Eccentric gaze in darkness evokes minor centripetal eye drifts in healthy subjects, as cerebellar control sufficiently compensates for the inherent deficiencies of the brainstem gaze-holding network. This behavior is commonly described using a leaky integrator model, which assumes that eye velocity grows linearly with gaze eccentricity. Results from previous studies in patients and healthy subjects suggest caution when this assumption is applied to eye eccentricities larger than 20 degrees. To obtain a detailed characterization of the centripetal gaze-evoked drift, we recorded horizontal eye position in 20 healthy subjects. With their head fixed, they were asked to fixate a flashing dot (50 ms every 2 s)that was quasi-stationary displacing(0.5 deg/s) between ±40 deg horizontally in otherwise complete darkness. Drift velocity was weak at all angles tested. Linearity was assessed by dividing the range of gaze eccentricity in four bins of 20 deg each, and comparing the slopes of a linear function fitted to the horizontal velocity in each bin. The slopes of single subjects for gaze eccentricities of ±0−20 deg were, in median,0.41 times the slopes obtained for gaze eccentricities of ±20−40 deg. By smoothing the individual subjects' eye velocity as a function of gaze eccentricity, we derived a population of position-velocity curves. We show that a tangent function provides a better fit to the mean of these curves when large eccentricities are considered. This implies that the quasi-linear behavior within the typical ocular motor range is the result of a tuning procedure, which is optimized in the most commonly used range of gaze. We hypothesize that the observed non-linearity at eccentric gaze results from a saturation of the input that each neuron in the integrating network receives from the others. As a consequence, gaze-holding performance declines more rapidly at large eccentricities.

Objective: To evaluate the effectiveness of systemic high-dose dexamethasone therapy for sudden sensorineural hearing loss in comparison to the previous treatment regimen at our clinic with systemic prednisone 100 mg daily for 7 days analyzed in a previous study. Methods: We conducted a retrospective review of an electronic patient data base of 79 patients with idiopathic sudden sensorineural hearing loss. The standard treatment was orally applied dexamethasone (1st to 3rd day: 40 mg daily, 4th to 6th day: 10 mg daily) in an ambulant setting. The primary endpoint was change in hearing threshold from the initial audiogram to an audiogram at least 4 weeks later. Factors that were analyzed included patient's age, interval between onset of symptoms and start of treatment, presence or absence of dizziness and tinnitus, the audiogram pattern, severity of hearing loss and hearing in the opposite ear. Hearing gain was expressed either as absolute or relative hearing gain. Functionally relevant recovery of hearing was defined as the final pure-tone average (PTA) of 30 dB or less (or the same as the PTA of the opposite ear ± 10 dB). Furthermore, we calculated the percentage of patients with complete, partial and no recovery as defined in the recently published Clinical Practice Guideline of the American Academy of Otolaryngology - Head and Neck Surgery Foundation. We then compared our results with the previous treatment regimen carried out at our clinic. Results: The average initial PTA hearing loss in the affected ear compared to baseline PTA of the unaffected ear was 51.5 ± 20.9 dB (mean ± SD). The mean absolute hearing gain was 44.4 ± 18.1 dB. The mean relative hearing gain was 86 ± 19%. Of the total, 87% had functionally relevant recovery of hearing. All of our patients showed partial (24%) or complete recovery (76%). No difference in recovery rate could be detected between patients with start of therapy within 24 h and patients with beginning of therapy within 7 days. We found a correlation between the severity of hearing loss and functionally relevant recovery. A mild hearing loss was noted in 34% of patients, with an average relative hearing gain of 89% and a functionally relevant recovery in 96% of them; the 9% of patients with initial deafness showed a mean relative hearing gain of 69% and a functionally relevant recovery in 43%. The audiogram pattern with low- or high-frequency hearing loss showed the best recovery rate; the poorest recovery rate was found in patients with initial deafness. Con-clusion: Application of high-dose orally applied dexamethasone seems to improve the recovery outcomes in comparison to prednisone 100 mg p.o. for 7 days.

We studied the horizontal oculomotor neural integrator in healthy human subjects during gaze holding in darkness. We found large variability among subjects with respect to the estimated time constants and the integrator's null position. We also found that individual subjects could demonstrate significantly nonlinear drift velocities as a function of eye position. Nevertheless, a consistent trend did not emerge. Consequently, cross subject averaging eliminates idiosyncratic nonlinear patterns and the average can be approximated by a linear function inside the range that was tested. Abstract-We studied the horizontal oculomotor neural integrator in healthy human subjects during gaze holding in darkness. We found large variability among subjects with respect to the estimated time constants and the integrator's null position. We also found that individual subjects could demonstrate significantly nonlinear drift velocities as a function of eye position. Nevertheless, a consistent trend did not emerge. Consequently, cross subject averaging eliminates idiosyncratic nonlinear patterns and the average can be approximated by a linear function inside the range that was tested.

Gain modulation is believed to be a common integration mechanism employed by neurons to combine information from various sources. Although gain fields have been shown to exist in some cortical and subcortical areas of the brain, their existence has not been explored in the brainstem. In the present modeling study, we develop a physiologically relevant simplified model for the angular vestibulo-ocular reflex (VOR) to show that gain modulation could also be the underlying mechanism that modifies VOR function with sensorimotor context (i.e. concurrent eye positions and stimulus intensity). The resulting nonlinear model is further extended to generate both slow and quick phases of the VOR. Through simulation of the hybrid nonlinear model we show that disconjugate eye movements during the VOR are an inevitable consequence of the existence of such gain fields in the bilateral VOR pathway. Finally, we will explore the properties of the predicted disconjugate component. We will demonstrate that the apparent phase characteristics of the disconjugate response vary with the concurrent conjugate component.

Studies on the behavior of the vestibulo-ocular reflex (VOR) reveal that the monocular reflex gain is adjusted according to target position relative to each eye. In this paper, we present a nonlinear approach in modeling the viewing-context dependency of the slow-phase angular VOR. We show that including appropriate nonlinearities in the responses of premotor neurons in the brainstem is sufficient to account for the online modulation of the VOR with target position. This approach allows very complex behaviors in response to sensory patterns without resorting to currently assumed cortical computations. A local premotor topology with nonlinear properties has repercussions in the study of all ocular reflexes, since it implies context dependent dynamics in all behavioral responses (pursuit, optokinetic, VOR, saccades, etc.) that share this network. Local nonlinearities in spinal circuits could similarly influence the context dependence of other motor systems (such as stretch reflex modulation during rhythmic walking).