Optimized Signal Analysis to Quantify the Non-Linear Behaviour of the Electrically Evoked Vestibulo-Ocular Reflex in Patients with a Vestibular Implant

Abstract

Introduction: Different eye movement analysis algorithms are used in vestibular implant research to quantify the electrically evoked vestibulo-ocular reflex (eVOR). Often, standard techniques are used as applied for quantification of the natural VOR in healthy subjects and patients with vestibular loss. However, in previous research, it was observed that the morphology of the VOR and eVOR may differ substantially. In this study, it was investigated if the analysis techniques for eVOR need to be adapted to optimize a truthful quantification of the eVOR (VOR gain, orientation of the VOR axis, asymmetry, and phase shift).

Methods: "Natural" VOR responses were obtained in six age-matched healthy subjects, and eVOR responses were obtained in eight bilateral-vestibulopathy patients fitted with a vestibular implant. Three conditions were tested: "nVOR" 1-Hz sinusoidal whole-body rotations of healthy subjects in a rotatory chair, "eVOR" 1-Hz sinusoidal electrical vestibular implant stimulation without whole-body rotations in bilateral-vestibulopathy patients, and "dVOR" 1-Hz sinusoidal whole-body rotations in bilateral-vestibulopathy patients using the chair-mounted gyroscope output to drive the electrical vestibular implant stimulation (therefore also in sync 1 Hz sinusoidal). VOR outcomes were determined from the obtained VOR responses, using three different eye movement analysis paradigms: (1) peak eye velocity detection using the raw eye traces; (2) peak eye velocity detection using full-cycle sine fitting of eye traces; (3) peak eye velocity detection using half-cycle sine fitting of eye traces.

Results: The type of eye movement analysis algorithm significantly influenced VOR outcomes, especially regarding the VOR gain and asymmetry of the eVOR in bilateral-vestibulopathy patients fitted with a vestibular implant. Full-cycle fitting lowered VOR gain in the eVOR condition (mean difference: 0.14 ± 0.06 95% CI, p = 0.018). Half-cycle fitting lowered VOR gain in the dVOR condition (mean difference: 0.08 ± 0.04 95% CI, p = 0.009). In the eVOR condition, half-cycle fitting was able to demonstrate the asymmetry between the excitatory and inhibitory phases of stimulation in comparison with the full-cycle fitting (mean difference: 0.19 ± 0.12 95% CI, p = 0.024). The VOR axis and phase shift did not differ significantly between eye movement analysis algorithms. In healthy subjects, no clinically significant effect of eye movement analysis algorithms on VOR outcomes was observed.

Conclusion: For the analysis of the eVOR, the excitatory and inhibitory phases of stimulation should be analysed separately due to the inherent asymmetry of the eVOR. A half-cycle fitting method can be used as a more accurate alternative for the analysis of the full-cycle traces.

Keywords: Bilateral vestibular areflexia; Bilateral vestibulopathy; Eye movement analysis algorithm; Neural prosthesis; Signal fitting; Vestibular implant; Vestibular prosthesis; Vestibulo-ocular reflex.

Fig. 1

Examples of the stimulus traces (rotatory chair horizontal velocity) and raw eye velocity traces of one HL subject undergoing whole-body rotations (nVOR), and two BV patients fitted with a VI in the eVOR (subject sitting static on an immobile chair) and dVOR (subject sitting in the rotatory chair) conditions. LAN, lateral ampullary nerve electrode; SAN, superior ampullary nerve electrode.

Fig. 2

a–d Visualization of the main steps of the analysis: (a) fitting the sine curve to the full cycle, as well as to each half cycle separately; (b) calculation of the total eye velocity as the magnitude of the vector with coordinates equal to the horizontal and vertical eye velocities; (c) detection of the peak stimulus and peak total eye velocity in each half cycle in all traces; (d) calculation of the main outcome measures: VOR gain, asymmetry, angle for the VOR axis, and phase shift. For the angle, the position of the peak total eye velocity was used to extract corresponding horizontal and vertical eye velocities. Red and blue lines represent excitatory and inhibitory phases of stimulation, respectively. α and β, angles of the excitatory and inhibitory phases of stimulation, respectively; γ, absolute angle between the direction of the excitatory and inhibitory total eye velocities; nVOR, whole-body rotation in healthy subjects; eVOR, electrical stimulation in VI patients without whole-body rotations; dVOR, electrical stimulation in VI patients with whole-body rotations; V, eye velocity; hor, horizontal; vert, vertical; arctan, arctangent; A, amplitude; f, linear frequency; φ₀, initial phase.

Fig. 3

A one-cycle example of the raw, full-cycle fitted, and half-cycle fitted VOR response in a HL subject undergoing whole-body rotations (nVOR) and in two VI patients in two different conditions (eVOR; dVOR). For the VI patients, the excitatory phase of stimulation corresponded to the whole-body rotation to the side of implantation. SAN, superior ampullary nerve electrode; LAN, lateral ampullary nerve electrode; eVOR, electrical stimulation in VI patients without whole-body rotations; dVOR, electrical stimulation in VI patients with whole-body rotations.

Fig. 4

Mean ± SD of the VOR gain across subjects (a), asymmetry (b), angle of the VOR axis (c), and phase shift (d) calculated between the values obtained when using analysis of the raw traces, full-cycle fitting (f-cycle), and half-cycle fitting (h-cycle) fitted traces. nVOR, whole-body rotation in healthy subjects; eVOR, electrical stimulation in VI patients without whole-body rotations; dVOR, electrical stimulation in VI patients with whole-body rotations; ***p < 0.001; **p < 0.01; *p ≤ 0.5.