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Characterization of pulse amplitude and pulse rate modulation for a human vestibular implant during acute electrical stimulation
Abstract
Objective:
The vestibular system provides essential information about balance and spatial orientation via the brain to other sensory and motor systems. Bilateral vestibular loss significantly reduces quality of life, but vestibular implants (VIs) have demonstrated potential to restore lost function. However, optimal electrical stimulation strategies have not yet been identified in patients. In this study, we compared the two most common strategies, pulse amplitude modulation (PAM) and pulse rate modulation (PRM), in patients.
Approach:
Four subjects with a modified cochlear implant including electrodes targeting the peripheral vestibular nerve branches were tested. Charge-equivalent PAM and PRM were applied after adaptation to baseline stimulation. Vestibulo-ocular reflex eye movement responses were recorded to evaluate stimulation efficacy during acute clinical testing sessions.
Main results:
PAM evoked larger amplitude eye movement responses than PRM. Eye movement response axes for lateral canal stimulation were marginally better aligned with PRM than with PAM. A neural network model was developed for the tested stimulation strategies to provide insights on possible neural mechanisms. This model suggested that PAM would consistently cause a larger ensemble firing rate of neurons and thus larger responses than PRM.
Significance:
Due to the larger magnitude of eye movement responses, our findings strongly suggest PAM as the preferred strategy for initial VI modulation.
... Our group, using a different approach, decided to implement a basic stimulation paradigm based on our first acute experiments in humans. In those experiments we identified that current amplitude modulations of a charge balanced, cathodic-first, biphasic pulse train (phase durations of 200-400 s and rates of 200-400 pulses-per-second -pps) were an effective paradigm to evoke controlled vestibuloocular responses (50). We also decided, as a first approximation, to assume a linear relationship between electrical stimulation and the evoked eye movement response. ...
... The basic electrical stimulation profile consisted of trains of charge-balanced, cathodic-first biphasic pulses. The parameters under investigation were: current amplitude (0 to the maximum allowed by the electrode impedance and the implant compliance limits, see Table 1), phase duration (50,100,200, and 400 s), and pulse rate (100, 200, 400, and 800 pulses-per-second -pps). We evaluated the effect of either phase duration or pulse rate at a time, while the other was held constant. ...
... For the variable pulse rate experiments, we set the phase duration to 200µs. These parameters were chosen for consistency with our previous results, where they have shown to be an effective stimulation profile for the vestibular implant (30,31,39,41,42,44,45,50,54). ...
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 each either phase duration or 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.
... For the eVOR, frequency-dependent behavior was detected for a broad frequency range and was found to be similar to the natural frequency dependency of the angular vestibuloocular reflex (aVOR) [van de Berg et al., 2015;Guinand et al., 2017]. Furthermore, the VCR could be evoked and improvements of the dynamic visual acuity and gait were established [Guyot et al., 2011b;Perez Fornos et al., 2014;Pelizzone et al., 2014;van de Berg et al., 2015;Guinand et al., 2015bMcCrum et al., 2016;Nguyen et al., 2016Nguyen et al., , 2017Perez Fornos et al., 2017;van de Berg et al., 2017] ( Table 2). The variability in artificially evoked vestibular responses can be partially explained by the neural convergence as both the artificially and naturally stimulated neurons can provide information to the convergent neurons [Curthoys and Markham, 1971;Markham and Curthoys, 1972;Kushiro et al., 2000;Zhang et al., 2001Zhang et al., , 2002Goto et al., 2004;Uchino et al., 2005Uchino et al., , 2011. ...
... Motion modulation around a baseline stimulus can be accomplished by pulse frequency modulation, pulse amplitude modulation, or a combination of the two (comodulation). The latter has only been investigated in animal and neural network models so far [Guyot et al., 2011b;Davidovics et al., 2012;Nguyen et al., 2016]. ...
... Frequency modulation is most similar to the natural neural coding of the vestibular system and could therefore be expected to be the most effective [Fernandez and Goldberg, 1971]. However, in several studies, amplitude modulation has been shown to be more effective in evoking eye movements than frequency modulation [Guyot et al., 2011b;Perez Fornos et al., 2014;Nguyen et al., 2016]. Davidovics et al. [2012] suggested that this might be explained by a depletion of the synaptic vesicle pool induced by the continuous firing of the recruited afferents during the baseline adaptation. ...
Background:
In patients with bilateral vestibulopathy, the regular treatment options, such as medication, surgery, and/or vestibular rehabilitation, do not always suffice. Therefore, the focus in this field of vestibular research shifted to electrical vestibular stimulation (EVS) and the development of a system capable of artificially restoring the vestibular function. Key Message: Currently, three approaches are being investigated: vestibular co-stimulation with a cochlear implant (CI), EVS with a vestibular implant (VI), and galvanic vestibular stimulation (GVS). All three applications show promising results but due to conceptual differences and the experimental state, a consensus on which application is the most ideal for which type of patient is still missing.
Summary:
Vestibular co-stimulation with a CI is based on "spread of excitation," which is a phenomenon that occurs when the currents from the CI spread to the surrounding structures and stimulate them. It has been shown that CI activation can indeed result in stimulation of the vestibular structures. Therefore, the question was raised whether vestibular co-stimulation can be functionally used in patients with bilateral vestibulopathy. A more direct vestibular stimulation method can be accomplished by implantation and activation of a VI. The concept of the VI is based on the technology and principles of the CI. Different VI prototypes are currently being evaluated regarding feasibility and functionality. So far, all of them were capable of activating different types of vestibular reflexes. A third stimulation method is GVS, which requires the use of surface electrodes instead of an implanted electrode array. However, as the currents are sent through the skull from one mastoid to the other, GVS is rather unspecific. It should be mentioned though, that the reported spread of excitation in both CI and VI use also seems to induce a more unspecific stimulation. Although all three applications of EVS were shown to be effective, it has yet to be defined which option is more desirable based on applicability and efficiency. It is possible and even likely that there is a place for all three approaches, given the diversity of the patient population who serves to gain from such technologies.
... The Geneva-Maastricht group is the pioneer in human research related to vestibular implants. This group has achieved several fundamental milestones: (i) the development of special surgical approaches and their validation in acute intra-operative studies [48][49][50][51][52], (ii) the first chronic implantations in humans [53], (iii) the establishment of efficient stimulation strategies [54], and more recently (iv), the demonstration of useful rehabilitation with their vestibular implant prototype devices, both for basic vestibular reflexes [55][56][57] and for activities with clinical significance [58]. The Baltimore group started their investigations with animal models, where they addressed an important clinical issue by demonstrating that hearing could be preserved effectively during vestibular implantation with their particular device design and surgical technique [59]. ...
... It is therefore routinely used in cochlear and retinal implant recipients. The advantage of amplitude modulation has recently also been verified experimentally in vestibular implant recipients [53,54,66]. ...
Our senses are the main information channels through which we perceive and interact with the world. Consequently, the physical and social functioning of patients suffering from severe sensory disabilities is limited on several levels. This has motivated the development of a novel therapeutic alternative: “artificial senses”, more commonly known as sensory neuroprostheses. In order to restore lost function, sensory neuroprostheses attempt to take advantage of the information transfer pathway common to all senses: (i) transduction of the physical stimulus by sensory receptors, (ii) transmission of relevant information to primary sensory areas in the brain by sensory afferents, and (iii) analysis and integration of the information at multiple levels in the central nervous system. Neurosensory deficits might occur upon damage to any of the structures involved in this process. However, damage to the peripheral sensory receptor is often the cause of neurosensory loss. Most sensory neuroprostheses attempt to “replace” the malfunctioning or missing peripheral sensory organ by directly delivering basic sensory information to the brain using electrical currents. If the prosthesis is able to deliver enough consistent information, the brain will be able to correctly interpret it and useful rehabilitation can be achieved. This review presents the main challenges related to the development, implementation and translation to clinical practice of these devices: (i) sensory information needs to be efficiently delivered to specific neural targets (e.g., peripheral afferents or specific central nuclei); (ii) then the expected physiological response must be evoked and quantified; (iii) the restoration of basic sensory abilities can lead to useful rehabilitation in meaningful everyday activities; (iv) optimal prospects require specific rehabilitation therapy and lifelong medico-technical follow-up. To conclude, the current state and future of sensory neuroprostheses will be discussed. This will include current clinical and technical challenges, future prospects, and the potential of these devices to improve our fundamental knowledge of sensory physiology and neurosensory deficits.
... The sense of balance and spatial orientation is strongly connected with the correct functionality of the vestibular system. It contributes to the stabilization of gaze during head motion through the vestibulo-ocular reflex and to postural control and spatial orientation by other pathways, such as proprioception [2]. The vestibular system is composed of three semicircular canals (SCC) and two otolith organs, utricle and saccule. ...
The vestibular system is responsible for our sense of balance and spatial orientation. Recent studies have shown the possibility of partially restoring the function of this system using vestibular implants. Electrical modeling is a valuable tool in assisting the development of these implants by analyzing stimulation effects. However, previous modeling approaches of the vestibular system assumed quasi-static conditions. In this work, an extended modeling approach is presented that considers the reactive component of impedance and the electrode-tissue interface and their effects are investigated in a 3D human vestibular computer model. The Fourier finite element method was employed considering the frequency-dependent electrical properties of the different tissues. The electrode-tissue interface was integrated by an instrumental electrode model. A neuron model of myelinated fibers was employed to predict the nerve responses to the electrical stimulus. Morphological changes of the predicted voltage waveforms considering the dielectric tissue properties were found compared to quasi-static simulations, particularly during monopolar electrode configuration. Introducing the polarization capacitance and the scar tissue around the electrode in combination with a power limitation leads to a considerable current reduction applied through the active electrode and, consequently, to reduced voltage amplitudes of the stimulus waveforms. The reactive component of impedance resulted in better selectivity for the excitation of target nerves compared to the quasi-static simulation at the expense of slightly increased stimulus current amplitudes. We conclude that tissue permittivity and effects of the electrode-tissue interface should be considered to improve the accuracy of the simulations.
... Our sense of balance and spatial orientation strongly depends on the correct functionality of our vestibular system. It contributes to the stabilization of gaze during head motion through the vestibulo-ocular reflex and to postural control and spatial orientation by other pathways (Nguyen et al., 2016). Figure 1 depicts the anatomy of the inner ear. ...
Our sense of balance and spatial orientation strongly depends on the correct functionality of our vestibular system. Vestibular dysfunction can lead to blurred vision and impaired balance and spatial orientation, causing a significant decrease in quality of life. Recent studies have shown that vestibular implants offer a possible treatment for patients with vestibular dysfunction. The close proximity of the vestibular nerve bundles, the facial nerve and the cochlear nerve poses a major challenge to targeted stimulation of the vestibular system. Modeling the electrical stimulation of the vestibular system allows for an efficient analysis of stimulation scenarios previous to time and cost intensive in vivo experiments. Current models are based on animal data or CAD models of human anatomy. In this work, a (semi-)automatic modular workflow is presented for the stepwise transformation of segmented vestibular anatomy data of human vestibular specimens to an electrical model and subsequently analyzed. The steps of this workflow include (i) the transformation of labeled datasets to a tetrahedra mesh, (ii) nerve fiber anisotropy and fiber computation as a basis for neuron models, (iii) inclusion of arbitrary electrode designs, (iv) simulation of quasistationary potential distributions and (v) analysis of stimulus waveforms on the stimulation outcome. Results obtained by the workflow based on human datasets and the average shape of a statistical model revealed a high qualitative agreement and a quantitatively comparable range compared to data from literature, respectively. Based on our workflow, a detailed analysis of intra- and extra-labyrinthine electrode configurations with various stimulation waveforms and electrode designs can be performed on patient specific anatomy, making this framework a valuable tool for current optimization questions concerning vestibular implants in humans.
... Many research groups around the world are now investigating the feasibility, technical aspects and biomechanical issues of this option (10)(11)(12)(13). The first results of a motion-modulated vestibular prosthesis in humans were previously published by the Geneva-Maastricht group and provided clear evidence for the feasibility of a clinically useful VI in humans (14)(15)(16)(17)(18). ...
Objective
Patients with bilateral vestibulopathy (BV) can still have residual “natural” function. This might interact with “artificial” vestibular implant input (VI-input). When fluctuating, it could lead to vertigo attacks. Main objective was to investigate how “artificial” VI-input is integrated with residual “natural” input by the central vestibular system. This, to explore (1) whether misalignment in the response of “artificial” VI-input is sufficiently counteracted by well-aligned residual “natural” input and (2) whether “artificial” VI-input is able to influence and counteract the response to residual “natural” input, to show feasibility of a “vestibular pacemaker.”
Materials and methods
Five vestibular electrodes in four BV patients implanted with a VI were available. This involved electrodes with a predominantly horizontal response and electrodes with a predominantly vertical response. Responses to predominantly horizontal residual “natural” input and predominantly horizontal and vertical “artificial” VI-input were separately measured first. Then, inputs were combined in conditions where both would hypothetically collaborate or counteract. In each condition, subjects were subjected to 60 cycles of sinusoidal stimulation presented at 1 Hz. Gain, asymmetry, phase and angle of eye responses were calculated. Signal averaging was performed.
Results
Combining residual “natural” input and “artificial” VI-input resulted in an interaction in which characteristics of the resulting eye movement responses could significantly differ from those observed when responses were measured for each input separately (p < 0.0013). In the total eye response, inputs with a stronger vector magnitude seemed to have stronger weights than inputs with a lower vector magnitude, in a non-linear combination. Misalignment in the response of “artificial” VI-input was not sufficiently counteracted by well-aligned residual “natural” input. “Artificial” VI-input was able to significantly influence and counteract the response to residual “natural” input.
Conclusion
In the acute phase of VI-activation, residual “natural” input and “artificial” VI-input interact to generate eye movement responses in a non-linear fashion. This implies that different stimulation paradigms and more complex signal processing strategies will be required unless the brain is able to optimally combine both sources of information after adaptation during chronic use. Next to this, these findings could pave the way for using the VI as “vestibular pacemaker.”
... These differences in shape could indicate differences in neuronal survival (Stypulkowski and Van den Honert, 1984;Lai and Dillier, 2000). In previous studies with these subjects, we reported activation of the vestibular-ocular reflex through vestibular stimulation (Perez Fornos et al., 2014;Guinand et al., 2015;Nguyen et al., 2016). Peripheral vestibular neurons should be therefore present. ...
The peripheral vestibular system is critical for the execution of activities of daily life as it provides movement and orientation information to motor and sensory systems. Patients with bilateral vestibular hypofunction experience a significant decrease in quality of life and have currently no viable treatment option. Vestibular implants could eventually restore vestibular function. Most vestibular implant prototypes to date are modified cochlear implants to fast-track development. These use various objective measurements, such as the electrically evoked compound action potential (eCAP), to supplement behavioral information. We investigated whether eCAPs could be recorded in patients with a vestibulo-cochlear implant. Specifically, eCAPs were successfully recorded for cochlear and vestibular setups, as well as for mixed cochlear-vestibular setups. Similarities and slight differences were found for the recordings of the three setups. These findings demonstrated the feasibility of eCAP recording with a vestibulo-cochlear implant. They could be used in the short term to reduce current spread and avoid activation of non-targeted neurons. More research is warranted to better understand the neural origin of vestibular eCAPs and to utilize them for clinical applications.
... These devices implement amplitude and not rate modulation stimulation strategies. Second, our previous studies have demonstrated that amplitude modulation is an efficient way of activating the vestibular system, even more efficient than rate modulation in our particular setting involving distant stimulation of neural targets (13,28,29). On the other hand, we arbitrarily chose to implement a linear transfer function that avoids any theoretical assumptions regarding the relationship between the electrical stimulus and the vestibular response. ...
The purpose of this study was to evaluate whether it is possible to restore the high-frequency angular vestibulo-ocular reflex (aVOR) in patients suffering from a severe bilateral vestibulopathy (BV) and implanted with a vestibular implant prototype. Three patients (S1–3) participated in the study. They received a prototype vestibular implant with one to three electrode branches implanted in the proximity of the ampullary branches of the vestibular nerve. Five electrodes were available for electrical stimulation: one implanted in proximity of the left posterior ampullary nerve in S1, one in the left lateral and another one in the superior ampullary nerves in S2, and one in the right lateral and another one in the superior ampullary nerves in S3. The high-frequency aVOR was assessed using the video head impulse test (EyeSeeCam; EyeSeeTec, Munich, Germany), while motion-modulated electrical stimulation was delivered via one of the implanted vestibular electrodes at a time. aVOR gains were compared to control measurements obtained in the same patients when the device was not activated. In three out of the five tested electrodes the aVOR gain increased monotonically with increased stimulation strength when head impulses were delivered in the plane of the implanted canal. In these cases, gains ranging from 0.4 to values above 1 were measured. A “reversed” aVOR could also be generated when inversed stimulation paradigms were used. In most cases, the gain for excitatory head impulses was superior to that recorded for inhibitory head impulses, consistent with unilateral vestibular stimulation. Improvements of aVOR gain were generally accompanied by a concomitant decrease of corrective saccades, providing additional evidence of an effective aVOR. High inter-electrode and inter-subject variability were observed. These results, together with previous research, demonstrate that it is possible to restore the aVOR in a broad frequency range using motion-modulated electrical stimulation of the vestibular afferents. This provides additional encouraging evidence of the possibility of achieving a useful rehabilitation alternative for patients with BV in the near future.
Background: A combined vestibular (VI) and cochlear implant (CI) device, also known as the vestibulocochlear implant (VCI), was previously developed to restore both vestibular and auditory function. A new refined prototype is currently being investigated. This prototype allows for concurrent multichannel vestibular and cochlear stimulation. Although recent studies showed that VCI stimulation enables compensatory eye, body and neck movements, the constraints in these acute study designs prevent them from creating more general statements over time. Moreover, the clinical relevance of potential VI and CI interactions is not yet studied. The VertiGO! Trial aims to investigate the safety and efficacy of prolonged daily motion modulated stimulation with a multichannel VCI prototype.
Methods: A single-center clinical trial will be carried out to evaluate prolonged VCI stimulation, assess general safety and explore interactions between the CI and VI. A single-blind randomized controlled cross-over design will be implemented to evaluate the efficacy of three types of stimulation (i.e. two types of motion-modulated stimulation versus unmodulated baseline stimulation). Furthermore, this study will provide a proof-of-concept for a VI rehabilitation program. A total of minimum eight, with a maximum of 13, participants suffering from bilateral vestibulopathy and severe sensorineural hearing loss in the ear to implant will be included and followed over a five-year period. A VCI will be implanted into all three semicircular canals via the intralabyrinthine approach, and into the cochlea. After CI-rehabilitation, the VI will be fitted and one day of baseline testing will be planned before three periods of prolonged VI stimulation take place. Efficacy will be evaluated by collecting functional (i.e. image stabilization) and more fundamental (i.e. vestibulo-ocular reflexes, self-motion perception) outcomes. Hearing performance with a VCI and patient-reported outcomes will be included as well.
Discussion: The proposed schedule of fitting, stimulation and outcome testing allows for a comprehensive evaluation of the feasibility and long-term safety of a multichannel VCI prototype. This design will give insights into vestibular and hearing performance during VCI stimulation. Results will also provide insights into the expected daily benefit of prolonged VCI stimulation, paving the way for cost-effectiveness analyses and a more comprehensive clinical implementation of electrical vestibulocochlear stimulation in the future.
Trial registration: ClinicalTrials.gov: NCT04918745. Registered 28 April 2021
Cochlear implants are very well established in the rehabilitation of hearing loss and are regarded as the most successful neuroprostheses to date. While a lot of progress has also been made in the neighboring field of specific vestibular implants, some diseases affect the entire inner ear, leading to both hearing and vestibular hypo-or dysfunction. The proximity of the cochlear and vestibular organs suggests a single combined implant as a means to alleviate the associated impairments. While both organs can be stimulated in a similar way with electric pulses applied through implanted electrodes, the typical phase durations needed in the vestibular system seem to be substantially larger than those typically needed in the cochlear system. Therefore, when using sequential stimulation in a combined implant, the pulse stream to the cochlea is interrupted by comparatively large gaps in which vestibular stimulation can occur. We investigate the impact of these gaps in the auditory stream on speech perception. Specifically, we compare a number of stimulation strategies with different gap lengths and distributions and evaluate whether it is feasible to use them without having a noticeable decline in perception and quality of speech. This is a prerequisite for any practicable stimulation strategy of a combined system and can be investigated even in recipients of a normal cochlear implant. Our results show that there is no significant deterioration in speech perception for the different strategies examined in this paper, leaving the strategies as viable candidates for prospective combined cochleo-vestibular implants.
Gravity is a pervasive environmental stimulus, and accurate graviception is required for optimal spatial orientation and postural stability. The primary graviceptors are the vestibular organs, which include angular velocity (semicircular canals) and linear acceleration (otolith organs) sensors. Graviception is degraded in patients with vestibular damage, resulting in spatial misperception and imbalance. Since minimal therapy is available for these patients, substantial effort has focused on developing a vestibular prosthesis or vestibular implant (VI) that reproduces information normally provided by the canals (since reproducing otolith function is very challenging technically). Prior studies demonstrated that angular eye velocity responses could be driven by canal VI-mediated angular head velocity information, but it remains unknown whether a canal VI could improve spatial perception and posture since these behaviors require accurate estimates of angular head position in space relative to gravity. Here, we tested the hypothesis that a canal VI that transduces angular head velocity and provides this information to the brain via motion-modulated electrical stimulation of canal afferent nerves could improve the perception of angular head position relative to gravity in monkeys with severe vestibular damage. Using a subjective visual vertical task, we found that normal female monkeys accurately sensed the orientation of the head relative to gravity during dynamic tilts, that this ability was degraded following bilateral vestibular damage, and improved when the canal VI was used. These results demonstrate that a canal VI can improve graviception in vestibulopathic animals, suggesting that it could reduce the disabling perceptual and postural deficits experienced by patients with severe vestibular damage.
Background
Most questionnaires currently used for assessing symptomatology of vestibular disorders are retrospective, inducing recall bias and lowering ecological validity. An app-based diary, administered multiple times in daily life, could increase the accuracy and ecological validity of symptom measurement. The objective of this study was to introduce a new experience sampling method (ESM) based vestibular diary app (DizzyQuest), evaluate response rates, and to provide examples of DizzyQuest outcome measures which can be used in future research.Methods
Sixty-three patients diagnosed with a vestibular disorder were included. The DizzyQuest consisted of four questionnaires. The morning- and evening-questionnaires were administered once each day, the within-day-questionnaire 10 times a day using a semi-random time schedule, and the attack questionnaire could be completed after the occurrence of a vertigo or dizziness attack. Data were collected for 4 weeks. Response rates and loss-to-follow-up were determined. Reported symptoms in the within-day-questionnaire were compared within and between patients and subgroups of patients with different vestibular disorders.ResultsFifty-one patients completed the study period. Average response rates were significantly higher than the desired response rate of > 50% (p < 0.001). The attack-questionnaire was used 159 times. A variety of neuro-otological symptoms and different disease profiles were demonstrated between patients and subgroups of patients with different vestibular disorders.Conclusion
The DizzyQuest is able to capture vestibular symptoms within their psychosocial context in daily life, with little recall bias and high ecological validity. The DizzyQuest reached the desired response rates and showed different disease profiles between subgroups of patients with different vestibular disorders. This is the first time ESM was used to assess daily symptoms and quality of life in vestibular disorders, showing that it might be a useful tool in this population.
Electrical stimulus is one of the common stimulating methods, and Galvanic vestibular stimulation (GVS) is the oldest form as an electrical stimulation. Nevertheless, GVS is still considered as a secondary stimulating tool for the medical purposes. Even though some unarguable findings have made using GVS, its use has been limited because of its ambiguity as an input source. For better understanding, many previous studies mainly focused on its functional effects, like the ocular reflexes. However, its fundamental effects on the neural activities are still elusive, such as the dominant influences by different parameters of GVS. Here we compared the effects on the neuronal responses by applying two different parameters, strength and rate, of GVS. To assess the dominance on the neuronal responses to these parameters, we designed three independent stimuli. Those stimuli were multiply applied to obtain the responding slopes based on the mechanism of non-associative learning processes, and the effects on the neurons were calculated as an inner angle between two responding slopes. Out of 23 neurons, 15 (65.2%) units were affected more by the strength with a statistical significance (p = 0.047). The ranges of the inner angles also implied the strength (− 3.354°~2.063°) mainly modulated by the neuronal responses comparing with those by the rate (− 2.001°~1.975°). The dominance of the parameters was closely related with the neuronal sensitivity to stimulation (SE) (p = 0.018), while there were few relations with the neuronal regularity, directional preference (DP), and the physiological response (PR) (p > 0.059). Thus, the neural information related with the dominance was delivered by the irregular neurons, and these types of neurons should be the targets for the stimulation.
Graphical abstract
Electrical stimulation of vestibular afferent neurons to partially restore semicircular canal sensation of head rotation and the stabilizing reflexes that sensation supports has potential to effectively treat individuals disabled by bilateral vestibular hypofunction. Ideally, a vestibular implant system using this approach would be integrated with a cochlear implant, which would provide clinicians with a means to simultaneously treat loss of both vestibular and auditory sensation. Despite obvious similarities, merging these technologies poses several challenges, including stimulus pulse timing errors that arise when a system must implement a pulse-frequency-modulation encoding scheme (as is used in vestibular implants to mimic normal vestibular nerve encoding of head movement) within fixed-rate continuous interleaved sampling (CIS) strategies used in cochlear implants. Pulse timing errors caused by temporal discretization inherent to CIS create stair-step discontinuities of the vestibular implant's smooth mapping of head velocity to stimulus pulse frequency. In this study, we assayed electrically-evoked vestibulo-ocular reflex responses in two rhesus macaques using both a smooth pulse frequency modulation map (sPFM) and a discretized map corrupted by temporal errors typical of those arising in a combined cochlear/vestibular implant (dPFM). Responses were measured using 3D scleral coil oculography for prosthetic electrical stimuli representing sinusoidal head velocity waveforms that varied over 50-400°/s and 0.1-5Hz. Pulse timing errors produced negligible effects on responses across all canals in both animals, indicating that temporal discretization inherent to implementing a pulse-frequency-modulation coding scheme within a cochlear implant's CIS fixed pulse timing framework need not sacrifice performance of the combined system's vestibular implant portion.
Galvanic vestibular stimulation (GVS) plays an important role in the quest to understand sensory signal processing in the vestibular system under normal and pathological conditions. It has become a highly relevant tool to probe neuronal computations and to assist in the differentiation and treatment of vestibular syndromes. Following its accidental discovery, GVS became a diagnostic tool that generates eye movements in the absence of head/body motion. With the possibility to record extracellular and intracellular spikes, GVS became an indispensable method to activate or block the discharge in vestibular nerve fibers by cathodal and anodal currents, respectively. Bernie Cohen, in his attempt to decipher vestibular signal processing, has used this method in a number of hallmark studies that have added to our present knowledge, such as the link between selective electrical stimulation of semicircular canal nerves and the generation of directionally corresponding eye movements. His achievements paved the way for other major milestones including the differential recruitment order of vestibular fibers for cathodal and anodal currents, pronounced discharge adaptation of irregularly firing afferents, potential activation of hair cells, and fiber type-specific activation of central circuits. Previous disputes about the structural substrate for GVS are resolved by integrating knowledge of ion channel-related response dynamics of afferents, fiber type-specific innervation patterns, and central convergence and integration of semicircular canal and otolith signals. On the basis of solid knowledge of the methodology, specific waveforms of GVS are currently used in clinical diagnosis and patient treatment, such as vestibular implants and noisy galvanic stimulation.
A detailed electric model of current transmission through vestibular labyrinth tissues is suggested based on the anatomic structure of the labyrinth taking into account electrophysical properties of hair and basilar cells of neuroepithelium. Formulas for the impedance of the vestibular organ are derived and phase shifts of the stimulating current are calculated based on experimental data on the electrophysical and anatomic characteristics of vestibular labyrinth tissues of a guinea pig. The dispersion of the impedance is investigated for the frequencies in the range 101–5·104 Hz. It is shown that the phase shift of the current relative to the voltage applied between the electrode and the vestibular nerve is nonmonotonic in character and depends on the frequency. A minimum negative phase shift of the current is observed at f = 200 Hz. Taking into account of the cellular structures of the hair and basilar cells in the electric circuit shows that in the examined frequency range they bring significant contribution to the total impedance. The suggested electric model and the results of calculations can provide the basis for diagnostics of vestibular labyrinth diseases and design of vestibular implants of a new type.
An electric model of current transmission through tissues of the vestibular labyrinth of a patient is suggested. To stimulate directly the vestibular nerve in surgical operation, terminations of the electrodes are implanted through the bone tissue of the labyrinth into the perilymph in the vicinity of the vestibular nerve. The biological tissue of the vestibular labyrinth surrounding the electrodes and having heterogeneous composition possesses conductive and dielectric properties. Thus, when a current pulse from the vestibular implant is applied to one of the electrodes, conductive disturbance currents may arise between the electrodes and the vestibular nerves that can significantly deteriorate the direct signal quality. To study such signals and to compensate for the conductive disturbance currents, an equivalent electric circuit with actual electric impedance properties of tissues of the vestibular system is suggested, and the time parameters of the conductive disturbance current transmission are calculated. It is demonstrated that these parameters can reach large values. The suggested electric model and the results of calculations can be used for perfection of the vestibular implant.
Our senses are the main information channels through which we perceive and interact with the world. Consequently, patients suffering from severe sensory disabilities are limited at numerous levels of physical and social functioning. This has motivated the development of a novel therapeutic alternative: sensory neuroprostheses. In order to restore lost function, sensory neuroprostheses attempt to take advantage of the information transfer pathway common to all senses: (1) transduction of the physical stimulus by sensory receptors, (2) transmission of relevant information to the primary sensory areas in the brain by sensory afferents, and (3) analysis and integration of the information to generate perception and action. Neurosensory deficits might occur upon damage of any of the structures involved in the process. However, damage to the peripheral sensory receptor can be often the cause of neurosensory loss. Sensory neuroprostheses attempt to “replace” the malfunctioning or missing peripheral sensory organ by directly delivering basic sensory information to the brain using electrical currents. If the prosthesis is able to deliver enough consistent information, the brain will correctly interpret it and useful rehabilitation can be achieved. I have had the opportunity to contribute to this multidisciplinary field at diverse aspects of the development of retinal, cochlear, and vestibular implants. I have chosen to present the main challenges related to the implementation of these devices as a step-to-step approach in the form a collection of selected articles: (1) sensory information should be efficiently delivered to peripheral afferents (Chapter 2); (2) then the expected physiological response can be evoked and quantified (Chapter 3); (3) the restoration of basic sensory abilities can lead to useful rehabilitation in meaningful every-day activities (Chapter 4); (4) however, sensory pathophysiology can fundamentally limit our ability to transmit the appropriate message to the brain (Chapter 5). Finally, Chapter 6 presents the good clinical outcomes that can be achieved, highlighting the importance of proper technical and rehabilitation follow-up. To conclude, in Chapter 7 the present and future of sensory neuroprostheses will be discussed. This will specifically include current clinical and technical challenges, future prospects, as well as the potential of these devices of improving our fundamental knowledge of sensory physiology and neurosensory deficits.
The vestibular system incorporates multiple sensory pathways to provide crucial information about head and body motion. Damage to the semicircular canals, the peripheral vestibular organs that sense rotational velocities of the head, can severely degrade the ability to perform activities of daily life. Vestibular prosthetics address this problem by using stimulating electrodes that can trigger primary vestibular afferents to modulate their firing rates, thus encoding head movement. These prostheses have been demonstrated chronically in multiple animal models and acutely tested in short-duration trials within the clinic in humans. However, mainly, due to limited opportunities to fully characterize stimulation parameters, there is a lack of understanding of "optimal" stimulation configurations for humans. Here, we model possible adaptive plasticity in the vestibular pathway. Specifically, this model highlights the influence of adaptation of synaptic strengths and offsets in the vestibular nuclei to compensate for the initial activation of the prosthetic. By changing the synaptic strengths, the model is able to replicate the clinical observation that erroneous eye movements are attenuated within 30 minutes without any change to the prosthetic stimulation rate. Although our model was only built to match this time point, we further examined how it affected subsequent pulse rate modulation (PRM) and pulse amplitude modulation (PAM). PAM was more effective than PRM for nearly all stimulation configurations during these acute tests. Two non-intuitive relationships highlighted by our model explain this performance discrepancy. Specifically, the attenuation of synaptic strengths for afferents stimulated during baseline adaptation and the discontinuity between baseline and residual firing rates both disproportionally boost PAM. Comodulation of pulse rate and amplitude has been experimentally shown to induce both excitatory and inhibitory eye movements even at high baseline stimulation rates. We also modeled comodulation and found synergistic combinations of stimulation parameters to achieve equivalent output to only amplitude modulation. This may be an important strategy to reduce current spread and misalignment. The model outputs reflected observed trends in clinical testing and aspects of existing vestibular prosthetic literature. Importantly, the model provided insight to efficiently explore the stimulation parameter space, which was helpful, given limited available patient time.
Bilateral vestibular hypofunction (BVH) probably represents a heterogeneous disorder with different types of clinical pictures, with and without vertigo. In spite of increasingly sophisticated electrophysiological testing, still many challenges are met when establishing a diagnosis of BVH. Here, we review the main challenges, which are a reflection of its often difficult clinical presentation and the lack of diagnostic standards regarding the implementation and interpretation of vestibular tests. These challenges show that there is an urgent need for standardization. The resulting decisions should be used for the development of uniform diagnostic criteria for BVH, which are, at present, not yet available.
The vestibulo-ocular reflex (VOR) shows frequency-dependent behavior. This study investigated whether the characteristics of the electrically evoked VOR (eVOR) elicited by a vestibular implant, showed the same frequency-dependency. Twelve vestibular electrodes implanted in seven patients with bilateral vestibular hypofunction (BVH) were tested. Stimuli consisted of amplitude-modulated electrical stimulation with a sinusoidal profile at frequencies of 0.5, 1, and 2 Hz. The main characteristics of the eVOR were evaluated and compared to the " natural " VOR characteristics measured in a group of age-matched healthy volunteers who were subjected to horizontal whole body rotations with equivalent sinusoidal velocity profiles at the same frequencies. A strong and significant effect of frequency was observed in the total peak eye velocity of the eVOR. This effect was similar to that observed in the " natural " VOR. Other characteristics of the (e)VOR (angle, habituation-index, and asymmetry) showed no significant frequency-dependent effect. In conclusion, this study demonstrates that, at least at the specific (limited) frequency range tested, responses elicited by a vestibular implant closely mimic the frequency-dependency of the " normal " vestibular system.
The vestibular system plays a crucial role in the multisensory control of balance. When vestibular function is lost, essential tasks such as postural control, gaze stabilization, and spatial orientation are limited and the quality of life of patients is significantly impaired. Currently, there is no effective treatment for bilateral vestibular deficits. Research efforts both in animals and humans during the last decade set a solid background to the concept of using electrical stimulation to restore vestibular function. Still, the potential clinical benefit of a vestibular neuroprosthesis has to be demonstrated to pave the way for a translation into clinical trials. An important parameter for the assessment of vestibular function is the vestibulo-ocular reflex (VOR), the primary mechanism responsible for maintaining the perception of a stable visual environment while moving. Here we show that the VOR can be artificially restored in humans using motion-controlled, amplitude modulated electrical stimulation of the ampullary branches of the vestibular nerve. Three patients received a vestibular neuroprosthesis prototype, consisting of a modified cochlear implant providing vestibular electrodes. Significantly higher VOR responses were observed when the prototype was turned ON. Furthermore, VOR responses increased significantly as the intensity of the stimulation increased, reaching on average 79% of those measured in healthy volunteers in the same experimental conditions. These results constitute a fundamental milestone and allow us to envision for the first time clinically useful rehabilitation of patients with bilateral vestibular loss.
No adequate treatment exists for individuals who remain disabled by bilateral loss of vestibular (inner ear inertial) sensation despite rehabilitation. We have restored vestibular reflexes using lab-built multichannel vestibular prostheses (MVPs) in animals, but translation to clinical practice may be best accomplished by modification of a commercially available cochlear implant (CI). In this interim report, we describe preliminary efforts toward that goal. We developed software and circuitry to sense head rotation and drive a CI's implanted stimulator (IS) to deliver up to 1Kpulses/s via 9 electrodes implanted near vestibular nerve branches. Studies in two rhesus monkeys using the modified CI revealed in vivo performance similar to our existing dedicated MVPs. A key focus of our study was the head-worn unit (HWU), which magnetically couples across the scalp to the IS. The HWU must remain securely fixed to the skull to faithfully sense head motion and maintain continuous stimulation. We measured normal and shear force thresholds at which HWU-IS decoupling occurred as a function of scalp thickness and calculated pressure exerted on the scalp. The HWU remained attached for human scalp thicknesses from 3-7.8mm for forces experienced during routine daily activities, while pressure on the scalp remained below capillary perfusion pressure.
Purpose: Adults with bilateral vestibular hypofunction (BVH) experience significant disability. A systematic review assessed evidence for vestibular rehabilitation (VR). Number of studies: 14 studies. Materials/methods: Search identification of studies based on inclusion criteria: (a) population: adults with BVH of peripheral origin; (b) interventions: vestibular exercises, balance training, education, or sensory prosthetics; (c) comparison: single interventions or compared to another psychophysical intervention, placebo, or healthy population; (d) outcomes: based on International Classification of Functioning, Disability and Health (ICF) Body Functions and Structure, Activity, and Participation; (e) study designs: prospective and interventional, Levels of Evidence I to III per Centre of Evidence-based Medicine grading. Coding and appraisal based on ICF framework and strength of evidence synthesis. Results: Five Level II studies and nine Level III studies: All had outcomes on gaze and postural stability, five with outcomes on gait speed and perceptions of oscillopsia and disequilibrium.Conclusions: (a) Moderate evidence strength on improved gaze and postural stability (ICF-Body Functions) following exercise-based VR; (b) Inadequate number of studies supporting benefit of VR on ICF-Participation outcomes; (c) Sensory prosthetics in early phase of development. Clinical relevance: Moderate evidence strength in support of VR from an impairment level; clinical practice and research needed to explore interventions extending to ICF-Activity and Participation.
Currently, there is no evidence of an effective treatment for patients with bilateral vestibulopathy (BV). Their main complaints are oscillopsia and imbalance. Opinions about the impact of BV on their quality of life are controversial, and their handicap is not always recognized, even among otoneurologists. The aim of this study was to objectively assess the health status of BV patients in order to evaluate the need for pursuing efforts toward the development of new treatments.
The short-form health survey (SF-36), the dizziness handicap inventory (DHI), the short falls efficacy scale-international (short FES-I), and an oscillopsia severity questionnaire were submitted to 39 BV patients. The SF-36 scores were compared to the scores of a general Dutch population. The DHI scores were correlated to the oscillopsia severity scores. The short FES-I scores were compared to scores in an elderly population. Residual otolithic function was correlated to all scores, and hearing to SF-36 scores.
Compared to the general Dutch population, the BV patients scored significantly worse on the "physical functioning", "role physical", "general health", "vitality", and "social functioning" SF-36 variables (p < 0.05). The DHI scores were strongly correlated with the oscillopsia severity scores (r = 0.75; p < 0.000001). The short FES-I scores indicated a slight to moderate increase in the patients' fear of falling. No significant score differences were found between BV patients with residual otolithic function and patients with complete BV. There was no correlation between hearing status and SF-36 scores.
The results correlate with our clinical impression that BV has a strong negative impact on physical and social functioning, leading to a quality-of-life deterioration. There is a clear need for a therapeutic solution. Efforts toward the development of a vestibular implant are justified.
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.
An implantable prosthesis that stimulates vestibular nerve branches to restore sensation of head rotation and vision-stabilizing reflexes could benefit individuals disabled by bilateral loss of vestibular (inner ear balance) function. We developed a prosthesis that partly restores normal function in animals by delivering pulse frequency modulated (PFM) biphasic current pulses via electrodes implanted in semicircular canals. Because the optimal stimulus encoding strategy is not yet known, we investigated effects of varying biphasic current pulse frequency, amplitude, duration, and interphase gap on vestibulo-ocular reflex (VOR) eye movements in chinchillas. Increasing pulse frequency increased response amplitude while maintaining a relatively constant axis of rotation. Increasing pulse amplitude (range 0-325 μA) also increased response amplitude but spuriously shifted eye movement axis, probably due to current spread beyond the target nerve. Shorter pulse durations (range 28-340 μs) required less charge to elicit a given response amplitude and caused less axis shift than longer durations. Varying interphase gap (range 25-175 μs) had no significant effect. While specific values reported herein depend on microanatomy and electrode location in each case, we conclude that PFM with short duration biphasic pulses should form the foundation for further optimization of stimulus encoding strategies for vestibular prostheses intended to restore sensation of head rotation.
Objective:
To assess, for the first time in a human with a long-term vestibular loss, a modified approach to the ampullae and the feasibility of evoking a VOR by ampullar stimulation.
Materials and methods:
Peroperative stimulation of the ampullae, using the ampullar approach, was performed under full anesthesia during cochlear implantation in a 21-year-old female patient, who had experienced bilateral vestibular areflexia and sensorineural hearing loss for almost 20 years.
Results:
The modified ampullar approach was performed successfully with as minimally invasive surgery as possible. Ampullar stimulation evoked eye movements containing vectors congruent with the stimulated canal. As expected, the preliminary electrophysiological data were influenced by the general anesthesia, which resulted in current spread and reduced maximum amplitudes of eye movement. Nevertheless, they confirm the feasibility of ampullar stimulation.
Conclusion:
The modified ampullar approach provides safe access to the ampullae using as minimally invasive surgery as possible. For the first time in a human with long-term bilateral vestibular areflexia, it is shown that the VOR can be evoked by ampullar stimulation, even when there has been no vestibular function for almost 20 years. This approach should be considered in vestibular surgery, as it provides safe access to one of the most favorable stimulus locations for development of a vestibular implant.
In normal individuals, the vestibular labyrinths sense head movement and mediate reflexes that maintain stable gaze and posture. Bilateral loss of vestibular sensation causes chronic disequilibrium, oscillopsia, and postural instability. We describe a new multichannel vestibular prosthesis (MVP) intended to restore modulation of vestibular nerve activity with head rotation. The device comprises motion sensors to measure rotation and gravitoinertial acceleration, a microcontroller to calculate pulse timing, and stimulator units that deliver constant-current pulses to microelectrodes implanted in the labyrinth. This new MVP incorporates many improvements over previous prototypes, including a 50% decrease in implant size, a 50% decrease in power consumption, a new microelectrode array design meant to simplify implantation and reliably achieve selective nerve-electrode coupling, multiple current sources conferring ability to simultaneously stimulate on multiple electrodes, and circuitry for in vivo measurement of electrode impedances. We demonstrate the performance of this device through in vitro bench-top characterization and in vivo physiological experiments with a rhesus macaque monkey.
Efforts are being made toward the development of a vestibular implant. If such a device is to mimic the physiology of the vestibular system, it must first be capable of restoring a baseline or "rest" activity in the vestibular pathways and then modulating it according to the direction and velocity of head movements. The aim of this study was to assess whether a human subject could adapt to continuous electrical stimulation of the vestibular system, and whether it was possible to elicit artificial smooth oscillatory eye movements via modulation of the stimulation.
One bilaterally deaf patient with bilateral vestibular loss received a custom-modified Med-E1 cochlear implant in which one electrode was implanted in the vicinity of the left posterior ampullary nerve. This electrode was activated with biphasic pulse trains of 400-micros phase duration delivered at a repetition rate of 200 pulses per second. The resulting eye movements were recorded with 2-dimensional binocular video-oculography.
Successive "on-off" cycles of continuous electrical stimulation resulted in a progressively shorter duration of the nystagmic response. Once the adapted state was reached upon constant stimulation, amplitude or frequency modulations of electrical stimulation produced smooth oscillatory conjugated eye movements.
Although this is a case study of one patient, the results suggest that humans can adapt to electrical stimulation of the vestibular system without too much discomfort. Once the subject is in the adapted state, the electrical stimulation can be modulated to artificially elicit smooth eye movements. Therefore, the major prerequisites for the feasibility of a vestibular implant for human use are fulfilled.
Do central and peripheral motor pathways associated with an amputated limb retain at least some functions over periods of years? This problem could be addressed by evaluating the response patterns of nerve signals from peripheral motor fibers during transcranial magnetic stimulation (TMS) of corticospinal tracts. The aim of this study was to record for the first time TMS-related responses from the nerves of a left arm stump of an amputee via intrafascicular longitudinal flexible multi-electrodes (tfLIFE4) implanted for a prosthetic hand control. After tfLIFE4 implant in the stump median and ulnar nerves, TMS impulses of increasing intensity were delivered to the contralateral motor cortex while tfLIFE4 recordings were carried out. Combining TMS of increasing intensity and tfLIFE4 electrodes recordings, motor nerve activity possibly related to the missing limb motor control and selectively triggered by brain stimulation without significant electromyographic contamination was identified. These findings are entirely original and indicate that tfLIFE4 signals are clearly driven from M1 stimulation, therefore witnessing the presence in the stump nerves of viable motor signals from the CNS possibly useful for artificial prosthesis control.
By sensing three-dimensional (3D) head rotation and electrically stimulating the three ampullary branches of a vestibular nerve to encode head angular velocity, a multichannel vestibular prosthesis (MVP) can restore vestibular sensation to individuals disabled by loss of vestibular hair cell function. However, current spread to afferent fibers innervating non-targeted canals and otolith end organs can distort the vestibular nerve activation pattern, causing misalignment between the perceived and actual axis of head rotation. We hypothesized that over time, central neural mechanisms can adapt to correct this misalignment. To test this, we rendered five chinchillas vestibular deficient via bilateral gentamicin treatment and unilaterally implanted them with a head-mounted MVP. Comparison of 3D angular vestibulo-ocular reflex (aVOR) responses during 2 Hz, 50°/s peak horizontal sinusoidal head rotations in darkness on the first, third, and seventh days of continual MVP use revealed that eye responses about the intended axis remained stable (at about 70% of the normal gain) while misalignment improved significantly by the end of 1 week of prosthetic stimulation. A comparable time course of improvement was also observed for head rotations about the other two semicircular canal axes and at every stimulus frequency examined (0.2-5 Hz). In addition, the extent of disconjugacy between the two eyes progressively improved during the same time window. These results indicate that the central nervous system rapidly adapts to multichannel prosthetic vestibular stimulation to markedly improve 3D aVOR alignment within the first week after activation. Similar adaptive improvements are likely to occur in other species, including humans.
There is no effective treatment available for individuals unable to compensate for bilateral profound loss of vestibular sensation, which causes chronic disequilibrium and blurs vision by disrupting vestibulo-ocular reflexes that normally stabilize the eyes during head movement. Previous work suggests that a multichannel vestibular prosthesis can emulate normal semicircular canals by electrically stimulating vestibular nerve branches to encode head movements detected by mutually orthogonal gyroscopes affixed to the skull. Until now, that approach has been limited by current spread resulting in distortion of the vestibular nerve activation pattern and consequent inability to accurately encode head movements throughout the full 3-dimensional (3D) range normally transduced by the labyrinths. We report that the electrically evoked 3D angular vestibulo-ocular reflex exhibits vector superposition and linearity to a sufficient degree that a multichannel vestibular prosthesis incorporating a precompensatory 3D coordinate transformation to correct misalignment can accurately emulate semicircular canals for head rotations throughout the range of 3D axes normally transduced by a healthy labyrinth.
The cochlear implant is the most successful of all neural prostheses developed to date. It is the most effective prosthesis in terms of restoration of function, and the people who have received a cochlear implant outnumber the recipients of other types of neural prostheses by orders of magnitude. The primary purpose of this article is to provide an overview of contemporary cochlear implants from the perspective of two designers of implant systems. That perspective includes the anatomical situation presented by the deaf cochlea and how the different parts of an implant system (including the user's brain) must work together to produce the best results. In particular, we present the design considerations just mentioned and then describe in detail how the current levels of performance have been achieved. We also describe two recent advances in implant design and performance. In concluding sections, we first present strengths and limitations of present systems and then offer some possibilities for further improvements in this technology. In all, remarkable progress has been made in the development of cochlear implants but much room still remains for improvements, especially for patients presently at the low end of the performance spectrum.
This experiment, which extends a previous investigation (Pozzo et al. 1990), was undertaken to examine how head position is controlled during natural locomotor tasks in both normal subjects (N) and patients with bilateral vestibular deficits (V). 10 normals and 7 patients were asked to perform 4 locomotor tasks: free walking (W), walking in place (WIP), running in place (R) and hopping (H). Head and body movements were recorded with a video system which allowed a computed 3 dimensional reconstruction of selected points in the sagittal plane. In order to determine the respective contribution of visual and vestibular cues in the control of head angular position, the 2 groups of subjects were tested in the light and in darkness. In darkness, the amplitude and velocity of head rotation decreased for N subjects; these parameters increased for V subjects, especially during R and H. In darkness, compared to the light condition, the mean position of a line placed on the Frankfort plane (about 20-30 degrees below the horizontal semi-circular canal plane) was tilted downward in all conditions of movement, except during H, for N subjects. In contrast, this flexion of the head was not systematic in V subjects: the Frankfort plane could be located above or below earth horizontal. In V subjects, head rotation was not found to be compensatory for head translation and the power spectrum analysis shows that head angular displacements in the sagittal plane contain mainly low frequencies (about 0.3-0.8 Hz). The respective contribution of visual and vestibular cues in the control of the orientation and the stabilization of the head in space is discussed.
Head kinematics were studied in ten normal subjects while they executed various locomotor tasks. The movement of the body was recorded with a video system which allowed a computer reconstruction of motion of joint articulations and other selected points on the body in three dimensions. Analyses focus on head translation along the vertical axis and rotation in the sagittal plane. This was done by recording the displacement of a line approximating the plane of horizontal semi-circular canals (the Frankfort plane: F-P). Four conditions were studied: free walking (W) walking in place (WIP) running in place (R) and hopping (H). In the 4 experimental conditions, amplitude and velocity of head translation along the vertical axis ranged from 1 cm to 25 cm and 0.15 m/s to 1.8 m/s. In spite of the disparities in the tasks regarding the magnitude of dynamic components, we found a significant stabilization of the F-P around the earth horizontal. Maximum amplitude of F-P rotation did not exceed 20 degrees in the 4 situations. Vertical angular velocities increased from locomotion tasks to the dynamic equilibrium task although the maximum values remained less than 140 degrees/s. Predominant frequencies of translations and rotations in all the tasks were within the range 0.4-3.5 Hz and harmonics were present up to 6-8 Hz. During walking in darkness, mean head position is tilted downward, with the F-P always below the earth horizontal. Darkness did not significantly influence the amplitude and velocity of head angular displacement during W, WIP and R, but during H the amplitude decreased by 37%. Residual head angular displacement is found to compensate for head translation during the 4 conditions. Our study emphasizes the importance of head stabilization as part of the postural control system and described as a basis for inertial guidance.
Studies of the neural basis of learning and memory in intact animals must, by their nature, start "from the top" by choosing a behavior that can be modified through learning, revealing how iaeuronal activity gives rise to that behavior, and then investigating, in the awake, behaving animal, changes in neural signaling that are associated with learning. Such studies also must recognize that the learning and memory expressed in the behavior of an animal will reflect both the properties of the neural network that mediates the behavior and the nature of the underlying changes in the operation of cells or synapses. In the past 10 years, there has been an explosion of information about learning and memory in the vestibulo-ocular reflex (VOR) of the awake, behaving monkey. At the same time, there have been unprecedented advances in understanding mechanisms of cellular plasticity such as long-term potentiation (LTP) in the hippocampus and long-term depression (LTD) in the cerebellum. A prerequisite for understanding learning and memory is to elevate specific mechanisms of cellular plasticity into cellular mechanisms of learning by establishing their function in the context of a neural system that mediates learning and memory in a particular behavior. Our review synthesizes the
Acute unilateral vestibulopathy, or vestibular neuritis, is the second most common cause of vertigo. To quantify the involvement of the different semicircular canal (SCC) afferents in this disease, we studied the three-dimensional (3D) properties of the vestibuloocular reflex (VOR) in 16 patients 3-10 days after onset of symptoms. Using 3D magnetic search coil eye movement recordings, we measured the speed and axis of eye rotation during spontaneous nystagmus and during rotation in the planes of the different SCCs. In all patients, spontaneous nystagmus axes clustered between the direction expected with involvement of just one horizontal SCC and the direction expected with combined involvement of the horizontal and anterior SCC on one side. Likewise, dynamic asymmetries were found only during rotations about axes which stimulated the ipsilesional horizontal or ipsilesional anterior SCCs. No asymmetry was found when the ipsilesional posterior SCC was stimulated. Thus, both measurements suggest that vestibular neuritis is a partial and not a complete unilateral vestibular lesion and that this partial lesion affects the superior division of the vestibular nerve which includes the afferents from the horizontal and anterior SCCs.
We have developed and tested a prosthetic semicircular canal that senses angular head velocity and uses this information to modulate the rate of current pulses applied to the vestibular nerve via a stimulating electrode. In one squirrel monkey, the lateral canals were plugged bilaterally and the prosthesis was secured to the animal's head with the angular velocity sensor parallel to the axis of the lateral canals. In the first experiment, the stimulating electrode was placed near the ampullary nerve of one lateral canal. Over a period of two weeks, the gain of the horizontal VOR during yaw axis rotation gradually increased, although the response magnitude remained relatively small. In the second experiment, the stimulating electrode was placed near the ampullary nerve of the posterior canal, but the orientation of the velocity sensor remained parallel to the axis of the lateral canals. Over a one-week period, the axis of the VOR response gradually shifted towards alignment with the (yaw) axis of head rotation. Chronic patterned stimulation of the eighth nerve can therefore provide adequate information to the brain to generate a measurable VOR response, and this can occur even if the prosthetic yaw rotation cue is provided via a branch of the VIIIth nerve that doesn't normally carry yaw rotational cues. The results provided by this pilot study suggest that it may be feasible to study central adaptation by chronically modifying the afferent vestibular cue with a prosthetic semicircular canal.
Background:
The concept of the vestibular implant is primarily to artificially restore the vestibular function in patients with a bilateral vestibular loss (BVL) by providing the central nervous system with motion information using electrical stimulation of the vestibular nerve. Our group initiated human trials about 10 years ago.
Methods:
Between 2007 and 2013, 11 patients with a BVL received a vestibular implant prototype providing electrodes to stimulate the ampullary branches of the vestibular nerve. Eye movements were recorded and analyzed to assess the effects of the electrical stimulation. Perception induced by electrical stimulation was documented.
Results:
Smooth, controlled eye movements were obtained in all patients showing that electrical stimulation successfully activated the vestibulo-ocular pathway. However, both the electrical dynamic range and the amplitude of the eye movements were variable from patient to patient. The axis of the response was consistent with the stimulated nerve branch in 17 out of the 24 tested electrodes. Furthermore, in at least 1 case, the elicited eye movements showed characteristics similar to those of compensatory eye movements observed during natural activities such as walking. Finally, diverse percepts were reported upon electrical stimulation (i.e., rotatory sensations, sound, tickling or pressure) with intensity increasing as the stimulation current increased.
Conclusions:
These results demonstrate that electrical stimulation is a safe and effective means to activate the vestibular system, even in a heterogeneous patient population with very different etiologies and disease durations. Successful tuning of this information could turn this vestibular implant prototype into a successful artificial balance organ.
Loss of peripheral vestibular function results in debilitating postural, perceptual, and visual symptoms. A new approach to treating this clinical problem is to replace some aspects of peripheral vestibular function with a prosthesis that senses head motion and provides this information to the brain by stimulating the vestibular nerve. In this paper, I review studies done in animals over the past 15 years which lay the groundwork for transferring this approach to human patients with severe peripheral vestibular damage. The animal studies demonstrate that the visual and perceptual defects associated with peripheral vestibular damage can be improved with a vestibular implant, but the data on postural control remain less conclusive at this point in time.
Although vestibular disorders are common and often disabling, they remain difficult to diagnose and treat. For these reasons, considerable interest has been focused on developing new ways to identify peripheral and central vestibular abnormalities and on new therapeutic options that could benefit the numerous patients who remain symptomatic despite optimal therapy. In this review, I focus on the potential utility of psychophysical vestibular testing and vestibular prosthetics. The former offers a new diagnostic approach that may prove to be superior to the current tests in some circumstances; the latter may be a way to provide the brain with information about head motion that restores some elements of the information normally provided by the vestibular labyrinth.
Copyright © 2015 the authors 0270-6474/15/355089-08$15.00/0.
Bilateral vestibular deficiency (BVD) due to gentamicin ototoxicity can significantly impact quality of life and result in large socioeconomic burdens. Restoring sensation of head rotation using an implantable multichannel vestibular prosthesis (MVP) is a promising treatment approach that has been tested in animals and humans. However, uncertainty remains regarding the histopathologic effects of gentamicin ototoxicity alone or in combination with electrode implantation. Understanding these histological changes is important because selective MVP-driven stimulation of semicircular canals (SCCs) depends on persistence of primary afferent innervation in each SCC crista despite both the primary cause of BVD (e.g., ototoxic injury) and surgical trauma associated with MVP implantation. Retraction of primary afferents out of the cristae and back toward Scarpa's ganglion would render spatially selective stimulation difficult to achieve and could limit utility of an MVP that relies on electrodes implanted in the lumen of each ampulla. We investigated histopathologic changes of the inner ear associated with intratympanic gentamicin (ITG) injection and/or MVP electrode array implantation in 11 temporal bones from six rhesus macaque monkeys. Hematoxylin and eosin-stained 10-μm temporal bone sections were examined under light microscopy for four treatment groups: normal (three ears), ITG-only (two ears), MVP-only (two ears), and ITG + MVP (four ears). We estimated vestibular hair cell (HC) surface densities for each sensory neuroepithelium and compared findings across end organs and treatment groups. In ITG-only, MVP-only, and ITG + MVP ears, we observed decreased but persistent ampullary nerve fibers of SCC cristae despite ITG treatment and/or MVP electrode implantation. ITG-only and ITG + MVP ears exhibited neuroepithelial thinning and loss of type I HCs in the cristae but little effect on the maculae. MVP-only and ITG + MVP ears exhibited no signs of trauma to the cochlea or otolith end organs except in a single case of saccular injury due to over-insertion of the posterior SCC electrode. While implanted electrodes reached to within 50-760 μm of the target cristae and were usually ensheathed in a thin fibrotic capsule, dense fibrotic reaction and osteoneogenesis were each observed in only one of six electrode tracts examined. Consistent with physiologic studies that have demonstrated directionally appropriate vestibulo-ocular reflex responses to MVP electrical stimulation years after implantation in these animals, histologic findings in the present study indicate that although intralabyrinthine MVP implantation causes some inner ear trauma, it can be accomplished without destroying the distal afferent fibers an MVP is designed to excite.
The vestibular organs are very important to generate reflexes critical for stabilizing gaze and body posture. Vestibular diseases significantly reduce the quality of life of people who are affected by them. Some research groups have recently started developing vestibular neuroprostheses to mitigate these symptoms. However, many scientific and technological issues need to be addressed to optimise their use in clinical trials. We developed a computational model able to mimic the response of human vestibular nerves and which can be exploited for 'in-silico' testing of new strategies to design implantable vestibular prostheses. First, a digital model of the vestibular system was reconstructed from anatomical data. Monopolar stimulation was delivered at different positions and distances from ampullary nerves. The electrical potential induced by the injected current was computed through finite-element methods and drove extra-cellular stimulation of fibers in the vestibular, facial, and cochlear nerves. The electrical activity of vestibular nerves and the resulting eye movements elicited by different stimulation protocols were investigated. A set of electrode configurations was analyzed in terms of selectivity at increasing injected current. Electrode position along the nerve plays a major role in producing undesired activity in other non-targeted nerves, whereas distance from the fiber does not significantly affect selectivity. Indications are provided to minimize misalignment in non-optimal electrode locations. Eye movements elicited by the different stimulation protocols are calculated and compared to experimental values, for the purpose of model validation.
Animal experiments and limited data in humans suggest that electrical stimulation of the vestibular end organs could be used to treat loss of vestibular function. In this paper we demonstrate that canal specific two dimensionally (2D) measured eye velocities are elicited from intermittent brief 2s biphasic pulse electrical stimulation in four human subjects implanted with a vestibular prosthesis. The 2D measured direction of the slow phase eye movements changed with the canal stimulated. Increasing pulse current over a 0-400 μA range typically produced a monotonic increase in slow phase eye velocity. The responses decremented or in some cases fluctuated over time in most implanted canals, but could be partially restored by changing the return path of the stimulation current. Implantation of the device in Meniere's patients produced hearing and vestibular loss in the implanted ear. Electrical stimulation was well tolerated producing no sensation of pain, nausea, or auditory percept with stimulation that elicited robust eye movements. There were changes in slow phase eye velocity with current and over time, and changes in electrically evoked compound action potentials produced by stimulation and recorded with the implanted device. Perceived rotation in subjects was consistent with the slow phase eye movements in direction, and scaled with stimulation current in magnitude. These results suggest that electrical stimulation of the vestibular end organ in human subjects provided controlled vestibular inputs over time, but in Meniere's patients this apparently came at the cost of hearing and vestibular function in the implanted ear.
Copyright © 2013, Journal of Neurophysiology.
Many neuroprosthetic applications require the use of very small, flexible multi-channel microelectrodes (e.g. polyimide-based film-like electrodes) to fit anatomical constraints. By arranging the electrode contacts on both sides of the polyimide film, selectivity can be further increased without increasing size. In this work, two approaches to create such double-sided electrodes are described and compared: sandwich electrodes prepared by precisely gluing two single-sided structures together, and monolithic electrodes created using a new double-sided photolithography process. Both methods were successfully applied to manufacture double-sided electrodes for stimulation of the vestibular system. In a case study, the electrodes were implanted in the semicircular canals of three guinea pigs and proven to provide electrical stimulation of the vestibular nerve. For both the monolithic electrodes and the sandwich electrodes, long-term stability and functionality was observed over a period of more than 12 months. Comparing the two types of electrodes with respect to the manufacturing process, it can be concluded that monolithic electrodes are the preferred solution for very thin electrodes (<20 μm), while sandwich electrode technology is especially suitable for thicker electrodes (40-50 μm).
Researchers have succeeded in partly restoring damaged vestibular functionality in several animal models. Recently, acute interventions have also been demonstrated in human patients. Our previous work on a vestibular implant for humans used predefined stimulation patterns; here we present a research tool that facilitates motion-modulated stimulation. This requires a system that can process gyroscope measurements and send stimulation parameters to a hybrid vestibular-cochlear implant in real-time. To match natural vestibular latencies, the time from sensor input to stimulation output should not exceed 6.5 ms. We describe a system based on National Instrument's CompactRIO platform that can meet this requirement and also offers floating point precision for advanced transfer functions. It is designed for acute clinical interventions, and is sufficiently powerful and flexible to serve as a development platform for evaluating prosthetic control strategies. Amplitude and pulse frequency modulation to predetermined functions or sensor inputs have been validated. The system has been connected to human patients, who each have received a modified MED-EL cochlear implant for vestibular stimulation, and patient tests are ongoing.
A functional vestibular prosthesis can be implanted in human such that electrical stimulation of each semicircular canal produces canal-specific eye movements while preserving vestibular and auditory function.
A number of vestibular disorders could be treated with prosthetic stimulation of the vestibular end organs. We have previously demonstrated in rhesus monkeys that a vestibular neurostimulator, based on the Nucleus Freedom cochlear implant, can produce canal-specific electrically evoked eye movements while preserving auditory and vestibular function. An investigational device exemption has been obtained from the FDA to study the feasibility of treating uncontrolled Ménière's disease with the device.
The UW/Nucleus vestibular implant was implanted in the perilymphatic space adjacent to the three semicircular canal ampullae of a human subject with uncontrolled Ménière's disease. Preoperative and postoperative vestibular and auditory function was assessed. Electrically evoked eye movements were measured at 2 time points postoperatively.
Implantation of all semicircular canals was technically feasible. Horizontal canal and auditory function were largely, but not totally, lost. Electrode stimulation in 2 of 3 canals resulted in canal-appropriate eye movements. Over time, stimulation thresholds increased.
Prosthetic implantation of the semicircular canals in humans is technically feasible. Electrical stimulation resulted in canal-specific eye movements, although thresholds increased over time. Preservation of native auditory and vestibular function, previously observed in animals, was not demonstrated in a single subject with advanced Ménière's disease.
Bilateral loss of vestibular sensation can be disabling. We have shown that a multichannel vestibular prosthesis (MVP) can partly restore vestibular sensation as evidenced by improvements in the 3-dimensional angular vestibulo-ocular reflex (3D VOR). However, a key challenge is to minimize misalignment between the axes of eye and head rotation, which is apparently caused by current spread beyond each electrode’s targeted nerve branch. We recently reported that rodents wearing a MVP markedly improve 3D VOR alignment during the first week after MVP activation, probably through the same central nervous system adaptive mechanisms that mediate cross-axis adaptation over time in normal individuals wearing prisms that cause visual scene movement about an axis different than the axis of head rotation. We hypothesized that rhesus monkeys would exhibit similar improvements with continuous prosthetic stimulation over time. We created bilateral vestibular deficiency in four rhesus monkeys via intratympanic injection of gentamicin. A MVP was mounted to the cranium, and eye movements in response to whole-body passive rotation in darkness were measured repeatedly over 1 week of continuous head motion-modulated prosthetic electrical stimulation. 3D VOR responses to whole-body rotations about each semicircular canal axis were measured on days 1, 3, and 7 of chronic stimulation. Horizontal VOR gain during 1 Hz, 50 °/s peak whole-body rotations before the prosthesis was turned on was
A vestibular neural prosthesis was designed on the basis of a cochlear implant for treatment of Menieres disease and other vestibular disorders. Computer control software was developed to generate patterned pulse stimuli for exploring optimal parameters to activate the vestibular nerve. Two Rhesus monkeys were implanted with the prototype vestibular prosthesis and they were behaviorally evaluated post implantation surgery. Horizontal and vertical eye movement responses to patterned electrical pulse stimulations were collected on both monkeys. Pulse amplitude modulated (PAM) and pulse rate modulated (PRM) trains were applied to the lateral canal of each implanted animal. Robust slow-phase nystagmus responses following the PAM or PRM modulation pattern were observed in both implanted monkeys in the direction consistent with the activation of the implanted canal. Both PAM and PRM pulse trains can elicit a significant amount of in-phase modulated eye velocity changes and they could potentially be used for efficiently coding head rotational signals in future vestibular neural prostheses.
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. Co-modulation 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.
An implantable prosthesis that stimulates vestibular nerve branches to restore sensation of head rotation and vision-stabilizing reflexes could benefit individuals disabled by bilateral loss of vestibular sensation. The normal vestibular system encodes head movement by increasing or decreasing firing rate of the vestibular afferents about a baseline firing rate in proportion to head rotation velocity. Our multichannel vestibular prosthesis emulates this encoding scheme by modulating pulse rate and pulse current amplitude above and below a baseline stimulation rate (BSR) and a baseline stimulation current. Unilateral baseline prosthetic stimulation that mimics normal vestibular afferent baseline firing results in vestibulo-ocular reflex (VOR) eye responses with a wider range of eye velocity in response to stimuli modulated above baseline (excitatory) than below baseline (inhibitory). Stimulus modulation about higher than normal baselines resulted in increased range of inhibitory eye velocity, but decreased range of excitatory eye velocity. Simultaneous modulation of rate and current (co-modulation) above all tested baselines elicited a significantly wider range of excitatory eye velocity than rate or current modulation alone. Time constants associated with the recovery of VOR excitability following adaptation to elevated BSRs implicate synaptic vesicle depletion as a possible mechanism for the small range of excitatory eye velocity elicited by rate modulation alone. These findings can be used toward selecting optimal baseline levels for vestibular stimulation that would result in large inhibitory eye responses while maintaining a wide range of excitatory eye velocity via co-modulation.
Profound bilateral loss of vestibular hair cell function can cause chronically disabling loss of balance and inability to maintain stable vision during head and body movements. We have previously shown that chinchillas rendered bilaterally vestibular-deficient via intratympanic administration of the ototoxic antibiotic gentamicin regain a more nearly normal 3-dimensional vestibulo-ocular reflex (3D VOR) when head motion information sensed by a head-mounted multichannel vestibular prosthesis (MVP) is encoded via rate-modulated pulsatile stimulation of vestibular nerve branches. Despite significant improvement versus the unaided condition, animals still exhibited some 3D VOR misalignment (i.e., the 3D axis of eye movement responses did not precisely align with the axis of head rotation), presumably due to current spread between a given ampullary nerve’s stimulating electrode(s) and afferent fibers in non-targeted branches of the vestibular nerve. Assuming that effects of current spread depend on relative orientation and separation between nerve branches, anatomic differences between chinchilla and human labyrinths may limit the extent to which results in chinchillas accurately predict MVP performance in humans.
Recently, we demonstrated that it was possible to elicit vertical eye movements in response to electrical stimulation of the posterior ampullary nerve. In order to develop a vestibular implant, a second site of stimulation is required to encode the horizontal movements.
Three patients with disabling Meniere's disease were included in the study. Before a labyrinthectomy via a standard transcanal approach was performed, their lateral and anterior ampullary nerves were surgically exposed under local anesthesia through a procedure we recently developed. The attic was opened, the incus and malleus head were removed, and a small well was drilled above the horizontal portion of the facial nerve canal to place an electrode. This electrode was used to deliver balanced biphasic trains of electrical pulses.
The electrical stimuli elicited mainly horizontal nystagmus without simultaneous stimulation of the facial nerve.
It is possible to stimulate electrically the lateral and superior ampullary nerves without simultaneous stimulation of the facial nerve. Because the nerves run close to each other, electrical stimulation provoked eye movements that were not purely horizontal, but also had some vertical components. Nevertheless, this site can be used to encode horizontal movements, because central adaptation may correct unnatural afferent vestibular cues delivered by a prosthetic sensor. The range of stimulus intensities that produced a response was broad enough for us to envision the possibility of encoding eye movements of various speeds.
To facilitate design of a multichannel vestibular prosthesis that can restore sensation to individuals with bilateral loss of vestibular hair cell function, we created a virtual labyrinth model. Model geometry was generated through 3-dimensional (3D) reconstruction of microMRI and microCT scans of normal chinchillas (Chinchilla lanigera) acquired with 30-48 μm and 12 μm voxels, respectively. Virtual electrodes were positioned based on anatomic landmarks, and the extracellular potential field during a current pulse was computed using finite element methods. Potential fields then served as inputs to stochastic, nonlinear dynamic models for each of 2,415 vestibular afferent axons with spiking dynamics based on a modified Smith and Goldberg model incorporating parameters that varied with fiber location in the neuroepithelium. Action potential propagation was implemented by a well validated model of myelinated fibers. We tested the model by comparing predicted and actual 3D angular vestibulo-ocular reflex (aVOR) axes of eye rotation elicited by prosthetic stimuli. Actual responses were measured using 3D video-oculography. The model was individualized for each animal by placing virtual electrodes based on microCT localization of real electrodes. 3D eye rotation axes were predicted from the relative proportion of model axons excited within each of the three ampullary nerves. Multiple features observed empirically were observed as emergent properties of the model, including effects of active and return electrode position, stimulus amplitude and pulse waveform shape on target fiber recruitment and stimulation selectivity. The modeling procedure is partially automated and can be readily adapted to other species, including humans.
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.
The spontaneous activity and dynamic responses to sinusoidal horizontal head angular acceleration of type II horizontal semicircular canal related neurons in the medial vestibular nucleus (MVN) were recorded bilaterally in decerebrate Mongolian gerbils (Meriones unguiculatus) under three experimental conditions: normal labyrinths intact, acutely following unilateral labyrinthine lesion, and four to seven weeks following labyrinthine lesion. The number of type II neurons detected contralateral to the lesion was greatly reduced both in the acutely hemilabyrinthectomized animals and following compensation. The gain of the responses was depressed bilaterally acutely following the lesion. A greater reduction in response gain was noted in cells contralateral to the lesion. The gain of the contralateral type II responses increased with time such that in the compensated animal bilaterally symmetric gains were recorded. While the significant changes which occur in the gain of type II neurons with recovery from peripheral vestibular lesions can largely be attributed to type I neurons on the other side of the midline, changes in type I neurons were not entirely reflected in the type II population. The spontaneous activity of type II neurons did not undergo any significant changes following the labyrinthine lesion. We present a model utilizing the dynamic responses to estimate the functional recovery of commissural connections in compensated animals. The overall gain of the contralateral type I to ipsilateral type I commissural polysynaptic pathway appears to improve, while the efficacy in the reverse direction remains depressed, suggesting that modifications in commissural connections, particularly involving the type II to type I connections within the MVN on the injured side, mediate aspects of behavioral recovery.
Single fiber recordings from the electrically stimulated auditory nerve yield post-stimulus time (PST) histograms demonstrating several response patterns. With pulsatile stimulation of the cochlea, the PST histogram for most fibers at threshold consists of a long-latency (500-800 microseconds), broad response peak with significant latency variability. At increased stimulus intensities, the response pattern changes to a short-latency (300-500 microseconds), high-synchrony peak. In preparations where stimulation is applied directly to the axons of the auditory nerve, the response pattern consists solely of a short-latency, high-synchrony peak. It is postulated that threshold excitation of normal auditory neurons occurs on the dendritic processes. At higher stimulus intensities, the site of excitation appears to shift to the axonal region of the cells. Two additional response patterns to electrical stimulation which are attributed to synaptic excitation of the auditory neurons via the hair cells are described.
Experiments were concerned with the long-term adaptive changes that occur in the primate vestibuloocular reflex (VOR) when the visual input associated with head movements is disturbed by various optical devices, including telescopic spectacles (magnification 2.0 and 0.5), fixed-field spectacles (field of view fixed with respect to the head; hence, equivalent here to 'zero power' lenses), and dove prism spectacles (providing left-right reversal of vision).
An important part of the vestibulo-ocular reflex is a group of cells in the caudal pons, known as the neural integrator, that converts eye-velocity commands, from the semicircular canals for example, to eye-position commands for the motoneurons of the extraocular muscles. Previously, a recurrently connected neural network model was developed by us that learns to simulate the signal processing done by the neural integrator, but it uses an unphysiological learning algorithm. We describe here a new network model that can learn the same task by using a local, Hebbian-like learning algorithm that is physiologically plausible. Through the minimization of a retinal slip error signal the model learns, given randomly selected initial synaptic weights, to both integrate simulated push-pull semicircular canal afferent signals and compensate for orbital mechanics as well. Approximately half of the model's 14 neurons are inhibitory, half excitatory. After learning, inhibitory cells tend to project contralaterally, thus forming an inhibitory commissure. The network can, of course, recover from lesions. The mature network is also able to change its gain by simulating abnormal visual-vestibular interactions. When trained with a sine wave at a single frequency, the network changed its gain at and near the training frequency but not at significantly higher or lower frequencies, in agreement with previous experimental observations. Commissural connections are essential to the functioning of this model, as was the case with our previous model. In order to determine whether a commissure plays a similar role in the real neural integrator, a series of electrical perturbations were performed on the midlines of awake, behaving juvenile rhesus monkeys and the effects on the monkeys' eye movements were examined. Eye movements were recorded using the coil system before, during, and after electrical stimulation in the midline of the pons just caudal to the abducens nuclei, which reversibly made the integrator leaky. Eye movements were also recorded from two of the monkeys before and after a midline electrolytic lesion was made at the location where stimulation produced a leaky integrator. This lesion disabled the integrator irreversibly. The eye movements that were produced by the monkeys as a result of these perturbations were then compared with eye movements produced by the model after analogous perturbations. The results are compatible with the hypothesis that integration comes about by positive feedback through lateral inhibition effected by an inhibitory commissure.
The goal of this study was to identify stimulus parameters and electrode geometries that were effective in selectively stimulating targeted neuronal populations within the central nervous system (CNS). Cable models of neurons that included an axon, initial segment, soma, and branching dendritic tree, with geometries and membrane dynamics derived from mammalian motoneurons, were used to study excitation with extracellular electrodes. The models reproduced a wide range of experimentally documented excitation patterns including current-distance and strength-duration relationships. Evaluation of different stimulus paradigms was performed using populations of fifty cells and fifty fibers of passage randomly positioned about an extracellular electrode(s). Monophasic cathodic or anodic stimuli enabled selective stimulation of fibers over cells or cells over fibers, respectively. However, when a symmetrical charge-balancing stimulus phase was incorporated, selectivity was greatly diminished. An anodic first, cathodic second asymmetrical biphasic stimulus enabled selective stimulation of fibers, while a cathodic first, anodic second asymmetrical biphasic stimulus enabled selective stimulation of cells. These novel waveforms provided enhanced selectivity while preserving charge balancing as is required to minimize the risk of electrode corrosion and tissue injury. Furthermore, the models developed in this study can predict the effectiveness of electrode geometries and stimulus parameters for selective activation of specific neuronal populations, and in turn represent useful tools for the design of electrodes and stimulus waveforms for use in CNS neural prosthetic devices. © 2000 Biomedical Engineering Society.
PAC00: 8717Nn, 8719La, 8719Nn, 8717Aa
The design of a prototype semicircular canal prosthesis is presented along with preliminary results. This device measures angular velocity of the head (+/-500 degrees/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 x 31 mm x 25 mm, which can be mounted on the top of an animal's 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.
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 (approximately 60Hz). 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.
To review how the properties of sounds are "coded" in the normal auditory system and to discuss the extent to which cochlear implants can and do represent these codes.
Data are taken from published studies of the response of the cochlea and auditory nerve to simple and complex stimuli, in both the normal and the electrically stimulated ear. REVIEW CONTENT: The review describes: 1) the coding in the normal auditory system of overall level (which partly determines perceived loudness), spectral shape (which partly determines perceived timbre and the identity of speech sounds), periodicity (which partly determines pitch), and sound location; 2) the role of the active mechanism in the cochlea, and particularly the fast-acting compression associated with that mechanism; 3) the neural response patterns evoked by cochlear implants; and 4) how the response patterns evoked by implants differ from those observed in the normal auditory system in response to sound. A series of specific issues is then discussed, including: 1) how to compensate for the loss of cochlear compression; 2) the effective number of independent channels in a normal ear and in cochlear implantees; 3) the importance of independence of responses across neurons; 4) the stochastic nature of normal neural responses; 5) the possible role of across-channel coincidence detection; and 6) potential benefits of binaural implantation.
Current cochlear implants do not adequately reproduce several aspects of the neural coding of sound in the normal auditory system. Improved electrode arrays and coding systems may lead to improved coding and, it is hoped, to better performance.
Gentamicin is toxic to vestibular hair cells, but its effects on vestibular afferents have not been defined. We treated anesthetized chinchillas with one injection of gentamicin (26.7 mg/ml) into the middle ear and made extracellular recordings from afferents after 5-25 (early) or 90-115 days (late). The relative proportions of regular, intermediate, and irregular afferents did not change after treatment. The spontaneous firing rate of regular afferents was lower (P < 0.001) on the treated side (early: 44.3 +/- 16.3; late: 33.9 +/- 13.2 spikes x s(-1)) than on the untreated side (54.9 +/- 16.8 spikes x s(-1)). Spontaneous rates of irregular and intermediate afferents did not change. The majority of treated afferents did not measurably respond to tilt or rotation (82% in the early group, 76% in the late group). Those that did respond had abnormally low sensitivities (P < 0.001). Treated canal units that responded to rotation had mean sensitivities only 5-7% of the values for untreated canal afferents. Treated otolith afferents had mean sensitivities 23-28% of the values for untreated otolith units. Sensitivity to externally applied galvanic currents was unaffected for all afferents. Intratympanic gentamicin treatment reduced the histological density of all hair cells by 57% (P = 0.04). The density of hair cells with calyx endings was reduced by 99% (P = 0.03), although some remaining hair cells had other features suggestive of type I morphology. Type II hair cell density was not significantly reduced. These findings suggest that a single intratympanic gentamicin injection causes partial damage and loss of vestibular hair cells, particularly type I hair cells or their calyceal afferent endings, does not damage the afferent spike initiation zones, and preserves enough hair cell synaptic activity to drive the spontaneous activity of vestibular afferents.