Biomedical subjects

H Collewijn

Publications and source records attributed to H Collewijn.

At least 19 recordsLinked to original sources

PubMed1992

Muscarinic nature of cholinergic receptors in the cerebellar flocculus involved in the enhancement of the rabbit's optokinetic response.

Intrafloccular micro-injection of the aselective cholinergic agonist carbachol enhances the optokinetic reflex (OKR)17. Histochemical and physiological studies have identified cholinergic receptors of the muscarinic as well as nicotinic type in the cerebellar cortex, and both have been implicated in cholinergic transmission. The present study was undertaken to elucidate the receptor type involved in the control of OKR. For that purpose, effects of injections of the nicotinic N1 agonist DMPP on the OKR and vestibulo-ocular reflex (VOR) were compared with injections of the muscarinic agonist betanechol and the aselective cholinergic agonist carbachol. Injection of betanechol mimicked the enhancement of the OKR by carbachol, while DMPP had no effect. We conclude that muscarinic receptors are involved in the positive modulatory action of the cholinergic system in the cerebellar flocculus.

Animals↗

PubMed1992

Cholinergic and noradrenergic stimulation in the rabbit flocculus have synergistic facilitatory effects on optokinetic responses.

A recent study (Exp. Brain Res., 85 (1991) 475-481) showed that injection of the cholinergic agonist carbachol into the cerebellar flocculi had a pronounced facilitatory effect on the gains of the optokinetic (OKR) and vestibulo-ocular (VOR) reflexes, suggesting a positive modulatory role of the cholinergic system in the flocculus. Because many behavioral and electrophysiological studies throughout the brain have revealed a functional relationship between acetylcholine (ACh) and noradrenaline (NA), the present study was undertaken to compare the effects of floccular injection of the ACh agonist carbachol, the beta-adrenergic agonist isoproterenol and the conjoint injection of both of these substances on the basic gain of the VOR and the OKR. Carbachol and isoproterenol both significantly raised the gain of the OKR, by 0.14 and 0.11 respectively. Neither of the two substances significantly affected the gain of the VOR in light or darkness. Conjoint injection of the same amounts of carbachol and isoproterenol resulted in an increase in the gain of the OKR by 0.29 without significant changes in the gains of the VOR in the light or in darkness. These results suggest a synergistic and positive modulatory role of ACh and NA in the flocculus.

Animals↗

PubMed1992

Enhancement of optokinetic and vestibuloocular responses in the rabbit by cholinergic stimulation of the flocculus.

Bilateral microinjections into the cerebellar flocculus of the rabbit of carbachol, a general cholinergic agonist, profoundly affect vestibuloocular (VOR) and optokinetic (OKR) reflexes. For sinusoidal stimuli (0.15 Hz, 5 deg peak to peak), the gain of the OKR was strongly increased, while the gain of the VOR was moderately increased. These effects were partially mimicked by floccular injection of the acetylcholinesterase inhibitor eserine. Floccular injection of the muscarinic blocker atropine significantly lowered the gain of the OKR. The effects of the nicotinic blocker mecamylamine were not significant. Optokinetic nystagmus (OKN) in response to constant stimulus velocities (1-30 deg/second) showed a markedly accelerated buildup and a shortened optokinetic after-nystagmus (OKAN) after floccular injections of carbachol. The steady-state gain of OKN remained unaffected. None of the described effects occurred after floccular injection of the solvent, saline. It is postulated that cholinergic cerebellar afferents, one probable source of which are the vestibular nuclei, enhance the optokinetic and vestibular modulation of floccular Purkinje cells.

Animals↗

PubMed1992

Foveation dynamics in congenital nystagmus. I: Fixation.

Congenital nystagmus (CN) has been described as a 'fixation' nystagmus implying an inability to fixate a target. However, each cycle of CN contains a target-foveation period during which the eye velocity is at, or near, zero. Prolongation of foveation time, reduction of retinal image velocity and cycle-to-cycle foveation repeatability all contribute to increased visual acuity. We developed several methods to accurately measure the dynamics of foveation in CN; their use is illustrated on an individual with typical idiopathic CN and no afferent defects. During eight 5-second intervals of fixation on a stationary target, the horizontal standard deviation (SD) of the mean foveation position (FPOS) was 12.82 minarc and the SD of foveation velocity was 118.36 minarc/sec. The SD of the means of total eye position and of the non-foveating peak of the CN were 43.17 and 25.32 minarc respectively. The mean foveation-time interval (eye velocity less than or equal to 4 degrees/sec) was 57.27 msec. The SD FPOS for the best 1-second interval (4 successive CN cycles), in a typical 5-second record, was 0.71 minarc. Histograms revealed peaks of eye position at 0 +/- 10 minarc and of eye velocity at 0 +/- 240 minarc/sec. The small vertical component of the CN (16 minarc peak-to-peak) had a SD of 6.56 minarc. A nystagmus foveation function related to visual acuity was derived that was more sensitive than CN intensity. The increased visual acuity resulting from the use of convergence or base-out prisms was due to increased foveation time. Although it might appear that CN is a defect of fixation, this individual with CN had strong fixation reflexes in the sense that he was able to accurately (within 1 minarc) achieve (interbeat) and maintain (intrabeat) target foveation for appreciable periods of time. Our data support the hypothesis that individuals with idiopathic CN do not have a primary disturbance of fixation.

Fixation, Ocular↗

PubMed1992

Foveation dynamics in congenital nystagmus. II: Smooth pursuit.

It has been shown that, during 5 seconds of fixation, an individual with congenital nystagmus (CN) can repeatedly (beat-to-beat) foveate (SD = 12.87 minarc) and maintain low retinal slip velocities (SD = 118.36 minarc/sec). Smooth pursuit data from several CN subjects showed that eye velocities during these foveation intervals approximated target velocity. Despite some claims that CN is caused by absent or "reversed" smooth pursuit, those with CN hardly ever experience oscillopsia or exhibit any accompanying symptoms of such deficits in pursuit; they are able to master sports requiring tracking of rapidly moving small objects (e.g. racquetball or handball). We developed and describe several new methods to accurately assess the function of smooth pursuit in an individual with typical idiopathic CN. We investigated the dynamics of CN foveation periods during smooth pursuit to test the hypothesis that eye velocities would match target velocities during these periods. Unity or near-unity instantaneous (beat-to-beat) pursuit gains of both experimenter-moved and subject-moved targets at peak velocities ranging from only a few deg/sec up to 210 degrees/sec were measured. The dynamic neutral zone was found to shift oppositely to target direction by amounts proportional to the increase in target speed. Our methods proved that eye velocity is made to match target velocity during the foveation intervals and support the conclusion that smooth pursuit in individuals with CN is functioning normally in the presence of the CN oscillation. In addition, we hypothesize that the same fixation mechanism that prevents oscillopsia during fixation of stationary targets, also does so during pursuit.

Fovea Centralis↗

PubMed1992

Foveation dynamics in congenital nystagmus. III: Vestibulo-ocular reflex.

It has been shown that, during fixation of a stationary target with a fixed head, an individual with congenital nystagmus (CN) can repeatedly (beat-to-beat) foveate (within 13 minarc) and maintain low retinal slip velocities (less than 4 degrees/sec). With the head in motion, vestibuloocular reflex (VOR) data showed eye velocities during these foveation periods that approximation head velocity. Despite some claims that the VOR of CN subjects was deficient or absent, individuals with CN hardly ever complain of oscillopsia or exhibit any of the symptoms that would accompany such deficits in the VOR, whether during simple walking and running or while skiing down a mogul field. We developed and describe several different and unrelated methods to accurately assess the function of the VOR in an individual with typical idiopathic CN. We investigated the dynamics of CN foveation periods during head rotation to test the hypothesis that eye velocities would match head velocities during these periods. At about 1 Hz, horizontal VOR instantaneous (beat-to-beat) gains were 0.96 in the light and 0.94 in the dark while imaging a stationary target. Vertical VOR gains were 1.00 and 0.99 for these two conditions at the same frequency; the CN was horizontal. Also, during the VOR there is a CN neutral-zone shift comparable to that found during smooth pursuit. Our methods demonstrated that gaze velocity was held constant during foveation periods and we conclude that the VOR in this subject is functioning normally in the presence of the CN oscillation. Based on our findings in this and previous studies, we hypothesize that CN may be due to a peripheral instability.

Fovea Centralis↗

PubMed1992

Optokinetic nystagmus in the rabbit and its modulation by bilateral microinjection of carbachol in the cerebellar flocculus.

1. In the alert, pigmented rabbit, eye movements were recorded during optokinetic nystagmus (OKN) and during optokinetic after nystagmus (OKAN). These responses were elicited by steps in surround-velocity ranging from 5-110 degrees/s during binocular as well as monocular viewing. 2. In the baseline condition, OKN showed an approximately linear build-up of eye velocity to a steady-state, followed by a linear decay of eye velocity during OKAN after the lights were turned off. Build-up during binocular viewing was characterized by a constant, maximum eye-acceleration (about 1 degree/s2) for stimulus velocities up to 60 degrees/s. OKAN, instead, was characterized by a fixed duration (about 10 s) for stimulus velocities up to 20 degrees/s. Steady-state eye velocity saturated at about 50 degrees/s. 3. Monocular stimulation in the preferred (nasal) direction elicited a build-up that was on average twice as slow as during binocular stimulation. Steady-state velocity during monocular stimulation saturated at about 20 degrees/s. OKAN was of equal duration as during binocular stimulation. In the non-preferred direction, a very irregular nystagmus was elicited without velocity build-up. The stronger response to binocular stimulation, compared to the responses under monocular viewing condition in either nasal and temporal direction suggests potentiation of the signals of either eye during binocular viewing. 4. OKN and OKAN were re-assessed after intra-floccular micro-injection of the nonselective cholinergic agonist carbachol. In the binocular viewing condition, eye-acceleration during build-up was strongly enhanced from 1 degree/s2 before to 2.5 degrees/s2 after injection. The saturation level of steady-state eye velocity was also increased, from 50 degrees/s before to more than 60 degrees/s after carbachol. The duration of OKAN, however, was shortened from 10 s before to 6 s after injection. The response to monocular stimulation in the preferred direction revealed similar changes. 5. The flocculus appears to be involved in the control of the dynamics of OKN in the rabbit. Cholinergic mechanisms affect the floccular control of the rate at which slow-phase velocity can be built up and the rate of decay of eye velocity during OKAN. Cholinergic stimulation of the flocculus enhances the dynamics of OKN, while velocity storage is shortened.

Animals↗

PubMed1992

Visually induced cycloversion and cyclovergence.

Binocular cyclorotatory (torsional) eye movements in response to visual patterns, which oscillated sinusoidally in the frontal plane, were recorded with scleral induction coils in human subjects. Conjugate cycloversion and disjunctive cyclovergence were directly compared by in-phase and out-of-phase oscillation of the same pattern. Stimulus motion had a frequency of 0.2 Hz and amplitudes of 2-8 deg. Both response types had a similar and low gain (about 0.2 averaged over all subjects). Cycloversion showed no time lag, while cyclovergence lagged by about 600 msec. Non-fusible patterns were effective in eliciting cycloversion, but not cyclovergence. Apart from this, the nature of the pattern (randomly distributed dots, regular rows of dots, horizontal or vertical grating, Julesz stereogram or images with a pictorial significance) had only the slightest effect on the magnitude of the responses.

Adult↗

PubMed1992

Nonconjugate adaptation of human saccades to anisometropic spectacles: meridian-specificity.

Recently it has been demonstrated that saccades become different in size in the two eyes if a subject is adapted to anisometropic spectacles, which provide visual images of different magnitude to the two eyes. These nonconjugate adaptations adequately meet the requirements of those spectacles and, once acquired, they persist (with some reduction) even during monocular viewing. We now demonstrate that such nonconjugate adaptations of saccades can be meridian-specific, if there is a pressure for such meridian-specificity. This pressure was provided by means of a cylindrical spectacle-lens. Adaptations along a vertical, horizontal or oblique meridian did not transfer to the orthogonal meridian. These results demonstrate a capability of saccadic adaptation to deal with calibration problems restricted not only to one eye, but even to one specific plane of muscular action. Our results also suggest that the meridian-specific adaptations of oblique saccades take place at a stage before the decomposition of motor commands into separate horizontal and vertical components. The meridian-specific nonconjugacies were also expressed in smooth-pursuit eye movements. Post-saccadic drift adapted only along the horizontal meridian.

Adaptation, Ocular↗

PubMed1991

Effects of alpha-noradrenergic substances on the optokinetic and vestibulo-ocular responses in the rabbit: a study with systemic and intrafloccular injections.

The effects of microinjection of alpha-noradrenergic agonists and antagonists in the flocculus on the basic gain and adaptibility of vestibulo-ocular and optokinetic responses were investigated. A complementary, previous investigation had shown that the adaptation, but not the basic performance, of compensatory oculomotor responses were markedly influenced by beta-noradrenergic mechanisms in the flocculus. In contrast, the present experiments with bilateral, intrafloccular injections of phenylephrine, prazosin, clonidine and idazoxan failed to reveal any effect of alpha 1- or alpha 2-noradrenergic mechanisms on either basic performance or adaptation of compensatory eye movements. Intravenous administration of clonidine, however, reduced the gain of the optokinetic and vestibulo-ocular responses by about 70 and 50%, respectively, at dosages of 0.07 mg/kg. Recovery from this effect took about 1.5 h. A higher dosage of clonidine (0.7 mg/kg) had a similar, but longer lasting effect, and also markedly increased the frequency of spontaneous saccades. Intravenous administration of phenylephrine did not affect the oculomotor responses. It is concluded that the control of oculomotor responses is not susceptible to alpha-noradrenergic influences at the level of the flocculus, but that alpha 2-agonistic action inhibits these responses through an extra-floccular structure.

Adaptation, Physiological↗

PubMed1991

Control of vergence: gating among disparity inputs by voluntary target selection.

The ability of human beings to shift their vergence between multiple disparity stimuli was investigated. The stimulus was a stereogram consisting of a single bar (1 x 0.3 degree) projected in the center of a larger circular pattern (28 degrees dia) of dots (0.3 degree dia). In the initial condition, the subjects perceived a single bar in the center of a cluster of dots, all lying in a single depth plane. The subjects were instructed to fixate either the bar or one of the dots close to the bar. Stepwise changes of target-vergence of either the bar, or of all dots, or of both configurations in opposite directions, were imposed in a random sequence. Under these conditions, ocular vergence was controlled by the target-vergence of the selected target at all times, even if this implied a loss of binocular fusion for the non-selected target. The effect of target selection per se, without concomitant changes in retinal position of the selected target, was studied in two experienced subjects with stabilized image techniques. The subjects viewed a configuration containing short vertical bars placed at either side of a long vertical bar. The short bars on different sides of the long bar had opposite (crossed or uncrossed) disparities. After stabilization of the configuration while the subject fixated the long bar, subjects attempted to fixate the short bars alternatingly. Due to the stabilization the ensuing eye movements did not affect the retinal positions, and thus the disparity, of the bars. Attempted fixation of a parafoveally viewed, short bar induced vergence responses in the appropriate direction.(ABSTRACT TRUNCATED AT 250 WORDS)

Attention↗

PubMed1991

Cholinergic modulation of optokinetic and vestibulo-ocular responses: a study with microinjections in the flocculus of the rabbit.

In spite of a large body of histochemical evidence for a cholinergic system in the cerebellum, particularly in lobules IX and X, the physiological role of such a system has remained obscure. In view of the important role of these same lobules in the control of the vestibulo-ocular (VOR) and optokinetic (OKR) responses, we tested the effect of microinjections of cholinergic (ant)agonists in the flocculus of the rabbit on these reflexes. Very marked effects were found. Bilateral floccular injection of the aspecific cholinergic agonist carbachol raised the gain of the OKR by about 0.46 above the baseline values, while the gain of the VOR in darkness was raised by about 0.14. These effects were statistically significant and persisted for several hours. Similar, but smaller effects were obtained after injection of eserine, an inhibitor of acetylcholinesterase. Thus, the effects could be produced by increasing the naturally present amount of acetylcholine. Microinjections of the nicotinic blocker mecamylamine reduced the gain of the VOR and OKR, although these effects did not reach statistical significance. The muscarinic blocker atropine significantly reduced the gain of the OKR, but not of the VOR. The present results argue strongly for an important physiological role of the cholinergic system in the cerebellum. Specifically, acetylcholine appears to be involved in the modulation of oculomotor reflexes through the flocculus.

Animals↗

PubMed1991

Long-term nonconjugate adaptation of human saccades to anisometropic spectacles.

It is generally believed that saccades follow Hering's law in the sense that they are equally large in the two eyes. We demonstrated that saccades are different in size in the two eyes in 8 habitual wearers of anisometropic spectacles, which have lenses of different refractive powers, and therefore supply each eye with a differently sized visual image. The eye provided with the larger visual image made larger saccades than its fellow eye. This nonconjugate adaptation was almost complete for both horizontal and vertical saccades. Post-saccadic drift was also asymmetrically adapted: it reduced any fixation-disparity present at saccadic offset. The nonconjugate adaptation was also expressed in smooth-pursuit eye movements. In addition, these nonconjugate adaptations were present during monocular viewing, which shows that they were hard-programmed.

Adaptation, Ocular↗

PubMed1991

Short-term nonconjugate adaptation of human saccades to anisometropic spectacles.

It has been demonstrated before that the long-term wearing of anisometropic spectacles may induce nonconjugate adaptations of saccades. Saccades then become different in size in the two eyes. We examined the time-course and the limits of such adaptations of horizontal and vertical saccades during the short-term (1-6 hr) wearing of anisometropic spectacles. After only 1 hr of conditioning to 2 D of anisometropia, the nonconjugate size-adaptations were almost complete along the horizontal meridian. For progressively larger anisometropias (up to 8 D) the adaptative nonconjugacies after 1 hr became also systematically larger. An anisometropia larger than 6 D did not further increase the rate of adaptation during the first 6 hr of conditioning, which suggests that about 6 D of difference in spectacle correction, causing size differences of about 12%, may be the upper limit of the nonconjugate adaptive range of the saccadic subsystem. Post-saccadic drift of horizontal saccades was also adequately changed. In addition, nonconjugate adaptations had developed in smooth-pursuit eye movements. All of these plastic changes persisted during monocular viewing, indicating that the basic programming of these eye movements was changed.

Adaptation, Ocular↗

PubMed1991

Effects of GABAergic and noradrenergic injections into the cerebellar flocculus on vestibulo-ocular reflexes in the rabbit.

The role of the vesitibulo-cerebellum of the rabbit in the control of the vestibulo-ocular response (VOR) and optokinetic response (OKR) reflexes was investigated by bilateral microinjections, into the flocculus, of substances affecting GABAergic or noradrenergic neurotransmission. GABA, the main transmitter through which cerebellar interneurons inhibit Purkinje cells directly or indirectly, acts normally through GABAA receptors (mainly located in the granular layer) and GABAB receptors (predominantly located in the molecular layer). Despite this different distribution, floccular injections of the GABAA agonist muscimol and of the GABAB agonist baclofen had a similar effect, presumably by profound inhibition of Purkinje cells. This effect consisted of a reduction in the gain of the VOR (in darkness and in light) as well as of the OKR by at least 50%. This provides firm evidence that the net effect of normal Purkinje-cell activity in the flocculus is to enhance the VOR and OKR, rather than to inhibit these responses, as is sometimes supposed. Intrafloccular injections of the beta-noradrenergic agonist isoproterenol or the beta-noradrenergic antagonist sotalol did not affect the basic magnitude of the VOR and OKR. However, these substances markedly affected the adaptive processes, which cause the VOR and OKR to change its magnitude when this is no longer adequate in stabilizing the retinal image. By a suitable combination of vestibular and optokinetic stimuli, consistent upward changes in the gain of these reflexes could be reliably and reproducibly induced in uninjected animals. Floccular injections of sotalol impaired these adaptive changes markedly, whereas injections of isoproterenol enhanced the adaptation, particularly of the VOR measured in darkness. These findings strongly suggest that the effectuation of adaptive changes of vestibular, and possibly other, motor control systems is strongly facilitated by the noradrenergic innervation of the flocculus, which is normally provided by the locus coeruleus (LC), by way of the beta-receptor system, although the activity of this system does not directly affect the signal transmission supporting the basic reflexes as such.

Adaptation, Physiological↗

PubMed1991

Changes in VOR adaptation after local injection of beta-noradrenergic agents in the flocculus of rabbits.

Noradrenaline (NA) has been implicated as a neuromodulator in plasticity, presumably facilitating adaptive processes. Since the flocculus receives noradrenergic afferents, and ablation of the flocculus interferes with the normal adaptive changes in the VOR gain, experiments were performed to find out whether bilateral injection of monoaminergic substances into the flocculus of rabbits could modify the adaptive changes of the VOR. The visual world surrounding the rabbit was oscillated in opposite direction to the platform on which the rabbit was mounted, which resulted in an adaptive increase in the VOR gain; this adaptation was measured either in light or in darkness. Floccular injection of the beta-agonist isoproterenol did not greatly affect the adaptation of the VOR measured in light. In darkness, however, the increase in gain after injection of isoproterenol was larger than during normal adaptation. The beta-antagonist sotalol reduced the adaptation of the VOR gain significantly in light as well as in darkness. In a control condition without pressure for adaptation (only intermittent testing of the VOR gain over a period of 2.5 h), the gain of the VOR was not significantly affected by similar injections of beta-adrenergic agents. We conclude that the noradrenergic system facilitates the adaptation of the VOR gain to retinal slip in rabbits without affecting the VOR gain directly. At least part of this influence is exerted through beta-receptors located in the cerebellar flocculus.

Adaptation, Physiological↗

PubMed1990

Injections of beta-noradrenergic substances in the flocculus of rabbits affect adaptation of the VOR gain.

Noradrenaline (NA) has been implicated as a neuromodulator in plasticity, presumably facilitating adaptive processes. Recent experiments by others have suggested a modulatory role of NA in adaptive changes in the vestibulo-ocular reflex (VOR). These experiments showed that general depletion of brain NA resulted in a decreased ability to produce adaptive changes in the VOR gain. In order to identify the specific brain region responsible for these effects, as well as the nature of the adrenoceptors involved, we injected beta-adrenergic substances bilaterally into the flocculus of rabbits. The flocculus is known to receive noradrenergic afferents and, moreover, ablation of the flocculus interferes strongly with the normal adaptive changes in the VOR gain. We injected the beta-agonist isoproterenol and the beta-antagonist sotalol, and compared the adaptive capacity of the rabbits after these injections to that in a situation without injection. The rabbit was oscillated in a direction opposite to the direction of motion of the platform on which the rabbit was mounted, a condition which normally results in an increase in the VOR gain, measured either in light or in darkness. Injection of the beta-agonist did not greatly affect the adaptation of the VOR measured in the light. In darkness, the increase in gain after the injection of isoproterenol was larger than in the non-injection experiments in 9 out of 10 rabbits. The beta-antagonist sotalol reduced the adaptation of the VOR gain significantly in the light, as well as in darkness. In a control condition without pressure for adaptation (only intermittent testing of the VOR gain over a period of 2.5 h), the gain of the VOR either remained unaffected or was only slightly affected by similar injections of beta-adrenergic agents in individual rabbits. For the group as a whole, these effects were insignificant. We conclude from these results that noradrenergic systems facilitate the adaptation of the VOR gain to retinal slip in rabbits, without affecting the VOR gain directly. At least part of this influence is exerted through beta-receptors located in the cerebellar flocculus.

Adaptation, Physiological↗

PubMed1990

New directions for oculomotor research.

This paper reviews major trends in the study of the oculomotor system since Westheimer published his doctoral research on this topic 35 years ago. Westheimer introduced the use of linear system analysis for the study of eye movements, an approach used a great deal by others ever since. Westheimer himself abandoned this approach within a decade, in part, because this kind of analysis becomes ambiguous when predictive properties of oculomotor system performance become prominent. We discuss the implications of ignoring the prominence of predictive eye movements and describe recent evidence for their prevelence and power. This leads us to propose that a new approach to the study of oculomotor performance is required. We also discuss the recent trend to apply the "connectionist" (or "neural network") approach in studies of the oculomotor system, and point out that the "symbolic", rather than the "adaptive", nature of predictive eye movements makes successful extension of these models to oculomotor performance unlikely. Our new approach emphasizes the use of natural stimulation in subjects free from bodily restraints. Accurate measurement of eye, head and torso movements under such conditions has become possible recently and data obtained in this manner has led to the discovery of a number of unexpected characteristics of oculomotor system performance. These developments have encouraged us to abandon the modular view of the oculomotor system, popular since Dodge launched the modern era of oculomotor research in 1903, which postulates five, or more, largely independent "subsystems". We suggest that only two subsystems (a fast saccadic and a somewhat slower smooth) are used to fixate and track a central representation of objects located in three-dimensional space. We show that this two-subsystem approach is consistent with current knowledge of oculomotor system neuroanatomy and neurophysiology.

Adult↗