Unit activity in vestibular nucleus of the alert monkey during horizontal angular acceleration and eye movement.

Unit Activity Monkey

in Vestibular

During

Nucleus

Horizontal

Angular

Acceleration

and Eye Movement

ALBERT

AND

F. FUCHS

Regional Primate Research Otolaryngology, University

JOSEPH

KIMM

Center and Departments of Washington, Seattle,

THE ROLE OF vestibuloocular reflexes is to help stabilize the visual world on the retina during movements of the head. If a sinusoidal change in position is applied to the head, the position of the eye in the head also describes a sine wave- which is essentially opposite and almost equal to the head position. In the monkey this compensation has been shown to be extremely effective over the frequency range of 0.0145 Hz (37) and even up to rates of 6.5 Hz (Fig. 1). The input to the reflex is provided by the semicircular canals, which sense head acceleration. Since a signal approximately equal to and opposite head position is required, the intervening neural connections between the canals and the globe may be regarded as performing a double integration in time

(from

acceleration

to position),

or equiva-

lently as delaying the input sinusoidal acceleration by one-half period or 180”. About

half of the total

180” phase

delay

or lag is accomplished by the time the processed

afferent

signal

nerve. Single-unit mary vestibular strated that over

reaches

recordings

of the Alert

the 8th

from

pri-

afferents have demonthe frequency range of

of Physiology and Biophysics Washington 98 I 9 5

and

frequencies, the neural discharge patterns of 8th nerve fibers approximately represent head velocity (i.e., a single integration of input acceleration) at least over the frequency range of 0.1-2.0 Hz. The end organ is by no means a perfect integrator since the phase lag decreases at both higher and lower frequencies (7). Therefore, over the range 0.1-2 Hz, about 100” of additional phase lag must still be provided bv neural elements between the vestibular nerve and the extraocular muscles. The majority of fibers in the 8th nerve project to the ipsilateral vestibular nucleus. Each nucleus communicates with its contralateral neighbor through commissural inhibitory interneurons and probably

via

more

diffuse

reticular

pathways

(2 1, 36). It is possible that neural networks set up between the bilateral nuclei could provide part of the required phase lag so that discharge patterns in some vestibular nucleus neurons would be delayed

relative to 8th nerve activity. Unfortunately, all of the data from the vestibular nuclei have been obtained in animals that were anesthetized or decerebrate, conditions

which

affect

alertness

and

0.1-2.0 Hz, the maximum firing rate lags maximum head acceleration by about 73” (7). These data largely supported the tor-

compromise

transmission

through

commissural

and

pathways.

sion pendulum which predicted

vestibular nuclear angular acceleration

model the

of the neural

end organ discharge

likely

the In such preparations the firing frequency of reticular

neurons lags the input by about 80" over the

characteristics from the physical p roper-

frequency range 0.25-1.7

Hz (28). A pre-

ties of the canals, the end&mph, &d-the cupula . Since a perfect integrator produces a constant 90” phase lag over all

liminary

laboratory

Received for publication

neural activity

February 3, 1975.

report

from

our

indi-

cated similar results in the awake monkey (20). that,

Therefore, in terms

it has been concluded of phase information,

leaving the vestibular nu-

1140

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CANAL Stimulus frequency

AND

OCULOMOTOR

UNITS

(Hz)

0.19 J

C u

0.46 =r I

1.48 u

3.12 21

6.45 )[

1. Eye-movement responses to horizontal sinusoidal accelerations of the head in the dark. Upper trace shows head position with a + 10” excursion. Lower trace shows horizontal eye position measured by the bitemporal electrooculogram with an upward deflection representing a rightward movement. Eye-movement calibration marks indicate 30”; time calibration marks indicate 1 s. Note ability of vestibular-induced eye movements to compensate for head rotations over an almost loo-fold variation in stimulus frequency. FIG.

clei is not much different from that entering via the 8th nerve. Some phase lag is contributed by the relationship of firing frequency’ of oculomotor neurons to the resultant eye movement. This relationship, which applies for voluntary and vestibularevoked eye movements, can be described by a first-order differential equation with a time constant of about 0.2 s (32, 37). Such a first-order element introduces a phase lag, which increases from 7” at 0.1 Hz to about 70” at 2 Hz. Therefore, a phase lag ranging from 93” at 0.1 Hz to 30” at 2 Hz must still be provided by other neural elements interposed between the vestibular and oculomotor nuclei. Connections between the vestibular nuclei and the various oculomotor nuclei are accomplished by a variety of routes. The classically described monosynaptic pathway via the medial longitudinal fasciculus (MLF) should merely forward the information in the vestibular nucleus without introducing any significant phase lags. Therefore, extrapolating from the

IN

VIII

NUCLEUS

1141

data on the anesthetized cat, the MLF would provide a signal that is almost in phase with head velocity. Parallel routes via the reticular formation are possible on the basis of anatomic connections (15, 2 1, 23). A reticular pathway has been suggested as the location for a “lossy” integrator or delay element which would supply most of the remaining phase lag (33). The notion of a brain stem integrator involved in eye movements has been supported by stimulation studies in the reticular formation (3). The first object of this series of experiments was to record from neurons within the vestibular ocular pathway that may be part of the circuitry that phase shifts the signal from the vestibular nerve. This paper describes firing patterns of units within the vestibular nuclei which were tested under various sinusoidal accelerations to determine the characteristics of the nuclear signal in the unanesthetized, alert monkey. A study under way will describe the firing patterns of neurons in the surrounding reticular formation obtained under similar conditions in an attempt to test the hypothesis that neurons in the brain stem participate in an integration of the signal from the vestibular nuclei. In addition to their role in subserving reflexive eye movements in response to head acceleration, the vestibular nuclei have also been implicated in the control of voluntary eye movement. In 1933 Spiegel (39) observed that eye movements generated by stimulation of the feline visual cortex were abolished by lesions of the vestibular nuclei and concluded that the commands for voluntary eye movements were funneled through these nuclei. More recent studies have indeed revealed neurons in the simian vestibular nuclei whose discharge characteristics were similar to either oculomotor neurons or eyemovement neurons described elsewhere in the brain stem (8, 18, 25, 30). Furthermore, units in the vestibular nucleus not only discharged with the slow phase of vestibular nystagmus, but also exhibited either the appropriate burst or pause during the fast phase (2, 5), suggesting that the neural pattern necessary for nystag-


A. F. FUCHS

1142

AND

mic eye movements is already present in the vestibular nuclei. Therefore, the second object of these experiments was to investigate the behavior of vestibular nucleus cells during voluntary eye movements. METHODS

Four rhesus monkeys (Macaca mulatta), weighing 2.5-3.5 kg, were maintained in specially constructed restraining chairs. During daily recording sessions the chairs were placed on a vestibular stimulator which oscillated the monkey in a horizontal plane about the vertical axis. While being oscillated the monkey was simultaneously required to perform a visualtracking task which involved pressing one button illuminated at random from an array attached to the chair. This made it possible to test the effects of either the vestibular stimulation or eye movements independently, or to investigate their simultaneous contribution to the discharge patterns of vestibular nucleus neurons. Stimuli and behavioral conditions Figure 2 details the monkey’s experimental test situation. Sinusoidal oscillations in the

BUTTON

FIG. 2. Schematic button-pressing task.

diagram

of the apparatus

J. KIMM

horizontal plane were provided by a simple DC motor and a modified slider-crank linkage. The motor rotation was first transformed into a linear reciprocating motion by a rigidly mounted slider assembly, then reconverted through an eccentric on the n-shaped yoke housing to a sinusoidal oscillation about the vertical axis. The yoke held a horizontal plate which accepted a cylindrical monkey chair whose compact dimensions were designed to provide the minimal moment of inertia compatible with the monkey’s comfort. With a monkey in place it was possible to apply sinusoidal oscillations of t20” at frequencies of 0.05-1.0 Hz or oscillations of +: 10’ at frequencies of 1.0-7.0 Hz; over the frequency range most studied (0.2-1.0 Hz) the average total harmonic distortion of the applied acceleration (to the 8th harmonic, see later) ranged between 1 and 2.2%. The head was anchored in its normal upright position to the chair by a ball and socket arrangement (9) so that the axis of rotation approximately bisected the interaural line. Under these conditions any oscillation applied to the chair was directly communicated to the skull and the labyrinths. With the head held upright the monkey’s horizontal canals were inclined upward at about 30” from the plane of applied acceleration. A poten-

ARRAY

which

oscillates

the monkey

and

providesand CO In trols

the


CANAL

AND

OCULOMOTOR

tiometer mounted on the shaft recorded the position of the chair and, hence, of the monkey’s head. An array of lighted buttons attached to a large opaque sphere could be fastened to the chair in front of the monkey to provide visual targets which rotated with the animal (Fig. 2). The buttons were located everv 15’ over t45” on the horizontal equator and from - 15 to +30” on the vertical meridian. The monkey’s task was to press the button that was illuminated, a response which was rewarded about every third press with a small dollop of applesauce (Fig. 2). Different fixation positions and calibrated saccades resulted when the animal changed its direction of gaze from one button to another.

Recording conditions Both horizontal and vertical eye movements were measured by DC electrooculography with Ag-AgCl electrodes chronically implanted in the bony orbit (9). Extracellular unit potentials were obtained through Epoxylite-insulated tungsten microelectrodes which were advanced through a stainless steel cannula by means of a hydraulic microdrive. The best electrodes usually had an exposed conical tip about 7.5 by 10 pm; this conical surface area was increased by the deposit of iron particles, which resulted in a tip impedance at 1 kHz of about 3-5 MO. Unit activity was led through a conventional FET stage to a Tektronix 3A9 amplifier with a band pass of 0.1-10 kHz. Signals proportional to horizontal and vertical eye position, buttontarget position, chair position, and unit activity were stored on a Hewlett Packard tape’recorder (model 3960, O-5 kHz, -3 dB) and subsequently written out either on moving film or on a Bell and Howell Visicorder (O-5 kHz, -3 dB). The accuracy of time determinations through the entire record and playback process was ?5%. A .s the electrode was advanced into the brain the animal was continuallv oscillate d with a sinusoidal search stimuius of 0.5 Hz (amplitude usually +20”). Therefore, it is unlikely that any silent vestibular cells with horizontal sensitivity were overlooked. The sensitivity of neurons to vestibular stimuli or eye movement was identified on-line by a combination of a dot raster display and audio monitor. Neurons with vestibular sensitivity were subjected first to low stimulus frequencies (O-l .O Hz); unfortunate1 y, higher frequencies (l-6 Hz) required a mechanical change of DC motors which often traumatized the unit. The effects of vestibular stimulation on neurons with eye-movement sensitivity were explored

UNITS

IN

VIII

NUCLEUS

1143

by requiring the monkey to press the same recessed button repeatedly while being oscillated at either 0.5 or 1.0 Hz. By varying the location of the fixed button the behavior of the unit over the entire eye movement range could be determined.

Data analysis To quantify the vestibular sensitivity of a neuron, the steady-state unit response was averaged over 10 consecutive stimulus cycles, a compromise between the time required to gather the data (and hold the unit) and the time required to count by hand the action potentials in the response. Each stimulus cycle was divided into 24 equal bins of 15” each, and the averaged number of spikes within the bin was assigned to the middle of the bin. A similar average was obtained for the analog of chair position. The paired digitized data were fed to a CDC 6400 computer which performed a Fourier analysis on both waveforms. The phase shift of averaged unit activity relative to chair (and hence head) acceleration was estimated as the difference in phase between their fundamental components. Harmonic distortion in both the chair analog and unit response was determined from the- 2nd through 8th harmonics by using the for mula (41) ..

8 1 J Ai x 2

% total har manic

distortion

=

i=2

100

A,

where A = a mplitude of ith harmonic, A1 = amplitude of fundamental. In the lo-cycle average for units that also responded with eye movements, allowances were made for saccadic and position sensitivity. For vestibular plus saccade units (described in RESULTS), averaging was suspended in those bins which included a saccade and additional cycles were averaged until each bin contained at least 10 entries. For vestibular plus position units, unit activity in response to vestibular stimulation was averaged at a given eye position only when the calibrated EOG monitor indicated that the eye was at the desired location. Again, bins that contained saccades were eliminated from the average. For units with position sensitivity, the relationship of firing rate to eye position was constructed by requiring the monkey to press the entire sequence of buttons in the horizontal and vertical arrays; the firing rates associated with at least three presses at the same button location (and hence eye position) were averaged to obtain the firing rate-eye position characteristic. It was occasionally impossible to complete the entire stimulus sequence for a unit so that


A. F. FUCHS

1144

AND

the resting rate with the chair stopped was not obtained. Fortunately, for units with only vestibular or vestibular plus saccade sensitivity (N = 53), the DC firing rate determined from the Fourier analysis at 0.2-0.5 Hz was a linear function of the resting rate (RR), according to the relation DC = 0.98 RR + 6.4 (r = 0.92). Therefore, the resting rate was determined either by averaging the num ber of spikes occurrin .g in 10 l-s i ntervals with the animal station&y or by using the above formula. Histological reconstruction of recording sites At the end of the experiment the animal was a nd perdeeply anes thetized with Nembutal fused with normal saline and 10% formaldehyde. Frozen sections of the brain stem were cut every 30 pm, mounted, and stained with cresyl violet. The anatomic location of each unit was established in reference to electrolytic marking lesions placed at the end of particularly fruitful

tracks

apart

(25).

Penetrations

in the ipsilateral

were

brain

rostra1 tip of the abducens tral tips of the X and XII

made

1 mm

stem from

nucleus cranial

the

to the rosnuclei (i.e.,

from P1.5 to P6.0 and from 0 to L7 in the atlas of Smith et al. (38)). In our experience, it has been difficult to delimit the extent of the vestibular nuclei and especially to establish the boundaries of the superior, medial, lateral, an d inferior groups. ’Therefore, we sent a set of brain stem slides to M. Carpen ter (College of Physicians,

Columbia

University)

and,

based

on

his own extensive studies in the monkey, he kindly outlined the nuclei on our sections. Using his anatomy and our reconstructions, 127 units could be conservatively identified as lying within the vestibular nuclear complex. Of these, 77% were located in the medical vestibular nucleus, nucleus, and 6% in 17% in the lateral (Deiters’) the superior nucleus. None of the unit types described in RESULTS were localized solely to any one

of the

above

nuclei,

but

generally

were

dis-

tributed more or less equally throughout all three. No count was kept of neurons unresponsive to vestibular stimulation or eye movement, nor was any attempt made to drive neurons with somatic stimuli, Based on the criteria itemized in detail elsewhere (25), we believe that the large majority of our unit recordings were taken from cell somata rather than axons. RESULTS

Our ultimate objective is to describe and compare the fi ring p atterns of neurons at the various stations of the ves-

J. KIMM

tibuloocular pathway. The horizontal component of the pathway is examined here since the firing patterns of motoneurons subserving horizontal eye movement have been extensively documented (9, 19, 32, 34, 37) and may be compared with single-fiber recordings in the 8th nerve from the same preparation (24). Therefore, discharge patterns of neurons in the vestibular complex (mostly the medial nucleus, see METHODS) were tested for responses to horizontal angular acceleration of the head and conjugate (versional) eye movements. In a total of 127 units, approximately half (58 units; 45.5%) responded to the vestibular stimulus only, while most of the rest responded independently to both the vestibular stimulus and some component of eye movement. Within the latter group neurons could be divided into those that showed a change of firing frequency with saccades only (38 units; 30%) and those whose firing rate was primarily a function of eye position (2 1 units; 16.5%). A small number of neurons in our sample (10 units; 8%) responded with eye movement alone. Vestibular

only units

The typical vestibular only unit responded to vestibular stimulation over a range of horizontal angular accelerations (0.2-0.93 Hz, Fig. 3), but exhibited no change in activity related to eye movement alone (0.0 Hz, Fig. 3). At low peak angular accelerations (0.2 Hz corresponds to a maximum acceleration of 3 1.50/s2), the firing frequency was continuously modulated throughout the entire cycle. Although there was some variation from cycle to cycle, the discharge rate averaged over 10 cycles (Fig. 4, top panel) closely resembled a sine function that was modulated symmetrically about the unit’s resting rate. The peak firing rate occurred approximately as the head rotated through its maximum velocity. As the stimulus frequency was increased (with a concomitant increase in acceleration), the firing rate of about half of the neurons was driven to zero during part of the cycle (Fig. 3,0.5 Hz). The frequency at which cutoff occurred was a function of the resting rate and the depth


CANAL

AND

OCULOMOTOR

UNITS

IN

VIII

1145

NUCLEUS

0.93

0.5

0.2

, ,.. . .. .

, , . . ,, . . , , , ,. , .. . ,. . . ,

00.

C-1

I

Discharge characteristics of a type I vestibular only neuron (monkey 2 U 5:2) as a function of the frequency of head acceleration (0.0-0.93 Hz). In each panel of this figure and Fig. 5, the top trace represents head acceleration (a downward sine wave minimum represents a peak in ipsilateral acceleration), the second trace is an extracellular recording of unit activity, the third trace represents horizontal eye position (upward deflection is an ipsilateral movement), and the fourth trace represents vertical eye position (upward deflection is an upward eye movement). Horizontal eye-movement calibration marks represent 30”. The time calibration mark represents 1 s. Peak chair acceleration ranges from 3 1.5”/s2 at 0.2 Hz to 670°/s2 at 0.93 Hz. FIG.

3.

of modulation, but almost all units exhibited cutoff at frequencies = 1 Hz. The peak angular acceleration associated with cutoff was about 700°/s2. Of 58 vestibular only neurons, 25 were excited by ipsilateral head rotations toward the recording site (type I neurons after the nomenclature of Duensing and Schaefer (5)) and 33 were excited by contralateral head rotations away from the recording site (type II neurons (5)). The resting rates of type I neurons (46.9 approximately spikes/s t 33.1 SD) were the same (0.05 < P < 0.1, t test for difference of means) as the resting rates of type II neurons (37.1 t 23.8 SD); only 4 of the vestibular only neurons were silent in the absence of vestibular stimulation. Since a search stimulus was always present, silent cells were not overlooked and their small number accurately reflects the paucity of silent cells within the nucleus of alert animals. In addition, as measured by the amplitude of the fundamental component of the Fourier analysis of discharge rate, the sensitivity to angular acceleration at 0.93 Hz (220”) was greater (P < 0.02, t test)

for type I (53.5 spikes/s+ 33.5 SD) than for type II neurons (35.4 t 20.2). Both type I and type II neurons exhibited the same general discharge characteristics so that the comparison of sensitivities was not corrupted by populations in different degrees of cutoff. None of the vestibular only neurons exhibited any changes in activity with saccadic, smooth pursuit, or fixation eye movements. A recent study (22) has shown that while an animal is fixating a target rotating with him, flocculus Purkinje cells exhibit an increase in their depth of modulation over discharge rates measured during normal compensatory eye movements in complete darkness. Since the flocculus can monosynaptically inhibit cells of the vestibular nuclei, discharge patterns in such cells should reflect the different effects of cerebellar inhibition in the fixation versus compensation conditions. Unfortunately, the animals in this study were only occasionally subjected to complete darkness and not required to perform extended fixations so that the interesting fixation versus compensation


1146

A. F. FUCHS

0.93

AND

J. KIMM

Hz Monk2 U5:2

t4 0.93

Hz

a

0.93

Time

Monk I U8:2

Hz

1radians

K

)

4. Discharge characteristics of a type I vestibular only neuron (top panel) and a type II vestibular plus saccade neuron (bottom panel) averaged over 10 stimulus cycles. The horizontal angular chair position (solid line) and the angular acceleration applied to the head (dashed lines) are depicted in the middle panel for the three imposed frequencies. In all three panels, the time axis is plotted in radians to normalize the abscissa for different stimulus periods; the second cycle in each panel is identical to the first to aid in visual interpretation of the periodic events. For the vestibular plus saccade unit, the averaging process was discontinued for the duration of each saccade. The averaging technique is described in detail in the text. FIG.

behavior of these and other vestibular nuclear neurons cannot be addressed. Vestibular @us eye-movement units PLUS SACCADE. (Figure 5~9.) About one-fourth of the vestibular nucleus neurons in our sample exhibited changes in firing rate to both vestibular stimuli and saccadic eye movements. In the absence of horizontal angular acceleration these units discharged at a relatively constant rate, which was interrupted by either a cessation of activity (32 units) or burst of activity (6 units) for saccades in one or more directions. During adequate

VESTIBULAR

horizontal stimuli, vestibular plus saccade units responded to the sinusoidal accelerations with a periodic modulation in firing rate whose maximum, like vestibular only units, occurred approximately as the head passed through its maximum angular velocity. Whenever the appropriate saccade occurred, the ongoing vestibular activity was interrupted by either a pause or burst of spikes. If the duration of each saccadic interruption is eliminated from a 1O-cycle average of unit activity (Fig. 4, lowest panel), the modulation of discharge rate of the representative pause unit (Fig. 5A) clearly resembles that of a vestibular only


CANAL

AND

OCULOMOTOR

A.

Vesti

6.

Vest ibular

bular

UNITS

IN

VIII

NUCLEUS

114’7

+ Saccade

+

Position

0.0

FIG. 5. Discharge characteristics of representative vestibular plus eye-movement neurons during vestibular stimulation and eye movement. A: vestibular plus saccade unit (monkey I, U&Z) exhibits an increasing rate for contralateral accelerations (type II) which is interrupted by saccades in all directions including the vertical (note downward saccade in 4th cycle; 0.93 Hz). In the absence of vestibular stimulation (0.0 Hz), the unit exhibits a relatively constant rate of 62 spikes/s except for the saccadic interruptions. B: a vestibular plus position unit (monkey I, u3:6), which for ipsilateral accelerations (type I) exhibits an increasing rate that is superimposed on a firing level established by the position of the eye. The top two panels trace the unit’s behavior as the monkey sequentially fixates buttons from an extreme ipsilateral position (top left) to an extreme contralateral position (bottom right) of gaze while being oscillated at 0.93 Hz. The bottom panel demonstrates the constant discharge rate during fixation, the increasing rate with contralateral eye position, and the pause in activity for ipsilateral saccades in the absence of vestibular stimulation (0.0 Hz).

unit (Fig. 4, upper panel) with roughly symmetrical sinusoidal modulation about resting rate at low stimulus frequencies and the tendency toward cutoff at frequencies approaching 1 Hz. Of the 32 pause units, 18 were type I neurons with an average resting rate of 78.7 t 31.9 spikes/s and 14 were type II neurons with an average resting rate of 96.3 t 36.8 spikes/s; these average resting rates were not statistically different (P > 0.15). As with vestibular only neurons, the sensitivity of type I neurons to horizontal angular acceleration was greater (P < 0.04) than for type II neurons (97.4 t 46.0 vs. 65.4 t 23.1 spikes/s at 0.93 Hz). Once again, both type I and type II neurons exhibited the same

degree of cutoff on the average. Both resting rates and sensitivities for pause units were higher than for vestibular only units. If a unit exhibited an increase in activity for horizontal rotations in a particular direction, the pause in activity always occurred at least for those saccades with a component in the same direction. Therefore, a type I unit recorded in the right vestibular nucleus exhibited an increasing rate for rightward (clockwise) angular rotations and a pause for right saccades; similarly, a type II neuron (only one example in our sample) in the right vestibular nucleus exhibited an increasing rate for leftward (counterclockwise) rotations and a pause for left saccades. In 12 of 18 type 1 and 1 of 11 type II neurons,


1148

A. F. FUCHS

AND

if head rotation in a particular direction increased unit firing rate, a pause occurred for only those saccades in the same but no other direction. The remaining type I neurons and 10 of the 11 type II neurons paused for saccades in all directions including the vertical. For all pause units the duration of the complete cessation (8 units) or decrease (24 units) in activity was typically somewhat longer than the duration of the saccade. The relation between saccadic and pause duration is shown in Fig. 6 for type I units that paused for saccades in either one or all directions and for type II units that paused for all directions. The linear regression lines representing these data have very similar slopes and lie largely above the line of slope 1, suggesting that there is little to differentiate these 300

1

250-j Monk4

U12:6

J

1. KIMM

neurons on the basis of their saccadic pause behaviors. Pauses in activity are a function only of saccade duration and not of magnitude, since the saccades and accompanying pauses made by the drowsy monkey were longer than the equal size but shorter duration saccades and pauses executed by the alert animal. The onset of the decrease in unit activity, as judged by the first lengthened interspike interval, occurred an average of 7.1 t 2.4 ms prior to the saccade in just over 50% of the neurons and an average of 1.3 t 1.7 ms into the saccade in the remainder of the units. During fixation these units exhibited a very constant firing rate independent of eye position. Of the six vestibular plus saccade units that exhibited a burst of firing, five were type I and one was type II. As with the pause units, if a unit exhibited an increase in activity for rotations in a particular direction, the burst always occurred for saccades in the same direction. For all the burst neurons the increase in activity began at the onset of the saccade or later; therefore, these neurons had eyemovement characteristics similar to the burst following units reported previously (25). The mean resting rate of burst neurons (8 1 .O t 39.9 spikes/s) was comparable to pause units; however, their sensitivities (37.1 t 11.2 spikes/s at 0.93 Hz +20”) were only about one-half those of ‘pause units and more comparable to those of vestibular only cells. PLUS POSITION. (Figure 5B.) Just under one-fifth of the neurons in our sample (21 units) exhibited changes in firing rate with both adequate vestibular stimulation and eye position, as demonstrated for the representative unit in Fig. 5B. In the absence of vestibular plus position stimulation, vestibular neurons increase their firing rates as the eye deviates in a certain on-direction. The on-direction was essentially horizontal for 17 neurons and vertical for 4. The increase in firing with eye deviation in the on-direction was always monotonic, but the firing frequency versus eye position characteristic occasionally could best be approximated by two straight lines with

VESTIBULAR 0

L’

1

50

I

100 Saccode

I

150 duration (msec)

I

200

I

250

FIG. 6. Relationship between the pause in activity accompanying a saccade and the duration of the saccade for vestibular plus pause neurons. Points have been obtained from the-unit monkey I U8:2 illustrated in Fig. 4 (center panel) and- 5A and demonstrate the-range of data. A regression line provides an accurate fit (r = 0.94) of the experimental points for this unit (type II) which pauses for all saccades. Similar regression lines (average correlation coefficients of 0.86) are shown for a variety of units from other monkeys which pause for all saccades (monkey 4 U12:6, type II; monkey 2 U5:1, type I) or only ipsilateral saccades (monkey 2, UlO:2 and 10:4, type I). The dotted line would obtain if pause duration were exactly equal to saccade duration.


CANAL

different

slopes,

AND

similar

OCULOMOTOK

to those

UNITS

(16). their

Most neurons steady firing

key maintained fixation The

off-direction.

this threshold

tibular

far (>30”) in the

for steady firing

average slope (K) versus eye position in Fig. 7 for all 21 steady firing with

in the orbit in magnitude

in our sample when the mon-

relationship of the firing characteristic

NUCLEUS

1149

and -was approximately equal for all positions. For exam-

ple, in-the unit of Fig. 5B, when the mon-

between

key looked

and the

silateral (off) direction, the unit firing rate averaged over 10 cycles exhibited a DC

frequency is shown

rate

tibular

eye position,

Hz,

most

ves-

plus position neurons (18 units) saccades 5B). For

approximately

of 31 spikes/s

units. In addition to the

exhibited changes in activity with in one or more directions (Fig.

VIII

seemed to be simply superimposed on the steady rate set by th e position of the eYe

reported

for neurons in the pontine reticular formation ceased

IN

and

modulation

k20”);

when

20’

a maximum

the

animal

modulation

was 41 spikes/s.

panied

of firing

saccades

in the off-

was looking

straight ahead, the DC rate increased to 97 spikes/s, but the maximum vestibular eye positions the difference

those

ves-

of 39 spikes/s (0.93

13 of these units, a pause in firing accomat least

in the ip-

frequency,

For

the

two

in the peaks

as measured

by the

3 of the 13 paused for saccades phase shift of discharge rate relative to

direction;

in all directions. The remaining 5 neurons exhibited a burst in firing during but not

angular 1”.

before saccades in the on-direction.

For 11 of 1’7 vestibular plus position neurons, if the unit activity increased for horizontal accelerations in a particular di-

When

the

animal

was

subjected

to

sinusoidal horizontal angular acceleration,

rection,

acceleration

(see later),

it also increased

was only

vestibular plus position neurons exhibited a periodic modulation in firing rate whose maximum was approximately in phase with maximum angular velocity. It was

for voluntary

eye

firing

not necessary that the eye actually be mov-

and for contralateral

ing for the modulation to occur, as can be seen from the second and sixth cycles in Fig. 5B. The vestibular modulation

of these units were type I. For the remaining six vestibular plus position units, in-

movements in the opposite direction, For examp le, the unit in Fig. 5B increased its rate

for

ip sila tera 1 head

creases in firing either

vestibular

rotations

eye deviations. Ten

rate were elicited by stimuli

or eye movements

in the same direction; four of the six were type 11 neurons. Of the four neurons

with

vertical

posi-

tion sensitivity, the on-direction was down for three units and up for one. These units had fir lng frequency versus vertical eye position cha.racteristics compa rable to those

described

for the horizontal

vestibu-

lar plus position units described above 2.7, 1.0, 1.2, 1.1). Since they exhib(K = ited

l

--I

>45”

t

I

45”

15

30 OFF

FIG.

7.

eye-position threshold position

neurons

Slope

(K)

Of

characteristic for steady neurons (0) .

0 Threshold the

(deg

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of

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ON

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rate with horizontal angular acceleration, we feel that these units probabl y sub served primarily the anterior or posterior canals. Three of these neurons did not display a clear change in firing rate with saccades; one paused for saccades in all directions.

versus

of

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abducens motoneurons (9). About 6-B ms prior to an abducting saccade in the


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ipsilateral eye they emitted a highfrequency burst of spikes whose duration increased with the duration of the saccade. The discharge frequency of spikes within the burst was a function of saccadic velocity; “brisk” saccades which attained high maximum velocities were accompanied by higher discharge rates than equalamplitude “lazy” saccades with lower maximum velocities. If a saccade carried the eye lateral to a certain position in the orbit (the threshold, T), the fixation subsequent to the saccade was accompanied by a steady firing rate with low interspikeinterval variability. As the eye moved still further lateral, the firing rate increased with eye position according to an approxi; mately linear function which could be characterized by a slope, K (spikes/s per deg) and an intercept, 7 (deg). The relationship between K and 7 (the threshold) for eyemovement only neurons is shown in Fig. 7. If a medial saccade occurred while the unit was firing steadily, the unit either decreased its rate or ceased firing completely. When the animal was oscillated the behavior of these units remained solely a function of eye movement and was not driven by the vestibular stimulus per se. of vestibular-induced During episodes compensatory eye movements, a sinusoidal applied acceleration of 0.93 Hz (+20”) caused a roughly sinusoidal modulation of unit activity which, similar to abducens motoneurons, preceded the sinusoidal eye movement by an average of 20.5 t 6.4” (or lagged acceleration by 159.5”). On the other hand, when the animal fixated a button that rotated with him, thereby successfully defeating the vestibuloocular reflex and allowing no eye movement relative to the head, the unit responded with an essentially constant rate appropriate only to the position of the eye in the orbit. Although our present sample contains relatively few eye-movement only neurons, we have likely underestimated the proportion of such units in the vestibular nuclei. In earlier studies of the reticular formation (25), we often mistook the vestibular nuclei for the abducens nucleus based on the “singing” activity of its neurons. It may be possible that these eye-movement neurons lie in a fairly localized region of the

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vestibular complex which was simply not sufficiently explored in these four animals. In summary, the previous sections demonstrate that, on the basis of their response to eye movements, neurons in the vestibular nuclei can be divided into at least four populations. Also, the earlier data demonstrate that additional characteristics further differentiate vestibular neurons with and without eye-movement These differences are preresponses. sented in Fig. 8 for all our units and can be summarized as follows: 1) Vestibular plus eye-movement neurons have higher resting rates on the average than vestibu81% of vestibular plus lar only neurons; saccade and vestibular plus position units had resting rates (determined with the eyes directed straight ahead) greater than 50 spikes/s, whereas 73% of vestibular only neurons had resting rates of less than of resting 50 spikes/s. The distribution rates of vestibular only units appears to be unimodal (Fig. 8) and is skewed toward

15 VEST ONLY

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l2B vest + saccade vest + posltion 10

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. 0 VEST ONLY VEST + EYE MOVEMENT l

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FIG. 8. A: distribution of resting rates of neurons in the v estibular nuclei according - to their eyemovement response. B : sensitivity of vestibular neurons as a function of their resting rate. Sensitivity is measured as the amplitude of the fundamental component of the Fourier analysis of discharge rate at 0.93 Hz; peak-to-peak sinusoidal angular acceleration applied to the-head at 0.93 Hz was 670°/s2.


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which nonlinearities have distorted the input sinusoid. A casual inspection of Fig. 4 reveals that the lo-cycle averaged firing rate is not perfectly sinusoidal, even at the lower stimulus frequencies which produce a relatively symmetrical modulation about the resting rate. Obvious nonlinearities are present in the form of small irregularities on the averaged waveform, together with slightly asymmetric rising and falling phases. For example, at 0.2 Hz the total harmonic distortion (to the eighth harmonic, not including the DC term) was 10.4% for unit 5:2 (Fig. 4, top panel) and 10.3% for unit 8:2 (Fig. 4, bottom panel); the distortion was distributed fairly uniformly over all the harmonics. At least part of this percentage can be attributed to the l-2% distortion already contributed by the stimulus. Except for two units whose rates cut off during over half of the stimulus cycle, the average total harmonic distortion for 27 units tested at 0.2 Hz (both vestibular only and vestibular plus saccade) ranged from as little as 8% to as much as 36% (mean = 13.8 t 7.7%). However, at 0.2 Hz (31.5”/s2), the depth of modulation in firing rate was often less than 30 spikes/s so that an unComparison of four unit populations usual burst (or pause) of spikes occurring using Fourier analysis in only one of the 10 cycles selected at Except for the abducen s-like neu rons in random would have a large effect. For th e medial nucleus, all of the units appear example, the 36% distortion was largely to show the same qualitative changes of the result of an averaged response with firing rate in response to a sinusoidal an- a single bin in which the firing rate gular acceleration, i.e., a periodic mod ula- dropped to half of its expected value. tion whose maximum occurs appr ‘OXlClearly, if more than 10 cycles had been mate1y when head velocity reaches its averaged, the contribution of the perturbamaximum. The object of this section will tion would have been minimized, resulting be to compare quantitatively the vestibu- in less distortion. lar response of vestibular only, vestibular The total harmonic distortion at 0.2 Hz s saccade, and vestibular plu s position (13.7%) is apparently greater than similar PlU units to determine if there -is reason to distortion measures (7.3% unrestricted further divide these units on the basis of harmonic distortion to the 10th harmonic) their response to vestibular stimuli. Since calculated for the simian 8th nerve (7). the firing rate of vestibular nucleus However, no direct comparisons can be neurons is a periodic function (Fig. 5), it made because of potential differences in can be completely described by a Fourier the distortion analysis programs, the series that dissects the unit response into a number and selection of the cycles averfundamental component at the same fre- aged, and the distortion of the input quency as the applied angular accelera- stimulus waveform. tion and higher harmonic components At stimulus frequencies of 0.93 Hz whose presence indicates the degree to (*20”), the total harmonic distortion for

the lower resting rates; the distribution of resting rates of vestibular plus saccade units appears to be bimodal with peaks at 60-70 and at 1 lo-120 spikes/s. 2) Vestibular plus eye-movement neurons have deeper depths of firing rate modulation than vestibular only units; 61% of vestibular plus saccade or position units had sensitivities (as measured by the amplitude of the fundamental component of the unit response to accelerations at 0.93 Hz, 220”) greater th .an 60 spikes/s, whereas 8 1% of vestibular only neurons had sensitivities less than 60 s$kes/s. Although, on the avplus position neurons erage, vestibular had sensitivities only slightly greater than vestibular only neurons (by lo-2070 at 0.93 Hz), sensitivities of vestibular plus saccade units were 60-70% greater than vestibular only neurons (at 0.93 Hz). Since units stopped firing when the sensitivity exceeded the resting rate, Fig. 8B demonstrates that at 0.93 Hz, about half (53%) of the units (data points above a line of slope 1) exhibit cutoff. Therefore, this graph substantiates our earlier observation that most units cut off at peak head accelerations of about 700°/s2 (or equivalently at peak velocities of about 115”ls).


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the same units ranged from 8.0 to 36.7% with the mean of 17.8% being barely larger than the value at 0.2 Hz. Actually, our sequence of stimulus presentations provided more data at 0.93 Hz than at 0.2 Hz; the mean of 24.3 t 12.4% collected from 75 neurons at 0.93 Hz probably provides a better figure for the distortion across the entire population. The total harmonic distortion for vestibular plus saccade neurons was less (18.9% t 7.6; N = 32) than for vestibular only neurons (28.3% t 13.8; N = 43). The increased distortion at higher frequencies was contributed pri marily by the seco nd and third harmonics. Simulated firing patterns fed into our computer program showed that the second harm onic resu lted largely from rectification of the averaged fi&rg rate, whereas the third harmonic was contributed by skewing of the averaged firing rate toward the rising phase of the response. Skewing of the response was just noticeable on visual inspection of the averaged waveform, and ;he average third harmonic distortion (amplitude third harmonic per amplitude - fundamental x 100) for 16 vestibular only and vestibular plus saccade neurons increased only from 7.3% at 0.2 Hz to 12.3% at 0.93 Hz. At. 0.93 H z, the average second harmonic drs tortion measured in the same manner was 13%. Melvill Jones and Milsum (29) noticed similar skewing of firing patterns in the vestibular nucleus of the decerebrate cat, but it was only at very low stimulus frequencies (~0.016 Hz) that the effect became obvious. Although the plots of averaged dsi ch arge patterns of individual neurons are distorted, amplitude nonlinearities have relatively little effect when determining the location in the stiml ~1~s cycle where the unit reaches its maximum or minimum firing rate. These locations objectively have been determined bY measuring the phase shift of the fundamental component of the firing rate relative to the applied acceleration. Figure 9 shows the phase cal culations for vestibular on1y, vestibular p lus saccade, and vestibular plus position neurons. Over the frequ ency range betw een 0.2 and 0.93 H z, the mean phase lag relative

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of units

0

rype I

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cn 1 vest + position-

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FIG. 9. Phase lag of averaged unit responses relative to applied acceleration for vestibular only, vestibular plus saccade, and vestibular plus position neurons. Left, mean phase lag and standard deviation as a function of stimulus frequency; units divided not only according to eye-movement sensitivity but also according to whether they respond to ipsilateral (type I, n ) or contralateral (type II, 0) acceleration. U-shaped characteristic associated with each unit population (-, l ) shows phase shifts obtained from 8th nerve of squirrel monkey (6). Right, distribution of phase lags for individual units within various populations at stimulus frequency 0.93 Hz.

to acceleration for all the units lies between 55 and 88”. The distribution of phase lags is typified by the histograms at the right of Fig. 9 for the stimulus frequency of 0.93 Hz. For both the vestibular plus saccade and vestibular plus position neurons, type I and type II units had essentially identical mean phase shifts with similar unimodal distributions which peaked between 70 and 90’. (An apparent increase in phase of type II over type I vestibular plus saccade units was not statistically significant.) Furthermore, if the entire population of vestibular plus saccade neurons is compared with the entire population of vestibular plus position neurons, the probability that their mean *

a


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phase lags differ is less than 5%. Finally, type II vestibular only neurons also have a unimodal distribution of phase lags that peaks between 80 and 90”; the mean phase lag of these neurons is different from the mean of the entire population of vestibular plus eye-movement neurons (P < 0.01). Since it is difficult to assign a functional significance to a difference in mean phase lag of at most lo”, we conclude that, to a good first approximation, the mean phase lags of vestibular plus saccade, vestibular plus position, and type II vestibular only neurons are essentially equal. On the other hand, type I vestibular only units have a much wider distribution of phase lags, with almost half (12/25) of the units exhibiting phase shifts of less than 50” at stimulus frequencies of 0.93 Hz. Of particular interest are the neurons with discharge patterns that are approximately in phase with head acceleration. Figure 10 illustrates three such neurons recorded from a single electrode track in the rostra1 part of the vestibular nuclear complex of monkey 1 just lateral to the

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abducens nucleus. Units 1:8, 1:7, and I :5 had phase shifts relative to ipsilateral acceleration of 13, -22, and 9”, respectively, and were all located in the lateral vestibular nucleus; in monkey 2, two other units with similar phase shifts were confined to the medial nucleus. All these neurons responded with head acceleration rather than head position (position and acceleration are 180” out of phase for sinusoids) since lower frequencies of head rotation which provided lower accelerations for the same amplitude of head position were associated with lower discharge rates. Units with phase shifts near 0” were very rare compared with units with phase shifts near 80” and, as can be seen from unit 1:6 whose phase shift is 3”, similar units could also be found in the dorsal medullary reticular formation. Because of the nonlinearities mentioned above, assumptions must be made to calculate an amplitude plot to complement the phase plots of Fig. 9. Previous studies have “completed’ the rectified response by extending the firing frequency to negative values (7, 29). In our labora-

. “..’

., *.l** ;: ““i+ . *. . *. *. l 5 ‘... t 0 -.a..

15

30

FIG. 10. Discharge characteristics and anatomical location of some units from monkey I (1:8, 1:7, and 1~5) whose averaged firing rates were approximately in phase with ipsilateral head acceleration (arrows). A single oblique electrode track can be seen running lateral to VI nucleus with reconstructed units I .??, 1~7, 1.4, and probably 1.3 lying in lateral vestibular nucleus, unit 1 :I in superior vestibular nucleus, and unit I:6 in dorsal medullary reticular formation. Ordinate for all units represents IO-cycle averaged firing rate in spikes per second. Original records are shown for unit I:5 at upper right.


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1154

tory gain has been calculated by taking the ratio of the amplitude of the fundamental in the Fourier analysis describing the firing rate to the amplitude of applied acceleration. With this definition the averaged gain decreases with frequency for all types of units (Fig. 11A). Although, as noted earlier, the absolute gain for type I neurons is generally higher than that for 3

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type II neurons, the decrement in gain with frequency is similar for all unit types with a slope of - 1.5 (or equivalently 30 dB/decade) on the average. Another measure for the gain or sensitivity of vestibular units to head rotation can be obtained by relating discharge frequency to angular velocity of the head. The maximum increment of unit firing above its resting rate is plotted against maximum head velocity in Fig. 11B. Of 11 vestibular plus saccade and 20 vestibular only neurons that were analyzed, 13 showed characteristics that were quite linear (Fig. 1 lB, units 13.4, 6:3, 8.=2, and 7:2). Another 9 units, typified by unit 5:2, had maximum firing frequency-velocity characteristics which, on the average, were linear but had an aberrant data point (at about 27”/s for unit 5:2). The remaining 9 units exhibited a monotonically increasing relation between maximum firing rate and velocity but the characteristic exhibited saturation at higher velocities. As determined by the slope of the linear characteristics, the vestibular plus saccade. neurons had higher average sensitivities (0.87 t 0.2 spikes/s per deg per s2) than the vestibular only neurons (0.52 t 0.23), a fact that has already been demonstrated for a single velocity in Fig. 8B. DISCUSSION

Maximum

60 velocl ty (deg /secj

FIG. 11. Sensitivity of vestibular nucleus neurons to different stimulus frequencies and head velocities. A: gain of individual neuron categories as determined by ratio of magnitude of fundamental component of Fourier analysis of averaged discharge rate to magnitude of applied acceleration. B: relationship of maximum change in firing rate above Units chosen to resting to maximum h .ead velocity. demonstrate an essentially linear characteristic (13.4, 613, 8:2, 7:2), a characteristic with one aberrant point (5:2), and a saturating characteristic (2.3, 6~2). Note that units 5:2 and 8:2have been discussed previously (Figs. 3-5).

Earlier studies in anesthetized animals have demonstrated that, over the range of accelerations encountered during normal head rotation, unit activity in the vestibular nuclei is essentially a function of head velocity (29). Our results show that when an animal is able to move his eyes, over half of these same units discharge in relation to eye movement, particularly those voluntary eye movements that would aid the compensatory eye movements elicited by the vestibular stimulation. The chronic preparation, therefore, allows a much more complete description of these neurons and may, when combined with recordings from the MLF, provide some additional information as to the probable destination of their axons. The large majority (88%) of the vestibu-

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lar nucleus neurons encountered in this bit, 67% of the neurons are type I and study showed similar responses to hori27% are type II (5). In the two studies zontal angular accelerations of the head. using decerebrate cats, 62 and 67% of the At sinusoidal oscillations of 0.2-0.93 Hz neurons were type I and 38 and 29% (peak accelerations from 3 1.5 to 670°/s2), were type II (28, 35). Unlike other the unit discharge averaged over 10 cycles species, no units in our sample increased lags head acceleration by 80.0 t 11.8” their rate for both ipsilateral and con(N = 2 11, data from 115 neurons at one tralateral rotations (type III neurons). A basic difference between the cat and or more stimulus frequencies), whether or nucleus not the unit also responds with eye the monkey is that cat vestibular movement. l The mean phase lag correneurons have lower spontaneous firing sponds closely to the 73 t 8’ obtained at rates in the absence of vestibular stimula0.2-0.5 Hz in the 8th nerve of the anestion. Of the cells described by Melvill Jones and Milsum (28), 26% were silent; thetized squirrel monkey (7), suggesting acthat most cells in the nuclei are not in- of the 74% that were spontaneously tive, none reached resting firing rates in volved in further processing of the phase excess of 70 spikes/s and the average rate information carried by the 8th nerve. of spontaneously active cells was only These findings also suggest that under our behavioral conditions (an important 20.2 t 14.1 spikes/s. In our sample of 127 monkey, only qualifier that will be discussed later) the units in the unanesthetized 4 cells were silent in the absence of vesnumerous anatomically demonstrated tibular stimulation, 36% had resting rates connections from the contralateral nuclei and the cerebellum or reticular formain excess of 70 spikes/s, and the entire had a mean of 70.22 23.5 tion, all of which should be viable in the population alert monkey, have little effect on the spikes/s (Fig. 8A). Since feline 8th nerve fibers also have low resting rates (6), the phase shift of vestibular nucleus neurons. vestibular system may simply Furthermore, although the destinations of monkey’s our neurons were not identified, it is operate at higher rates than the cats. likely that at least some provide axons Despite the difference in resting rates between cat and mon key, both th e phase which ascend to the various oculomotor nuclei or descend to the cervical spinal shifts of the averaged neural activ ity relative to acceleration and the sensitivity (or cord; therefore, based on our results alone it would be reasonable to suggest gain) of vestibular nucleus neurons are remarkably similar in the two species. In that some of the monosynaptic connecthe cat, the gain over the frequency range tions reaching both neck and ocular 0.25-1.5 Hz is relatively constant at 0.76 motoneurons (2, 14, 43) provide a signal spikes/s per deg per s (28); in the monkey, that is nearly in phase with head velocity. averaged values at 0.5 and 0.93 Hz (220”) A much smaller number of vestibular would be 0.57 and 0.49 spikes/s per deg neurons had averaged discharge patterns per s, respectively. Over the frequency that lagged head acceleration by less than range 0.25-1.7 Hz, the mean phase shift 50”. All of these units were type I and of feline neurons was roughly constant at responded only to applied head accelera78.6O with a range from 46 to 110” (28). tion and not to eye movement (Fig. 10). In the unanesthetized monkey there From 0.2 to 1.0 Hz in the monkey the constant was an almost equal percentage of type I phase shift was also relatively with a mean at 0.5 Hz of 77.2”; almost all neurons (53%) and type II neurons (47%). Other studies on mammalian vesthe neurons fell within the range of phase tibular nucleus neurons have found a shifts between 50 and 110”. Since most of the neurons in both studies were recorded greater population of type I than type II neurons. In the lightly anesthetized rablargely from the medial nucleus, there is a strong species agreement: comparable cell 1 Vestibular plus position neurons are included in populations in the vestibular nuclei rethis population since they appear to receive comspond with a discharge pattern that pletely independent information regarding head velocity on one hand and eye position on the other. slightly leads head velocitv and is esssen-


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tially unchanged from the primary afferent activity recorded in the 8th nerve. Since commissural connections from the contralateral horizontal canal disinhibit type I neurons during ipsilateral head rotations, a possible role for the viable commissural pathway in the alert monkey might be to provide deeper modulation (higher sensitivities) in the nuclei than in the nerve. The data of Fernandez and Goldberg (7) are presented either as normalized gains or sensitivities measured as t + 00; unfortunately, a comparison of our data with their sensitivities would require a knowledge of gain at zero stimulus frequency in Fig. ll~?, an extrapolation that would be very arbitrary based on our limited data. Howver, a smaller population of 8th nerve neurons has been recorded in the alert monkey under similar stimulus conditions in our laboratory, allowing a direct comparison between sensitivities in the 8th nerve and nucleus (24). In 23 fiber recordings from the 8th nerve, the average sensitivity, as measured by the amplitude of the fundamental component of the Fourier analysis, was 62.9 t 32.0 spikes/s (0.93 Hz, t20”). By comparison, the sensitivities of type I vestibular only, vestibular plus saccade and vestibular plus position neurons were 53.5 t 33.5, 84.6 t 46.9, and 58.5 t 36.1 spikes/s, respectively. Therefore, with the possible exception of neurons, senvestibular plus saccade sitivities in the nerve and nucleus are very similar. However, a clear demonstration of the functional role of commissural connections must await unit recording in a chronic animal with unilateral plugged canals. Although the primary vestibular phase information from the canals apparently undergoes no further processing in the vestibular nuclei, the nuclei probably provide the first site2 in the classical vestibular ocular pathway where information concerning voluntary eye movements and the fast phase of vestibular nystagmus can be 2 Efferent fibers have been recorded goldfish and could tion directly to the similar eye-movement been demonstrated (24).

with eye-movement sensitivity in the 8th nerve of the rabbit and provide eye-movement informavestibular receptors. However, efferents have thus far not in the unanesthetized monlcey

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added to the vestibular signal. The basic nystagmic rhythm of an increase in activity during a slow vestibular induced eye movement interrupted by a pause in activity during a saccade in the opposite direction is already present in the vestibular plus saccade neurons (Fig. 5A). For example, a type I vestibular plus saccade neuron recorded in the right vestibular nucleus exhibits an increasing rate for rightward (clockwise) head rotations and a pause for right saccades. Since a rightward head rotation results in a leftward slow eye movement interrupted by rightward saccades (Fig. l), the firing pattern of type I pause neurons would be appropriate to participate in both the slow and fast phase of the vestibuloocular reflex. The characteristics of the pause in activity which leads the saccade by 7 ms for more than half of the neurons and has a duration proportional to saccade duration (Fig. 6) lend further support for the suggestion that these neurons could participate in the fast phase. The oculomotor activity of most vestibular plus position neurons also was appropriate to their vestibular responses. In 10 of 11 type I neurons a rightward head rotation (which would cause a leftward compensatory eye movement) caused increased neural activity in the absence of eye movement; the same neuron exhibited an increase in activity for leftward voluntary eye fixations (with little or no change in activity associated with the leftward saccade). Therefore, if the eye were already looking in the direction of the compensatory eye movement, the vestibular modulation would occur around a higher mean rate which might cause a target neuron in the abducens nucleus to be closer to threshold and, hence, be more sensitive to the superimposed vestibular stimulation. In our sample, no neurons that burst only prior to and during saccades were located within the confines of the vestibular nuclei, although a burst appropriate to the saccade would be available from our pure eye-movement only (burst-tonic) neurons. Since the quick phases of nystagmus are still present after midline lesions (42), it is likely that the activity as-


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sociated with saccades and the fast phase of nystagmus originates in the pons and ,’ does not depend on commissural interactions between opposite vestibular nuclei. Anatomical studies have determined that the rostra1 parts of the vestibular nuclei contain the cells which send ascending axons into the MLF of both cat (11, 40) and monkey (27). In the horizontal canal system of the cat and rabbit, monosynaptic excitatory and inhibitory connections onto motoneurons have been demonstrated from the rostra1 medial vestibular nucleus (2, 14), where many of our cells were isolated. Assuming similar synaptology in the monkey, is it possible to suggest which, if any, of the cell populations described in our study participates in this monosynap tic linkage? Since the rostra1 vestibular nuclei also project strongly to the cerebellum, the contralateral vestibular nucleus and the reticular formation (2 1, 27), arguments based solely on the anatomical location of neurons would be very speculative. Fortunately, two recent studies have provided evidence concerning the nature of vestibular and oculomotor information traveling in the simian MLF, thereby allowing a comparison with firing patterns in the vestibular nucleus. In the alert monkey, single-unit recordings from the MLF rostra1 to the abdutens nucleus reveal neurons with vestibular plus position characteristics for accelerations applied in the vertical plane (4). Although these fibers could possibly be descending from the mesencephalon rather than ascending, it is more likely that they are axons of vestibular nucleus neurons which are sensitive to vertical head oscillations and eye position in the same fashion that our vestibular plus position neurons were sensitive to horizontal accelerations and eye positions. However, . few if any horizontal vestibular plus position neurons have been recorded in the MLF so that the destination of these neurons remains a mystery. It seems unlikely that they connect to motoneurons since during fixation, motoneurons exhibit none of the vestibular modulation still present in vestibular plus position neurons. The destination of vestibular plus saccade neurons is also obscure. Al-

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though these neurons can be monosynaptically activated by 8th nerve stimulation axons of vestibular plus saccade (17) neurons are rare in the MLF (4, 31) and apparently nonexistent within the motor nuclei, at least in the cat (1, 26). Recently, evidence has been accumulating to suggest that burst-tonic activity, i.e., the motoneuron-like discharge pattern of our eye-movement only neurons, ascends in the MLF to drive horizontal ocular motoneurons. In the alert monkey, units exist in the MLF with burst-tonic discharge patterns appropriate to drive motoneurons in the medial rectus subgroup of the ipsilateral oculomotor nucleus (4, 3 1). Intracellular recordings from axons within the confines of the abducens nucleus (26) of the cat demonstrate a burst-tonic activity pattern during vestibular nystagmus; these same axons can be excited from the contralateral 8th nerve at polysynaptic latencies with stimulus strengths insufficient to excite the reticular formation; therefore, Maeda et al. (26) concluded that some of these fibers were axons of vestibular nucleus neurons. In fact, a large percentage of medial vestibular nucleus neurons whose axons ascend in the MLF are polysynaptically activated from the 8th nerve (43). Since burst-tonic neurons in the monkey vestibular nuclei are also polysynaptically activated from the 8th nerve, it seems reasonable to suggest that at least some of the bursttonic MLF fibers represent the ascending axons of our eye-movement only cells and probably impinge directly on ocular motoneurons. Although the above arguments suggested that some of our eye-movement only units may be involved in the vestibuloocular pathway, one study of vestibular nucleus neurons under a variety of tracking conditions has revealed. a population similar to our vestibular only neurons which seem related only to head movement (10). Even when an animal’s head was stabilized, a strain gauge revealed that he attempted to make head movements to acquire the target. Most of the vestibular only neurons in that study discharged with head torque, suggesting that similar neurons in our population are also con-


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cerned with head rather than eye movement. Although activity related to voluntary eye movement probably reaches oculomotor neurons from the vestibular nuclei, it is impossible to decide whether the 8th nucleus is, as Spiegel (39) suggested, a necessary prenuclear structure through which all eye-movement commands are funneled. Except for the apparent absence of neurons that only exhibit a burst of spikes for saccades, vestibular neurons respond with very stereotyped patterns to the entire repertoire of versional eye movements. Therefore, if the burst of activity associated with the saccade were contributed by the eyemovement only neurons, the vestibular nuclei would have all the discharge patterns that are present in the paramedian pontine reticular formation, a unilateral lesion of which causes complete paralysis of ipsilateral gaze (12). However, lesions of the vestibular nuclei are apparently much less disruptive to voluntary eye movements. In fact, lesions in rostra1 portions of the nuclei have no effect on optokinetic nystagmus, optokinetic afternystagmus, and the fast phases of nystagmus (either vestibular or optokinetic); nor do they result in gaze nystagmus or any clear abnormality of voluntary eye movements (42). Therefore, in spite of their large numbers of neurons related to most aspects of eye movements, the vestibular nuclei seem to be involved in different oculomotor functions than the pontine reticular formation. Perhaps the vestibular nuclei are most important when voluntary and vestibular eye movements are required to interact, a situation which has not yet been investigated in lesioned animals. Finally, it should be emphasized that the responses obtained from vestibular nucleus neurons in our study were obtained under relatively simple behavioral tracking conditions. In our situation, most of the monkey’s visual world was attached to the chair in which he was seated and rotated with him as he moved. If the monkey alternately fixates a spot rotating with him, a spot moving equal to and opposite the head rotation, or no spot at all

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in the dark, units in the vestibular nuclei exhibit different behaviors. For neurons similar to our eye-movement only units, Keller and Daniels (18) report that the depth of modulation associated with the velocities of voluntary smooth pursuit tended to be less than for vestibularinduced compensatory movements of equal eye velocity. Some burst- tonic neurons exhibit a phase shift which varies with tracking conditions, so that when both head rotation and compensatory eye movements occur simultaneously the phase lies somewhere between a pure eye movement (180” phase shift) and a pure vestibular (90” phase shift) signal (30). In addition to these short-term effects of tracking strategy on unit discharge, a more gradual (5-10 s) augmentation of unit discharge to head rotation can be obtained if an optokinetic pattern is also rotated in an opposite direction (13). Therefore, it is clear that further studies on the vestibular nuclei of alert preparations must be conducted with care taken to control and vary the animal’s tracking conditions. SUMMARY

Single units were recorded from the vestibular nuclei of unanesthetized monkeys that were rotated in the horizontal plane while simultaneously pressing individual buttons in a controlled array which turned with them. Using this behavioral paradigm, it was possible to 1) determine the relationship of unit discharge to eye movements measured by the DC-coupled electrooculogram and calibrated by the the button-press task, and 2) determine relationship of unit discharge to horizontal acceleration, either with or without the compensatory eye movements evoked by vestibular stimulation. Based on their responses during vestibular stimulation and/or eye movements, neurons in the vestibular nuclei (77% of our sample was in the medial nucleus) could be divided In a total of 127 into four groups. neurons, about half (58 units) responded to the vestibular stimulus only and exhibited no change in activity with eye movement. Most of the rest responded independently to both the vestibular


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stimulus and some component of eye movement; within this vestibular plus eye-movement group, neurons could be divided into those that showed a change of firing rate (usually a pause) with saccades only (38 units) and those whose firing rate was primarily a function of eye position (21 units). A small number of neurons in our sample (10 units) responded with eye movement alone and behaved essentially like abducens motoneurons. During sinusoidal horizontal head accelerations all of the units with vestibular sensitivity displayed a periodic modulation of discharge frequency about their resting rates. In the unanesthetized monkey, there was an almost equal number of type I units (responding to ipsilateral acceleration) and type II units (responding to contralateral acceleration). Over the frequency range 0.2-0.93 Hz (+20” amplitude, 3 1. 5-670°/s2 peak accelerations), the peak in discharge frequency for 88% of the units lagged the applied acceleration by an average of 80°. The peak in firing rate of a smaller number of type I vestibular only neurons occurred approximately in phase with head acceleration. Resting rates were generally greater for vestibular plus eye movement units than for vestibular only units; units with higher resting rates also tended to have greater depths of vestibular modulation. The relatively constant phase lag of 80° recorded in most neurons is comparable to phase lags recorded in the vestibular nerve. Therefore, under these behavioral conditions little if any additional phase delay has been contributed by the com-

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missural, cerebellar, and reticular connections viable in the alert monkey; as in the unalert cat, the output of most neurons in the vestibular nuclei roughly signals head velocity. However, the large repertoire of discharge patterns related to every aspect of voluntary and compensatory eYe movement suggests that the vestibular nuclei may be an important prenuclear structure for coordinating vestibular and oculomotor inputs to motoneurons. Units whose discharge rate paused for saccades while the animal was at rest also paused for saccades occurring during the ves tibular modulation; if acceleration in one direction caused an increase in unit activity, a pause in activity always occurred For saccades in the same direction. For units whose discharge rate increased with eccentric eye position, the vestibular modulation was simply superimposed on a steady rate determined by the unit’s eye-position sensitivity. If acceleration in one direction caused an increase in activity, fixations in the opposite direction also produced increased activity. Therefore, the discharge patterns of both unit types associated with voluntary eye movements were appropriate to participate in compensatory eye movements of vestibular origin. ACKNOWLEDGMENTS

We gratefully acknowledge the technical assistance of Val Kiefer and Greg Wilson and the support of the Instrumentation Development Division and Colony Staff of the Primate Center. We are also indebted to Marianne Houghton for typing the manuscript, Kate Schmitt for editorial advice, and Mike King and Steve Lisberger for critical review of the paper.

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Characteristics of head rotation and eye movement-related neurons in alert monkey vestibular nucleus.

Vertical eye movement related unit activity in the rostral mesencephalic reticular formation of the alert monkey.

Discharge patterns in nucleus prepositus hypoglossi and adjacent medial vestibular nucleus during horizontal eye movement in behaving macaques.

Vestibular nuclei activity in the alert monkey during suppression of vestibular and optokinetic nystagmus.

Oculomotor related interaction of vestibular and visual stimulation in vestibular nucleus cells in alert monkey.

Parietal cortex (2v) neuronal activity in the alert monkey during natural vestibular and optokinetic stimulation.

Eye movement evoked by stimulation of lateral posterior nucleus and pulvinar in the alert cat.

The interstitial nucleus of Cajal is involved in generating downward fast eye movement in alert cats.

Neuronal activity in the prepositus hypoglossi nucleus correlated with vertical and horizontal eye movement in the cat.

Firing characteristics of vestibular nuclei neurons in the alert monkey after bilateral vestibular neurectomy.

Projections of vertical eye movement-related neurons in the interstitial nucleus of Cajal to the vestibular nucleus in the cat.

Vertical and horizontal eye movement recording in the unrestrained cat.

Responses of peripheral vestibular neurons to angular and linear accelerations in the squirrel monkey.

Activity of eye-movement-related neurons in the region of the interstitial nucleus of Cajal during sleep.

Vertical eye movements during horizontal head impulse test: a new clinical sign of superior vestibular neuritis.

Afferent modulation of unit activity in globus pallidus and caudate nucleus: changes induced by vestibular nucleus and pyramidal tract stimulation.

Responses of non-eye movement central vestibular neurons to sinusoidal horizontal translation in compensated macaques after unilateral labyrinthectomy.

Neural basis for eye velocity generation in the vestibular nuclei of alert monkeys during off-vertical axis rotation.

Eye movement-related neurons in the red nucleus.

Subthalamic nucleus gamma activity increases not only during movement but also during movement inhibition.

Rhythmic Firing of Pedunculopontine Tegmental Nucleus Neurons in Monkeys during Eye Movement Task.

Activity of lateral vestibular nucleus neurons during locomotion in the decerebrate guinea pig.

Prefrontal and cingulate unit activity during timing behavior in the monkey.

Neurons with visual receptive field, eye movement and neck displacement sensitivity within and around the nucleus prepositus hypoglossi in the alert cat.