Experimental Brain Research

, Volume 210, Issue 3–4, pp 595–606 | Cite as

Cross-axis adaptation improves 3D vestibulo-ocular reflex alignment during chronic stimulation via a head-mounted multichannel vestibular prosthesis

  • Chenkai Dai
  • Gene Y. Fridman
  • Bryce Chiang
  • Natan S. Davidovics
  • Thuy-Anh Melvin
  • Kathleen E. Cullen
  • Charles C. Della SantinaEmail author
Research Article


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.


Vestibular nerve Vestibular prosthesis Vestibular implant Vestibulo-ocular reflex, VOR, labyrinth Bilateral vestibular deficiency Areflexia Adaptation Electrical stimulation 



We thank Lani Swarthout for assistance with animal care. This work was funded by NIH NIDCD grants R01DC009255, K08DC6216, R01DC2390, and 5F32DC009917. CDS, GYF, and BC are inventors on pending and awarded patents relevant to prosthesis technology, and CDS holds an equity interest in Labyrinth Devices LLC.


  1. Angelaki DE, Hess BJ (1998) Visually induced adaptation in three-dimensional organization of primate vestibuloocular reflex. J Neurophysiol 79(2):791–807PubMedGoogle Scholar
  2. Aw ST, Halmagyi GM, Haslwanter T, Curthoys IS, Yavor RA, Todd MJ (1996) Three-dimensional vector analysis of the human vestibuloocular reflex in responseto high-acceleration head rotations. II. responses in subjects with unilateral vestibular loss and selective semicircular canal occlusion. J Neurophysiol 76(6):4021–4030PubMedGoogle Scholar
  3. Baird RA, Desmadryl G, Fernandez C, Goldberg JM (1988) The vestibular nerve of the chinchilla 2. Relation between afferent response properties and peripheral innervation patterns in the semicircular canals. J Neurophysiol 60:182–203PubMedGoogle Scholar
  4. Baker J, Harrison RE, Isu N, Wickland C, Peterson B (1986) Dynamics of adaptive change in vestibulo-ocular reflex direction. II. Sagittal plane rotations. Brain Res 371(1):166–170PubMedCrossRefGoogle Scholar
  5. Baker JF, Wickland C, Peterson B (1987) Dependence of cat vestibulo-ocular reflex direction adaptation on animal orientation during adaptation and rotation in darkness. Brain Res 408:339–343PubMedCrossRefGoogle Scholar
  6. Black FO, Wade SW, Nashner LM (1996) What is the minimal vestibular function required for compensation? Am J Otol 17:401–409PubMedCrossRefGoogle Scholar
  7. Callan JW, Ebenholtz SM (1982) Directional changes in the vestibular ocular response as a result of adaptation to optical tilt. Vision Res 22:37–42PubMedCrossRefGoogle Scholar
  8. Chatelin V, Kim EJ, Driscoll C, Larky J, Polite C, Price L, Lalwani AK (2004) Cochlear implant outcomes in the elderly. Otol Neurotol 25(3):298–301PubMedCrossRefGoogle Scholar
  9. Chiang B, Fridman GY, Della Santina CC (2010) Design and performance of a multichannel vestibular prosthesis that restores semicircular canal sensation in macaques. IEEE Trans Neural Systems and Rehab Eng (in press)Google Scholar
  10. Cohen B, Suzuki J, Bender MB (1964) Eye movements from semicircular canal nerve stimulation in cat. Annals Otol Rhin Laryng 73:153–169Google Scholar
  11. Cremer PD, Minor LB, Carey JP, Della Santina CC (2000) Eye movements in patients with superior canal dehiscence syndrome align with the abnormal canal. Neurology 55(12):1833–1841PubMedGoogle Scholar
  12. Cullen KE (2008) Procedural learning: VOR. In: H. Eichenbaum (ed) Memory systems, vol. 3 of Learning and memory: a comprehensive reference (J.Byrne ed). Elsevier, Oxford, pp. 383–402Google Scholar
  13. Curthoys IS (1987) Eye movements produced by utricular and saccular stimulation. Aviat Space Environ Med 58(9):192–197Google Scholar
  14. Curthoys IS, Halmagyi GM (1995) Vestibular compensation: A review of the oculomotor, neural, and clinical consequences of unilateral vestibular loss. J Vestib Res 5(2):67–107PubMedCrossRefGoogle Scholar
  15. Davidovics NS, Fridman GY, Chiang B, Della Santina CC (2010) 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 Rehab Eng (in press, PubMed PMID: 20813652)Google Scholar
  16. Della Santina CC, Cremer PD, Carey JP, Minor LB (2002) Comparison of head thrust test with head autorotation test reveals that the vestibulo-ocular reflex is enhanced during voluntary head movements. Arch Otol Head Neck Surg. 128(9):1044–1054Google Scholar
  17. Della Santina CC, Migliaccio AA, Patel AH (2005a) Electrical stimulation to restore vestibular function development of a 3-D vestibular prosthesis. Conf Proc IEEE Eng Med Biol Soc 7:7380–7385PubMedGoogle Scholar
  18. Della Santina CC, Migliaccio AA, Park HJ, Anderson IW, Jiradejvong P, Minor LB and Carey JP (2005) 3D Vestibuloocular reflex, afferent responses and crista histology in chinchillas after unilateral intratympanic gentamicin. Abstract 813, ARO Midwinter Meeting Proceedings Google Scholar
  19. Della Santina CC, Migliaccio AA, Patel AH (2007) A multichannel semicircular canal neural prosthesis using electrical stimulation to restore 3-D vestibular sensation. IEEE Trans Biomed Eng 54:1016–1030PubMedCrossRefGoogle Scholar
  20. Della Santina CC, Migliaccio AA, Hayden R, Melvin TA, Fridman GY, Chiang B, Davidovics NS, Dai C, Carey JP, Minor LB, Anderson ICW, Park H, Lyford-Pike S, Tang S (2010) Current and future management of bilateral loss of vestibular sensation–An update on the Johns Hopkins Multichannel Vestibular Prosthesis Project. Cochlear Implants International 11(s2):2–11CrossRefGoogle Scholar
  21. du Lac S et al (2010) Signaling and plasticity of vestibular nerve synapses onto functionally distinct vestibular nucleus neurons. Abstract 535 ARO Midwinter Meeting ProceedingsGoogle Scholar
  22. Ebenholtz SM (1966) Adaptation to a rotated visual field as a function of degree of optical tilt and exposure time. J Exp Psychol 72:629–634PubMedCrossRefGoogle Scholar
  23. Fluur E, Mellström A (1970a) Utricular stimulation and oculomotor reactions. Laryngoscope 80:1701–1712PubMedCrossRefGoogle Scholar
  24. Fluur E, Mellström A (1970b) Saccular stimulation and oculomotor reactions. Laryngoscope 80:1713–1721PubMedCrossRefGoogle Scholar
  25. Fluur E, Mellström A (1971) The otolith organs and their influence on oculomotor movements. Exp Neurol 30:139–147PubMedCrossRefGoogle Scholar
  26. Fridman GY, Davidovics NS, Dai C, Della Santina CC (2010) Vestibulo-ocular reflex responses to a multichannel vestibular prosthesis incorporating a 3D coordinate transformation for correction of misalignment. JARO 11(3):367–381PubMedCrossRefGoogle Scholar
  27. Fukushima K, Fukushima J, Chin S et al (1996) Cross axis vestibulo-ocular reflex induced by pursuit training in alert monkeys. Neurosci Res 25:255–265PubMedCrossRefGoogle Scholar
  28. Furman JM, Wall C, Kamerer DB (1989) Earth horizontal axis rotational responses in patients with unilateral peripheral vestibular deficits. Ann Otol Rhinol Laryngol 98(7 Pt 1):551–555PubMedGoogle Scholar
  29. Gillespie MB, Minor LB (1999) Prognosis in bilateral vestibular hypofunction. Laryngoscope 109:35–41PubMedCrossRefGoogle Scholar
  30. Gong WS, Merfeld DM (2000) Prototype neural semicircular canal prosthesis using patterned electrical stimulation. Annals Biomed Eng 28:572–581CrossRefGoogle Scholar
  31. Gong WS, Merfeld DM (2002) System design and performance of a unilateral horizontal semicircular canal prosthesis. IEEE Trans Biomed Eng 49:175–181PubMedCrossRefGoogle Scholar
  32. Goto F, Meng H, Bai R, Sato H, Imagawa M, Sasaki M, Uchino Y (2003) Eye movements evoked by the selective stimulation of the utricular nerve in cats Auris Nasus Larynx 30(4):341–348Google Scholar
  33. Goto F, Meng H, Bai R, Sato H, Imagawa M, Sasaki M, Uchino Y (2004) Eye movements evoked by selective saccular nerve stimulation in cats. Auris Nasus Larynx 31(3):220–225PubMedCrossRefGoogle Scholar
  34. Grunbauer WM, Dieterich M, Brandt T (1998) Bilateral vestibular failure impairs visual motion perception even with the head still. Neuroreport 9(8):1807–1810PubMedCrossRefGoogle Scholar
  35. Harrison REW, Baker JF, Isu N, Wickland CR, Peterson BW (1986) Dynamics of adaptive change in vestibulo-ocular reflex direction I. Rotations in the horizontal plane. Brain Res 371:162–165PubMedCrossRefGoogle Scholar
  36. Hirvonen TP, Minor LB, Hullar TE, Carey JP (2005) Effects of intratympanic gentamicin on vestibular afferents and hair cells in the chinchilla. J Neurophysiol 93(2):643–655PubMedCrossRefGoogle Scholar
  37. Hullar TE, Williams CD (2006) Geometry of the semicircular canals of the chinchilla (Chinchilla laniger). Hear Res 213(1–2):17–24PubMedCrossRefGoogle Scholar
  38. Hullar TE, Della Santina CC, Hirvonen T, Lasker DM, Carey JP, Minor LB (2005) Responses of irregularly discharging chinchilla semicircular canal vestibular-nerve afferents during high-frequency head rotations. J Neurophysiol 93:2777–2786PubMedCrossRefGoogle Scholar
  39. Lasker DM, Hullar TE, Minor LB (2000) Horizontal vestibuloocular reflex evoked by high-acceleration rotations in the squirrel monkey. III. Responses after labyrinthectomy. J Neurophysiol 83:2482–2496PubMedGoogle Scholar
  40. Leigh RJ, Zee DS (2006) The neurology of eye movements. Oxford University Press, OxfordGoogle Scholar
  41. Leinfelder PJ, Black NM (1941) Experimental transposition of the extraocular muscles in monkeys. Am J Ophthalmol 24:1115–1120Google Scholar
  42. Lewis RF, Gong WS, Ramsey M, Minor L, Boyle R, Merfeld DM (2002) Vestibular adaptation studied with a prosthetic semicircular canal. J Vestib Res 12:87–94PubMedGoogle Scholar
  43. Lewis RF, Haburcakova C, Gong W, Makary C, Merfeld DM (2010) Vestibuloocular reflex adaptation investigated with chronic motion-modulated electrical stimulation of semicircular canal afferents. J Neurophysiol 103(2):1066–1079PubMedCrossRefGoogle Scholar
  44. Mack A, Rock I (1968) A re-examination of the Stratton effect: egocentric adaptation to a rotated visual image. Percept Psychophys 4:57–62CrossRefGoogle Scholar
  45. Malinvaud D, Vassias I, Reichenberger I, Rossert C, Straka H (2010) Functional organization of vestibular commissural connections in frog. J Neurosci 30(9):3310–3325PubMedCrossRefGoogle Scholar
  46. Merfeld DM, Gong WS, Morrissey J, Saginaw M, Haburcakova C, Lewis RF (2006) Acclimation to chronic constant-rate peripheral stimulation provided by a vestibular prosthesis. IEEE Trans Biomed Eng 53(11):2362–2372PubMedCrossRefGoogle Scholar
  47. Merfeld DM, Haburcakova C, Gong W, Lewis RF (2007) Chronic vestibulo-ocular reflexes evoked by a vestibular prosthesis. IEEE Trans Biomed Eng 54(6):1005–1015PubMedCrossRefGoogle Scholar
  48. Migliaccio AA, MacDougall HG, Minor LB, Della Santina CC (2005) Inexpensive system for real-time 3-dimensional video-oculography using a fluorescent marker array. J Neurosci Meth 143(2):141–150CrossRefGoogle Scholar
  49. Migliaccio AA, Minor LB, Della Santina CC (2010) Adaptation of the vestibulo-ocular reflex for forward-eyed foveate vision. J Physiol 588(20):3855–3867PubMedCrossRefGoogle Scholar
  50. Mikaellan H, Held R (1964) Two types of adaptation to an optically-rotated visual field. Am J Psychol 77:257–262CrossRefGoogle Scholar
  51. Minor LB (1998) Gentamicin-induced bilateral vestibular hypofunction. JAMA 279:541–544PubMedCrossRefGoogle Scholar
  52. Morant RB, Beller HK (1965) Adaptation of prismatically rotated visual fields. Science 148:530–531PubMedCrossRefGoogle Scholar
  53. Peng GC, Baker JF, Peterson BW (1994) Dynamics of directional plasticity in the human vertical vestibulo-ocular reflex. J Vestib Res 4(6):453–460PubMedGoogle Scholar
  54. Sadeghi SG, Minor LB, Cullen KE (2006) Dynamics of the horizontal vestibuloocular reflex after unilateral labyrinthectomy: response to high frequency, high acceleration, and high velocity rotations. Exp Brain Res 175(3):471–484PubMedCrossRefGoogle Scholar
  55. Sadeghi S, Minor LB, Cullen KE (2010) Neural correlates of motor learning: dynamic regulation of multimodal integration in the macaque vestibular system. J Neurosci 30(30):10158–10168PubMedCrossRefGoogle Scholar
  56. Schubert MC, Della Santina CC, Shelhamer M (2008) Incremental angular vestibulo-ocular reflex adaptation to active head rotation. Exp Brain Res 191(4):435–446PubMedCrossRefGoogle Scholar
  57. Schultheis LW, Robinson DA (1981) Directional plasticity of the vestibulo-ocular reflex in the cat. Ann. NY Acad Sci 374:504–512CrossRefGoogle Scholar
  58. Suzuki JI, Cohen B (1964) Head eye body + limb movements from semicircular canal nerves. Exp Neurology 10:393–405CrossRefGoogle Scholar
  59. Suzuki JI, Goto K, Tokumasu K, Cohen B (1969a) Implantation of electrodes near individual vestibular nerve branches in mammals. Ann Otol Rhinol Laryngol 78(4):815–826PubMedGoogle Scholar
  60. Suzuki JI, Tokumasu K, Goto K (1969b) Eye movements from single utricular nerve stimulation in the cat. Acta Otolaryngol 68(4):350–362PubMedCrossRefGoogle Scholar
  61. Trillenberg P, Shelhamer M, Roberts DC, Zee DS (2003) Cross-axis adaptation of torsional components in the yaw-axis vestibulo-ocular reflex. Exp Brain Res 148(2):158–165Google Scholar

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Chenkai Dai
    • 1
  • Gene Y. Fridman
    • 1
  • Bryce Chiang
    • 1
  • Natan S. Davidovics
    • 1
  • Thuy-Anh Melvin
    • 1
  • Kathleen E. Cullen
    • 2
  • Charles C. Della Santina
    • 1
    Email author
  1. 1.Departments of Otolaryngology—Head & Neck Surgery and Biomedical EngineeringVestibular NeuroEngineering Laboratory, Johns Hopkins University School of MedicineBaltimoreUSA
  2. 2.Department of PhysiologyMcGill UniversityMontrealCanada

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