J Neurophysiol 97: 604 – 617, 2007.
First published November 1, 2006; doi:10.1152/jn.00379.2006.
Interstitial Nucleus of Cajal Encodes Three-Dimensional Head Orientations in
Fick-Like Coordinates
Eliana M. Klier,1,2 Hongying Wang,1 and J. Douglas Crawford1
1
York Centre for Vision Research, Canadian Institutes of Health Research Group for Action and Perception, Departments of Psychology,
Biology and Kinesiology and Health Sciences, York University, Toronto, Ontario, Canada; and 2Department of Anatomy and
Neurobiology, Washington University School of Medicine, St. Louis, Missouri
Submitted 10 April 2006; accepted in final form 30 October 2006
INTRODUCTION
The goals of this study were 1) to determine the coordinate
system used by the brain stem to control head orientation
during gaze shifts and 2) to establish the relationship between
these coordinates and the neural strategies used to constrain the
redundant degrees of freedom observed in head movement.
Coordinate systems, and the reference frames in which they
operate, are crucial to representing and understanding the
locations and movements of objects (Crawford 1994; Simpson
and Graf 1985; Soechting and Flanders 1992). For example,
any three-dimensional (3D) orientation or rotation can be
described as a vector composed of components along three
coordinate axes (normally horizontal, vertical, and torsional),
where the latter roughly corresponds to rotation about the line
of sight (Crawford 1994; Simpson and Graf 1985). Experimentally, such coordinate systems can be defined with respect to
Address for reprint requests and other correspondence: E. M. Klier, Department of Anatomy and Neurobiology, Box 8108, Washington University
School of Medicine, 660 South Euclid Ave., St. Louis, MO 63110 (E-mail:
[email protected]).
604
arbitrary frames of reference such as the eye, head, or body
(Martinez-Trujillo et al. 2004; Schlag and Schlag-Rey 1987).
How the brain represents different directions of movement
and how it constrains these directions when it has more degrees
of freedom than necessary constitute a far more complex and
controversial topic. For example, in the gaze control system,
visual stimulus direction is initially encoded with respect to an
eye-fixed, two-dimensional (2D) retina, whereas the final motor output is encoded in 3D eye and head muscle coordinates,
embedded in the head and body frames, respectively. Thus the
sensory input specifies only a desired 2D gaze direction and not
the required amount of torsion. However, Donders’ law states
that only one 3D eye orientation is used for each of these gaze
directions (Donders 1848; Haslwanter 1995; Helmholtz 1867;
Straumann et al. 1991; Tweed and Vilis 1990). Thus the dual
question: what intermediate representations are used to code
eye and head movement directions and what is their role in the
implementation of Donders’ law?
Most of what we know about this topic comes from studies
of the oculomotor system with the head fixed (i.e., immobilized). Such studies showed that horizontal burst neurons
[located in the paramedian pontine reticular formation (PPRF)]
(Hepp and Henn 1983; Luschei and Fuchs 1972) are found
separate from torsional/vertical burst neurons [located in rostral interstitial nucleus of the medial longitudinal fasciculus
(riMLF)] (Crawford and Vilis 1992; Henn et al. 1991; King
and Fuchs 1979; Moschovakis 1997). Similarly, the horizontal
neural integrator [located in the nucleus prepositus hypoglossi
(NPH)] (Cannon and Robinson 1987; Cheron and Godaux
1987) is separate from the torsional/vertical integrator [located
in the interstitial nucleus of Cajal (INC)] (Crawford et al. 1991;
Dalezios et al. 1998; Fukushima 1991; Helmchen et al. 1998;
Moschovakis 1997).
For the horizontal component of the oculomotor system,
rightward movements are elicited by stimulating nuclei to the
right of the midline, whereas leftward movements are elicited
by stimulating nuclei to the left of the midline (Cohen and
Komatsuzaki 1972; Gandhi and Sparks 2000). For the vertical
system, nuclei on the right of the midline encode clockwise
(CW)-up and CW-down eye movements, whereas nuclei on the
left encode counterclockwise (CCW)-up and CCW-down eye
movements (Crawford et al. 1991; Vilis et al. 1989). This
framework agrees with both physical eye muscle anatomy and
the anatomy of the semicircular canals that formed the basis of
the phylogenetically older eye movement system—the vestibuloocular reflex (VOR). These canal/muscle-like coordinates
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Klier EM, Wang H, Crawford JD. Interstitial nucleus of Cajal
encodes three-dimensional head orientations in Fick-like coordinates.
J Neurophysiol 97: 604 – 617, 2007. First published November 1,
2006; doi:10.1152/jn.00379.2006. Two central, related questions in
motor control are 1) how the brain represents movement directions of
various effectors like the eyes and head and 2) how it constrains their
redundant degrees of freedom. The interstitial nucleus of Cajal (INC)
integrates velocity commands from the gaze control system into
position signals for three-dimensional eye and head posture. It has
been shown that the right INC encodes clockwise (CW)-up and
CW-down eye and head components, whereas the left INC encodes
counterclockwise (CCW)-up and CCW-down components, similar to
the sensitivity directions of the vertical semicircular canals. For the
eyes, these canal-like coordinates align with Listing’s plane (a behavioral strategy limiting torsion about the gaze axis). By analogy, we
predicted that the INC also encodes head orientation in canal-like
coordinates, but instead, aligned with the coordinate axes for the Fick
strategy (which constrains head torsion). Unilateral stimulation (50
␮A, 300 Hz, 200 ms) evoked CW head rotations from the right INC
and CCW rotations from the left INC, with variable vertical components. The observed axes of head rotation were consistent with a
canal-like coordinate system. Moreover, as predicted, these axes
remained fixed in the head, rotating with initial head orientation like
the horizontal and torsional axes of a Fick coordinate system. This
suggests that the head is ordinarily constrained to zero torsion in Fick
coordinates by equally activating CW/CCW populations of neurons in
the right/left INC. These data support a simple mechanism for controlling head orientation through the alignment of brain stem neural
coordinates with natural behavioral constraints.
INTERSTITIAL NUCLEUS OF CAJAL AND HEAD POSITION
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al. 2000). Gaze-shifts evoked by stimulation of the superior
colliculus (Klier et al. 2003) and frontal cortex (MartinezTrujillo et al. 2003) include head movements that obey the Fick
constraint, so presumably it is implemented at the level of the
brain stem, although nothing more is known about its physiological origin.
It was recently shown that electrical microstimulation of
such brain stem areas as the PPRF (Sparks et al. 2002) and
nucleus reticularis gigantocelluaris (Quessy and Freedman
2004) produce ramplike horizontal head rotations, much like
the effect of stimulating the horizontal brain stem system for
eye movements. In contrast it has long been known that
electrical stimulation of the midbrain regions in and around the
riMLF and INC produces torsional (i.e., roll) movements of the
head (Hassler 1972; Hassler and Hess 1954) and that these
areas project to the spinal cord centers for head movement
control through the interstitiospinal tract (Fukushima 1987).
Moreover, it was recently suggested that the INC is part of
the neural integrator for torsional/vertical head positions, similar to its role as an integrator for eye positions (Klier et al.
2002). Right INC inactivation causes drift of head posture
toward a counterclockwise shifted range, whereas left INC
inactivation causes drift toward a clockwise shifted range,
similar to the clinical symptoms of torticollis (Klier et al. 2002;
Medendorp et al. 1999). These findings suggest that the INC
may perform a function for the head similar to that for the eyes.
Based on these findings, we hypothesize that the INC controls head movements using a canal-like coordinate system, as
it does for the eye, with CW-vertical components controlled on
the right brain and CCW-vertical components controlled on the
left. In addition, we propose that, by analogy with the oculomotor system, the head’s neural integrator would use a coordinate system that aligns with the behavioral constraint of the
head (i.e., Fick coordinates). If this is the case, then electrical
stimulation of the INC should produce torsional/vertical rotations of the head—CW on the right side and CCW on the left
side—about axes that rotate with the orientation of the head.
METHODS
Surgery and equipment
Four monkeys (Macaca fascicularis) underwent aseptic surgery
under general anesthesia (isoflurane, 0.8 –1.2%) during which they
were each fitted with 1) an acrylic skullcap; 2) a stainless steel
chamber (centered at 5 anterior and 0 lateral in stereotaxic coordinates) that allowed access to the brain; and 3) a stainless steel
cylinder, used in combination with a bolt and screw, to immobilize the
head when required. 3D eye movement recordings were made possible by implanting two 5-mm-diameter scleral search coils in one eye
of each animal (one coil was placed in the nasal-superior quadrant,
whereas the second was located in the nasal-inferior quadrant, such
that the two were not parallel). 3D head movements were recorded by
two orthogonal coils mounted on a plastic base. The base was then
screwed onto a plastic platform on the skullcap during each experiment. Animals were given analgesic medication and prophylactic
antibiotic treatment during the postsurgical period and experiments
commenced after 2 wk of postoperative care. These protocols were in
accordance with the Canadian Council on Animal Care guidelines on
the use of laboratory animals and preapproved by the York University
Animal Care Committee.
The primate chair was placed such that each monkey’s head was at
the center of three mutually orthogonal magnetic fields (90, 125, and
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are 3D, orthogonal, and symmetric across the sagittal plane
(Crawford and Vilis 1992; Robinson 1985; Simpson and Graf
1985).
At first glance, these coordinates do not appear to correspond well with the 3D behavioral constraints observed in
visually guided eye movements. Saccades and smooth pursuit
obey a form of Donders’ law called Listing’s law (Ferman et al.
1987; Hastlwanter et al. 1991; Tweed et al. 1992). Listing’s
law determines torsion by constraining the eye to only those
orientations that can be reached from a central primary position
by rotations about axes that lie in a head-fixed Listing’s plane
(Haslwanter et al. 1991; Helmholtz 1867; Mok et al. 1992;
Tweed and Vilis 1990; van Rijn and van den Berg 1993). Put
simply, Listing’s law does not allow torsion around the headfixed torsional axis aligned with the primary gaze direction
(Westheimer 1957). Clearly, the saccade generator has the
capacity to violate Listing’s law because electrical stimulation
of the riMLF and INC produces ocular torsion (Crawford and
Vilis 1992; Crawford et al. 1991) that is corrected only by the
next endogenous eye movement (Crawford and Guitton 1997).
Moreover, in head-unrestrained conditions, the saccade generator produces finite torsional components to counterblanace the
torsional components of the VOR (Crawford and Vilis 1991;
Crawford et al. 1999; Klier et al. 2003; Tweed 1997). So how
is it then that these structures normally implement Listing’s
law?
The answer appears to be that, although the riMLF and INC
use a muscle/canal-like coordinate system, their coordinates do
not consistently align with head-fixed anatomical landmarks.
Instead, the axes align with Listing’s plane in the sense that the
vertical axis of rotation aligns with Listing’s plane and the axes
for torsional–vertical rotation are symmetric about Listing’s
plane (Crawford 1994; Crawford and Vilis 1992; Suzuki et al.
1995). Because the clockwise and counterclockwise components of torsional control are separated across the left and right
sides of the brain stem, coactivation of the INC on each side
would allow these components to cancel out and give zero
torsion in Listing’s plane. This becomes more complex during
head movements, in which case a bilateral imbalance is required to provide saccades with torsional components (Klier et
al. 2002). However, when the head is motionless, this organization provides a simple implementation of Listing’s law.
In comparison, far less is known about the neural control of
head movements, i.e., the neural coordinate systems for head
control and their relationship to the behavioral constraints
observed in head movement during gaze shifts (Corneil and
Elsley 2005; Corneil et al. 2002; Flanders 1988; Freedman and
Sparks 1997; Guitton 1992; Guitton et al. 2003; Keshner and
Peterson 1988; Klier et al. 2002; Martinez-Trujillo et al. 2004;
Peterson 2004; Sparks et al. 2002; Waitzman et al. 2002). Like
eye movements, 2D gaze commands do not constrain the
amount of torsion required in head orientation. However, head
movements obey another form of Donders’ law called the Fick
strategy (i.e., the observed head torsion is zero when measured
in Fick coordinates) where the vertical axis (for horizontal
rotation) remains fixed upright in the body but the torsional and
horizontal axes (for torsional and vertical rotations, respectively) rotate with the head (Glenn and Vilis 1992; Radeau et
al. 1994). This constraint does not appear to be mechanical in
origin because it can be voluntarily violated (i.e., by rolling the
head) or adapted to suit different task requirements (Ceylan et
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250 kHz), each 1 m in diameter. During each experiment, the monkey
sat in a modified Crist Instruments primate chair such that its head and
neck were free to move as desired. Specifically, the top plate was
removed and replaced by canvas cloth that buckled snugly at the back.
The upper body (to the shoulders) was prevented from rotating in the
yaw direction (i.e., movement around an earth-vertical axis) by the use
of plastic molding over the shoulders. Finally, each monkey also wore
a primate jacket (Lomir Biomedical) outfitted with four metal hoops
on the backside. Restraints running through these hoops and through
holes in the back of the primate chair further secured the upper body.
stimulations. The remaining sites were located on the outer edges of
the INC and produced inconsistent eye and head movements (possibly
resulting from current spread to the INC or other midbrain structures).
In M1 (monkey 1), six sites were examined in the right INC; in M2,
eight sites were investigated in the right INC and three sites in the left
INC; in M3, 2 sites were investigated in the right INC and five sites
in the left INC; and in M4, 28 sites were examined in the right INC
and 13 sites in the left INC. Postmortem, these sites were confirmed
histologically.
Data analysis
Experimental procedures
At the beginning of each headfree experiment, each monkey was required to fixate its own image,
for 5–10 s, in a 5 ⫻ 3-cm mirror. The mirror was located 0.75 m
directly in front of the monkey’s head and thus the head was oriented
directly straight ahead along the forward-pointing magnetic field. This
straight-ahead measure was sufficiently accurate for quantitative comparisons between controls and data recorded within a given experiment. Coil signals were measured at this position and were used as the
initial reference position for the head in space coordinates. This
reference position was then used to compute quaternions using a
method described previously (Tweed et al. 1990). The quaternions
were also transformed into linear angular measures of 3D head
position (Crawford and Guitton 1997) for statistical analysis. In this
way, any final head orientation could be described as a rotation vector
from the initial reference eye position.
QUANTIFICATION OF COIL SIGNALS.
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The raw head coil data were initially represented in an earth-fixed orthogonal coordinate system defined by the
magnetic fields that we call “space” coordinates. Quaternions calculated from these signals represent head orientations in space.
Next, head velocities were computed using the following formula
COORDINATE SYSTEMS.
␻ space ⫽ 2qq̇
where ␻space is angular head velocity relative to space, q is the head
quaternion, and qdot ⫽ (qold ⫺ qnew)/(time interval between qold and
qnew).
To put these head-in-space velocities into head coordinates, the
following formula was used
␻ head ⫽ q head ⫺1 ␻ space q head
Here, qhead is the head-in-space quaternion, qhead⫺1 is its inverse, ␻space
describes instantaneous head velocity relative to space, and the operation between the variables is quaternion multiplication. This is a
coordinate system transformation that rotates velocities from a spacefixed frame into a head-fixed frame. For example, if one were standing
upright and oscillating about the yaw axis at a constant frequency, the
head’s axis of rotation is purely vertical and aligns with the vertical
axis in space. If one were then to nod one’s head forward by 45°, then
the head-fixed and space-fixed vertical axes would no longer be
aligned. Computing the head’s new velocity would require the use of
this formula (i.e., a coordinate system transformation) to convert the
velocity of rotation from space coordinates into head coordinates,
where the vertical axis of rotation is now off space vertical by 45°.
SELECTION OF HEAD TRAJECTORIES. Each stimulation-induced head
movement produced a stereotyped movement of the head. Because we
were stimulating the INC, the elicited movements consisted of fairly
obvious abnormal torsional deviations (Klier et al. 2002). Thus the
beginning and end of each head movement was chosen manually by
viewing quaternion versus time traces of the head in space. This
method was also found to be more reliable than automatic-selection
algorithms that work well on natural gaze shifts.
COMPUTING THE CHARACTERISTIC VECTOR. The characteristic vector for each stimulation site represents the theoretical movement
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Before each experiment, the three magnetic fields were calibrated
using 1) an eye coil similar to the two implanted in the monkey’s eye
and 2) the same orthogonal coils that were later fixed to the monkey’s
head during the experiment (using a plastic base). During calibration,
these coils were mounted in the center of a Fick gimbal and rotated to
the cardinal positions in all three fields. The gains and biases of the
coils’ outputs were then adjusted such that maximum 8-V signals
were generated at these positions (Tweed et al. 1990).
At the beginning of each experiment, with the head fixed, a
tungsten microelectrode (0.5–1.5 M⍀ impedance; FHC) was slowly
lowered down a preselected track with the use of a hydraulic microdrive (Narishige model MO-99S). Neuronal activity was output on an
audio monitor. We first identified burst neurons in the superior
colliculus as a landmark (Klier et al. 2001) and subsequently moved
our electrodes anteriorly to the stereotaxic coordinates corresponding
to the INC. If burst-tonic activity was modulated along with corresponding vertical/torsional eye movements then the site was deemed
to be a potential INC site. Putative INC sites were further confirmed
by observing eye movements elicited after head-fixed stimulation. If
conjugate, ipsilateral eye movements, with mainly vertical and/or
torsional components, were elicited by stimulation then we classified
the site as an INC site (Crawford et al. 1991).
With the head free, the electrode would then be lowered through the
same track in which head-fixed recording and stimulation indicated
INC activity. Every 0.5 mm, stimulations with 200-ms pulse trains (50
␮A, 300 Hz) were delivered automatically every 3.3 s (by Grass
Instruments model S88) in dim light. Outputs from the eye and head
coils were simultaneously viewed on-line in an adjacent room as well
as recorded at 100 Hz for further off-line analysis (see Tweed et al.
1990). It should be noted that after each stimulation experiment, an
inactivation experiment was conducted in which muscimol was injected into the most responsive INC site. The results of the inactivation experiments are reported elsewhere (Klier et al. 2002).
The monkeys were untrained with respect to making gaze shifts and
were never required to make saccades with the head fixed for extended periods of time. As the stimulations were delivered, the
monkeys simply moved their eyes and heads freely and naturally.
Some of these movements were self-initiated, whereas others were
encouraged. One experimenter always stood hidden behind a hemispherical dome (barrier paradigm; Guitton et al. 1990) and motivated
the monkeys to use their entire eye/head motor ranges by presenting
the monkeys with novel visual objects and sounds. A second experimenter viewed the eye/head movements on-line and provided verbal
feedback about the range of initial positions obtained. This was done
to obtain the large range of initial eye and head positions necessary for
the quantifications described below.
As a control to the INC stimulation data, a “random” control
paradigm was run at the beginning of each head-free experiment. In
this paradigm, the monkeys were again required to look around freely
and encouraged to maximize their ocular and head motor ranges in the
same way described above. However, no stimulations were delivered
during these controls.
Of the 80 putative sites tested, 65 qualified to be included in this
study on the basis that head movements were evoked in ⬎50% of the
INTERSTITIAL NUCLEUS OF CAJAL AND HEAD POSITION
trajectory that would be elicited at a given site if the monkey was
looking straight ahead (i.e., 0° torsional, 0° horizontal, 0° vertical)
when the stimulation train was delivered. Individual characteristic
vectors for the eye-in-space (Es), head-in-space (Hs), and the eye-inhead (Eh) can be obtained by 1) selecting the 3D starting and ending
points of the eye and head trajectories; 2) computing the displacement
of each movement in the torsional, vertical, and horizontal dimensions; and 3) performing a multiple linear regression on the stimulation-induced displacements of Es, Hs, and Eh as a function of their
initial starting positions. This calculation, which takes into account
between 30 and 60 stimulations per site, results in three vectors (Es,
Hs, and Eh), which have their tail ends at the origin and extend to the
site-specific amplitude. This analysis was done so that one could
compare the stimulation-induced movements across different INC
sites.
The Fick strategy in normal gaze behavior
Our first goal was to confirm that our monkeys normally
obey the Fick constraint on head orientation during gaze shifts.
The details of Listing’s law and the Fick constraint during
head-free gaze shifts were previously described for some of the
Head-free fixations
Above
Side
50o Left
o
50 CW
50 Left
50o 50o
Up CCW
50o CCW
Above
o
50 CW
50o
Down
Right INC stimulation
Side
o
same monkeys elsewhere (Crawford et al. 1999; Klier et al.
2002, 2003), so here we will only summarize the directly
relevant head movement data. The boxed panels in Fig. 1 (top
left) show head orientations (F) extracted from the random
control paradigm (see METHODS), using only those orientations
during head fixation (i.e., head positions with velocities of
⬍10°/s) in a typical trial. These data are plotted in right-handed
coordinates (standard in previous studies on this topic), such
that a line joining the origin to each point provides a vector
parallel to the axis of rotation that would take the head from its
reference position to the actual plotted orientation. When the
right-hand thumb points along this vector, the fingers curl in
the direction of rotation. These vectors are plotted as they
would be viewed looking down from above (left panels) and
from the right side of the animal (right panels). Second-order
surfaces were fit to these fixation points (see METHODS) and
superimposed on the data (see Glenn and Vilis 1992). Similar
surface fits are shown for the remaining animals in the other
panels of the figure based on similar control head-fixation data
(not shown).
The torsional variance of such data is normally quantified as
the SD of torsion (in degrees) relative to the surface of best fit.
50o
CW
50o
50o 50o
Up CCW
M1Down
50o Right
50o CCW
50o
CW
50o Right
Left INC stimulation
M2
M3
M4
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FIG. 1. Fick strategy and 3-dimensional
(3D) head movements produced by interstitial nucleus of Cajal (INC) stimulation. Two
boxed panels (top left) show head-fixation
points during random head-free gaze shifts
(●) and the corresponding planes that were fit
to the fixation data. Remaining panels have
similar planes in the background illustrating
normal head ranges for each data set. Superimposed on these planes are the head-inspace trajectories and endpoints (●) that were
elicited by stimulating either the left (left 2
columns) or the right (right 2 columns) INC
in 4 monkeys (M1–M4). Trajectories are
plotted in 2 views that show all 3 dimensions
of movement. In the preceding views, torsion
is plotted as a function of vertical head position; in the side views, horizontal is plotted as
a function of torsional head position. Only
consistent trend is that left INC stimulations
produce counterclockwise (CCW) head
movements, whereas right INC stimulations
produce clockwise (CW) head movements.
These induced movements took the head out
of its normal torsional range (movement endpoints do not adhere to planes).
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RESULTS
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KLIER, WANG, AND CRAWFORD
On average, across animals, this was 5.54 ⫾ 1.52, showing that
head torsion was relatively (compared with horizontal and
vertical position), although not perfectly, constrained to zero.
In addition, the surfaces of best fit to each of the animal’s
control data sets showed a characteristic bow tie–like twist. It
was previously shown that such a twist results from rotating an
object in Fick coordinates where Fick torsion is held at zero
(Glenn and Vilis 1992; Radau et al. 1994). These planes can be
quantified by the so-called twist score, where an ideal Fick
twist score is ⫺1. In our monkeys the average twist score was
⫺0.78 ⫾ 0.16. All of these observations agree qualitatively
and quantitatively with previous measurements in the human
(Glenn and Vilis 1992; Radau et al. 1994) and in the monkey
(Crawford et al. 1999; Klier et al. 2003; Martinez-Trujillo et al.
2003).
The trajectories plotted in the remaining panels of Fig. 1
show the typical trajectories of head movement evoked by
stimulation of the left INC (left columns) and right INC (right
columns) in each animal (except for animal 1, where we were
unable to explore the left INC before the animal’s untimely
demise). For reference, these trajectories are superimposed on
the Fick surfaces fit to the control data of each animal. Left
INC stimulation ( first and second columns) caused consistent
CCW head movements (downward trajectories in above views
and leftward trajectories in side views). In contrast, right INC
stimulation (third and fourth columns) resulted in consistent
CW head movements (upward trajectories in above views and
rightward trajectories in side views). These trajectories resulted
in dramatic violations of the Fick strategy, often producing
transient head roll (or torticollis) in excess of 45°. In every
case, the range of final head orientations at the end of the
stimulus was significantly deviated along the torsional dimension from the normal Fick range of head orientations (paired
t-test, P ⬍ 0.05).
Stimulation-induced movements had variable vertical components (e.g., downward movements in M2, upward movements in M4, and upward/downward vertical movements in
M3). The horizontal components of these movements were
generally the smallest. Both of these components also showed
a variable position-dependent pattern. Sometimes stimulations
at one site produced movements with consistent horizontal
components (e.g., rightward movements in M4), whereas other
sites produced trajectories with small, position-dependent horizontal components (e.g., M3: the trajectories had rightward
components when the monkey’s initial head position was left
and leftward components when the monkey’s initial head
position was right). These position dependencies will be explained in a later section after we determine the INC’s intrinsic
coordinate system.
We summarized the different directions of head rotation
produced by left and right INC stimulation by examining the
velocities of the elicited head movements in all trials from each
animal. We first averaged the mean stimulation-induced velocities, component by component, at each site tested. We then
normalized these velocities by the mean speed at each site.
This produced a range of values, between 1 and ⫺1, from
which we could compare the relative effects of stimulation on
head velocities across the three components of head moveJ Neurophysiol • VOL
Neural coordinate systems
To quantify and compare the induced movements at all of
the stimulation sites, we first computed the characteristic vector of each site (see METHODS). This measure represents the
predicted head movement that would result from stimulation at
one site if the head was pointing directly straight ahead at the
time of stimulation (i.e., if head position was 0° torsional, 0°
vertical, and 0° horizontal when the stimulation was delivered).
This measure, one value per site, allowed us to compare the
effects of stimulation across INC sites.
The characteristic vectors for all sites, from all four monkeys, are shown in Fig. 4 (right INC sites are shown in gray;
left INC sites are shown in black). The above view (Fig. 4A),
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Violations of the Fick strategy during INC stimulation
ments and across animals (Fig. 2). For right INC stimulation
(Fig. 2, top panel), it is evident that the most consistent head
velocities were directed CW. In contrast, left INC stimulation
(Fig. 2, bottom panel), produced consistent head velocities in
the CCW direction. The vertical and horizontal velocity components were generally smaller than the torsional component
and—more important—these two components were variable
across sites. (Note that this is what the data look like when
plotted in arbitrary “space” or “magnetic field” coordinates; a
detailed site-by-site quantification of stimulus evoked amplitudes and directions will be provided below when we return to
this topic in the context of coordinate systems.) Thus as shown
previously for the oculomotor system (Crawford et al. 1991),
right INC stimulation consistently produced primarily CW
torsional deviations of the head, whereas left INC stimulation
produced mainly CCW head rotations.
Following the large torsional violations of Donders’ law
illustrated in Figs. 1 and 2, animals corrected most of this
torsion as part of the next endogenous gaze shift. Examples of
these correctional movements are illustrated in Fig. 3 for both
the left (top panels) and right (bottom panels) INC [notice that
final head positions (F) lie on or near the surface]. This
behavior is similar to eye movements induced by INC stimulation where their torsional position returns to Listing’s plane.
For the head, however, it cannot be determined with certainty
how much of these movements were passive and how much
were active (i.e., knowingly generated by the animal on finding
its head in an unusual, torted position) because we do not know
enough about the mechanical time constants of torsional head
rotation to make such estimates. However, because these torsional movements coincided with horizontal and vertical
movements, and because they followed similar time courses to
these other components (Fig. 3), it appears that they were at
least partially composed of active components. The final
ranges formed by the endpoints of these corrective movements,
after both left and right INC stimulation, showed a significantly
reduced torsional offset than the poststimulation ranges (the
reduction in torsional variance was from 7.95 to 4.98° in M1,
11.40 to 7.58° in M2, 10.22 to 6.33° in M3, and 10.17 to 6.36°
in M4; paired t-tests across all animals, P ⬍ 0.01), on average
reducing the torsional offset by 39.8%. However, their final
torsional positions were still significantly different from the
normal torsional ranges (Fig. 1, boxed panels) (paired t-test,
P ⬍ 0.05), suggesting that one or more subsequent movements
were required to completely return the head to its normal
torsional operating range.
INTERSTITIAL NUCLEUS OF CAJAL AND HEAD POSITION
609
plots torsional displacements in head positions (ordinate) as a
function of vertical displacements of head positions (abscissa),
i.e., as one would view the axes for these components of
rotation from above. The characteristic vectors generally consisted of a combination of vertical and torsional components,
where in most cases the torsional component was equal to or
greater than the vertical component. CV amplitudes were
generally ⬍30°, but individual movements could be much
larger. Again, the torsional components were always consistent
for right or left INC stimulation, whereas systematic vertical
components were more variable.
With respect to the oculomotor system, the riMLF and INC
appear to equally intermingle canal/muscle-like up-torsional
and down-torsional signals on each side of the brain (Crawford
et al. 1991; Fukushima 1991; Henn et al. 1991). As a result,
unilateral stimulation of the midbrain produces nearly pure
torsional eye movements (Crawford and Vilis 1992). If this
were the case for head control, one would also expect unilateral
INC stimulation to produce purely torsional eye rotations and
J Neurophysiol • VOL
fall along the ordinate in Fig. 4A. In contrast, if the INC
encoded head rotations using anatomically segregated canal
coordinates, one would expect the axes of stimulus-evoked
head movements to align with the individual vertical canal
axes, like the “X” superimposed in Fig. 4A. The data fall
between these two extremes, suggesting a partial anatomical
segregation between up and down signals with the INC. Unfortunately, we were not able to fully map the INC with
electrode penetrations in enough animals to confidently answer
whether this partial segregation has some consistent anatomic
basis, nor can we exclude that possibility.
The side view (Fig. 4B), which plots horizontal head positions (ordinate) as a function of torsional head positions (abscissa), again shows that head characteristic vectors from right
versus left INC stimulations are clearly segregated on either
side of the ordinate (CW movements to the right and CCW
movements to the left). In contrast, the horizontal components
were not generally elicited and, even when they were, they
were not very large. Five outliers (circled group) were col-
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FIG. 2. CW and CCW torsional head movements are segregated across the midline. Normalized components of eye
velocity were computed by dividing the average head velocities
by average head speed. Consistently, right INC stimulation
produced CW head rotations (top); left INC stimulation produced CCW head rotations (bottom). Vertical and horizontal
components of head rotation were also observed, but they were
smaller and variable. Data from M1 to M4 are plotted from left
to right.
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KLIER, WANG, AND CRAWFORD
Above
monkeys (Crawford et al. 1999) and is illustrated schematically
in Fig. 5, A and B. The colored vectors (rectangles connected
to the origin by solid lines) show different pointing directions
of the head, whereas the dotted/dashed loops (in matching
colors) show corresponding angular velocity loops for the
head. These velocity loops are composed of vectors that obey
the right-hand rule, but are scaled (distance from origin) by the
speed of rotation.
In Fig. 5B, head direction (viewed from the side) is set at
different vertical positions (e.g., red ⫽ head pointing down;
green ⫽ center; purple ⫽ up) while the head makes either
leftward (dotted loops) or rightward (dashed loops) gaze shifts.
(The velocity loops have different magnitudes for illustrative
Side
Left INC stimulation
o
50 CW
o
50 Left
50o
Down
o
50
CW
50o CCW
50o Right
Right INC stimulation
o
50 CW
o
50 Left
50o
CW
A
Above View
50o CW
o
50 CCW
50o Right
FIG. 3. Poststimulation head movements return to the Fick surface. First
head movement after each stimulation-induced head movement is plotted for a
left (top row) and right (bottom row) INC site, in both above (left column) and
side (right column) views. These head movements bring the head back toward
the normal head range (second-order surface fits in background). For the left
INC (M4), these movements are in a CW direction; for the right INC (M2),
these movements are in a CCW direction (i.e., in directions opposite to
stimulation-induced movement).
lected from one monkey, from one electrode penetration track,
on one day. The remaining CVs had horizontal components
⬍10°. Further, the alignment of these axes was not arbitrary. A
plane corresponding to the average second-order surface fit
from all four animals is illustrated in the background (surface
fits made to data taken from head fixations in the control
random movement paradigm). Note that the characteristic
vectors (i.e., the expected head rotations evoked from the
central reference positions) tend to align orthogonally to the
vertical axis of the Fick coordinates. Because both of these
tend to tilt backward/upward from the arbitrary magnetic field
coordinates, this would result in a spurious horizontal component to the torsional axes in field coordinates (this accounts for
some of the small systematic horizontal components plotted in
Fig. 1).
Again, our hypothesis was that the INC head controller uses
a canal-like coordinate system that aligns with the intrinsic
coordinates observed in head behavior (i.e., the Fick constraint), which is equivalent to setting torsion to zero in Fick
coordinates. The observation that the axes of head rotation
during INC stimulation tend to align orthogonally to the
vertical axis of the Fick surface (Fig. 4) is a necessary, but
insufficient, condition to conclude that the INC encodes head
movements in a Fick-like coordinate system. The more important test is to see how the stimulation-evoked head movement
axes depend on head orientation.
In a Fick coordinate system, similar to a telescope mount,
the horizontal axis (for vertical rotations) is nested in the
vertical axis, but the vertical axis (for horizontal rotations) is
fixed in space. One consequence for head control is that the
horizontal axis of rotation is dependent on position, whereas
the vertical axis of rotation is completely independent of
position. This was previously shown for head rotations in
J Neurophysiol • VOL
50
50o
o
Up
Down
50o CCW
B
Side View
50
o
Left
50o
50o
CCW
CW
50o Right
FIG. 4. Characteristic vectors of INC stimulation-induced head movements. Each data point represents the theoretical site-specific head movement
that would be elicited if the head was pointing directly straight ahead (torsion ⫽ 0; vertical ⫽ 0; horizontal ⫽ 0) when the stimulation was delivered.
These characteristic vectors allow us to compare the effects of stimulation
across different INC sites in different animals. Right INC stimulation is
indicated by the gray circles; left INC stimulation is shown by the black circles.
These populations are segregated in the side (A) and above (B) views on either
side of 0° torsion. Large torsional head deviations clearly stray from the normal
torsional range of the head (illustrated by planes generated from random
fixation data). Dashed “X” in the preceding view shows where data are
expected to lie if the INC were to encode head movements in semicircular
canal coordinates. Five circled data points are outliers collected in one animal,
in one track, on one day.
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50o
Down
INTERSTITIAL NUCLEUS OF CAJAL AND HEAD POSITION
A
150o/sec
CW
B
150o/sec
150o/sec
150o/sec
Down
CCW
Left
head
position
head
position
C
150o/sec
CW
D
150o/sec
150o/sec
Up
Down
head
position
head
position
axis
axis
150o/sec
purposes.) Here, the head rotates about a fixed vertical axis
independent of its vertical position, i.e., the velocity loops
overlap (Crawford et al. 1999).
In contrast, the horizontal axis (for vertical rotations) is
completely dependent on horizontal head orientation. As
shown in Fig. 5A, when the pointing direction of the head
(viewed here from above) steps from the left (purple vector) to
the right (red vector), the corresponding velocity loops for
vertical head rotations remain orthogonal to the head vectors,
i.e., they also step from left to right. (Here dashed loops
represent downward rotations and dotted loops represent upward rotations.) Notice that the angle between each gaze
direction and its correspondingly colored velocity loop remains
constant. All of these observations were previously confirmed
in behavioral data (Crawford et al. 1999). What cannot be
shown in normal behavioral data is that the torsional axis of
rotation in a Fick coordinate system is dependent on both
vertical and horizontal head orientation, so it would tilt horizontally with the head similar to the horizontal axes shown in
Fig. 5A, but unlike the axes in Fig. 5B, it would also tilt
vertically with the head. In other words, the torsional axis in a
Fick coordinate system should be fixed in the head.
This gives rise to two experimental predictions, one of
which we can test here. The first is that activation of the
J Neurophysiol • VOL
CCW
FIG. 5. Fick-like nature of head angular velocity axes during INC stimulation-induced
movements. A: theoretical behavior of vertical
head velocity during vertical head movements
(generated by bilateral INC stimulation) at different horizontal head positions. Different horizontal head positions (right to left) are indicated by the colored rectangles (red to purple).
Vertical angular head velocities (representing
the interaural axes of head rotation) are shown
by the correspondingly colored loops. Upward
head velocity loops produced are dotted; downward head velocity loops are dashed. As head
position moves from right to left, the corresponding head-fixed velocity loops of a Fick
gimbal also move, by the same amount, in the
same direction. B: theoretical behavior of horizontal head velocity during horizontal head
movements at different vertical head positions.
Head positions (down to up) are indicated by
the colored rectangles (red to purple). Angular
head velocities (representing the dorsoventral
axes of head rotation) are shown by the correspondingly colored loops. Rightward (dashed)
and leftward (dotted) head velocity loops, produced by stimulation of horizontal head control
centers, do not change position with changes in
head orientation as predicted by a Fick strategy
(i.e., the traces overlap and do not change orientation with changes in head position). Traces
are shown at different peak velocities to visualize how they overlap. C and D: real torsional
axes of head rotations during left (C) and right
(D) INC stimulation. Gaze direction of the
head, during the stimulation-induced movement, is indicated by the colored rectangles and
the center of each is connected to the origin by
a straight line. Axes of rotation are also shown
by the correspondingly colored head velocity
traces. Angles between gaze and the axis of
rotation appear to remain constant across different head-pointing directions.
horizontal centers for head rotation (Sparks et al. 2002) should
produce head rotations about a fixed vertical axis that is
independent of head elevation. The second, which we can test,
is that the primarily torsional axes of rotation produced by INC
stimulation should remain head fixed at different head orientations.
The latter prediction is confirmed in Fig. 5, C and D and in
Fig. 6. In Fig. 5C we show the head’s instantaneous axis of
rotation (squiggly traces) and the head’s gaze direction (i.e.,
head’s pointing direction) during five left INC stimulations,
using the same conventions as in Fig. 5A, but now showing real
data. Here, the direction of head rotation is CCW about a
mainly torsional axis, but notice that it does not remain fixed in
space. Instead, as the pointing direction of the head moves
from right to left (red to purple), the axes of rotation also move
in the same direction by roughly the same amount. Thus the
angle between the two appears to remain constant, suggesting
that the torsional axis of head rotation is fixed in the head.
Figure 5D depicts the same effect for right INC stimulation.
Here the axis of rotation is equally torsional and horizontal
when the head looks straight ahead (green velocity trace), but
it rotates horizontally with the head so that it can range from
nearly pure CW (blue velocity trace) to nearly pure CCW (red
velocity trace) in space coordinates.
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axis
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KLIER, WANG, AND CRAWFORD
In Fig. 6 we show how this pattern was quantified across all
sites and across all animals. First, Fig. 6, A and B describes
how the torsional axis of rotation is dependent on the horizontal position of the head. The abscissa describes the head’s
horizontal gaze direction, during stimulation, with the following conventions: if the head is pointing over the left shoulder,
then its gaze direction is 0°; if the head is pointing straight
ahead, then its head gaze direction is 90°; and if the head is
pointing over the right shoulder, then its gaze direction is 180°.
The ordinate uses this same convention to describe the corresponding axes of head rotation during stimulation. This convention was chosen because both the head gaze directions and
the head’s axes of rotations do not appear at the 0°/360° mark
and therefore do not produce discontinuities when plotting.
In Fig. 6A, data from two INC sites in one monkey are
shown. The top cluster (䊐) is from a left INC site (i.e., CCW
head rotation), whereas the bottom cluster (■) is from a right
INC site (i.e., CW head rotations). Each square represents the
position of the head’s axis of rotation (ordinate) plotted as a
J Neurophysiol • VOL
Relationship between coordinate systems and
position trajectories
Finally, because the axes of head rotation appear to obey a
Fick strategy, it is useful to directly illustrate that these axes are
fixed relative to the head and use this to explain the seemingly
complex position-dependent patterns in head-position trajectories that were observed in Fig. 1. Figure 7 first shows above
views of mean head velocities for a right INC site (top row)
and a left INC site (bottom row) in two different coordinate
frames: head (A and B) and space (C and D). If one draws a line
from each average velocity point to the origin, then that line
represents the average axis of rotation of the head, where the
length of the line determines the average speed of the movement and the direction of rotation is determined by the righthand rule (i.e., align the thumb of the right hand with the line
and the fingers of the right hand curl in the direction of head
rotation). Although the directions of head movement are as
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FIG. 6. Evidence for a Fick strategy. Top row: torsional axis of head
rotation and horizontal head position. A: for one CW INC site (■) and one
CCW INC site (䊐), the orientation of the head’s axis of rotation is plotted as
a function of the head’s pointing direction in the horizontal plane for each
stimulation-induced movement (see text for angle conventions). A regression
line was then fit through the data whose slope indicates how the head’s axis of
rotation changes with changes in horizontal head gaze. B: all regression lines
from all INC sites in one animal (see text for quantification of slopes in all
animals). Bottom row: like top row, but abscissa now indicates vertical changes
in head gaze. C: data from the same 2 sites as in A. D: regression lines are
shorter because animals had a narrower vertical head position range (as
compared with the larger horizontal head-position range in B).
function of the head’s average horizontal pointing direction
(abscissa) during one stimulation. A regression line was then fit
to all the data from that one site. Figure 6B depicts all the
regression lines from all the sites tested in one monkey. A
slope of zero would indicate that the head’s axis of rotation is
independent of the horizontal position of the head and thus
independent of the vertical axis of head rotation. In contrast, a
slope of one would imply that the head’s axis of rotation is
completely dependent on the vertical axis of head rotation and
therefore fits with a Fick strategy. The average slopes (⫾ SE),
computed for all four animals, were 1.123 ⫾ 0.037 (M1),
0.961 ⫾ 0.095 (M2), 0.932 ⫾ 0.066 (M3), and 0.976 ⫾ 0.061
(M4).
Figure 6, C and D is similar to Fig. 6, A and B, except for
describing how the torsional axis of rotations is dependent on
the vertical position of the head. Here, the abscissa describes
the head’s vertical gaze direction, during stimulation, with the
following conventions: if the head is pointing directly down,
then its gaze direction is 180°; if the head is pointing straight
ahead, then head gaze direction is 270°; and if the head is
pointing directly up, then its gaze direction is 360°. Again, this
convention was chosen because both the head-gaze directions
and the axes of rotations used by the head do not appear at the
360°/0° mark and therefore do not produce discontinuities
when plotting.
Once again, Fig. 6C depicts two clusters of data, one for a
left INC site (䊐, CCW head rotations) and one for a right INC
site (■, CW head rotations). This time, each square represents
the position of the head’s axis of rotation (ordinate) plotted as
a function of the head’s average vertical pointing direction
(abscissa). Again, regression lines were fit to all the stimulation
data from each site, and Fig. 6D shows all the regression lines
from all sites in one monkey. The average slopes (⫾ SE),
computed for all four animals, were 1.017 ⫾ 0.128 (M1),
0.875 ⫾ 0.238 (M2), 0.698 ⫾ 0.158 (M3), and 0.751 ⫾ 0.099
(M4). These slopes, which gather around a slope of one,
indicate that the head’s axis of rotation was dependent on the
vertical position of the head. Together, these results confirm
that the torsional axes of head rotation produced by unilateral
INC stimulation are head fixed. This complements the behavioral data (shown schematically in Fig. 5, A and B) to show that
the head truly uses a Fick-like controller.
INTERSTITIAL NUCLEUS OF CAJAL AND HEAD POSITION
Velocity
Head coord. (above)
A
500o/s
CW
Position
Space coord. (above)
C
o
500 /s
CW
Space coord. (above)
E
50
o
Space coord. (behind)
G
CW
50
o
Left
o
o
500 /s
50
Down
Up
o
500 /s
B
o
500 /s
o
CCW
CW
500 /s
D
o
500 /s
CCW
CW
50
F
o
50
o
CCW
o
Right
o
Left
50
H
CW
50
50o
Down
Up
CCW
500o/s
CCW
50o
50o
CCW
previously discussed (CW for right INC stimulation; CCW for
left INC stimulation), notice how these mean velocities (which
represent the head’s axis of rotation) change when plotted in
head coordinates (A and B) versus space coordinates (C and D).
The axes of rotation appear to be fixed in the former (i.e., the
dots seem to gather and lie along one line), but show more
variance in the latter. This is because the axes depend on, and
thus tilt, as a function of head position. Note that this analysis
could be done only with these stimulation-induced movements
that produce large torsional head rotations. Normal head movements, which are largely horizontal in direction, would likely
produce similar results in both head and space coordinates
because the vertical axis (for horizontal head movements)
remains space fixed in both cases. It is the torsional axis that
changes its behavior across the two coordinate frames.
To quantify this observation across all animals and all INC
sites, we computed the average and SDs of the mean velocity
vectors—in the torsional, vertical, and horizontal dimensions—and then conducted pairwise t-tests on the SDs between
head coordinates and space coordinates. We expected a significant difference in the SDs of the horizontal and vertical
components between these two conditions, with head coordinates consistently showing lower SDs than space coordinates.
The t-test results for the four monkeys were as follows (P
values ⬍0.05 indicate that variability was significantly lower
in head coordinates): M1: vertical P ⫽ 0.282, horizontal P ⫽
0.001; M2: vertical P ⫽ 0.009, horizontal P ⫽ 0.001; M3:
vertical P ⫽ 0.003, horizontal P ⫽ 0.012; M4: vertical P ⫽
0.000, horizontal P ⫽ 0.000. Thus there was a consistent trend
for SD to be lower in head coordinates than in space coordinates. This trend was significant in seven of eight comparisons
and most highly significant in the monkey with the greatest
number of INC sites tested (M4 with 41 sites compared with
M1, 6 sites; M2, 11 sites; and M3, 7 sites).
Figure 7 goes on to plot corresponding head positions in
above (E and F) and behind (G and H) views. The complex
position trajectories illustrated here (and in Fig. 1) are simply
the result of rotating the head about head-fixed torsional axes.
For example, with right INC stimulation (G), when the head
looks left a head-fixed CW rotation should produce downward
J Neurophysiol • VOL
FIG. 7. Head axes of rotation are encoded
in head coordinates. Each row illustrates mean
eye velocities in head coordinates (A and B)
and space coordinates (C and D) and corresponding position traces in above (E and F)
and behind (G and H) views. A right INC site
is shown in the top row; a left INC site is
shown in the bottom row. Head’s axis of
rotation is fixed when observed in head coordinates (A and B), but changes as a function of
head position in space coordinates (C and D).
This position dependency leads to the complex pattern of trajectories seen in Fig. 1 and
E and F, and also to the swirling pattern of
position traces in G and H, where the expected
pattern of head positions is depicted by the
dashed arrows.
Right
rotation components in space and looking right should produce
upward components. Looking up should produce leftward
movements and looking down should produces rightward
movements. This should give rise to a circling pattern in plots
of horizontal (ordinate) versus vertical (abscissa) position (G
and H), where head-fixed CW rotations produce a CCW
circling pattern and head-fixed CCW rotations produce a CW
circling pattern of position trajectories (dashed arrows). The
actual data plotted on these panels show this predicted pattern.
Thus this circling pattern (i.e., these position-dependent horizontal and vertical components in space coordinates) is consistent with and predicted by a head-fixed torsional axis in Fick
coordinates that rotates with gaze.
DISCUSSION
The INC forms part of the neural integrator for eye orientation (Crawford et al. 1991; Fukushima 1991; Helmchen
1998; King et al. 1981). Specifically, the INC appears to
integrate signals for holding the torsional and vertical components of eye position. We recently proposed that the INC
performs a similar function for head orientation (Klier et al.
2002). This was based on the finding that immediately after
muscimol inactivation of the INC, the head shows exponential,
position-dependent patterns of torsional and vertical drift similar to that seen in the eye, and that during INC stimulation the
head shows ramplike torsional rotations that tend to hold their
final orientation, at least until corrected by an active gaze shift.
Here, we have confirmed that the INC encodes head movements in vestibular-like or canal-like coordinates: stimulation
of the right INC produces CW-up and CW-down positions,
whereas the left INC produces CCW-up and CCW-down
orientations. Importantly, we showed that these coordinates
obey a Fick strategy in which the torsional and vertical axes of
head rotation are dependent on, and rotate with, the position of
the head, as in a Fick gimbal. In this way, when CW and CCW
signals from the two sides of the INC are balanced, torsion of
the head would be constrained to a 2D twisted surface that
obeys Donders’ law.
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500o/s
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Neural coordinate systems
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Implementation of Donders’ law
There is an intimate relationship between neural coordinate
systems and neural solutions to the degrees-of-freedom problem (e.g., Donder’s law for the eye and head). In the case of the
oculomotor system, the brain stem appears to use a canal- or
muscle-like coordinate system (Fukushima et al. 1980; Henn et
al. 1991) that aligns with the head-fixed Listing’s plane (Crawford 1994; Crawford and Vilis 1992; Suzuki et al. 1995) such
that CW torsion relative to Listing’s plane is represented in the
right midbrain and CCW is represented on the left. This unique
arrangement gives rise to a simple principle: to obtain zero
torsion movements and position vectors in Listing’s plane, the
brain must activate the riMLF and INC symmetrically across
the midline. It now appears that the position-dependent saccade
axis tilts required for Listing’s law (i.e., the half-angle rule) are
implemented by the eye muscles themselves (Demer 2002,
2006; Ghasia and Angelaki 2005; Klier et al. 2006).
The current investigation suggests that an analogous mechanism is used to control the head. However, the head does not
follow Listing’s law but rather the Fick strategy, so this
mechanism requires that the neural coordinate systems for head
control are arranged in Fick coordinates. If the neural coordinates for head control are organized like that of the eye (i.e.,
with up-CW and down-CW populations in the right midbrain
and up-CCW and down-CCW populations on the left), but
organized in Fick coordinates, then symmetric bilateral activa-
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It has long been established that stimulation of the midbrain
reticular formation produces roll movements of the head (Hassler 1972; Hassler and Hess 1954), although these earlier
researchers simply did not have the technology for quantitative
measurements of 3D eye and head kinematics available today.
However, our main observations support these earlier observations. Moreover, at first glance, the head-movement patterns
that we observed during microstimulation of the interstitial
nucleus of Cajal in the head-free monkey are consistent with
the pattern of eye movements elicited during head-fixed INC
stimulation (Crawford et al. 1991). Stimulating the right INC
produces large CW head movements, whereas left INC stimulation produces similar head movements, but in the CCW
direction. During unilateral pharmacological inactivation of the
INC (and to some extent the adjacent riMLF and cMRF), the
eye and head shift torsionally in the opposite directions (Crawford and Vilis 1992, 1993; Crawford et al. 1991; Fukushima
and Fukushima 1992; Fukushima et al. 1985; Helmchen et al.
1998; Klier et al. 2002; Suzuki et al. 1995; Waitzman et al.
2000a,b). These observations support the idea that the control
of torsional movement components (CW and CCW movements
for both the eye and the head) is segregated across the midline
of the midbrain (Crawford and Vilis 1992, 1993; Crawford et
al. 1991).
Even the systematic (i.e., nonposition-dependent) components of vertical head (and eye) rotation produced by INC
stimulation are much smaller and more variable than the
torsional components. Interpreted in light of the vestibular
inputs to the INC and the tuning directions of INC and riMLF
units during vestibular stimulation (Fukushima et al. 1980;
Henn et al. 1991), and the tonic eye position dependency of
INC units during fixation (King et al. 1981), this appears to be
because up- and down-tuned units are intermingled on each
side of the INC. Taken together with the torsional tuning
directions of these neurons (Fukushima et al. 1980; Henn et al.
1991) and the stimulation/inactivation data discussed above,
this suggests that the INC (and riMLF) oculomotor neurons are
organized into an eye muscle–like or vestibular canal–like
coordinate system, with up-CW and down-CW populations on
the right side and up-CCW and down-CCW populations on the
left.
Our current head data are consistent with this idea, but
interpreted in this light, suggest that up and down head movement units are not perfectly intermingled on each side (these
would cancel out to produce zero systematic vertical rotation).
Rather, different stimulation sites on each side appear to run
the gamut between sites encoding up-torsion to pure torsion to
down-torsion (Fig. 4, top). This suggests that there may be
some anatomic segregation of up/down head movement signals
in the INC, but at the level of anatomic resolution of advancing
different electrodes and, at the number of different penetrations
that we were able to obtain in each animal, we were not able to
find a consistent anatomic pattern to this segregation. Because
neck muscles are not presumably organized along the simple
lines of eye muscles (Corneil et al. 2001; Richmond et al.
2001), this general organization may result in part from vestibular input. Likewise, another unexplored possibility is that
the different axes of rotation that we obtained from different
INC sites correspond to activation of distinct muscle synergies.
As in the oculomotor system, head movements showed the
least systematic components in the horizontal direction during
INC stimulation and these appear to be even smaller or nonexistent (for most sites) when the vertical axis for horizontal
rotation is defined as aligning with the axis of rotation for the
Fick constraint observed in normal gaze-shifting head movements (Fig. 4, bottom). This is similar to the observation that
stimulation of midbrain oculomotor centers produces axes of
rotation that align orthogonally to Listing’s plane of the eye,
except that Listing’s plane is essentially fixed in the head
(Crawford 1994), whereas the Fick surface is essentially fixed
in the body (Misslisch et al. 1994).
Moreover, during INC stimulation, the head showed significant position-dependent movement components in both the
vertical and horizontal components. As shown in Figs. 5–7,
these arise because the stimulation-evoked axes were fixed in
the head, generating a particular circling pattern of horizontal
and vertical head-position dependencies in space (Fig. 7).
All of these observations are consistent with the idea that
both torsional and vertical head control by the INC are organized in a Fick-like coordinate system. Specifically, the torsional axis is fixed in the head such that it produces the
position-dependent patterns observed above in space coordinates (Fig. 7). This also explains similar position-dependent
patterns that we observed during torsional eye and head drift
after unilateral INC inactivation in the head-free monkey
(Farshadmanesh et al. 2005). However, this is only part of a
Fick-like coordinate system. To confirm this, one would have
to measure 3D axes of rotation during stimulation of the
horizontal head control system, which in contrast should produce horizontal rotations about a body-fixed vertical axis that
does not rotate with the head. The functional significance of
these observations will be considered in the next section.
INTERSTITIAL NUCLEUS OF CAJAL AND HEAD POSITION
Gaze, eye, and head control
Because the INC uses different strategies for eye and head
movements, does this imply that it encodes separate eye and
head commands (i.e., in contrast to a common gaze command)? Such a duality would not be hard to believe, especially
because the neural integrator is just one step removed from the
motoneurons of the eyes and head. However, this need not be
the case at the level of individual neurons. Again, the coordinate system of a given neural structure is determined, not only
by the computations made in the given area, but—more important— by the connections the area has with downstream
structures (Pellionisz and Llinás 1980; Smith and Crawford
2005). Thus the INC may project to eye motoneurons in one
way (which causes the eye axes to align with Listing’s plane)
and in a completely different way to the motoneurons of the
neck muscles (allowing the head’s axes to adopt a Fick strategy). In this manner, it is theoretically possible for the INC, as
well as other nuclei, to control different body parts in modalityspecific coordinates. However, although this may or may not
be true for some individual neurons, our view is that the INC
must have enough separate eye/head projections from different
units to be able to act as a dual, separate eye/head controller,
even if these are then nested within an overall circuit for gaze
control.
J Neurophysiol • VOL
This does raise the question of how the gaze control system
deals with different effectors and different internal coordinate
systems. If the assumption of a common gaze command in the
INC is true, then the fact that the coordinate axes for the eyes
and head do not align may lead to problems in eye– head
coordination. For example, a movement command along any of
the three coordinate axes would cause the eye and head to
move in different directions because these axes themselves are
not aligned. Note, however, that this potential dilemma is not
so great, given that Listing-like and Fick-like coordinates are
chosen by the brain. The Listing strategy ensures that the three
coordinate axes for eye movements are all fixed in the head.
Similarly, the Fick strategy ensures that both the torsional and
horizontal axes for head rotation are fixed in the head as well.
Therefore misalignment of these two strategies would occur
only with the vertical axis. For example, during an upward
head movement the space-fixed vertical axis for head rotations
would remain upright (relative to space), whereas the headfixed vertical axis for eye movements would tilt back with the
head. This becomes a lesser problem when one considers that
the head’s contribution to gaze is mainly horizontal, with only
very small vertical components. Nevertheless, we predict that
there are control signals that account for these differences.
Behavior-related coordinate systems and plasticity
If the coordinate axes of the head had been found to align
with anatomical structures such as the canals, eye muscles, or
some stereotaxic landmark, then head movements would likely
be fixed and unchangeable. However, because the head’s axes,
much like the eyes’, are aligned with a behavior-related strategy, then it is likely that different head movement strategies
can be learned. Proof of such plasticity has already been found
using a goggle paradigm (Ceylan et al. 2000; Crawford et al.
1999). In that situation, humans and monkeys wore opaque
goggles that occluded all vision except for a tiny aperture in
one eye. To look around, the monkey had to use its head to
cover a much larger area than before the occlusion (akin to
viewing a visual scene while using binoculars). When 3D head
movements were measured, it was found that the head quickly
abandoned its normal Fick strategy for a Listing strategy
(seemingly appropriate because the head was now moving like
an eye). What are the implications of this for an internal
coordinate system that aligns with these behavioral coordinates? How can it switch so fast?
Again, neural coordinates need not be hard wired because
they depend on upstream (and in this case) downstream neural
connections, which clearly change with different behavioral
sets (Constantin et al. 2004). Because Listing’s law and the
Fick strategy require two very different forms of positiondependent axes (half-angle rule for all axes in Listing’s, full
angle for Fick’s horizontal axis, and zero angle for Fick’s
vertical axis), this plasticity might seem to argue against a
mechanical implementation of these position dependencies for
the head. However, any set of mechanics can be used, undone,
or reinforced neurally—any of which would influence the
motor coordinates of the upstream neural structures—and it is
extremely difficult to know the source of the change in behavior without doing specific neurophysiological experiments.
Ultimately, the organization of the coordinate system used by
the INC probably arises from a combination of sensory inputs,
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tion of the up or down populations across the midline will
produce position vectors with zero torsion in Fick coordinates
(i.e., the Fick strategy observed in behavior; Glenn and Vilis
1992; Radau et al. 1994). Our data confirm this to be the case
for the INC. The other requirement for this neural coding
scheme, again not yet tested, is that the vertical axis for
horizontal head rotation is fixed in the body and aligns with the
vertical Fick axis observed in behavior. With any other
scheme, a simple activation of the horizontal population would
produce violations of Donder’s law. Finally, it remains to be
tested whether the position dependencies required to implement this scheme are provided by neurons, the neck musculoskeletal system, or some combination of the two.
The other aspect of the neural mechanism for Donder’s law
is that it must be able to violate (or produce different forms of)
Donders’ law when required and correct those violations when
necessary. Obviously, humans can voluntarily violate Donders’
law of the head at will (i.e., by rolling the head from side to
side), and we automatically modify it to suit different tasks
(Ceylan et al. 2000), so the Fick constraint is not fundamentally
mechanical. The system must choose to balance torsion at zero
(as described above) or selectively activate one side of the INC
to produce head torsion, as we observed in our INC stimulation
data. Further, we demonstrated the capacity of this system to
correct torsional violations of Donder’s law head after INC
stimulation—presumably by endogenously activating torsional
units on the opposite side of the midbrain. Thus as with the
oculomotor system, the head muscles may implement some of
the position dependencies of Donders’ law. Evidence for this
has come from anatomical studies showing that the atlas and
axis of the spinal column are fit together in such a way as to
facilitate a default Fick strategy (Richmond and Vidal 1998).
Ultimately, however, it is up to the CNS to choose to produce
torsional components or to constrain torsion to zero in some
coordinate system.
615
616
KLIER, WANG, AND CRAWFORD
plant mechanics, and the kinematic necessities of eye– head
coordination.
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