Visuomotor Cerebellum in Human and Nonhuman Primates

In this paper, we will review the anatomical components of the visuomotor cerebellum in human and, where possible, in non-human primates and discuss their function in relation to those of extracerebellar visuomotor regions with which they are connected. The floccular lobe, the dorsal paraflocculus, the oculomotor vermis, the uvula–nodulus, and the ansiform lobule are more or less independent components of the visuomotor cerebellum that are involved in different corticocerebellar and/or brain stem olivocerebellar loops. The floccular lobe and the oculomotor vermis share different mossy fiber inputs from the brain stem; the dorsal paraflocculus and the ansiform lobule receive corticopontine mossy fibers from postrolandic visual areas and the frontal eye fields, respectively. Of the visuomotor functions of the cerebellum, the vestibulo-ocular reflex is controlled by the floccular lobe; saccadic eye movements are controlled by the oculomotor vermis and ansiform lobule, while control of smooth pursuit involves all these cerebellar visuomotor regions. Functional imaging studies in humans further emphasize cerebellar involvement in visual reflexive eye movements and are discussed

Current Treatment of Vestibular, Ocular Motor Disorders and Nystagmus

Vertigo and dizziness are among the most common complaints with a lifetime prevalence of about 30%. The various forms of vestibular disorders can be treated with pharmacological therapy, physical therapy, psychotherapeutic measures or, rarely, surgery. In this review, the current pharmacological treatment options for peripheral and central vestibular, cerebellar and ocular motor disorders will be described. They are as follows for peripheral vestibular disorders. In vestibular neuritis recovery of the peripheral vestibular function can be improved by treatment with oral corticosteroids. In Menière's disease a recent study showed long-term high-dose treatment with betahistine has a significant effect on the frequency of the attacks. The use of aminopyridines introduced a new therapeutic principle in the treatment of downbeat and upbeat nystagmus and episodic ataxia type 2 (EA 2). These potassium channel blockers presumably increase the activity and excitability of cerebellar Purkinje cells, thereby augmenting the inhibitory influence of these cells on vestibular and cerebellar nuclei. A few studies showed that baclofen improves periodic alternating nystagmus, and gabapentin and memantine, pendular nystagmus. However, many other eye movement disorders such as ocular flutter opsoclonus, central positioning, or see-saw nystagmus are still difficult to treat. Although progress has been made in the treatment of vestibular neuritis, downbeat and upbeat nystagmus, as well as EA 2, state-of-the-art trials must still be performed on many vestibular and ocular motor disorders, namely Menière's disease, bilateral vestibular failure, vestibular paroxysmia, vestibular migraine, and many forms of central eye movement disorders

A model-based theory on the origin of downbeat nystagmus

The 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