Xiaoyan Shan

Effects of Intracranial Trochlear Neurectomy on the Structure of the Primate Superior Oblique Muscle

PURPOSE. Although cyclovertical strabismus in humans is frequently attributed to superior oblique (SO) palsy, anatomic effects of SO denervation have not been studied. Magnetic resonance imaging (MRI) and orbital histology was used to study the effects of acute trochlear (CN4) denervation on the monkey SO. METHODS. Five juvenile macaque monkeys were perfused with formalin for 5 weeks: 15 months after unilateral or bilateral 10-mm intracranial trochlear neurectomy. Denervated and fellow orbits were imaged by MRI, embedded whole in paraffin, serially sectioned at 10-mum thickness, and stained with Masson trichrome. Whole muscle and individual fiber cross sections were quantified in SO muscles throughout the orbit and traced larger fibers in one specimen where they were present. RESULTS. MRI demonstrated marked reduction in midorbital cross section in denervated SO muscles, with anterior shift of SO mass preserving overall volume. Muscle fibers exhibited variable atrophy along their lengths. Denervated orbital layer (OL) fiber cross sections were slightly but significantly reduced from control at most anteroposterior locations, but this reduction was much more profound in global layer (GL) fibers. Intraorbital and intramuscular CN4 were uniformly fibrotic. In one animal, there were scattered clusters of markedly hypertrophic GL fibers that exhibited only sparse myomyous junctions only anteriorly. CONCLUSIONS. CN4 denervation produces predominantly SO GL atrophy with relative OL sparing. Overall midorbital SO atrophy was evident by MRI as early as 5 weeks after denervation, as denervated SO volume shifted anteriorly. Occasional GL fiber hypertrophy suggests that at least some SO fibers extend essentially the full muscle length after trochlear neurectomy.

Lesions of the Cerebellar Nodulus and Uvula Impair Downward Pursuit

We studied sinusoidal (SIN) and step-ramp (SR) pursuit in two rhesus monkeys, before and after surgical lesions of the cerebellar nodulus and uvula (Nod/Uv). Eye movements were recorded using the magnetic field scleral search coil method. Pursuit targets were generated by an LCD projector and back-projected onto a tangent screen in an otherwise dark room. After the Nod/Uv lesions, both monkeys showed a reduced eye velocity during downward pursuit (SIN: 42% decrease in M1, 91% decrease in M2; SR: 37% decrease in M1, 85% decrease in M2). For SR, the decrease was seen only for the closed-loop response; initial eye acceleration did not change (P>0.05). Upward pursuit gains increased for SIN (M1: 9%, M2: 11%); they decreased for SR (M1: 27%, M2: 18%), but to a lesser degree than for downward pursuit. Horizontal pursuit was little changed in M1 but was reduced in one direction in M2, the animal with the larger lesion. The deficit in downward tracking was limited to foveal pursuit; ocular following of random-dot stimuli was retained, even when the target subtended only several degrees. Our findings support a critical role for the Nod/Uv in vertical pursuit, particularly for sustained downward pursuit. Finally, in both monkeys, the lesion increased spontaneous upward ocular drift in the dark (mean prelesion, 1.43 degrees/s; postlesion, 5.92 degrees/s), suggesting a role for the Nod/Uv in holding the eyes still and in the genesis of downbeat nystagmus.

The cerebellar nodulus/uvula integrates otolith signals for the translational vestibulo-ocular reflex

Background The otolith-driven translational vestibulo-ocular reflex (tVOR) generates compensatory eye movements to linear head accelerations. Studies in humans indicate that the cerebellum plays a critical role in the neural control of the tVOR, but little is known about mechanisms of this control or the functions of specific cerebellar structures. Here, we chose to investigate the contribution of the nodulus and uvula, which have been shown by prior studies to be involved in the processing of otolith signals in other contexts. Methodology/Principal Findings We recorded eye movements in two rhesus monkeys during steps of linear motion along the interaural axis before and after surgical lesions of the cerebellar uvula and nodulus. The lesions strikingly reduced eye velocity during constant-velocity motion but had only a small effect on the response to initial head acceleration. We fit eye velocity to a linear combination of head acceleration and velocity and to a dynamic mathematical model of the tVOR that incorporated a specific integrator of head acceleration. Based on parameter optimization, the lesion decreased the gain of the pathway containing this new integrator by 62%. The component of eye velocity that depended directly on head acceleration changed little (gain decrease of 13%). In a final set of simulations, we compared our data to the predictions of previous models of the tVOR, none of which could account for our experimental findings. Conclusions/ Significance Our results provide new and important information regarding the neural control of the tVOR. Specifically, they point to a key role for the cerebellar nodulus and uvula in the mathematical integration of afferent linear head acceleration signals. This function is likely to be critical not only for the tVOR but also for the otolith-mediated reflexes that control posture and balance.

Lesions of the Cerebellar Nodulus and Uvula in Monkeys: Effect on Otolith-Ocular Reflexes

We studied two rhesus monkeys before and after surgical ablation of the nodulus and uvula (Nod/Uv) of the cerebellum. Three-axis eye movements were recorded with the magnetic-field scleral search coil system during a variety of vestibular and ocular motor tasks. Here we describe the effects of the Nod/Uv lesions on dynamic (head translation) and static (head tilt) otolith-mediated vestibulo-ocular reflexes. The main findings were: 1. eye velocity during sinusoidal vertical translation (1.5 Hz) was reduced by 59% in the dark and 36% in the light; 2. eye velocity during steps of horizontal translation was reduced, but only in the dark and more so during the sustained (constant velocity) than the initial (acceleration) part of the response, and 3. there was a torsional nystagmus that depended on the position of roll head tilt, but static ocular counterroll was unchanged. These results suggest new roles for the Nod/Uv in the processing of otolith signals. This is likely important not only for facilitating gaze during linear head motion, but also for maintaining postural stability and ones orientation relative to gravity. The lesions appeared to have a greater effect on responses to vertical motion, particularly in the light (in contrast, responses to interaural translation in the light were nearly normal), suggesting a particular importance of the Nod/Uv in processing signals arising from the sacculi.

Enhancement of the Bias Component of Downbeat Nystagmus after Lesions of the Nodulus and Uvula

In two monkeys, we recorded spontaneous eye movements before and after ablation of the cerebellar nodulus and uvula (Nod/Uv). In both monkeys, there was an increase in upward ocular drift (downbeat nystagmus [DBN]) in darkness (M1: 1.5°/s pre, 3.4°/s post; M2: 1.3°/s pre, 7.0°/s post), but not in light. There was little effect of orbital position on drift velocity. These findings suggest that the Nod/Uv may play a role in the bias component of DBN.

Acute superior oblique palsy in the monkey: effects of viewing conditions on ocular alignment and modelling of the ocular motor plant.

We investigated the immediate and long-term changes in static eye alignment with acute superior oblique palsy (SOP) in the monkey. When the paretic eye was patched immediately after the lesion for 6-9 days, vertical alignment slowly improved. When the patch was removed and binocular viewing was allowed, alignment slowly worsened. In contrast when a monkey was not patched immediately after the lesion vertical alignment did not improve. We also show that a model of the eye plant can reproduce the observed acute deficit induced by SOP, but only by abandoning Robinsons symmetric simplification of the reciprocal innervation relationship within pairs of agonist-antagonist muscles. The model also demonstrated that physiologic variability in orbital geometry can have a large impact on SOP deficits.

The Effect of Acute Superior Oblique Palsy on Torsional Optokinetic Nystagmus in Monkeys

PURPOSE To investigate the effects of acquired superior oblique palsy (SOP) and corrective strabismus surgery on torsional optokinetic nystagmus (tOKN) in monkeys. METHODS The trochlear nerve was severed intracranially in two rhesus monkeys (M1 and M2). For each monkey, more than 4 months after the SOP, the ipsilateral inferior oblique muscle was denervated and extirpated. For M2, 4 months later, the contralateral inferior rectus muscle was recessed by 2 mm. tOKN was elicited during monocular viewing of a rotating stimulus that was rear projected onto a screen 43.5 cm in front of the animal. Angular rotation of the stimulus about the center was 40 deg/s clockwise or counterclockwise. RESULTS The main findings after trochlear nerve sectioning were (1) the amplitude and peak velocity of torsional quick and slow phases of the paretic eye was less than that in the normal eye for both intorsion and extorsion, and (2) the vertical motion of the paretic eye increased during both torsional slow and quick phases. After corrective inferior oblique surgery, both of these effects were even greater. CONCLUSIONS Acquired SOP and corrective inferior oblique-weakening surgery create characteristic patterns of change in tOKN that reflect alterations in the dynamic properties of the extraocular muscles involved in eye torsion. tOKN also provides information complementary to that provided by the traditional Bielschowsky head-tilt test and potentially can help distinguish among different causes of vertical ocular misalignment.

The Effect of Acute Superior Oblique Palsy on Vertical Pursuit in Monkeys

PURPOSE To investigate vertical smooth pursuit eye movements in monkeys with acute acquired superior oblique palsy (SOP). METHODS The trochlear nerve was severed intracranially in two rhesus monkeys. After surgery, the paretic eye was patched for 6 or 9 days, and then binocular viewing was allowed. Eye movements were measured with binocular, dual search coils, before and after surgery, under monocular viewing conditions. Vertical pursuit movements along the midline were elicited by using triangular-wave (20 deg/s, +/-20 degrees ) or step-ramp (20 deg/s) stimuli at a distance of 66 cm. RESULTS During the early post-lesion period, before binocular viewing was allowed, pursuit velocity of the paretic eye during triangular-wave tracking was lower than that of the normal eye. When the viewing eye crossed straight ahead, the changes in pursuit velocity conjugacy were similar for upward and downward tracking. After habitual binocular viewing was allowed, differences between upward and downward pursuit emerged. When measured approximately 30 days after lesioning, this directional asymmetry was less during the open-loop period of step-ramp tracking than during triangular-wave tracking. CONCLUSIONS Rhesus monkeys with acute acquired SOP show characteristic changes in vertical pursuit, with deficits for both upward and downward tracking, and differences between the initiation of step-ramp pursuit and the sustained response during triangular-wave tracking. The habitual viewing condition (monocular versus binocular) also affected the pattern of deficit.

Vertical alignment in monkeys with unilateral IV section: effects of prolonged monocular patching and trigeminal deafferentation

We investigated monocular viewing and trigeminal (V) deafferentation on the vertical deviation (VD) in monkeys following intracranial IV section. Two monkeys wore a patch for four to six weeks, one over the paretic eye and the other over the normal eye following IV section. Two other monkeys had combined IV and V section with the paretic eye patched postlesion. In monkeys with IV section alone, the VD lessened within the first week postlesion but then increased gradually with the same eye still patched. Thus binocular viewing was unnecessary for the later VD increase. With combined IV and V section, the VD also transiently lessened postlesion. We have proposed that the decrease in VD after IV section is adaptive, driven by an error signal using ocular proprioception and efference copy. Since V section did not eliminate the early decrease in VD, we suggest some orbital afference is transmitted centrally via other cranial nerves. However, the later increase in VD suggests either that the proprioceptive effect cannot be sustained or that mechanical changes supervene to increase the VD.

Quantitative Eye Movement Recordings in a Patient with Acquired Bilateral Superior Oblique Palsy Before and After a Bilateral Harada-Ito Procedure

Purpose We examined the effects of the Harada-Ito procedure on static and dynamic alignment in an adult with acquired bilateral superior oblique palsy (SOP). Methods 3D eye movements were recorded before and six weeks after a bilateral Harada-Ito procedure. Superior oblique muscle (SOM) size and contractility were assessed with orbital imaging. Results On MRI, the left SOM was smaller than the right. Little contractile thickening was present in down gaze for either eye. Preoperatively, the patient had a hypertropia: 1.9° right hypertropia (at down 20°, left 20°) and 6.4° left hypertropia (at down 20°, right 20°). Postoperatively, the vertical tropia in all positions was < 1°. Listings primary position rotated toward straight ahead for the RE but was unchanged for the LE. Postoperatively, for 40° upward saccades peak dynamic intrasaccadic extorsion decreased by 2.2–3.2° for both eyes and for 40° downward saccades by 2.3–3.6° for the RE but was unchanged for the LE. Saccade conjugacy improved and post-saccadic drift lessened for all vertical saccades. Conclusions The Harada-Ito procedure produced striking improvements in static and dynamic alignment in bilateral SOP. Some changes were binocular (decreased post-saccadic drift, improved saccade conjugacy, less dynamic extorsion for upward saccades) but others were much greater in the less paretic eye (torsional gradients from up to down gaze, less dynamic extorsion for downward saccades). Both central adaptive and peripheral mechanical changes explain these findings. Our results also imply that the Harada-Ito procedure has more effect when there is residual function of the SOM.