Multichannel Vestibular Prosthesis Employing Modulation of Pulse Rate and Current with Alignment Precompensation Elicits Improved VOR Performance in Monkeys

Abstract

An implantable prosthesis that stimulates vestibular nerve branches to restore the sensation of head rotation and the three-dimensional (3D) vestibular ocular reflex (VOR) could benefit individuals disabled by bilateral loss of vestibular sensation. Our group has developed a vestibular prosthesis that partly restores normal function in animals by delivering biphasic current pulses via electrodes implanted in semicircular canals. Despite otherwise promising results, this approach has been limited by insufficient velocity of VOR response to head movements that should inhibit the implanted labyrinth and by misalignment between direction of head motion and prosthetically elicited VOR. We report that significantly larger VOR eye velocities in the inhibitory direction can be elicited by adapting a monkey to elevated baseline stimulation rate and current prior to stimulus modulation and then concurrently modulating ("co-modulating") both rate and current below baseline levels to encode inhibitory angular head velocity. Comodulation of pulse rate and current amplitude above baseline can also elicit larger VOR eye responses in the excitatory direction than do either pulse rate modulation or current modulation alone. Combining these stimulation strategies with a precompensatory 3D coordinate transformation improves alignment and magnitude of evoked VOR eye responses. By demonstrating that a combination of co-modulation and precompensatory transformation strategies achieves a robust VOR response in all directions with significantly improved alignment in an animal model that closely resembles humans with vestibular loss, these findings provide a solid preclinical foundation for application of vestibular stimulation in humans.

Bilateral Vestibular Deficiency

“…34, 35 Restoring the function of one labyrinth through gene therapy 36 , stem cell interventions 37 or prosthetic interventions 38–46 yield significant benefits. For example, a multi-channel vestibular prosthesis (MVP) currently in development may partly restore unilateral semicircular canal function to BVD patients, thereby improving vestibulo-ocular reflex performance, visual acuity during head movement and postural stability 38, 39, 43–46 . An important consideration in its development is the device’s cost-utility.…”

Longitudinal performance of an implantable vestibular prosthesis

“…The studies have described the efficacy of these devices in driving vestibulo-ocular reflex (VOR) mediated eye movements with electrical stimulation in a range of species, including humans. Stimulation from such a neurostimulator produces robust vestibular nystagmus in association with electrical stimulation trains of brief biphasic pulses, which is comparable to eye movements produced naturally through the VOR (Thompson et al 2012; Phillips et al, 2011; Davidovics et al 2013). In addition to VOR, electrical stimulation has been shown to drive other modalities of the vestibular system, including producing postural and head movements (Mitchell et al 2013, Phillips et al 2013) and perceptual responses (Lewis et al 2013).…”

“…Much research effort by multiple groups has been spent on the development of an implantable single and multichannel vestibular neurostimulator over the past two decades (Fridman & Della Santina, 2012; Chiang et al, 2011; Cohen et al, 1964; Cohen and Suzuki, 1963; Bierer et al, 2012; Dai et al, 2011b,c, 2013; Davidovics et al, 2011, 2013; Della Santina et al, 2005, 2007; Fridman et al, 2010; Gong and Merfeld, 2000, 2002; Gong et al, 2008; Lewis et al, 2001, 2002, 2010, 2013; Merfeld et al, 2006, 2007; Nie et al, 2011, 2013; Phillips et al, 2011; Rubinstein et al, 2012; Sun et al, 2011; Suzuki and Cohen, 1964, Thompson et al, 2013; Valentin et al, 2013; Phillips et al, 2013; Golub et al, 2013; Perez Fornos et al, 2014; Guyot et al, 2011a, b, 2012; Wall et al, 2007; Van de Berg et al, 2012). The studies have described the efficacy of these devices in driving vestibulo-ocular reflex (VOR) mediated eye movements with electrical stimulation in a range of species, including humans.…”

Characterization of pulse amplitude and pulse rate modulation for a human vestibular implant during acute electrical stimulation

“…Though they did not compare PAM and PRM systematically based on injected charge as herein, they noted the lower effectiveness of PRM to modulate eye movement than PAM. In animal models, however, PAM and PRM were both effective depending on the baseline pulse rate and modulation levels, but were not compared systematically based on injected charge (Davidovics et al 2012, Davidovics et al 2013, Nie et al 2013.…”