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.

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.

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.

Treatment of the gravity dependence of downbeat nystagmus with 3,4-diaminopyridine.

The authors examined the effect of 3,4-diaminopyridine (DAP) on the gravity-dependent (GD) vertical ocular drift component of downbeat nystagmus in 11 patients with idiopathic cerebellar ataxia. With the head tilted downward (45 degrees ), DAP reduced slow phase velocity (SPV) in 7 of 11 patients by 36%. Its efficacy correlated with the GD modulation. DAP minimizes the gravity-independent velocity bias and may improve deficient inhibitory cerebellar control on overacting otolith-ocular reflexes.

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.

Do predictive mechanisms improve the angular vestibulo-ocular reflex in vestibular neuritis?

Recovery from vestibular neuritis (VN) is often incomplete which leads to persistent vestibular imbalance during rapid head movements. Patients with unilateral vestibular lesions have a larger gain of the horizontal vestibulo-ocular reflex during active compared to passive head movements. To test whether this gain increase is related to predictive mechanisms we studied 15 patients with VN and 14 control subjects during predictable and unpredictable passive horizontal head impulses in the light and darkness. The vestibulo-ocular reflex showed a significantly shorter latency and higher gain in the light for predictable head impulses towards the ipsilesional side. However, this effect is small and might contribute but cannot exclusively account for the gain increase during active head movements.

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.

Differential vestibular dysfunction in sudden unilateral hearing loss.

Auditory and vestibular function was examined in 29 patients with unilateral sensorineural hearing loss to identify characteristic vestibulocochlear lesion patterns. In 45%, a vestibular lesion was found, of which 53% had a combined impairment of the cochlea and the ipsilateral posterior semicircular canal, possibly reflecting vascular disease in the common cochlear artery.

Persistence of perilymph fistula mechanism in a completely paretic posterior semicircular canal.

The three dimensional eye movements (search coil technique) of a patient with a completely paretic left posterior semicircular canal as a result of a perilymph fistula (PLF) were studied. The patient still exhibited pressure induced nystagmus that obeyed Ewald's first law. This finding cannot be explained by otolith stimulation, but might indicate that PLF mechanisms either persist in canal plugging or act on the ampulla by directly deflecting the cupula.

Spontaneous nystagmus in dorsolateral medullary infarction indicates vestibular semicircular canal imbalance.

BACKGROUND: Spontaneous nystagmus caused by dorsolateral medullary infarction may be of vestibular origin. OBJECTIVES: To test if imbalance of the central pathways of the semicircular canals contributes to spontaneous nystagmus in dorsolateral medullary syndrome. METHODS: We examined four patients with dorsolateral medullary syndrome and recorded spontaneous nystagmus binocularly at gaze straight ahead with the three-dimensional search coil technique. The median slow phase velocity of the nystagmus was analysed in the light and in the dark, and the normalised velocity axes were compared with the rotation axes as predicted from anatomical data of the semicircular canal. RESULTS: The slow phase rotation axes of all patients aligned best with the rotation axes resulting from stimulation of the contralesional posterior and horizontal semicircular canals. This alignment cannot be explained by pure otolith imbalance. CONCLUSION: We propose that vestibular imbalance caused by an ipsilesional lesion of the central semicircular canal pathways of the horizontal and anterior semicircular canals largely accounts for spontaneous nystagmus in dorsolateral medullary syndrome.