Eye movements are now widely used as experimental tools in the neurosciences, including studies of memory and volition. The popularity of eye movements derives from their accessibility for measurement and analysis, combined with a broad understanding of their neural substrate. Clinicians mainly depend on basic aspects of gaze control to guide their diagnosis, such as how the brain makes the eyes move together (conjugacy). The proposed research takes aim at several of these basic aspects of the control of eye movements, including properties that are critical for vision to remain clear and single. It also applies one of these basic properties, the conjugacy of horizontal fast movements, to develop a simple model to study the common complaint of fatigue in multiple sclerosis (MS). The research strategy will be to investigate gaze abnormalities by applying and testing current models for the control of eye movements that have been developed from both basic and clinical studies: translational research. The three specific aims grow from work accomplished during the prior funding period: The first project concerns the beginning and ending of rapid eye movements (saccades). The first hypothesis to be tested is that the mechanism generating the beginning of saccades consists of a sudden, stereotyped activation of saccade-generating burst neurons when inhibition is removed from them (post-inhibitory rebound discharge). A second hypothesis is that the ending of saccades is determined by when the cerebellar fastigial nucleus switches firing from excitatory to inhibitory burst neurons. The second project aims to develop an ocular motor model for the phenomenon of fatigue in MS. Preliminary studies indicate that the peak velocity of adducting movements declines relative to the peak velocity of abducting movements during repetitive saccades (a fatigue test) made by MS patients but not by control subjects. The third project aims to better understand a form of acquired nystagmus (oculopalatal tremor) that impairs vision. A current model for these oscillations will be tested using detailed findings from a treatment trial of memantine versus gabapentin completed during the prior funding period.

Public Health Relevance

Taken together, the three proposed projects will provide new information concerning the pathogenesis and treatment of common and visually disabling disorders of eye movements. Eye movements will also be put to work as an experimental tool to investigate the mechanism of generalized fatigue, which afflicts most patients with MS.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY006717-26
Application #
8215703
Study Section
Special Emphasis Panel (ZRG1-IFCN-A (02))
Program Officer
Araj, Houmam H
Project Start
1986-12-01
Project End
2013-09-30
Budget Start
2012-02-01
Budget End
2013-09-30
Support Year
26
Fiscal Year
2012
Total Cost
$150,720
Indirect Cost
$54,720
Name
Case Western Reserve University
Department
Neurosciences
Type
Schools of Medicine
DUNS #
077758407
City
Cleveland
State
OH
Country
United States
Zip Code
44106
Shaikh, Aasef G (2016) Abnormal head oscillations in neuro-ophthalmology and neuro-otology. Curr Opin Neurol 29:94-103
Shaikh, Aasef G; Otero-Millan, Jorge; Kumar, Priyanka et al. (2016) Abnormal Fixational Eye Movements in Amblyopia. PLoS One 11:e0149953
Shaikh, Aasef G; Ghasia, Fatema F; DeLong, Mahlon R et al. (2015) Ocular palatal tremor plus dystonia - new syndromic association. Mov Disord Clin Pract 2:267-270
McCamy, Michael B; Otero-Millan, Jorge; Leigh, R John et al. (2015) Simultaneous recordings of human microsaccades and drifts with a contemporary video eye tracker and the search coil technique. PLoS One 10:e0128428
Shaikh, Aasef G; Ghasia, Fatema F (2015) Neuro-ophthalmology of type 1 Chiari malformation. Expert Rev Ophthalmol 10:351-357
Ghasia, Fatema F; Shaikh, Aasef G; Jacobs, Jonathan et al. (2015) Cross-coupled eye movement supports neural origin of pattern strabismus. Invest Ophthalmol Vis Sci 56:2855-66
Ghasia, Fatema F; Gulati, Deepak; Westbrook, Edward L et al. (2014) Viewing condition dependence of the gaze-evoked nystagmus in Arnold Chiari type 1 malformation. J Neurol Sci 339:134-9
Schneider, Rosalyn; Walker, Mark F (2014) Amplitude and frequency prediction in the translational vestibulo-ocular reflex. J Vestib Res 24:357-64
Shaikh, Aasef G; Ghasia, Fatema F (2014) Gaze holding after anterior-inferior temporal lobectomy. Neurol Sci 35:1749-56
Schneider, Rosalyn; Liao, Ke; Walker, Mark F et al. (2014) Behavior of the human translational vestibulo-ocular reflex during simultaneous head translation and rotation. J Vestib Res 24:329-33

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