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.