The goal of this career development proposal is to provide the educational and research training necessary for a career in ocular motor neuro-ophthalmology, with an emphasis on the role of the cerebellum in the three-axis (horizontal, vertical, and torsional) control of eye movements. The research plan involves a combination of experimental and modeling approaches with parallel studies in human cerebellar patients and non-human primates. Additional training components include formal instruction in statistics and data analysis, control system approaches to the ocular motor system, mentoring in neural modeling techniques, and additional instruction in clinical neuro-ophthalmology and strabismus. Although much has been learned about the cerebellar control of horizontal and vertical eye movements, studies of the cerebellar control of torsion are much more limited. The experiments in this proposal take advantage of recent advances in three-axis techniques to investigate the vestibulocerebellar, and particularly the floccular, contribution to eye torsion. Using a three-axis magnetic search coil technique, recordings will be made in human cerebellar patients and in primates before and after surgical floccular lesions. Experiments will address the control of three-axis eye velocity during eye movements evoked by visual (pursuit and optokinetic) and vestibular (low- and high-frequency) stimulation. The control of static torsion and binocular alignment will also be investigated. Later experiments will focus on the cerebellar contribution to the linear VOR and on the effects of lesions in other cerebellar regions on three-axis eye movement behavior. These experiments should provide a greater understanding of the pathophysiology of vestibulocerebellar lesions, as well the three-axis representation of visual and eye movement signals in the cerebellum. They also complement other recent studies dealing with peripheral mechanisms of torsion control. Finally, they may lead to a greater insight into the role of the cerebellum in compensating for lesions elsewhere in the ocular motor system, such as superior oblique pareses and other causes of strabismus. This might lead to better treatment for these disorders.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23EY000400-05
Application #
6665440
Study Section
Special Emphasis Panel (ZEY1-VSN (03))
Program Officer
Hunter, Chyren
Project Start
1999-09-30
Project End
2004-09-29
Budget Start
2003-09-30
Budget End
2004-09-29
Support Year
5
Fiscal Year
2003
Total Cost
$132,969
Indirect Cost
Name
Johns Hopkins University
Department
Neurology
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Shan, Xiaoyan; Tian, Jing; Ying, Howard S et al. (2008) The effect of acute superior oblique palsy on torsional optokinetic nystagmus in monkeys. Invest Ophthalmol Vis Sci 49:1421-8
Tian, Jing; Shan, Xiaoyan; Ying, Howard S et al. (2008) The effect of acute superior oblique palsy on vertical pursuit in monkeys. Invest Ophthalmol Vis Sci 49:3927-32
Shan, Xiaoyan; Ying, Howard S; Tian, Jing et al. (2007) Acute superior oblique palsy in monkeys: II. Changes in dynamic properties during vertical saccades. Invest Ophthalmol Vis Sci 48:2612-20
Shan, Xiaoyan; Tian, Jing; Ying, Howard S et al. (2007) Acute superior oblique palsy in monkeys: I. Changes in static eye alignment. Invest Ophthalmol Vis Sci 48:2602-11
Walker, Mark F; Tian, Jing; Zee, David S (2007) Kinematics of the rotational vestibuloocular reflex: role of the cerebellum. J Neurophysiol 98:295-302
Tian, Jing; Zee, David S; Walker, Mark F (2006) Eye-position dependence of torsional velocity during step-ramp pursuit and transient yaw rotation in humans. Exp Brain Res 171:225-30
Walker, Mark F; Zee, David S (2005) Asymmetry of the pitch vestibulo-ocular reflex in patients with cerebellar disease. Ann N Y Acad Sci 1039:349-58
Walker, Mark F; Zee, David S (2005) Cerebellar disease alters the axis of the high-acceleration vestibuloocular reflex. J Neurophysiol 94:3417-29
Walker, M F; Shelhamer, M; Zee, D S (2004) Eye-position dependence of torsional velocity during interaural translation, horizontal pursuit, and yaw-axis rotation in humans. Vision Res 44:613-20
Eggers, Sscott D Z; De Pennington, Nick; Walker, Mark F et al. (2003) Short-term adaptation of the VOR: non-retinal-slip error signals and saccade substitution. Ann N Y Acad Sci 1004:94-110

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