Partial restitution of lesion-induced deficits in the horizontal vestibulo-ocular reflex performance measured from the bilateral abducens motor output in frogs

Summary The responses of the bilateral abducens nerves to small table velocity steps in the dark were measured in four groups of animals: One group was intact prior to recording (controls), one group was hemi-labyrinthectomized the day before the recordings (acute HL), the horizontal canal nerve was sectioned the day before the recordings (acute HCN) in another and the last group was hemilabyrinthectomized between 60 and 90 days prior to recording (chronic HL). In controls (N = 6) the slopes of the change in discharge rate to increasingly larger velocity steps increased maximally with about 200 imp/s per 1°/s and decreased maximally with about –60 imp/s per 1°/s. This difference is explained by low resting rates and by recruitment of spontaneously inactive vestibular afferent, central vestibular and abducens neurons. Results obtained from acute HL (N = 4) and acute HCN (N = 4) animals were practically identical. In neither case was a spontaneous nystagmic activity pattern observed. Results differed from those obtained in controls due to an asymmetric reduction in responsiveness. Comparison of the slopes of the evoked increases and decreases in discharge rates of abducens nerves to increasingly larger velocity steps with those in controls show that normal abducens responses are predominantly controlled by crossed excitation and by uncrossed inhibition. Disinhibition and disfacilitation play minor roles. In chronic HL animals (N = 6) that had posturally recovered to a similar degree, responses evoked by steps towards the intact side at larger velocity steps were slightly reduced with respect to those in acute HL or HCN animals. Responses evoked by steps towards the lesioned side differed between individuals. They were either similar to those in controls (N = 1), to those in acute animals (N = 2) or lay between these two extremes (N = 3). The improvement in response to velocity steps towards the lesioned side in 4 of 6 animals is explained by an increase in activity released by disinhibition. This inhibition in turn is controlled by horizontal canal-dependent input from the intact side. Plugging of this canal abolished all direction-specific responses in this plane in the dark, suggesting that the partial restitution of function of horizontal reflex performance depends exclusively on signals derived from receptors of this canal.Prof. Precht died on March 12, 1985     

Physiological and behavioral identification of vestibular nucleus neurons mediating the horizontal vestibuloocular reflex in trained rhesus monkeys.

1. To describe in detail the secondary neurons of the horizontal vestibuloocular reflex (VOR), we recorded the extracellular activity of neurons in the rostral medial vestibular nucleus of alert, trained rhesus monkeys. On the basis of their activity during horizontal head and eye movements, neurons were divided into several different types. Position-vestibular-pause (PVP) units discharged in relation to head velocity, eye velocity, eye position, and ceased firing during some saccades. Eye and head velocity (EHV) units discharged in relation to eye velocity and head velocity in the same direction so that the two signals partially canceled during the VOR. Two cell types discharged in relation to eye position and velocity but not head velocity; other types discharged in relation to head velocity only. 2. The position in the neural path from the primary vestibular afferents to abducens motoneurons was examined for each type. Direct input from the vestibular nerve was indicated if the cell could be activated by shocks to the nerve at latencies less than or equal to 1.4 ms. A projection to abducens motoneurons was indicated if spike-triggered averaging of lateral rectus electromyographic (EMG) activity yielded responses with a sharp onset at monosynaptic latencies. 3. PVP neurons were the principal interneuron in the VOR "three-neuron arc." Eighty percent received primary afferent input, and 66% made excitatory connections with contralateral abducens motoneurons. Surprisingly few, approximately 11%, made inhibitory connections with ipsilateral abducens motoneurons. This imbalance in the ipsi- and contralateral projections was confirmed by measuring the EMG activity evoked by electrical microstimulation in regions where PVP neurons were located. 4. EHV neurons whose activity increased during contralaterally directed head or eye movements were also interneurons in the ipsilateral inhibitory pathway. Eighty-nine percent received ipsilateral primary afferent input, and 25% projected to ipsilateral abducens motoneurons. EHV neurons excited during ipsilateral movements received neither direct primary afferent input nor projected to either abducens nucleus. A small proportion of each of two other cell types having sensitivity to contralateral eye position made excitatory connections with contralateral abducens motoneurons. Other types rarely were activated from the eighth nerve or projected to the abducens nucleus. 5. The significance of the connections of VOR interneurons and the signals they convey is discussed for three situations: smooth pursuit of a moving target, suppression of the VOR, and the VOR itself. PVP neurons convey a signal with a ratio of eye position and velocity components that is inappropriate to drive motoneurons during pursuit or the VOR.(ABSTRACT TRUNCATED AT 400 WORDS)     

Electrical activity of the lateral rectus muscle and abducens nerve during unconditioned eye retraction induced by corneal stimulation in the cat

Horizontal eye movements, the electromyogram of the lateral rectus muscle and the evoked electroneurogram of the VIth nerve were recorded in the alert cat during air puff stimulation of the cornea. A burst of activity was observed in the lateral rectus muscle following air puff stimulation of the ipsilateral or contralateral eye. This activity produced rotational eye movement. The VIth nerve produced two volleys of activity that were interpreted as the R1 and R2 parts of the reflex. It can be concluded that the lateral rectus muscle participates in the ocular retraction following trigeminal stimulation. It is further suggested that motoneurons in the main abducens nucleus participate in the corneal reflex, permitting several final pathways for conditioned and unconditioned nictitating membrane extension.     

In vitro eye-blink reflex model: role of excitatory amino acids and labeling of network activity with sulforhodamine

Evidence is presented suggesting that the neural correlate of the eye-blink reflex can be evoked in an in vitro brainstem-cerebellum preparation from the turtle by using electrical rather than natural stimulation of cranial nerve inputs. Abducens nerve discharge is triggered by brief electrical stimulation of the ipsilateral trigeminal nerve. This discharge corresponds behaviorally to EMG recordings of extraocular muscles and eye retraction recorded in situ, in a reduced preparation. The abducens nerve discharge has two components: a short-duration response having a latency of 3–6 ms and a duration of 50-100 ms, followed by a long-duration component having a latency of 12–20 ms and a duration of several seconds. The long-duration component of the reflex is blocked by the NMDA receptor antagonist APV, while both reflex responses are blocked by the non-NMDA glutamate receptor antagonist CNQX. To visualize the spatial distribution of activity during the abducens nerve reflex, bath application of the activity-dependent dye sulforhodamine was used. During reflex activity, neurons in the ipsilateral trigeminal nucleus, principal abducens nucleus, and presumed interneurons ventrolateral to the principal abducens nucleus, labeled with the dye, in addition to areas in the raphe nucleus and reticular formation. In conditions where the long-duration component of the reflex was suppressed, sulforhodamine label was absent in the principal abducens nucleus and in the caudal brainstem. From these data it is hypothesized that the region of interneurons and the accessory abducens nucleus participate in the short-duration component of the reflex. This response is mediated by non-NMDA receptors. The principal abducens nucleus is postulated to contribute also to the short-duration portion of the reflex, but is primarily involved in the generation of the long-duration component. This component of the reflex is mediated principally by NMDA receptors. Sustained reflex activity is further postulated to originate from recurrent excitation in pathways within the caudal brainstem, particularly the reticular formation. This interpretation is consistent with the observed patterns of sulforhodamine label, the effects of local microinjections of APV, and the elimination of sustained activity when the caudal brainstem is transected. These data have implications for pathways that may underlie conditioning of the eye-blink response.     

Direction-specific differences in the magnitude of abducens nerve responses during off-vertical axis rotation are a basic property of the utriculo-ocular reflex in frogs

Abducens nerve multiunit responses were recorded in darkness from decerebrated frogs during steps of angular velocity about an axis tilted with respect to the earth vertical (off-vertical axis rotation, OVAR). Thereby, a rotating gravity vector activated utricular hair cells and modulated the abducens nerve discharge sinusoidally as a function of head position in space. As expected, a bias velocity response component and nystagmus-related changes in neural activity were absent, since frogs do not possess a functioning velocity storage mechanism. Responses increased as a function of the tilt angle and of the velocity and direction of the platform rotation. OVAR in the direction of the recorded abducens nerve (clockwise for the right and counterclockwise for the left abducens nerve) evoked significantly smaller responses than rotation in the opposite direction. The possible origin of these direction-specific response properties was further studied after lesioning various structures assumed to modify utriculo-ocular reflexes. Each of these lesions (ipsilateral hemilabyrinthectomy, cerebellectomy, contralateral canal nerve sections) had a specific effect on the recorded response properties, but none of them, nor combinations thereof, abolished the direction-specific characteristics of the responses as long as the contralateral utricular nerve branch remained intact. Our results demonstrate that direction-specificity is a property of the basic utriculo-ocular reflex that is independent of the velocity storage mechanism in the brainstem, of the intervestibular commissural system, of the inhibitory control by the cerebellum and of the central convergence of utricular and horizontal canal inputs. A simple, unidirectional interaction between central utricular neurons with adjacent functional polarization vectors is suggested as the basic element for the observed direction specificity.     

European vestibular experiments on the Spacelab-1 mission: 6. Yaw axis vestibulo-ocular reflex

Summary In two Spacelab-1 crew members the lateral eye movements evoked by active angular oscillation of the head in yaw at 1 Hz were recorded in-flight and post-flight. In one, the responses to passive angular oscillation in yaw at 0.2–1 Hz were also studied pre and post-flight. In the absence of visual fixation there was no significant change in the gain of either the active or passive vestibulo-ocular reflex (VOR) attributable to exposure to microgravity. However, when the subject fixated on a visual target that moved with his head the suppressed VOR gain was lower on the first post-flight test (performed 16 h after landing) than that obtained pre-flight or on subsequent post-flight tests.     

Long-term deficits in otolith, canal and optokinetic ocular reflexes of pigmented rats after unilateral vestibular nerve section

 Static and dynamic otolith, horizontal vestibular and optokinetic ocular reflexes were investigated in pigmented rats 1–6 and more months after unilateral vestibular nerve (UVN) section. Evoked responses were compared with published data from control rats studied under identical conditions. Static lateral tilt of UVN rats in the light evoked a vertical deviation in static eye position that was as large as in controls. In darkness, the evoked responses in UVN rats 6 months after the lesion were consistently smaller than in controls. Linear horizontal acceleration in darkness evoked vertical and torsional response components in UVN rats that were parallel-shifted towards lower gains and larger phase lags. Off-vertical axis rotation on a platform provoked responses that differed markedly from those recorded in intact rats with respect to the bias velocity component. These results suggest a permanent deficiency in the static and dynamic otolith-ocular reflex performance of UVN rats. Ocular responses to horizontal table velocity steps in darkness exhibited a direction-specific asymmetry in UVN rats. Step responses evoked by acceleration towards the intact side were larger in gain and longer in duration than responses evoked by acceleration towards the operated side. When compared with control data, responses to either side were reduced in UVN rats and the velocity store mechanism was barely activated by velocity steps towards the operated side. Responses evoked by horizontal optokinetic stimulation with constant pattern velocities were below control values in either direction. Slow-phase eye velocity saturated at much lower values than in intact rats, particularly during pattern motion towards the intact side. The duration of the optokinetic afternystagmus was asymmetrically reduced with respect to control data. Practically identical reductions in duration were found for vestibulo-ocular responses in the opposite directions. Behaving animals exhibited no obvious impairment in their spontaneous locomotory or exploratory activities. However, each UVN rat was impaired, even 2 years after the lesion, in its postural reaction to being lifted by the tail in the air. This observation suggests the presence of a permanent deficit in static and dynamic otolith-spinal reflexes that may be substituted on the ground by proprioceptive inputs. Received: 26 February 1997 / Accepted: 2 July 1997     

Role of proprioception in the control of lid position during reflex and conditioned blink responses in the alert behaving cat

The contribution of the orbicularis oculi muscle to the determination of lid position, and the putative role of eyelid proprioception in the control of reflex and conditioned eye blinks, were studied in alert behaving cats. Upper lid movements and the electromyographic activity of the orbicularis oculi muscle were recorded during reflexively evoked blinks and during the classical conditioning of the eyelid response. Blinks were evoked by air puffs, flashes and electrical stimulation of the supraorbitary branch of the trigeminal nerve. Eyelid responses were conditioned with a trace classical conditioning paradigm consisting of a short, weak air puff, followed 250 ms later by a long, strong air puff. Orbicularis oculi muscle activation during reflex blinks was independent of lid position and was not modified by the presence of weights acting in the upward or downward directions. Local anesthesia of the supraorbital nerve reduced blinks evoked by air puffs applied to the lower jaw, but did not affect flash-evoked blinks. No relationship was established between initial lid position and the first downward component of conditioned eyelid responses. In contrast, initial lid position was related to the first upward component of the same conditioned response.

It is concluded that orbicularis oculi motor units receive no feedback proprioceptive signals from the eyelid, other than those coming from cutaneous receptors, and that lid position is determined by the activity of the levator palpebrae superioris muscle. The lack of sensory information about lid position in facial motoneurons probably has some functional implications on the central control of cognitive and emotional facial expressions.     

Behavior of neurons in the abducens nucleus of the alert cat--III. Axotomized motoneurons

The effects of peripheral and central VIth nerve axotomy on abducens nucleus synaptic potentials of vestibular origin and the ultrastructure of intracellularly labeled abducens motoneurons were examined in the anesthetized cat. Subsequent experiments explored the activity of identified abducens motoneurons during spontaneous and vestibular induced eye movements in alert cats prepared for chronic recordings of eye movements, single units and field potentials. Following axotomy the typical disynaptic inhibition of abducens motoneurons induced by electrical stimulation of the ipsilateral vestibular nerve either disappeared or was reduced for 5-30 days. Disynaptic activation produced by contralateral VIIIth nerve stimulation was apparently not affected. These changes were accompanied at the ultrastructural level by a decrease of axosomatic pleiomorphic synaptic endings. No changes were observed in either the number or distribution of synaptic endings on proximal and distal dendrites. Although not expected by results obtained in acute experiments, axotomized motoneurons showed a decreased excitability in the behavioral paradigm. Amplitude of the abducens antidromic field potential was significantly reduced 4-6 days following axotomy and frequent failures were observed in the antidromic somadendritic invasion of single motoneurons. Somatic invasion was obtained by the simultaneous presentation of appropriate visual and/or vestibular synaptic activity. Chronic recordings of field potentials showed their amplitude to recover in 30-40 days. The spontaneous and vestibular induced activity of identified axotomized motoneurons during this period of time differed in several aspects from controls. Motoneurons could not maintain tonic activity during eye fixations and they showed short, low frequency, bursts of activity that followed, rather than preceded, on-directed saccades. In some cases axotomized motoneurons fired during horizontal off-directed and vertical saccades. Position and velocity gains of axotomized motoneurons were lower than control values. The effects of central axotomy were always larger and of longer duration than those following peripheral axotomy. Structural and functional properties influenced by axotomy seemed to recover in 2-3 months, but with independent time courses. The present results differ in many aspects from those described after axotomy in spinal and hypoglossal motoneurons. In addition, they point out that behavior or axotomized neurons in chronic preparations are not predictable on the basis of those described in acute experiments.     

Effects of kainic acid lesions of the nucleus reticularis tegmenti pontis on fast and slow phases of vestibulo-ocular and optokinetic reflexes in the pigmented rat

Summary The nucleus reticularis tegmenti pontis (NRTP) and adjacent pontine reticular formation were lesioned chemically using the neurotoxic agent kainic acid, and the effects of these lesions on horizontal ocular optokinetic and vestibular nystagmus were examined. Eye position was measured in the alert, NRTP-lesioned animals with the electromagnetic search coil technique. Optokinetic and vestibular stimuli consisted of steps of rotations or sinusoidal oscillations of a fullfield visual pattern surrounding the animal or of the animal in total darkness, respectively. In a first group of animals, small unilateral NRTP lesions were produced by placing a single kainic acid injection in the area of the left NRTP. In one third of the animals, ipsilateral quick phases of optokinetic and vestibular nystagmus were abolished. In the remaining animals, quick phases were deficient to various degrees or not affected at all. There were no changes in the characteristics of optokinetic step responses to ipsilateral pattern rotations which activate predominantly optokinetic pathways on the side of the brainstem lesion. In animals with ipsiversive quick phase deficits, contralateral pattern rotations elicited tonic eye deviations. In a second group of animals, large uni- or bilateral lesions were produced by injecting kainic acid into three separate rostral, middle and caudal levels of the right NRTP. These animals had uni- or bilateral quick phase deficits during optokinetic and vestibular nystagmus. Optokinetic nystagmus in response to velocity steps of pattern rotation towards the lesion side was strongly reduced in gain even in those animals that had no apparent deficits in the fast contraversive reset phases. In four out of six animals, responses to sinusoidal optokinetic pattern oscillations were reduced in gain and showed increased phase lags compared to controls. Vestibulo-ocular responses to velocity steps of head rotations were of normal gain but reduced in duration (measured from onset of stimulation to reversal of nystagmus). Sinusoidal vestibulo-ocular responses evoked by head oscillations exhibited reduced gain values and strongly increased phase leads in the frequency range below 0.5 Hz. The vestibular time constant was found to be around 4.5 s in animals with NRTP lesions compared to about 7.5 s in control animals. The present results show that large kainic acid lesions of the NRTP (and adjacent area) do not abolish optokinetic eye movements in the rat, in contrast to what has been reported after electrolytic lesions. The data suggest, however, that there is a failure of slow build-up of OKN slow phase velocity as well as a shortening of the vestibular time constant which correlates with the kainic acid lesions extending into rostromedial and caudal parts of the NRTP. The implications of these findings with respect to an involvement of these structures in velocity storage are discussed.Abbreviations CN cochlear nucleus - DpSC decussation, peduncle, superior, cerebellar - ip interpeduncular nucleus - MLF medial longitudinal fasciculus - NOT nucleus of optic tract - NRTPc nucleus reticularis tegmenti pontis, central subdivision - NRTPp nucleus reticularis tegmenti pontis, pericentral subdivision - p pontine nuclei - ph praepositus hypoglossi nucleus - pMC peduncle, middle cerebellar - pSC peduncle, superior cerebellar - Pyr pyramidal tract - Rcs raphe central superior - Rm raphe magnus - rpc reticular nucleus, pontine, caudal - rpo reticular nucleus, pontine, oral - TB trapezoid body - tM trapezoid nucleus, medial - tGd tegmental nucleus of von Gudden, dorsal - tGv tegmental nucleus of von Gudden, ventral - 5 trigeminal tract or trigeminal nerve - 5m mesencephalic trigeminal nucleus - 5mt motor trigeminal nucleus - 6n abducens nucleus - 7 facial nerve Prof. W. Precht died on March 12, 1985     

Floccular modulation of vestibuloocular pathways and cerebellum-related plasticity: An in vitro whole brain study

The isolated whole brain (IWB) preparation of the guinea pig was used to investigate the floccular modulation of vestibular-evoked responses in abducens and oculomotor nerves and abducens nucleus; for identification of flocculus target neurons (FTNs) in the vestibular nuclei and intracellular study of some of their physiological properties; to search for possible flocculus-dependent plasticity at the FTN level by pairing of vestibular nerve and floccular stimulations; and to study the possibility of induction of long-term depression (LTD) in Purkinje cells by paired stimulation of the inferior olive and vestibular nerve. Stimulation of the flocculus had only effects on responses evoked from the ipsilateral (with respect to the stimulated flocculus) vestibular nerve. Floccular stimulation significantly inhibited the vestibular-evoked discharges in oculomotor nerves on both sides and the inhibitory field potential in the ipsilateral abducens nucleus while the excitatory responses in the contralateral abducens nerve and nucleus were free from such inhibition. Eleven second-order vestibular neurons were found to receive a short-latency monosynaptic inhibitory input from the flocculus and were thus characterized as FTNs. Monosynaptic inhibitory postsynaptic potentials from the flocculus were bicuculline sensitive, suggesting a GABA(A)-ergic transmission from Purkinje cells to FTNs. Two of recorded FTNs could be identified as vestibulospinal neurons by their antidromic activation from the cervical segments of the spinal cord. Several pairing paradigms were investigated in which stimulation of the flocculus could precede, coincide with, or follow the vestibular nerve stimulation. None of them led to long-term modification of responses in the abducens nucleus or oculomotor nerve evoked by activation of vestibular afferents. On the other hand, pairing of the inferior olive and vestibular nerve stimulation resulted in approximately a 30% reduction of excitatory postsynaptic potentials evoked in Purkinje cells by the vestibular nerve stimulation. This reduction was pairing-specific and lasted throughout the entire recording time of the neurons. Thus in the IWB preparation, we were able to induce a LTD in Purkinje cells, but we failed to detect traces of flocculus-dependent plasticity at the level of FTNs in vestibular nuclei. Although these data cannot rule out the possibility of synaptic modifications in FTNs and/or at other brain stem sites under different experimental conditions, they are in favor of the hypothesis that the LTD in the flocculus could be the essential mechanism of cellular plasticity in the vestibuloocular pathways.     

Spacing practice sessions across days earlier rather than later in training improves performance of a visuomotor skill

Reduced depression of transmitter release from Ia afferents following previous activation (post-activation depression) has been suggested to be involved in the pathophysiology of spasticity. However, the effect of this mechanism on the myotatic reflex and its possible contribution to increased reflex excitability in spastic participants has not been tested. To investigate these effects, we examined post-activation depression in Soleus H-reflex responses and in mechanically evoked Soleus stretch reflex responses. Stretch reflex responses were evoked with consecutive dorsiflexion perturbations delivered at different intervals. The magnitude of the stretch reflex and ankle torque response was assessed as a function of the time between perturbations. Soleus stretch reflexes were evoked with constant velocity (175°/s) and amplitude (6°) plantar flexion perturbations. Soleus H-reflexes were evoked by electrical stimulation of the tibial nerve in the popliteal fossa. The stretch reflex and H-reflex responses of 30 spastic participants (with multiple sclerosis or spinal cord injury) were compared with those of 15 healthy participants. In the healthy participants, the magnitude of the soleus stretch reflex and H-reflex decreased as the interval between the stimulus/perturbation was decreased. Similarly, the stretch-evoked torque decreased. In the spastic participants, the post-activation depression of both reflexes and the stretch-evoked torque was significantly smaller than in healthy participants. These findings demonstrate that post-activation depression is an important factor in the evaluation of stretch reflex excitability and muscle stiffness in spasticity, and they strengthen the hypothesis that reduced post-activation depression plays a role in the pathophysiology of spasticity.     

Visual vestibular interaction: vestibulo-ocular reflex suppression with head-fixed target fixation

Summary In order to maintain clear vision, the images on the retina must remain reasonably stable. Head movements are generally dealt with successfully by counterrotation of the eyes induced by the combined actions of the vestibulo-ocular reflex (VOR) and the opto-kinetic reflex. We have studied how, in humans, the VOR gain (VORG) is modulated to provide appropriate eye movements in two situations: 1. fixation of a stationary object of the visual space while the head moves. This requires a visuo-vestibulo-ocular reaction to induce eye movements opposite in direction, and equal in velocity to head movements, and 2. fixation of an object moving with the head. Here, the visuo-vestibulo-ocular reaction should be totally suppressed. These two situations were compared to a basic condition in which, to induce pure VOR, the subjects (Ss) in darkness were not allowed a visual target. Eye movements were recorded in seated Ss during constant amplitude sinusoidal and pulse-like passive rotations applied around the vertical axis. Subjects were in total darkness (DARK condition) and performing mental arithmetic. Alternatively, they were provided with a small target, either stationary with respect to earth (earth-fixed target: EFT), or moving with them (chairfixed-target: CFT). The sinusoidal rotation experiment was used as baseline for the ensuing experiments and yielded control data in agreement with the literature. In particular, rotation in the dark showed a VORG of 0.6. With, for example, 0.8 s passive pulse rotations, typical responses in all three visual conditions were rigorously identical during the first 150 to 180 ms. They showed a delay of about 16 ms of the eye behind the head with no significant difference between passive whole-body and passive head-alone rotations. In all conditions, once the eyes had started to move, a rapid increase in eye velocity was observed during 75 to 80 ms, after which, the average VORG was 0.9 ± 0.15. During the following 50 to 100 ms, the gain remained around 0.9 in all three conditions. Beyond 180 ms, the VORG remained around 0.9 in DARK, increased slowly towards 1 or decreased towards zero in the EFT and CFT conditions, respectively. The time-course of these later events suggests that visual tracking mechanisms came into play to reduce retinal slip through smooth pursuit. Sinusoidal rotations, extensively used in VOR studies, do not seem to be a satisfactory stimulus to rapidly and precisely characterize VOR function, particularly in pathological cases. Our data suggest that rapid transient rotations are more appropriate.     

Eye movement responses to combined linear and angular head movement

Summary Lateral eye movements evoked by linear head motion were evaluated in human subjects by subtracting the eye movement responses to headcentred angular oscillation in the dark, about a vertical axis, from the responses evoked by similar oscillation with the head displaced 30 cm eccentrically from the axis. The centred oscillation gave a purely angular stimulus whereas the eccentric oscillation gave an additional tangential linear acceleration acting laterally to the head. The stimuli used were relatively unpredictable, enveloped sinewaves at 0.02 to 1.2 Hz, 60°/s peak angular velocity, 0.004 to 0.24 g peak tangential acceleration, and subjects were either given no instructions or were told to imagine fixating on targets at 60 cm or 5 m distance. Eye movements of significantly higher velocity were evoked in the eccentric position, particularly at the higher frequencies and when subjects imagined near targets. The increase in velocity of eye movement was attributed to the linear stimulus and probably derives from stimulation of the otolith organs. The frequency response of the gain (°/s/g) of these movements gave an approximate slope of –1, indicating that the eye velocity bears a constant proportionality to linear head velocity. The findings are in accord with the theoretical prediction that eye movements compensating for linear head motion should only be required for viewing near targets. These otolithic influences on eye movements could either the mediated by a direct otolith-ocular reflex which is subservient to viewing conditions or, alternatively, the otolith signals may modify the activity of other oculomotor mechanisms.A. M. Bronstein was supported by The Brain Research Trust     

Three-dimensional organization of vestibular-related eye movements to off-vertical axis rotation and linear translation in pigeons

During linear accelerations, compensatory reflexes should continually occur in order to maintain objects of visual interest as stable images on the retina. In the present study, the three-dimensional organization of the vestibulo-ocular reflex in pigeons was quantitatively examined during linear accelerations produced by constant velocity off-vertical axis yaw rotations and translational motion in darkness. With off-vertical axis rotations, sinusoidally modulated eye-position and velocity responses were observed in all three components, with the vertical and torsional eye movements predominating the response. Peak torsional and vertical eye positions occurred when the head was oriented with the lateral visual axis of the right eye directed orthogonal to or aligned with the gravity vector, respectively. No steady-state horizontal nystagmus was obtained with any of the rotational velocities (8–58°/s) tested. During translational motion, delivered along or perpendicular to the lateral visual axis, vertical and torsional eye movements were elicited. No significant horizontal eye movements were observed during lateral translation at frequencies up to 3 Hz. These responses suggest that, in pigeons, all linear accelerations generate eye movements that are compensatory to the direction of actual or perceived tilt of the head relative to gravity. In contrast, no translational horizontal eye movements, which are known to be compensatory to lateral translational motion in primates, were observed under the present experimental conditions. Received: 29 January 1999 / Accepted: 14 June 1999     

Discharge profiles of abducens, accessory abducens, and orbicularis oculi motoneurons during reflex and conditioned blinks in alert cats

The discharge profiles of identified abducens, accessory abducens, and orbicularis oculi motoneurons have been recorded extra- and intracellularly in alert behaving cats during spontaneous, reflexively evoked, and classically conditioned eyelid responses. The movement of the upper lid and the electromyographic activity of the orbicularis oculi muscle also were recorded. Animals were conditioned by short, weak air puffs or 350-ms tones as conditioned stimuli (CS) and long, strong air puffs as unconditioned stimulus (US) using both trace and delayed conditioning paradigms. Motoneurons were identified by antidromic activation from their respective cranial nerves. Orbicularis oculi and accessory abducens motoneurons fired an early, double burst of action potentials (at 4-6 and 10-16 ms) in response to air puffs or to the electrical stimulation of the supraorbital nerve. Orbicularis oculi, but not accessory abducens, motoneurons fired in response to flash and tone presentations. Only 10-15% of recorded abducens motoneurons fired a late, weak burst after air puff, supraorbital nerve, and flash stimulations. Spontaneous fasciculations of the orbicularis oculi muscle and the activity of single orbicularis oculi motoneurons that generated them also were recorded. The activation of orbicularis oculi motoneurons during the acquisition of classically conditioned eyelid responses happened in a gradual, sequential manner. Initially, some putative excitatory synaptic potentials were observed in the time window corresponding to the CS-US interval; by the second to the fourth conditioning session, some isolated action potentials appeared that increased in number until some small movements were noticed in eyelid position traces. No accessory abducens motoneuron fired and no abducens motoneuron modified their discharge rate for conditioned eyelid responses. The firing of orbicularis oculi motoneurons was related linearly to lid velocity during reflex blinks but to lid position during conditioned responses, a fact indicating the different neural origin and coding of both types of motor commands. The power spectra of both reflex and conditioned lid responses showed a dominant peak at approximately 20 Hz. The wavy appearance of both reflex and conditioned eyelid responses was clearly the result of the high phasic activity of orbicularis oculi motor units. Orbicularis oculi motoneuron membrane potentials oscillated at approximately 20 Hz after supraorbital nerve stimulation and during other reflex and conditioned eyelid movements. The oscillation seemed to be the result of both intrinsic (spike afterhyperpolarization lasting approximately 50 ms, and late depolarizations) and extrinsic properties of the motoneuronal pool and of the circuits involved in eye blinks.     

Eye movements evoked by proprioceptive stimulation along the body axis in humans

Proprioceptive input arising from torsional body movements elicits small reflexive eye movements. The functional relevance of these eye movements is still unknown so far. We evaluated their slow components as a function of stimulus frequency and velocity. The horizontal eye movements of seven adult subjects were recorded using an infrared device, while horizontal rotations were applied at three segmental levels of the body [i.e., between head and shoulders (neck stimulus), shoulders and pelvis (trunk stimulus), and pelvis and feet (leg stimulus)]. The following results were obtained: (1) Sinusoidal leg stimulation evoked an eye response with the slow component in the direction of the movement of the feet, while the response to trunk and neck stimulation was oriented in the opposite direction (i.e., in that of the head). (2) In contrast, the gain behavior of all three responses was similar, with very low gain at mid- to high frequencies (tested up to 0.4 Hz) but increasing gain at low frequencies (down to 0.0125 Hz). We show that this gain behavior is mainly due to a gain nonlinearity for low angular velocities. (3) The responses were compatible with linear summation when an interaction series was tested in which the leg stimulus was combined with a vestibular stimulus. (4) There was good correspondence of the median gain curves when eye responses were compared with psychophysical responses (perceived body rotation in space; additionally recorded in the interaction series). However, correlation of gain values on a single-trial basis was poor. (5) During transient neck stimulation (smoothed position ramp), the neck response noticeably consisted of two components – an initial head-directed eye shift (phasic component) followed by a shift in the opposite direction (compensatory tonic component). Both leg and neck responses can be described by one simple, dynamic model. In the model the proprioceptive input is fed into the gaze network via two pathways which differ in their dynamics and directional sign. The model simulates either leg or neck responses by selecting an appropriate weight for the gain of one of the pathways (phasic component). The interaction results can also be simulated when a vestibular path is added. This model has similarities to one we recently proposed for human self-motion perception and postural control. A major difference, though, is that the proprioceptive input to the gaze-stabilizing network is weak (restricted to low velocities), unlike that used for perception and postural control. We hold that the former undergoes involution during ontogenesis, as subjects depend on the functionally more appropriate vestibulo-ocular reflex. Yet, the weak proprioceptive eye responses that remain may have some functional relevance. Their tonic component tends to stabilize the eyes by slowly shifting them toward the primary head position relative to the body support. This applies solely to the earth-horizontal plane in which the vestibular signal has no static sensitivity. Received: 10 October 1997 / Accepted: 22 January 1998     

Effects of cerebellectomy on the cat's vertical vestibuloocular reflex

The effects of cerebellectomy on the semi-circular canal evoked responses recorded from individual vertical and oblique eye muscles were studied in cats anesthetized with Ketamine. The phase lag relative angular acceleration of the electromyographic response was consistantly smaller over the frequency range tested (0.02–1.0 Hz) in cerebellectomized than in intact animals. This finding indicates that the time constant of the central, neural integrator was shifted towards smaller values by the lesion.This was also suggested when the vertical eye movements generated by rotation about the pitch axis were recorded in the fully alert animal. In addition, the EOG data show that the phase of the VOR in the low frequency range was not altered following cerebellectomy suggesting that the macular influences were still present.When the EMG responses of the superior oblique (SO) and superior rectus (SR) muscles were studied in their presumed main mode, i.e. roll-canal and pitch-canal, respectively, no difference was noted in hemicerebellectomized animals when compared to intact control animals. However, when SO and SR were studied in pitch-canal and roll-canal rotation, respectively, dramatic changes in the response pattern were noted in lesioned animals.     

Postlesional vestibular reorganization improves the gain but impairs the spatial tuning of the maculo-ocular reflex in frogs

The ramus anterior (RA) of N.VIII was sectioned unilaterally. Two months later we analyzed in vivo responses of the ipsi- and of the contralesional abducens nerve during horizontal and vertical linear acceleration in darkness. The contralesional abducens nerve had become responsive again to linear acceleration either because of a synaptic reorganization in the vestibular nuclei on the operated side and/or because of a reinnervation of the utricular macula by regenerating afferent nerve fibers. Significant differences in the onset latencies and in the acceleration sensitivities allowed a separation of RA frogs in a group without and in a group with functional utricular reinnervation. Most important, the vector orientation for maximal abducens nerve responses was clearly altered: postlesional synaptic reorganization resulted in the emergence of abducens nerve responses to vertical linear acceleration, a response component that was barely detectable in RA frogs with utricular reinnervation and that was absent in controls. The ipsilesional abducens nerve, however, exhibited unaltered responses in either group of RA frogs. The altered spatial tuning properties of contralesional abducens nerve responses are a direct consequence of the postlesional expansion of signals from intact afferent nerve and excitatory commissural fibers onto disfacilitated 2nd-order vestibular neurons on the operated side. These results corroborate the notion that postlesional vestibular reorganization activates a basic neural reaction pattern with more beneficial results at the cellular than at the network level. However, given that the underlying mechanism is activity-related, rehabilitative training after vestibular nerve lesion can be expected to shape the ongoing reorganization.     

Spatial properties of vertical eye movement-related neurons in the region of the interstitial nucleus of Cajal in awake cats

Summary 1. Maximal activation directions of vertical burst-tonic and tonic neurons in the region of the interstitial nucleus of Cajal (INC) were examined in alert cats during vertical vestibulo-ocular reflex induced by sinusoidal rotation (at 0.11 Hz±10 deg, or 0.31 Hz±5 deg) in a variety of vertical planes using a null point analysis. The results were compared with the angles of anatomical and functional planes of vertical canals reported by Blanks et al. (1972) and Robinson (1982), and with the angles of vertical eye muscles measured in this study and by Ezure and Graf (1984). 2. Maximal activation directions of 23 cells (21 burst-tonic and 2 tonic neurons) were determined from their responses during rotation in 4 or more different vertical planes. All cells showed sinusoidal gain curves and virtually constant phase values except near the null regions, suggesting that their responses were evoked primarily by canal inputs. Phase values of 5 cells near the null regions depended on the rotation plane, suggesting additional otolith inputs. We used a measurement error range of ±10 deg for calculating the maximal activation directions from the null regions of individual cells and the values of error ranges of null calculation. Of the 23, the maximal activation directions of 7 cells were outside the measurement error ranges of vertical eye muscle angles and within the ranges of vertical canal angles (class A), those of 5 cells were within the ranges of eye muscle angles and outside the ranges of vertical canal angles (class B), and those of the remaining 11 cells were in the overlapping ranges for both angles (class C). Even if only the cells in which 5 or more measurement points were taken to determine maximal activation directions (n = 15), the results were similar. During vertical rotation with the head orientation +60 deg off the pitch plane, dissociation of cell activity and vertical compensatory eye movement was observed in 5 cells in class A or C that had null angles near +45 deg. These results suggest that the cells in class A and B carried individual vertical canal and oculomotor signals, respectively, although it is difficult to tell for the majority of cells (class C) which signals they reflected. Some cells in class A and C were antidromically activated from the medial longitudinal fasciculus at the level of abducens nucleus, suggesting that the signals carried by these cells may be sent to the lower brainstem. 3. Most burst-tonic neurons did not respond to horizontal rotation; significant responses were obtained in only 3 of 10 cells tested for which the gain was only 14–17% of their maximal vertical gain. There was no clear difference in gain or phase values of the responses to vertical rotation, or in eye position sensitivity (during spontaneous saccades) between cells whose responses coincided with individual vertical canal angles and those matching the angles of vertical recti muscles. The values of phase lag (re head acceleration during pitch rotation) and eye position sensitivity of these cells are still smaller compared to those of extraocular motoneurons reported by Delgado-Garcia et al. (1986), although they were larger than those of secondary vestibulo-ocular neurons (Perlmutter et al. 1988). All these results suggest that the signals carried by burst-tonic and tonic neurons in the INC region are different from oculomotor signals. 4. Similar analysis was done for comparison for 19 other cells that did not show close correlation with spontaneous eye movement but whose activity was clearly modulated by pitch rotation (pitch cells). More than a half (10/19) had maximal activation directions outside the measurement error ranges of individual vertical canal angles, and many shifted towards roll. Horizontal rotation produced responses with higher gain than burst-tonic neurons, suggesting a difference in the spatial response properties of burst-tonic and tonic neurons on one hand and pitch cells on the other.