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We have designed a straightforward approach to meeting the requirements of the RFP. We have chosen to study rhesus monkeys, performing both behavioral experiments and chronic stimulation and recording experiments.
In the stimulation and recording experiments, we will record primarily from the vestibular nuclei in regions where we have previously recorded neural activity related to VOR function. We will do so via a chronically implanted chamber, advancing specially constructed deep recording multi-channel electrodes (NeuroNexus Technologies) into the brain with a hydraulic microdrive. Drs. Fuchs, Phillips and Ling have considerable experience in using these procedures with single-unit electrodes, and Dr. Bierer has complementary experience in recording with multi-channel electrodes. We will also perform limited recording in the 8th nerve with single-unit electrodes as part of this proposal, primarily for the placement of 8th nerve microstimulation electrodes. Our primary means of stimulation will be with a specially constructed chronic fully implantable stimulation electrode array designed collaboratively by Dr. Rubinstein and Advanced Bionics. This electrode will allow for 4 bipolar stimulation sites within each of the canals and the otolith organs. Our strategy will be to characterize the sensitivity of individual neurons in the vestibular nuclei with en-bloc rotation in each canal plane, and then compare those responses to the response to electrical stimulation at each end organ. This solution allows for the fact that the vestibular nuclei are only weakly topographically organized, so a strict separation of inputs to individual neurons would not be anticipated.
In our long-term behavioral experiments, we will monitor eye and head movement behavior in two groups of monkeys. One group will receive recording and stimulation electrodes, and will also receive an eye and head induction coil to monitor behavior. The second group will receive a further experimental / surgical treatment, which will be 1) surgical labyrinthectomy, 2) canal plugging or 3) injection of gentamicin through the tympanic membrane of the implanted ear. We will observe the response to rotational stimuli, with and without simulated stochastic background activity presented with the chronically implanted labyrinthine stimulating electrodes. In addition, we will observe the head stability of implanted monkeys with and without stimulation. We will also observe the gaze movement, eye and head, of implanted monkeys with and without stimulation. After 6 months of such recording, we will add a signal related to head velocity, through a suitable transformation function (Fernandez and Goldberg, 1971) to the electrical stimulation. That signal will be derived from head velocity and acceleration transduced by the implanted head coil. This will test whether additional benefit beyond the benefit of background stimulation can be derived from the addition of head velocity information during head movement and head stabilization tasks.