The vestibular implant: frequency-dependency of the electrically evoked vestibulo-ocular reflex in humans

Raymond van de Berg, Nils Guinand, T A Khoa Nguyen, Maurizio Ranieri, Samuel Cavuscens, Jean-Philippe Guyot, Robert Stokroos, Herman Kingma, Angelica Perez-Fornos, Raymond van de Berg, Nils Guinand, T A Khoa Nguyen, Maurizio Ranieri, Samuel Cavuscens, Jean-Philippe Guyot, Robert Stokroos, Herman Kingma, Angelica Perez-Fornos

Abstract

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.

Keywords: bilateral vestibular areflexia; bilateral vestibulopathy; neural prosthesis; vestibular implant; vestibular prosthesis; vestibulo-ocular reflex.

Figures

Figure 1
Figure 1
Illustration of the electrical stimulation paradigm. Stimulation was delivered to one vestibular electrode at a time. Patients first received baseline electrical stimulation that consisted of constant amplitude trains of biphasic, cathodic-first pulses (upper-left panel). Baseline stimulation was presented at a fixed pulse rate of 400 pulses per second. Its intensity corresponded to 50% of each electrode's previously measured dynamic range (DR; current range between the vestibular threshold -THRS- and the upper comfortable level -UCL-). Once patients were in “adapted” state, the baseline stimulation could be modulated in amplitude using a signal with a sinusoidal profile (see lower-left panel). The strength (i.e., intensity) of the modulation was kept constant and its frequency was varied between 0.5 and 2 Hz. The right panel shows an example of such an amplitude modulated stimulation signal (blue trace). The envelope of the modulation signal (red dotted lines) has been highlighted for clarity.
Figure 2
Figure 2
Illustration of eye movement data processing. The figure presents eye movement data tracings for patient BVH1-LAN. Two steps are illustrated for each modulation frequency: raw eye position (e.g., before any processing was performed) and processed eye velocity data.
Figure 3
Figure 3
Normalized total peak eye velocity (PEV) vs. modulation frequency. (A) Each panel represents individual results obtained during stimulation for each stimulation site (SAN, LAN, PAN). (B) Mean results (±SEM) calculated across patients for each stimulation site (gray plots) and for all electrodes together (black plot).
Figure 4
Figure 4
Angle of eye movements vs. modulation frequency. (A) Each panel represents individual results obtained during stimulation for each stimulation site (SAN, LAN, PAN). (B) Mean results (±SEM) calculated across patients for each stimulation site (gray plots) and for all electrodes together (black plot).
Figure 5
Figure 5
Habituation-index vs. modulation frequency. (A) Each panel represents individual results obtained during stimulation for each stimulation site (SAN, LAN, PAN). (B) Mean results (±SEM) calculated across patients for each stimulation site (gray plots) and for all electrodes together (black plot).
Figure 6
Figure 6
Asymmetry-index vs. modulation frequency. (A) Each panel represents individual results obtained during stimulation for each stimulation site (SAN, LAN, PAN). (B) Mean results (±SEM) calculated across patients for each stimulation site (gray plots) and for all electrodes together (black plot).
Figure 7
Figure 7
Comparison of the main characteristics of the eVOR to the “natural” VOR. The eVOR is represented as mean group results of the BVH-group (gray bars and circles ±SEM). The “natural” VOR is represented as mean group results of the group of healthy volunteers (white bars and circles ±SEM). (A) Normalized total peak eye velocity (PEV) vs. modulation frequency. (B) Angle of the VOR responses vs. modulation frequency. (C) Habituation-index vs. modulation frequency. (D) Asymmetry-index vs. modulation frequency.

References

    1. Aw S. T., Todd M. J., Aw G. E., Weber K. P., Halmagyi G. M. (2008). Gentamicin vestibulotoxicity impairs human electrically evoked vestibulo-ocular reflex. Neurology 71, 1776–1782. 10.1212/01.wnl.0000335971.43443.d9
    1. Barnes G. R. (1993). Visual-vestibular interaction in the control of head and eye movement: the role of visual feedback and predictive mechanisms. Prog. Neurobiol. 41, 435–472. 10.1016/0301-0082(93)90026-O
    1. Bartl K., Lehnen N., Kohlbecher S., Schneider E. (2009). Head impulse testing using video-oculography. Ann. N.Y. Acad. Sci. 1164, 331–333. 10.1111/j.1749-6632.2009.03850.x
    1. Bierer S. M., Ling L., Nie K., Fuchs A. F., Kaneko C. R. S., Oxford T., et al. . (2012). Auditory outcomes following implantation and electrical stimulation of the semicircular canals. Hear. Res. 287, 51–56. 10.1016/j.heares.2012.03.012
    1. Black F. O., Wade S. W., Nashner L. M. (1996). What is the minimal vestibular function required for compensation? Am. J. Otol. 17, 401–409.
    1. Brandt T., Huppert T., Hüfner K., Zingler V. C., Dieterich M., Strupp M. (2010). Long-term course and relapses of vestibular and balance disorders. Restor. Neurol. Neurosci. 28, 69–82. 10.3233/RNN-2010-0504
    1. Buettner U. W., Henn V., Young L. R. (1981). Frequency response of the vestibulo-ocular reflex (VOR) in the monkey. Aviat. Space Environ. Med. 52, 73–77.
    1. Clément G., Flandrin J. M., Courjon J. H. (2002). Comparison between habituation of the cat vestibulo-ocular reflex by velocity steps and sinusoidal vestibular stimulation in the dark. Exp. Brain Res. 142, 259–267. 10.1007/s00221-001-0930-7
    1. Crane B. T., Demer J. L. (1997). Human gaze stabilization during natural activities: translation, rotation, magnification, and target distance effects. J. Neurophysiol. 78, 2129–2144.
    1. Curthoys I., Halmagyi G. M. (1995). Vestibular compensation: a review of the oculomotor, neural, and clinical consequences of unilateral vestibular loss. J. Vestib. Res. 5, 67–107. 10.1016/0957-4271(94)00026-X
    1. Dai C., Fridman G. Y., Chiang B., Davidovics N. S., Melvin T.-A., Cullen K. E., et al. . (2011c). Cross-axis adaptation improves 3D vestibulo-ocular reflex alignment during chronic stimulation via a head-mounted multichannel vestibular prosthesis. Exp. Brain Res. 210, 595–606. 10.1007/s00221-011-2591-5
    1. Dai C., Fridman G. Y., Chiang B., Rahman M. A., Ahn J. H., Davidovics N. S., et al. . (2013). Directional plasticity rapidly improves 3D vestibulo-ocular reflex alignment in monkeys using a multichannel vestibular prosthesis. J. Assoc. Res. Otolaryngol. 14, 863–877. 10.1007/s10162-013-0413-0
    1. Dai C., Fridman G. Y., Davidovics N. S., Chiang B., Ahn J. H., Della Santina C. C. (2011b). Restoration of 3D vestibular sensation in rhesus monkeys using a multichannel vestibular prosthesis. Hear. Res. 281, 74–83. 10.1016/j.heares.2011.08.008
    1. Dai C., Fridman G. Y., Della Santina C. C. (2011a). Effects of vestibular prosthesis electrode implantation and stimulation on hearing in rhesus monkeys. Hear. Res. 277, 204–210. 10.1016/j.heares.2010.12.021
    1. Davidovics N. S., Fridman G. Y., Chiang B., Della Santina C. C. (2011). Effects of biphasic current pulse frequency, amplitude, duration, and interphase gap on eye movement responses to prosthetic electrical stimulation of the vestibular nerve. IEEE Trans. Neural Syst. Rehabil. Eng. 19, 84–94. 10.1109/TNSRE.2010.2065241
    1. Davidovics N. S., Fridman G. Y., Della Santina C. C. (2012). Co-modulation of stimulus rate and current from elevated baselines expands head motion encoding range of the vestibular prosthesis. Exp. brain Res. 218, 389–400. 10.1007/s00221-012-3025-8
    1. Davidovics N. S., Rahman M. A., Dai C., Ahn J., Fridman G. Y., Della Santina C. C. (2013). Multichannel vestibular prosthesis employing modulation of pulse rate and current with alignment precompensation elicits improved VOR performance in monkeys. J. Assoc. Res. Otolaryngol. 14, 233–248. 10.1007/s10162-013-0370-7
    1. Della Santina C. C., Migliaccio A. A., Patel A. H. (2007). A multichannel semicircular canal neural prosthesis using electrical stimulation to restore 3-d vestibular sensation. IEEE Trans. Biomed. Eng. 54(6 Pt 1), 1016–1030. 10.1109/TBME.2007.894629
    1. Dow E. R., Anastasio T. J. (1997). Induction of periodic alternating nystagmus in intact goldfish by sinusoidal rotation. Neuroreport 8, 2755–2759. 10.1097/00001756-199708180-00022
    1. Dow E. R., Anastasio T. J. (1999). Analysis and modeling of frequency-specific habituation of the goldfish vestibulo-ocular reflex. J. Comput. Neurosci. 7, 55–70. 10.1023/A:1008967511172
    1. Feigl G. C., Fasel J. H., Anderhuber F., Ulz H., Rienmüller R., Guyot J.-P., et al. . (2009). Superior vestibular neurectomy: a novel transmeatal approach for a denervation of the superior and lateral semicircular canals. Otol. Neurotol. 30, 586–591. 10.1097/MAO.0b013e3181ab9164
    1. Fridman G. Y., Davidovics N. S., Dai C., Migliaccio A. A., Della Santina C. C. (2010). Vestibulo-ocular reflex responses to a multichannel vestibular prosthesis incorporating a 3D coordinate transformation for correction of misalignment. J. Assoc. Res. Otolaryngol. 11, 367–381. 10.1007/s10162-010-0208-5
    1. Fridman G. Y., Della Santina C. C. (2013). Safe direct current stimulator 2: concept and design, in Proceedings of the Annual International Conference of the IEEE Engineering in Medicine and Biology Society (Osaka: ), 3126–3129.
    1. Goldberg J. M., Smith C. E., Fernandez C. (1984). Relation between discharge regularity and responses to externally applied galvanic currents in vestibular nerve afferents of the squirrel monkey. J. Neurophysiol. 51, 1236–1256.
    1. Golub J. S., Ling L., Nie K., Nowack A., Shepherd S. J., Bierer S. M., et al. . (2014). Prosthetic implantation of the human vestibular system. Otol. Neurotol. 35, 136–147. 10.1097/MAO.0000000000000003
    1. Gong W., Merfeld D. M. (2002). System design and performance of a unilateral horizontal semicircular canal prosthesis. IEEE Trans. Biomed. Eng. 49, 175–181. 10.1109/10.979358
    1. Guinand N., Boselie F., Guyot J. P., Kingma H. (2012). Quality of life of patients with bilateral vestibulopathy. Ann. Otol. Rhinol. Laryngol. 121, 471–477. 10.1177/000348941212100708
    1. Guyot J.-P., Sigrist A., Pelizzone M., Kos M. I. (2011). Adaptation to steady-state electrical stimulation of the vestibular system in humans. Ann. Otol. Rhinol. Laryngol. 120, 143–149. 10.1177/000348941112000301
    1. Hain T. C., Cherchi M., Yacovino D. A. (2013). Bilateral vestibular loss. Semin. Neurol. 33, 195–203. 10.1055/s-0033-1354597
    1. Hayden R., Sawyer S., Frey E., Mori S., Migliaccio A. A., Della Santina C. C. (2011). Virtual labyrinth model of vestibular afferent excitation via implanted electrodes: validation and application to design of a multichannel vestibular prosthesis. Exp. Brain Res. 210, 623–640. 10.1007/s00221-011-2599-x
    1. Ito M., Shiida T., Yagi N., Yamamoto M. (1974). Visual influence on rabbit horizontal vestibulo-ocular reflex presumably effected via the cerebellar flocculus. Brain Res. 65, 170–174. 10.1016/0006-8993(74)90344-8
    1. Jäger J., Henn V. (1981a). Habituation of the vestibulo-ocular reflex (VOR) in the monkey during sinusoidal rotation in the dark. Exp. Brain Res. 41, 108–114. 10.1007/BF00236599
    1. Jäger J., Henn V. (1981b). Vestibular habituation in man and monkey during sinusoidal rotation. Ann. N.Y. Acad. Sci. 374, 330–339. 10.1111/j.1749-6632.1981.tb30880.x
    1. Kim K. S., Minor L. B., Della Santina C. C., Lasker D. M. (2011). Variation in response dynamics of regular and irregular vestibular-nerve afferents during sinusoidal head rotations and currents in the chinchilla. Exp. Brain Res. 210, 643–649. 10.1007/s00221-011-2600-8
    1. Lewis R. F., Gong W., Ramsey M., Minor L., Boyle R., Merfeld D. M. (2003). Vestibular adaptation studied with a prosthetic semicircular canal. J. Vestib. Res. 12, 87–94.
    1. Lewis R. F., Haburcakova C., Gong W., Makary C., Merfeld D. M. (2010). Vestibuloocular reflex adaptation investigated with chronic motion-modulated electrical stimulation of semicircular canal afferents. J. Neurophysiol. 103, 1066–1079. 10.1152/jn.00241.2009
    1. Lewis R. F., Nicoucar K., Gong W., Haburcakova C., Merfeld D. M. (2013). Adaptation of vestibular tone studied with electrical stimulation of semicircular canal afferents. J. Assoc. Res. Otolaryngol. 14, 331–340. 10.1007/s10162-013-0376-1
    1. McCall A. A., Yates B. J. (2011). Compensation following bilateral vestibular damage. Front. Neurol. 2:88. 10.3389/fneur.2011.00088
    1. Merfeld D. M., Gong W., Morrissey J., Saginaw M., Haburcakova C., Lewis R. F. (2006). Acclimation to chronic constant-rate peripheral stimulation provided by a vestibular prosthesis. IEEE Trans. Biomed. Eng. 53, 2362–2372. 10.1109/TBME.2006.883645
    1. Merfeld D. M., Haburcakova C., Gong W., Lewis R. F. (2007). Chronic vestibulo-ocular reflexes evoked by a vestibular prosthesis. IEEE Trans. Biomed. Eng. 54(6 Pt 1), 1005–1015. 10.1109/TBME.2007.891943
    1. Migliaccio A. A., Meierhofer R., Della Santina C. C. (2011). Characterization of the 3D angular vestibulo-ocular reflex in C57BL6 mice. Exp. Brain Res. 210, 489–501. 10.1007/s00221-010-2521-y
    1. Perez Fornos A., Guinand N., van de Berg R., Stokroos R., Micera S., Kingma H., et al. . (2014). Artificial balance: restoration of the vestibulo-ocular reflex in humans with a prototype vestibular neuroprosthesis. Front. Neurol. 5:66. 10.3389/fneur.2014.00066
    1. Porciuncula F., Johnson C. C., Glickman L. B. (2012). The effect of vestibular rehabilitation on adults with bilateral vestibular hypofunction: a systematic review. J. Vestib. Res. 22, 283–298. 10.3233/VES-120464
    1. Rubinstein J. T., Bierer S., Kaneko C., Ling L., Nie K., Oxford T., et al. . (2012). Implantation of the semicircular canals with preservation of hearing and rotational sensitivity: a vestibular neurostimulator suitable for clinical research. Otol. Neurotol. 33, 789–796. 10.1097/MAO.0b013e318254ec24
    1. Sadeghi S. G., Minor L. B., Cullen K. E. (2007). Response of vestibular-nerve afferents to active and passive rotations under normal conditions and after unilateral labyrinthectomy. J. Neurophysiol. 97, 1503–1514. 10.1152/jn.00829.2006
    1. van de Berg R., Guinand N., Guyot J.-P., Kingma H., Stokroos R. J. (2012). The modified ampullar approach for vestibular implant surgery: feasibility and its first application in a human with a long-term vestibular loss. Front. Neurol. 3:18. 10.3389/fneur.2012.00018
    1. van de Berg R., Guinand N., Stokroos R. J., Guyot J.-P., Kingma H. (2011). The vestibular implant: quo vadis? Front. Neurol. 2:47. 10.3389/fneur.2011.00047
    1. Wall C., Furman J. M. (1989). Eyes open versus eyes closed: effect on human rotational responses. Ann. Otol. Rhinol. Laryngol. 98, 625–629. 10.1177/000348948909800811
    1. Wall C., Kos M. I., Guyot J.-P. (2007). Eye movements in response to electric stimulation of the human posterior ampullary nerve. Ann. Otol. Rhinol. Laryngol. 116, 369–374. 10.1177/000348940711600509
    1. Wall C., Merfeld D. M., Rauch S. D., Black F. O. (2003). Vestibular prostheses: the engineering and biomedical issues. J. Vestib. Res. 12, 95–113.
    1. Ward B. K., Agrawal Y., Hoffman H. J., Carey J. P., Della Santina C. C. (2013). Prevalence and impact of bilateral vestibular hypofunction: results from the 2008 US National Health Interview Survey. JAMA Otolaryngol. Head Neck Surg. 139, 803–810. 10.1001/jamaoto.2013.3913
    1. Weissman B. M., DiScenna A. O., Ekelman B. L., Leigh R. J. (1989). Effect of eyelid closure and vocalization upon the vestibulo-ocular reflex during rotational testing. Ann. Otol. Rhinol. Laryngol. 98, 548–550. 10.1177/000348948909800710
    1. Zee D., Leigh J. (2006). The vestibular-optokinetic system, in The Neurology of Eye Movements, eds Gilman S., Herdman W. (New York, NY: Oxford University Press; ), 72.
    1. Zingler V. C., Weintz E., Jahn K., Mike A., Huppert D., Rettinger N., et al. . (2008). Follow-up of vestibular function in bilateral vestibulopathy. J. Neurol. Neurosurg. Psychiatry 79, 284–288. 10.1136/jnnp.2007.122952

Source: PubMed

Sponsors et collaborateurs

Les conditions médicales

Interventions en matière de drogue

3
S'abonner