Wangsong Gong

Prototype neural semicircular canal prosthesis using patterned electrical stimulation.

AbstractThe design of a prototype semicircular canal prosthesis is presented along with preliminary results. This device measures angular velocity of the head (±500°/s) using a piezoelectric vibrating gyroscope. With a digital filter this velocity is filtered to match the dynamic characteristics of the semicircular canals, which are the physiological rotation sensors of the vestibular system. This digitally filtered signal is used to modulate the pulse rate of electrical stimulation. The pulse rate is varied between 50 and 250 Hz via a sigmoidal lookup table relating pulse rate to angular velocity; the steady-state rate is 150 Hz. A current source utilizes these timing pulses to deliver charge balanced, cathodic-first, biphasic, current pulses to the nerves innervating the semicircular canal via platinum electrodes. Power is supplied via lithium batteries. dc/dc converters are used to generate regulated ±5 V supplies from the batteries. All of the components are contained in a small, lightweight, Nylon box measuring roughly 43 mm×31 mm×25 mm, which can be mounted on the top of an animals head. This device has been tested in guinea pigs having surgically implanted platinum electrodes, and the results show that the prosthesis can provide a rotational cue to the nervous system.

System design and performance of a unilateral horizontal semicircular canal prosthesis

We have reported preliminary results regarding a prototype semicircular canal prosthesis and concluded that it can provide rotational cues to the nervous system. This paper presents the system design of the prosthesis, and also reports the prosthesis system performance and effectiveness. The prosthesis delivers electrical pulses to the nerve branch innervating the horizontal semicircular canal on one side via implanted electrodes. To allow us to encode both directions of angular velocity, the baseline stimulation pulse frequency was set at 150 Hz, which is somewhat higher than the average firing rate of afferents innervating the semicircular canals in normal guinea pigs (/spl sim/ 60 Hz). A sensor measures angular velocity to modulate (increase or decrease) the pulse rate. The prosthetic system was provided to a guinea pig whose horizontal canals were surgically plugged. The animal responded to the baseline stimulation initially and adapted to the baseline stimulation in roughly one day. After this baseline adaptation the animal responded to yaw rotation, showing that the function of the canals was partially restored. The experiments also show that the nervous system adapts to the artificial rotational cue provided via electrical stimulation.

Acclimation to Chronic Constant-Rate Peripheral Stimulation Provided by a Vestibular Prosthesis

We are developing two types of vestibular prosthetics that electrically stimulate afferent neurons. One type replaces absent sensory function by providing stimulation that modulates above and below a baseline established with the head stationary. The other type provides constant stimulation and is turned on only when necessary, for example, to override unnatural variations like those experienced by patients suffering from Menieres syndrome; this prosthesis does not provide motion information. Both prostheses require neural plasticity, which we investigated by providing chronic constant-rate stimulation to semicircular canal neurons in three guinea pigs. The stimulation was alternately switched on or off for eight consecutive weeks before being switched daily. A brisk horizontal nystagmus was measured when the stimulation was first turned on and then dissipated over the course of a day. The nystagmus demonstrated an after-effect in the opposite direction when the stimulation was turned off. The nystagmus that we measured after just a few (2 to 5) off-to-on transitions returned to baseline more rapidly than when first turned on. In fact, after many such off-to-on or on-to-off transitions, little nystagmus was evoked by turning the stimulation on or off. These findings show that the brain acclimates to constant-rate stimulation

Vestibulo-Ocular Responses Evoked Via Bilateral Electrical Stimulation of the Lateral Semicircular Canals

We investigated the vestibulo-ocular responses (VORs) evoked by bilateral electrical stimulation of the nerves innervating horizontal semicircular canals in squirrel monkeys and compared these responses to those evoked by unilateral stimulation. In response to sinusoidal modulation of the electrical pulse rate, the VOR for bilateral stimulation roughly equals the addition of the responses evoked by unilateral right ear and unilateral left ear stimulation; the VOR time constants were about the same for bilateral and unilateral stimulation and both were much shorter than for normal animals. In response to individual pulse stimulation, the VOR evoked by bilateral stimulation closely matches the point-by-point addition of responses evoked by unilateral right ear and unilateral left ear stimulation. We conclude that, to first order, the VOR responses evoked by bilateral stimulation are the summation of the responses evoked by unilateral stimulation. These findings suggest that-from a physiologic viewpoint-unilateral and bilateral vestibular prostheses are about equally viable. Given these findings, one possible advantage of a bilateral prosthesis is higher gain. However, at least for short-term stimulation such as that studied herein, no inherent advantage in terms of the response time constant (ldquovelocity storagerdquo) was found.

Development of a closed-loop neural prosthesis for vestibular disorders

Vestibular disorders can cause severe problems including spatial disorientation, imbalance, nausea, visual blurring, and even cognitive deficits. The CLONS project is developing a closed-loop, sensory neural prosthesis to alleviate these symptoms [1]. In this article, we outline the different components necessary to develop this prosthetic. A short version of this work was presented in the NEUREL 2010 [1]. Conceptually, the prosthesis restores vestibular information based on inertial sensors rigidly affixed to the user. These sensors provide information about rotational velocity of the head; the prosthetic then transfers the information to the vestibular nerve via electrical stimulation. Here we present a project overview, development details, and summarize our progress in animal models and selected human volunteers.

Electrical Stimulation of Semicircular Canal Afferents Affects the Perception of Head Orientation

Patients with vestibular dysfunction have visual, perceptual, and postural deficits. While there is considerable evidence that a semicircular canal prosthesis that senses angular head velocity and stimulates canal ampullary nerves can improve vision by augmenting the vestibulo-ocular reflex, no information is available regarding the potential utility of a canal prosthesis to improve perceptual deficits. In this study, we investigated the possibility that electrical stimulation of canal afferents could be used to modify percepts of head orientation. Two rhesus monkeys were trained to align a light bar parallel to gravity, and were tested in the presence and absence of electrical stimulation provided by an electrode implanted in the right posterior canal. While the monkeys aligned the light bar close to the true earth-vertical without stimulation, when the right posterior canal was stimulated their responses deviated toward their left ear, consistent with a misperception of head tilt toward the right. The deviation of the light bar from the earth-vertical exceeded the torsional deviation of the eyes, indicating that the perceptual changes were not simply visual in origin. Eye movements recorded during electrical stimulation in the dark were consistent with isolated activation of right posterior canal afferents, with no evidence of otolith stimulation. These results demonstrate that electrical stimulation of canal afferents affects the perception of head orientation, and therefore suggest that motion-modulated stimulation of canal afferents by a vestibular prosthesis could potentially improve vestibular percepts in patients lacking normal vestibular function.

Responses evoked by a vestibular implant providing chronic stimulation

Patients with bilateral vestibular loss experience dehabilitating visual, perceptual, and postural difficulties, and an implantable vestibular prosthesis that could improve these symptoms would be of great benefit to these patients. In previous work, we have shown that a one-dimensional, unilateral canal prosthesis can improve the vestibulooccular reflex (VOR) in canal-plugged squirrel monkeys. In addition to the VOR, the potential effects of a vestibular prosthesis on more complex, highly integrative behaviors, such as the perception of head orientation and posture have remained unclear. We tested a one-dimensional, unilateral prosthesis in a rhesus monkey with bilateral vestibular loss and found that chronic electrical stimulation partially restored the compensatory VOR and also that percepts of head orientation relative to gravity were improved. However, the one-dimensional prosthetic stimulation had no clear effect on postural stability during quiet stance, but sway evoked by head-turns was modestly reduced. These results suggest that not only can the implementation of a vestibular prosthesis provide partial restitution of VOR but may also improve perception and posture in the presence of bilateral vestibular hypofunction (BVH). In this review, we provide an overview of our previous and current work directed towards the eventual clinical implementation of an implantable vestibular prosthesis.

Attenuation of Eye Movements Evoked by a Vestibular Implant at the Frequency of the Baseline Pulse Rate

We are developing a vestibular implant to electrically stimulate vestibular neurons in the semicircular canals in order to alleviate vertigo, which is a commonly occurring problem. However, since electrical stimulation causes synchronous (phase-locked) neural responses, such electrical stimulation might also cause inappropriate vestibuloocular eye movements, which might, in turn, cause visual blurring. We investigated the eye movements evoked in the guinea pig using electric stimulation with a constant rate of 250 pulses per second (pps), and measured 0.010° peak-to-peak eye movements on an average at 250 Hz, with an average peak velocity amplitude of 8.1°/s, which might cause visual blurring. However, after half an hour of stimulation, that component reduced to 1.6°/s (0.0020° peak-to-peak). The average time constant for this reduction was 5.0 min. After one week of constant stimulation, the 250-Hz response component was only slightly smaller, at 1.2°/s (0.0015° peak-to-peak). We conclude that although an electrical prosthesis with a resting rate of 250 pps may cause some visual blurring when first turned on, such blurring is very likely to attenuate and be imperceptible within several minutes.

Spatial and temporal properties of eye movements produced by electrical stimulation of semicircular canal afferents

To investigate the characteristics of eye movements produced by electrical stimulation of semicircular canal afferents, we studied the spatial and temporal features of eye movements elicited by short-term lateral canal stimulation in two squirrel monkeys with plugged lateral canals, with the head upright or statically tilted in the roll plane. The electrically induced vestibuloocular reflex (eVOR) evoked with the head upright decayed more quickly than the stimulation signal provided by the electrode, demonstrating an absence of the classic velocity storage effect that improves the dynamics of the low-frequency VOR. When stimulation was provided with the head tilted in roll, however, the eVOR decayed more rapidly than when the head was upright, and a cross-coupled vertical response developed that shifted the eyes rotational axis toward alignment with gravity. These results demonstrate that rotational information provided by electrical stimulation of canal afferents interacts with otolith inputs (or other graviceptive cues) in a qualitatively normal manner, a process that is thought to be mediated by the velocity storage network. The observed interaction between the eVOR and graviceptive cues is of critical importance for the development of a functionally useful vestibular prosthesis. Furthermore, the presence of gravity-dependent effects (dumping, spatial orientation) despite an absence of low-frequency augmentation of the eVOR has not been previously described in any experimental preparation.

Vestibular prosthesis tested in rhesus monkeys

We are studying the effectiveness of a semicircular canal prosthesis to improve postural control, perception of spatial orientation, and the VOR in rhesus monkeys with bilateral vestibular hypofunction. Balance is examined by measuring spontaneous sway of the body during quiet stance and postural responses evoked by head turns and rotation of the support surface; perception is measured with a task derived from the subjective visual vertical (SVV) test during static and dynamic rotation in the roll plane; and the angular VOR is measured during rotation about the roll, pitch, and yaw axes. After the normal responses are characterized, bilateral vestibular loss is induced with intratympanic gentamicin, and then multisite stimulating electrodes are chronically implanted into the ampullae of all three canals in one ear. The postural, perceptual, and VOR responses are then characterized in the ablated state, and then bilateral, chronic electrical stimulation is applied to the ampullary nerves using a prosthesis that senses angular head velocity in three-dimensions and uses this information to modulate the rate of current pulses provided by the implanted electrodes. We are currently characterizing two normal monkeys with these paradigms, and vestibular ablation and electrode implantation are planned for the near future. In one prior rhesus monkey tested with this approach, we found that a one-dimensional (posterior canal) prosthesis improved balance during head turns, perceived head orientation during roll tilts, and the VOR in the plane of the instrumented canal. We therefore predict that the more complete information provided by a three-dimensional prosthesis that modulates activity in bilaterally-paired canals will exceed the benefits provided by the one-dimensional, unilateral approach used in our preliminary studies.