Probing Early Motion Processing With Eye Movements: Differences of Vestibular Migraine, Migraine With and Without Aura in the Attack Free Interval.

BACKGROUND: Migraineurs, in between headache attacks, have a different sensitivity to sensory motion stimuli compared to non-migraineurs. METHODS: This cross-sectional laboratory study examines the motion processing in migraineurs using ocular following responses (OFR) elicited by large field random dot patterns and open-loop smooth pursuit eye movements (PS) elicited by a single target moving on a homogenous background. Eye movements were recorded with a video-oculographic system (EyeSeeTec® ) and stimuli presented on a CRT at 100 Hz repetition rate to horizontal stimuli of a velocity of 2.5 to 160°/s. Eye movements were analyzed during the open loop period. RESULTS: We recorded 43 migraine patients: 14 migraine with (MwA), 19 without aura (MwoA), 10 vestibular migraine (VM), and 16 healthy controls. ANOVA analysis of OFR responses amplitudes showed significant differences in the subgroup (control, MwA, MwoA, and VM) (F3,409 =29.8, P < .001), stimulus velocity (F6,406 =12.6, P < .001), and interaction (F18,394 =1.9, P = .015). Fitting the OFR response velocity tuning by a "Weibull" function showed that the subgroups were different in the linear scaling factor (F4,53 = 4.3, P < .001) but not in parameters defining the overall form of the tuning function. In contrast, the initial open-loop responses of PS were not changed compared to control for the three different migraine subgroups. CONCLUSION: From the findings, we hypothesize that in the migraine subtypes, MwA and VM, there is different sensory motion information processing for OFR compared to MwoA and control, not explained by a neuronal hyperexcitability in V5. OFR might be a possible subclinical marker in the future to diagnose MwA and VM.

Vergence deficits in patients with cerebellar lesions.

The cerebellum is part of the cortico-ponto-cerebellar circuit for conjugate eye movements. Recent animal data suggest an additional role of the cerebellum for the control of binocular alignment and disconjugate, i.e. vergence eye movements. The latter is separated into two different components: fast vergence (to step targets) and slow vergence (to ramp and sinusoidal targets). The aim of this study was to investigate whether circumscribed cerebellar lesions affect these dynamic vergence eye movements. Disconjugate fast and slow vergence, conjugate smooth pursuit and saccades were binocularly recorded by a scleral search coil system in 20 patients with acute cerebellar lesions (all ischemic strokes except for one) and 20 age-matched healthy controls. Patients showed impairment of slow vergence while fast vergence was unaffected. Slow vergence gain to sinusoidal targets was significantly reduced, both in convergence and divergence direction. Divergence but not convergence velocity to ramp targets was reduced. Conjugate smooth pursuit eye movements to sinusoidal and to step-ramp targets were impaired. Patients had saccadic hypometria. All defects were particularly expressed in patients with vermis lesions. In contrast to recent animal data fast vergence was not impaired in any of our patient subgroups. We conclude that (i) the human cerebellum, in particular the vermis, is involved in the processing of dynamic vergence eye movements and (ii) cerebellar lesions elicit dissociable effects on fast and slow vergence.

Human vergence eye movements to oblique disparity stimuli: evidence for an anisotropy favoring horizontal disparities.

Binocular disparities applied to large-field patterns elicit vergence eye movements at ultra-short latencies. We used the electromagnetic search coil technique to record the horizontal and vertical positions of both eyes while subjects briefly viewed (150 ms) large patterns that were identical at the two eyes except for a difference in position (binocular disparity) that was varied in direction from trial to trial. For accurate alignment with the stimuli, the horizontal and vertical disparity vergence responses (HDVRs, VDVRs) should vary as the sine and cosine, respectively, of the direction of the disparity stimulus vector. In a first experiment, using random-dots patterns (RDs) with a binocular disparity of 0.2 degrees , this was indeed the case. In a second experiment, using 1-D sine-wave gratings with a binocular phase difference (disparity) of 1/4-wavelength, it was not the case: HDVRs were maximal when the grating was vertical and showed little decrement until the grating was oriented more than approximately 65 degrees away from vertical, whereas VDVRs were maximal when the grating was horizontal and began to decrement roughly linearly when the grating was oriented away from the horizontal. We attribute these complex directional dependencies with gratings to the aperture problem, and the HDVR data strongly resemble the stereothresholds for 1-D gratings, which are minimal when the gratings are vertical and remain constant for orientations up to approximately 80 degrees away from the vertical when expressed as spatial phase disparities [Morgan, M. J., & Castet, E. (1997). The aperture problem in stereopsis. Vision Research, 37, 2737-2744.]. To explain this constancy of stereothresholds, Morgan and Castet (1997) postulated detectors sensitive to the phase disparity of the gratings seen by the two eyes (rather than their linear separation along some fixed axis, such as the horizontal). However, because (1) our VDVR data with gratings did not show this constancy and (2) the available evidence strongly suggests that there are no major differences in the disparity detectors mediating the initial HDVR and VDVR, we sought an alternative explanation for our data. We show that the dependence of the initial HDVR and VDVR on grating orientation can be successfully modeled by a bias in the number and/or efficacy of the detectors that favors horizontal disparities.

The eyelid and its contribution to eye movements.

Lid and electromyographic recordings have contributed significantly to our understanding of clinical lid disorders. Tonic lid disorders (e.g. ptosis, blepharospasm, lid retraction, blepharocolysis) can be distinguished from dynamic lid disorders (lid lag) and from specific deficits of eye-lid coordination (e.g. lid nystagmus). Electromyographic recordings allow the identification of specific lid disorders that benefit from effective therapeutic interventions, e.g., botulinum toxin injections. Rapid lid closure (blink), which exerts substantial neural influence on oculomotor systems without obscuring vision, can be used for the diagnosis of brainstem disease.

Blink amplitude but not saccadic hypometria indicates carriers of Parkin mutations.

We investigated saccades, eyelid blinks, and their interaction in symptomatic (n = 22) and asymptomatic (n = 31) subjects with (n = 19) and without (n = 34) Parkin mutations. Saccadic hypometria was correlated with clinical symptoms of Parkinson's disease, irrespective of mutational status. By contrast, blink amplitude was increased in carriers of Parkin mutations independent of their clinical status. Saccade main sequence and blink effects on saccades were normal. We propose that increased blink amplitude may serve as an endophenotype in carriers of Parkin mutations.

Pontine lesions may cause selective deficits of "slow" vergence eye movements.

To address the role of pontine nuclei in vergence control, eye movements to ramp ('slow vergence') and step targets ('fast vergence') were recorded in two patients with unilateral mediolateral pontine infarctions and in ten healthy controls. 'Slow' vergence and conjugate smooth pursuit eye movements were impaired while 'fast' vergence was not. We conclude that like smooth pursuit signals, vergence signals are distributed in the pontine nuclei.

Seesaw nystagmus associated with involuntary torsional head oscillations.

OBJECTIVE: To assess the diagnostic value of eye-head coupling in seesaw nystagmus (SSN). BACKGROUND: SSN is a rare binocular disorder characterized by alternating skew deviation and conjugate ocular torsion. METHODS: We examined a patient with a congenital nystagmus that switched to a pendular SSN on near viewing and was associated with involuntary torsional head oscillations. RESULTS: The binocular torsional eye movements were in phase with the clinically visible head oscillations (i.e., head movements were not compensatory for the torsional eye movements). CONCLUSION: This finding suggests that torsional eye-head coupling in pendular SSN has a common pathologic origin. We suggest that alternating vertical disparity of both eyes in pendular SSN is compatible with an oscillating signal acting on an intact vestibular system. The absence of brainstem lesions on high-resolution MRI supports this assumption.

Perilymph fistula associated with pulse-synchronous eye oscillations.

Three-dimensional eye movements (scleral search coil system) were recorded in a patient with a surgically acquired perilymph fistula of the left horizontal semicircular canal. Spontaneous horizontal pendular nystagmus was found to be related to the heart rate and may be caused by pressure transfer of blood pulses to the labyrinth. In addition, a contralesional horizontal jerk nystagmus was elicited by Valsalva maneuver, indicating that Ewald's first law may not only be valid for excitation but also for inhibition.

Localizing value of torsional nystagmus in small midbrain lesions.

BACKGROUND: The topodiagnostic value and specificity of nystagmus in patients with mesencephalic lesions and its relation to tonic torsional deficits and vertical saccade deficits is controversial and anecdotal. METHODS: The authors examined 11 patients with vascular MRI-identified mesencephalic lesions and clinical evidence of vertical-torsional nystagmus on gaze straight ahead, focusing on the three-dimensional nystagmus components recorded with the three-dimensional search coil technique. RESULTS: Combined lesions of the rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF) and the interstitial nucleus of Cajal (iC) are much more frequent than riMLF and, in particular, iC lesions alone. Eight patients showed contralesional torsional nystagmus with a conjugate vertical component on gaze straight ahead and had anatomic (MRI) and clinical evidence (slowing of vertical saccades) for riMLF involvement. Tonic ocular torsion and the subjective visual vertical were shifted to the contralesional side (n = 7). Torsional nystagmus to the ipsilesional side was uncommon (n = 3) and found in patients with midbrain lesions involving the iC, all of whom also had decreased time constants of the slow phases of gaze-evoked nystagmus. CONCLUSIONS: Contrary to previous proposals, contralesional torsional nystagmus was the most frequent direction and is probably not compensatory for contralesional tonic ocular torsion. Small amplitude vertical saccades with normal velocities in association with ipsilesional torsional nystagmus may indicate isolated iC lesions. Torsional nystagmus following mesencephalic lesions may last for years and may help to distinguish rostral (riMLF) from caudal (iC) midbrain lesions.

Vestibular influence on the binocular control of vertical-torsional nystagmus after lesions in the interstitial nucleus of Cajal.

The interstitial nucleus of Cajal (iC) is a center of the velocity-to-position integration for vertical and torsional eye movements. In addition, iC has projections to and from the vestibular nuclei. Therefore the vestibular influence on the binocular alignment of vertical-torsional nystagmus after unilateral reversible iC inactivations was investigated in the alert monkey using 3D binocular search-coil recordings. The nystagmus was compared with the eye muscle rotation axes, which were corrected for the tonic ocular torsion elicited by the iC inactivation. Rotation axes of nystagmus were different for both eyes and revealed a co-activation of eye muscles similar to the effects of electrical stimulation of the anterior canal nerve. This suggests that, in addition to the deficient neural integrator, a vestibular imbalance contributes to the vertical-torsional nystagmus after iC inactivations.

Unilateral muscimol inactivations of the interstitial nucleus of Cajal in the alert rhesus monkey do not elicit seesaw nystagmus.

Seesaw-nystagmus (SSN) is a unique form of nystagmus with disconjugate vertical and conjugate torsional eye movements. Although rare, this disorder serves as a model for neuronal binocular control of the alignment of vertical-torsional eye movements of both eyes. The pathomechanism of SSN, however, is unclear. Studies in patients have suggested that the jerk SSN is associated with a midbrain lesion, i.e. a lesion of the interstitial nucleus of Cajal (iC), a center of integration of vertical and torsional eye movements. To test this hypothesis, we examined three dimensional binocular eye movements after reversible local inactivations of the iC and its immediate vicinity in the midbrain of the alert monkey. Inactivations were induced by muscimol microinjections. Eye movements were recorded with binocular scleral search coils. Isolated inactivations of neither the iC nor its immediate vicinity in the midbrain (including the adjacent rostral interstitial nucleus of the medial longitudinal fascicle, riMLF) elicited a disconjugate vertical/torsional nystagmus (SSN). However, there was a direction-specific right/left asymmetry in which a larger vertical amplitude was associated with the contralesional eye and a larger torsional amplitude with the ipsilesional eye, indicating a vestibular imbalance. We conclude that, first, iC lesions do not elicit SSN and, second, that apart from the gaze holding deficit a vestibular imbalance contributes to the vertical/torsional nystagmus after iC lesions.

Short-latency disparity vergence eye movements: dependence on the preëxisting vergence angle.

We recorded the vergence eye movements that are elicited at ultra-short latencies when binocular disparities are applied to large-field patterns (Busettini, C., Miles, F.A. and Krauzlis, R.J. (1996). J. Neurophysiol., 75: 1392-1410) and determined their dependence on the preëxisting vergence angle (PVA). The search coil technique was used to record the movements of both eyes in four healthy subjects (two with presbyopia). Using dichoptic viewing, the two eyes saw identical images each consisting of a fixation cross at the centre of a random-dot pattern in a circular aperture. The subject fixated the crosses and then the images (crosses, random dots, windows) moved horizontally (1.5 degrees/s) in opposite directions so as to bring the eyes to the desired horizontal vergence position without changing the accommodation demand. After a further 800-1200 ms to permit fusion at this new vergence angle (now, the PVA), a disparity step was applied and, 200 ms later, the screen changed to uniform grey, marking the end of the trial. The disparity steps could have one of six magnitudes and four directions (crossed, uncrossed, right-hyper, left-hyper) while the PVA was varied systematically. The horizontal and vertical disparity vergence responses (DVRs) of one of the presbyopes consistently showed robust linear dependence on the PVA (r(2)>0.96). The horizontal DVRs of the other three subjects showed no sensitivity to the PVA and their vertical DVRs showed only very weak dependence. The experiment was repeated on one of the non-presbyopes after cycloplegia, but the outcome was the same, indicating that the negative findings were not due to the influence of the vergence-accommodation response. Our data indicate that the DVRs can be scaled by the PVA, but most subjects do not show this effect, perhaps because they relied on other distance cues that are uninformative in our experimental situation.

Tracking in 3-D space under natural viewing condition.

To track a small visual target in 3-D space, the two eyes have to move in different directions and/or at different velocities. This tracking might be accomplished by a disjunctive pursuit system, which uses separate motion processing of each individual eye but no disparity signal (hypothesis 1), or by the conjugate pursuit and the vergence system (hypothesis 2). To test the validity of the two hypotheses we recorded eye movements in five healthy human subjects with the scleral search-coil method. A small dim laser stimulus was presented on an earth horizontal platform. A position-ramp stimulus was presented in eight different directions: rightward or leftward, convergence or divergence, or a combination of them. We compared a fusible with an un-fused and a monocular viewing condition to assess whether a disparity signal is needed for 3-D tracking. Fusion was prevented by a vertical prism. We compared the monocular with the prism viewing condition to examine the effect of retinal motion signals of either one or both eyes on the tracking performance in the absence of disparity signals. Results revealed severe impairment of tracking in depth, while tracking in pure horizontal directions remained unaffected during the prism and monocular as compared to the binocular viewing condition. These data support hypothesis 2.

Eye movement abnormalities in spinocerebellar ataxia type 17 (SCA17).

BACKGROUND: Spinocerebellar ataxia type 17 (SCA17) is associated with an expansion of CAG/CAA trinucleotide repeats in the gene encoding the TATA-binding protein. In this quantitative characterization of eye movements in SCA17 mutation carriers, we investigated whether eye movement abnormalities originate from multiple lesion sites as suggested by their phenotypic heterogeneity. METHODS: Eye movements (saccades, smooth pursuit) of 15 SCA17 mutation carriers (mean age 36.9 years, range 20 to 54 years; mean disease duration 7.3 years, range 0 to 20 years; 2 clinically unaffected, 13 affected) were compared with 15 age-matched control subjects using the video-based two-dimensional EYELINK II system. RESULTS: Smooth pursuit initiation (step-ramp paradigm) and maintenance were strongly impaired, i.e., pursuit latency was increased and acceleration decreased, whereas latency and position error of the first catch-up saccade were normal. Visually guided saccades were hypometric but had normal velocities. Gaze-evoked nystagmus was found in one-third of the mutation carriers, including downbeat and rebound nystagmus. There was a pathologic increase in error rates of antisaccades (52%) and memory-guided saccades (42%). Oculomotor disorders were not correlated with repeat length. Smooth pursuit impairment and saccadic disorders increased with disease duration. CONCLUSIONS: Several oculomotor deficits of spinocerebellar ataxia type 17 (SCA17) mutation carriers are compatible with cerebellar degeneration. This is consistent with histopathologic and imaging (morphometric) data. In contrast, increased error rates in antisaccades and memory-guided saccades point to a deficient frontal inhibition of reflexive movements, which is probably best explained by cortical dysfunction and may be related to other phenotypic SCA17 signs, e.g., dementia and parkinsonism.