum voluntary head rotation angle in the horizontalplane plotted against mean spontaneous head position in CDpatients. Patients were identified with different symbols for eachgroup. Black filled symbols correspond to the fiveBTX-A-untreated patients.
Proprioception and orientation in dystonia 2775
(Eklund, 1972; Bove et al., 2001, 2002) and it did so in our
normal subjects tested during stance. In CD patients, during
quiet upright stance, the effects of neck muscle vibration were
different from normal, since when all the patients’ data
collapsed were analysed, there was no effect of vibration
on posture. The absence or reduction of postural responses
was also seen by Lekhel et al. (1997) when the dorsal neck
muscles were vibrated.
Interestingly enough, during quiet upright stance, patients
belonging to the RIGHT and LEFT group revealed behaviours
reminiscent of that observed under the stepping-in-place con-
dition. In fact, these patients correctly responded only to
vibration of the same side of the neck that produced rotation
during stepping-in-place. It should be noted that in both
stepping-in-place and upright stance conditions, the ‘correct’
responses of CD patients implied body rotations or medio-
lateral displacements of similar amplitude to those observed
in normal subjects. The INS group showed no significant
medio-lateral displacements induced by vibration during
stance, and the same insensitivity to vibration was observed
during stepping-in-place. However, a small backward dis-
placement occurred, which was significantly different with
respect to the control condition when either side of the
neck was vibrated. This effect might be explained as a
postural response to a vibratory input interpreted by the
patients as if vibration were applied in front of them, rather
than laterally. This would correspond to a wrong central inter-
pretation of the input signal. In these otherwise ‘insensitive’
patients, therefore, vibration appears to have some postural
effects on the sagittal plane. Since these patients were not
those with the head turned most, the wrong interpretation
would not depend on the mechanisms responsible for the
abnormal head posture, as shown for other motor functions
(Anastasopoulos et al., 1998). In passing, all CD patients had
on average a posture slightly but significantly inclined
forward (body pitch) with respect to normals under all the
experimental conditions, but more so without vibration,
perhaps in the search for a ‘safer’ posture, as occurs in normals
on closing the eyes (Schieppati and Nardone, 1991;
Schieppati et al., 1994) or in spastic patients (Nardone
et al., 2001).
Reference frame for spatial orientationThe vibration effect on body orientation would be related to
the capacity of the neck proprioceptive input (in this case an
asymmetric lateralized input) to modify coherently the ego-
centric body-centred coordinate system that allows us to estim-
ate our body position with respect to the environment. The
vibration-induced input from one SCM muscle would mimic
head rotation toward the vibrated side, since during head
turning to one side it is the ipsilateral SCM which is being
lengthened passively, while the muscle opposite to the rota-
tion direction contracts and shortens (Mazzini and Schieppati,
1992). The tonic neck afferent signals thus elicited would
converge onto central networks and give an estimation of
the head and trunk posture. In fact, the imbalance of neck
proprioceptive inputs can modify the ‘representation’ of the
spatial orientation scheme in the context of whole body
control, inducing postural, visual and oculomotor responses
(Popov et al., 1999; Bove et al., 2001, 2002).
Normal subjects, who voluntarily rotated the head, showed
no significant modification in the body orientation under con-
trol or vibration conditions. From this finding, it seems that the
tonic afferent input connected with the abnormal head posture
is not enough to change the reference frame for orientation, at
least during stepping-in-place. Obviously, in the normal sub-
jects, voluntary head turning, as opposed to lateralized vibra-
tion, is accompanied by the brain activity connected to the
volition to turn the head (or the ‘efference copy’; von Holst
and Mittelstaedt, 1950), which can succeed in adapting
the reference frame during deliberate maintenance of
neck torsion.
In the CD patients, the abnormal spontaneous head posture
was ineffective, as was the deliberate rotation in the normal
subjects. In the patients, the trunk and the body do not appear
to match the vibration-induced sensory input from the neck, or
to re-align the trunk to the head, at least during stepping-
in-place. Perhaps as a consequence of their abnormal head
posture, they simply become less sensitive to neck muscle
vibration. Possibly, they have learned to rely less on the
proprioceptive sensory input from the SCM (or other neck
muscles) for their orientation during their navigation, and
rely more for this task on the input from other muscle
groups not influenced by the head posture, e.g. the trunk
paraspinal muscles (Anastasopoulos et al., 1998; De Nunzio
et al., 2003).
These findings do not allow the establishment of whether
proprioceptive abnormalities are a cause of the abnormal neck
muscle contractions or a consequence of an imbalance in other
systems controlling neck movements, e.g. the vestibular sys-
tem (Bronstein and Rudge, 1986; Mazzini and Schieppati,
1994; Colebatch et al., 1995; Munchau and Bronstein,
2001). On the other hand, neck input shapes the output of
the vestibular nucleus and its contribution to posture, gaze and
perception (Gdowski and McCrea, 1999, 2000, in the
primate). Admittedly, we are not in the position to interpret
the ‘insensitivity’ to vibration in these patients in the light
of any possible subclinical vestibular deficit or of the abnor-
mal interaction between proprioceptive neck and (normal)
vestibular input. Perhaps, on the basis of a recent suggestion
of Anastasopoulos et al. (2003), the abnormal response to
lateral neck vibration in CD patients can be explained as
the consequence of an offset of a non-sensory set point signal
in the neck proprioceptive loop for head-on-trunk control. It is
also difficult to draw conclusions from one snapshot of a
population of patients with a different natural history of dis-
ease. We can only note that the mean disease duration of the
INS group (12.4 6 6.1 years) was longer than that in the
RIGHT and LEFT groups (RIGHT, 7.3 6 6.1 years;
LEFT, 7.3 6 3.5 years), while the mean age was not different
in the three groups.
2776 M. Bove et al.
ConclusionsOne may hypothesize that the reference system used in the
control of body orientation in space by the CD patients during
a locomotor task is refractory to proprioceptive lateral input
from the neck or that the input has been re-addressed or
biased, whereby the vibration to both sides produces an
orientation shift in the same sense. This refractoriness or
distortion would be either primitive, connected to the patho-
genesis of the disease, or the result of an adaptive process,
whereby the proprioceptive input from muscles having an
abnormal length or tone is being progressively cancelled. If
anything, it seems that this refractoriness increases and occu-
pies both sides with the progress of the disease. This phenom-
enon might also entrain a slow shift from a reference system
based on the head position to a more reliable reference based
on another part of the body, such as the trunk; in this process,
head posture control is obviously lost.
AcknowledgementsThis work was supported by a grant from the Italian Ministero
Istruzione Universita Ricerca (MIUR), FIRB 2001 and
PRIN 2003.
References
Abbruzzese G, Berardelli A. Sensorimotor integration in movement disorders.
[Review]. Mov Disord 2003; 18: 231–40.
Abbruzzese G, Marchese R, Buccolieri A, Gasparetto B, Trompetto C.
Abnormalities of sensorimotor integration in focal dystonia: a transcranial
magnetic stimulation study. Brain 2001; 124: 537–45.
Anastasopoulos D, Mergner T. Canal–neck interaction in vestibular nuclear
neurons of the cat. Exp Brain Res 1982; 46: 269–80.
Anastasopoulos D, Bhatia K, Bisdorff A, Bronstein AM, Gresty MA, Marsden
CD. Perception of spatial orientation in spasmodic torticollis. Part I: the
postural vertical. Mov Disord 1997a; 12: 561–9.
Anastasopoulos D, Bhatia K, Bronstein AM, Marsden CD, Gresty MA.
Perception of spatial orientation in spasmodic torticollis. Part 2: the visual
vertical. Mov Disord 1997b; 12: 709–14.
Anastasopoulos D, Nasios G, Psilas K, Mergner T, Maurer C, Lucking CH.
What is straight ahead to a patient with torticollis? Brain 1998; 121:
91–101.
Anastasopoulos D, Nasios G, Mergner T, Maurer C. Idiopathic spasmodic
torticollis is not associated with abnormal kinesthetic perception from neck
proprioceptive and vestibular afferences. J Neurol 2003; 250: 546–55.
Biguer B, Donaldson IM, Hein A, Jeannerod M. Neck muscle vibration
modifies the representation of visual motion and direction in man. Brain
1988; 111: 1405–24.
Bonanni M, Newton R. Test–retest reliability of the Fukuda Stepping Test.
Physiother Res Int 1998; 3: 58–68.
Bottini G, Karnath HO, Vallar G, Sterzi R, Frith CD, Frackowiak RS, Paulesu
E. Cerebral representations for egocentric space: functional–anatomical
evidence from caloric vestibular stimulation and neck vibration. Brain
2001; 124: 1182–96.
Bove M, Diverio M, Pozzo T, Schieppati M. Neck muscle vibration disrupts
steering of locomotion. J Appl Physiol 2001; 91: 581–8.
Bove M, Courtine G, Schieppati M. Neck muscle vibration and spatial orien-
tation during stepping in place in humans. J Neurophysiol 2002; 88:
2232–41.
Boyadjian A, Marin L, Danion F. Veering in human locomotion: the role of
the effectors. Neurosci Lett 1999; 265: 21–4.
Brandt T. Cervical vertigo—reality or fiction? [Review]. Audiol Neurootol
1996; 1: 187–96.
Brandt T, Bronstein AM. Cervical vertigo. J Neurol Neurosurg Psychiatry
2001; 71: 8–12.
Bronstein AM, Rudge P. Vestibular involvement in spasmodic torticollis.
J Neurol Neurosurg Psychiatry 1986; 49: 290–5.
Burke D, Hagbarth KE, Lofstedt L, Wallin BG. The responses of human
muscle spindle endings to vibration during isometric contraction. J Physiol
(Lond) 1976a; 261: 673–93.
Burke D, Hagbarth KE, Lofstedt L, Wallin BG. The responses of human
muscle spindle endings to vibration of non-contracting muscles. J Physiol
(Lond) 1976b; 261: 695–711.
Cohen LA. Role of eye and neck proprioceptive mechanisms in body orienta-
tion and motor coordination. J Neurophysiol 1961; 24: 1–11.
Colebatch JG, Di Lazzaro V, Quartarone A, Rothwell JC, Gresty M. Click-
evoked vestibulocollic reflexes in torticollis. Mov Disord 1995; 10: 455–9.
Couch JR. Dystonia and tremor in spasmodic torticollis. Adv Neurol 1976; 14:
245–58.
Courtine G, Pozzo T, Lucas B, Schieppati M. Continuous, bilateral Achilles’
tendon vibration is not detrimental to human walking. Brain Res Bull 2001;
55: 107–15.
De Nunzio A, Stapley P, Schmid M, Courtine G, Schieppati M. Trunk muscle
vibration disrupts the steering of locomotion. Proceedings of the 3rd
International Posture Symposium, Smolenice, Slovakia; 2003.
Eklund G. General features of vibration-induced effects on balance. Uppsala J
Med Sci 1972; 77: 112–24.
Filippi GM, Errico P, Santarelli R, Bagolini B, Manni E. Botulinum A toxin
effects on rat jaw muscle spindles. Acta Otolaryngol 1993; 113: 400–4.
Fransson PA, Karlberg M, Sterner T, Magnusson M. Direction of
galvanically-induced vestibulo-postural responses during active and
passive neck torsion. Acta Otolaryngol 2000; 120: 500–3.
Fukuda T. The stepping test. Two phases of the labyrinthine reflex. Acta
Otolaryngol 1959; 50: 95–108.
Gilio F, Curra A, Lorenzano C, Modugno N, Manfredi M, Berardelli A.
Effects of botulinum toxin type A on intracortical inhibition in patients
with dystonia. Ann Neurol 2000; 48: 20–6.
Gdowski GT, McCrea RA. Integration of vestibular and head movement
signals in the vestibular nuclei during whole body rotation. J Neurophysiol
1999; 82: 436–49.
Gdowski GT, McCrea RA. Neck proprioceptive inputs to primate vestibular
nucleus neurons. Exp Brain Res 2000; 135: 511–26.
Goodwin GM, McCloskey DI, Matthews PB. The contribution of muscle
afferents to kinaesthesia shown by vibration induced illusions of
movement and by the effects of paralysing joint afferents. Brain 1972;
95: 705–48.
Gurfinkel VS, Ivanenko YP, Levik YS, Babakova IA. Kinaesthetic reference
for human orthograde posture. Neuroscience 1995; 68: 229–43.
Hallett M. Is dystonia a sensory disorder? Ann Neurol 1995; 38: 139–40.
Hlavacka F, Njiokiktjien C. Postural responses evoked by sinusoidal galvanic
stimulation of the labyrinth. Influence of head position. Acta Otolaryngol
1985; 99: 107–12.
Ivanenko YP, Grasso R Lacquaniti F. Effect of gaze on postural responses to
neck proprioceptive and vestibular stimulation in humans. J Physiol
(London) 1999; 519: 301–14.
Ivanenko YP, Grasso R, Lacquaniti F. Neck muscle vibration makes walking
humans accelerate in the direction of gaze. J Physiol (Lond) 2000; 525:
803–14.
Jankovic J, Leder S, Warner D, Schwartz K. Cervical dystonia: clinical
findings and associated movement disorders. Neurology 1991; 41:
1088–91.
Karnath HO. Subjective body orientation in neglect and the interactive
contribution of neck muscle proprioception and vestibular stimulation.
Brain 1994; 117: 1001–12.
Karnath HO, Christ K, Hartje W. Decrease of controlateral neglect by neck
muscle vibration and spatial orientation of trunk midline. Brain 1993; 116:
383–96.
Karnath HO, Sievering D, Fetter M. The interactive contribution of neck
muscle proprioception and vestibular stimulation to subjective ‘straight
ahead’ orientation in man. Exp Brain Res 1994; 101: 140–6.
Proprioception and orientation in dystonia 2777
Karnath HO, Konczak J, Dichgans J. Effect of prolonged neck muscle
vibration on lateral head tilt in severe spasmodic torticollis. J Neurol
Neurosurg Psychiatry 2000; 69: 658–60.
Kavounoudias A, Gilhodes JC, Roll R, Roll JP. From balance regulation to
body orientation: two goals for muscle proprioceptive information
processing? Exp Brain Res 1999; 124: 80–8.
Kogler A, Lindfors J, Odkvist LM, Ledin T. Postural stability using different
neck positions in normal subjects and patients with neck trauma. Acta
Otolaryngol 2000; 120: 151–5.
Ledin T, Hafstrom A, Fransson PA, Magnusson M. Influence of neck
proprioception on vibration-induced postural sway. Acta Otolaryngol
2003; 123: 594–9.
Leis AA, Dimitrijevic MR, Delapasse JS, Sharkey PC. Modification of
cervical dystonia by selective sensory stimulation. J Neurol Sci 1992;
110: 79–89.
Lekhel H, Popov K, Anastasopoulos D, Bronstein A, Bhatia K, Marsden CD,
et al. Postural responses to vibration of neck muscles in patients with
idiopathic torticollis. Brain 1997; 120: 583–91.
Lund S. Postural effects of neck muscle vibration in man. Experientia 1980;
36: 1398.
Lyon IN, Day BL. Control of frontal plane body motion in human stepping.
Exp Brain Res 1997; 115: 345–56.
Matthews PB. Proprioceptors and their contribution to somatosensory
mapping: complex messages require complex processing. [Review]. Can
J Physiol Pharmacol 1988; 66: 430–8.
Mazzini L, Schieppati M. Preferential activation of the sternocleidomastoid
muscles by the ipsilateral motor cortex during voluntary rapid head rota-
tions in humans. In: Berthoz A, Vidal PP, Graf W, editors. The head–neck
sensory motor system, Oxford: Oxford University Press; 1992. p. 597–600.
Mazzini L, Schieppati M. Short-latency neck muscle responses to vertical
body tilt in normal subjects and in patients with spasmodic torticollis.
Electroencephalogr Clin Neurophysiol 1994; 93: 265–75.
Munchau A, Bronstein AM. Role of the vestibular system in the pathophy-
siology of spasmodic torticollis. [Review]. J Neurol Neurosurg Psychiatry
2001; 71: 285–8.
Munchau A, Corna S, Gresty MA, Bhatia KP, Palmer JD, Dressler D, et al.
Abnormal interaction between vestibular and voluntary head control in
patients with spasmodic torticollis. Brain 2001; 124: 47–59.
Nardone A, Galante M, Lucas B, Schieppati M. Stance control is not affected
by paresis and reflex hyperexcitability: the case of spastic patients. J Neurol
Neurosurg Psychiatry 2001; 70: 635–43.
Naumann M, Reiners K. Long-latency reflexes of hand muscles in idiopathic
focal dystonia and their modification by botulinum toxin. Brain 1997; 120:
409–16.
Norre ME, Forrez G, Beckers A. Vestibulospinal findings in two syndromes
with spontaneous vertigo attacks. Ann Otol Rhinol Laryngol 1989; 98:
191–5.
Nutt JG, Muenter MD, Aronson A, Kurland LT, Melton LJ. Epidemiology of
focal and generalized dystonia in Rochester, Minnesota. Mov Disord 1988;
3: 188–94.
Pompeiano O, Manzoni D, Barnes CD. Responses of locus coeruleus neurons
to labyrinth and neck stimulation. [Review]. Prog Brain Res 1991; 88:
411–34.
Popov KE, Lekhel H, Faldon M, Bronstein AM, Gresty MA. Visual
oculomotor responses induced by neck vibration in normal subjects and
labyrinthine-defective patients. Exp Brain Res 1999; 128: 343–52.
Priori A, Berardelli A, Mercuri B, Manfredi M. Physiological effects
produced by botulinum toxin treatment of upper limb dystonia.
Changes in reciprocal inhibition between forearm muscles. Brain 1995;
118: 801–7.
Roll JP, Vedel JP. Kinaesthetic role of muscle afferents in man, studied by
tendon vibration and microneurography. Exp Brain Res 1982; 47: 177–90.
Roll JP, Vedel JP, Roll R. Eye, head and skeletal muscle spindle feedback in
the elaboration of body references. Prog Brain Res 1989; 80: 113–23.
Rosales RL, Arimura K, Takenaga S, Osame M. Extrafusal and intrafusal
muscle effects in experimental botulinum toxin-A injection. Muscle Nerve
1999; 19: 488–96.
Schieppati M, Nardone A. Free and supported stance in Parkinson’s
disease. The effect of posture and ‘postural set’ on leg muscle responses
to perturbation, and its relation to the severity of the disease. Brain 1991;
114: 1227–44.
Schieppati M, Hugon M, Grasso M, Nardone A, Galante M. The limits of
equilibrium in young and elderly normal subjects and in parkinsonians.
Electroencephalogr Clin Neurophysiol 1994; 93: 286–98.
Schieppati M, Nardone A, Schmid M. Neck muscle fatigue affects postural
control in man. Neuroscience 2003; 121: 277–85.
Siggelkow S, Kossev A, Moll C, Dauper J, Dengler R, Rollnik JD. Impaired
sensorimotor integration in cervical dystonia: a study using transcranial
magnetic stimulation and muscle vibration. J Clin Neurophysiol 2002; 19:
232–9.
Stell R, Thompson PD, Marsden CD. Botulinum toxin in spasmodic
torticollis. J Neurol Neurosurg Psychiatry 1988; 51: 920–3.
Tarantola J, Nardone A, Tacchini E, Schieppati M. Human stance stability
improves with the repetition of the task: effect of feet position and visual
condition. Neurosci Lett 1997; 228: 75–8.
Taylor J, McCloskey DI. Illusions of head and visual target displacement
induced by vibration of neck muscles. Brain 1991; 114: 755–9.
Tinazzi M, Rosso T, Fiaschi A. Role of the somatosensory system in primary
dystonia. [Review]. Mov Disord 2003; 18: 605–22.
Tsui JK. Botulinum toxin as a therapeutic agent. [Review]. Pharmacol Ther
1996; 72: 13–24.
von Holst E, Mittelstaedt H. Das Reafferenzprinzip. Weschselwirkung
zwischen Zentralnervensystem und Peripherie. Naturwissenschaften
1950; 37: 464–76.
Wierzbicka MM, Gilhodes JC, Roll JP. Vibration-induced postural
posteffects. J Neurophysiol 1998; 79: 143–50.
Wober C, Schnider P, Steinhoff N, Trattnig S, Zebenholzer K, Auff E.
Posturographic findings in patients with idiopathic cervical dystonia before
and after local injections with botulinum toxin. Eur Neurol 1999;
41: 194–200.
2778 M. Bove et al.