Longterm impairment of cat optokinetic nystagmus following visual cortical lesions

Summary Binocular and monocular gain of optokinetic nystagmus (OKN), OKN dynamics, vestibulo-ocular reflex (VOR) and VOR adaptation were measured in 5 normal cats and in 5 cats which underwent bilateral visual cortical lesions involving the 17–18 complex at least 4 months before testing. We observed longterm deficits after bilateral lesions involving area 17 and variable parts of area 18 but failed to observe deficits after 18–19 lesions. These deficits were limited to the OKN gain and the build-up time constant of OKN; the VOR and the optokinetic after-nystagmus (OKAN) time constant were within normal limits. Our results suggest that areas 17–18 operate in parallel to control the encoding of retinal slip velocity at the level of the nucleus of the optic tract (NOT) and the accessory optic system (AOS), which are known to represent the initial stage of the optokinetic pathways.     

Single unit activity in the nucleus of the basal optic root (nBOR) during optokinetic,vestibular and visuo-vestibular stimulations in the alert pigeon (Columbia livia)

Summary Extracellular recordings were performed in the nucleus of the basal optic root (nBOR) of alert pigeons during optokinetic nystagmus (OKN), vestibulo-ocular reflex (VOR) and combined visuo-vestibular stimulation. Cell identification was assessed either by histological control or by electrophysiological testing (antidromic response to vestibulo-cerebellar or oculomotor complex stimulation). 1) OKN was induced in 8 directions by a binocular stimulation. During the fast phase of OKN, optokinetic after nystagmus (OKAN) or reversed OKAN, most cells showed an inhibition which varied in magnitude independent of the direction of stimulation. A few cells however showed a phasic discharge for some OKN directions. 2) During the slow phase of OKN induced by a binocular stimulation, cells displayed either a tonic activation or a more or less strong inhibition according to the direction of the OKN. Cells were classified in 4 groups, according to their degree of directional specificity. The best OKN direction (slow phase) for maximal cell activation was upwards and naso-upwards, and next to best, nasotemporal and downwards. Maximal cell inhibition occurred during downward, and for some cells during upward, directions. 3) During OKN induced by stimulating the eye contralateral to the recorded nBOR, cell responses resembled those obtained during binocular stimulation, but, during ipsilaterally induced OKN, the cells lost their directional specificity. As a result of binocular integration, neuronal activation seems to originate from contralateral input whereas cell inhibition would mainly come from ipsilateral input. 4) During sinusoidal optokinetic stimulation induced in the temporo downward-naso upward axis, cells showed a more or less marked modulation (according to their directional selectivity) that was closely in phase with the stimulation velocity, and therefore probably with retinal slip. 5) nBOR cells appeared generally unaffected during both the slow phase and the fast phase of the VOR. However, some cells showed a slight but irregular modulation which might imply a weak vestibular input. During visuo-vestibular stimulation, the response resembled that obtained with sinusoidal optokinetic stimulation but the fast phase inhibition was often strengthened in the downwards direction (fast phase).     

Effects of midline medullary lesions on velocity storage and the vestibulo-ocular reflex

Summary 1. Crossing fibers were sectioned at the midline of the medulla caudal to the abducens nucleus in four cynomolgus monkeys. In two animals the lesions caused the time constant of horizontal and vertical per- and post-rotatory nystagmus to fall to 5–8 s. The slow rise in optokinetic nystagmus (OKN), as well as optokinetic after-nystagmus (OKAN) and cross-coupling of horizontal to vertical OKN and OKAN were abolished. Steady state velocities could not be maintained during off-vertical axis rotation (OVAR). Pitch and yaw nystagmus were affected similarly. We conclude that the ability to store activity related to slow phase eye velocity, i.e., velocity storage, was lost in these monkeys for nystagmus about any axis. Velocity storage was partially affected by a small midline lesion in the same region in a third animal. There was no effect of a more superficial midline section in a fourth monkey, and it served as a control. 2. The gain (eye velocity/head velocity) of the vestibuloocular reflex (VOR) was unaffected by the midline lesions. Saccades were normal, as was the ability to hold the eyes in eccentric gaze positions. The gain of the fast component of OKN increased in one monkey to compensate for the loss of the slow component. 3. One animal was tested for its ability to adapt the gain of the VOR due to visual-vestibular mismatch after lesion. Average changes in gain in response to wearing magnifying (2.2 x) and reducing (0.5 x) lenses, were + 35% and — 30%, respectively. This is within the range of normal monkeys. Thus, a midline lesion that abolished velocity storage did not alter that animal's ability to adapt the gain of the VOR. 4. Lesions that reduced or abolished velocity storage interrupted crossing fibers in the rostral medulla, caudal to the abducens nuclei. Cells that contributed axons to this portion of the crossing fibers are most likely located in central portions of the medial vestibular nucleus (MVN) and/or in rostral portion of the descending vestibular nucleus (DVN). The implication is that velocity storage arises from neurons in MVN and DVN whose axons cross the midline.Supported by NS-00294, SFB 220-D8 and Core Center Grant EY-01867     

Unidirectional habituation of vestibulo-ocular responses by repeated rotational or optokinetic stimulations in the cat

Summary 1.Unilateral habituation of the vestibuloocular reflex was produced in adult cats stimulated by repeated unidirectional velocity steps (vestibular training) or by a continuously moving visual surround (optokinetic training). — 2. Unidirectional vestibular training produced a strong asymmetry of vestibuloocular responses (VOR). Responses to velocity steps applied to the trained labyrinth were decreased both in gain and in time-constant. This effect generalized to responses to sinusoidal oscillations (0.03 Hz to 0.1 Hz), i.e. to a stimulus not used during training. — No spontaneous nystagmus was ever observed in spite of the dynamic VOR asymmetry. — 3. Unilateral vestibular habituation produced by vestibular training appeared to be a long-lasting phenomenon. It was still present 10 days after the end of training. — 4. Optokinetic responses were not affected by vestibular training. — 5. Unidirectional optokinetic training produced an increase in the slow phase velocity of optokinetic nystagmus (OKN) by about 25% in both directions. This effect did not persist for more than a few minutes. A marked spontaneous nystagmus was recorded in the dark after each session of optokinetic training, with a slow phase in the direction opposite to the previous OKN. — 6. VOR in response to velocity steps and to sinusoidal oscillations were decreased unilaterally after optokinetic training. This effect was of short duration, however, and disappeared within the interval between training sessions. This lack of retention contrasted with the prolonged effect of vestibular training.Supported by INSERM (France) and by CNR (Italy)     

The eye movements of the dark-reared cat

Summary Cats reared in total darkness to adulthood have abnormal eye movements. A spontaneous nystagmus is found in the dark before any visual experience. The eye movements evoked by vestibular or optokinetic stimulation are less effective at compensation than for a normal cat. The vestibuloocular reflex (VOR) has a low gain (around 0.3) and a frequency dependent phase relation. The efficiency of optokinetic nystagmus (OKN) is poorer than for a normal cat, except for downwards stimulus movement which is followed better than normal. OKN is poorest in response to a stimulus viewed monocularly moving in the nasal to temporal direction. Neither VOR nor OKN of a dark-reared cat recover in efficiency within 5 months of the animal being brought into the light. A normal cat put into the dark for 135 days shows none of these abnormalities except an occasional spontaneous nystagmus.This research was supported by USPHS grant EY02248 and by grants from the M.R.C. (MT5201) and NSERC (A9939) of CanadaL. R. Harris was in receipt of a Wellcome travel grant     

Optokinetic-vestibular interaction in patients with increased gain of the vestibulo-ocular reflex

We studied optokinetic nystagmus (OKN), optokinetic afternystagmus (OKAN) and visual-vestibular interaction in five patients with markedly elevated vestibulo-ocular reflex (VOR) gain due to cerebellar atrophy. All had impaired smooth pursuit, decreased initial slow phase velocity of OKN, and impaired ability to suppress the VOR with real or imagined targets. OKN slow phase velocity gradually built up over 25–45 s, reaching normal values for low stimulus velocities (30 deg/s). Initial velocity of OKAN was increased, but the rate of decay of OKAN was normal. These findings can be explained by models that include separate velocity storage and variable gain elements shared by the vestibular and optokinetic systems.     

Suppression of OKN and VOR by afterimages and imaginary objects

Summary Optokinetic nystagmus (OKN) is suppressed if attention is directed to a centrally placed afterimage superimposed on a moving display. Imagining a stationary object has little or no effect. An afterimage does not provide the retinal slip and misfoveation error signals provided by a stationary object and we have shown that an effective error signal does not arise from occlusion or masking of the display by the afterimage. Although a lack of relative motion between afterimage and moving display could indicate when OKN gain is one, there is no unique relative motion signal associated with a gain of zero. Subjects could partially inhibit the vestibulo-ocular reflex (VOR) in the dark when they imagined a head-fixed object. They could suppress the response more effectively by attending to an afterimage, but the suppression was still only partial. When OKN and VOR were evoked simultaneously, pursuit movements of the eyes could not be suppressed until the vestibular inputs had subsided. We conclude that signals associated with OKN, are fully available to the mechanism that assesses the headcentric motion of objects but that signals associated with VOR are only partially available to that mechanism.This study was part of DCIEM research contract 97711-3-7595/ 8SE83-00221     

Effects of posterior parietal lesions (area 7) on VOR in monkeys

Summary Unilateral ablations of area 7 were performed in three adult monkeys. Vestibulo-ocular reflex (VOR) was tested in the dark by sinusoidal rotations at different frequencies. Following lesion of area 7, spontaneous nystagmus was observed in the dark, with the fast phase directed toward the lesioned side. The same lesion induced a strong VOR asymmetry due to a gain decrease when the animal was rotated toward the side contralateral to the lesion and an increase when rotated toward the opposite side. These VOR deficits were transient: spontaneous nystagmus was no longer present after the first post-operative week whereas the VOR asymmetry lasted for 2 to 4 weeks after the lesion. It is concluded that area 7 might be involved in an ipsilateral control of the slow component of VOR. These results support the idea that posterior parietal cortex plays a role in body reference stabilization.     

Effects of lesions of the nucleus of the optic tract on optokinetic nystagmus and after-nystagmus in the monkey

Summary 1. The nucleus of the optic tract (NOT) and the dorsal terminal nucleus (DTN) of the accessory optic system were lesioned electrolytically or with kainic acid in rhesus monkeys. When lesions involved NOT and DTN, peak velocities of optokinetic nystagmus (OKN) with slow phases toward the side of the lesion were reduced, and optokinetic after-nystagmus (OKAN) was reduced or abolished. The jump in slow phase eye velocity at the onset of OKN was smaller in most animals, but was not lost. Initially, there was spontaneous nystagmus with contralateral slow phases. OKN and OKAN with contralateral slow phases were unaffected. 2. Damage to adjacent regions had no effect on OKN or OKAN with two exceptions: 1. A vascular lesion in the MRF, medial to NOT and adjacent to the central gray matter, caused a transient loss of the initial jump in OKN. The slow rise in slow phase velocity was prolonged, but the gain of OKAN was unaffected. There was no effect after a kainic acid lesion in this region in another animal. 2. Lesions of the fiber tract in the pulvinar that inputs to the brachium of the superior colliculus caused a transient reduction in the buildup and peak velocity of OKN and OKAN. 3. In terms of a previous model (Cohen et al. 1977; Waespe et al. 1983), the findings suggest that the indirect pathway that activates the velocity storage integrator in the vestibular system to produce the slow rise in ipsilateral OKN and OKAN, lies in NOT and DTN. Activity for the rapid rise in OKN, carried in the direct pathway, is probably transmitted to the pontine nuclei and flocculus via an anatomically separate fiber path-way that lies in the MRF. A fiber tract in the pulvinar that inputs to the brachium of the superior colliculus appears to carry activity related to retinal slip from the visual cortex to NOT and DTN.Abbreviations used in Figures BIC brachium of the inferior colliculus - BSC brachium of the superior colliculus - C caudate nucleus - CG central gray - CL Centralis lateralis - dbc decussation of the brachium conjunctivum - DTN dorsal terminal nucleus of the accessory optic system - IC inferior colliculus - Hb habenular nucleus - hc habenular commissure - LD lateralis dorsalis - LGn lateral geniculate nucleus - MD medialis dorsalis - MGn medial geniculate nucleus - MLF median longitudinal fasciculus - MRF mesencephalic reticular formation - cMRF central mesencephalic reticular formation - NL nucleus limitans - NLL nucleus of the lateral lemniscus - NOT nucleus of the optic tract - PB parabigeminal nucleus - pc posterior commissure - Pi pineal gland - PON pretectal olivary nucleus - Pt pretectum - Pulv pulvinar - R nucleus reticularis - RN red nucleus - RpN raphe nucleus - RTP nucleus reticularis tegmenti pontis - SC superior colliculus - SCpit superior cerebellar peduncle - VPL ventralis postero-lateralis - VPM ventralis posteromedialis - III oculomotor nucleus - IV trochlear nucleus - IVn trochlear nerve - Vm mesencephalic trigeminal nucleus     

Role of the nucleus geniculatus lateralis ventralis (GLv) in the optokinetic reflex: a lesion study in the pigeon

Summary Several functions have been proposed for the avian GLv (color vision, pupillary reflex, optomotor mechanisms). In the present paper we have examined the role of the GLv in optomotor responses. For this purpose, horizontal and vertical optokinetic nystagmus (OKN) were quantified in response to different stimulation velocities, before and after chemical (kaïnic acid) lesions. Unilateral lesion of the GLv produced a marked increase of the horizontal OKN gain when the eye contralateral to the lesion was stimulated in the temporonasal (T-N) direction and, to a lesser extent, when the ipsilateral eye was stimulated in the naso-temporal (N-T) direction. Biocular integration was reduced after the lesion, since the biocular stimulation corresponding to these two monocular stimulations (ipsiversive to the lesion) produced only a moderate gain increase. When stimulations were delivered in the opposite direction (contraversive to the lesion), the horizontal OKN gain was slightly increased for the N-T monocular stimulation of the eye contralateral to the lesion, but was unchanged for other stimulations. A bilateral lesion of the GLv provoked only a slight increase of the horizontal OKN gain. The vertical OKN was not affected by the GLv lesions. Thus, the GLv system is probably involved in the modulation of optomotor responses and could mediate visuo-optokinetic interactions, each nucleus (and its associated system) exerting an inhibitory (or disfacilitatory) effect on the horizontal OKN in one direction.     

Effects of lesions of the nucleus of the optic tract on optokinetic nystagmus and after-nystagmus in the monkey

1. The nucleus of the optic tract (NOT) and the dorsal terminal nucleus (DTN) of the accessory optic system were lesioned electrolytically or with kainic acid in rhesus monkeys. When lesions involved NOT and DTN, peak velocities of optokinetic nystagmus (OKN) with slow phases toward the side of the lesion were reduced, and optokinetic after-nystagmus (OKAN) was reduced or abolished. The jump in slow phase eye velocity at the onset of OKN was smaller in most animals, but was not lost. Initially, there was spontaneous nystagmus with contralateral slow phases. OKN and OKAN with contralateral slow phases were unaffected. 2. Damage to adjacent regions had no effect on OKN or OKAN with two exceptions: 1. A vascular lesion in the MRF, medial to NOT and adjacent to the central gray matter, caused a transient loss of the initial jump in OKN. The slow rise in slow phase velocity was prolonged, but the gain of OKAN was unaffected. There was no effect after a kainic acid lesion in this region in another animal. 2. Lesions of the fiber tract in the pulvinar that inputs to the brachium of the superior colliculus caused a transient reduction in the buildup and peak velocity of OKN and OKAN. 3. In terms of a previous model (Cohen et al. 1977; Waespe et al. 1983), the findings suggest that the indirect pathway that activates the velocity storage integrator in the vestibular system to produce the slow rise in ipsilateral OKN and OKAN, lies in NOT and DTN. Activity for the rapid rise in OKN, carried in the direct pathway, is probably transmitted to the pontine nuclei and flocculus via an anatomically separate fiber pathway that lies in the MRF. A fiber tract in the pulvinar that inputs to the brachium of the superior colliculus appears to carry activity related to retinal slip from the visual cortex to NOT and DTN.     

Contribution of eye muscle proprioception to velocity-response characteristics of eye movements: involvement of the cerebellar flocculus.

The vestibulo-ocular reflex (VOR) and optokinetic nystagmus (OKN) were examined in alert pigmented rabbits following interruption of proprioceptive afferents from the extraocular muscles in one eye by surgical section of the ophthalmic branch of the trigeminal nerve (V1 nerve). Deficits were mainly produced in movement dynamics of the ipsilateral eye including reduction of (1) the VOR gain at a high frequency of head rotation, (2) the OKN gain and (3) the velocity of quick eye movements in the OKN. In some of the rabbits examined, the cerebellar flocculus was lesioned by local injection of kainic acid before severance of the V1 nerve. No significant additional reductions of VOR or OKN gains were produced by V1 nerve section in the flocculus-lesioned rabbits. These results suggest that proprioceptive signals from eye muscles act to improve VOR and OKN dynamics through the neuronal mechanisms involving the cerebellar flocculus.     

Nystagmus induced by electrical stimulation of the vestibular and prepositus hypoglossi nuclei in the monkey: evidence for site of induction of velocity storage

Summary Electrical stimulation of the vestibular nuclei (VN) and prepositus hypoglossi nuclei (PPH) of alert cynomolgus monkeys evoked nystagmus and eye deviation while they were in darkness. At some sites in VN, nystagmus and after-nystagmus were induced with characteristics suggesting that velocity storage had been excited. We analyzed these responses and compared them to the slow component of optokinetic nystagmus (OKN) and to optokinetic after-nystagmus (OKAN). We then recorded unit activity in VN and determined which types of nystagmus would be evoked from the sites of recording. Nystagmus and eye deviations were also elicited by electrical stimulation of PPH, and we characterized the responses where unit activity was recorded in PPH. Horizontal slow phase velocity of the VN storage responses was contralateral to the side of stimulation. The rising time constants and peak steady-state velocities were similar to those of OKN, and the falling time constants of the after-nystagmus and of OKAN were approximately equal. Both the induced after-nystagmus and OKAN were habituated by stimulation of the VN. When horizontal after-nystagmus was evoked with animals on their sides, it developed yaw and pitch components that tended to shift the vector of the slow phase velocity toward the spatial vertical. Similar cross-coupling occurs for horizontal OKAN or for vestibular post-rotatory nystagmus elicited in tilted positions. Thus, the storage component of nystagmus induced by VN stimulation had the same characteristics as the slow component of OKN and the VOR. Positive stimulus sites for inducing nystagmus with typical storage components were located in rostral portions of VN. They lay in caudal ventral superior vestibular nucleus (SVN), dorsal portions of central medial vestibular nucleus (MVN) caudal to the abducens nuclei and in adjacent lateral vestibular nucleus (LVN). More complex stimulus responses, but with contralateral after-nystagmus, were induced from surrounding regions of ventral MVN and LVN, rostral descending vestibular nucleus and the marginal zone between MVN and PPH. Vestibular-only (VO), vestibular plus saccade (VPS) and tonic vestibular pause (TVP) units were identified by extracellular recording. Stimulation near type I lateral and vertical canalrelated VO units elicited typical storage responses with after-nystagmus in 23 of 29 tracks (79%). Stimulus responses were more complex from the region of neurons with oculomotor-related signals, i.e., TVP or VPS cells, although after-nystagmus was also elicited from these sites. Effects of vestibular nerve and nucleus stimulation were compared. Nerve stimulation evoked nystagmus with both a rapid and slow component and after-nystagmus. There was a more prominent rapid rise in slow phase velocity, higher peak velocities, shorter latencies and a shorter falling time constant from nerve than from nucleus stimulation. This indicates more prominent activation of rapid pathways from nerve stimulation. From a comparison of nerve- and nucleus-induced nystagmus, we infer that there was predominant activation of the network responsible for velocity storage by electrical stimulation at many sites in the VN. Microstimulation at sites in PPH elicited nystagmus with ipsilateral slow phases or ipsilateral eye deviations. Slow phase eye velocity changed rapidly at the onset of nystagmus, and peak eye velocities were about 10–15°/s lower than from VN stimulation. The nystagmus had no slow component, and it was not followed by after-nystagmus. Only burst or burst-tonic neurons were recorded in PPH. Stimulation at sites of recording of these units induced either nystagmus with a rapid component or ipsilateral eye deviation. We conclude that the slow component of optokinetic and vestibular nystagmus, attributable to velocity storage is produced in the VN, not in the PPH. We postulate that VO neurons lying in caudal ventral portions of SVN, dorsal portions of MVN and adjacent LVN are part of the network that generates velocity storage.     

The effect of muscimol micro-injections into the fastigial nucleus on the optokinetic response and the vestibulo-ocular reflex in the alert monkey

Eye movements of four macaque monkeys were investigated after unilateral micro-injections of the GABA agonist muscimol (1 g in 1 l NaCl) into the caudal fastigial nucleus, i.e. the fastigial oculomotor region. Spontaneous eye movements in the dark and in the light were tested, as well as those evoked by vestibular stimulation in the dark (sinusoidal: 0.1–0.2 Hz, ±40–100 deg/s, velocity trapezoid acceleration 40 deg/s², constant velocity 120 deg/s), optokinetic stimulation (sinusoidal: 0.1–0.2 Hz, ±40–100 deg/s, constant velocity 60–100 deg/s), and visual-vestibular conflict stimulation. With these stimuli, smooth pursuit mechanisms (fast build-up of optokinetic slow phase velocity), the vestibulo-ocular reflex (VOR) and the velocity storage mechanism were investigated. Muscimol injections consistently led to specific eye movement changes which were maximal 30–60 min after the injection and lasted 4–6 h. The fast initial rise of OKN slow phase velocity to the contralateral side decreased by 45% (range 24%–82%) of its pre-injection value, while it was virtually unaltered on the ipsilateral side (average decrease of 1%, range from a decrease of 20% to an increase of 32%). For conflict ramp stimulation, the suppression of vestibular nystagmus was less (decrease of 50%, range 12–82%) towards the contralateral side while it remained unchanged on the ipsilateral side. The VOR in the dark and the velocity storage mechanism were not altered. For the latter, the slow build-up of optokinetic nystagmus velocity, the optokinetic afternystagmus (OKAN) and the time constant of decay for the vestibular nystagmus were evaluated. There was no spontaneous nystagmus in the light or dark and no gazeholding deficit. These data support evidence that the fastigial oculomotor region contributes direction-specifically to smooth pursuit mechanisms, without affecting the VOR and the velocity storage mechanism.     

Nystagmus induced by stimulation of the nucleus of the optic tract in the monkey

Summary 1. The nucleus of the optic tract (NOT) was electrically stimulated in alert rhesus monkeys. In darkness stimulation evoked horizontal nystagmus with ipsilateral slow phases, followed by after-nystagmus in the same direction. The rising time course of the slow phase velocity was similar to the slow rise in optokinetic nystagmus (OKN) and to the charge time of optokinetic after-nystagmus (OKAN). The maximum velocity of the steady state nystagmus was approximately the same as that of OKAN, and the falling time course of the after-nystagmus paralled OKAN. 2. Increases in frequency and duration of stimulation caused the rising and falling time constants of the nystagmus and after-nystagmus to become shorter. Changes in the falling time constant of the after-nystagmus were similar to changes in the time constant of OKAN produced by increases in the velocity or duration of optokinetic stimulation. 3. Stimulus-induced nystagmus was combined with OKN, OKAN and per- and post-rotatory nystagmus. The slow component of OKN as well as OKAN could be prolonged or blocked by stimulation, leaving the rapid component of OKN unaffected. Activity induced by electrical stimulation could also sum with activity arising in the semicircular canals to reduce or abolish post-rotatory nystagmus. 4. Positive stimulus sites for inducing nystagmus were located in the posterolateral pretectum. This included portions of NOT that lie in and around the brachium of the superior colliculus and adjacent regions of the dorsal terminal nucleus (DTN). 5. The data indicate that NOT stimulation had elicited the component of OKN which is responsible for the slow rise in slow phase velocity and for OKAN. The functional implication is that NOT, and possibly DTN, are major sources of visual information related to retinal slip in the animal's yaw plane for semicircular canal-related neurons in the vestibular nuclei. Analyzed in terms of a model of OKN and OKAN (Cohen et al. 1977; Waespe et al. 1983), the indirect pathway, which excites the velocity storage mechanism in the vestibular system to produce the slow component of OKN and OKAN, lies in NOT in the monkey, as it probably also does in cat, rat and rabbit. Pathways carrying activity for the rapid rise in slow phase velocity during OKN or for ocular pursuit appear to lie outside NOT.Supported by NIH grants EY02296, EY04148, EY01867 and PSC-CUNY FRAP award 6-63231     

Effects on the chicken monocular OKN of unilateral microinjections of GABAA antagonist into the mesencephalic structures responsible for OKN

Summary The SR 95531, a GABA_A antagonist was microinjected into either the pretectum nuclei, (nucleus Superficialis Synencephali nSS) or the nBOR (nucleus Ectomammillaris nEM) of chickens. Monocular optokinetic nystamus (OKN) of each eye was recorded by the search coil technique before and after unilateral intracerebral drug administration. Before injection, monocular horizontal OKN in chickens, as in other lower vertebrates, displays a directional asymmetry: the stimulation in the Temporo-Nasal (T-N) direction is more efficient in evoking OKN than is stimulation in the Naso-Temporal (N-T) direction. Unilateral microinjections of SR 95531 into either the nSS or nEM induce a reversible increase of gain in OKN directed by the contralateral eye for both directions of stimulation. However administration into the nSS increased directional asymmetry by increasing the T-N component slow phase velocity more strongly than the N-T component slow phase velocity. On the other hand, the unilateral administration of the drug into the nEM suppressed the directional OKN asymmetry by increasing the N-T component slow phase velocity more strongly than the T-N component slow phase velocity. These results indicate that the drug suppresses GABAergic inhibition at the mesencephalic level. Moreover the nSS seems especially involved in monocular OKN in response to a T-N stimulation, while the nEM seems more involved in the OKN response to N-T stimulation. The increase in gain of OKN directed by the ipsilateral eye to microinjected nuclei could account for the strong interactions existing between these mesencephalic structures responsible for horizontal OKN.     

Neuronal substrates of motor learning in the velocity storage generated during optokinetic stimulation in the squirrel monkey

Chronic motor learning in the vestibuloocular reflex (VOR) results in changes in the gain of this reflex and in other eye movements intimately associated with VOR behavior, e.g., the velocity storage generated by optokinetic stimulation (OKN velocity storage). The aim of the present study was to identify the plastic sites responsible for the change in OKN velocity storage after chronic VOR motor learning. We studied the neuronal responses of vertical eye movement flocculus target neurons (FTNs) during the optokinetic after-nystagmus (OKAN) phase of the optokinetic response (OKR) before and after VOR motor learning. Our findings can be summarized as follows. 1) Chronic VOR motor learning changes the horizontal OKN velocity storage in parallel with changes in VOR gain, whereas the vertical OKN velocity storage is more complex, increasing with VOR gain increases, but not changing following VOR gain decreases. 2) FTNs contain an OKAN signal having opposite directional preferences after chronic high versus low gain learning, suggesting a change in the OKN velocity storage representation of FTNs. 3) Changes in the eye-velocity sensitivity of FTNs during OKAN are correlated with changes in the brain stem head-velocity sensitivity of the same neurons. And 4) these changes in eye-velocity sensitivity of FTNs during OKAN support the new behavior after high gain but not low gain learning. Thus we hypothesize that the changes observed in the OKN velocity storage behavior after chronic learning result from changes in brain stem pathways carrying head velocity and OKN velocity storage information, and that a parallel pathway to vertical FTNs changes its OKN velocity storage representation following low, but not high, gain VOR motor learning.     

Directional asymmetries of human optokinetic nystagmus

Summary Optokinetic nystagmus in the four principal directions was investigated on the occurrence of directional asymmetries in 7 normal human subjects. Instructions were aimed at obtaining a stare type of OKN. The movement of both eyes was recorded simultaneously with a scleral sensor-coil method. Subjects viewed a full-field random dot pattern rotating at velocities of 9 to 57 deg/s binocularly, as well as monocularly with either eye. Gain was always less than 0.85 and decreased when the pattern velocity increased. Horizontal and vertical nystagmus differed in a number of respects. (1) We found no evidence for an overall asymmetry for rightward or leftward, motion. However, human OKN showed a clear preference for upward stimulus motion. Mean gain was ca. 0.15 larger for upward than for downward motion. (2) The decrease of the gain of OKN as a function of increasing stimulus velocity was steeper for vertical than for the horizontal direction. (3) The eyes moved nearly perfectly yoked for vertical pattern movement, irrespective of the viewing conditions. In contrast, during horizontal OKN the gain of the eye tracking in the nasal direction was higher (by about 4%) than the gain of the other eye moving simultaneously in the temporal direction. This difference persisted irrespective of the viewing conditions and appears to be motor, not sensory in origin. In addition, for any direction of the pattern motion a statistically significant increase of the gain occurred when the pattern motion was seen binocularly instead of monocularly with either eye.     

Deficits in vertical and torsional eye movements after uni- and bilateral muscimol inactivation of the interstitial nucleus of Cajal of the alert monkey

The mesencephalic interstitial nucleus of Cajal (iC) is considered the neural integrator for vertical and torsional eye movements and has also been proposed to be involved in saccade generation. The aim of this study was to elucidate the function of iC in neural integration of different types of eye movements and to distinguish eye movement deficits due to iC impairment from that of the immediately adjacent rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF). We addressed the following questions: (1) According to the neural integrator hypothesis, all eye movements including the saccadic system and the vestibulo-ocular reflex (VOR) share a common neural integrator. Do iC lesions impair gaze-holding function for vertical and torsional eye positions and the torsional and vertical VOR gain to a similar degree? (2) What are the dynamic properties of vertical and torsional eye movements deficits after iC lesions, e.g., the specificity of torsional and vertical nystagmus? (3) Is iC involved in saccade generation? We performed 13 uni- and three bilateral iC inactivations by muscimol microinjections in four alert monkeys. Three-dimensional eye movements were studied under head-stationary conditions during vertical and torsional VOR. Under static conditions, unilateral iC injections evoked a shift of Listing’s plane to the contralesional side (up to 20°), which increased (ipsilesional ear down) or decreased (ipsilesional ear up) by additional static vestibular stimulation in the roll plane, i.e., ocular counterroll was preserved. The monkeys showed a spontaneous torsional nystagmus with a profound downbeat component. The fast phases of torsional nystagmus always beat toward the lesion side (ipsilesional). Pronounced gaze-holding deficit for torsional and vertical eye positions (neural integrator failure) was reflected by the reduction of time constants of the exponential decay of the slow phase to 330–370 ms. Whereas the vertical oculomotor range was profoundly decreased (up to 50%) and vertical saccades were reduced in amplitude, saccade velocity remained normal and horizontal eye movements were not affected. Bilateral iC injections reduced the shift of Listing’s plane caused by unilateral injections, i.e., back toward the plane of zero torsion. Torsional nystagmus reversed its direction and ceased, whereas vertical nystagmus persisted. In contrast to unilateral injection, there was additional upbeating nystagmus. Time constants of the position integrator of the gaze-holding system did not differ between unilateral and bilateral injections. The range of stable vertical eye positions and saccade amplitude was smaller when compared with unilateral injections, but the main sequence remained normal. Dynamic vestibular stimulation after unilateral iC injections had virtually no effect on torsional and vertical VOR gain and phase at the same time when time constants already indicated severe integrator failure. Torsional VOR elicited a constant slow-phase velocity offset up to 30° toward the contralesional side, i.e., in the opposite direction to spontaneous torsional nystagmus. Likewise, vertical VOR showed a velocity offset in an upward direction, i.e., opposite to the spontaneous downbeat nystagmus. Contralesional torsional and upward vertical quick phases were missing or severely reduced in amplitude but showed normal velocity. In contrast, bilateral iC injections reduced the gain of the torsional and vertical VOR by 50% and caused a phase lead of 10–20° (eye compared with head velocity). We propose that the slow-phase velocity offset during torsional and vertical VOR reflects a vestibular imbalance. It therefore appears likely that the vertical and torsional nystagmus after iC lesions is not only caused by a neural integrator failure but also by a vestibular imbalance. Unilateral iC injections have clearly differential effects on the VOR and the gaze-holding function. These results are not compatible with a single common neural integrator model, which would predict a much stronger VOR gain reduction and phase advance, as found in our data. Our data support the existence of multiple integrators in iC with parallel processing.     

Gaze-stabilizing deficits and latent nystagmus in monkeys with brief, early-onset visual deprivation: eye movement recordings

The normal development and the capacity to calibrate gaze-stabilizing systems may depend on normal vision during infancy. At the end of 1 yr of dark rearing, cats have gaze-stabilizing deficits similar to that of the newborn human infant including decreased monocular optokinetic nystagmus (OKN) in the nasal to temporal (N-T) direction and decreased velocity storage in the vestibuloocular reflex (VOR). The purpose of this study is to determine to what extent restricted vision during the first 2 mo of life in monkeys affects the development of gaze-stabilizing systems. The eyelids of both eyes were sutured closed in three rhesus monkeys (Macaca mulatta) at birth. Eyelids were opened at 25 days in one monkey and 40 and 55 days in the other two animals. Eye movements were recorded from each eye using scleral search coils. The VOR, OKN, and fixation were examined at 6 and 12 mo of age. We also examined ocular alignment, refraction, and visual acuity in these animals. At 1 yr of age, visual acuity ranged from 0.3 to 0.6 LogMAR (20/40-20/80). All animals showed a defect in monocular OKN in the N-T direction. The velocity-storage component of OKN (i.e., OKAN) was the most impaired. All animals had a mild reduction in VOR gain but had a normal time constant. The animals deprived for 40 and 55 days had a persistent strabismus. All animals showed a nystagmus similar to latent nystagmus (LN) in human subjects. The amount of LN and OKN defect correlated positively with the duration of deprivation. In addition, the animal deprived for 55 days demonstrated a pattern of nystagmus similar to congenital nystagmus in human subjects. We found that restricted visual input during the first 2 mo of life impairs certain gaze-stabilizing systems and causes LN in primates.