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J Appl Physiol 96: 2301-2316, 2004;
doi:10.1152/japplphysiol.00008.2004
8750-7587/04 $5.00
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INVITED REVIEW
HIGHLIGHTED TOPICS
Neural Control of Movement
Probing the human vestibular system with galvanic stimulation
Richard C. Fitzpatrick1 and Brian L.
Day2
1Prince of Wales Medical Research Institute, Sydney, New South Wales
2031, Australia; and 2MRC Human Movement Group, Sobell Department of
Motor Neuroscience and Movement Disorders, Institute of Neurology, University
College London, London, WC1N 3BG United Kingdom
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ABSTRACT |
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Galvanic vestibular stimulation (GVS) is a simple, safe, and specific
way to elicit vestibular reflexes. Yet, despite a long history, it
has only recently found popularity as a research tool and is rarely
used clinically. The obstacle to advancing and exploiting GVS is
that we cannot interpret the evoked responses with certainty because
we do not understand how the stimulus acts as an input to the
system. This paper examines the electrophysiology and anatomy of the
vestibular organs and the effects of GVS on human balance control
and develops a model that explains the observed balance responses. These
responses are large and highly organized over all body segments and
adapt to postural and balance requirements. To achieve this, neurons
in the vestibular nuclei receive convergent signals from all
vestibular receptors and somatosensory and cortical inputs. GVS sway
responses are affected by other sources of information about balance
but can appear as the sum of otolithic and semicircular canal
responses. Electrophysiological studies showing similar activation
of primary afferents from the otolith organs and canals and their
convergence in the vestibular nuclei support this. On the basis of
the morphology of the cristae and the alignment of the semicircular
canals in the skull, rotational vectors calculated for every mode of
GVS agree with the observed sway. However, vector summation of
signals from all utricular afferents does not explain the observed
sway. Thus we propose the hypothesis that the otolithic component of
the balance response originates from only the pars medialis of the
utricular macula.
balance; standing;
reflex; posture
GALVANIC VESTIBULAR STIMULATION (GVS) has been used for over a century as a means to
discover and then look at the function of the vestibular system. In
his 1820 dissertation, Bohemian physiologist Johann Purkyne (81)
reported that a galvanic current flowing through the head upset
balance and equilibrium. Eduard Hitzig (46),
starting his experiments as an army doctor during the
Franco-Prussian war, noted that nystagmus was one consequence of
applying an electric current to the brains of dogs and humans, including
the exposed brain of one wounded soldier. Thus we have the first
evidence that the two motor outputs of the vestibular system can be
driven by a galvanic stimulus. It was Josef Breuer (8) who
finally demonstrated the vestibular origin of these phenomena by
combining galvanic stimulation with labyrinthectomy in animals. The
first description of its perceptual output may have come much
earlier, in 1790, from Alessandro Volta himself (103). In between putting the electrodes of his newly invented battery
in his ears and his subsequent collapse, he briefly experienced the
sensations of an explosion inside his head, spinning, and the sound
of boiling tenacious matter. The spinning was likely the
manifestation of vestibular stimulation and the boiling either
auditory stimulation or the sound of flesh boiling. The explosion
needs no further explanation: a pile of 30–40 Zn/Ag elements
generates 
30 V! Hitzig and Breuer also came across the perceptual
phenomenon, but they were more specific about their experiences. Camis
(10)
reported that these gentlemen put "the two electrodes to the
two mastoid processes, and experienced a sensation of falling
towards the side of the cathode."
As its early history
shows, the GVS technique is very simple. The electrodes are now
placed on the mastoid processes rather than in the ears. Just a
switch and a battery are needed, 6 V is more than enough, although
for experimental applications, the stimulus is usually delivered by
a controlled current source at levels of 1 mA. The stimulus is most commonly delivered with an anodal
electrode on the mastoid process behind one ear and a cathodal
electrode behind the other ear, i.e., bilateral bipolar GVS. However,
other configurations are bilateral monopolar GVS with electrodes of
the same polarity at both ears and a distant reference electrode and
unilateral monopolar GVS with a stimulating electrode at just one
ear. When the small current flows for 1 or 2 s, it causes a person
to sway if they are standing or perceive illusory movements if they
are not. The simplicity of the technique, however, belies the
complexity of the body response it evokes.
The virtual signal of
head movement produced by GVS has a potent effect on whole body
motor control, evoking reflex electromyographic responses and a
highly organized balance response involving the entire body. However,
these responses are not hard wired but are very sensitive to the
task at hand, the balance and orientation of the body, and the
information coming from all other sensory sources. We therefore
believe that a balance system organizes a whole body response to the
vestibular signal. It seems that the balance system interprets the
GVS-evoked input as a real head movement in space, one that was
unplanned and one that came from a movement of the body. Such an
input represents a threat to balance to which the balance system
must respond.
Apart from its
simplicity, GVS is attractive as a tool to probe vestibular function
and the balance system because it delivers a pure disturbance at the
receptor level, uncomplicated by inputs to other sensory channels. At
least in its early stages, it reveals the operation of the balance
system to a pure vestibular perturbation. The purpose of this paper
is to consider the available data on human balance responses to GVS
in light of the physiology and anatomy of the vestibular organs and
to draw some conclusions about the nature of the afferent vestibular
signal evoked by GVS and how it produces its effects on human
balance.
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VESTIBULAR ELECTROPHYSIOLOGY |
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There have been no direct recordings from human vestibular afferents; therefore,
we can only reckon their behavior by data obtained from a wide range
of species. Of extreme value here is the elegant research and
detailed electrophysiological data of Jay Goldberg and colleagues,
which include primate afferent responses to GVS.
Kinetic
Stimuli
Discharge
rates. In all species studied, the vestibular primary
afferent neurons, which innervate the cristae and maculae, discharge
spontaneously at rest when no stimulus is applied. This means that,
with rate coding, a neuron can respond to accelerations in both
directions. Spontaneous discharge rates vary across species. Mean
rates of 13 s-1 have been reported in stingrays (63),
30–40 s-1 in rats and guinea pigs (14, 16),
45–55 s-1 in chinchillas (38), 65–90 s-1 in squirrel monkeys (28, 40),
and 90–115 s-1 in macaque monkeys (15).
Regularity. Primary afferents can be classified as regular or irregular
according to the pattern of their resting discharge (28, 39, 40),
although this may be more a convenience of description, as
regularity is more a continuum than discrete populations (4, 37). The
degree of regularity or automaticity of a neuron is determined by a
combination of the size of its afterhyperpolarization relative to
the size and rate of its excitatory postsynaptic potentials (EPSPs).
Sensitivity. Afferent firing rates increase or decrease depending on
amplitude and direction of an imposed acceleration. For the squirrel
monkey, this dynamic range is 0–300 s-1 at about the
65–90 s-1 resting discharge rate, with an average gain or
sensitivity of 2 s-1 per deg·s-2 for the semicircular
canals and 33 s-1/g for the otolith organs (27, 40). On
average, irregular neurons have slightly lower tonic rates than
regular neurons but are more sensitive to acceleration stimuli and
have shorter refractory periods than regular neurons. The response
of regular units is predominantly tonic; that of irregular units tends
to be more phasic. Responses are greater for excitatory than for
inhibitory stimuli, particularly for irregular units. As might be
expected in a system where a continuous discharge is modulated,
there does not appear to be a threshold value in these responses;
they are continuous about the resting values. Adaptation in the
primary afferents with a sustained acceleration stimulus is mixed. In
some units, adaptation is clear, particularly to inhibitory stimuli,
whereas many units show no adaptation. Adaptations of behavioral
responses, such as the vestibuloocular reflex, are greater than
adaptations seen in the afferent or vestibular nuclei, implying that
much of the adaptation occurs further down the reflex pathways (14).
Primary
afferent projections. As with the other senses,
vestibular afferent pathways show a great deal of convergence. Each
primary afferent innervates many hair cells (26, 31),
and the secondary vestibular neurons of the vestibular nuclei
receive input from many primaries. There is some correlation between
the physiological properties of the primary afferents and the
morphology of the target neurons. Large secondary neurons are
innervated by irregular afferents with more terminal boutons almost
exclusively, whereas small neurons are innervated by both types of
afferents. Firing of secondary neurons is not secure, and summation
of many EPSPs is necessary (53). Regular
units tend to be smaller and have localized dendritic connections
centrally, whereas the irregular units are large and influence a
large dendritic area (26, 30,
85). The
point to be made here is that the macula is not simply an array of
transmitting receptors but is concerned with significant complex and
adaptive processing of the raw hair cell signal, analogous to the
retinal processing of optical signals [see Ross (83) for
review].
Projections
of the vestibular nuclei. The secondary vestibular
neurons of the vestibular nuclei project to many areas of the central
nervous system (CNS), including the oculomotor nuclei, the spinal
cord, and the flocculus of the cerebellum (45), as
well as a thalamocortical pathway.
Even by the level of
the secondary neuron, there is convergence of afferents from the
semicircular canals and otolith organs (23, 51) and
from otolith afferents from both sides of the striola and both sides
of the head (100, 102). Thus spinal-projecting neurons of the lateral vestibular
nucleus respond optimally to movement in directions such as pure
roll that are not encoded by any single canal (51),
and a higher level of spatial tuning increases the direction
specificity of secondary otolith neurons to linear acceleration (2). Also
at this level, there is a large convergence of afferents from the
neck (52, 112) so that a complex descending output of these neurons can
come from a mix of signals denoting head on body and head in space. This
convergent input from the semicircular canals and otolith organs
seen onto spinal-projecting secondary neurons is infrequent for
oculomotor-projecting neurons (86, 101, 114, 115).
At the secondary
neuron level, there is also temporal filtering of the vestibular
signal. The transduction mechanics of the semicircular canals act as
a low-pass filter so that the afferent canal signal largely
resembles an angular velocity response. The process, known as
velocity storage (82), is
a further neuronal filtering or integration, so that, even at very
low frequencies, the vestibular secondary neuron's response is
related to angular velocity. A similar filtering exists for otolith
signals. Whereas primary afferents respond in proportion to linear
acceleration, most central otolith neurons respond in proportion to
linear velocity (2). This
is particularly so at low frequencies (<0.5 Hz), which are most
significant for balance control.
Vestibular
cortex. In monkeys, small areas of the somatosensory
cortex, within area 3a, receive bilateral vestibular projections (75),
and small areas of the parietal cortex, area 2v, receive mostly
contralateral vestibular projections (36). The
ventral-posterior and lateral-posterior nuclei of the posterolateral
thalamus are the thalamic areas concerned with this vestibular
sensory function and cortical projection (50).
There is also a
cortical efferent limb. In cats, stimulating cortical cells in area
2, and less so area 3a, affects the discharge of most ipsilateral
vestibular-nucleus neurons with spinal projections that respond to
sinusoidal tilts. They were either facilitated, inhibited, or a
mixture of the two. Thus these areas should be able to modulate
vestibular reflexes acting on the neck and limbs (113).
Galvanic
Stimuli
Site
of action. Galvanic stimuli are still effective when the
labyrinth is excised, but typical responses are not seen after section
of the eighth cranial nerves (80, 92). The
modulation by GVS of primary afferents occurs no further central
than Scarpa's ganglion because the effects can be recorded in these
neurons (14). Goldberg et al. (41) showed that cathodal GVS applied in the perilymphatic space
and anodal GVS applied to the afferent nerve fiber at a more
proximal point both caused excitatory responses. This is consistent with
the spike trigger zone of the primary afferent being the point of
GVS action as both stimuli will cause an outward depolarizing
current at this trigger site. Thus GVS can be considered to modulate
the hyperpolarization of the neuroepithelia of the cristae and
maculae. These findings imply that GVS bypasses the transduction
mechanism of the hair cells. It should be possible to distinguish
peripheral vestibular lesions from more central lesions by comparing
vestibular responses to galvanic and kinetic stimuli.
Irregular
afferents affected. About three-quarters of
primary afferents are regular firing (4, 37),
and anatomically they make strong connections to both
vestibulospinal and vestibuloocular output pathways of the
vestibular nuclei (45). However,
it is the irregular primary afferents that respond to GVS, whereas
regular units are only slightly modulated even by large stimulus currents
(25, 37, 41). Spinal-projecting
secondary neurons are innervated more by irregular afferents,
whereas oculomotor-projecting neurons receive more from regular
afferents (45),
although these variations are <20% each side of an even split. Cerebellar-projecting
units are intermediate. Because the irregular units carry the GVS
signal, we would expect the GVS signal to be relayed to all CNS
areas that receive vestibular projections. Furthermore, as
sensitivity of afferent units to GVS and kinetic stimuli parallel
one another by virtue of the underlying electrophysical properties
of the units (37, 41),
the CNS distribution should reflect that of naturally occurring
vestibular afferent signals. This probably applies equally to
afferents regardless of their canal or otolith origin. Anodal and
cathodal GVS affect the discharge of semicircular canal afferents in
the same way as ipsilateral and contralateral angular accelerations,
and GVS responses are the same for afferents from the otolith organs
and the semicircular canals (63).
Phasic
and tonic responses. For the entire population,
the GVS-evoked afferent discharge rate is not constant over time
with a maintained stimulus current; however, on an individual basis,
the discharge pattern varies. Several records show adaptation of
firing rate during maintained GVS after a step change of the
stimulus current (41, 58, 63). Adaptation,
or a phasic response that subsided to baseline over 1–2 s, was seen
in 7% of the primary units and 23% of the secondary units that
Courjon et al. (14)
recorded from in the rat. Most other units had a tonic pattern of
discharge for the duration of the stimulus. In agreement with this
phasic response, when sinusoidal GVS is applied, there is some phase
advance in the modulated afferent signal by 14 deg at the primary
level and a further 25 deg at the secondary unit along with a modest
increase in gain across the physiological frequency range (25).
Central
effects. With the body immobilized during functional
magnetic resonance imaging, GVS at intensities that produce illusions
of movement activates the cerebral cortex near the temporoparietal
junction, the central sulcus, and the intraparietal sulcus (60, 61). These
areas, PIVC and areas 3aV and 2v, correspond to the "vestibular
cortex" in monkeys.
Galvanic
vs. kinetic stimuli. Can we equate galvanic and
kinetic stimuli? In the squirrel monkey, afferent responses to GVS
applied in the perilymphatic space range from 0 to nearly 300 s-1
in an almost linear manner for currents between 70 µA cathodal and
70 µA anodal (41). This
should represent the dynamic range of the system. Angular
accelerations of the order of ±150 deg/s2 are required to
obtain responses across the same dynamic range (40). We
can assume therefore that these values represent the equivalent
dynamic ranges for afferent discharge and angular acceleration. What
we don't know is the relationship between current density at the
organ produced by percutaneous GVS and the much smaller perilymphatic
stimulus currents.
Consider three
responses to percutaneous transmastoid GVS in human subjects: one
ocular, one postural, and one perceptual. GVS at 2 mA produces
ocular torsion with a tonic response of 4–12 deg/s and a phasic
response of 0.67–2 deg/s2 (87). In
a subject without sensation mediated by large fibers from the neck
down, GVS between 0.5 and 1.5 mA produced a continuous compensatory
roll of the trunk and head at 1–2 deg/s (18).
Percutaneous GVS of 1 mA produced perceptions of body rotation that subjects
matched to actual accelerations of 2–3 deg/s2 (34). Assuming
that discharge rates are equivalent for humans and monkeys, each
observation indicates that the commonly used 1-mA current would
produce an afferent response equivalent to perhaps no more than 2%
of the dynamic range. Although as experimenters we often wish for a
bit more gain from our stimuli, it is probably fortunate that there
is sufficient insulation here to prevent us accessing to the full
dynamic range of this system.
Let us choose an
approximate scaling of afferent response to stimulus, say 1 mA gives
a 4 s-1 response, and apply it to each vestibular signal.
From the data of Ref. 40, the average gain, or sensitivity, of vestibular responses
to kinetic stimuli is 2 s-1 per deg·s-2 for
semicircular canal afferents and 33.3 s-1/g for otolith
afferents. Thus, with 1 mA GVS, a single afferent fiber would signal
angular acceleration of 2 deg/s2 if it innervated the semicircular
canals and either linear acceleration of 1.18 m/s2 (0.12
g) or 28.4 deg tilt if it innervated the utricular macula. However,
these are not the net population signals because each fiber signals
movement in a different direction. A vector sum based on the
morphology of the receptor organs is necessary to calculate a
resultant. That summation is considered in the next section.
In many ways, the
physiological and morphological properties and connectivity within
the afferent vestibular system appear to form a continuum. However,
it is one with much diversity. Thus the different associations of
physiological properties, morphologies, and connections might
provide for different aspects of vestibular sensation and vestibular
control, a hypothesis presented in detail by Goldberg (37).
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VESTIBULAR ANATOMY |
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Unlike natural stimuli, GVS has no direction. The entire population of
susceptible afferents are affected regardless of the alignment of
the hair cells that they innervate. The direction sensitivity of the
semicircular canals is obtained by resolving head movement into
three vectors. All hair cell receptors in the crista of each canal
are aligned along the circumferential axis of the canal and have the
same directional sensitivity. The anatomic orientation of the canals
therefore determines the direction of these three vectors. Within
the otolith organs, the hair cells are aligned in a multitude of
directions across the macular surfaces. Spatial encoding of the
entire population response provides directional sensitivity. Thus,
to look at the effects of GVS on the semicircular canal system, we
can consider the net effect on only three canal vectors. For the
otolith organs, we have to consider a vast array of vectors from the
otolith hair cells because the net GVS response will come from the
histological pattern of cell orientation within the neuroepithelial
surface.
Semicircular
Canals
The semicircular
canals sense angular acceleration and velocity of the head. Three
canals on each side of the head are approximately orthogonal (11). The
horizontal canals respond maximally to yaw. The anterior and
posterior canals are oriented vertically at 45 deg to the sagittal axis, so that both canals respond to
pitch and roll movements. The mirror symmetry of the canals across
the head means that, for natural stimuli, the two horizontal canals
provide similar, although inverse signals. Thus yaw rotation of the
head to the left increases the firing of afferents from the left
horizontal canal but decreases the firing rate from the right
horizontal canal. This push-pull arrangement about the tonic
discharge rate will improve the amplitude and directional sensitivity
of the canal system. The other canals operate similarly as the
anterior canal is aligned with the contralateral posterior canal.
The hair cell
neuroepithelium, or crista, is within an ampulla at the end of each
canal with the cilia embedded in a gelatinous cupula that occludes
the ampulla. The hair cells are oriented according to the plane of
the canal. Figure 1
shows the orientation of the hair cells relative to the three canals
(labeled a, p, and h) and the utricle (labeled u). A single hair
represents the orientation of all cells in the crista, with the
kinocilium drawn as the thick line at one end of the array of
stereocilia. As the crista moves with the head, the cupula and
stereocilia are deflected by the inertial reaction force of the
endolymph. Deflection in the direction of the kinocilia, as shown
for the left labyrinth in Fig. 1,
depolarizes the afferent fiber and increases its firing rate above
tonic levels. The arrows in Fig. 1 show
the natural rotational stimuli that would produce these excitatory
responses. When the stereocilia are deflected away from the
kinocilia, shown for the right labyrinth, hyperpolarization reduces
the firing rate.
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GVS will alter the
firing pattern of canal afferents in a way that has no natural
rotational equivalent. Cathodal GVS will increase the firing rate of
all responsive afferents, regardless of their direction specificity.
Thus, for the horizontal canal, this would signify a natural yaw
with the nose moving toward the ipsilateral, or cathodal, side (Fig. 1,
left horizontal canal). The same increased firing induced by
cathodal GVS in afferents of the anterior and posterior canals will
signify ipsilateral ear-down roll, and the signals from both canals
should add (Fig. 1, left
of roll; the canals overlap in this view). Because they are aligned
at 45 deg to the sagittal axis of the skull, the anterior canal will
also indicate nose-down pitch and the posterior canal a similar
nose-up pitch (Fig. 1,
left of pitch). These opposing signals have no natural equivalent
and should cancel because they are equal in size and opposite in
direction. Thus, considering all three canals, the pattern of
afferent discharge evoked by GVS will signal rotation with yaw and
roll components relative to the plane of the vestibular apparatus. Furthermore,
the roll component should be larger than the yaw component because
of the vector addition of signals from both vertical canals.
By hyperpolarizing the
afferents, anodal GVS will decrease the firing rate of all
responsive afferents, regardless of their direction specificity. This
means that for each canal anodal and cathodal stimulation will
produce signals of rotation in opposite directions. Anodal responses
are shown for the right canals in Fig. 1. The
directions are reversed horizontally because of the mirror symmetry
of the canals on either side of the head.
To complicate matters,
the canals are not aligned in the plane of the head and are not
quite orthogonal so they will not add and cancel quite as neatly as
this model suggests. The entire canal structure tilts backward by 30 deg from the head horizontally, and this gives the
horizontal canals a roll component at the expense of yaw. The
vertical canals develop a yaw component at the expense of roll,
while maintaining sensitivity to the pitch component. Fortunately,
however, we can calculate the vector for each canal because their
planar relationships relative to Reid's stereotactic line (inferior
orbital rim to auditory canal) have been accurately measured (7). From
these data, Fig. 2 shows the GVS angular acceleration unit vectors (right-hand rule)
for each canal. Considering these as unit vectors means that we are
assuming that the same stimulus will produce equally sized responses
from each canal. The vectors are oriented for anodal stimulation on
the right and cathodal on the left, that is, bilateral bipolar GVS.
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The lateral view shows
the vector components of GVS angular acceleration signals in the
sagittal plane for each canal (
p, a, h) and their resultant (r). Thus, for example, anodal GVS produces
from the right horizontal canal a signal of rotation about an axis
that is directed mostly upward, slightly backward, and slightly
laterally (h, marked by asterisk in Fig. 2). The
resultant vector of the three right canals is largely backward with
smaller upward and lateral components. The vectors for cathodal GVS
on the left side will have identical vertical and sagittal
components but inverted lateral components. Summing vectors from
both sides, we predict that bilateral bipolar GVS will evoke an
afferent signal of rotation about an axis in the sagittal plane
directed backward and slightly upward (mean of 18.8 deg) from Reid's
line. When the head is in the normal anatomic upright position,
Reid's line is nearly horizontal. Thus, during normal upright
standing, the afferent discharge evoked by bilateral bipolar GVS
will signal roll with a small yaw component, both directed toward
the cathodal electrode as shown by resultant vector L ± R
in Fig. 2.
The length of the canal
affects canal sensitivity because the longer the canal, the greater
the pressure that the endolymph exerts on the cupula (70, 76, 96). The
human canals differ in size (11):
the posterior canal is the longest (18–22 mm), then the anterior
(15–20 mm), and finally the lateral (12–15 mm). The nervous system
may need to calibrate the signals from each canal to produce a
constant spatial representation. For example, if the shorter length
of the horizontal canal means a smaller signal, it would need to be
"amplified" so that yaw is represented on the same scale
as the movements signaled by the other canals. How much would this
process affect the net GVS canal vector? Redoing the calculations
after the unit vectors are scaled inversely with the canal length
produces a net vector that is angled backward and upward by 27.1 deg
from Reid's line. The signal is still mostly roll toward the
cathode, but the yaw component is slightly larger.
Otolith
Organs
The otolith organs,
utricle and saccule, sense linear acceleration of the head in space
or the equivalent change in the gravitational acceleration vector
when the head is tilted. The macula of each organ contains
20,000–30,000 hair cells arrayed across an approximately planar
surface. The cilia of the hair cells are embedded in a gelatinous
membrane made denser than the surrounding endolymph by the inclusion
of calcium crystals or otoconia. When gravitoinertial forces move
the membrane, the stereocilia are deflected. As they bend toward the
kinocilium, they increase the firing rate of the associated afferent
fibers; when they bend the other way, they decrease it.
The plane of the
utricular macula is inclined backward from the horizontal by 30 deg and slopes away laterally by 10 deg (48, 72),
approximately in the plane of the horizontal semicircular canal. Thus
the utricular afferents predominantly signal lateral and sagittal
components of head acceleration. The saccular macula is aligned with
the sagittal plane and therefore its afferents signal vertical and
anteroposterior components of head acceleration. The maculae are
ellipsoid rather than strictly planar (48, 71,
72)
with the utricular macula concave up and the saccular concave medially.
This means a greater spread in the directions of movement that can
be detected from each organ. However, the effect is relatively
small; for the purpose of estimating an average otolith vector, only
the planar orientation will be considered here.
The hair cells are
aligned over the surface of the maculae in an orderly fanlike
pattern so that the optimal direction response for each hair cell is
related to its position on the macular surface. Figure 3
illustrates the alignments of the otolith maculae and their hair
cells. On either side of a striola that divides the utricular macula
into the pars medialis (also known as pars interna) and pars
lateralis (also know as pars externa), the hair cells are aligned in
opposite directions so that the kinocilia are always toward the
striola. Thus, for any imposed acceleration, one set of cells will
maximally increase and another will maximally decrease their resting
discharge rates. With the kinocilia toward the striola, ipsilateral
acceleration, or contralateral tilt, will increase the firing of
pars lateralis units and decrease it from pars medialis units. The
hair cells of the saccular macula have their kinocilia directed away
from the striola saccular. Thus upward acceleration will increase
firing from the pars externa and decrease firing from the pars interna.
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Real acceleration
causes direction-related differences in firing rates across the
afferent population. We assume that the CNS performs the equivalent
of a vector summation on the responses of the entire array of hair
cells to derive a meaningful representation of direction and
amplitude of the acceleration. GVS, in contrast, will have the same
effects on all susceptible afferents without favor for any
direction. The vector sum will now be determined by the position and
alignment of the striola on the macular surface, as this determines
the number of units that signal different directions. If the hair
cell population is exactly balanced so that the net anterior, left,
and down vectors cancel the net posterior, right, and up vectors,
then GVS will produce a zero net vector from the otolith organs. However,
the populations are not exactly balanced. In guinea pigs and
squirrel monkeys, the utricular striola is closer to the lateral
edge, making the pars medialis larger than the pars lateralis (29, 59). In
agreement with this, contralateral linear acceleration, or ipsilateral
ear-down tilt, increases the firing rate of more than half of the
utricular afferents in squirrel monkeys and cats (27, 62).
The prevailing direction is the other way in chinchillas, in which
the pars medialis makes the smaller 40% contribution (30).
A recent detailed
study of 43 human macula utriculi by Tribukait and Rosenhall (99)
shows a much more even balance of the pars medialis and pars
lateralis areas: 47% medialis to 53% lateralis. Based on this human
utricular direction sensitivity and the relative changes in firing
rates for acceleration and galvanic stimuli (40, 41), Fig. 4
shows the expected firing pattern of utricular afferents that signal
lateral acceleration or tilt. These are shown for the head
stationary and level (Fig. 4A), accelerating laterally (Fig. 4B), and stationary during bilateral bipolar GVS (Fig. 4C). The bars represent the signal amplitude (rate x sensitivity) of pars
medialis and pars lateralis. The net acceleration signal, shown as
the black bar, is the vector sum of the four signals. When the head
is stationary, the firing from each side cancels and there is a zero
net signal (S0). Acceleration to one side increases the
discharge of pars lateralis on that side and pars medialis on the
other side, whereas it decreases the discharge of the complementary
sides of the utriculi. Thus vectorial combination of the four
signals gives a large signal of the acceleration (SA).
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Cathodal GVS increases
the firing rate of utricular afferents innervating both sides of the
striola. The imbalance of hair cell alignment leaves a net response
that would normally indicate acceleration to cathodal side. On the
contralateral macula, anodal GVS will produce a much smaller
imbalance that would normally indicate acceleration to the anodal
side. Summing the net signals from both sides leaves a signal that
would indicate a small acceleration toward the cathodal side. Thus
bilateral bipolar GVS should produce a utricular firing pattern
consistent with a natural stimulus of linear acceleration toward the
cathodal side or tilt toward the anodal side (Fig. 4, SG).
However, GVS will produce only a small net acceleration signal
because, for each utricle, the pars medialis and lateralis signals
will nearly cancel with vector summation. We estimate that, for
equivalent changes in discharge rates, the GVS response would only
be 6% of the acceleration response (Fig. 4,
compare SA with SG). Furthermore, GVS applied
to one side only will cancel in this way without involving the
contralateral utricle, so that no form of GVS, monopolar or bipolar,
unilateral or bilateral, can be expected to produce a large afferent
signal from the otolith organs. This is a very different situation
from the semicircular canal responses to GVS where there is no
cancellation of roll and yaw signals.
This analysis can now
be extended to consider the two dimensions of the utricular surface.
Tribukait and Rosenhall (99) measured the areas of the macula utriculi that correspond
to eight different compass directions of the striola and used these
to calculate an average sensitivity for anteroposterior as well as
mediolateral accelerations. Their results indicate that the utricle
should be 25% more sensitive to lateral acceleration than medial
acceleration and 38% more sensitive to posterior acceleration than
anterior acceleration. They also calculated the direction of maximal
excitatory sensitivity for pars lateralis as lateral, 29.7 deg posterior,
and for pars medialis as medial, 22.5 deg anterior. These represent
the directions of the population-weighted vector. If we assume that,
on average, the spontaneous and GVS-evoked firing rates of macular
afferents are not direction specific, scaling these vectors by the
firing rate will give the vector signal represented by the afferent
population firing. In Fig. 5A, these are plotted for the left and right macula utriculi for
the neutral or resting discharge condition and for anodal and cathodal
GVS. The resultant of the pars medialis and pars lateralis vectors
are shown as the thick white arrows. Vector dN is drawn for
the stimulus conditions and represents the difference between the
GVS afferent signal and the neutral or resting signal. These show
that cathodal stimulation evokes signals of posterolateral acceleration
from each utricle, whereas anodal stimulation evokes signals of
anteromedial acceleration.
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These net GVS
utricular vectors from each side are added in different combinations
to predict the total GVS utricular signal for every combination of
stimulus polarity delivered either unilaterally or bilaterally. Figure 5B shows the resultant vectors for bilateral anodal (vector
b+), unilateral anodal (vector u+), bilateral bipolar (vector
bb), unilateral cathodal (vector u-), and bilateral
cathodal GVS (vector b-). Thus this model predicts that 1)
bilateral bipolar GVS will produce a signal of acceleration toward
the cathodal electrode or tilt toward the anode, 2) bilateral
unipolar GVS will produce a forward acceleration signal, or backward
tilt, with anodal current and the opposite for cathodal current, and
3) unipolar GVS will produce a signal of oblique
acceleration, contralateral and forward for an anodal electrode or
ipsilateral and backward for a cathodal electrode.
The saccules respond
to sagittal and vertical acceleration. The striola of the saccule is
approximately along the center line of the macula so that GVS-evoked
signals from each side of the striola will largely cancel each
other. There are no data available on the hair cell populations for
the saccular macula; therefore, it is not possible to determine
whether a residual acceleration signal is expected. A net saccular
GVS signal could affect the total anteroposterior acceleration
signal from the otolith organs but not the lateral acceleration
signal. Any net vertical signal is probably not significant for
normal balance.
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BALANCE RESPONSES |
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GVS produces a signal of head movement that has a potent effect on
whole body motor control. In the trunk and limbs, it evokes reflex
responses seen in the electromyogram (EMG), and these result in a
well-organized body movement. However, the response is not hard
wired. The pattern of muscle activity, hence the movement response,
is exquisitely sensitive to many factors. Above all, for a response
to appear in any given muscle, it is usually necessary that the
muscle be engaged in a balance task. For example, the EMG responses
that are evoked in leg muscles of a freely standing subject
disappear when seated, even when the muscles are activated by
comparable amounts in the two situations (9, 33). Similarly,
if subjects cannot stabilize themselves with the legs, when standing
on a wobbly board for example, and use the arm to balance by holding
onto an earth-fixed support, then responses appear in arm muscles (9). The
response is distributed in proportion to the load borne by each limb
(68, 69),
and relatively small changes in standing posture can also influence
the response. Standing with the feet a few centimeters apart
compared with standing with feet together, which has the effect of
stabilizing the lower body (21), dramatically attenuates the leg muscle response (20).
Observations such as
these lead us to conclude that the whole body response to GVS is
organized by the balance system. It seems that the balance system
interprets the GVS-evoked input as a real head movement in space
arising from an unplanned body movement. Such an input would
represent a threat to balance, and so the balance system responds
with a counteraction. In reality, of course, the counteracting
response is inappropriate and further destabilizing because the
vestibular signal is fictitious. Nevertheless, the response, at
least in its early stages, reveals the operation of the balance
system to a pure vestibular perturbation.
Electromyography
After the onset of a
step current, short- and medium-latency EMG responses can be
observed in muscles of the upper limbs (5, 9),
the trunk (1, 3),
and the lower limbs (9, 33, 73, 107, 110). After a constant GVS current is stopped, equivalent but reversed
"off" responses imply that these reflexes are driven by
the change in the vestibular nerve discharge rate rather than its
absolute level (108).
Size
and direction. The short-latency and medium-latency EMG responses
are in opposite directions (Fig. 6). In keeping with the effects of GVS on vestibular
afferents, both increase with stimulus current (12),
although it appears that a bigger stimulus is required to evoke the
short-latency response than the medium-latency response (33). Both
responses are inverted in antagonist muscles if they are also active
in the balance task (Fig. 6B). The medium-latency response is normally larger in
amplitude, and its direction and size correlates with the observed
pattern of whole body sway (9, 33). It
is also more susceptible to changes in other sources of sensory
input. For example, Britton et al. (9)
observed that visual input can nearly abolish the medium-latency
response without affecting the short-latency response. The earlier
response can produce small segmental movements but has no effect on
whole body movement (33). However, because this is a response to an abrupt
nonphysiological perturbation, this does not mean that the pathways
underlying the short-latency response have no role in the vestibular
control of balance in normal situations.
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EMG responses are seen
only in muscles engaged in balance; therefore, we can assume that
there is a task-dependent gating of descending vestibulospinal
influences. However, in subjects lying prone, the amplitude of the
soleus H-reflex is increased by 3–4% with 4-mA unilateral GVS or
decreased with the opposite polarity (55),
and this is influenced by turning the head to the side (54). Thus
a small vestibulospinal influence can still be seen in muscles that
seemingly have no role in balance control.
Latency. The short-latency EMG responses are seen at 40 ms in the arm and at 55–65 ms in the leg (5, 9, 33, 106). This is shown for one subject in Fig. 6C. With the assumption that both responses are based on the
same afferent volley reaching the vestibular nuclei, the conduction
velocity within the spinal cord is estimated to be 60–80 ms-1, very similar to the conduction
velocities of the corticospinal tract calculated from responses to
percutaneous electrical stimulation and transcranial magnetic
stimulation of the motor cortex (67, 84). However,
the vestibulospinal latencies are 30 ms longer than the corticospinal latencies. The need to
demodulate the modulated firing rate of the irregular vestibular
afferents could explain this central time as two pulse intervals
with a mean firing rate of 70 Hz correspond to 30 ms.
The medium-latency EMG
response to GVS appears at 110–120 ms in the lower limbs (5, 9, 33, 106), less than this in the paraspinal muscles (1, 3),
but it is >20 ms later in the arm (9). Thus
this response is not produced by the same system that appears to
release immediately the shorter latency response. This and the
complex nature of the GVS response suggest that the vestibular
signal is processed by a balance system that uses information from
many sources and produces a unified response according to the
current demands for maintaining balance.
Faradic
stimulation. Galvanic stimulation is the application of
direct current for a long period. However, it is worth considering the
effects of brief pulses of the type commonly used to stimulate peripheral
axons. When delivered for longer than the chronaxie (0.9–1.8 ms),
they produce a single brief movement of the head in cats (92). In
human subjects, transmastoid electrical stimulation at 5 mA for 2 ms
evokes short-latency biphasic EMG responses in the ipsilateral
sternoclei-domastoid muscle (109) and bilaterally in the masseter muscles (22). It
would appear therefore that a brief stimulus of this type produces a
single synchronous activation of vestibular afferents. Irregular
afferents, being closer to threshold most of the time (91),
are likely to make the greater contribution to this response. This
synchronization is seen when short stimuli (50 µs) are delivered
within the perilymphatic space (41) but
is followed by a lengthening of the subsequent interspike interval. Thus
the behavioral responses to this type of stimulus, and this might
include small ocular or head movements that are commonly seen at the
onset of prolonged GVS, are likely to be manifestations of
synchronous recruitment of afferent fibers rather than modulation of
their discharge rates.
These brief stimuli
create prominent responses in the musculature of the neck and are
associated with movements of the head on the trunk rather than
movements of the whole body. This suggests passage to the cervical
spinal cord through the medial vestibulospinal tract rather than the
lateral vestibulospinal tract, which projects predominantly to the
lumbosacral segments. The continuity of the medial vestibulospinal
tract with the medial longitudinal fasciculus and its connections
with the abducens, trochlear, and oculomotor nuclei indicate that
the system concerned with stabilizing the eyes and head might
respond preferentially to these stimuli.
Modulated
GVS. In a few studies, the stimulus current has been delivered
as continuously varying sinusoidal (13, 79) or
stochastic (32, 78)
waveforms of alternating polarity. Responses indicate that these stimuli
modulate afferent firing by the same means as the continuous tonic
stimulus. They also indicate that the neural response can extend to
frequencies much higher than the normal behavioral limits of
vestibular responses.
Balance
Responses
When a subject stands
normally with the head facing forward, the balance response to
bilateral bipolar GVS is directed laterally. However, in a beautiful
demonstration that revived much interest in GVS, Lund and Broberg (64)
showed that the direction of the response depends critically on the
orientation of the head relative to the feet (64). If
the subject turns the head to face various directions in the
horizontal plane, i.e., the head yaws, then the balance response is
redirected so that the body moves along the interaural line. This
fundamental behavior has been the premise of all subsequent studies.
Figure 7
shows sway responses recorded by Pastor et al. (77)
with the head turned in five different directions while the feet
remained in the same alignment (77). The
strong convergence of proprioceptive afferent axons from the neck
onto the second-order vestibular neurons of the vestibular nuclei
could underlie this remapping of the GVS response. However, it is
not quite that straightforward. Lund and Broberg also showed that it
does not matter how the head orientation is achieved. Whether it is
by simply turning the head at the neck, turning at the trunk, or a
combination of both, the response is the same. This implies that the
pattern of muscle activity evoked by GVS takes into account the
orientation of all body segments from the head to the feet. Here it
is worth noting that if, by experimental means, my perception of the
direction that my head is facing is distorted, then the direction of
my balance response is determined by my illusion rather than by
the reality (44). Clearly,
this is no straightforward conduit from vestibular afferent to
muscle contraction. The transformation of the vestibular signal must
be through a very elaborate system of balance control.
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Coordinate
transformation. This directional tuning of the GVS response
reflects the operation of what is often described as a coordinate
transformation. This process is absolutely essential if vestibular
information is to assist balancing the whole body. The need arises
because, with the vestibular organs fixed inside the skull, the hair
cells can only signal head movement and, because the receptors rely
on inertial forces, those signals are referenced to external
gravitoinertial space. The head, however, can adopt a whole range of
positions relative to the body and relative to the earth. Consider a
vestibular signal of sideways movement when you are standing and
facing straight ahead. It says that your body, or at least the upper
part of it, is falling sideways. If, however, you were looking over
one shoulder it would mean that you are falling backward or forward.
Completely different patterns of muscle activation are required to
arrest these different falls. To control balance, therefore, the
brain has to combine vestibular information with all those other
signals that tell it how the various body segments are orientated to
each other.
Sensory
Interactions
Sensory input from
many sources other than the vestibular organs is used to maintain
balance. Proprioceptive, visual, cutaneous receptors in the feet or
elsewhere, receptors in the abdomen, and undoubtedly receptors in
other locations can all provide information to the balance system. Although
each sensory channel has different qualities in terms of resolution,
bandwidth, and importance for whole body and segmental balance, the
availability and sensitivity of one input can alter the reliance
placed on the others. Some of the evidence for this comes from GVS
studies.
When visual input
about body sway is available, the whole body GVS sway response gets
smaller (6, 9, 64, 74, 111), and this stabilizing effect is graded depending on the
richness of the visual cues (19). Loss
of somatosensory input leads to a massive increase in the GVS sway
response. This may happen with an unstable support surface (33, 47),
with hypothermic anesthesia of the feet (65), or
through peripheral neuropathy (47). With complete loss of somatosensory input, the GVS
response is an order of magnitude greater (18). Conversely,
the tactile cues provided by lightly touching a stable reference
with the fingertip reduce the sway response (9).
These competitive
effects from other sensory channels can occur through two processes.
One is by influencing or selecting the initial response through gain
changes in vestibular and other sensory pathways, a system something
like proportional representation voting. The other effect is on
terminating the developing vestibular response. At some stage in the
sway response to GVS, a threshold is reached at which the balance
system, getting conflicting information from other sources, says
"no more" and disregards the vestibular input. This
threshold may explain the common observation that some subjects seem
to accept the stimulus and sway a long way, whereas others react as
if fighting it with multiple corrections. Standing with the legs
apart decreases the size of the GVS sway response (20) (Fig. 8),
whereas decreasing it by tandem Romberg stance makes the sway
response so large that it is nearly impossible to maintain balance (105). Standing on compliant surfaces, such as a piece of foam
rubber, also increases the size of the sway response (33, 105). Apart from effects on sensory input, the altered dynamic
coupling of muscle contraction and load with these manipulations
could also influence the final tilted position of the body.
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There is, however,
something different and compelling about GVS as a perturbation to
the balance system. It is obvious that if a physical perturbation,
such as being pushed to the side, is anticipated then it can be
negated by an appropriate anticipatory response. In the same way, an
unexpected visual stimulus that disturbs balance has no effect when
self-delivered and expected (43). GVS
is different because the evoked sway response is identical for
unexpected or self-delivered stimuli, and this effect does not appear
to adapt with time (42). Why this should be is uncertain. It may reflect a
different entry level of vestibular input to the balance system or a
decoupling of the efferent signal from the reafference that comes
from the sway response. The very small cortical area receiving
vestibular input, compared with the vast regions allotted to visual
and somatosensory sensation, may also be relevant.
Sway
Profile
At the onset of
stimulation, the body moves and leans toward one side; after 1 or 2
s, however, the motion stops, leaving the body tilted (49). Figure 8,
redrawn from Day et al. (20), shows typical responses. All body segments contribute to
the response so that, as well as leaning, the body also becomes
slightly bent (20). The head tilts on the trunk, the trunk tilts on the
pelvis, and the pelvis tilts with respect to the ground. In
agreement with inverted EMG responses of the same size that occur
when the stimulus ceases, the body segments return approximately to
their starting orientation (20). It is interesting to note that, until recently, this
static change in alignment of the body has led researchers
interested in balance control to believe that the effects of GVS are
mediated through activation of the otolithic or graviceptive system,
whereas those interested in ocular control have explained the
GVS-evoked eye movements by activation of semicircular canal
afferents.
A
continuous response. At first glance, the GVS
response appears to consist of a static tilt response of all body
segments, as if the GVS signal was itself mimicking a static tilt of
the head. The greater the stimulation current the greater the
virtual tilt. However, the response to the GVS signal produces a
true destabilization of the body that activates other sensory
systems, producing further compensatory reactions. Thus the reduced
sway seen with GVS when additional input is available or the support
is stable could be explained by the earlier and more effective recruitment
of these reactions, and the opposite could explain the larger
responses seen when sensory input is limited or the support is
compliant. This process no doubt explains the very different amounts
of static tilt produced by GVS without any difference in subjects'
perceptions of the alignment of the vertical (105).
This
"interference" from other balance responses provides a somewhat
misleading picture of the nature of the GVS signal. This is evident
in the response to GVS of a "deafferented" subject, subject
IW, who had lost all large-fiber somatosensory afferent input
from his whole body below the collar line (94). Figure 9A shows this subject's responses to GVS while seated with eyes closed
(18). Normal
subjects, when seated, tilt the head and trunk by very small amounts
during GVS. In subject IW it differed in two important ways. First,
it was an order of magnitude larger than normal. This is not
surprising in a subject with no other information about body
orientation and movement. Second, and of greater relevance here, the
response consisted of a continuous tilt throughout the stimulation
period rather than reaching a new level of static tilt. This
continuous tilting behavior can be demonstrated in healthy standing
subjects by using small stimulation intensities and reducing the
destabilizing effect of the response by tethering the subject's feet
to the ground (104). These responses are shown in Fig. 9B. These results show us that, when feedback from
nonvestibular sensory systems is removed or made less relevant, the
response remains unbridled and shows itself as a continuous tilting
response.
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Both studies that
demonstrated the pattern of continuous sway (18, 104) showed that the response could be described accurately as
the sum of step and ramp responses (Fig. 9C). Although it is possible that either the otolithic or canal
signal with appropriate processing within the nervous system could
produce such a response, the most parsimonious explanation is that
an otolithic signal of altered gravitational alignment produces a
step response and that a semicircular canal signal of rotation
produces a ramp response. When the stimulus stops, the realignment component
is reversed, but the body remains in a tilted position because the
movement signal simply stops rather than reverses.
Sway
Size
It appears from Fig. 9 that
the step and ramp contributions to the total sway response are not
dissimilar and, if they are otolith and canal responses, that we
should expect GVS to produce signals to the balance system from the
canals and otolith organs of approximately equal size. The roll
signal produced by bilateral bipolar GVS (Fig. 2A) is of "physiological" magnitude in that GVS does
not produce a signal from another canal that cancels a significant
part of the signal. In other words, GVS produces a total signal that
reflects the altered firing rates of the individual afferents in
much the same way that a movement stimulus would. In contrast, the
same change in the firing rate of utricular afferents would only
produce a very small "nonphysiological" signal because the
push-pull arrangement across the striola, which augments the signal
with movement stimuli, largely cancels the GVS signal (illustrated
in Fig. 5A). It does not seem sensible to accept that these large sway
responses can be explained by the small imbalance in afferent
populations from each side of the striola (99).
The coefficient of
variation of the difference between the pars medialis and pars
lateralis areas will be much larger than the coefficient of
variation of the pars medialis area; we calculated 105 vs. 8% from
data of Tribukait and Rosenhall (99). Thus
their data indicate that, between subjects, sway amplitudes in the
highest decile should be 250% that of the middle decile, whereas the
lowest decile should be about the same size but in the opposite direction.
Even with the inconsistencies of delivering percutaneous GVS and the
different weightings that subjects may place on vestibular inputs,
GVS does not produce this range of responses. What is more, in 7 of
the 43 maculae studied by Tribukait and Rosenhall, the pars medialis
was larger than the pars lateralis; however, among countless
subjects in GVS studies, sway toward the cathodal side has never
been reported.
Thus we construe that
the GVS-evoked utricular signal to the balance system is much larger
and less variable than can be explained by the small residual
after-vector summation of the signals from the entire population of
utricular afferents.
Sway
direction. Probably since the observations of Hitzig and
Breuer, it has been known that the polarity of the stimulating electrodes
determines the direction of the responses to GVS. In a subject
standing normally, the response to bilateral bipolar GVS is a
movement of the body toward the side of the anodal electrode (12). Reversing
the stimulus polarity causes a balance response in the opposite
direction, as illustrated by the mirror responses in Fig. 7. This
presumably arises because afferents previously excited by cathodal
current become inhibited by anodal current and vice versa, resulting
in an oppositely directed virtual head movement.
In addition to the
relative sizes of otolithic and canal responses discussed above,
their directions need to be considered. If both otolithic and
semicircular canal signals contribute to produce the sway profiles
shown in Fig. 9,
then both sway responses must have the same direction. Do the
GVS-evoked changes in firing of the otolithic and canal afferents
account for this?
Bilateral
bipolar GVS. The signal from the semicircular canals during
bilateral bipolar GVS will indicate a large roll and small yaw, both
toward the cathodal side (Fig. 2). Hence, the observed sway toward the anodal side appears to
be the appropriate balance response. Now consider the response to a
utricular signal. A signal derived by the vector summation of all
parts of the utricle, as shown in Fig. 5A, will indicate a small acceleration toward the cathodal side
or tilt toward the anodal side so that realignment of the body by
swaying toward the cathodal side would be the appropriate response. This
however is opposite the observed sway. If, however, we consider a
utricular signal that is the vector summation of afferents from
partes mediali only (Fig. 5B), then the signal will indicate a large acceleration toward
the anodal side or tilt toward the cathode. The observed sway toward
the anodal side then becomes the appropriate response.
Unilateral
GVS. Further insight into vestibular function and the
action of GVS comes from stimulating just one side of the head. The
nonstimulating electrode is usually placed on the forehead, although
it can be on more distant regions, even the arm (97). This
mode of GVS evokes sway responses that have a trajectory oblique to
the interaural axis rather than in line with it (66, 74, 89, 90).
The lateral component
of the oblique sway produced by unilateral GVS is either toward an
anodal electrode or away from a cathodal electrode and by equal
amounts in each direction (90). Furthermore, vector summation of separate sway responses
to oppositely directed unilateral stimuli give a resultant that is
not different from the sway produced by bilateral bipolar GVS. Severac
Cauquil et al. (90) reasoned that the CNS must use the discrepancy between left
and right vestibular activity to orientate balance responses. The
sagittal components of the oblique sway are forward when cathodal
current is applied to either ear and backward when anodal current is
applied.
Compare these sway
responses with the expected responses of the vestibular afferents. From
Fig. 2B, anodal GVS should produce a semicircular canal signal of
roll away from the stimulus side and a small signal of backward
pitch. The pitch component will be less than one-quarter of the roll
component. We therefore expect anodal stimulation of the canals to
produce a sway largely toward the stimulus side and slightly
forward. Thus the afferent signal from the semicircular canals
predicts the sway toward the stimulus side but not the backward
sway. A small forward sway is expected. The net utricular response
to anodal GVS signals contralateral and forward acceleration or
ipsilateral and backward tilt (Fig. 5A). Here, both predictions of sway, away from the anodal side
and forward, are wrong. Again, a utricular signal from the pars
medialis only (Fig. 5B) provides the correct prediction of sway toward the anode
and forward.
Another observation
that supports the idea that the utricular signal could be derived
from the pars medialis only is the observation by Severac Cauquil et
al. (90)
that the oblique sway produced by unilateral GVS had lateral
components twice as large (196%) as the anteroposterior components. This
is exactly the prediction of the pars medialis model (Fig. 5B) and not the prediction of the total utricle model (Fig. 5A). Of course it is possible that sway is better detected and
corrected in the sagittal plane than in the lateral plane. However,
as Fig. 7
shows, the sagittal and lateral components are similar when oblique
sway is produced by turning the head with bilateral GVS (77),
indicating that this effect is minimal.
Bilateral
unipolar GVS. The reasoning above also holds for this mode
of GVS. Subjects sway forward with cathodal GVS on both sides and
backward with anodal GVS on both sides. Figure 2B indicates that bilateral anodal GVS will produce a semicircular canal
signal of a small backward pitch with no roll component, which means
that the observed backward sway cannot be a response to the signal
from the semicircular canals. As above, it cannot be explained by
the total utricular signal of Fig. 5A, but it is the prediction of the pars medialis model of Fig. 5B. The pars medialis model also correctly predicts that the
sagittal sway produced by bilateral unipolar GVS is less than
one-half the size of the lateral sway produced by bilateral bipolar
GVS (88).
Origin
of the otolith signal. If we accept that the
morphological data define the weighting of the utricular afferent
response to GVS, from all of the above considerations we must
conclude that the sway response does not come from the total
utricular signal. However, the responses from just the pars medialis
of the utricle (Fig. 5B) have all of the characteristics to explain the sway
response. First, it is in the right direction. With anodal GVS,
unilateral or bilateral, pars medialis afferents will signal
backward acceleration or forward tilt and with cathodal GVS they will
signal forward acceleration or backward tilt. Second, the pars
medialis afferents alone will signal much larger tilts than the
entire utricle because the signal is not cancelled by afferents from
pars lateralis. Third, it will remain reasonably consistent between
subjects. Finally, the lateral acceleration signal of the pars
medialis afferents is much larger than the sagittal acceleration
signal. All of these factors agree with the observed sway responses
to each mode of GVS. It would, of course, be very useful to include
saccular GVS vectors into the model, but detailed morphological data
are not available.
There is evidence that
the two regions of the utricle may be specialized to provide for
different behavioral responses to tilt and translational movements. In
cats, local stimulation within the pars medialis produces torsional
vestibuloocular reflex (VOR) responses, whereas in the pars
lateralis it evokes a lateral VOR (35). Stimulation
of discrete branches of the utricular nerve produces eye movements
that are either predominantly torsional or predominantly horizontal
(95). Torsional
movements are appropriate responses to tilt of the head, whereas
horizontal movements are appropriate for lateral translation. There
are also behavioral correlates to support this hypothesis of
different roles for the two regions. Unilateral loss of vestibular
function causes a loss of sensitivity for detecting roll toward the
deafferented labyrinth but not toward the functioning labyrinth (17, 98).
Because the utricular pars medialis responds to ipsilateral tilt,
this is consistent with it having a dominant role in responses to
tilt. An opposite response is seen with translational accelerations. With
acute unilateral vestibular deafferentation, horizontal VOR
responses are diminished or absent when the functioning utricle is
accelerated medially, but they are preserved with lateral
acceleration (56, 57). Thus
horizontal VOR, the normal response to translational acceleration,
appears to be driven by pars lateralis afferents and not pars
medialis afferents. As Tribukait and Rosenhall (99)
point out, these are large effects that cannot be explained by the
relatively small discrepancy in afferent populations from each side
of the striola.
The division of the macular
surface into parts having opposite polarities therefore may be a
part of the evolutionary solution to the dilemma of acceleration and
gravity equivalence (24). Appropriate responses to each contingency could be ready
and calibrated and then selected on the basis of the present task,
behavior, and sensory inputs that resolve the signal duality.
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SUMMARY AND CONCLUSIONS |
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The vestibular signal of head movement produced by GVS has large and
predictable effects on the balance system. Electrophysiological studies
show that the afferent signal for these responses can originate from
both the otolith organs and the semicircular canals. By the level of
the secondary neurons in the vestibular nuclei, convergence of
signals from all vestibular receptors and somatosensory and cortical
inputs creates a signal that is highly organized and adapted to the
needed posture and balance requirements. In most situations, GVS
produces a plateau-shaped sway response in which the body segments
realign leaving the body bent and tilted toward the anodal
electrode. The plateau shape arises because the developing sway
response is arrested by a response to other conflicting sensory
information. However, when that other sensory input is not
available, the sway response is a continuous movement and is best
described by the sum of a step and a ramp response. Consistent with
the responses of vestibular primary afferents, the two components
are likely to correspond with otolithic and semicircular canal
responses. On the basis of the morphology of the cristae and the
alignment of the semicircular canals in the skull, GVS rotational
vectors can be calculated for every mode of GVS, and these agree
with the observed movements. This is not so for the otolithic system
in which the net GVS acceleration signal calculated by vector summation
of all utricular afferents is too small, too variable, and in the
wrong direction to explain the sway responses. However, the
GVS-evoked sway is consistent with the balance response originating
from only one part of the utricular macula, the pars medialis.
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ACKNOWLEDGMENTS |
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GRANTS
This work was supported
by the National Health and Medical Research Council of Australia and
the Medical Research Council of Great Britain.
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FOOTNOTES |
Address for reprint requests and other correspondence: R. C. Fitzpatrick,
Prince of Wales Medical Research Institute, Easy St., Randwick, NSW 2031,
Australia (E-mail: r.fitzpatrick@unsw.edu.au ).
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