Departments of 1Physiology and 2Biomedical Engineering, McGill University, Montreal, Quebec H3G 1Y6, Canada
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ABSTRACT |
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Cullen, Kathleen E., Henrietta L. Galiana, and Pierre A. Sylvestre. Comparing Extraocular Motoneuron Discharges During Head-Restrained Saccades and Head-Unrestrained Gaze Shifts. J. Neurophysiol. 83: 630-637, 2000. Burst neurons (BNs) in the paramedian pontine reticular formation provide the primary input to the extraocular motoneurons (MNs) during head-restrained saccades and combined eye-head gaze shifts. Prior studies have shown that BNs carry eye movement-related signals during saccades and carry head as well as eye movement-related signals during gaze shifts. Therefore MNs receive signals related to head motion during gaze shifts, yet they solely drive eye motion. Here we addressed whether the relationship between MN firing rates and eye movements is influenced by the additional premotor signals present during gaze shifts. Neurons in the abducens nucleus of monkeys were first studied during saccades made with the head stationary. We then recorded from the same neurons during voluntary combined eye-head gaze shifts. We conclude that the activity of MNs, in contrast to that of BNs, is related to eye motion by the same dynamic relationship during head-restrained saccades and head-unrestrained gaze shifts. In addition, we show that a standard metric-based analysis [i.e., counting the number of spikes (NOS) in a burst] yields misleading results when applied to the same data set. We argue that this latter approach fails because it does not properly consider the system's dynamics or the strong interactions between eye and head motion.
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INTRODUCTION |
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To generate saccadic eye movements, motoneurons
(MNs) are required to provide signals to the extraocular muscles to
overcome the restraining forces of the orbital tissues. The schema
shown in Fig. 1A illustrates
the classic model for saccade generation. There are two main features
to this circuit: first, the output of the oculomotor burst neurons
(BNs) of the paramedian pontine reticular formation drives the MNs
during saccades. Second, the output of the BNs is also sent to the
neural integrator (NI), which in turn provides the MNs with the tonic
signal that holds the eye steady in its new post-saccadic position. In
the most prominent version of this model, an eye position signal (E)
and an eye velocity signal () are carried to the MNs by the NI
and BNs, respectively. Because the primary drive to MNs during saccades is from BNs, the integrated firing rate of a BN [i.e., the number of
spikes (NOS) generated during the saccade-related burst] should be
well related to the integral of the accompanying saccadic eye velocity
profile (i.e., the amplitude of the saccade). Indeed, a number of
studies have reported a strong relationship between BNs-NOS and saccade
amplitude in head-restrained animals, where saccade size and duration
are relatively small (Cullen and Guitton 1997a
;
Scudder et al. 1988
; Strassman et al.
1986a
,b
). In this special case, the NOS generated by MNs is
similarly related to saccade amplitude (Sylvestre and Cullen
1999
).
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Under natural conditions, where the head is not restrained, a
combination of rapid eye and head movements [i.e., a gaze shift, where
gaze (G) = eye-in-head (E) + head-in-space (H)] is frequently used to redirect the visual axis in space (humans:
André-Deshays et al. 1988; Barnes
1979
; Guitton and Volle 1987
; Laurutis
and Robinson 1986
; Pélisson et al.
1988
; Zangemeister and Stark 1982a
,b
; and monkeys: Bizzi et al. 1971
; Crawford et al.
1999
; Dichgans et al. 1973
; Morasso et
al. 1973
; Tomlinson 1990
; Tomlinson and Bahra 1986a
,b
). Here, the size and duration of gaze shifts can be much larger than during head-restrained saccades. Recent studies of
BN discharge dynamics have demonstrated that most BNs carry head as
well as eye movement-related signals during gaze shifts (Cullen
and Guitton 1997b
). However, BNs provide a primary input to the
extraocular MNs during head-restrained saccades (reviewed in
Moschovakis et al. 1996
), and combined eye-head gaze
shifts (Cullen and Guitton 1997a
,b
; Roy and
Cullen 1998
). Thus during gaze shifts, MNs receive a signal
that is related to head as well as eye motion, but ultimately drive the
extraocular muscles of the eyes alone.
It is therefore logical to ask whether an analysis of MNs would reveal
that these neurons' discharges during gaze shifts are best correlated
with eye motion (as predicted by their projections) or with gaze motion
(as predicted by their input). On the one hand, because MNs ultimately
drive the extraocular muscles of the eyes alone, it might be expected
that they should encode only eye movement-related signals during gaze
shifts, and that the input/output relationship between extraocular
motoneuron activity and eye motion should be comparable with that
observed during saccades. If this is the case, then the head
movement-related signal carried to the abducens nucleus by BNs must be
subtracted out at the level of the MNs by the inputs of other premotor
cells. On the other hand, it is also possible that the input/output
relationship between extraocular motoneuron activity and eye motion is
altered during gaze shifts. For example, during gaze shifts, agonist
and antagonist MN pools might carry comparable head movement-related signals, which are later subtracted out via agonist/antagonist muscle
interactions in the orbit. In a preliminary report, Phillips and
colleagues (1996) presented data from a single abducens
nucleus neuron that showed qualitatively similar burst-tonic and pause activity for saccades and gaze shifts in the ipsilateral
(ON) and contralateral (OFF) directions,
respectively. More recently, they performed a metric (i.e., NOS-based)
analysis of abducens nucleus neuron (ABN) ON
direction discharges during gaze shifts (Ling et al.
1999a
,b
). However, the question of whether neuronal activity
and eye motion are related by the same dynamic relationship during
head-restrained saccades and head-unrestrained gaze shifts has remained unanswered.
In the present study, we addressed this question by recording from the
same ABNs during both saccades and gaze shifts. Neuronal discharges
were analyzed using two different approaches. First, a metric analysis
method (i.e., counting the NOS) was used to determine whether the
discharges of neurons in the abducens nucleus were better related to
eye or gaze movement (i.e., eye or gaze amplitude). This analysis
approach has been commonly used by oculomotor researchers to study
brain stem mechanisms of saccade generation (see reviews from
Fuchs et al. 1985; Hepp et al. 1989
;
Moschovakis et al. 1996
). Second, a dynamic analysis
method was also applied to the same neural discharges during saccades
and gaze shifts, by postulating a simple first-order model (FR = b + kE + r
, Fig. 1A), or alternatively a second-order model that
included an exponentially decaying (or "slide") term (FR = b + kE + r
+ uË
c
R) that has
been shown to provide more accurate descriptions of ABN activity during
saccades (Sylvestre and Cullen 1999
). These models were
used to describe motoneuronal firing rates with respect to eye (E),
gaze (G), or E and head (H) motion during saccades and gaze shifts. We
conclude that the same dynamic eye movement-based models can be used
to describe motoneuronal discharges during head-restrained saccades and
combined eye-head gaze shifts. In addition, we found that a classic
NOS-based analysis can lead to the erroneous conclusion that ABN
discharges, and by extension premotor neuron discharges, are better
correlated with gaze than with eye motion. We demonstrate that this
apparent correlation is physiologically meaningless and is due to
1) the dynamics of the system being improperly
considered, and 2) the correlation of eye and head
motion during gaze shifts.
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METHODS |
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Two monkeys (Macaca mulatta) were prepared for
chronic extracellular recordings. The surgical techniques have been
previously described (Sylvestre and Cullen 1999). All
experimental protocols were approved by the McGill University Animal
Care Committee and complied with the guidelines of the Canadian Council
on Animal Care. During the experiments, the trained monkey was seated
in a primate chair that was fixed to the suprastructure of a vestibular turntable. Head-restrained saccades and head-unrestrained gaze shifts
were elicited by stepping a laser target between horizontal positions
(±35° range) in predictable and random trials. In addition, large
amplitude gaze shifts (up to 75°) were obtained using a "barrier"
paradigm in which a food target appeared unexpectedly on either side of
an opaque screen facing the monkey (Cullen and Guitton
1997a
). Smooth pursuit eye movements were elicited by sinusoidal target motion (40°/s peak velocity, 0.5 Hz). Behavioral paradigms, target and turntable motion, and data storage were controlled by a QNX-based real-time data acquisition system (REX) (Hayes et al. 1982
). Gaze and head position signals,
target position, vestibular turntable velocity, and unit activity were
recorded on DAT tape for later playback and analysis. Off-line, the
position signals were low-pass filtered at 250 Hz (8-pole Bessel
filter) and sampled at 1,000 Hz. The sampled gaze and head position
signals were digitally filtered at 125 Hz, and eye position was
calculated as the difference between gaze and head position. Position
signals were digitally differentiated to obtain velocity signals.
Extracellular single-unit activity was recorded using enamel-insulated
tungsten microelectrodes (7-10 M impedance, Frederick Haer) as has
been described elsewhere (Sylvestre and Cullen 1999
). The abducens nucleus was identified based on its stereotypical discharge patterns during eye movement and whole-body rotation paradigms (Robinson 1970
). The location of each neuron,
in the present study, was confirmed using three-dimensional
reconstructions of electrode tracts; units that were located in regions
>0.5 mm from the estimated center of the abducens nucleus were not
included. Each neuron's eye position threshold was plotted versus its
eye velocity sensitivity during sinusoidal smooth pursuit. We then compared our data to that of Fuchs et al. (1988)
and
concluded that our sample contained ~70% MNs (see also
Broussard et al. 1995
; Sylvestre and Cullen
1999
).
The spike train of each ABN was determined using a windowing circuit
(BAK) that was manually set to generate a pulse coincident with the
rising phase of each action potential. The neural discharge was
represented using a spike density function in which a Gaussian function
(5 ms standard deviation) was convolved with the spike train
(Cullen et al. 1996). Saccade and gaze shift onsets and offsets were defined using a ±20°/s gaze velocity criteria. Neuronal lead times relative to movement onset were determined by 1)
measuring the latency between the occurrence of the first spike in the
burst and the onset of gaze motion and 2) using a
first-order model (see Eq. 1 in RESULTS) to
optimize the lead time, td,
simultaneously with the other model parameters (Sylvestre and
Cullen 1999
). The number of spikes in a burst (NOS) was defined
as the number of spikes that a neuron produced in the time interval
between movement onset and offset (Henn and Cohen 1973
)
and was computed after shifting the firing rate by
td. (Note that the NOS measurements did not differ significantly if the 1st spike estimate of lead time was
used.) A NOS value corrected for the position sensitivity of ABNs
(NOSC) was also computed for each saccade/gaze
shift following the method used by Delgado-Garcia et al.
(1986a
,b
) in their analysis of ABNs: first, the tonic firing
rate immediately preceding movement onset was subtracted from the
firing rate, and second, the remaining firing rate was integrated. For
each unit, optimal model fits (see Eqs. 1 and 2
in RESULTS) were also obtained from an ensemble of
20
ipsilaterally directed saccades or gaze shifts using least-square algorithms (Cullen et al. 1996
). A dynamic model's
ability to estimate neuronal discharges was assessed by calculating the
variance-accounted-for (VAF = {1
[var (mf
fr)/var (fr)]}, where mf represents the modeled firing rate and fr represents the actual firing
rate). Statistical significance was determined using a paired
Student's t-test.
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RESULTS |
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Ten neurons were sufficiently well isolated during head-restrained saccades, head-restrained smooth pursuit, and head-unrestrained gaze shifts, to allow the quantitative analysis included in this report. Figure 1B illustrates the discharge of an example ABN (unit B90_3) during a head-restrained saccade. This neuron was typical in that the first spike in its burst led ipsilateral saccades by 4 ± 1 ms [mean value pooled over all units (Meanp): 4.2 ± 0.8 ms, mean ± SD] when the head was restrained. For each ABN, the total number of spikes (NOS) generated during the saccadic burst was proportional to the amplitude of the saccadic eye movement (Meanp: slope = 1.1 ± 0.5, intercept = 3.0 ± 2.5, R = 0.85 ± 0.08).
Once a neuron was fully characterized during head-restrained paradigms,
the monkey's head was slowly and carefully released to allow full
freedom of head motion. During this critical transition, the unit's
activity and waveform were monitored on an oscilloscope to ensure that
the cell remained undamaged and well isolated. Figure 1C
illustrates the discharge of our example neuron during a voluntarily
generated gaze shift. This neuron was typical in that the onset of its
burst led ipsilateral gaze shifts by 6 ± 3 ms
(Meanp: 5.0 ± 1.3 ms). For ABNs, the NOS
was better correlated with the amplitude of the gaze shift
(Meanp: R = 0.75 ± 0.18) than with the amplitude of the eye movement component
(Meanp: R = 0.65 ± 0.22).
Indeed, the NOS was better related to gaze than to eye motion for most
(80%) of the neurons in this study. This result is illustrated for our
example neuron in Fig. 1C (insets). Correcting
the NOS for the tonic discharge of ABNs (NOSC;
see METHODS) did not significantly alter these conclusions
(70% of units were better correlated with gaze motion). Given that
ABNs control the motion of the eye, this finding is, at first glance, rather surprising. However, it is important to note that both the
NOS-based and NOSC-based analyses did
not properly consider the dynamics of the input-output
relationship between ABN firing rates and eye motion; inherent to both
approaches is the assumption that a neuron's firing rate (FR) is
solely proportional to eye velocity () during saccades and gaze
shifts (i.e., FR
, and by extension
FR
, thus NOS
E), which is not the case. This is an
important point that we shall now consider in detail.
We first addressed the question of whether dynamic eye-based
models that accurately describe ABN activity during head-restrained saccades could be used to predict head-unrestrained discharges of ABNs
during gaze shifts. Stated differently, if the dynamic relationship
between neuronal activity and eye movement is constant, it should be
possible to use the same eye movement-based model to describe the
discharges of ABNs during saccades and combined eye-head gaze shifts.
To test this prediction, we utilized two dynamic models based on either
a simple first-order approximation of eye plant dynamics
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(1) |
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(2) |
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For our sample of neurons, eye-based model predictions (using Eq. 1) well approximated the neuronal discharges during gaze shifts
[Meanp: variance-accounted-for for model
predictions (VAFpred) = 0.31 ± 0.20].
This result is illustrated for example neuron B90_3 in Fig. 2B (thick black line). In
contrast, gaze-based models in which E and were replaced by G
and
in Eq. 1, respectively, provided a poor
prediction of unit discharges (Meanp:
VAFpred =
0.71 ± 0.98). This is also
illustrated, for our example neuron, in Fig. 2B (thick gray
line). Note that a negative VAFpred indicates that the predicted model fit is worse than simply fitting the data with
a mean value. Comparable results were obtained when a more accurate
representation of ABN discharges during saccades, Eq. 2
(Sylvestre and Cullen 1999
), was utilized
(Meanp: VAFopt head-restrained = 0.69 ± 0.16; Meanp:
VAFpred head-unrestrained = 0.38 ± 0.18 vs.
0.07 ± 0.54, eye-based vs. gaze-based models, respectively). In addition, we found that the values estimated for the
parameters of eye-based models during gaze shifts were not
significantly different from those estimated during saccades (P > 0.05). Finally, when H and
terms were
added to eye-based Eqs. 1 and 2, no significant
improvements in VAFopt were observed (P > 0.05), and the estimated head movement parameters
were not significantly different from zero (P > 0.05).
In summary, although the NOS and NOSC analyses imply a gaze sensitivity on ABN discharges during gaze shifts, ABN firing rates are well determined by eye plant dynamics alone. Furthermore, our dynamic analyses indicate that ABN discharges are related to eye motion by the same dynamic relationship during head-restrained saccades and head-unrestrained gaze shifts.
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DISCUSSION |
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In this study, we have applied dynamic analysis techniques to ABN discharges recorded during saccades made with the head-restrained, and during combined eye-head gaze shifts. This approach provided an objective comparison between the discharges of these neurons during saccadic eye movements that 1) were not accompanied by head motion and 2) were accompanied by head motion. Such a comparison is important to understand how the brain stem simultaneously processes eye and head motor signals during gaze shifts. Based on the results of our analysis, we conclude that models of ABN discharges obtained during head-restrained saccades can adequately represent the discharge of these same neurons during combined eye-head gaze shifts.
Previous studies of gaze shifts have demonstrated that eye
movement-based dynamic models of premotor BNs activity are
parametrically altered when comparing saccades to gaze shifts
(Cullen and Guitton 1997a,b
). During gaze shifts, the
discharge frequency of BNs was shown to be approximately proportional
to the sum of
and
signals. Therefore with respect to
MNs (i.e., the ABNs of the present study), the question arises as to
how the BN discharge, given that it contains a signal proportional to
, is transformed into the eye-only motor command that is
required to properly drive eye motion. One possibility is that the
agonist and antagonist MNs encode comparable
-related signals
that are subsequently nulled at the level of the oculomotor plant via
the interaction of the agonist/antagonist muscle pair. However, the
results of the present study indicate that this is not the case; the
relationship between agonist ABN firing rate and eye motion does not
change when the head is moving, and the head movement-related
information carried by ABNs is negligible. Consequently, during
combined eye-head gaze shifts, the inappropriate signals (i.e.,
-related) carried to the abducens nucleus by BNs must be offset
by other premotor cells. We propose that projections to the abducens
motor nucleus from premotor cells in the vestibular nucleus/nucleus
prepositus complex contribute to offsetting the
signal.
A second conclusion of this study is that a standard metric-based
analysis [i.e., counting the number of spikes (NOS) in a burst] is
inappropriate in the study of combined eye-head gaze shifts. This
finding can be better understood by considering recent models of
coordinated eye-head gaze shifts. A number of published gaze control
models, with a structure similar to that shown in Fig.
3A, predict temporal coupling
between eye and head movements during gaze shifts (Fuller et al.
1983; Galiana and Guitton 1992
; Guitton
and Volle 1987
; Guitton et al. 1984
,
1990
; Laurutis and Robinson 1986
;
Pélisson and Prablanc 1986
; Pélisson
et al. 1988
; Roucoux et al. 1980
;
Tomlinson 1990
; Tomlinson and Bahra
1986a
,b
; see review by Guitton 1992
). The
inset of Fig. 3A illustrates examples of the
coupling that we observed during gaze shifts.
increased with
the eye contribution and remained high toward the end of the gaze shift
despite a decrease (and sometimes an actual plateau or reversal) in
ocular velocity.
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It has been proposed that premotor neuron/motoneuron discharge metrics
will appear more linearly related to gaze shift amplitude than to eye
movement amplitude when eye and head motion are coupled (Galiana
and Guitton 1992). The result of the present study, as well as
other recent reports (Ling et al. 1999a
,b
), demonstrate that this, in fact, is the case for ABN discharges (Fig. 1C,
insets). In Fig. 3, B and C, we further
emphasize this finding by plotting the cumulative NOS in an ABN burst
versus current eye and gaze amplitude, respectively, for the same
neuron that was illustrated in Figs. 1 and 2 (unit
B90_3). The neural responses for the same four example
gaze shifts that were plotted in the inset of Fig. 3A are shown (gray traces). It is clear that the NOS-gaze
phase plane plot trajectories are fairly linear, whereas the NOS-eye phase plane trajectories are significantly curved.
Two important conclusions can be made based on the relationships shown
in Fig. 3, B and C. First, Ling and
colleagues (1999b) argued that during gaze shifts, the last
spikes in the burst are "consumed" by the oculomotor plant, because
the eye movement is constrained by the mechanical limits of the orbit.
We show that this is not the case because, during gaze shifts, the eye
often plateaued or turned around well before reaching the mechanical limits of eye rotation (i.e., <30°; Fig. 3B). Second, the
results in Fig. 3, B and C, can be accounted for
by a first-order model of oculomotor plant dynamics. We integrated the
first-order eye-based dynamic model of unit B90_3
during two of the example gaze shifts to obtain the predicted
cumulative NOS (black traces). The modeled NOS-eye and NOS-gaze phase
plane plot trajectories showed trends that are comparable with the
actual data. The resultant cumulative NOS yielded a nonlinear
relationship with eye displacement, and paradoxically a more linear
relationship with gaze displacement. There are two reasons why this
occurs: 1) the NOS and gaze shift size are both increasing
monotonically, whereas the eye in the orbit can reach plateaus and even
reverse its direction during gaze shifts (compare the insets
of Fig. 3, B and C), and 2) ABN activity will be correlated mainly with eye velocity only for short-lived saccades where the eye plant acts as an integrator of
high-frequency inputs. During larger, longer-lasting gaze shifts, eye
plant dynamics begin to play a more important role: the eye plant no
longer acts as a simple integrator and the NOS-eye relationship breaks
down and, in fact, is no longer appropriate.
In summary, ABN activity always remains appropriately related to eye position through the dynamics of the eye plant during both head-restrained saccades and head-unrestrained gaze shifts. The apparent strong correlation between the NOS generated by ABNs and gaze metrics is therefore simply incidental to the fact that eye and head trajectories are strongly correlated and together form a monotonically increasing gaze trajectory. We conclude that, although metric-based analyses are commonly used to characterize brain stem neurons during rapid eye movements, it is crucial that the system dynamics be properly considered in the study of gaze control.
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ACKNOWLEDGMENTS |
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We are grateful to J. E. Roy for contributing to the data collection and for several valuable suggestions. We thank D. Guitton, M. Huterer, and A. Dubrovsky for critically reading the manuscript. We also thank M. Drossos, W. Kucharski, and A. Smith for outstanding technical assistance.
This study was supported by the Medical Research Council and by the Natural Sciences and Engineering Research Council of Canada.
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FOOTNOTES |
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Address for reprint requests: K. E. Cullen, Dept. of Physiology, 3655 Drummond St., Rm. 1220, McGill University, Montreal, Quebec H3G 1Y6, Canada.
The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Received 24 June 1999; accepted in final form 8 September 1999.
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REFERENCES |
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