Loss of Afferent Vestibular Input Produces Central Adaptation and Increased Gain of Vestibular Prosthetic Stimulation.

Implanted vestibular neurostimulators are effective in driving slow phase eye movements in monkeys and humans. Furthermore, increases in slow phase velocity and electrically evoked compound action potential (vECAP) amplitudes occur with increasing current amplitude of electrical stimulation. In intact monkeys, protracted intermittent stimulation continues to produce robust behavioral responses and preserved vECAPs.

Prosthetic implantation of the human vestibular system.

Hypothesis: A functional vestibular prosthesis can be implanted in human such that electrical stimulation of each semicircular canal produces canal-specific eye movements while preserving vestibular and auditory function.

Background: A number of vestibular disorders could be treated with prosthetic stimulation of the vestibular end organs. We have previously demonstrated in rhesus monkeys that a vestibular neurostimulator, based on the Nucleus Freedom cochlear implant, can produce canal-specific electrically evoked eye movements while preserving auditory and vestibular function.

No-go neurons in the cerebellar oculomotor vermis and caudal fastigial nuclei: planning tracking eye movements.

The cerebellar dorsal vermis lobules VI-VII (oculomotor vermis) and its output region (caudal fastigial nuclei, cFN) are involved in tracking eye movements consisting of both smooth-pursuit and saccades, yet, the exact role of these regions in the control of tracking eye movements is still unclear. We compared the neuronal discharge of these cerebellar regions using a memory-based, smooth-pursuit task that distinguishes discharge related to movement preparation and execution from the discharge related to the processing of visual motion signals or their memory. Monkeys were required to pursue (i.

Longitudinal performance of a vestibular prosthesis as assessed by electrically evoked compound action potential recording.

Electrical stimulation of the vestibular end organ with a vestibular prosthesis may provide an effective treatment for vestibular loss if the stimulation remains effective over a significant period of time after implantation of the device. To assess efficacy of electrical stimulation in an animal model, we implanted 3 rhesus monkeys with a vestibular prosthesis based on a cochlear implant. We then recorded vestibular electrically evoked compound action potentials (vECAPs) longitudinally in each of the implanted canals to see how the amplitude of the response changed over time.

An experimental vestibular neural prosthesis: design and preliminary results with rhesus monkeys stimulated with modulated pulses.

A vestibular neural prosthesis was designed on the basis of a cochlear implant for treatment of Meniere's disease and other vestibular disorders. Computer control software was developed to generate patterned pulse stimuli for exploring optimal parameters to activate the vestibular nerve. Two rhesus monkeys were implanted with the prototype vestibular prosthesis and they were behaviorally evaluated post implantation surgery.

Auditory outcomes following implantation and electrical stimulation of the semicircular canals.

We measured auditory brainstem responses (ABRs) in eight Rhesus monkeys after implantation of electrodes in the semicircular canals of one ear, using a multi-channel vestibular prosthesis based on cochlear implant technology. In five animals, click-evoked ABR thresholds in the implanted ear were within 10 dB of thresholds in the non-implanted control ear. Threshold differences in the remaining three animals varied from 18 to 69 dB, indicating mild to severe hearing losses.

Memory-based smooth pursuit: neuronal mechanisms and preliminary results of clinical application.

Using a memory-based smooth-pursuit task, macaque monkeys were trained to pursue (i.e., go) or not pursue (i.

Neuronal activity in the caudal frontal eye fields of monkeys during memory-based smooth pursuit eye movements: comparison with the supplementary eye fields.

Recently, we examined the neuronal substrate of predictive pursuit during memory-based smooth pursuit and found that supplementary eye fields (SEFs) contain signals coding assessment and memory of visual motion direction, decision not-to-pursue ("no-go"), and preparation for pursuit. To determine whether these signals were unique to the SEF, we examined the discharge of 185 task-related neurons in the caudal frontal eye fields (FEFs) in 2 macaques. Visual motion memory and no-go signals were also present in the caudal FEF but compared with those in the SEF, the percentage of neurons coding these signals was significantly lower.

A preformed scleral search coil for measuring mouse eye movements.

Mice are excellent subjects for use of genetic-manipulation techniques to study the basis of pathological and normal physiology and behavior; however behavioral analyses of associated phenotypes is often limited. To improve the accuracy and specificity of repeated measurements of vestibular function, we developed a miniaturized, contact-lens scleral search coil to measure mouse eye movements. We describe the physical attributes and document its functionality by measuring vestibuloocular responses in normal mice.

Memory and decision making in the frontal cortex during visual motion processing for smooth pursuit eye movements.

Cortical motor areas are thought to contribute "higher-order processing," but what that processing might include is unknown. Previous studies of the smooth pursuit-related discharge of supplementary eye field (SEF) neurons have not distinguished activity associated with the preparation for pursuit from discharge related to processing or memory of the target motion signals. Using a memory-based task designed to separate these components, we show that the SEF contains signals coding retinal image-slip-velocity, memory, and assessment of visual motion direction, the decision of whether to pursue, and the preparation for pursuit eye movements.

System identification from multiple short-time-duration signals.

System identification problems often arise where the only modeling records available consist of multiple short-time-duration signals. This motivates the development of a modeling approach that is tailored for this situation. An identification algorithm is presented here for parameter estimation based on minimizing the simulated prediction error, across multiple signals.

Activity changes in monkey superior colliculus during saccade adaptation.

Saccades are eye movements that are used to foveate targets rapidly and accurately. Their amplitude must be adjusted continually, throughout life, to compensate for movement inaccuracies due to maturation, pathology, or aging. One possible locus for such saccade adaptation is the superior colliculus (SC), the relay for cortical commands to the premotor brain stem generator for saccades.

The vestibular-related frontal cortex and its role in smooth-pursuit eye movements and vestibular-pursuit interactions.

In order to see clearly when a target is moving slowly, primates with high acuity foveae use smooth-pursuit and vergence eye movements. The former rotates both eyes in the same direction to track target motion in frontal planes, while the latter rotates left and right eyes in opposite directions to track target motion in depth. Together, these two systems pursue targets precisely and maintain their images on the foveae of both eyes.

Effect of pharmacological inactivation of nucleus reticularis tegmenti pontis on saccadic eye movements in the monkey.

The superior colliculus (SC) provides signals for the generation of saccades via a direct pathway to the brain stem burst generator (BG). In addition, it sends saccade-related activity to the BG indirectly through the cerebellum via a relay in the nucleus reticularis tegmenti pontis (NRTP). Lesions of the oculomotor vermis, lobules VIc and VII, and inactivation of the caudal fastigial nucleus, the cerebellar output nucleus to which it projects, produce saccade dysmetria but have little effect on saccade peak velocity and duration.

Saccade-related, long-lead burst neurons in the monkey rostral pons.

The paramedian pontine reticular formation contains the premotoneuronal cell groups that constitute the saccadic burst generator and control saccadic eye movements. Despite years of study and numerous investigations, the rostral portion of this area has received comparatively little attention, particularly the cell type known as long-lead burst neurons (LLBNs). Several hypotheses about the functional role of LLBNs in saccade generation have been proposed, although there is little information with which to assess them.

Evidence for wide range of time scales in oculomotor plant dynamics: implications for models of eye-movement control.

Oculomotor-plant dynamics are not well characterised, despite their importance for modelling eye-movement control. We analysed the time course of the globe's return after horizontal displacements in three rhesus monkeys lightly anaesthetised with ketamine. The eye-position traces were well fitted by a sum of four exponentials (time constants 0.

Pursuit-related neurons in the supplementary eye fields: discharge during pursuit and passive whole body rotation.

The primate frontal cortex contains two areas related to smooth-pursuit: the frontal eye fields (FEFs) and supplementary eye fields (SEFs). To distinguish the specific role of the SEFs in pursuit, we examined discharge of a total of 89 pursuit-related neurons that showed consistent modulation when head-stabilized Japanese monkeys pursued a spot moving sinusoidally in fronto-parallel planes and/or in depth and with or without passive whole body rotation. During smooth-pursuit at different frequencies, 43% of the neurons tested (17/40) exhibited discharge amplitude of modulation linearly correlated with eye velocity.

Neurons in the caudal frontal eye fields of monkeys signal three-dimensional tracking.

To maintain optimal clarity of objects moving in three dimensions, precise coordination of binocular eye movements is required in frontal-eyed primates. Caudal parts of the frontal eye fields (FEFs) contain smooth pursuit neurons and the discharge of the majority of them is related to vergence eye movements as well. However, whether or not those pursuit neurons carry true binocular signals has not been tested critically.

Linear regression of eye velocity on eye position and head velocity suggests a common oculomotor neural integrator.

The oculomotor system produces eye-position signals during fixations and head movements by integrating velocity-coded saccadic and vestibular inputs. A previous analysis of nucleus prepositus hypoglossi (nph) lesions in monkeys found that the integration time constant for maintaining fixations decreased, while that for the vestibulo-ocular reflex (VOR) did not. On this basis, it was concluded that saccadic inputs are integrated by the nph, but that the vestibular inputs are integrated elsewhere.

Evidence against a moving hill in the superior colliculus during saccadic eye movements in the monkey.

Saccadic eye movements of different sizes and directions are represented in an orderly topographic map across the intermediate and deep layers of the superior colliculus (SC), where large saccades are encoded caudally and small saccades rostrally. Based on experiments in the cat, it has been suggested that saccades are initiated by a hill of activity at the caudal site appropriate for a particular saccade. As the saccade evolves and the remaining distance to the target, the motor error, decreases, the hill moves rostrally across successive SC sites responsible for saccades of increasingly smaller amplitudes.

Evidence that the superior colliculus participates in the feedback control of saccadic eye movements.

There is general agreement that saccades are guided to their targets by means of a motor error signal, which is produced by a local feedback circuit that calculates the difference between desired saccadic amplitude and an internal copy of actual saccadic amplitude. Although the superior colliculus (SC) is thought to provide the desired saccadic amplitude signal, it is unclear whether the SC resides in the feedback loop. To test this possibility, we injected muscimol into the brain stem region containing omnipause neurons (OPNs) to slow saccades and then determined whether the firing of neurons at different sites in the SC was altered.