# Sensory Systems/Neurosensory Implants/Vestibular Implants
## Vestibular Implants
### Introduction

People with damaged vestibular systems experience a combination of symptoms that may include hearing and vision disturbances, vertigo, dizziness, and spatial disorientation. Currently, there are no effective treatments for patients with weak or damaged vestibular systems. Over the past decade, scientists have developed an electrical stimulating device, similar to cochlear implants, that would restore semicircular canal function. Vestibular implants are intended to restore balance in patients with a damaged vestibular system. Figure shows a vestibular implant prototype, which is a modified cochlear implant designed by MED-EL (Innsbruck, Austria).
This vestibular neuroprosthesis prototype contains four major components: an electrical stimulator, three extracochlear electrodes that are placed in the ampullae of each semicircular canal, and an intracochlear array. When the vestibular implant is turned on, trains of electrical stimulation in the form of charge-balance, biphasic pulses are delivered down each extracochlear electrode toward a respective vestibular nerve . Ultimately, the electrical stimulation would restore balance in a patient by stabilizing gaze via the vestibulo-ocular reflex (VOR). Progress toward an implantable prosthesis has shown promising results to effectively restore normal vestibular sensory transduction of head rotations. However, achieving an accurate stimulation paradigm to chronically encode three-dimensional head movements without causing undesired neuronal activity remains one of several key challenges.

### Vestibular prosthesis evolution (1963-2014)

In 1963, Cohen and Suzuki
introduced the notion of vestibular prosthesis by demonstrating that eye movements can be induced via electrical stimulation of the ampullary branch of a vestibular nerve. Studies that followed were driven to engineer a continuous and accurate stimulation model for rehabilitating patients with different types of vestibular disorders, such as bilateral loss of vestibular function (BVL) and Meniere's disease
. Four decades after Cohen and Sukui's pioneering work, Merfeld and colleagues developed the first vestibular device for generating smooth eye movements by electrically stimulating the vestibular nerve
. The feasibility of neuro-electronic vestibular devices had further inspired researchers to integrate a motion-detection system to measure head movements. Santina and colleagues
used gyroscopic sensors to measure movements in three-dimensional space and encoded this information to generate signals that control muscles of each eye via the vestibular nerve. As of late 2012, only two groups in the world have conducted vestibular implant studies on humans: a team led by Jay Rubinstein at the University of Washington and a joint-effort between a team led by Herman Kingma at the Maastrict University of Medical Center in the Netherlands and second group led by Jean-Phillippe Guyot at Hopitaux Universitaries de Geneve, Switzerland . Jay Rubinstein led the first vestibular clinical study in 2010. Rubinstein and colleagues had successfully installed a vestibular pacemaker to reduce or cease involuntary vertigo attacks in patients diagnosed with Meniere's disease . This device was combined with a handheld controller to start and stop a range of electrical stimuli that can be directed to any or all electrodes, but did not code for motion . Unfortunately, the vestibular pacemaker in implanted patients had resulted in both the auditory and vestibular function deteriorating considerably
. A new direction has been taken from this group to explore a different electrical stimulation paradigm by incorporating information about motion . The second attempt for human clinical studies was carried by Kingma, Guyot, and colleagues in 2012. Vestibular implants used in this study were prototyped by MED-EL. Perez-Fornos and colleagues
demonstrated that patients achieved a level of satisfactory functional recovery that allows them to exercise everyday activities such as walking.
Current progress is being made through ongoing university-industry partnerships. There are four leading University and/or industry partnerships working toward a vestibular prosthesis for clinical applications. These teams include: Rubinstein at the University of Washington and Cochlear Ltd (Lane Cove, Australia), Della Santina's team at the Vestibular NeuroEngineering Laboratory [Johns Hopkins School of Medicine, Baltimore, MD, USA], Daniel Merfeld's team at the Jenks Vestibular Physiology Laboratory at Harvard [Massachusetts Eye and Ear Infirmary, Boston, MA, USA], and a joint-effort between Herman Kingma, Jean-Philippe Guyot, and MED-EL.

### Future directions in research

The state-of-the-art vestibular implant technology is a two-step system that produces electrical stimulations to three ampullary nerves in response to rotations around a respective axis (anterior, posterior, or horizontal canals). However, the biophysics of prosthetic nerve stimulation remains a challenge to mimic normal sensory transduction. Even though much is already known about how vestibular nerve afferents encode head movements, it is not yet understood how to design a noninvasive stimulus encoding strategy for a multichannel prosthesis. Active research has continued to focus on overcoming design and signal transduction limitations.
Current neural prostheses are intended to excite neural tissues in which they are implanted, but the effect of continuous excitatory stimulations can yet cause neurological deficits . Ultimately, a device that can both excite head motion in one direction and inhibit movement in the opposite direction is much desired. The latest prototype system developed by Santina and colleagues, SCSD1, has shown that direct current stimulations can evoke excitatory and inhibitory VOR responses . Their results demonstrate that effects of introducing the vestibular system to an artificial baseline can possibly alter the dynamic ranges of excitatory and inhibitory thresholds in unpredicted ways. On the other hand, clinical studies show that it is possible for humans to adapt within a reasonably short time (a few minutes) to the absence and presence of artificial neural activity . Once adaptation is reached, then one can tune the amplitude and frequency modulations of the stimulation to elicit smooth eye movements of different speeds and directions .
Another type of design limitation of electrical prosthesis is current to spread away from the targeted nerve tissue and cause stimulations in the wrong canal
. As a consequence, this current spread induces misalignment between the axis of the eye and head rotation . Therefore, the mechanisms underlying directional neural plasticity can provide well-aligned responses for humans. Other studies suggest infrared nerve stimulation is advantageous for targeting specific neurons and less obtrusive to nearby populations of neurons
. The use of optics would allow higher spatial selectivity and improved surgical access .
In addition, a fundamental challenge underlying the development of vestibular prosthesis is accounting for ways in which information from vestibular end organs can elicit particular movements. It has been shown that reflex and perceptual responses are dependent on which vestibular afferent inputs are stimulated . Surgical practices are examined for accurate placements of the electrode with respect to the afferents, which in the end could greatly influence the ability to stimulate a desired response.
Because the auditory and vestibular areas of the inner ear are connected, the spread of current beyond the target ampullary nerves and/or risks of surgery could interfere with cochlear nerve activity. It is likely that humans with implants will experience a risk of hearing loss, as observed in rhesus monkeys . Santina and colleagues
found that implantation of electrodes caused up to 14 dB of hearing loss and delivery of electrical stimulation further reduced hearing by 0.4-7.8 dB. This study suggests that current spread to cochlear hair cells may cause random activity in nearby cochlear regions.
* 1 2 3 4 5 6 Perez Fornos, A.; Guinand, N.; Van De Berg, R.; Stokroos, R.; Micera, S.; Kingma, H.; Pelizzone, M.; and Guyot, J. (2014). "Artificial balance: restoration of the vestibulo-ocular reflex in humans with a prototype vestibular neuroprosthesis". Frontiers in Neurology. 5.{{cite journal}}: CS1 maint: multiple names: authors list (link)
* ↑ Cohen, B. and Suzuki, J. (1963). "Eye movements induced by ampullary nerve stimulation". The American journal of physiology. 204: 347–351.{{cite journal}}: CS1 maint: multiple names: authors list (link)
* 1 2 3 4 5 Golub, J. S.; Ling, L.; Nie, K.; Nowack, A.; Shepherd, S. J.; Bierer, S. M.; Jameyson, E.; Kaneko, C. R.; Phillips, J. O.; and Rubinstein, J. T. (2014). "Prosthetic Implantation of the Human Vestibular System". Otology & Neurotology. 1: 136–147.{{cite journal}}: CS1 maint: multiple names: authors list (link)
* ↑ Gong, W. and Merfeld, D. M. (2000). "Prototype neural semicircular canal prosthesis using patterned electrical stimulation". Annals of Biomedical Engineering. 28: 572–581.{{cite journal}}: CS1 maint: multiple names: authors list (link)
* ↑ Lewis, R. F.; Haburcakova, C.; Gong, W.; Makary, C.; and Merfeld, D. M. (2010). "Vestibuloocular Reflex Adaptation Investigated With Chronic Motion-Modulated Electrical Stimulation of Semicircular Canal Afferents". Journal of Neurophysiology. 103: 1066–1079.{{cite journal}}: CS1 maint: multiple names: authors list (link)
* ↑ Dai, C.; Fridman, G. Y.; Chiang, B.; Davidovics, N.; Melvin, T.; Cullen, K. E. and Della Santina, Charles C. (2011). "Cross-axis adaptation improves 3D vestibulo-ocular reflex alignment during chronic stimulation via a head-mounted multichannel vestibular prosthesis". Experimental Brain Research. 210: 595–606.{{cite journal}}: CS1 maint: multiple names: authors list (link)
* ↑ Dai, C.; Fridman, G. Y.; Davidovics, N.; Chiang, B.; Ahn, J. and Della Santina, C. C. (2011). "Restoration of 3D Vestibular Sensation in Rhesus Monkeys Using a Multichannel Vestibular Prosthesis". Hearing Research. 281: 74–83.{{cite journal}}: CS1 maint: multiple names: authors list (link)
* ↑ Dai, Chenkai and Fridman, Gene Y. and Chiang, Bryce and Rahman, Mehdi A. and Ahn, Joong Ho and Davidovics, Natan S. and Della Santina, Charles C. (2013). "Directional Plasticity Rapidly Improves 3D Vestibulo-Ocular Reflex Alignment in Monkeys Using a Multichannel Vestibular Prosthesis". Journal of the Association for Research in Otolaryngology. 14: 863–877.{{cite journal}}: CS1 maint: multiple names: authors list (link)
* ↑ Davidovics, Natan S. and Rahman, Mehdi A. and Dai, Chenkai and Ahn, JoongHo and Fridman, Gene Y. and Della Santina, Charles C. (2013). "Multichannel Vestibular Prosthesis Employing Modulation of Pulse Rate and Current with Alignment Precompensation Elicits Improved VOR Performance in Monkeys". Journal of the Association for Research in Otolaryngology. 14: 233–248.{{cite journal}}: CS1 maint: multiple names: authors list (link)
* 1 2 3 Phillips, Christopher and DeFrancisci, Christina and Ling, Leo and Nie, Kaibao and Nowack, Amy and Phillips, James O. and Rubinstein, Jay T. (2013). "Postural responses to electrical stimulation of the vestibular end organs in human subjects". Experimental Brain Research. 229: 181–195.{{cite journal}}: CS1 maint: multiple names: authors list (link)
* ↑ Fridman, Gene Y. and Della Santina, Charles C. (2013). "Safe Direct Current Stimulation to Expand Capabilities of Neural Prostheses". IEEE Trans Neural Syst Rehabil Eng. 21: 319–328.{{cite journal}}: CS1 maint: multiple names: authors list (link)
* 1 2 Guyot, Jean-Philippe and Sigrist, Alain and Pelizzone, Marco and Kos, Maria I. (2011). "Adaptation to steady-state electrical stimulation of the vestibular system in humans". Annals of Otology, Rhinology & Laryngology. 120: 143–149.{{cite journal}}: CS1 maint: multiple names: authors list (link)
* 1 2 3 Harris, David M. and Bierer, Steven M. and Wells, Jonathon D. and Phillips, James O. (2009). "Optical nerve stimulation for a vestibular prosthesis". Processing of SPIE. 5.{{cite journal}}: CS1 maint: multiple names: authors list (link)
* ↑ Della Santina, Charles C. and Migliaccio, Americo A. and Patel, Amit H. (2007). "A multichannel semicircular canal neural prosthesis using electrical stimulation to restore 3-D vestibular sensation". IEEE transactions on bio-medical engineering. 54: 1016–1030.{{cite journal}}: CS1 maint: multiple names: authors list (link)
* 1 2 Lumbreras, Vicente and Bas, Esperanza and Gupta, Chhavi and Rajguru, Suhrud M. (2014). "Pulsed Infrared Radiation Excites Cultured Neonatal Spiral and Vestibular Ganglion Neurons by Modulating Mitochondrial Calcium Cycling". Journal of Neurophysiology.{{cite journal}}: CS1 maint: multiple names: authors list (link)
* 1 2 Dai, Chenkai and Fridman, Gene Y. and Della Santina, Charles C. (2011). "Effects of vestibular prosthesis electrode implantation and stimulation on hearing in rhesus monkeys". Hearing Research. 277: 204–210.{{cite journal}}: CS1 maint: multiple names: authors list (link)