Although seldom reaching the level of conscious perception, vestibular sensation – transduction of head rotation, orientation and translation into activity on the vestibular nerves – provides essential input to reflexes that maintain steady vision and posture.[1
] When the vestibular nervous system functions normally, the angular vestibulo-ocular reflex (AVOR) stabilizes the eyes with respect to space during head rotations in any direction, using sensory input from the vestibular labyrinths of both ears to generate appropriate control signals for the extraocular muscles attached to each eye. Without this gaze-stabilizing mechanism to keep images still on the retina, visual acuity falls dramatically during head rotations typical of walking, driving and other activities of daily life.[2
Normally, head rotation is transduced by a set of 6 semicircular canals (SCC
), 3 in each ear. Each SCC is a fluid-filled canal that approximates three quarters of a toroid and is attached to the vestibule
(central chamber of the inner ear) at each end. The fluid within the SCC acts as an inertial load for detection of the component of head rotation about the axis perpendicular to the plane of the SCC. Head rotation generates a moment on the fluid ring within the SCC, causing relative movement between the fluid and SCC walls. This fluid movement deforms the gelatinous membrane (the cupula
) that blocks the canal lumen within an enlarged bulb at one end of the SCC (the ampulla
). Just beneath the cupula lies a specialized neurosensory epithelium (the crista
), within which are hair cells, so named for their bundles of hair-like mechanosensitive stereocilia, which extend from each hair cell into the cupula. Deformation of the cupula causes shear stresses that bend the stereocilia, modulating neurotransmitter release from hair cells and ultimately modulating the nonzero baseline firing rates of afferent nerve fibers that synapse with the hair cells. All axons from one crista coalesce to form an ampullary nerve
for that crista’s SCC, and all axons within one ampullary nerve encode the component head rotation about the corresponding SCC’s axis. (Fibers within one ampullary nerve differ in several other important respects, including sensitivity, frequency response, stochastic properties and response to efferent innervation.[4
The SCCs are arranged across the midline into approximately coplanar, mutually orthogonal pairs: the left and right horizontal SCCs form a horizontal
pair; the left-anterior [LA] and right-posterior [RP] form a LARP
pair, and the right-anterior [RA] and left-posterior [LP] SCC form a RALP
pair. (Due to its anterosuperior location in the labyrinth, the anterior SCC is also commonly referred to as the superior semicircular canal. We will use these terms interchangeably. Similarly, the horizontal SCC is often called the lateral SCC.) Each inner ear’s 3 SCCs are arranged to form a (nearly) orthogonal set, so that the pattern of activity on the 3 ampullary nerves of a single inner ear’s vestibular labyrinth represent a (nearly) orthogonal decomposition of any head rotation into 3 independent components, each representing the projection of the head rotation’s angular velocity vector onto the axis of one SCC.[5
] The two SCC comprising a coplanar pair share are arranged in antisense orientation: a leftward head rotation increases firing rates of axons in the ampullary nerve of the left horizontal SCC and decreases the firing rates in the right horizontal SCC’s ampullary nerve. Similarly, a head rotation exciting the LA ampullary nerve (a nose-downward, counter-clockwise rotation as viewed from behind) inhibits the RP SCC, and a head rotation exciting the LP ampullary nerve (a nose-upward, counter-clockwise rotation as viewed from behind) inhibits the RA SCC. Differencing and integration of these complementary inputs in the vestibular and oculomotor nuclei of the brainstem generate complementary oculomotor nerve output signals that drive extraocular muscles controlling the angular position and velocity of the eyes with respect to the head. Interestingly, each eye’s 6 muscles are arranged in 3 complementary pairs that are approximately coplanar with the corresponding SCC planes, minimizing the neural computational load that would otherwise be required to effectively perform a transformation between coordinate frames of reference. Equally interesting is the vestibular nervous system’s ability to perform such transformations when visual and vestibular sensation conflict over more than a few minutes. A subject rotated in the horizontal plane while attempting to visually fixate a scene being moved to simulate a pitch head rotation will subsequently exhibit pitch eye rotations during horizontal head rotation in darkness, an effect called cross-axis adaptation
The AVOR acts as an open loop control system via a direct three-neuron reflex arc that does not require moment by moment visual feedback and is thus freed from the ~100 msec delay inherent to visual processing.[8
] The AVOR thus works in darkness, and it has a very short latency. In normal humans subjected to passive sinusoidal or transient head rotation in light or darkness over the range of head movements typical of walking, jogging or even vigorous head shaking (>300°/s and >5000°/s2
over ~0.5–16 Hz), the AVOR gain (conventionally defined as the absolute value of the ratio of eye and head velocity about the axis of head rotation for sinusoids [or of acceleration for transients]) is near 1 and its latency is only 7–9 ms.[9
]. The gain of the AVOR in darkness falls as head rotation frequency decreases below ~0.1 Hz, where vision-dependent tracking mechanisms dominate. In contrast, vision-dependent neural circuits mediating smooth pursuit (reflexive following of images on the retinal foveae) and optokinetic nystagmus (reflexive tracking of the movement of the peripheral visual fields) fail as gaze-stabilizing mechanisms for head movements above ~0.5 Hz and ~50°/s.[12
] The AVOR and visual mechanisms are thus complementary, combining to maintain stable gaze across the physiologically relevant range of head movements.
An analogous reflex stabilizing the eyes during head translation (the linear VOR, or LVOR
) are driven by sensation of linear acceleration, which is mediated by the utricle
in each ear’s vestibule while collectively are called the otolith endogans
. Each of these sensors transduces translational acceleration of a proofing mass affixed to its macula
, a neurosensory epithelium analogous to the SCC’s cristae except that it is approximately planar and its hair cells are not uniformly oriented. While not entirely flat, the utricular macula lies approximately in a horizontal plane, so utricular nerve axons predominantly carry information about head translational acceleration along directions within the horizontal plane. Similarly, the saccular macula approximates a vertical plane. Departures from planarity for each ensure that the two sensors combined span the range of possible three dimensional translations. In addition to driving the LVOR (which is dominated by the AVOR for far targets but not for visual targets close to the eyes,[13
] otolith endorgans provide the essential sensory input to vestibulocolic and vestibulospinal reflexes that stabilize the head and body during standing and walking.
Bilateral loss of vestibular sensation, as can occur after ototoxic drug exposure, infection, trauma or other insults to the inner ear, disables these reflexes and results in illusory movement of the visible world during head motion, postural instability and chronic disequilibrium.[14
] While many victims of bilateral vestibular sensory loss ultimately learn to compensate by enlisting visual and proprioceptive cues to partly supplant missing vestibular sensation, those who fail to compensate suffer significant disability. The lives of these individuals could be significantly improved by an implantable neuroelectronic prosthesis that mimics the normal vestibular labyrinth by measuring head rotation, decomposing it into orthogonal components parallel to the planes of the SCC, and selectively encoding it via electrical stimuli that recreate an appropriate pattern of activity in afferent nerve fibers of the ampullary branches of the vestibular nerve.
Evidence supporting the feasibility of this approach was provided by classic studies of Cohen, Suzuki and their colleagues,[17
] who described the extraocular muscle activation patterns and direction of conjugate (in SCC coordinates) eye movements in response to electrical stimulation of single and multiple ampullary nerves, corroborating and extending earlier studies of electrical and hydrodynamic stimulation of individual cristae.[22
] Coupled with studies of vestibular nerve afferent responses to galvanic stimuli,[25
] advances in miniaturization of rotational accelerometers, and experience gained from decades of cochlear implant development,[28
] these studies laid a foundation for development of a head-mounted, implanted prosthesis for emulation of SCC sensation.
Gong and Merfeld described the first single-channel prototype of such a prosthesis.[30
] In otherwise normal guinea pigs and squirrel monkeys rendered unresponsive to head rotation by surgical plugging of semicircular canals, that device generated partly compensatory eye movements for head rotations about its single axis of rotational sensitivity. Repeated switching of the device between powered and off states revealed progressive reduction in the time required to adapt to each state transition, suggesting that the vestibular nervous system not only adapts to prosthetic input, but learns to do so more quickly with experience.[32
] Misalignment of the prosthesis sensor’s axis away from that of the implanted SCC resulted in apparent cross-axis adaptation, suggesting correction of minor misalignments of the device and SCC is within the adaptive range of brainstem neural circuitry mediating the AVOR.[33
] Along with these tantalizing results came new challenges. The AVOR gain they observed was significantly less than that of the normal AVOR before canal plugging, suggesting more intense stimuli or more optimal stimulus coupling to the vestibular nerve is needed. In addition, extension of this approach to a multi-channel, multi-electrode device (with assay of eye movement responses in 3 dimensions) is necessary to encode head rotations in all directions.
Unfortunately, the three ampullary and two macular branches of the vestibular nerve are all close to each other in humans[34
] and even closer in small research animals.[35
] Spurious stimulation of vestibular nerve branches other than the intended target can cause poor control of eye movement direction, corrupting attempts to independently control different ampullary nerves. (Emulation of otolith endorgan transduction represents an even greater challenge, and published attempts have yielded conflicting results, probably due to the close proximity of axons representing different directions within each macule and macular nerve.[36
]) Limiting stimulus intensities to those below the threshold of spurious stimulation prevents one from using sufficiently intense stimuli to encode head rotations over more than a small subset of the normal physiologic range. This problem is especially acute for the ampullary nerves of the horizontal and superior cristae, which are especially close to each other and to the utricular nerve. I Extension of the single-channel prosthesis approach to a multi-channel device able to restore normal 3-dimensional AVOR function therefore represents a significant biomedical engineering challenge.
We describe the design, development, circuit performance and in vivo testing of a multi-channel vestibular prosthesis that simultaneously encodes head rotations in all 3 dimensions (3D), resolves them into semicircular canal plane components, and presents them as pulse-frequency-modulation encoded stimuli to the ampullary nerves innervating 3 or more SCC. We compare the electrically-evoked AVOR-mediated eye movements in vestibular-deficient chinchillas (Chinchilla laniger) to the 3D AVOR of normal animals during head rotation. Finally, we discuss considerations for evolution of this device toward a vestibular prosthesis for treatment of humans disabled by loss of vestibular sensation.