Single unit firing patterns in the vestibular nuclei related to voluntary eye movements and passive body rotation in conscious monkeys

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Brain Research, 71 (1974) 215-224 © Elsevier Scientific Publishing Company, Amsterdam - Printed in The Netherlands

Colloque C.N.R.S. no. 226 Comportement moteur et activit6s nerveuses programm~es Aix-en-Provence, 7-9 sept. 1973

S I N G L E U N I T F I R I N G P A T T E R N S IN T H E VESTIBULAR N U C L E I R E L A T E D TO V O L U N T A R Y EYE MOVEMENTS A N D PASSIVE BODY R O T A T I O N IN CONSCIOUS M O N K E Y S

F. A. MILES

Laboratory of Neurophysiology, National Institute of Mental Health, U.S. Department of Health, Education and Welfare, Bethesda, Md. 20014 (U.S.A.)

SUMMARY

Single unit recordings were made in the vestibular nuclei of conscious monkeys trained on a fixation task to facilitate experimental manipulation of the animal's eye movements. Experiments centred around cells in the medial and superior vestibular nuclei whose activity correlated closely with eye movements. Some neurones fired tonically in relation to the position of the eyes in the orbits, others only transiently in relation to the movement of the eyes, and yet others showed both relationships; occasional units showed maintained firing which was independent of eye position and was suppressed during saccadic eye movements. Thus, each saccade was accompanied by a step, pulse, or pulse-step change in the firing of individual neurones. In some units the earliest changes in firing preceded the eye movement, whilst in others they occurred during the movement. Many neurones were strongly directional, firing only in relation to movements of the eyes to one or other side of the orbits, whilst others - - especially the pulse-type units - - often fired in relation to all eye movements. The precision of the coupling between single unit firing and eye movements was very impressive in most of these neurones, but under certain experimental conditions the firing patterns of some of them could be dissociated from eye movements. It is felt that the apparent eye-movement relationships seen in such units when the animal's head was fixed in position may in fact have been associated with attempted head movements.

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R~SUM~ Des enregistrements unitaires ont 6t6 r6alis6s dans les noyaux vestibulaires de singes entraln6s & une tache de fixation destin6e ~. faciliter la manipulation exp6rimentale des mouvements oculaires de l'animal. Les exp6riences ont 6t6 centr6es sur les cellules des noyaux vestibulaires m6dian et sup6rieur dont l'activit6 6tait 6troitement correl6e aux mouvements des yeux. Certains neurones d6chargent uniquement en relation avec la position des yeux dans l'orbite, d'autres seulement de mani6re transitoire en relation avec le mouvement des yeux, et d'autres encore montrent les deux types de relations; certaines unit6s pr6sentent une d6charge continue qui est ind6pendante de la position des yeux et est supprim6e pendant les mouvements saccadiques des yeux. Donc chaque saccade est accompagn6e d'un changement 'tonique' (step), 'phasique' (pulse) ou 'toniqueph-asique' (step-pulse) de la d6charge des neurones. Pour certaines unit6s, le d6but du changement pr6c6de le mouvement des yeux, tandis que pour d'autres il se produit pendant le mouvement. Beaucoup de neurones sont fortement directionnels, d6chargeant uniquement lors de mouvements des yeux vers Fun ou l'autre c6t6 de l'orbite, tandis que d'autres, surtout des unit6s de type 'pulse' d6chargent souvent en relation avec tousles mouvements des yeux. La pr6cision de la liaison entre d6charge unitaire et mouvement des yeux est tr6s impressionnante pour la plupart des neurones, mais dans certaines conditions exp6rimentales les patterns de d6charge de certains d'entre eux ont pu ~tre dissoci6s des mouvements des yeux. I1 semble que la relation apparente avec les mouvements des yeux que pr6sente de telles unit6s lorsque l'animal a la t~te fix6e puisse &re en fait associ6e ~t des tentatives de mouvements de la t6te.

The vestibular-ocular reflex functions to stabilise the eye in space by generating compensatory eye movements to counteract movements of the head. Recent work suggests that this reflex compensates for all head movements, both active and passive, and that the eyes are subject to continuous vestibular adjustment 1. The rapid saccadic eye movements which shift gaze from one object of interest to another, and the smooth tracking movements which ensue if that object should move, must be programmed and superimposed on this ongoing vestibular drive. It has been argued that since, phylogenetically, vestibular control of the eyes most probably predated visual, then the neural machinery originally evolved to generate the slow compensatory movements and rapid resetting saccades characteristic of vestibular nystagmus might also mediate the 'more recent' visually guided movements 11. The lesion studies of Spiegel 15 led to the suggestion that the vestibular nuclei might be involved in the programming of all eye movements (though more recent lesion studies on the vestibular nucleP 6 produced less dramatic deficits in eye movements). Duensing and Schaefer also reported some years ago that some of the neurones in the vestibular nuclei in the rabbit changed firing not only in relation to movements of the head but also during saccadic eye movementsL The present study was under-

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taken to investigate the possible involvement of the vestibular nuclei in the programming of eye movements in the monkey. The approach used here involved microelectrode recordings in the vestibular nuclei in conscious monkeys, and concentrated on individual units whose firing patterns correlated with the animal's saccadic eye movements. Three rhesus monkeys were used and each was trained to press a bar which switched on a small spot of light on a screen facing him and to release the bar only after the light dimmed. If the animal succeeded in releasing the bar within 0.5 sec of this dimming, then he was rewarded with a drop of water; all of the animal's fluid intake was earned by working at this task. Using this approach, the monkeys were trained to fixate a small spot of light and maintain this fixation even if the position of the spot was changed. Thus, it was possible to induce the animal to generate saccadic eye movements of known magnitude and direction merely by changing the position of the fixation target. This behavioural task requires immense vigilance from the animal and cannot be performed with peripheral vision, hence successful performance could only be achieved by the animal if he made the required eye movements. Oculograms recorded from implanted electrodes confirmed the nature of the animal's eye movements whilst he was performing the task and were used as a response trigger for data display: correlations between eye movements and individual neurone firing patterns were made on-line by using a raster display in which each action potential was represented as a spot on the screen of a storage oscilloscope; the oculogram signals generated by the eye movements were used to initiate sweeps o f the oscilloscope and the pulses representing action potentials were displayed after passing through a delay line. In this way unit firing patterns during successive saccade trials were displayed in rows on the storage oscilloscope; the delay facility allowed one to observe the unit firing before, as well as during and after, the eye movements. A major advantage of this form of display is that it readily reveals not only the nature of the correlation between eye position and unit firing but also its timing and consistency.

Unitary activity correlated with eye movements Upon isolating an eye-movement correlated unit, the animal was induced to make a variety of eye movements with various amplitudes, directions, and start positions. The recording sites of selected neurones were marked with electrolytic lesions and in the present study all were located in the medial and superior vestibular nuclei; not all neurones were so marked and hence the possibility that some may have been outside the vestibular nuclei cannot be totally excluded. Suffice it to say that representatives of each of the types which will be described here have been found in these areas. Most of the firing patterns encountered could be grouped into one of 4 main classes. (1) "Burst' units: show high-frequency bursts of firing in relation to saccadic eye movements in one or several directions. The vigour of the burst varies with the direction and magnitude of the saccade. Most units fired more vigorously in relation to saccades directed towards the ipsilateral side, the duration of the bursts correlating with the duration of the eye movement which, of course, in turn relates to its magnitude. One animal occasionally generated saccades varying widely in velocity, and

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at such times the number of spikes in the burst varied little for eye movements between given pairs of targets; the duration of the burst correlated closely with the duration of the saccade over a wide range, hence the frequency varied accordingly. Thus, in this case it was possible to demonstrate a close relationship between the frequency of the burst and the velocity of the saccade. The start of the burst was usually abrupt and preceded the eye movement by 5-15 msec; however, some units commenced at a low rate much earlier (more than 50 msec before the eye movement). Likewise, the end of the burst was usually fairly abrupt, but some units continued to fire at a low rate for 50 msec or more after the main burst. Some of these 'burst' units showed tonic firing which was unrelated to eye movement, and in those with a strong directional preference the maintained firing would be suppressed during saccadic eye movements in the non-preferred direction. None of the 'burst' neurones fired in relation to slow visual tracking eye movements though they fired continuously during the slow drift eye movements characteristic of the drowsy animal. Similar burst neurones have been described in the monkey brain stem reticular formation3,S,9,14. (2) 'Pause' units: fired steadily during fixation but paused during saccadic eye movements. Maintained rates ranged from 50 to 150/sec and were fairly stable for given units. The pause in firing usually correlated quite well with the duration of the saccade and the last spike before the pause usually preceded the eye movement by 10-30 msec. Most units stopped firing during all saccades, though in some units saccades in some directions were accompanied by a pause which was much briefer than the eye movement. None of these 'pause' neurones changed their tonic firing rate during slow tracking eye movements. 'Pause' units have also been described by other workers in monkey brain stem s . (3) 'Burst-tonic" units: showed tonic firing which was related to static eye position and transient changes in firing during saccades. The tonic level of firing increased progressively as the eyes moved in a particular direction (the 'on' direction) and was little changed by orthogonal movement. Saccades in the on-direction for the neurone were accompanied by transient bursts - - similar in characteristics to those seen in pure 'burst' units - - followed by an increase in the tonic frequency to a rate commensurate with the new eye position. Saccades in the off-direction were accompanied by the converse - - a transient pause followed by a resumption of firing at a new reduced rate. On-directions were mostly ipsilateral. Saccades orthogonal to the on-off axis were usually accompanied by a very brief pause or no change in firing, though weak bursts were sometimes seen. The earliest changes in firing associated with saccades usually preceded the eye movement by 5-15 msec, though occasional units did not alter their firing rate until the eye movement was under way. These 'burst-tonic' neurones are very similar to oculomotor neurones in their pattern of firing 5-7,12,t:3, and a recent study s on monkey brain stem also reported their presence in the medial vestibular nucleus. (4) 'Tonic' units: displayed maintained firing during fixation, at a frequency which was related to static eye position, and showed either no change or a pause during saccades. As with the tonic firing of the 'burst-tonic' units, the frequency of

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discharge changed progressively as the eyes moved in a particular direction, and was little affected by purely orthogonal movements. Some 'tonic' units paused during all saccades, others only during those made in the off-direction. When saccades were made in the on-direction, the unit usually assumed the firing rate appropriate to the new eye position sometime during the later stages of the eye movement. Again, similar units have been reported in other studies on monkey brain stem s . (5) Miscellaneous units. Each of the above groupings encompasses neurone types which vary widely in the details of their firing patterns and the overall impression is one of a continuum rather than widely separate entities. Thus, some 'burst' units generated tonic firing with extremely eccentric fixation and might be thought of as 'burst-tonic' neurones with a very high threshold position relationship. Conversely, many 'burst-tonic' units only showed appreciable bursting with very large saccades (in excess of 35 °) and hence looked like simple 'tonic' neurones for much of the time. Some 'burst-tonic' neurones generated bursts during all saccades, even when made in the off-direction for the tonic component. A few of these displayed tonic rates which increased with deviations of the eyes away from the centre of gaze, in all directions except upwards. Other 'burst-tonic' neurones showed brief pauses immediately before or after the burst but only to eye movements directed towards a particular quadrant. It is clear that the rigid categorizations employed above are for descriptive purposes only and the nervous system may not be so ordered.

Unitary activity correlated with passive rotation of the animal All of the above recordings were taken from animals whose heads were secured to the stationary primate chair through implanted bolts; more recently, single unit data have been obtained during sinusoidal rotation, when the chair was oscillated back and forth about a vertical axis whilst the monkey continued to work on the fixation task. Usually the chair was oscillated through 40 ° with cycle periods of 315 sec, and it was very clear that the neurones in the vestibular nuclei which responded to this input fired in phase with chair velocity. This accords with previous studies on monkey primary vestibular afferents a. In common with findings in cat and rabbit vestibular nuclei (see ref. 10 for refs.), some neurones responded to ipsilateral movement, others to contralateral. Unitary activity correlated with both eye movements and passive body rotation Some of the neurones which appeared to be responding to the vestibular stimulation also fired in relation to eye movements, a phenomenon also noted by Duensing and SchaeferL These were mostly 'pause' and strongly directional 'burst' units, the latter always responding to those movements o f the chair which carried the eyes in the off-direction for that neurone, e.g., a unit which bursts with rightward saccadic eye movements would fire during leftward chair movements. In addition, these neurones sometimes showed bursts in the absence of any eye movement. During the course of these experiments it became clear that even some 'bursttonic' neurones did not always fire solely in relation to the movements of the eyes in

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the orbits. Three experimental paradigms were employed, and it is important to note that the animal's head was secured to the special primate chair t h r o u g h o u t : (1) The chair was stationary, and the animal endeavoured to track a target which oscillated back and forth; this was an attempt to obtain a sinusoidal pattern o f horizontal eye movements. (2) The chair was oscillated about a vertical axis while the animal fixated a distant stationary target; this was an attempt to obtain a pattern o f eye movements similar to those produced in the previous situation, but now by moving the animal instead o f the target. (3) The chair was oscillated exactly as in (2), but the m o n k e y ' s fixation target was m o u n t e d on a bracket extending f r o m the chair and hence moved with the animal; here, the m o n k e y had to try to suppress the compensatory eye movements which n o r m a l l y a c c o m p a n y such head rotations. It should be stated at the outset that most o f the eye m o v e m e n t correlated neurones seemed to fire purely in relation to eye movements no matter what experimental conditions prevailed. However, Fig. 1 shows an example of a 'burst-tonic' unit in the right medial vestibular nucleus whose activity could be dissociated f r o m eye movements. F r o m the top part o f Fig. 1 it is clear that when the chair was stationary this neurone increased its firing nicely in relation to leftward eye movements (indicated by d o w n w a r d deflection of the oculogram); yet it is apparent f r o m the centre o f Fig. 1 that when the chair was moved with the target, so that the eyes were reasonably stationary in the orbits, the neurone continued to modulate its activity with each cycle, but now in relation to rightward chair movement; when the animal was fixating a stationary target whilst being oscillated, so that rightward head movements were coupled with compensatory leftward eye movements (bottom part o f Fig. 1), then the neurone showed its most extreme modulation. Scrutiny o f the phase relationships reveals that when only the eyes are moving the unit modulation is in phase with eye position, whilst when only the chair is moving it is more in phase with chair velocity; when both eyes and chair are moving but 180 ° out o f phase with one another then the unit modulation sharpens and takes on an intermediate phase relationship, lagging rightward chair velocity and yet leading leftward eye position. The analysis of this p h e n o m e n o n is still at an early stage but in every one of the 10 neurones o f this type seen so far, the eye and chair m o v e m e n t phase relationships

Fig. 1. Activity of a neurone in the right medial vestibular nucleus in relation to chair and eye movements. Top: unit activity during visual tracking of a target undergoing sinusoidal oscillations whilst the animal's head is held stationary. Middle: unit activity during oscillation of the primate chair about a vertical axis whilst the monkey fixates a target mounted so that it moves with him and hence his eyes are stationary in the orbits. Bottom: unit activity during oscillation of the primate chair about a vertical axis whilst the monkey fixates a distant stationary target. Data were displayed on a 6-channel rectilinear pen-recorder (Brush 260). The gaze was computed on-line by summing the horizontal oculogram (EOGH) and an index of head position derived from a potentiometer mounted on the chair spindle. Note that the target, gaze, oculogram and head position monitors are all displayed at the same gain and upward deflections indicate rightward movements. The reciprocal interval plot (RIP) was derived from a reciprocal interval meter with a built-in sample-and-hold device and cut-off filter (set at 2 Hz in this instance) to facilitate immediate readout of gross unit frequency changes on the pen-recorder.

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were very similar, that is, they were excited in association with ipsilaterally directed chair movements and contralateral eye positions. Further analysis of the eye movement relationships of such neurones showed that even when the chair was completely stationary their firing was not related to eye position per se; this can be seen in Fig. 2 which shows the further analysis of the unit already partly characterised in Fig. l: here the animal tracked an oscillating target whilst the chair was stationary, but in each of three different positions, so that the eyes had to undergo the same oscillations but in different parts of the orbits. The target moved through ± 20 ° and when the chair was shifted 20 ° to the right, then the eyes oscillated between their central gaze position and 40 ° left, and likewise when the chair was facing 20 ° to the left, the eyes moved in the same way but from their central gaze position to 40 ° right. (Note that the oculogram gain loses its linearity for orbital positions beyond the range ± 25°.) Although the animal's tracking performance left much to be desired, it is nonetheless clear that the unit's modulation was greatest when the eyes were oscillating in the left-hand side of the orbits and indeed was fairly weak when the eyes were making similar movements in the right-hand side; this might, of course, merely reflect a non-linear position relationship for this neurone, but closer scrutiny reveals that there was no tight coupling between eye position and firing rate in the three conditions so that a given firing rate does not uniquely encode a given orbital position. In particular, it is clear that the modulation minima are very similar in the three cases even though the eyes are in very different positions each time. Such apparently puzzling relationships would seem to indicate that the activity of these neurones is related to some behaviour which is closely associated with eye movements in some contexts but not others. Subsequent measurements of head torque, as an index of attempted head movements by the animal, revealed that the monkey was often attempting to move his head in association with his eyes. However, because there can be considerable variability from time to time, a more definitive answer to the question of whether these neurones relate to attempted head movements must await simultaneous recordings of unit activity and head torque. For the present, however, it probably represents the simplest working hypothesis. In conclusion, it is clear that there are neurones within the vestibular nuclei whose activity is always strongly coupled to eye movements and reflects various aspects of oculomotor firing patterns and which might therefore be involved in programming eye movements. On the other hand, under the special circumstances of the present experiments some neurones showed activity which seemed to correlate with eye movements in some situations and not in others, and hence are unlikely to be involved in oculomotor programming and there is reason to believe that they may in fact be involved in the programming of head movements. The work reported here was done whilst the author was a Visiting Fellow in the Laboratory of Neurophysiology, NIMH, NIH, and was supported in part by a Fight for Sight Postdoctoral Research Fellowship from Fight for Sight, Inc., New York City, and in part by a fellowship from the Foundations' Fund for Research in Psychiatry.

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1 BIZZI, E., KALIL, R. E., AND TAGLIASCO, V., Eye-head coordination in monkeys: Evidence for centrally patterned organization, Science, 173 (1971) 452-454. 2 DUENS]NG, F., UND SCHAEFER, K.-P., Die Aktivit~it einzelner Neurone im Bereich der Vestibulariskerne bei Horizontalbeschleunigungen unter besonderer Ber/icksichtigung des vestibul~iren Nystagmus, Arch. Psychiat. Nervenkr., 198 (1958) 225-252. 3 DUENSING, F., UND SCHAEFER, K.-P., Die Neuronenaktivit/it in der Formatio reticularis des Rhombencephalons beim vestibul~iren Nystagmus, Arch. Psychiat. Nervenkr., 196 (1957) 265-290. 4 FERNANDEZ, C-, AND GOLDBERG, J. M., Physiology of peripheral neurons innervating the semicircular canals of the squirrel monkey. II. The response to sinusoidal stimulation and the dynamics of the peripheral vestibular system, J. Neurophysiol., 34 (1971) 661-675. 5 FUCHS~ A. F., AND LUSCHEI, E. S., Firing patterns of abducens neurons of alert monkeys in relationship to horizontal eye movement, J. Neurophysiol., 33 (1970) 382-392. 6 FUCHS, A. F., AND LUSCHE1, E. S., The activity of single trochlear nerve fibers during eye movements in the alert monkey, Exp. Brain Res., 13 (1971) 78-89. 7 HENN, V., AND COHEN, B., Quantitative analysis of activity in eye muscle motoneurons during saccadic eye movements and positions of fixation, J. Neurophysiol., 36 (1973) I 15-126. 8 LUSCHEI, E. S., AND FUCHS, A. F., Activity of brainstem neurones during eye movements of alert monkeys, J. Neurophysiol., 35 (1972) 445-461. 9 MATSUNAMI, K.-I., Saccadic eye movement and neurons in the central gray area in awake monkeys, Brain Research, 38 (1972) 217 221. 10 MELVILLE JONES, G., Transfer function of labyrinthine volleys through the vestibular nuclei. In A. BROOAL AND O. POMPEIANO(Eds.), Basic Aspects of Central Vestibular Mechanisms, Progress in Brain Research, Vol. 37, Elsevier, Amsterdam, t972, pp. 139-156. 11 ROBINSON, D. A., The oculomotor control system: a review, Proc. 1EEE, 56 (1968) 1032-1049. 12 ROBINSON, D. A., Oculomotor unit behavior in the monkey, J. Neurophysiol., 33 (1970) 393-404. 13 SCrimLER, P. H., The discharge characteristics of single units in the oculomotor and abducens nuclei of the unanesthetized monkey, Exp. Brain Res., 10 (1970) 347-362. 14 SPARKS, D. L., ANt) TRAVlS, R. P., JR., Firing patterns of reticular formation neurons during horizontal eye movements, Brain Research, 33 (1971) 477-481. 15 SPI~EL, E., Physio-pathotogy of voluntary and reflex innervation of ocular movements, Arch. Ophthal., 8 (1932) 738-753. 16 UEMURA, T., ANt) COHEN, B., Vestibulo-ocular reflexes: effects of vestibular nuclear lesions. In A. BROt)AL AND O. POMPmANO (Eds.), Basic Aspects of Central Vestibular Mechanisms, Progress in Brain Research, Vol. 37, Elsevier, Amsterdam, 1972, pp. 515-528.