"Leaky" and "Unstable" Neural Integrator Can Coexist-Paradox Observed in Multiple Sclerosis

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Title "Leaky" and "Unstable" Neural Integrator Can Coexist-Paradox Observed in Multiple Sclerosis
Creator Palak Gupta, Aasef G. Shaikh
Affiliation Departments of Neurology and Biomedical Engineering (P.G., A.G.S.), Case Western Reserve University, Cleveland, Ohio; Neurological Institute (P.G., A.G.S.), University Hospitals Cleveland Medical Center, Cleveland, Ohio; and Daroff-Dell'Osso Ocular Motor Laboratory (P.G., A.G.S.), Louis Stokes Cleveland VA Medical Center, Cleveland, Ohio
Abstract The mechanism for stable gaze-holding requires a neural integrator that converts pulse of neural discharge to steady firing rate. The integrator is feedback-dependent, impaired feedback manifests as either "unstable" integration when it is too much or "leaky" when it is too little. The "unstable" integrator is known to cause sinusoidal oscillations of the eyes called pendular nystagmus, whereas the "leaky" integrator causes jerky eye oscillations called gaze-evoked nystagmus. We hypothesized that integrator can be simultaneously leaky and unstable. Mechanistically, some parts of network are served by increased feedback gain (unstable network), while other part would be decreased feedback gain (leaky). Both leaky and unstable, the network converges on the ocular motor plant, leading to simultaneously present gaze-evoked jerk and sinusoidal nystagmus. We tested our hypothesis by measuring eye movements with search coil technique in 7 multiple sclerosis patients. Five of these patients had gaze-evoked nystagmus and superimposed pendular nystagmus. The gaze-evoked nystagmus depicted all the features of "leaky" integrator, that is, the drifts were always toward the null that was located at the central eye-in-orbit orientation, there were no drifts at null, and the drift velocity increased as the eyes moved farther away from the null. The pendular nystagmus had all the features of "unstable" integrator, that is, constant 4- to 6-Hz frequency, eye-in-orbit position dependence of the oscillation amplitude, and the voluntary saccade causing an oscillatory phase reset. These features were then simulated in a computational model conceptualizing our hypothesis of simultaneously leaky and unstable neural integrator.
OCR Text Show
Date 2020-06
Language eng
Format application/pdf
Type Text
Publication Type Journal Article
Source Journal of Neuro-Ophthalmology, June 2020, Volume 40, Issue 2
Publisher Lippincott, Williams & Wilkins
Holding Institution Spencer S. Eccles Health Sciences Library, University of Utah, 10 N 1900 E SLC, UT 84112-5890
Rights Management © North American Neuro-Ophthalmology Society
ARK ark:/87278/s6s52gg6
Setname ehsl_novel_jno
ID 1592944
Reference URL https://collections.lib.utah.edu/ark:/87278/s6s52gg6
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