JOURNALOFNEUROPHYSIOLOGY Vol. 68, No. 1, July 1992. Printed

in U.S.A.

Discharge Patterns of Levator Palpebrae Superioris Motoneurons During Vertical Lid and Eye Movements in the Monkey ALBERT

F. FUCHS,

WOLFGANG

BECKER,

LEO LING,

THOMAS

P. LANGER,

AND CHRIS

R. S. KANEKO

Regional Primate Research Center, University of Washington, Seattle, Washington 98195; and Sektion Neurophysiologie, Universitat Urn, D- 7900 Urn, Germany SUMMARY

AND

CONCLUSIONS

1. We recorded single-unit activity in the caudal central nucleus(CCN) of the oculomotor complex in monkeys trained to make vertical saccadic,smooth-pursuit,and fixation eye movements.We confirmedthat our recordingswerefrom motoneurons innervating the upper lid, becausesmalllesionsplacedat the sites of responsiveunits were recovered among neurons labeled by horseradishperoxidase(HRP) injections into the levator palpebrae superiorismuscle. 2. For fixations above a thresholdlid position, levator motoneuronsdischargedat a steadyrate, which increasedlinearly with upward lid position. The averageposition sensitivity during fixation was2.9 spikes/sper deg,and the averagelid motoneuron was recruited into steadyfiring when the eye waslooking 10” down. 3. During upward saccades,levator motoneuronsdischargeda burst of spikesthat began,on average,7.3 msbeforethe lid movement if the saccadestartedfrom a straight-aheadposition; the lead time decreasedconsiderablyas the initial eye and lid positions shifted downward. The firing rate usually reachedits peak ( 130280 spikes/s)at the very onsetof the burst and declinedgradually during the courseof the saccade.The steadyrate associatedwith the new fixation position was reachedabout halfway during the saccade.All units exhibited a pausein firing during the initial half of largedownward saccades; during smallsaccades, the pausewas inconspicuousor absent. 4. During vertical sinusoidalsmoothpursuit, levator motoneurons exhibited a sinusoidalmodulation in firing rate, which led eyeposition by an averageof 23” at 0.3 Hz. The averagevelocity sensitivity calculatedfrom suchdata was0.63 spikes/sper deg/s. 5. Although they exhibit a number of qualitative similarities, the dischargepatternsof levator motoneuronsand superiorrectus motoneuronsdiffer in severalrespects.First, during a blink, when the lid undergoesa large depressionbut the eye exhibits only a brief transient displacement,levator motoneurons ceasefiring completely,whereassuperiorrectusmotoneuronscontinueto discharge. Second,for all types of coordinated lid and eye movements,levator motoneuronsdischargeat lower firing ratesthan do superiorrectusmotoneurons.Third, during saccades, levator motoneurons have lessconspicuousand shorter-lastingburstsand pausesthan do motoneuronsinvolved in rotating the eye. 6. During upwardgaze,the qualitative similarity of their bursttonic dischargepatternssuggests that levator and superiorrectus motoneuronsreceiveinput signalsthat originate from a common source,but that the signalsare processeddifferently to deal with the different loadsfacing these muscles.If the lid starts from a depressed position, a surprisinglysmall fraction of the lid motoneuron pool seemssufficient to initiate an upward lid saccade. During downward gaze,an incomplete pausein lid motoneuron activity coupledwith the passiveelasticforcesin the orbit appears to be all that is involved in the production of downward lid saccades.Finally, during blinks when eye and lid movementsare

uncoordinated,the levator clearly must receive an inhibitory input, whereasthe superiorrectus doesnot. INTRODUCTION

To protect the eyes without obstructing vision, the eyelids must move with vertical eye movements. The concur-

rent vertical movements of the eye and the upper lid are remarkably similar ( Becker and Fuchs 1988 ) . One would be hard pressed to distinguish between lid and eye movements on the basis of their time courses during smooth-pursuit, steady fixation, and even saccadic eye movements. The similarity is so striking that we named the lid movements accompanying saccadic eye movements “lid saccades.” On the basis of their similar time courses, one might conclude that the patterns of innervation to the levator palpebrae superioris muscle, which raises the lid, and to the superior rectus muscle, which elevates the eye, must be very similar. This tight correspondence should break down only during blinks, when the upper lid undergoes an initial large depression and then a subsequent elevation while the eye experiences only a small transient deflection whose details depend on the eye position at the onset of the blink (Collewijn et al. 1985; Riggs et al. 1987). The discharge of putative motoneurons innervating the vertical rectus muscles is well documented (Schiller 1970; Robinson 1970; King et al. 198 1). During fixation, a superior rectus motoneuron discharges at a steady rate that increases linearly as the eye fixates at more upward positions. Before an upward saccade, these motoneurons discharge a burst of spikes, which continues until just before the saccade lands, whereupon the firing rate falls to that appropriate for the new fixation position. During horizontal saccades, a similar burst-tonic discharge pattern occurs in abducens motoneurons and also in the electromyogram (EMG) of the lateral rectus muscle, which they innervate (Collins et al. 1975 ) . This burst-tonic firing pattern is thought to cause a pulse-step pattern of muscle force, which overcomes the viscoelastic properties of the target muscles and the connective tissues of the orbit to generate the high saccadic velocities. Indeed, it is well documented that the lateral rectus muscle produces a pulsestep pattern of force during saccades ( Collins et al. 1975; Robinson 1964; Robinson et al. 1969). We previously reported two lines of circumstantial evidence that levator motoneurons behave like the motoneurons involved in rotating the eye, hereafter called “eye moto-

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movements,we measuredlid and eye position by examining single video frameswhere an oscilloscopetrace of eye position was superimposed on a frontal close-upof the monkey’seyes.In monkey 2 we implanted a preformed oval searchcoil (5 x 7 mm), consistingof five turns of fine wire, into the upper lid of the left eye. With the animal under generalanesthesia,an incision was madein the skin acrossthe upper lid, and a pouch wasdissected away from the eyelash.The coil wasslippedinto the pouch, and the protruding wire leadswere run subdermallyto a plug on the animal’shead.The rationale for measuringlid movementsasan angular displacementand the methodsfor calibratingthe lid coil signalare discussedelsewhere( Becker and Fuchs 1988). The animalswere trained to follow a light spot that wasrearprojectedonto a translucentscreenat a distanceof 0.7 m. Vertical eye and lid movementsand fixations at various elevationswere evokedby vertical displacementsof the targetspot,either stepwise (to elicit saccades)or sinusoidal(to elicit smooth-pursuitmovements) within a rangefrom 30” down to 25” up. Lid blinks were elicited by brief air puffs, which were generatedremotely by a syringe bulb and delivered to a point near the outer canthus through a long tube. Vertical and horizontal eye position, lid position, their derivatives (eye and lid velocity, obtainedby electronicdifferentiation), target position, and unit activity were recordedon FM tape. The data from monkey 1 were written out on a high-speedrecorder (Bell & Howell datagraphNo. 5- 134), and instantaneousfiring frequency was determined manually from interspike intervals. The data from monkey 2 were digitized and analyzedby interactive computer programs,which enabledthe userto point out the onsetand termination of the vertical eyeand lid position during either a saccadeor a blink, the timesof occurrenceof the peakeye and lid velocities,and the beginningand endof the phasicactivity, either a burst or a pause,associatedwith the rapid movement. Burst onsetwastaken asthe first shortenedinterspikeinterval and burst end asthe last interspikeinterval beforethe steadypostsaccadic firing rate was attained. Pauseonset wastaken asthe first lengthenedinterspike interval. In monkey 1 thesemeasureswere madewith a ruler on high-speedrecordsof unit activity and eye position. To control for the compatibility of the two methods,we digitized four units of monkey 1 and subjectedthem to computer analysis. Once the salientpoints of the dischargepattern and the associated movementshad been identified, a computer program calculateda variety of lid/eye movement measures (e.g., movement size, peak velocity, duration) and firing rate parameters(e.g., burst frequency, number of spikes,unit lead time, burst/pause METHODS duration). After all the movementswereanalyzed, different combinations of firing rate and movement parameterswere plotted Recording conditions againsteachother and fit with linear regressions. To determinethe Extracellular action potentialswere recordedfrom the vicinity averagedischargepatternsduring rapid lid movements(saccades of the oculomotor complex in six rhesusmacaques(Macaca mu- and blinks), a computer program accumulatedthe number of Zatta). Most of our single-unitdata were obtained from two ani- spikesoccurring during 8-mstime bins for 6-30 movementsof mals,called“recording monkeys” or monkeysI and 2. Four other similaramplitudealignedon movementonset.The specificstrateanimals,called “anatomic monkeys,” servedassubjectsfor ana- gies for the analysisof unit activity during fixation, saccades, tomic studiesto confirm the location of our putative levator moto- smoothpursuit, and blinks are detailedin the appropriatesection neurons.Unit activity wasrecordedby tungstenmicroelectrodes, OfRESULTS. which were protected by a guide tube and loweredinto the brain through a chronically implanted recording chamber(Fuchs and Anatomic preparation Luschei 1970). Eye movementswere measuredby meansof the electromagIn the two recordingmonkeys,we locatedlevator motoneurons netic searchcoil method (Fuchs and Robinson 1966). The pick- by their characteristicbehavior during blinks (seeRESULTS) and up coil consistedof three turns of fine wire that were wrapped then placedmicrolesionsat suchsitesby delivering a 15-s 30-PA under the four rectus musclesof the left eye and connectedto a anodalcurrent through the recordingelectrode.Microlesionsalso socketfixed to the animal’shead. The animals’headswere held were placedat the locationsof similarly identified neuronsin the within magneticfield coils by chronically implanted stabilization first two anatomicmonkeys,which had beenusedin other recordlugs (Fuchs and Luschei 1970). In monkey 1, after we beganto ing experiments.At the conclusionof the recordingexperiments, suspectthat our neuronal population was concerned with lid the monkeys were deeply anesthetizedand perfusedwith saline

neurons” to distinguish them from lid motoneurons (Becker and Fuchs 1988). First, for upward saccades, the levator muscle of humans exhibited a burst of EMG activity that was greater than the subsequent steady activity required to hold the lid in its elevated position. Second, when humans attempted upward saccades while the lid was held, the levator generated a pulse-step pattern of isometric force. On the other hand, there also are reasons to expect that the innervation patterns of lid and eye muscles might be different. First, each eye muscle is one of a pair of antagonistic muscles, which act in a synergistic fashion, whereas the levator palpebrae superior-is is thought to act alone during vertical gaze shifts (Evinger et al. 1984). Vertical lid position apparently is determined by a balance between upward levator force and the elastic forces opposing lid elevation; the opposing elastic forces during elevation would result, in part, from an increased transverse stretch in the upper lid because its effective center of rotation is lower than the center of rotation of the eyeball (Kennard and Smyth 1963). Only during blinks and winks is the levator paired with the antagonistic orbicularis oculi of the upper lid. Second, although no detailed comparison exists, the mechanical load of the levator appears to be quite different from that of eye muscles, which at least face a much larger moment of inertia. Finally, the fiber composition of eye muscles differs appreciably from that of the levator muscle, which lacks multiply innervated fibers and does not have separate global and orbital layers (Porter et al. 1989). While gathering cells for another study, we discovered a thin layer of upward burst-tonic neurons located at the dorsal edge of the oculomotor and trochlear nuclei. The behavior of these neurons during vertical eye movements and blinks suggested that their discharge was related to movements of the upper lid, rather than the eye. These cells were located in the caudal central nucleus (CCN), where levator motoneurons reside (Porter et al. 1989). We will now show that, in all likelihood, we have recorded from levator motoneurons and that the discharge patterns of these neurons differ from those of vertical eye motoneurons in several important respects.

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DISCHARGE

PATTERNS

OF

SIMIAN

followedby 10%Formalin. Frozen sectionswere cut every 40 pm, mounted on microscopeslides,and stainedwith cresyl violet for histologicalreconstructionof the lesionsand the electrodetracks. In the lasttwo anatomicmonkeys,the location of levator motoneurons was determined by injecting horseradishperoxidase (HRP) into the right levator palpebraesuperiorismuscle.With the monkey under anesthesia,the levator wasapproachedthrough the roof of the orbit and carefully isolatedfrom all surrounding orbital tissueby blunt dissection.In the first HRP monkey, which alsohad a lesionat the site of a putative lid motoneuron (Figs. 2 and 3), paraffin wasinjected around the levator to prevent HRP from reachingthe other muscles.Becausethis procedurewasnot completely successful in preventing contamination of the superior rectusmuscle,the levator of the secondHRP animal wasisolated by Teflon film beforethe paraffin wasinjected. In eachanimal the wound wascarefully closedand the animalwasreturned to its cage after it had receivedthe appropriateanalgesics. After 24 h, the monkeys were anesthetizedand perfusedintracardially with a phosphate-bufferedsolution of 1%paraformaldehyde and 2%glutaraldehyde.The brainswereexposed,blocked in either the transverseor stereotaxicplanes,and removedinto 0.1 M phosphatebuffer with 30% sucrose.After the excesstissuewas trimmed, the blocked brains were placed in sucrosebuffer and held in a refrigerator overnight. The next day, the brains were sectionedand reactedby the standardprotocol for tetramethylbenzidine ( Mesulam 1978) . RESULTS

General observations All of the 44 cells described in this study displayed firing patterns that were qualitatively similar to those exhibited by the cell illustrated in Fig. 1. For steady vertical eye (V) and lid (L) positions, all units discharged at a constant. firing rate that increased as the eye looked upward and the lid was elevated simultaneously. Upward saccadic eye movements were accompanied by a burst of spikes, whereas downward saccades usually were accompanied by a decrease in firing rate. Although this burst-tonic discharge was reminiscent of that displayed by eye motoneurons, it differed in several respects. First, the steady discharge rate invariably was lower. Second, the burst associated with upward saccades was relatively weak, and the slowing of activity for downward saccades often was barely perceptible. Finally, the most distinctive discharge characteristic was the firing pattern during blinks. During a blink, when the upper lid comes down (-) ) but the eye undergoes only a brief movement of small amplitude (Riggs et al. 1987), there was a complete cessation of neuronal discharge. In contrast, superior rectus motoneurons, which also exhibit a burst-tonic discharge pattern for upward eye movements (King et al. 198 1 ), exhibit little change in activity during blinks. Neurons with discharge properties like those in Fig. 1 could be recorded over only a very thin region (typically 0.3- 1.O mm), and it was not unusual to encounter only one or two related units per penetration. Invariably, they were encountered just dorsal to cells that had the “brisker” bursttonic patterns typical of eye motoneurons. This brisker activity was frequently of the downward burst-tonic variety characteristic of trochlear motoneurons. The lesion in Fig. 2B was made at the site of the neuron described in Fig. 1 and the lesion in Fig. 2A at the site of a neuron with similar

LEVATOR

+50

235

MOTONEURONS

L

+40 +30 +20 arcs'

J

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+20

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+lO O -10

0 llil'J

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FIG. 1. Discharge properties of a typical putative levator palpebrae superior-is motoneuron. This neuron was recorded at the site of the lesion shown in Fig. 2B. Levator motoneurons exhibit a weak burst-tonic discharge pattern for vertical eye (V) and lid (L) movements but, unlike superior rectus motoneurons, cease firing during blinks (down phase of blink indicated by +), although the eye remains relatively stationary.

discharge characteristics. Both lesions lay just dorsal to the trochlear nucleus. Although it was impractical to make lesions at the site of every interesting unit, the dorsoventral sequence of firing patterns was so reproducible that we are confident that all of the units described in this paper lay just dorsal to eye motoneurons. Finally, in the vicinity of units like that characterized in Fig. 1, brief, high-frequency, multiunit background activity often accompanied every blink (see Fig. 8). Thus the presence of such blink-related background activity provided an additional indicator when we were recording from the population of dorsally lying neurons.

Location of levator motoneurons Several studies have shown that the dorsal region of the caudal oculomotor complex blends with the region just dorsal to the rostra1 part of the trochlear nucleus to form a separate nucleus, the CCN, which contains the cell bodies of levator motoneurons (Porter et al. 1989; Warwick 1953 ) . Figure 2, A and C, also shows the location of some of the motoneurons labeled by HRP injected into the right levator muscle. The vast majority of all of the labeled neurons were found bilaterally in an area that clearly comprised the CCN. The labeled cells stretched caudally from the dorsal midoculomotor complex to the region dorsal to the rostra1 trochlear nucleus ( Fig. 3). Labeled neurons outside the CCN lay in regions known to contain superior rectus motoneurons (Porter et al. 1983). Porter et al. ( 1989) also observed labeled cells outside the CCN after similar injections. They suggested that these were actually superior rectus motoneurons that had been labeled owing to the “unavoidable spread” of the tracer to the underlying rectus muscle. In a second animal we placed a small levator injection after isolating the levator (see METHODS) and obtained bilateral labeling confined to the CCN (not shown). On the basis of I) their recording locations dorsal to eye motoneurons; 2) their histological locations revealed by marking lesions such as those in Fig. 2, A and C, amidst labeled CCN neurons; and 3) their distinctive behavior during blinks, we conclude that the neurons whose firing patterns we will now describe are levator motoneurons, and we

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Fuchs 1988), although the lower margin of the lid is elevated by 30” when the eye is in its primary position. Consequently, in what follows, the discussion of the static characteristics of levator motoneurons will be referred to eye position, but the relations apply equally well to relative lid position. In monkey 2 we recorded both eye and lid position as illustrated in Fig. 1. Linear rate-position relations similar to that shown in Fig. 4 were obtained for 35 of the 44 units recorded (average correlation coefficient, r = 0.96). The static behavior of these neurons can therefore be characterized by a slope (the static position sensitivity in spikes/s per deg) and an intercept (the threshold position of the lid or eye, in degrees) at which the unit is recruited into steady firing. Two units displayed clearly nonlinear relations whose slopes became steeper ifthe eyes looked > 10” upward. Their position sensitivities were taken as the slopes of the best-fitting lines for data around the primary direction of gaze, i.e., &lo”. The remaining seven neurons either exhibited a large variability

I

A-

B

RG. 2. Sections (in transverse plane in A and C in stereotaxic plane in B) through the mesencephalon, illustrating the locations of lesions placed at the sites of putative levator motoneurons in 2 monkeys. Discharge properties of the neuron recorded at the site in Bare illustrated in Figs. 1,4, and 6. C: the section in A is shown at higher magnification to illustrate the relation of the lesion to cells labeled by a horseradish peroxidase injection into the right levator palpebrae superioris muscle. Calibration bars indicate 500 hrn in A and B and 100 pm in C.

will subsequently refer to them as such. Neurons with characteristics like those depicted in Fig. 1, however, may also lie outside the CCN; in one animal, a lesion at the site of a putative levator neuron was retrieved at the dorsal edge of the oculomotor complex but 1 mm off the midline.

Discharge characteristics of ievator motoneurons STATIC CHARACTERISTICS.When lid position was held steady, levator motoneurons discharged at a very regular rate, which increased as the lid was raised (Fig. 1). The relation between steady firing rate and lid position (Fig. 4, top scale) for this unit was remarkably linear. The firing rate of levator motoneurons also is linearly related to eye position (Fig. 4, bottom scale). This relation is a consequence of the tight correlation between eye and lid position in all primates, a correlation that holds not only during static fixation but also during dynamic vertical eye movements such as saccades and smooth pursuit (Becker and Fuchs 1988 ). Therefore, in monkey I, which provided two-thirds of our cells, we. initially did not appreciate that lid movement was the crucial variable, and we measured only eye movements. When we did take video pictures of the upper lid during different vertical eye positions (see METHODS), the results confirmed that lid and eye position were tightlY CoDDIed ( r = 0.97 ) a The slope of the relation between lid and eye position is essentially one (Becker and

DSCP /--

6

-

_

^_ _ _ _ __

Location of labeled cells in the oculomotor complex after injection of horseradish peroxidase into the right levator palpebrae superioris muscle. A-D: rostra1 to caudal transverse sections spaced at 160-pm intervals, progressing from the caudal oculomotor (I&d) through the rostra1 trochlear (IVth) nuclei. C and D: shaded area demarcates the reconstrutted site of a lesion placed at the location of a neuron with firing properties similar to those illustrated in Fig. 1. The morphology of the neurons labeled in C is shown in Fig. 2C. CCN, caudal central nucleus; DSCP, decussation of the superior cerebellar peduncle; mlf, medial longitudinal fasciculus; PAG, periaqueductal gray. FIG. 3.

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DISCHARGE Lid Position 20

30

(deg) 40

PATTERNS

OF SIMIAN

* 50

60

l-0 EOye Position FIG. 4. Relation between firing rate and steady vertical lid position (top scale) and eye position (bottom scale) of the typical levator motoneuron recorded at the site marked by the lesion shown in Fig. 2 B. Each point represents instantaneous firing rate during steady fixation averaged from 10 interspike intervals. Data points are fit by a linear regression line (Y = 0.99 for firing rate relative to either eye or lid position) whose slope defines the neuron’s position sensitivity (KS) and whose intercept with the x-axis gives the neuron’s threshold ( T) for steady firing.

in firing rate on repeated fixations at the same vertical position or could be investigated for only a small range of fixation positions. For all seven, however, the firing rate increased monotonically with eye position and could be reasonably approximated with a straight line (average correlation coefficient, r = 0.87). Figure 5 (insets) shows histograms of the position sensitivities and thresholds for all 44 neurons. The mean sensitivity was 3.4 spikes/s per deg, but individual values showed a 1O-fold range from 1.2 to 12.6 spikes/s per deg. The thresholds were evenly distributed from - 30’ down to - 15 Oup, which corresponds to lid positions from -0 to 45O up, respectively. Therefore the number of neurons recruited into activity increases almost linearly as the eye and lid are raised from a depressed position (staircase curve in Fig. 5 ). During fixation at the primary position of gaze, where the upper lid is elevated by - 30”, - 70% of the lid neurons were active and had a mean discharge rate of 3 1 spikes/s. Units were recruited according to their position sensitivities over most of the vertical eye-position range (cf. scatter plot of position sensitivity vs. threshold in Fig. 5). From eye positions of 30’ down to 10’ up, the sensitivity increased linearly with threshold at a slope of 0.064 spikes/s/deg per deg (dashed line in Fig. 5). However, four units that were recruited at positions > 10’ up had sensitivities that were much larger than would be expected from such a linear relation; their data were not included in the regression calculation. Eliminating the data for these four units from the calculation of mean sensitivity above would yield a mean of 2.9 spikes/s per deg, which is closer to the median of 2.7 spikes/s per deg and is probably more representative. In humans, vertical lid position is correlated not only with vertical eye position but also, weakly, with horizontal eye position. For example, during lateral gaze, the upper lid, especially that of the abducted eye, is raised in most humans. This elevation seems to be of neural rather than mechanical origin because it is present and often exagger-

LEVATOR

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237

ated in patients with sixth nerve paresis (Ticho 197 1) . For several neurons in monkey I, we required the animal to fixate at different horizontal positions but at a constant vertical position. Of 10 neurons tested, 8 displayed discharge rates that were constant for all eye positions to one side of the primary direction of gaze and increased at a mean rate of 0.9 1 spikes/s per deg on the other side, either to the left or to the right. The same neurons had a mean vertical position sensitivity of 2.95 spikes/s per deg. However, it is difficult to interpret the modulation of firing rate with horizontal eye position because it is not known whether in the monkey, as in man, lid elevation during lateral gaze occurs predominantly in the abducting eye. DYNAMIC CHARACTERISTICS. Owing to the close correspondence between lid and eye position during fixation, we could deduce the relation between firing rate and static lid position from measures of vertical eye position. Although there is also a tight coupling of lid and eye movement during vertical saccades, small differences in timing do occur (Becker and Fuchs 1988). Moreover, the lid movement during blinks is completely different from the concomitant eye movement (Fig. 1) (Collewijn et al. 1985; Riggs et al. 1987). For these reasons, we shall base our quantitative description of the dynamic behavior of levator motoneurons on the 15 units obtained from monkey 2, in which we recorded instantaneous lid movements. We shall supplement this description by observations in monkey 1.

Smooth-pursuit movements The smooth-pursuit sensitivity of levator motoneurons was assessed during the nearly sinusoidal lid movements elicited when the monkeys tracked a target moving sinusoidally in the vertical direction. Six levator motoneurons recorded in monkey 2 were subjected to an interactive computer analysis, which allows the instantaneous firing rate during each cycle to be fitted by a sine wave whose size and

100 1 80

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Eye Position Lid Position

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FIG. 5. Position sensitivity and recruitment threshold for levator motoneurons. The staircase curve shows the percentage of active neurons as a function of eye position and lid position. The data points indicate position sensitivity (KS) of individual neurons as a function of their recruitment threshold ( T); the dashed line represents the linear regression (Y = 0.80) of sensitivity on threshold (top 4 units on the right not included). Histograms on Zeflshow distributions of static position sensitivities and threshold eye positions.

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phase shift are adjustable. The program averages these parameters for at least five cycles and calculates the neuron’s dynamic position ( Ko) and velocity (R) sensitivities (Fuchs et al. 1988). Dynamic position sensitivities ranged from 2.4 to 4.4 spikes/s per deg (mean 3.4) and were similar to the static position sensitivities determined from the rate-position curves (range, 1.8-4.6 spikes/s per deg with a mean of 2.6). Velocity sensitivities ranged from 0.54 to 0.78 spikes/ s per deg/s (mean, 0.68). The time constant (7 = R/ Ko) of this first-order approximation of the instantaneous firing rate ranged from 0.16 to 0.28 s (mean, 0.2 1). All of these measures represent means of the data averaged for each unit at all the frequencies tested for that unit (range, 0.250.6 Hz). With our limited set of data, it was impossible to discern a trend as a function of frequency for any of the measures. For 11 neurons recorded in monkey 1, we estimated the velocity sensitivity by averaging the interspike intervals between a fixed number of spikes (6- 10) during the epoch when the eye was tracking at a constant velocity across a fixed vertical position (usually 10’ up). The mean value obtained, 0.58 spikes/s per deg/s (range, 0.15-0.98), was in good agreement with the results of the computer analysis of the six neurons from monkey 2. Blinks and saccades Figure 6 illustrates the firing patterns of our representative unit (depicted in Fig. 1 and located in Fig. 2 B) during vertical saccades (Fig. 6, A, C, and D) and blinks (E). The onset of a blink was always preceded by a rapid and complete inhibition of the discharge rate. For the neuron of Fig. 6, the last spike occurred an average of 22 ms before the first detectable lid depression; for all 15 neurons, this blink lead time ranged from 10 to 59 ms (Fig. 7A) with a mean of 29.2 ms (median, 25 ms). In most cases the lowest lid position was reached within 50-60 ms of blink onset, and the blink amplitude exceeded 60”; consequently, mean downward lid velocity was - 1,200” / s, and peak lid velocities were as high as 2,400” /s (Fig. 6E). In contrast, the lid was elevated much more slowly, reaching peak velocities of only 470-600’ /s (mean of 540’ /s for a mean blink amplitude of 62’ ) . Levator motoneurons resumed firing after the lowest lid position had been reached and, except for two units, also after the first detectable upswing in lid position. The timing of the reappearance of unit activity with respect to the onset of lid upswing was rather variable from unit to unit, ranging from 26 ms before to 58 ms after; across all units, the onset of activity lagged lid upswing by 23 ms, on average (median, 18 ms; n = 13). For the unit in Fig. 6E, the time course of the firing rate resembled the upswing of the lid movement but not the concomitant eye movement, which varied considerably from blink to blink. Clearly, this unit discharged with lid and not eye position. Seven other neurons had similar firing patterns during the upswing, whereas five exhibited a weak overshoot in firing that could occur at any time during the upswing. The pattern seen during upward lid saccades was quite different (Fig. 6, A and B). In all 15 neurons of monkey 2, upward lid saccades were accompanied by a sudden burst of activity. In five, the burst lead time (measured from the 1st shortened interspike interval to movement onset) seemed

LANGER,

AND

KANEKO

to depend on initial lid position; for four, burst lead time decreased with increasing downward initial lid positions (at rates ranging from 0.06 to 0.34 ms/deg), whereas in one unit burst lead time increased with downward lid positions (at 0.19 ms/deg). The remaining neurons either exhibited no changes with initial lid position or could not be tested over a sufficiently large range of positions. Other factors, such as the size of the saccade or the presaccadic discharge rate, were not tested rigorously but seemed to have no obvious effects on lead time. When all saccades regardless of their starting position were pooled for a given neuron, the average burst lead time was 7.5 ms (range, 0.6-10.5 ms; Fig. 7C). When the possible dependence on starting position was taken into account by calculating the lead times for saccades beginning from a straight-ahead eye position (either from the linear regression of latency on position or by pooling saccades with starting positions in the vicinity of 0’ ) , an almost identical average ( 7.3 ms) was obtained. In monkey 1 the dependence of burst lead time on initial lid position, or more precisely presaccadic steady firing, was more dramatic. For 11 neurons, burst lead times were determined in three conditions. When eye and lid saccades started from below the threshold for steady firing, the burst lagged the onset of the eye saccade by 6.3 ms (range, 27.ms lag to 5-ms lead). When presaccadic activity was at an intermediate rate, the burst led by 2.2 ms (range, 8.7.ms lag to 9.4-ms lead). When the burst rose out of an elevated discharge level, it led the saccade by 5.7 ms (range, 2-ms lag to 12-ms lead). Similar figures were obtained when neurons evaluated at less than three conditions were included, i.e., 6.1 -ms lag, 3.5.ms lead, and 5.6-ms lead, respectively ( n = 19,22, and 13 ) . Because simian eye saccades lead the concomitant lid saccades by 0.5-2.0 ms (Becker and Fuchs 1988 ), we assume that the above figures underestimate the lead (and overestimate the lag) of the burst by 0.5-2.0 ms. In most neurons ( 12/ 15) of monkey 2, the burst frequency reached its peak during the first 8-ms bin after saccade onset (Fig. 6 B). In two others, peak firing occurred during the second bin (Fig. 6A) and, in one, during the third bin. For saccades between 10 and 20”, the shortest interspike intervals ranged from 3.6 to 7.7 ms, i.e., peak instantaneous frequencies were 133-280 spikes/s; the peak instantaneous burst frequency (calculated from the 8-ms bin containing the most spikes) ranged from 57 to 188 spikes/s. The burst discharge dropped to the postsaccadic steady rate about halfway through the saccade, as can be seen from the slopes of the regression of burst duration on saccade duration, which averaged 0.44 (range, 0.19-0.92; Fig. 7E). The amount by which the peak burst rate exceeded the presaccadic rate increased with peak saccadic lid velocity for all 15 units. The relation was fit by a straight line with an average slope of 0.23 t 0.058 (SD) spikes/s per deg/s and an average correlation coefficient of 0.8 1 t 0.13. These values for velocity sensitivity were smaller than those calculated from smooth-pursuit movements; the six neurons that had pursuit velocity sensitivities ranging from 0.54 to 0.78 spikes/s per deg/s exhibited saccadic velocity sensitivities of only 0.19 to 0.27 spikes/s per deg/s. Within the range of lid positions explored in our study, the amount of overshoot in peak firing rate relative to the

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postsaccadic steady discharge (i.e., the “pulse” component) pulse amplitudes of 20, 26, and 45 spikes/s. Finally, four showed no signs of saturation as the final lid position, and units had no discernible burst at all. hence the postsaccadic firing rate, increased. For lid sacLarge downward lid saccades generally were accompacades with a 550’ /s mean velocity ( 11 of 15 units provided nied by a transient decrease of levator motoneuron activity below the steady discharge associated with the postsaccadic at least 1 data set at or near this velocity), the pulse amplitude ranged from 64 to 200 spikes/s (mean value 122 lid position (Fig. 6, C and D) . This depression was rarely as spikes/s) . extensive as that during the downward component of a For 28 neurons in monkey 1, the burst characteristics blink and, for some small saccades, it was barely noticeable were quite variable. Seven had clear bursts; four had pulse at all (see rasters 4,7,8, 10 and 11, Fig. 6 D) . When activity components of 29,53,56, and 80 spikes/s for 10’ saccades. was clearly suppressed, however, the suppression often ocSeventeen neurons had weak or unreliable bursts; three had curred only during the initial part of the movement for both Downloaded from www.physiology.org/journal/jn by ${individualUser.givenNames} ${individualUser.surname} (129.186.138.035) on January 11, 2019.

240

FUCHS, BECKER,

LING, LANGER,

large and small saccades (Fig. 6, C and D). The decrease of firing associated with downward lid saccades always began before saccade onset. In contrast to the sudden change in activity for upward saccades, the activity before downward lid saccades usually exhibited a gradual slowing (Fig. 6D), which, in monkey 1, began an average of 37 ms (range, 14-68 ms; n = 13) before the onset of movement. The gradual slowing gave way to a precipitous drop in firing rate - 18.6 ms, on average, before the lid movement (range, 1 l-34 ms; n = 15 neurons; Fig. 7 B). To estimate when the inhibition underlying the sudden decrease in firing rate actually began, we subtracted one-half the average presaccadic interspike interval (Fuchs and Luschei 1970) and obtained an average lead time of 10.7 ms (range, 5-25 ms). Most levator motoneurons resumed firing well before the end of a downward lid saccade. For any given neuron, the time at which the activity resumed depended on the postsaccadic steady firing frequency; the higher this rate, the earlier firing would resume. For example, for a final rate of 50 spikes/s, the increase occurred -20 ms before the end of the saccade, or about halfway through a 20° saccade.

Background activity during blinks At >50% of the sites at which levator motoneurons were recorded, a distinct “background” discharge was audible during the pauses of motoneuron firing associated with eye blinks. In a few cases, such as that in Fig. 8, the discharge was large enough to resolve into unit activity. From such cases, it became clear that the activity reflected a burst of spikes, which was associated exclusively with blinks and could reach 700 spikes/s. If the blink occurred during PAUSE

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steady fixation, the burst began an average of 14.3 ms (range, 6-22 ms; n = 14 units) before the onset of the lid movement, but clearly after the onset of the pause in levator motoneuron activity (Fig. 8). If, however, the blink occurred during an upward saccade, the first impulses of the levator motoneuron burst blended with the first spikes of the blink-related activity; as the blink depressed the lid, the motoneuron gradually ceased firing until only the background discharge remained. DISCUSSION

Two pieces of evidence led us to conclude that the units we describe here indeed are levator motoneurons. First, their discharge was not related to vertical eye movements because the blink-related pauses in activity were correlated with lid but not eye movement (Fig. 6E). Second, they were located just dorsal to the oculomotor and trochlear nuclei in a region known to contain levator motoneurons (Porter et al. 1989) (Figs. 2 and 3). The depth over which they were recorded, the behavior of neurons in their vicinity, and the reconstructed locations of lesions placed at the sites where they were isolated confirmed that we were recording in the CCN of the oculomotor complex. It is possible, of course, that some of the neurons in the CCN, like those in both the abducens and oculomotor nuclei (Langer et al. 1985; Steiger and Biittner-Ennever 1978), are interneurons rather than motoneurons. However, filling both levator muscles labels the vast majority, if not all, of the CCN neurons (J. Porter, personal communication), so if interneurons exist at all, they are much less numerous than in eye motoneuron pools. Therefore we confidently refer to our neurons as levator motoneurons. In many respects, the discharge patterns of simian levator motoneurons could be predicted on the basis of the pattern of EMG activity recorded from the human levator muscle (Becker and Fuchs 1988). In particular, the simultaneous discharge of many levator motoneurons could produce the multiunit burst-tonic pattern in the levator EMG during upward saccades. Even some of the details of motoneuron and EMG activity are similar. For example, the pause in motoneuron activity lasted only for the first half of a downward saccade, as did the pause in human EMG activity.

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Furthermore, the early decline of motoneuron activity that preceded the frank pause by an average of 40 ms (Fig. 6E) is reflected in the early (50-65 ms) decline of levator EMG activity (Becker and Fuchs 1988). Also, the cessation of activity preceding a blink had a similar lead in simian motoneurons (an average of 22 ms) and in human levator EMG activity ( lo-20 ms). Finally, from the levator motoneurons with the longest lead times, we can infer that the multiunit EMG burst in the monkey levator would precede upward saccades by - 8- 10 ms, whereas the average lead of human levator EMG activity was lo- 11 ms. Comparison of levator and vertical eye motoneuron discharge patterns During all vertical eye movements except blinks, levator motoneurons have discharge patterns that are qualitatively similar to those of vertical eye motoneurons. The similarities include 1) a burst-tonic firing pattern for upward saccades, 2) a nearly linear relation between firing rate and eye (or lid) position (e.g., King 1976; King et al. 198 1; Robinson 1970) and 3) a monotonic relation between recruitment threshold and position sensitivity (King 1976; King et al. 1981). However, the parameters describing the discharge of lid and upward eye motoneurons also display several subtle differences. Table 1 provides a quantitative comparison of these parameters for levator motoneurons and putative upward eye motoneurons from data obtained by similar methods in our laboratory. For steady fixations, the average position sensitivity of levator motoneurons was somewhat less than that of upward eye motoneurons. Also, levator motoneurons had higher thresholds, on average, and, therefore, were active over a smaller range of eye positions. It was our impression that lid motoneurons discharged at lower peak rates during upward saccades than did the deeper upward burst-tonic neurons in the III nucleus. Unfortunately, peak burst rate data are not available for upward oculomotor neurons, but trochlear motoneurons, which discharge with downward saccades, reach rates that are at least double

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those of levator motoneurons. The burst in levator motoneurons peaked early and often ended well before the saccade, and the pause for downward saccades often lasted only for the first half of the movement and was preceded by an early (40-ms lead), gradual decrease in activity. Again, similar data are not available for upward oculomotor motoneurons, but trochlear motoneurons exhibit a burst that remains relatively constant throughout the saccade and a pause that continues until just before the saccade ends. All of the discharge parameters for abducens neurons are roughly twice as large as those for lid and vertical eye motoneurons (Table 1) . Several other characteristics of lid motoneurons, however, are reminiscent of those of abducens motoneurons. First, for both motoneuron pools, the velocity sensitivity calculated during saccades is less than that determined during low-frequency smooth-pursuit movements (Fuchs et al. 1988). Also, like lid motoneurons, the burst lead in abducens motoneurons shows a dependence on presaccadic eye position, including a change from burst lead to lag if the eye starts from far in the off-direction (A. F. Fuchs, unpublished results). Because, in addition, the burst leads for III nucleus neurons listed in Table 1 were obtained with electrooculographic measures of eye position, which underestimate saccade onset by l-2 ms, the lead times of lid and vertical eye motoneurons are probably about the same. How is the close coordination between the upper lid and vertical eye movements achieved?

The hierarchy between eye and lid movements would seem to be obvious; the lid must accompany the eye wherever it wishes to go! Hence it seems logical to assume that the lid control signal is derived either 1) directly from the activity of vertical rectus motoneurons or 2) from a common premotor source that reflects the primordial vertical eye control signal. In the first scenario, a copy of the oculomotor command carried by superior rectus motoneurons would be sent to the CCN via some premotor structure. Such a structure might be the supraoculomotor area, which, because of its location just dorsal to the oculomotor complex (Schmidtke and Biittner-Ennever 1992), might TABLE 1. Comparisonof dischargeparametersof levator and be within range of the collaterals of eye motoneurons that various eyemotoneurons are known to exist, at least for the cat (Evinger 1988). If superior rectus motoneurons have the same quantitative T BLead Rbmax KS s KT R,, discharge characteristics as trochlear motoneurons, both the pulse and step components of the superior rectus moto-10 0.06 LMN 2.9 0.68 7.5 130-280 neuron firing pattern would have to be scaled down, and, in 3.4 -15 0.13 0.6 4.4 IIL, VI 3.5*, 6.2 -31*, -11 0.18 1.36 6-8* 300-800* addition, the pulse would have to be high-pass filtered to NIV 3.8 -23 3 200-550 account for both the rapid fall of levator motoneuron activAll entries are mean values. For the lid motoneurons, K, and Tare based ity during upward saccades and its early resumption after on 40 units from both monkeys; R,, and BLead are from monkey 2 and are downward saccades. For the second scenario, two structures project to both based on 17 and 15 units, respectively. BLead for trochlear fibers and III,, neurons were obtained with electrooculographic recordings, which undermotoneuron pools and thus are candidates for a common estimate lead time by l-2 ms (Hepp et al. 1989). K’, static position sensitivsource: the rostra1 interstitial nucleus of the medial longituity (spikes/s per deg); T, vertical or horizontal eye position threshold (deg); dinal fasciculus (riMLF) and the interstitial nucleus of CaSKT, slope of regression of K, on T (spikes/s per deg/deg); R,, , velocity 198 I ; Schmidtke and Buttnersensitivity during 0.3 Hz smooth pursuit (spikes/s per deg/s); BLead, lead jal (INC) ( Buttner-Ennever of burst relative to lid or eye saccade (ms); Rbmax, range of maximum Ennever 1992; Steiger and Buttner-Ennever 1979). Bedischarge rates during burst (spikes/s); LMN, levator motoneurons; III,,, cause the riMLF contains only vertical burst neurons neurons in the oculomotor nucleus with upward “on” directions (King et (Buttner et al. 1977; King and Fuchs 1979), the eye/lid al. 198 1); VI, identified abducens motoneurons (Fuchs et al. 1988); NIV, position signal presumably would have to be generated elsetrochlear nerve fibers (Fuchs and Luschei 197 1). *Data from unidentified where. In contrast, neurons in the INC have a burst-tonic abducens neurons (Fuchs and Luschei 1970). Downloaded from www.physiology.org/journal/jn by ${individualUser.givenNames} ${individualUser.surname} (129.186.138.035) on January 11, 2019.

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discharge pattern. The pattern is characterized by rather modest bursts and pauses for saccades and mean position sensitivities that are comparable with those of levator motoneurons [ INC burst-tonic neurons: 2.6 spikes/s per deg (King et al. 198 1); levator motoneurons: 2.7 spikes/s per deg] . The average lead times for bursts in INC neurons (4.0 ms) are comparable with those for levator motoneurons if one considers the 2-ms underestimation of lead times obtained from electrooculographic eye movement measurements (Hepp et al. 1989) and the possible effects of eye position on lead time (see above). Therefore the INC bursttonic discharge pattern would seem appropriate to drive levator motoneurons, but would have to be “improved” if superior rectus motoneurons display the precise saccadic behavior shown by trochlear motoneurons. In a sense, this improvement would be the inverse of the nonlinear processing considered in the first scenario. In addition to an input related to vertical eye movement, levator motoneurons, but not superior rectus or inferior oblique motoneurons, must receive an inhibitory input that produces the pause in firing during blinks. This inhibition cannot be delivered solely by the high-frequency burst of background activity because the burst lags the onset of the pause in levator motoneuron activity and terminates before it resumes (Fig. 8). Instead, the relative timing of the levator pause and the background burst are reminiscent of similar patterns of human EMG activity in the levator and orbicularis oculi muscles, respectively (Bjork and Kugelberg 1953, their Fig. 3 ) . The burst in the orbicularis ( Evinger et al. 1984, their Fig. 4), like that of the background activity near levator motoneurons, ends as the lid begins the upward phase of a blink trajectory (the downward phase of the eye movement in Fig. 8). Consequently, the burst of background activity in the CCN could be a facsimile of the motoneuron activity directed to the orbicularis muscle. Perhaps the pause in levator motoneuron activity is initiated by some other earlier input and then is held off by this corollary inhibitory burst. Why the earlier inhibitory input cannot also be detected as fiber activity is unclear, but perhaps it acts at a premotor level.

the discharge characteristics of levator motoneurons accountfor the generation of lid saccades?

Do

Upward lid saccades made from depressed eye positions appear to have the same timing relative to the onset of the eye saccade as those initiated with the eye straight ahead. However, the bursts of many of our lid motoneurons actually lagged saccade onset if the eye movement originated from a depressed starting position. Although similar lags occur for some abducens motoneurons when saccades begin far in their off directions, the situations for the eye and lid muscles are quite different. When the medial rectus actively rotates the eye nasally, the lateral rectus is lengthened, and it stores elastic energy; this energy can be released suddenly by inhibiting the medial rectus, thereby compensating for the late burst in some abducens motoneurons. In contrast, the lowering of the eyelid and the lengthening of the levator during downward eye movements apparently is accomplished only by passive elastic forces (Evinger et al. 199 1; Kennard and Smvth 1963 ): therefore, even if the

AND KANEKO

levator should absorb some elastic energy when the lid is lowered, there is no means to liberate this energy to start an upward lid saccade. We can only suggest that the upward saccade is initiated by those few lid motoneurons whose discharge leads the saccade even for depressed starting positions and that additional levator motoneurons are recruited during the saccade. Our EMG recordings from the human levator during upward saccades do show a buildup of burst activity that is consistent with this suggestion. The situation is different for the upward movements that return the lid after a blink. Lid closure during blinks is helped by active contraction of the orbicularis oculi muscle, which clearly lengthens the levator palpebrae superioris and thereby transfers elastic energy to it; conceivably, this energy could be liberated to initiate the return movement once the orbicularis oculi is inhibited. Thus the observation that many lid motoneurons resumed firing only after the return movement had begun is less enigmatic than the lag of burst activity during some upward saccades. Finally, the slow buildup of levator activity during lid elevation at the end of the blink is compatible with the relatively low (compared with saccades of similar size) peak velocity of these movements (Fig. 6, A, B, and E). Downward lid saccades are almost as fast as upward ones. Yet, to our knowledge, no active forces contribute to downward saccades. Instead, they are thought to result from passive forces that take over as the levator muscle relaxes (Evinger et al. 199 1; Kennard and Smyth 1963 ) . Unless the mechanical system comprising the levator muscle, the upper lid, and their associated orbital tissues is very nonlinear, one would expect that downward lid saccades require a pulse of excess force similar to that driving upward lid saccades. In fact, a certain amount of excess force does occur, because levator EMG activity falls briefly below the postsaccadic level required to hold the lid in its depressed position ( Becker and Fuchs 1988 ) . However, this pulse of inactivation is much smaller than the pulse of activation that occurs during upward saccades. Moreover, the time course of inactivation seems inappropriate for two reasons. First, a gradual decrease in levator motoneuron activity begins almost 40 ms before the saccade, but the lid remains stable. Second, the levator pause returns to its postsaccadic level well before the end of the saccade (Fig. 6 D) and as early as halfway through the movement (Fig. 6C). It is difficult to imagine, therefore, how this pattern of motoneuron activity, which resembles that of the human levator EMG, can produce the observed lid movement by itself. Nor is there any evidence that the orbicularis muscles of the upper lid, which participate in blinks and squints, contribute materially to the generation of downward lid saccades. Although they do exhibit a small, transient activation during large downward saccades (Evinger et al. 199 1), weakening of the orbicularis by injection of botulinurn toxin or by deafferentation in Bell’s palsy does not affect the trajectory of downward lid saccades (Evinger et al. 199 1; Gordon 195 1). Therefore the downward lid saccade apparently is the sole example of a fast movement that is generated largely, if not solely, by passive elastic forces. We are grateful for the participation of J. L. McFarland in parts of this experiment. It is also a pleasure to acknowledge the technical contributions

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of S. Usher in all phases of the data collection. We acknowledge the skillful support of G. Knitter for animal care and D. Hasund for surgical assistance. Finally, we appreciate the editorial assistance of K. Elias. This work was supported by National Eye Institute Grants EY-00745 and EY-06558 and Division of Research Resources Grant RR00 166 to the Regional Primate Research Center. W. Becker was supported by the Deutsche Forschungsgemeinschaft Grant Be 783. Address for reprint requests: A. F. Fuchs, Regional Primate Research Center SJ-50, University of Washington, Seattle, WA 98 195. Received 2 December 199 1; accepted in final form 6 March 1992. REFERENCES W. AND FUCHS, A. F. Lid-eye coordination during vertical gaze changes in man and monkey. J. Neurophysiol. 60: 1227-1252, 1988. BJ~RK, A. AND KUGELBERG, E. The electrical activity of the muscles of the eye and eyelids in various positions and during movement. Electroencephalography Clin. Neurophysiol. 5: 595-602, 1953. B~TTNER, U., BUTTNER-ENNEVER, J. A., AND HENN, V. Vertical eye movement related unit activity in the rostra1 mesencephalic reticular formation of the alert monkey. Brain Rex 130: 239-252, 1977. B~TTNER-ENNEVER, J. A. Anatomy of medial rectus subgroups in the oculomotor nucleus of the monkey. In: Progress in Oculomotor Research, edited by A. F. Fuchs and W. Becker. New York: Elsevier/ North-Holland, 198 1, p. 247-252. COLLEWIJN, H., VAN DER STEEN, J., AND STEINMAN, R. M. Human eye movements associated with blinks and prolonged eyelid closure. J. Neurophysiol. 54: 1 l-27, 1985. COLLINS, C. C., O’MEARA, D., AND SCOTT, A. B. Muscle tension during unrestrained human eye movements. J. Physiol. Lond. 245: 351-369, 1975. EVINGER, C. Extraocular motor nuclei: location, morphology and afferents. In: Neuroanatomy of the Oculomotor System, Reviews of Oculomotor Research, edited by J. A. Buttner-Ennever. New York: Elsevier, 1988, vol. 2, p. 81-l 17. EVINGER, C., MANNING, K. A., AND SIBONY, P. A. Eyelid movements: mechanisms and normal data. Invest. Ophthalmol. Visual Sci. 32: 387BECKER,

400, 1991. EVINGER, C., SHAW,

M. D., PECK, C. K., MANNING, K. A., AND BAKER, R. Blinking and associated eye movements in humans, guinea pigs, and rabbits. J. Neurophysiol. 52: 323-339, 1984. FUCHS, A. F. AND LUSCHEI, E. S. Firing patterns of abducens neurons of alert monkeys in relationship to horizontal eye movement. J. Neurophysiol. 33: 382-392, 1970. FUCHS, A. F. AND LUSCHEI, E. S. The activity of single trochlear nerve fibres during eye movements in the alert monkey. Exp. Brain Res. 13:

78-89,1971. FUCHS, A. F. AND ROBINSON,

D. A. A method for measuring horizontal and vertical eye movement chronically in the monkey. J. Appl. Physiol.

21: 1068-1070, 1966. FUCHS, A. F., SCUDDER,

C. A., AND KANEKO, C. R. S. Discharge patterns and recruitment order of identified motoneurons and internuclear neurons in the monkey abducens nucleus. J. Neurophysiol. 60: 1874- 1895, 1988. GORDON, G. Observations upon the movements of the eyelids. Br. J. Ophthalmol. 35: 339-351, 1951. HEPP, K., HENN, V,, VILIS, T., AND COHEN, B. Brainstem regions related

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to saccade generation. In: The Neurobiology of Saccadic Eye Movements, edited by R. H. Wurtz and M. E. Goldberg. Amsterdam: Elsevier, 1989, p. 105-212. KENNARD, D. W. AND SMYTH, G. L. The causes of downward eyelid movement with changes of gaze, and a study of the physical factors concerned. J. Physiol. Land. 166: 178-190, 1963. KING, W. M. Quantitative Analysis of the Activity of Neurons in the Accessory Oculomotor Nuclei and the Mesencephalic Reticular Formation of Alert Monkeys in Relation to Vertical Eye Movements Induced by Visual and Vestibular Stimulation ( PhD thesis). Seattle, WA: Univ. of Washington, 1976. KING, W. M. AND FUCHS, A. F. Reticular control of vertical saccadic eye movements by mesencephalic burst neurons. J. Neurophysiol. 42: 86 l876,1979. KING, W.

M., FUCHS, A. F., AND MAGNIN, M. Vertical eye movement-related responses of neurons in midbrain near interstitial nucleus of Cajal. J. Neurophysiol. 46: 549-562, 198 1. LANGER, T., FUCHS, A. F., CHUBB, M. C., SCUDDER, C. A., AND LISBERGER, S. G. Floccular efferents in the rhesus macaque as revealed by autoradiography and horseradish peroxidase. J. Comp. Neural. 235: 2637, 1985. MESULAM,

M.-M. Tetramethyl benzidine for horseradish peroxidase neurohistochemistry: a non-carcinogenic blue reaction-product with superior sensitivity for visualizing neural afferents and efferents. J. Histothem. Cytochem. 26: 106-l 17, 1978. PORTER, J. D., BURNS, L. A., AND MAY, P. J. The morphological substrate for eyelid movements: innervation and structure of primate levator palpebrae superioris and orbicularis oculi muscles. J. Comp. Neural. 287:

64-81, PORTER,

1989.

J. D., GUTHRIE, B. L., AND SPARKS, D. L. Innervation of monkey extraocular muscles: localization of sensory and motor neurons by retrograde transport of horseradish peroxidase. J. Comp. Neural. 2 18: 208219, 1983. RIGGS, L. A., KELLY, J. P., MANNING, K. A., AND MOORE, R. K. Blink-related eye movements. Invest. Ophthalmol. Visual Sci. 28: 334-342, 1987. ROBINSON,

D. A. The mechanics of human saccadic eye movement. J. Physiol. Land. 174: 245-264, 1964. ROBINSON, D. A. Oculomotor unit behavior in the monkey. J. Neurophysiol. 33: 393-404, 1970. ROBINSON, D. A., O’MEARA, D. M., SCOTT, A. B., AND COLLINS, C. C. Mechanical components of human eye movements. J. Appl. Physiol. 26:548-553,1969. SCHILLER, P. H.

The discharge characteristics of single units in the oculomotor and abducens nuclei of the unanesthetized monkey. Exp. Brain Rex 10: 347-362, 1970. SCHMIDTKE, K. AND BUTTNER-ENNEVER, J. A. Nervous control of eyelid function: a review of clinical, experimental, and pathological data. Brain. In press. STEIGER, H.-J. AND B~TTNER-ENNEVER, J. A. Relationship between motoneurons and internuclear neurons in the abducens nucleus: a double retrograde tracer study in the cat. Brain Res. 148: 18 1-188, 1978. STEIGER, H.-J. AND B~~TTNER-ENNEVER, J. A. Oculomotor nucleus afferents in the monkey demonstrated with horseradish peroxidase. Brain Res. 160: 1-15, 1979. TICHO, U. Synkinesis of upper lid elevation occurring in horizontal eye movements. Acta Ophthalmol. 49: 232-238, 197 1. WARWICK, R. Representation of the extra-ocular muscles in the oculomotor nuclei of the monkey. J. Comp. Neural. 98: 449-503, 1953.

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