Vestibuloocular reflex adaptation investigated with chronic motion-modulated electrical stimulation of semicircular canal afferents

Abstract

To investigate vestibuloocular reflex (VOR) adaptation produced by changes in peripheral vestibular afference, we developed and tested a vestibular "prosthesis" that senses yaw-axis angular head velocity and uses this information to modulate the rate of electrical pulses applied to the lateral canal ampullary nerve. The ability of the brain to adapt the different components of the VOR (gain, phase, axis, and symmetry) during chronic prosthetic electrical stimulation was studied in two squirrel monkeys. After characterizing the normal yaw-axis VOR, electrodes were implanted in both lateral canals and the canals were plugged. The VOR in the canal-plugged/instrumented state was measured and then unilateral stimulation was applied by the prosthesis. The VOR was repeatedly measured over several months while the prosthetic stimulation was cycled between off, low-sensitivity, and high-sensitivity stimulation states. The VOR response initially demonstrated a low gain, abnormal rotational axis, and substantial asymmetry. During chronic stimulation the gain increased, the rotational axis improved, and the VOR became more symmetric. Gain changes were augmented by cycling the stimulation between the off and both low- and high-sensitivity states every few weeks. The VOR time constant remained low throughout the period of chronic stimulation. These results demonstrate that the brain can adaptively modify the gain, axis, and symmetry of the VOR when provided with chronic motion-modulated electrical stimulation by a canal prosthesis.

Fig. 1.

Horizontal eye velocity plotted against time during yaw-axis sinusoidal rotation at 0.5 Hz. Traces show the eye movement responses in the normal monkeys, following bilateral plugging of the lateral canals and after the prosthesis was first activated in the low-sensitivity state. Peak velocity of head rotation was 80°/s. Vestibuloocular reflex (VOR) responses were symmetric for monkey S in the normal state, but monkey N had a spontaneous nystagmus in the dark in the normal state, which measured 4.0°/s during this test session, and this biased the VOR in the positive direction. The VOR response in monkey N was symmetric, however, about this biased zero. After the prosthesis was activated, monkey N had a leftward (positive) VOR bias that reflected the small, residual spontaneous nystagmus produced by the tonic electrical stimulation of the right ear that remained after 30 min of tonic stimulation in the dark.

Fig. 2.

Horizontal eye velocity vs. time during leftward (positive) and rightward (negative) yaw-axis velocity steps (0–80°/s) in the normal, plugged, and prosthesis-on states. The amplitude of the step response was symmetric in the normal state in both monkeys, although monkey N again demonstrated a positive bias due to spontaneous nystagmus in the dark. After the prosthesis was activated, both animals show evidence of a small VOR bias due to the residual spontaneous nystagmus that was present after 30 min of tonic stimulation in the dark. The small bias (∼2°/s) is negative (rightward) in monkey S due to left ear stimulation and is positive (leftward) in monkey N due to right ear stimulation.

Fig. 3.

VOR gain constants during the entire period of prosthetic stimulation, calculated from the transfer function fit to the VOR gains measured during sinusoidal rotation over a frequency range of 0.01 to 1.0 Hz. The first stimulation period is to the left of the vertical dashed line and these data were previously published for monkey S (Merfeld et al. 2007; Fig. 7). Circles are values in the canal-plugged state with the prosthesis off, light diamonds are the low-sensitivity state of prosthetic stimulation, and dark squares are the high-sensitivity state of prosthetic stimulation. For monkey S, the gap between the end of the first period of low-sensitivity stimulation and the start of high-sensitivity stimulation indicates a period where the power supply of the prosthesis failed.

Fig. 4.

VOR gains produced by velocity steps in the canal-plugged state (gray icons) and during the first cycle of low-sensitivity prosthetic stimulation (black icons). Diamonds are the average of the gains produced by rotations ipsilateral and contralateral to the stimulated ear ([gain_ipsi + gain_contra]/2); squares are the difference between the gains produced by ipsilateral and contralateral rotations (gain_ipsi − gain_contra) and reflect the asymmetry of the VOR response to velocity steps.

Fig. 5.

Rotational axis of the eye in the frontal plane calculated from the velocity step data, in the canal-plugged state (gray diamonds) and during the first period of low-sensitivity prosthetic stimulation (black diamonds). The axis is defined as the tan⁻¹ (peak horizontal eye velocity/peak vertical eye velocity). A purely horizontal eye movement response, which is perfectly compensatory for the yaw-axis head rotation, has an axis of 90° and a purely vertical response has an axis of 0°.

Fig. 6.

VOR time constants during the entire period of prosthetic stimulation, calculated from the transfer function fit to the VOR phase measured during sinusoidal rotation over a frequency range of 0.01 to 1.0 Hz. The first stimulation period is to the left of the vertical dashed line. Light diamonds are the low-sensitivity state of prosthetic stimulation and dark squares are the high-sensitivity state of prosthetic stimulation. Time constants could not be accurately calculated in the canal-plugged state with the prosthesis off because of the very low VOR gains.

Fig. 7.

Horizontal eye position and velocity responses in monkey N elicited by single cathodic electrical pulses with durations of 1,000 μs and amplitudes of 150 μA. Traces are the average of 20–25 individual responses and were obtained with the prosthesis off, prior to electrical stimulation (first column) and after each of the 3 periods of high-sensitivity stimulation were completed (see Fig. 3; monkey N, circles = prosthesis-off).

Fig. 8.

Temporal bone histology in monkey N showing anatomic details of the left (nonstimulated) and right (stimulated) ears. The top panels show the position of the electrode tract with respect to the crista (Cr). The bottom panels show the lateral canal ampullary nerves in both ears and Scarpa's ganglion on the right.

Fig. 9.

Schematic diagram showing changes in activity in the vestibular nuclei after a unilateral labyrinthectomy (A) and the changes in nuclear activity we hypothesized may occur after prosthesis activation in an animal with bilateral lateral canal plugs (B). Labyrinthectomy eliminates both the tonic and motion-modulated activity in the afferent vestibular nerve; canal plugging does not affect the tonic level of activity but appreciably attenuates the motion-modulated component. Both types of lesions are indicated by an “” through the canal ampullary nerve. I, type I vestibular neurons; II, type II vestibular neurons; OMN, ocular motor neurons; PC, Purkinje cells. Black arrows represent excitatory connections and gray arrows inhibitory connections.