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1.
J Neurophysiol ; 132(2): 335-346, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38865580

RESUMO

Saccade adaptation plays a crucial role in maintaining saccade accuracy. The behavioral characteristics and neural mechanisms of saccade adaptation for an externally cued movement, such as visually guided saccades (VGS), are well studied in nonhuman primates. In contrast, little is known about the saccade adaptation of an internally driven movement, such as memory-guided saccades (MGS), which are guided by visuospatial working memory. As the oculomotor plant changes because of growth, aging, or skeletomuscular problems, both types of saccades need to be adapted. Do both saccade types engage a common adaptation mechanism? In this study, we compared the characteristics of amplitude decrease adaptation in MGS with VGS in nonhuman primates. We found that the adaptation speed was faster for MGS than for VGS. Saccade duration changed during MGS adaptation, whereas saccade peak velocity changed during VGS adaptation. We also compared the adaptation field, that is, the gain change for saccade amplitudes other than the adapted. The gain change for MGS declines on both smaller and larger sides of adapted amplitude, more rapidly for larger than smaller amplitudes, whereas the decline in VGS was reversed. Thus, the differences between VGS and MGS adaptation characteristics support the previously suggested hypothesis that the adaptation mechanisms of VGS and MGS are distinct. Furthermore, the result suggests that the MGS adaptation site is a brain structure that influences saccade duration, whereas the VGS adaptation site influences saccade peak velocity. These results should be beneficial for future neurophysiological experiments.NEW & NOTEWORTHY Plasticity helps to overcome persistent motor errors. Such motor plasticity or adaptation can be investigated with saccades. Thus far our knowledge is primarily about visually guided saccades, an externally cued movement, which we can make only when the object is visible at the time of saccade. However, as the world is complex, we can make saccades even when the object is not visible. Here, we investigate the adaptation of an internally driven movement: the memory-guided saccade.


Assuntos
Adaptação Fisiológica , Macaca mulatta , Movimentos Sacádicos , Movimentos Sacádicos/fisiologia , Animais , Adaptação Fisiológica/fisiologia , Masculino , Percepção Visual/fisiologia , Memória de Curto Prazo/fisiologia , Feminino , Memória/fisiologia
2.
Front Neurol ; 14: 1198274, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37780695

RESUMO

Introduction: Loss of the vestibulo-ocular reflex (VOR) affects visual acuity during head movements. Patients with unilateral and bilateral vestibular deficits often use saccadic eye movements to compensate for an inadequate VOR. Two types of compensatory saccades have been distinguished, covert saccades and overt saccades. Covert saccades occur during head rotation, whereas overt saccades occur after the head has stopped moving. The generation of covert saccades is part of a central vestibular compensation process that improves visual acuity and suppresses oscillopsia. Understanding the covert saccade mechanism may facilitate vestibular rehabilitation strategies that can improve the patient's quality of life. To understand the brain mechanisms underlying covert saccades at the neural level, studies in an animal model are necessary. In this study, we employed non-human primates whose vestibular end organs are injured. Methods: We examined eye movement during the head-impulse test, which is a clinical test to evaluate the vestibulo-ocular reflex. During this test, the monkeys are required to fixate on a target and the head is rapidly and unexpectedly rotated to stimulate the horizontal semi-circular canals. Results: Similar to human subjects, monkeys made compensatory saccades. We compared these saccades with catch-up saccades following a moving target that simulates the visual conditions during the head impulse test. The shortest latency of the catch-up saccades was 250 ms, which indicates that it requires at least 250 ms to induce saccades by a visual signal. The latency of some compensatory saccades is shorter than 250 ms during the head impulse test, suggesting that such short latency compensatory saccades were not induced visually. The peak velocity of the short latency saccades was significantly lower than that of longer latency saccades. The peak velocity of these longer latency saccades was closer to that of visually guided saccades induced by a stepping target. Conclusion: These results are consistent with studies in human patients. Thus, this study demonstrates, for the first time, compensatory covert saccades in vestibular impaired monkeys.

3.
ACS Appl Mater Interfaces ; 14(4): 5673-5681, 2022 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-35043617

RESUMO

Emerging energy-efficient neuromorphic circuits are based on hardware implementation of artificial neural networks (ANNs) that employ the biomimetic functions of memristors. Specifically, crossbar array memristive architectures are able to perform ANN vector-matrix multiplication more efficiently than conventional CMOS hardware. Memristors with specific characteristics, such as ohmic behavior in all resistance states in addition to symmetric and linear long-term potentiation/depression (LTP/LTD), are required in order to fully realize these benefits. Here, we demonstrate a Li-based composite memristor (LCM) that achieves these objectives. The LCM consists of three phases: Li-doped TiO2 as a Li reservoir, Li4Ti5O12 as the insulating phase, and Li7Ti5O12 as the metallic phase, where resistive switching correlates with the change in the relative fraction of the metallic and insulating phases. The LCM exhibits a symmetric and gradual resistive switching behavior for both set and reset operations during a full bias sweep cycle. This symmetric and linear weight update is uniquely enabled by the symmetric bidirectional migration of Li ions, which leads to gradual changes in the relative fraction of the metallic phase in the film. The optimized LCM in ANN simulation showed that exceptionally high accuracy in image classification is realized in fewer training steps compared to the nonlinear behavior of conventional memristors.

4.
Adv Mater ; 34(6): e2106913, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34773720

RESUMO

Memristors integrated into a crossbar-array architecture (CAA) are promising candidates for nonvolatile memory elements in artificial neural networks. However, the relatively low reliability of memristors coupled with crosstalk and sneak currents in CAAs have limited the realization of the full potential of this technology. Here, high-reliability Na-doped TiO2  memristors grown in situ by atomic layer deposition (ALD) are demonstrated, where reversible Na migration underlies the resistive-switching mechanism. By employing ALD growth with an aqueous NaOH reactant in deionized water, uniform implantation of Na dopants is achieved in the crystallized TiO2  thin films at 250 °C without post-annealing. The resulting Na-doped TiO2  memristors show electroforming-free and self-rectifying resistive-switching behavior, and they are ideally suited for selectorless CAAs. Effective addressing of selectorless nodes is demonstrated via electrical measurement of individual memristors in a 6 × 6 crossbar using a read current of less than 1 µA with negligible sneak current at or below the noise level of ≈100 pA. Finally, the long-term potentiation and depression synaptic behavior from these Na-doped TiO2  memristors achieves greater than 99.1% accuracy for image-recognition tasks using a convolutional neural network based on the selectorless of crossbar arrays.

5.
Otol Neurotol ; 41(6): 810-816, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32229758

RESUMO

OBJECTIVE: To determine if Menière's disease is associated with fluctuations in afferent excitability in four human subjects previously implanted with vestibular stimulators. STUDY DESIGN: Longitudinal repeated measures. SETTING: Tertiary referral center, human vestibular research laboratory. PATIENTS: Four human subjects with previously uncontrolled Menière's disease unilaterally implanted in each semicircular canal with a vestibular stimulator. One subject had only two canals implanted. INTERVENTION(S): Repeated measures of electrically-evoked slow phase eye velocity and vestibular electrically-evoked compound action potentials (vECAP) over 2 to 4 years. MAIN OUTCOME MEASURE(S): Slow phase eye velocity and N1-P1 vECAP amplitudes as a function of time. RESULTS: There were statistically significant fluctuations in electrically evoked slow phase eye velocity over time in at least one semicircular canal of each subject. vECAP N1-P1 amplitudes measured at similar time intervals and stimulus intensities seem to show somewhat correlated fluctuations. One of the subjects had a single Menière's attack during this time period. The others did not. CONCLUSIONS: In these four subjects originally diagnosed with Menière's disease, there was fluctuating electrical excitability of the ampullar nerve of at least one canal in each subject. These fluctuations occurred without active symptoms of Menière's disease.


Assuntos
Doença de Meniere , Vestíbulo do Labirinto , Humanos , Canais Semicirculares
6.
Audiol Neurootol ; 25(1-2): 96-108, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31968338

RESUMO

BACKGROUND: A combined vestibular and cochlear prosthesis may restore hearing and balance to patients who have lost both. To do so, the device should activate each sensory system independently. OBJECTIVES: In this study, we quantify auditory and vestibular interactions during interleaved stimulation with a combined 16-channel cochlear and 6-channel vestibular prosthesis in human subjects with both hearing and vestibular loss. METHODS: Three human subjects were implanted with a combined vestibular and cochlear implant. All subjects had severe-to-profound deafness in the implanted ear. We provided combined stimulation of the cochlear and vestibular arrays and looked for interactions between these separate inputs. Our main outcome measures were electrically evoked slow-phase eye velocities during nystagmus elicited by brief trains of biphasic pulse stimulation of the vestibular end organs with and without concurrent stimulation of the cochlea, and Likert scale assessments of perceived loudness and pitch during stimulation of the cochlea, with and without concurrent stimulation of the vestibular ampullae. RESULTS: All subjects had no auditory sensation resulting from semicircular canal stimulation alone, and no sensation of motion or slow-phase eye movement resulting from cochlear stimulation alone. However, interleaved cochlear stimulation did produce changes in the slow-phase eye velocities elicited by electrical stimulation. Similarly, interleaved semicircular canal stimulation did elicit changes in the perceived pitch and loudness resulting from stimulation at multiple sites in the cochlea. CONCLUSIONS: There are significant interactions between different sensory modalities during stimulation with a combined vestibular and cochlear prosthesis. Such interactions present potential challenges for stimulation strategies to simultaneously restore auditory and vestibular function with such an implant.


Assuntos
Cóclea/fisiopatologia , Implantes Cocleares , Perda Auditiva Neurossensorial/cirurgia , Audição/fisiologia , Equilíbrio Postural/fisiologia , Doenças Vestibulares/cirurgia , Vestíbulo do Labirinto/fisiopatologia , Percepção Auditiva/fisiologia , Implante Coclear/métodos , Feminino , Perda Auditiva Neurossensorial/fisiopatologia , Testes Auditivos , Humanos , Masculino , Pessoa de Meia-Idade , Canais Semicirculares/cirurgia , Resultado do Tratamento , Doenças Vestibulares/fisiopatologia
7.
Otol Neurotol ; 41(1): 68-77, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31834185

RESUMO

OBJECTIVE: Auditory and vestibular outcomes after placement of a vestibular-cochlear implant in subjects with varying causes of vestibular loss. STUDY DESIGN: Prospective case study. SETTING: Tertiary referral center. PATIENTS: Three human subjects received a vestibular-cochlear implant. Subject 1 had sudden hearing and vestibular loss 10 years before implantation. Subjects 2 and 3 had bilateral Menière's disease with resolution of acute attacks. All subjects had severe-profound deafness in the implanted ear and bilateral vestibular loss. INTERVENTION: Vestibular-cochlear implant with electrode positions confirmed by CT. MAIN OUTCOME MEASURES: Electrically-evoked vestibular and cochlear compound action potentials (ECAPs), speech perception, and electrically-evoked slow-phase eye velocities. RESULTS: Subject 1 had no vestibular ECAP, but normal cochlear ECAPs and cochlear implant function. She had minimal eye-movement with vestibular stimulation. Subject 2 had vestibular ECAPs. This subject had the largest eye velocities from electrical stimulation that we have seen in humans, exceeding 100 degrees per second. Her cochlear implant functions normally. Subject 3 had vestibular and cochlear ECAPs, and robust eye-movements and cochlear implant function. CONCLUSION: The etiology of vestibular loss appears to have a profound impact on sensitivity of vestibular afferents in distinction to cochlear afferents. If this dichotomy is common, it may limit the application of vestibular implants to diagnoses with preserved sensitivity of vestibular afferents. We speculate it is due to differences in topographic organization of Scarpa's versus the spiral ganglion. In two subjects, the second-generation device can produce higher velocity eye movements than seen in the four subjects receiving the first-generation device.


Assuntos
Implantes Cocleares , Terapia por Estimulação Elétrica/instrumentação , Terapia por Estimulação Elétrica/métodos , Perda Auditiva/cirurgia , Potenciais de Ação/fisiologia , Implante Coclear/métodos , Potenciais Evocados/fisiologia , Feminino , Humanos , Masculino , Estudos Prospectivos , Resultado do Tratamento
8.
Front Neurosci ; 12: 88, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29867306

RESUMO

Electrical vestibular neurostimulation may be a viable tool for modulating vestibular afferent input to restore vestibular function following injury or disease. To do this, such stimulators must provide afferent input that can be readily interpreted by the central nervous system to accurately represent head motion to drive reflexive behavior. Since vestibular afferents have different galvanic sensitivity, and different natural sensitivities to head rotational velocity and acceleration, and electrical stimulation produces aphysiological synchronous activation of multiple afferents, it is difficult to assign a priori an appropriate transformation between head velocity and acceleration and the properties of the electrical stimulus used to drive vestibular reflex function, i.e., biphasic pulse rate or pulse current amplitude. In order to empirically explore the nature of the transformation between vestibular prosthetic stimulation and vestibular reflex behavior, in Rhesus macaque monkeys we parametrically varied the pulse rate and current amplitude of constant rate and current amplitude pulse trains, and the modulation frequency of sinusoidally modulated pulse trains that were pulse frequency modulated (FM) or current amplitude modulated (AM). In addition, we examined the effects of differential eye position and head position on the observed eye movement responses. We conclude that there is a strong and idiosyncratic, from canal to canal, effect of modulation frequency on the observed eye velocities that are elicited by stimulation. In addition, there is a strong effect of initial eye position and initial head position on the observed responses. These are superimposed on the relationships between pulse frequency or current amplitude and eye velocity that have been shown previously.

9.
J Assoc Res Otolaryngol ; 17(1): 19-35, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26438271

RESUMO

Implanted vestibular neurostimulators are effective in driving slow phase eye movements in monkeys and humans. Furthermore, increases in slow phase velocity and electrically evoked compound action potential (vECAP) amplitudes occur with increasing current amplitude of electrical stimulation. In intact monkeys, protracted intermittent stimulation continues to produce robust behavioral responses and preserved vECAPs. In lesioned monkeys, shorter duration studies show preserved but with somewhat lower or higher velocity behavioral responses. It has been proposed that such changes are due to central adaptive changes in the electrically elicited vestibulo-ocular reflex (VOR). It is equally possible that these differences are due to changes in the vestibular periphery in response to activation of the vestibular efferent system. In order to investigate the site of adaptive change in response to electrical stimulation, we performed transtympanic gentamicin perfusions to induce rapid changes in vestibular input in monkeys with long-standing stably functioning vestibular neurostimulators, disambiguating the effects of implantation from the effects of ototoxic lesion. Gentamicin injection was effective in producing a large reduction in natural VOR only when it was performed in the non-implanted ear, suggesting that the implanted ear contributed little to the natural rotational response before injection. Injection of the implanted ear produced a reduction in the vECAP responses in that ear, suggesting that the intact hair cells in the non-functional ipsilateral ear were successfully lesioned by gentamicin, reducing the efficacy of stimulation in that ear. Despite this, injection of both ears produced central plastic changes that resulted in a dramatically increased slow phase velocity nystagmus elicited by electrical stimulation. These results suggest that loss of vestibular afferent activity, and a concurrent loss of electrically elicited vestibular input, produces an increase in the efficacy of a vestibular neurostimulator by eliciting centrally adapted behavioral responses without concurrent adaptive increase of galvanic afferent activation in the periphery.


Assuntos
Adaptação Fisiológica , Próteses Neurais , Implantação de Prótese , Vestíbulo do Labirinto/inervação , Potenciais de Ação , Animais , Estimulação Elétrica , Movimentos Oculares/fisiologia , Gentamicinas/toxicidade , Macaca mulatta , Reflexo Vestíbulo-Ocular , Vestíbulo do Labirinto/fisiologia
10.
J Neurophysiol ; 113(10): 3866-92, 2015 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-25652917

RESUMO

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 2 s 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.


Assuntos
Implante Coclear/métodos , Estimulação Elétrica/métodos , Doença de Meniere/terapia , Reflexo Vestíbulo-Ocular/fisiologia , Canais Semicirculares/fisiologia , Idoso , Biofísica , Movimentos Oculares , Feminino , Audição/fisiologia , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Rotação , Fatores de Tempo
11.
Hear Res ; 322: 200-11, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25245586

RESUMO

Loss of vestibular function may be treatable with an implantable vestibular prosthesis that stimulates semicircular canal afferents with biphasic pulse trains. Several studies have demonstrated short-term activation of the vestibulo-ocular reflex (VOR) with electrical stimulation. Fewer long-term studies have been restricted to small numbers of animals and stimulation designed to produce adaptive changes in the electrically elicited response. This study is the first large consecutive series of implanted rhesus macaque to be studied longitudinally using brief stimuli designed to limit adaptive changes in response, so that the efficacy of electrical activation can be studied over time, across surgeries, canals and animals. The implantation of a vestibular prosthesis in animals with intact vestibular end organs produces variable responses to electrical stimulation across canals and animals, which change in threshold for electrical activation of eye movements and in elicited slow phase velocities over time. These thresholds are consistently lower, and the slow phase velocities higher, than those obtained in human subjects. The changes do not appear to be correlated with changes in electrode impedance. The variability in response suggests that empirically derived transfer functions may be required to optimize the response of individual canals to a vestibular prosthesis, and that this function may need to be remapped over time. This article is part of a Special Issue entitled .


Assuntos
Movimentos Oculares , Próteses Neurais , Equilíbrio Postural , Implantação de Prótese/instrumentação , Vestíbulo do Labirinto/inervação , Animais , Comportamento Animal , Impedância Elétrica , Estimulação Elétrica , Macaca mulatta , Teste de Materiais , Modelos Animais , Nistagmo Fisiológico , Desenho de Prótese , Fatores de Tempo
12.
Otol Neurotol ; 35(1): 136-47, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24317220

RESUMO

HYPOTHESIS: 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. BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.


Assuntos
Doença de Meniere/cirurgia , Implantação de Prótese , Canais Semicirculares/cirurgia , Potenciais Evocados Miogênicos Vestibulares/fisiologia , Vestíbulo do Labirinto/cirurgia , Estimulação Elétrica , Audição/fisiologia , Humanos , Masculino , Doença de Meniere/fisiopatologia , Pessoa de Meia-Idade , Reflexo Vestíbulo-Ocular/fisiologia , Canais Semicirculares/fisiopatologia , Resultado do Tratamento , Vestíbulo do Labirinto/fisiopatologia
13.
Exp Brain Res ; 229(2): 181-95, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23771587

RESUMO

A multichannel vestibular prosthesis that delivers electrical stimulation to the perilymph of individual semicircular canals is a potential new treatment modality for patients with vestibular deficiencies. Most research in this field has evaluated the efficacy of this approach by its ability to reproduce eye movements in response to head rotations. Our group has developed such a device and implanted it in four human subjects with intractable unilateral Meniere's disease. This allows us to evaluate individual semicircular canal contribution to the control of balance and posture in human subjects. In this report, we demonstrate that electrical stimulation trains delivered to the perilymph of individual semicircular canals elicit postural responses specific to the particular canal stimulated, with some current spread to adjacent end organs. Modulation of stimulation current modulates the amplitude of the postural response. However, eye movements elicited by the same electrical stimuli were not consistent with postural responses in magnitude or direction in all subjects. Taken together, these findings support the feasibility of a vestibular prosthesis for the control of balance and illustrate new challenges for the development of this technology.


Assuntos
Estimulação Elétrica/métodos , Movimentos Oculares/fisiologia , Reflexo Vestíbulo-Ocular/fisiologia , Canais Semicirculares/fisiopatologia , Doenças Vestibulares/fisiopatologia , Nervo Vestibular/fisiopatologia , Idoso , Feminino , Movimentos da Cabeça/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Nervo Vestibular/fisiologia , Vestíbulo do Labirinto/fisiopatologia
14.
IEEE Trans Biomed Eng ; 60(6): 1685-92, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23358943

RESUMO

A vestibular neural prosthesis was designed on the basis of a cochlear implant for treatment of Meniere's 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.


Assuntos
Implantes Cocleares , Estimulação Elétrica/métodos , Implantes Experimentais , Processamento de Sinais Assistido por Computador/instrumentação , Animais , Eletrodos , Potenciais Evocados/fisiologia , Movimentos Oculares/fisiologia , Macaca mulatta , Desenho de Prótese , Vestíbulo do Labirinto/cirurgia
15.
Otol Neurotol ; 33(5): 789-96, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22699989

RESUMO

HYPOTHESIS: It is possible to implant a stimulating electrode array in the semicircular canals without damaging rotational sensitivity or hearing. The electrodes will evoke robust and precisely controlled eye movements. BACKGROUND: A number of groups are attempting to develop a neural prosthesis to ameliorate abnormal vestibular function. Animal studies demonstrate that electrodes near the canal ampullae can produce electrically evoked eye movements. The target condition of these studies is typically bilateral vestibular hypofunction. Such a device could potentially be more widely useful clinically and would have a simpler roadmap to regulatory approval if it produced minimal or no damage to the native vestibular and auditory systems. METHODS: An electrode array was designed for insertion into the bony semicircular canal adjacent to the membranous canal. It was designed to be sufficiently narrow so as to not compress the membranous canal. The arrays were manufactured by Cochlear, Ltd., and linked to a Nucleus Freedom receiver/stimulator. Seven behaviorally trained rhesus macaques had arrays placed in 2 semicircular canals using a transmastoid approach and "soft surgical" procedures borrowed from Hybrid cochlear implant surgery. Postoperative vestibulo-ocular reflex was measured in a rotary chair. Click-evoked auditory brainstem responses were also measured in the 7 animals using the contralateral ear as a control. RESULTS: All animals had minimal postoperative vestibular signs and were eating within hours of surgery. Of 6 animals tested, all had normal postoperative sinusoidal gain. Of 7 animals, 6 had symmetric postoperative velocity step responses toward and away from the implanted ear. The 1 animal with significantly asymmetric velocity step responses also had a significant sensorineural hearing loss. One control animal that underwent canal plugging had substantial loss of the velocity step response toward the canal-plugged ear. In 5 animals, intraoperative electrically evoked vestibular compound action potential recordings facilitated electrode placement. Postoperatively, electrically evoked eye movements were obtained from electrodes associated with an electrically evoked vestibular compound action potential wave form. Hearing was largely preserved in 6 animals and lost in 1 animal. CONCLUSION: It is possible to implant the vestibular system with prosthetic stimulating electrodes without loss of rotational sensitivity or hearing. Because electrically evoked eye movements can be reliably obtained with the assistance of intraoperative electrophysiology, it is appropriate to consider treatment of a variety of vestibular disorders using prosthetic electrical stimulation. Based on these findings, and others, a feasibility study for the treatment of human subjects with disabling Ménière's disease has begun.


Assuntos
Movimentos Oculares/fisiologia , Audição/fisiologia , Percepção de Movimento/fisiologia , Implantação de Prótese/métodos , Canais Semicirculares/cirurgia , Potenciais de Ação/fisiologia , Animais , Potenciais Evocados Auditivos do Tronco Encefálico/fisiologia , Testes Auditivos , Neuroestimuladores Implantáveis , Macaca mulatta , Reflexo Vestíbulo-Ocular/fisiologia , Rotação , Canais Semicirculares/fisiologia
16.
Hear Res ; 287(1-2): 51-6, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22504025

RESUMO

We measured auditory brainstem responses (ABRs) in eight Rhesus monkeys after implantation of electrodes in the semicircular canals of one ear, using a multi-channel vestibular prosthesis based on cochlear implant technology. In five animals, click-evoked ABR thresholds in the implanted ear were within 10 dB of thresholds in the non-implanted control ear. Threshold differences in the remaining three animals varied from 18 to 69 dB, indicating mild to severe hearing losses. Click- and tone-evoked ABRs measured in a subset of animals before and after implantation revealed a comparable pattern of threshold changes. Thresholds obtained five months or more after implantation--a period in which the prosthesis regularly delivered electrical stimulation to achieve functional activation of the vestibular system--improved in three animals with no or mild initial hearing loss and increased in a fourth with a moderate hearing loss. These results suggest that, although there is a risk of hearing loss with unilateral vestibular implantation to treat balance disorders, the surgery can be performed in a manner that preserves hearing over an extended period of functional stimulation.


Assuntos
Implante Coclear/instrumentação , Implantes Cocleares , Canais Semicirculares/inervação , Vestíbulo do Labirinto/inervação , Estimulação Acústica , Animais , Limiar Auditivo , Implante Coclear/efeitos adversos , Estimulação Elétrica , Eletroencefalografia , Potenciais Evocados Auditivos do Tronco Encefálico , Movimentos Oculares , Perda Auditiva/etiologia , Perda Auditiva/fisiopatologia , Macaca mulatta , Masculino , Desenho de Prótese , Tempo de Reação , Medição de Risco , Fatores de Tempo
17.
Artigo em Inglês | MEDLINE | ID: mdl-23367327

RESUMO

Electrical stimulation of the vestibular end organ with a vestibular prosthesis may provide an effective treatment for vestibular loss if the stimulation remains effective over a significant period of time after implantation of the device. To assess efficacy of electrical stimulation in an animal model, we implanted 3 rhesus monkeys with a vestibular prosthesis based on a cochlear implant. We then recorded vestibular electrically evoked compound action potentials (vECAPs) longitudinally in each of the implanted canals to see how the amplitude of the response changed over time. The results suggest that vECAPs, and therefore electrical activation of vestibular afferent fibers, can remain largely stable over time following implantation.


Assuntos
Potenciais de Ação , Próteses e Implantes , Animais , Estudos Longitudinais , Macaca mulatta , Vestíbulo do Labirinto/cirurgia
18.
Otol Neurotol ; 32(1): 88-97, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21192375

RESUMO

OBJECTIVE: We recorded intraoperative and postoperative electrically evoked compound action potentials (ECAPs) in rhesus monkeys implanted with a vestibular neurostimulator. The objectives were to correlate the generation of slow-phase nystagmus or eye twitches induced by electrical stimulation of the implanted semicircular canal with the presence or absence of the vestibular ECAP responses and to assess the effectiveness of ECAP monitoring during surgery to guide surgical insertion of electrode arrays into the canals. DESIGN: Four rhesus monkeys (a total of 7 canals) were implanted with a vestibular neurostimulator modified from the Nucleus Freedom cochlear implant. ECAP recordings were obtained during surgery or at various intervals after surgery using the Neural Response Telemetry feature of the clinical Custom Sound EP software. Eye movements during electrical stimulation of individual canals were recorded with a scleral search coil system in the same animals. RESULTS: Measurable vestibular ECAPs were observed intraoperatively or postoperatively in 3 implanted animals. Robust and sustained ECAPs were obtained in 3 monkeys at the test intervals of 0, 7, or greater than 100 days after implantation surgery. In all 3 animals, stimulation with electrical pulse trains produced measurable eye movements in a direction consistent with the vestibulo-ocular reflex from the implanted semicircular canal. In contrast, electrically evoked eye movements could not be measured in 3 of the 7 implanted canals, none of which produced distinct vestibular ECAPs. In 2 animals, ECAP waveforms were systematically monitored during surgery, and the procedure proved crucial to the success of vestibular implantation. CONCLUSION: Vestibular ECAPs exhibit similar morphology and growth characteristics to cochlear ECAPs from human cochlear implant patients. The ECAP measure is well correlated with the functional activation of eye movements by electrical stimulation after implantation surgery. The intraoperative ECAP recording technique is an efficient tool to guide the placement of electrode array into the semicircular canals.


Assuntos
Potenciais de Ação/fisiologia , Potenciais Evocados/fisiologia , Nervo Vestibular/fisiologia , Animais , Estimulação Elétrica , Eletrodos Implantados , Macaca mulatta , Nistagmo Fisiológico/fisiologia , Reflexo Vestíbulo-Ocular/fisiologia
19.
Artigo em Inglês | MEDLINE | ID: mdl-22255103

RESUMO

Loss of vestibular function results in imbalance, disorientation, and oscillopsia. Several groups have designed and constructed implantable devices to restore vestibular function through electrical stimulation of the vestibular nerve. We have designed a two-part device in which the head motion sensing and signal processing elements are externally mounted to the head, and are coupled through an inductive link to a receiver stimulator that is based on a cochlear implant. The implanted electrode arrays are designed to preserve rotational sensitivity in the implanted ear. We have tested the device in rhesus monkeys by rotating the animals in the plane of the implanted canals, and then using head velocity and acceleration signals to drive electrical stimulation of the vestibular system. Combined electrical and rotational stimulation results in a summation of responses, so that one can control the modulation of eye velocity induced by sinusoidal yaw rotation.


Assuntos
Próteses e Implantes , Nervo Vestibular/fisiopatologia , Animais , Implantes Cocleares , Macaca mulatta
20.
Artigo em Inglês | MEDLINE | ID: mdl-21097347

RESUMO

An implanted vestibular neurostimulator has been developed based on commercial cochlear implant technology. It has been implanted chronically in Rhesus monkeys and the physiology of electrical stimulation of the vestibular periphery has been studied. We are currently proposing a human feasibility study of implantation of the device for the treatment of incapacitating Meniere's disease. Because no animal model of Meniere's disease exists, signal processing for such a device must be based on prior observations of human subjects who have suffered Meniere's attacks while their eye-movements could be quantified. Based on such data, and on the leading theories for the pathophysiology of a Meniere's attack, our animal data suggests that fixed amplitude, constant frequency biphasic pulse trains should be adequate to suppress the symptoms of an attack when they occur. The intensity of the stimuli and efficacy of vertigo suppression should be readily modulated either by amplitude or frequency adjustments.


Assuntos
Neuroestimuladores Implantáveis , Processamento de Sinais Assistido por Computador , Vestíbulo do Labirinto/fisiologia , Animais , Humanos , Macaca mulatta/fisiologia
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