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Marti

Fakultäten » Medizinische Fakultät » Neurologie, Klinik für » Prof. Dr. Dominik Straumann » Marti

Completed research project

Title / Titel

Adaptive mechanisms of cerebellar eye movements: An fMRI study of afternystagmus induced by asymmetric smooth pursuit stimulation in healthy subjects and cerebellar patients

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Abstract (PDF, 14 KB)

Summary / Zusammenfassung

The cerebellum is fundamentally involved in generation and control of eye movements, and, consequently, cerebellar diseases lead to specific ocular motor disorders (for review, see(Leigh and Zee 2006)). Also, an important contribution of the cerebellum to higher-level neural processing for visual functions has been suggested in the recent past . However, essential aspects of cerebellar ocular motor neurophysiology still lack understanding and, for many of the cerebellar eye movement disorders, effective treatments are missing.
In the past few years, we have investigated various cerebellar ocular motor disorders with particular focus on downbeat nystagmus (DBN), a spontaneous vertical nystagmus, whose pathomechanism remains unclear (Marti et al. 2002; Marti et al. 2003; Sprenger et al. 2006; Straumann et al. 2000). Derived from our own experimental data as well as from earlier anatomical and neurophysiological findings, we recently compiled a new hypothesis on the origin of DBN, which is based on the inherent asymmetry of vertical gaze-velocity sensitive Purkinje cells (PCs) (Marti et al. 2005b). The huge majority of these vertical PCs have downward on-directions and inhibit brainstem target neurons with predominantly upward on-directions. Loss of floccular PCs, e.g. due to cerebellar degeneration, will lead to a disinhibition of their brainstem target neurons and therefore to spontaneous upward drift. To test our hypothesis, we designed a computational model of vertical eye movements, which was derived from clinical knowledge. We also have established a human model to study vertical nystagmus (Marti et al. 2005a). Our experiments demonstrated that prolonged asymmetric smooth pursuit stimulation represents a useful technique to evoke strong and enduring vertical (and horizontal) nystagmus in healthy human subjects.
We currently concentrate on adaptive processes of eye movements. The importance of the cerebellum for modification of various motor behaviors, e.g. locomotion, prism-adaptation or modification of the vestibulo-ocular reflex, is well known. Similarly, the cerebellum seems to play a major role for mechanisms and processes involved in adaptation of eye movements, as can already be suspected from clinical observations: For example, upbeat nystagmus (UBN) typically is of only short duration, while DBN persists. Most probably, adaptive mechanisms controlled by intact cerebellar structures gradually attenuate the downward ocular drift in patients with UBN due to focal brainstem lesions, but intact cerebellar structures. Facilitation and enhancement of such adaptive processes may probably offer important new therapeutic options for these diseases.
The paradigm of asymmetric smooth pursuit stimulation is well suited to study in detail aspects of adaptation and modification of ocular motor disorders. Prolonged exposure to unidirectional smooth pursuit evokes a strong afternystagmus in direction of the former pursuit, reflecting the state of adaptation within the smooth pursuit system (Marti et al. 2005a). Specifically, we plan, in both healthy human subjects and cerebellar patients, a combined ocular motor and fMRI study of the activation patterns during the stimulated phase compared to the activation patterns during the afternystagmus phase without any visual stimulation. The analysis and comparison of the activation patterns will shed light on the different structures, which are involved in the generation of afternystagmus, and will indicate to what extent ocular motor adaptation processes in cerebellar patients still are operating. Another important aspect of the study is the evaluation of the role of functional brain imaging in the diagnosis of brainstem and cerebellar ocular motor disorders. On a long-term perspective, we aim to establish functional imaging as the alternative to animal experiments for studies of anatomical and pathophysiological issues. To conclude, the current application will enable us to continue the investigation of cerebellar ocular motor neurology and to contribute to the development of new diagnostic and therapeutic measures for cerebellar diseases.

Publications / Publikationen

Marti S, Bockisch CJ, Straumann D (2005a) Prolonged asymmetric smooth-pursuit stimulation leads to downbeat nystagmus in healthy human subjects. Invest Ophthalmol Vis Sci 46:143-149
Marti, S., Palla, A., and Straumann, D. Barbecue Whole-Body Position Modulates Cerebellar Downbeat Nystagmus. Ann.N.Y.Acad.Sci 1004, 490-491. 2003.
Ref Type: Abstract
Marti S, Palla A, Straumann D (2002) Gravity dependence of ocular drift in patients with cerebellar downbeat nystagmus. Ann Neurol 52:712-721
Marti S, Straumann D, Glasauer S (2005b) The origin of downbeat nystagmus: an asymmetry in the distribution of on-directions of vertical gaze-velocity Purkinje cells. Ann N Y Acad Sci 1039:548-553
Sprenger A, Rambold H, Sander T, Marti S, Weber K, Straumann D, Helmchen C (2006) Treatment of the gravity dependence of downbeat nystagmus with 3,4-diaminopyridine. Neurology 67:905-907
Straumann D, Zee DS, Solomon D (2000) Three-dimensional kinematics of ocular drift in humans with cerebellar atrophy. J Neurophysiol 83:1125-1140

Keywords / Suchbegriffe

cerebellum, ocular motor, smooth pursuit, adaptation, fMRI

Project leadership and contacts /
Projektleitung und Kontakte

Dr. Sarah Marti, MD (Project Leader)	sarah.marti@usz.ch
Prof. med. Dominik Straumann, MD	dominik@neurol.unizh.ch
Prof. Bruno Weber, PhD	bweber@pharma.uzh.ch
Dr. Valerie Treyer, PhD	valerie.treyer@usz.ch