Table A1.

Main results of vestibular implant research.

Findings	Animal research	Type of animal	Main results and references	Human research	Main results and references
Electric stimulation of the canal nerves induces a nystagmus which corresponds to the plane of the canal which is innervated by the stimulated nerve branch	Yes	Guinea pig Squirrel monkey Chinchilla	Stimulation of the anterior canal shows vertical eye movements (Gong and Merfeld, 2000) Stimulation of the horizontal canal evokes primarily horizontal responses (Gong and Merfeld, 2002; Lewis et al., 2002, 2010; Merfeld et al., 2007; Gong et al., 2008) Acute stimulation using a multichannel prosthesis shows eye responses already aligned somewhat with head rotation axes, but significant misalignment is evident (Della Santina et al., 2007; Fridman et al., 2010; Dai et al., 2011a)	Yes	Blue-lined stimulation of the posterior ampullary nerve shows a primarily vertical response (Wall and Guyot, 2007) Stimulation of LAN and SAN shows a predominantly horizontal response with a vertical component (Guyot et al., 2011a)
Gain is increased by a higher current	Yes	Guinea pig Squirrel monkey Chinchilla	Eye movements are measurable at a current of 19 μA and become greater at higher current levels (Gong and Merfeld, 2000) The magnitude of the response is roughly proportional to stimulation current pulse level (Gong et al., 2008) Increasing stimulus current amplitude increases VOR magnitude (Della Santina et al., 2007; Fridman et al., 2010)	Yes	Blue-lined PAN stimulation evokes a fairly linear increase of response with increasing input amplitude over the range of 300 μA to 1 mA (Wall and Guyot, 2007; Guyot et al., 2011b) LAN-stimulation ranges from 120 to 1000 μA, which might be enough to encode eye movements of different velocities (Guyot et al., 2011a)
Gain increases with stimulus frequency and modulation sensitivity	Yes	Guinea pig Squirrel monkey	Increases in the stimulation frequency are matched by increases in the magnitude of the eye movement responses. Clear eye responses are observed from 40.5 Hz (Gong and Merfeld, 2000) Gain roughly doubles for each doubling of the stimulation sensitivity (Lewis et al., 2002, 2010; Merfeld et al., 2007)	Yes	Blue-lined stimulation of PAN shows that slow component velocity rapidly increases with increasing pulse repetition rate from 25 pps to a maximum of 200 pps (Wall and Guyot, 2007)
Gain is significantly increased by stimulation period and transitions between stimulation states	Yes	Squirrel monkey Chinchilla	The VOR shows adaptive capabilities during chronic stimulation and cycling of stimulation state, evidenced by an increase in gain (Lewis et al., 2010) 3D VOR response remains relatively high and constant during 7 days of continuous stimulation (Dai et al., 2011a)	No
Bilateral stimulation increases the gain	Yes	Squirrel monkey	VOR responses evoked by bilateral stimulation are the summation of the responses evoked by bilateral stimulation, demonstrating a gain constant of 0.24 (normal = 0.26; Gong et al., 2008)	No
The vestibular system adapts to (supra)normal baseline stimulation	Yes	Guinea pig Squirrel monkey Chinchilla	The first time stimulation is turned on, all guinea pigs acclimate within a day or so (Merfeld et al., 2006) The nystagmus evoked by baseline stimulation disappears within 6 h to 1 day of the chronic stimulation turned on (Lewis et al., 2002, 2010; Merfeld et al., 2007) Activation of prosthesis causes a brisk nystagmus, which adapts to a slow phase velocity of <5°/s in all components within 20 min. (Della Santina et al., 2007)	Yes	When continuous electrical stimulation at 400 μA is turned on for the first time, strong nystagmic beats are almost absent from recordings after 27 min (Guyot et al., 2011b)
The vestibular system adapts to static baseline stimulation, but not to dynamic modulation	Yes	Guinea pig Squirrel monkey	Sinusoidally modulated stimulation yields a sinusoidally modulated VOR, even after acclimation to the baseline stimulation (Merfeld et al., 2006) Animals show horizontal VORs for periods exceeding 90 days when pulse-rate is modulated, while nystagmus evoked by baseline stimulation has disappeared (Merfeld et al., 2007; Lewis et al., 2010)	Yes	Once a patient is in an adapted state, it is possible to elicit smooth oscillatory eye movements by modulating the amplitude or frequency of the stimulation (Guyot et al., 2011b)
The vestibular system adapts to different stimulation states	Yes	Guinea pig Squirrel monkey	After many off-to-on or on-to-off transitions, little nystagmus is evoked by turning the stimulation on or off (Merfeld et al., 2006) The spontaneous nystagmus evoked by stimulation gradually attenuates and remains relatively small during subsequent periods of chronic stimulation of different stimulation states (Lewis et al., 2010)	Yes	Successive “on–off” cycles of continuous electrical stimulation result in a progressively shorter duration of the nystagmic response (Guyot et al., 2011b)
Cross-axis adaptation is possible in the vestibular system	Yes	Squirrel monkey Chinchilla	A horizontal VOR can develop even if the stimulated posterior canal is orthogonal to the velocity sensor of the prosthesis (Lewis et al., 2002) Cross-axis adaptation considerably improves 3D VOR alignment during the first week of chronic stimulation (Dai et al., 2011a)	No
Time constant of the evoked VOR is smaller than the time constant of the prosthesis	Yes	Squirrel monkey	The time constant of the VOR response was smaller than the time constant of the prosthesis (Merfeld et al., 2007; Gong et al., 2008; Lewis et al., 2010)	No
Improvement in VOR-symmetry is still uncertain	Yes	Squirrel monkey Chinchilla	During the first 2 weeks of stimulation, there is a decline in difference between the ipsi- and contralateral gains of 71–78% when stimulated in the low sensitivity mode (Lewis et al., 2010) VOR-asymmetry did not change significantly during 1 week of prosthetic use (Dai et al., 2011a)	No
Misalignment of VOR-axis improves significantly during prosthetic use	Yes	Squirrel monkey Chinchilla	During chronic stimulation, the initial VOR-axis (45°–56°) is shifted in the plane closer to the compensatory orientation of 90° (73°–83.5°; Lewis et al., 2010) Seven days of continuous prosthetic use shows a significant improvement in VOR alignment (Dai et al., 2011a)	No