Experimental Brain Research

, 188:613

A model-based theory on the origin of downbeat nystagmus

Authors

    • Neurology DepartmentZurich University Hospital
  • Dominik Straumann
    • Neurology DepartmentZurich University Hospital
  • Ulrich Büttner
    • Department of NeurologyLudwig Maximilians University
    • Bernstein Center for Computational Neuroscience
  • Stefan Glasauer
    • Department of NeurologyLudwig Maximilians University
    • Bernstein Center for Computational Neuroscience
Research Article

DOI: 10.1007/s00221-008-1396-7

Cite this article as:
Marti, S., Straumann, D., Büttner, U. et al. Exp Brain Res (2008) 188: 613. doi:10.1007/s00221-008-1396-7

Abstract

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.

Keywords

CerebellumEye movementsModelingDownbeat nystagmus

Abbreviations

4-AP

4-Aminopyridine

3,4-DAP

3,4-Diaminopyridine

DBN

Downbeat nystagmus

DCN

Deep cerebellar nuclei

DLPN

Dorsolateral pontine nuclei

DV

Dorsal vermis

FEF

Frontal eye field

FEFsem

Smooth pursuit subregion of the FEF

FL

Floccular lobe

FN

Fastigial nucleus

FTN

Floccular target neurons

INC

Interstitial nucleus of Cajal

MLF

Medial longitudinal fasciculus

MST

Middle superior temporal area

MT

Middle temporal area

NRTP

Nucleus reticularis tegmentum pontis

OMN

Ocular motor neurons

PC

Purkinje cell

PMT

Paramedian tract

SCC

Semicircular canal

SVN

Superior vestibular nucleus

SP

Smooth pursuit

UBN

Upbeat nystagmus

VOR

Vestibulo-ocular reflex

VTT

Ventral tegmental tract

Y

Y-group

Copyright information

© Springer-Verlag 2008