Simultaneous activation of multiple vestibular pathways upon electrical stimulation of semicircular canal afferents.

BACKGROUND AND PURPOSE: Vestibular implants seem to be a promising treatment for patients suffering from severe bilateral vestibulopathy. To optimize outcomes, we need to investigate how, and to which extent, the different vestibular pathways are activated. Here we characterized the simultaneous responses to electrical stimuli of three different vestibular pathways. METHODS: Three vestibular implant recipients were included. First, activation thresholds and amplitude growth functions of electrically evoked vestibulo-ocular reflexes (eVOR), cervical myogenic potentials (ecVEMPs) and vestibular percepts (vestibulo-thalamo-cortical, VTC) were recorded upon stimulation with single, biphasic current pulses (200 µs/phase) delivered through five different vestibular electrodes. Latencies of eVOR and ecVEMPs were also characterized. Then we compared the amplitude growth functions of the three pathways using different stimulation profiles (1-pulse, 200 µs/phase; 1-pulse, 50 µs/phase; 4-pulses, 50 µs/phase, 1600 pulses-per-second) in one patient (two electrodes). RESULTS: The median latencies of the eVOR and ecVEMPs were 8 ms (8-9 ms) and 10.2 ms (9.6-11.8 ms), respectively. While the amplitude of eVOR and ecVEMP responses increased with increasing stimulation current, the VTC pathway showed a different, step-like behavior. In this study, the 200 µs/phase paradigm appeared to give the best balance to enhance responses at lower stimulation currents. CONCLUSIONS: This study is a first attempt to evaluate the simultaneous activation of different vestibular pathways. However, this issue deserves further and more detailed investigation to determine the actual possibility of selective stimulation of a given pathway, as well as the functional impact of the contribution of each pathway to the overall rehabilitation process.

Influence of systematic variations of the stimulation profile on responses evoked with a vestibular implant prototype in humans.

OBJECTIVE: To explore the impact of different electrical stimulation profiles in human recipients of the Geneva-Maastricht vestibular implant prototypes. APPROACH: Four implanted patients were recruited for this study. We investigated the relative efficacy of systematic variations of the electrical stimulus profile (phase duration, pulse rate, baseline level, modulation depth) in evoking vestibulo-ocular (eVOR) and perceptual responses. MAIN RESULTS: Shorter phase durations and, to a lesser extent, slower pulse rates allowed maximizing the electrical dynamic range available for eliciting a wider range of intensities of vestibular percepts. When either the phase duration or the pulse rate was held constant, current modulation depth was the factor that had the most significant impact on peak velocity of the eVOR. SIGNIFICANCE: Our results identified important parametric variations that influence the measured responses. Furthermore, we observed that not all vestibular pathways seem equally sensitive to the electrical stimulus when the electrodes are placed in the semicircular canals and monopolar stimulation is used. This opens the door to evaluating new stimulation strategies for a vestibular implant, and suggests the possibility of selectively activating one vestibular pathway or the other in order to optimize rehabilitation outcomes.

Cervical myogenic potentials and controlled postural responses elicited by a prototype vestibular implant.

Gaze stabilization and postural control are two key functions of the vestibular system. In consequence, oscillopsia and chronic imbalance are the two main complaints of patients presenting with a severe bilateral vestibular function loss. The vestibular implant is emerging as a promising treatment for this group of patients whose quality of life is significantly impaired. Although the final aim of the vestibular implant should be to restore vestibular function as a whole, until now the research has focused mainly on the restoration of the vestibulo-ocular reflex to improve gaze stabilization. In this study, we aimed to explore whether the vestibulo-collic and vestibulo-spinal pathways could be activated and controlled with the electrical stimuli provided by our vestibular implant prototype. This was first explored and demonstrated with recordings of electrically elicited cervical vestibular evoked myogenic potentials (ecVEMPs). ecVEMPs with characteristics similar to the classical acoustically elicited cervical vestibular evoked myogenic potentials (cVEMPs) were successfully evoked in five out of the eight tested patients. Amplitudes of the electrically elicited N-P complex varied, ranging from 44 to 120 µV. Mean latencies of the N and P waves were of 9.71(± 1.17) ms and 17.24 ms (± 1.74), respectively. We also evaluated the possibility of generating controlled postural responses using a stepping test. Here, we showed that controlled and consistent whole-body postural responses can be effectively obtained with rapid changes in the "baseline" (constant rate and amplitude) electrical activity delivered by the vestibular implant in two out of the three tested subjects. Furthermore, obtained amplitude of body rotations was significantly correlated with the intensity of stimulation and direction of body rotations correlated with the side of the delivered stimulus (implanted side). Altogether, these data suggest that the vestibular implant could also be used to improve postural control in patients with bilateral vestibulopathy.

Reliability of parylene-based multi-electrode arrays chronically implanted in adult rat brains, and evidence of electrical stimulation on contact impedance.

OBJECTIVE: The goal of this study was to evaluate the long-term behavior of the surface electrode through electrochemical characterization and follow-up of implanted parylene/platinum microelectrodes. APPROACH: To this aim, we designed and manufactured specific planar electrodes for cortical implantation for a rat model. This work was included in the INTENSE® project, one of the goals of which was to prove the feasibility of selective neural recording or stimulation with cuff electrodes around the vagus nerve. MAIN RESULTS: After a 12-week implantation in a rat model, we can report that these microelectrodes have withstood in vivo use. Regarding the biocompatibility of the electrodes (materials and manufacturing process), no adverse effect was reported. Indeed, after the three-month implantation, we characterized limited tissue reaction beneath the electrodes and showed an increase and a stabilization of their impedance. Interestingly, the follow-up of the electrochemical impedance combined with electrical stimulation highlighted a drop in the impedance up to 60% at 1 kHz after ten minutes of electrical stimulation at 110 Hz. SIGNIFICANCE: This study gives evidence of the biocompatibility of the parylene platinum contact array designed for the project and confirms the effect of stimulation on the contact impedance.

Evaluation of chronically implanted subdural boron doped diamond/CNT recording electrodes in miniature swine brain.

When implantable recording devices for brain or neural electrical activity are designed, the number of available materials for electrodes is quite limited. The material must be biocompatible with respect to ISO10993, its electrochemical properties must remain stable and the response of cells or tissues can be mitigated, especially on the glial scar. This involves electrode characterization pre- implantation and impedance spectroscopy during chronic implantation, in order to evaluate both electrode properties and performance. This study was aimed at a comparison of the long-term behavior of a nanostructured boron-doped diamond (BDD) with a nanostructured Platinum Iridium (PtIr) electrode. Firstly, a batch of cortical grids with bare and modified contacts (2 mm in diameter) was engineered for implantation. Secondly a miniature swine model was developed. This study highlighted the predominant role of electrode surface roughness on the quality of recordings. Rough PtIr contacts and BDD coated ones showed comparable behavior after three-month implantation with a slight increase of the modulus of the impedance and a tissue capsule. Nevertheless, immunohistochemistry analysis did not exhibit either a toxic or irritation reaction. With regard to biocompatibility, promising long term results are shown for both materials.

Intracranial application of near-infrared light in a hemi-parkinsonian rat model: the impact on behavior and cell survival.

OBJECT The authors of this study used a newly developed intracranial optical fiber device to deliver near-infrared light (NIr) to the midbrain of 6-hydroxydopamine (6-OHDA)-lesioned rats, a model of Parkinson's disease. The authors explored whether NIr had any impact on apomorphine-induced turning behavior and whether it was neuroprotective. METHODS Two NIr powers (333 nW and 0.16 mW), modes of delivery (pulse and continuous), and total doses (634 mJ and 304 J) were tested, together with the feasibility of a midbrain implant site, one considered for later use in primates. Following a striatal 6-OHDA injection, the NIr optical fiber device was implanted surgically into the midline midbrain area of Wistar rats. Animals were tested for apomorphine-induced rotations, and then, 23 days later, their brains were aldehyde fixed for routine immunohistochemical analysis. RESULTS The results showed that there was no evidence of tissue toxicity by NIr in the midbrain. After 6-OHDA lesion, regardless of mode of delivery or total dose, NIr reduced apomorphine-induced rotations at the stronger, but not at the weaker, power. The authors found that neuroprotection, as assessed by tyrosine hydroxylase expression in midbrain dopaminergic cells, could account for some, but not all, of the observed behavioral improvements; the groups that were associated with fewer rotations did not all necessarily have a greater number of surviving cells. There may have been other "symptomatic" elements contributing to behavioral improvements in these rats. CONCLUSIONS In summary, when delivered at the appropriate power, delivery mode, and dosage, NIr treatment provided both improved behavior and neuroprotection in 6-OHDA-lesioned rats.