Head movements evoked in alert rhesus monkey by vestibular prosthesis stimulation: implications for postural and gaze stabilization

Diana E Mitchell, Chenkai Dai, Mehdi A Rahman, Joong Ho Ahn, Charles C Della Santina, Kathleen E Cullen, Diana E Mitchell, Chenkai Dai, Mehdi A Rahman, Joong Ho Ahn, Charles C Della Santina, Kathleen E Cullen

Abstract

The vestibular system detects motion of the head in space and in turn generates reflexes that are vital for our daily activities. The eye movements produced by the vestibulo-ocular reflex (VOR) play an essential role in stabilizing the visual axis (gaze), while vestibulo-spinal reflexes ensure the maintenance of head and body posture. The neuronal pathways from the vestibular periphery to the cervical spinal cord potentially serve a dual role, since they function to stabilize the head relative to inertial space and could thus contribute to gaze (eye-in-head + head-in-space) and posture stabilization. To date, however, the functional significance of vestibular-neck pathways in alert primates remains a matter of debate. Here we used a vestibular prosthesis to 1) quantify vestibularly-driven head movements in primates, and 2) assess whether these evoked head movements make a significant contribution to gaze as well as postural stabilization. We stimulated electrodes implanted in the horizontal semicircular canal of alert rhesus monkeys, and measured the head and eye movements evoked during a 100 ms time period for which the contribution of longer latency voluntary inputs to the neck would be minimal. Our results show that prosthetic stimulation evoked significant head movements with latencies consistent with known vestibulo-spinal pathways. Furthermore, while the evoked head movements were substantially smaller than the coincidently evoked eye movements, they made a significant contribution to gaze stabilization, complementing the VOR to ensure that the appropriate gaze response is achieved. We speculate that analogous compensatory head movements will be evoked when implanted prosthetic devices are transitioned to human patients.

Conflict of interest statement

Competing Interests: CDS is an inventor on pending and awarded patents relevant to prosthesis technology, and is CEO of and holds an equity interest in Labyrinth Devices LLC. The terms of these arrangements are being managed by the Johns Hopkins University in accordance with its conflict of interest policies. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials. Patents: Della Santina CC, Lie TS, Chiang B, “Systems and methods for testing vestibular and oculomotor function,” International Utility Patent Application No. PCT/US2009/40486, filed 14.04.2009; claims priority to U.S. Provisional Patent Application No. 61/124,122, filed 14.04.2008. Della Santina CC, Faltys MA, “Dual cochlear/vestibular stimulator with control signals derived from motion and speech signals,” United States Patent 7,647,120 (awarded 12.01.2010; published 09.06.2007 continuation in part of US Patent 7,225,028). Della Santina CC, Faltys MA, “Dual cochlear/vestibular stimulator with control signals derived from motion and speech signals,” United States Patent 7,225,028 (awarded 29.05.2007; published 12/1/2005 derivative of provisional patent filed 05.28.2004) Della Santina CC, Fridman GY, Chiang B, “Implantable Vestibular Prosthesis,” Pub No: WO/2011/088130; Intl App No.: PCT/US2011/021005; Pub Date: 21.07.2012; Intl Filing Date: 12.01.2011. Della Santina CC, Andreou AA, Kalayjian Z, Fridman G, Chiang B, Georgiou J, “High-Voltage CMOS Neuroelectronic Interface For Multichannel Vestibular Prosthesis,” Pub No: WO/2012/018631; Intl App No.: PCT/US2011/045384; Pub Date: 09.02.2012; International Filing Date:26.07.2011. Jäger A, Garnham C, Hessler R, Zimmerling M, Della Santina CC, Fridman Gene, “Vestibular Implant System With Low Battery Alert,” Pub No:WO/2012/177589; Intl App No.:PCT/US2012/043069; Pub Date: 27.12.2012; International Filing Date: 19.06.2012.

Figures

Figure 1. VCR and VOR responses to…
Figure 1. VCR and VOR responses to increasing current amplitudes.
A, Pathways connecting the vestibular nerve to neck or extraocular motoneurons. B-D, Average head (blue) and eye (red) movement traces, in monkey J and B, evoked using current amplitudes of 50 (B), 75 (C), and 100% (D) of the maximum for pulse trains delivered at 300pps lasting 100ms. Gray bars indicate stimulus duration and shading represents standard error. Note that for some velocity traces the standard error is smaller than the line thickness. Movements away from implanted side are upwards. Arrows show rebound effect due to the release of inhibition. Insets show peak head and eye velocities for the corresponding traces. EOM, extraocular motoneuron; INC, interstitial nucleus of Cajal; MRST, medial reticulospinal tract; MN, motoneuron; VST, vestibulospinal tract; VN, vestibular nuclei.
Figure 2. Average VCR and VOR responses…
Figure 2. Average VCR and VOR responses to increasing pulse rates.
A-D, Average head (blue) and eye (red) movement traces, in monkey J and B, evoked using increasing pulse rates of 50 (A), 100 (B), 200 (C) and 300pps (D) at maximum current amplitude. E-G, Plots of peak head and eye velocities as a function of pulse rate for current amplitudes of 50 (E), 75 (F), 100% (G) of the maximum.
Figure 3. VCR and VOR response latency…
Figure 3. VCR and VOR response latency and relative contribution to gaze.
A-B, Latency of evoked eye or head movements using a 2 standard deviation (A) or slope intercept measurement (B). C, Plots of eye versus head movement amplitude during pulse trains delivered at 50, 100, 200 and 300pps. D, Top panels show the contribution of head and eye to instantaneous gaze velocity during pulse trains delivered at the maximum current amplitude and 300pps. Bottom traces show the contribution of head and eye to cumulative gaze position. The average gaze velocity (top panels) and position (bottoms panels) traces are also plotted for comparison.
Figure 4. Interaction of vestibular-driven head and…
Figure 4. Interaction of vestibular-driven head and eye movements.
A, Average gaze, eye and head position (top panels) and velocity (bottom panels) traces during stimulations when the head was restrained and free. Gray bars indicate stimulus duration and shading represents standard error. B, Plots of average gaze movement amplitude during pulse trains delivered at 50, 100, 200 and 300pps when head-restrained versus free. D, Plots of average eye movement amplitude during pulse trains delivered at 50, 100, 200 and 300pps when head-restrained versus free.

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