Project

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Ocular motor plasticy following vestibular tone asymmetry in humans

Applicant Hegemann Stefan
Number 122535
Funding scheme Project funding (Div. I-III)
Research institution ORL-Klinik Universitätsspital Zürich
Institution of higher education University of Zurich - ZH
Main discipline Neurophysiology and Brain Research
Start/End 01.08.2009 - 28.02.2013
Approved amount 340'000.00
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All Disciplines (2)

Discipline
Neurophysiology and Brain Research
Pathophysiology

Keywords (14)

oculomotor; neural integrator; adaptation; human; brain function; retinal image stabilisation; nystagmus; galvanic vestibular stimulation; caloric vestibular stimulation; vestibular tone asymmety; time constant; 3-D eye movements; neural model; vestibular

Lay Summary (English)

Lead
Lay summary
The goal of this study is to better understand immediate adaptive processes of the human brain to sudden vestibular asymmetry like in unilateral vestibular deficits (UVD), caloric (CS) and galvanic vestibular stimulation (GVS). Until now, mainly central adaptation of the physiologic vestibulo-ocular reflex (VOR) and long-term adaptive processes after central and peripheral vestibular lesions have been investigated. A key reaction being observed in most patients with acute UVD is Alexander's law (AL). It states that the velocity of eye drift during nystagmus is dependent on horizontal gaze position. AL is believed to be generated by short term adaptive changes in the oculomotor neural integrator (NI). Integration of eye velocity into eye position signals - in a mathematical sense - is necessary to enable eccentric gaze holding and is performed by a neural network referred to as the oculomotor NI. Lack of integration leads to centripetal eye drift resulting in gaze evoked nystagmus. Gaze evoked nystagmus is assumed to combine with the constant vestibular eye drift of peripheral nystagmus leading to AL. AL usually develops during the first 30 s of nystagmus and is considered a fast adaptive mechanism to help stabilizing gaze at least in one direction. Thus, AL seems optimally suited to study vestibuo-ocular adaptation. Furthermore, the oculomotor NI is the most thoroughly investigated NI so far, providing solid physiological data to depart with. However, there exists no three-dimensional analysis of AL, it is not completely understood how exactly integration is performed by the brain, how adaptation of the NI is triggered and what role it plays in central compensation. To understand these fundamental processes we will pursue the following aims: 1) Investigate eye movemnts in 3-D to get information about the NI in three dimensions and the effect of different stimuli, like caloric or galvanic stimulation to detect, which signals cause the adaptation. 2) Investigate the effect of different error signals (e.g. with or without retinal image stabilization) and find out which ones are important and which not. and 3) Create improved models of the human horizontal and vertical/torsional oculomotor NI and try to combine these models into a 3-D NI-model. The project elucidates major physiological principles of short term adaptive neuronal plasticity to vestibular disturbances, NI function and mutual interaction of multiple integrators. The results will have impact on understanding brain function in general and specifically ocular motor control. In addition it reveals pathomechanisms of vestibular disorders as well as their central compensation in humans.
Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants

Employees

Publications

Publication
Eye position dependency of nystagmus during constant vestibular stimulation.
Bockisch Christopher J, Khojasteh Elham, Straumann Dominik, Hegemann Stefan C A (2013), Eye position dependency of nystagmus during constant vestibular stimulation., in Experimental Brain Research, 18(3), 161-170.
Effectiveness of Systemic High-Dose Dexamethasone Therapy for Idiopathic Sudden Sensorineural Hearing Loss.
Egli Gallo Doris, Khojasteh Elham, Gloor Martina, Hegemann Stefan C A (2013), Effectiveness of Systemic High-Dose Dexamethasone Therapy for Idiopathic Sudden Sensorineural Hearing Loss., in Audiology & neuro-otology, 18(3), 161-170.
A mechanism for eye position effects on spontaneous nystagmus.
Khojasteh Elham, Bockisch Christopher J, Straumann Dominik, Hegemann Stefan C A (2012), A mechanism for eye position effects on spontaneous nystagmus., in Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and, 2012, 3572-5.
A re-examination of the time constant of the oculomotor neural integrator in human.
Khojasteh Elham, Bockisch Christopher J, Straumann Dominik, Hegemann Stefan C A (2012), A re-examination of the time constant of the oculomotor neural integrator in human., in Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and, 2012, 4780-3.
Development of eye position dependency of slow phase velocity during caloric stimulation.
Bockisch Christopher J, Khojasteh Elham, Straumann Dominik, Hegemann Stefan C A (2012), Development of eye position dependency of slow phase velocity during caloric stimulation., in PloS one, 7(12), 51409-51409.
Adaptation des okulomotorischen neuralen Integrators während konstanter angulärer Beschleunigung.
Trinh Beckey (2011), Adaptation des okulomotorischen neuralen Integrators während konstanter angulärer Beschleunigung..
Alexanders Gesetz - Entwicklung der Geschwindigkeit der langsamen Phase des Nystagmus abhängig von der Augenposition während kalorischer Prüfung
Susac Martina (2010), Alexanders Gesetz - Entwicklung der Geschwindigkeit der langsamen Phase des Nystagmus abhängig von der Augenposition während kalorischer Prüfung.

Collaboration

Group / person Country
Types of collaboration
Prof. Dr. D. Zee director of the Vestibular/Eye Movement Testing Laboratory at Johns Hopkins United States of America (North America)
- in-depth/constructive exchanges on approaches, methods or results
PD Dr.-Ing. S. Glasauer,Senior Scientist, Center for Sensorimotor Research, Department of Neurology Germany (Europe)
- in-depth/constructive exchanges on approaches, methods or results

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
36th MidWinter Meeting 16.02.2013 Baltimore, Maryland, USA
27th Bárány Society Meeting 10.06.2012 Uppsala, Sweden
Pre-Bárány Meeting 16.08.2010 Reykholt, Borgarfjörður, Iceland


Associated projects

Number Title Start Funding scheme
118069 Three-dimensional kinematical analysis of ocular motor disorders in humans 01.10.2007 Project funding (Div. I-III)

Abstract

The goal of this study is to better understand immediate adaptive processes of the human brain to sudden vestibular asymmetry like in unilateral vestibular deficits (UVD), caloric stimulation (CS) and galvanic vestibular stimulation (GVS). Until now, mainly central adaptation of the physiologic vestibulo-ocular reflex (VOR) and long-term adaptive processes after central and peripheral vestibular lesions have been investigated. A key reaction being observed in most patients with acute UVD is Alexander’s law (AL). It states that the velocity of eye drift during nystagmus is dependent on horizontal gaze position. AL is believed to be generated by short term adaptive changes in the oculomotor neural integrator (NI). Integration of eye velocity into eye position signals - in a mathematical sense - is necessary to enable eccentric gaze holding and is performed by a neural network referred to as the oculomotor NI. Lack of integration leads to centripetal eye drift resulting in gaze evoked nystagmus. Gaze evoked nystagmus is assumed to combine with the constant vestibular eye drift of peripheral nystagmus leading to AL. AL usually develops during the first 30 s of nystagmus and is considered a fast adaptive mechanism to help stabilizing gaze at least in one direction. Thus, AL seems optimally suited to study vestibuo-ocular adaptation. Furthermore, the oculomotor NI is the most thoroughly investigated NI so far, providing solid physiological data to depart with. However, there exists no three-dimensional analysis of AL, it is not completely understood how exactly integration is performed by the brain, how adaptation of the NI is triggered and what role it plays in central compensation. To understand these fundamental processes we will pursue the following aims:Aim 1: peripheral nystagmus after UVD usually has not only horizontal but also vertical and torsional components. It is of interest, whether these components also show AL and to what extend relative to the nystagmus velocity, i.e. whether AL affects also the vertical/torsional NI and whether AL will be aligned with the vestibular drift direction. Since torsional nystagmus does not displace images from the fovea, torsional stability seems less important for visual acuity and might, therefore, induce less or no NI-adaptation. In contrast to the NI for horizontal eye movements consisting of a separate population of neurons, the NI neurons for vertical and torsional eye movements are mixed in the N. Cajal. Thus, it is important to know, whether NI adaptation affects vertical and torsional components the same way or differentially, the latter indicating independent vertical and torsional integration, as we hypothesize. To answer these questions we will measure AL 3-D in all gaze directions in patients with acute UVD. Aim 2: we will perform experiments in patients with benign paroxysmal positioning nystagmus (BPPN) and in healthy volunteers using CS and GVS. This enables us to control to a certain extend the onset (CS
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