Effects of ablation of flocculus and paraflocculus of eye movements in primate

Zee, David S.; Yamazaki, A; Butler, Paul; Gücer, G.

doi:10.1152/jn.1981.46.4.878

Cited by 786 publications

(446 citation statements)

References 24 publications

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“…1) for vertical eye movements is based on a previous proposal of how the cerebellum contributes to gaze holding (Glasauer 2003). The core assumption of this model is that the cerebellar FL is an integral part of vertical (and horizontal) gaze holding (as found experimentally, e.g., Zee et al 1981), which in our model is achieved by an eye-velocity feedback loop including an internal model of the eye plant to minimize errors between desired eye velocity (zero in case of fixation) and currently estimated eye velocity. To sufficiently explain ocular motor findings in cerebellar DBN, the model has to include structures and pathways (i) subserving gaze holding, (ii) of the angular VOR, (iii) mediating otolith signals, (iv) for vertical smooth pursuit eye movements, and (v) a saccadic burst generator for vertical saccades.…”

Section: Methodsmentioning

confidence: 99%

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A model-based theory on the origin of downbeat nystagmus

et al. 2008

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A model-based theory on the origin of downbeat nystagmus AbstractThe pathomechanism of downbeat nystagmus (DBN), an ocular motor sign typical for vestibulo-cerebellar lesions, remains unclear. Previous hypotheses conjectured various deficits such as an imbalance of central vertical vestibular or smooth pursuit pathways to be causative for the generation of spontaneous upward drift. However, none of the previous theories explains the full range of ocular motor deficits associated with DBN, i.e., impaired vertical smooth pursuit (SP), gaze evoked nystagmus, and gravity dependence of the upward drift. We propose a new hypothesis, which explains the ocular motor signs of DBN by damage of the inhibitory vertical gaze-velocity sensitive Purkinje cells (PCs) in the cerebellar flocculus (FL). These PCs show spontaneous activity and a physiological asymmetry in that most of them exhibit downward on-directions. Accordingly, a loss of vertical floccular PCs will lead to disinhibition of their brainstem target neurons and, consequently, to spontaneous upward drift, i.e., DBN. Since the FL is involved in generation and control of SP and gaze holding, a single lesion, e.g., damage to vertical floccular PCs, may also explain the associated ocular motor deficits. To test our hypothesis, we developed a computational model of vertical eye movements based on known ocular motor anatomy and physiology, which illustrates how cortical, cerebellar, and brainstem regions interact to generate the range of vertical eye movements seen in healthy subjects. Model simulation of the effect of extensive loss of floccular PCs resulted in ocular motor features typically associated with cerebellar DBN: (1) spontaneous upward drift due to decreased spontaneous PC activity, (2) gaze evoked nystagmus corresponding to failure of the cerebellar loop supporting neural integrator function, (3) asymmetric vertical SP deficit due to low gain and asymmetric attenuation of PC firing, and (4) gravity-dependence of DBN caused by an interaction of otolith-ocular pathways with impaired neural integrator function.

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Section: Methodsmentioning

confidence: 99%

“…The performance of the brainstem integrator is supported by feedback pathways through the FL, which augments the time constant of the inherently leaky 3 brainstem integrator (Zee et al 1981). In our model, these pathways consist in a negative velocity feedback loop (bold pathway in Fig.…”

Section: Gaze Holdingmentioning

confidence: 99%

A model-based theory on the origin of downbeat nystagmus

et al. 2008

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“…Early investigators thus classified this disease as a cerebellar ataxia syndrome and gave A-T its iconic name [1, 4, 6-8, 13, 23]. Many of the neurologic deficits apparent in individuals with A-T, such as gaze-evoked nystagmus, periodic alternating nystagmus (PAN), ocular motor apraxia, impaired smooth pursuit, saccadic dysmetria, ataxia, and kinetic tremor, point to degeneration of the cerebellar cortex [4,7,20,24,25,32,33].…”

Section: Introductionmentioning

confidence: 99%

Effects of 4-aminopyridine on nystagmus and vestibulo-ocular reflex in ataxia-telangiectasia

et al. 2013

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Ataxia-telangiectasia (A-T) is a progressive neurodegenerative disorder with prominent eye movement deficits localizing to the cerebellum. We sought to determine if 4-aminopyridine (4-AP), which putatively enhances the precision of Purkinje neurons, could improve the disorders of eye movements and vestibular function in A-T. The influence of 4-AP on disorders of eye movements and vestibular function was studied in four A-T patients. The effects on the cerebellar control of vestibulo-ocular reflex (VOR) was quantitatively assessed by the decay time constant of per-and post-rotational nystagmus during constant velocity en bloc rotations. The length of the VOR time constant determines the fidelity of the vestibular velocity storage, a neural mechanism that increases the bandwidth of VOR under cerebellar control. The VOR time constant was not increased in A-T patients. The latter is explained by the extent of cerebellar lesion as previously described in A-T and other cerebellar disorders. Nevertheless, 4-AP shortened the VOR time constant during horizontal rotations. Severe disinhibition of velocity storage in subjects with putatively profound cerebellar degeneration manifest periodic alternating nystagmus (PAN). Among two A-T subjects who manifested PAN, 4-AP reduced the peak slow phase velocity of the more severely affected individual and abrogated the PAN in the other. Two A-T subjects manifested horizontal and vertical spontaneous nystagmus (SN) in primary gaze, 4-AP reduced its slow phase velocity. We conclude that in subjects with A-T 4-AP has a prominent effect on the ocular motor and vestibular deficits that are ascribed to the loss of cerebellar Purkinje neurons. Effects of 4-aminopyridine on nystagmus and vestibulo-ocular reflex in ataxia-telangiectasia Nevertheless, 4-AP shortened the VOR time constant during horizontal rotations.Severe disinhibition of velocity storage in subjects with putatively profound cerebellar degeneration manifest periodic alternating nystagmus (PAN). Among two A-T subjects who manifested PAN, 4-AP reduced the peak slow-phase velocity of the more severely affected individual and abrogated the PAN in the other. Two A-T subjects manifested horizontal and vertical spontaneous nystagmus (SN) in primary gaze, 4-AP reduced its slow-phase velocity.We conclude that in subjects with A-T 4-AP has a prominent effect on the ocular motor and vestibular deficits that are ascribed to the loss of cerebellar Purkinje neurons.Introduction:

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“…At present, the role of the cerebellum in developing DPN is not clearly established. Growing evidence suggests that an imbalance in the vertical vestibulo-ocular reflex (vVOR) generates DPN [7], [20]. Purkinje cells, that are selectively involved in SCA6, are connected directly with the vestibular nucleus [20].…”

Section: Discussionmentioning

confidence: 99%

Downbeat positioning nystagmus is a common clinical feature despite variable phenotypes in an FHM1 family

et al. 2008

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Clinical examination and mutational analysis were carried out in three patients of a Japanese familial hemiplegic migraine (FHM) pedigree. Each affected member demonstrated a broad clinical spectrum that included hemiplegic migraine with progressive cerebellar ataxia, migraine without aura, and episodic ataxia. Despite this variability, all members exhibited marked downbeat positioning nystagmus, and magnetic resonance images (MRI) all showed cerebellar atrophy predominantly of the cerebellar vermis. All affected members had a T666M missense mutation in the protein encoded by the CACNA1A gene (calcium channel, voltage-dependent, P/Q type, alpha 1A subunit). Although clinical features associated with the T666M CACNA1A mutation are highly variable, downbeat positioning nystagmus may be an important clinical feature of this disease.

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Effects of ablation of flocculus and paraflocculus of eye movements in primate

Cited by 786 publications

References 24 publications

A model-based theory on the origin of downbeat nystagmus

A model-based theory on the origin of downbeat nystagmus

Effects of 4-aminopyridine on nystagmus and vestibulo-ocular reflex in ataxia-telangiectasia

Downbeat positioning nystagmus is a common clinical feature despite variable phenotypes in an FHM1 family

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