Superior Canal Dehiscence Syndrome: Relating Clinical Findings With Vestibular Neural Responses From a Guinea Pig Model.

HYPOTHESIS: In superior canal dehiscence (SCD), fluid displacement of the endolymph activates type I vestibular hair cells in the crista of the affected canal and thus irregular superior canal (SC) neurons in Scarpa's ganglion, which provides the neurophysiological basis for the clinical presentation of SCD. BACKGROUND: Patients with SCD display sound- and vibration-induced vertigo/nystagmus and increased amplitudes of vestibular evoked myogenic potentials. METHODS: Extracellular recordings from n = 25 primary vestibular neurons of 16 female guinea pigs were analyzed. We recorded from the same vestibular neuron before, during and after creating the dehiscence and after closing the dehiscence. Neurobiotin labeling was employed in n = 11 neurons. RESULTS: After SCD, previously unresponsive irregular SC neurons displayed a stimulus-locked increase in discharge during application of air-conducted sound (ACS) or bone-conducted vibration (BCV) for a broad range of frequencies (ACS: 200-4000 Hz; BCV: 500-1500 Hz). This typical response was only observed for irregular SC neurons (n = 19), but not regular SC neurons, or irregular/regular horizontal canal neurons (n = 2 each), and was abolished after closing the dehiscence. Eleven irregular SC neurons responsive to ACS and/or BCV were traced back to calyx synapses in the central crista of the affected superior canal by neurobiotin labeling. CONCLUSIONS: Stimulus-locked activation of irregular SC neurons by ACS and BCV is the neurophysiological basis for sound- and vibration-induced vertigo/nystagmus and increased VEMP amplitudes in SCD. The results of the present study help to improve vestibular diagnostics in patients with suspected SCD.

Phase-locking of irregular guinea pig primary vestibular afferents to high frequency (>250 Hz) sound and vibration.

Phase-locking of cochlear neurons to sound has been of great value in understanding cochlear transduction. Phase-locking has also been reported previously in irregular vestibular afferents, but detailed information about it is sparse. We measured the phase-locking of guinea pig irregular otolithic neurons and canal neurons (after a semicircular canal dehiscence allowed them to respond) to both sound and vibration stimuli. Irregular vestibular afferents from both otoliths and canals have a range of preferred phase angles which systematically increase as frequency is increased from 250 Hz to above 1000 Hz. Surprisingly vestibular afferents show more precise phase-locking than comparable auditory afferents as reported by Palmer and Russell (1986), and they do so up to higher frequencies. This high precision implies a very sharp, fast threshold for evoking an action potential with minimal variability, and so has implications for the current controversy about hair-cell-afferent transmission in the vestibular system. Following recent evidence, we suggest that potassium in the unique type I-calyx synapse may be a major factor in generating this very precise phase-locking.

The response of guinea pig primary utricular and saccular irregular neurons to bone-conducted vibration (BCV) and air-conducted sound (ACS).

UNLABELLED: This study sought to characterize the response of mammalian primary otolithic neurons to sound and vibration by measuring the resting discharge rates, thresholds for increases in firing rate and supra-threshold sensitivity functions of guinea pig single primary utricular and saccular afferents. Neurons with irregular resting discharge were activated in response to bone conducted vibration (BCV) and air conducted sound (ACS) for frequencies between 100 Hz and 3000 Hz. The location of neurons was verified by labelling with neurobiotin. Many afferents from both maculae have very low or zero resting discharge, with saccular afferents having on average, higher resting rates than utricular afferents. Most irregular utricular and saccular afferents can be evoked by both BCV and ACS. For BCV stimulation: utricular and saccular neurons show similar low thresholds for increased firing rate (around 0.02 g on average) for frequencies from 100 Hz to 750 Hz. There is a steep increase in rate change threshold for BCV frequencies above 750 Hz. The suprathreshold sensitivity functions for BCV were similar for both utricular and saccular neurons, with, at low frequencies, very steep increases in firing rate as intensity increased. For ACS stimulation: utricular and saccular neurons can be activated by high intensity stimuli for frequencies from 250 Hz to 3000 Hz with similar flattened U-shaped tuning curves with lowest thresholds for frequencies around 1000-2000 Hz. The average ACS thresholds for saccular afferents across these frequencies is about 15-20 dB lower than for utricular neurons. The suprathreshold sensitivity functions for ACS were similar for both utricular and saccular neurons. Both utricular and saccular afferents showed phase-locking to BCV and ACS, extending up to frequencies of at least around 1500 Hz for BCV and 3000 Hz for ACS. Phase-locking at low frequencies (e.g. 100 Hz) imposes a limit on the neural firing rate evoked by the stimulus since the neurons usually fire one spike per cycle of the stimulus. CONCLUSION: These results are in accord with the hypothesis put forward by Young et al. (1977) that each individual cycle of the waveform, either BCV or ACS, is the effective stimulus to the receptor hair cells on either macula. We suggest that each cycle of the BCV or ACS stimulus causes fluid displacement which deflects the short, stiff, hair bundles of type I receptors at the striola and so triggers the phase-locked neural response of primary otolithic afferents.

Cross-species comparison of anticipatory and stimulus-driven neck muscle activity well before saccadic gaze shifts in humans and nonhuman primates.

Recent studies have described a phenomenon wherein the onset of a peripheral visual stimulus elicits short-latency (<100 ms) stimulus-locked recruitment (SLR) of neck muscles in nonhuman primates (NHPs), well before any saccadic gaze shift. The SLR is thought to arise from visual responses within the intermediate layers of the superior colliculus (SCi), hence neck muscle recordings may reflect presaccadic activity within the SCi, even in humans. We obtained bilateral intramuscular recordings from splenius capitis (SPL, an ipsilateral head-turning muscle) from 28 human subjects performing leftward or rightward visually guided eye-head gaze shifts. Evidence of an SLR was obtained in 16/55 (29%) of samples; we also observed examples where the SLR was present only unilaterally. We compared these human results with those recorded from a sample of eight NHPs from which recordings of both SPL and deeper suboccipital muscles were available. Using the same criteria, evidence of an SLR was obtained in 8/14 (57%) of SPL recordings, but in 26/29 (90%) of recordings from suboccipital muscles. Thus, both species-specific and muscle-specific factors contribute to the low SLR prevalence in human SPL. Regardless of the presence of the SLR, neck muscle activity in both human SPL and in NHPs became predictive of the reaction time of the ensuing saccade gaze shift ∼70 ms after target appearance; such pregaze recruitment likely reflects developing SCi activity, even if the tectoreticulospinal pathway does not reliably relay visually related activity to SPL in humans.

Loud preimpact tones reduce the cervical multifidus muscle response during rear-end collisions: a potential method for reducing whiplash injuries.

BACKGROUND CONTEXT: Neck muscle responses after unexpected rear-end collisions consist of a stereotypical combination of postural and startle responses. Prior work using surface electromyography (EMG) has shown that the superficial neck muscle responses can be attenuated when a loud tone (105 dB) is presented 250 milliseconds before impact, but the accompanying response of the deeper multifidus muscles remains unknown. Quantifying this response in multifidus is important because this muscle attaches directly to the cervical facet capsule and can potentially increase the strain in the capsule during an impact and contribute to whiplash injury. PURPOSE: To investigate if a loud preimpact tone decreases the cervical multifidus muscle response during rear-end perturbations. STUDY DESIGN: After approval by the University Clinical Ethics Review Board, human volunteers experienced a series of three whiplash-like perturbations. PATIENT SAMPLE: Twelve subjects with no history of neurologic disorders or whiplash injury were recruited to participate in this experiment. OUTCOME MEASURES: Bilateral indwelling EMG of multifidus at the C4 and C6 levels, surface EMG of sternocleidomastoid (SCM) and C4 paraspinals (PARAs), and kinematics of the head/neck were measured. METHODS: Subjects experienced three whiplash-like perturbations (peak acceleration of 19.5 m/s(2)) preceded by either no tone or a loud tone (105 dB) presented 250 milliseconds before sled acceleration onset. RESULTS: The loud tone decreased the muscle activity of C6 multifidus (42%) and C4 PARAs (30%), but did not affect the C4 multifidus or SCM activity. Peak head kinematic responses (extension angle: 6%, retraction: 9%, linear forward acceleration: 9%, and angular acceleration in extension: 13%) were also decreased by the loud preimpact tone. CONCLUSIONS: The attenuation of peak C6 multifidus activity and head kinematic responses suggests that a loud preimpact tone may reduce the strain in the cervical facet capsule, which may reduce the risk of whiplash injury during rear-end collisions.

Dynamic and opposing adjustment of movement cancellation and generation in an oculomotor countermanding task.

Adaptive adjustments of strategies help optimize behavior in a dynamic and uncertain world. Previous studies in the countermanding (or stop-signal) paradigm have detailed how reaction times (RTs) change with trial sequence, demonstrating adaptive control of movement generation. Comparatively little is known about the adaptive control of movement cancellation in the countermanding task, mainly because movement cancellation implies the absence of an outcome and estimates of movement cancellation require hundreds of trials. Here, we exploit a within-trial proxy of movement cancellation based on recordings of neck muscle activity while human subjects attempted to cancel large eye-head gaze shifts. On a subset of successfully cancelled trials where gaze remains stable, small head-only movements to the target are actively braked by a pulse of antagonist neck muscle activity. The timing of such antagonist muscle recruitment relative to the stop signal, termed the "antagonist latency," tended to decrease or increase after trials with or without a stop-signal, respectively. Over multiple time scales, fluctuations in the antagonist latency tended to be the mirror opposite of those occurring contemporaneously with RTs. These results provide new insights into the adaptive control of movement cancellation at an unprecedented resolution, suggesting it can be as prone to dynamic adjustment as movement generation. Adaptive control in the countermanding task appears to be governed by a dynamic balance between movement cancellation and generation: shifting the balance in favor of movement cancellation slows movement generation, whereas shifting the balance in favor of movement generation slows movement cancellation.

Validation of a within-trial measure of the oculomotor stop process.

The countermanding (or stop signal) task requires subjects try to withhold a planned movement upon the infrequent presentation of a stop signal. We have previously proposed a within-trial measure of movement cancellation based on neck muscle recruitment during the cancellation of eye-head gaze shifts. Here, we examined such activity after either a bright or dim stop signal, a manipulation known to prolong the stop signal reaction time (SSRT). Regardless of stop signal intensity, subjects generated an appreciable number of head-only errors during successfully cancelled gaze shifts (compensatory eye-in-head motion ensured gaze stability), wherein subtle head motion toward a peripheral target was ultimately stopped by a braking pulse of antagonist neck muscle activity. Both the SSRT and timing of antagonist muscle recruitment relative to the stop signal increased for dim stop signals and decreased for longer stop signal delays. Moreover, we observed substantial variation in the distribution of antagonist muscle recruitment latencies across our sample. The magnitude and variance of the SSRTs and antagonist muscle recruitment latencies correlated positively across subjects, as did the within-subject changes across bright and dim stop signals. Finally, we fitted our behavioral data with a race model architecture that incorporated a lower threshold for initiating head movements. This model allowed us to estimate the efferent delay between the completion of a central stop process and the recruitment of antagonist neck muscles; the estimated efferent delay remained consistent within subjects across stop signal intensity. Overall, these results are consistent with the hypothesis that neck muscle recruitment during a specific subset of cancelled trials provides a peripheral expression of oculomotor cancellation on a single trial. In the discussion, we briefly speculate on the potential value of this measure for research in basic or clinical domains and consider current issues that limit more widespread use.

Greater benefits of multisensory integration during complex sensorimotor transformations.

Multisensory integration enables rapid and accurate behavior. To orient in space, sensory information registered initially in different reference frames has to be integrated with the current postural information to produce an appropriate motor response. In some postures, multisensory integration requires convergence of sensory evidence across hemispheres, which would presumably lessen or hinder integration. Here, we examined orienting gaze shifts in humans to visual, tactile, or visuotactile stimuli when the hands were either in a default uncrossed posture or a crossed posture requiring convergence across hemispheres. Surprisingly, we observed the greatest benefits of multisensory integration in the crossed posture, as indexed by reaction time (RT) decreases. Moreover, such shortening of RTs to multisensory stimuli did not come at the cost of increased error propensity. To explain these results, we propose that two accepted principles of multisensory integration, the spatial principle and inverse effectiveness, dynamically interact to aid the rapid and accurate resolution of complex sensorimotor transformations. First, early mutual inhibition of initial visual and tactile responses registered in different hemispheres reduces error propensity. Second, inverse effectiveness in the integration of the weakened visual response with the remapped tactile representation expedites the generation of the correct motor response. Our results imply that the concept of inverse effectiveness, which is usually associated with external stimulus properties, might extend to internal spatial representations that are more complex given certain body postures.

Ultrasound-guided insertion of intramuscular electrodes into suboccipital muscles in the non-human primate.

The head-neck system is highly complex from a biomechanical and musculoskeletal perspective. Currently, the options for recording the recruitment of deep neck muscles in experimental animals are limited to chronic approaches requiring permanent implantation of electromyographic electrodes. Here, we describe a method for targeting deep muscles of the dorsal neck in non-human primates with intramuscular electrodes that are inserted acutely. Electrode insertion is guided by ultrasonography, which is necessary to ensure placement of the electrode in the target muscle. To confirm electrode placement, we delivered threshold electrical stimulation through the intramuscular electrode and visualized the muscle twitch. In one animal, we also compared recordings obtained from acutely- and chronically-implanted electrodes. This method increases the options for accessing deep neck muscles, and hence could be used in experiments for which the invasive surgery inherent to a chronic implant is not appropriate. This method could also be extended to the injection of pharmacological agents or anatomical tracers into specific neck muscles.

Neck muscle responses evoked by transcranial magnetic stimulation of the human frontal eye fields.

Transcranial magnetic stimulation (TMS) provides a non-invasive means of investigating brain function. Whereas TMS of the human frontal eye fields (FEFs) does not induce saccades, electrical stimulation of the monkey FEF evokes eye-head gaze shifts, with neck muscle responses evoked at stimulation levels insufficient to evoke a saccade. These animal results motivated us to examine whether TMS of the FEF (TMS-FEF) in humans evokes a neck muscle response. Subjects performed memory-guided saccades to the left or right while TMS (two pulses at 20 Hz) was delivered on 30% of trials to the left FEF coincident with saccade instruction. As reported previously, TMS-FEF decreased contralateral saccade reaction times. We simultaneously recorded the activity of splenius capitis (SPL) (an ipsilateral head turner). TMS-FEF evoked a lateralized increase in the activity of the right SPL but not the left SPL, consistent with the recruitment of a contralateral head-turning synergy. In some subjects, the evoked neck muscle response was time-locked to stimulation, whereas in others the evoked response occurred around the time of the saccade. Importantly, evoked responses were greater when TMS was applied to the FEF engaged in contralateral saccade preparation, with even greater evoked responses preceding shorter latency saccades. These results provide new insights into both the nature of TMS and the human oculomotor system, demonstrating that TMS-FEF engages brainstem oculomotor circuits in a manner consistent with a general role in eye-head gaze orienting. Our results also suggest that pairing neck muscle recordings with TMS-FEF provides a novel way of assaying the covert preparation of oculomotor plans.

A within-trial measure of the stop signal reaction time in a head-unrestrained oculomotor countermanding task.

The countermanding (or stop-signal) task, which requires the cancellation of an impending response on the infrequent presentation of a stop signal, enables study of the contextual control of movement generation and suppression. Here we present a novel and empirical measure of the time needed to cancel an impending gaze shift by recording neck muscle activity during a head-unrestrained oculomotor countermanding paradigm. On a subset of stop signal trials, subjects generated small head movements toward a target even though gaze remained stable due to a compensatory vestibular-ocular reflex. On such trials, we observed a burst of antagonist neck muscle activity during the small head-only error. Such antagonist neck muscle activity served as an active braking pulse as its magnitude scaled with the kinematics of the head-only error. This activity was selective for trials in which the head was arrested in mid-flight and did not appear on trials without a stop signal, on noncancelled stop signal trials when the gaze shift was completed, or on stop signal trials without head motion. Importantly, the timing of this antagonist activity related best to the onset of the stop signal (lagging it by ∼180 ms), and strongly correlated with behavioral estimates of the time needed to cancel a movement (the stop signal reaction time). These results are consistent with the notion that such selective antagonist neck muscle activity arises as a peripheral expression of the oculomotor stop process that successfully cancelled the gaze shift. Studying movement cancellation within nested systems like the head-unrestrained gaze shifting system offers a unique opportunity for investigating underlying neural mechanisms as the overall goal (i.e., to cancel a gaze shift) can be achieved despite motion of other components; on such individual trials, the oculomotor stop process is expressed as an active braking pulse.

On the relation between ocular torsion and visual perception of line orientation.

A recent study by Poljac et al. [Poljac, E., Lankheet, M. J. M., & van den Berg, A. (2005). Perceptual compensation for eye torsion. Vision Research, 45(4), 485-496] concluded that there was complete perceptual compensation for ocular torsion, although they did not directly measure ocular torsion. Using a similar eccentric-gaze paradigm to induce changes in torsion, which were directly measured, we found inconsistent torsional eye movements at eccentric fixation, and also failed to detect a significant relationship between ocular torsion and the perception of line orientation. We then used a stimulus known to induce large changes in ocular torsion: on-centre yaw rotation. This stimulus induced a consistent change in the torsional position of the eye which positively correlated to subjects' visual perception of horizontal.

Cognitive demand affects the gain of the torsional optokinetic response.

Cognitive tasks such as mental arithmetic and fixation of imagined targets are known to affect vestibular nystagmus. Here we show that another cognitive task-subject's active control of the rotation of a single moving visual line in an otherwise darkened room-influences the gain of the torsional optokinetic response to that single moving visual line.

Changes in ocular torsion position produced by a single visual line rotating around the line of sight--visual "entrainment" of ocular torsion.

A large- or full-field visual stimulus slowly rotating around the naso-occipital axis of an observer causes both eyes to tort, and many of the factors controlling this optokinetic torsional response have been identified. The present study reports that a single line rotating about the line of sight can cause both eyes to tort in the same direction as the stimulus but with a low gain. We have used the term 'entrainment' to describe this torsional response. This paper reports some of the factors associated with entrainment. Video measures of 3-d eye position were recorded while the subject made settings of a simple visual line to subjective visual horizontal (SVH) and vertical (SVV) using the standard method-of-adjustment paradigm. The visual line was composed of 11 light-emitting diodes; the line subtended a visual angle of 19 degrees, and moved at a constant speed of 4.8 degrees /s. Settings were made in an otherwise darkened room, and also in the light. Subjects were required to maintain fixation of the central LED while making settings from starting positions 10 or 20 degrees either side of gravitational horizontal or vertical. We show that entrainment of ocular torsion by the single moving visual line is low in gain but a reliable and repeatable effect and that (1) there are considerable individual differences between subjects but within-subject consistency, (2) all subjects show larger and more consistent torsional entrainment for lines moving to SVH than lines moving to SVV, (3) the strongest entrainment generally occurs within about 10 degrees of the target position, and (4) entrainment is also present in the light, though with slightly reduced gain.