Shawn D. Newlands

Multimodal Coding of Three-Dimensional Rotation and Translation in Area MSTd: Comparison of Visual and Vestibular Selectivity

Recent studies have shown that most neurons in the dorsal medial superior temporal area (MSTd) signal the direction of self-translation (i.e., heading) in response to both optic flow and inertial motion. Much less is currently known about the response properties of MSTd neurons during self-rotation. We have characterized the three-dimensional tuning of MSTd neurons while monkeys passively fixated a central, head-fixed target. Rotational stimuli were either presented using a motion platform or simulated visually using optic flow. Nearly all MSTd cells were significantly tuned for the direction of rotation in the absence of optic flow, with more neurons preferring roll than pitch or yaw rotations. The preferred rotation axis in response to optic flow was generally the opposite of that during physical rotation. This result differs sharply from our findings for translational motion, where approximately half of MSTd neurons have congruent visual and vestibular preferences. By testing a subset of neurons with combined visual and vestibular stimulation, we also show that the contributions of visual and vestibular cues to MSTd responses depend on the relative reliabilities of the two stimulus modalities. Previous studies of MSTd responses to motion in darkness have assumed a vestibular origin for the activity observed. We have directly verified this assumption by recording from MSTd neurons after bilateral labyrinthectomy. Selectivity for physical rotation and translation stimuli was eliminated after labyrinthectomy, whereas selectivity to optic flow was unaffected. Overall, the lack of MSTd neurons with congruent rotation tuning for visual and vestibular stimuli suggests that MSTd does not integrate these signals to produce a robust perception of self-rotation. Vestibular rotation signals in MSTd may instead be used to compensate for the confounding effects of rotatory head movements on optic flow.

Central projections of the saccular and utricular nerves in macaques

The central projections of the utricular and saccular nerve in macaques were examined using transganglionic labeling of vestibular afferent neurons. In these experiments, biotinylated dextran amine was injected directly into the saccular or utricular neuroepithelium of fascicularis (Macaca fascicularis) or rhesus (Macaca mulatta) monkeys. Two to 5 weeks later, the animals were killed and the peripheral vestibular sensory organs, brainstem, and cerebellum were collected for analysis. The principal brainstem areas of saccular nerve termination were lateral, particularly the spinal vestibular nucleus, the lateral portion of the superior vestibular nucleus, ventral nucleus y, the external cuneate nucleus, and cell group l. The principal cerebellar projection was to the uvula with a less dense projection to the nodulus. Principle brainstem areas of termination of the utricular nerve were the lateral/dorsal medial vestibular nucleus, ventral and lateral portions of the superior vestibular nucleus, and rostral portion of the spinal vestibular nucleus. In the cerebellum, a strong projection was observed to the nodulus and weak projections were present in the flocculus, ventral paraflocculus, bilateral fastigial nuclei, and uvula. Although there is extensive overlap of saccular and utricular projections, saccular inputs to the lateral portions of the vestibular nuclear complex suggest that saccular afferents contribute to the vestibulospinal system. In contrast, the utricular nerve projects more rostrally into areas of known concentration of vestibulo‐ocular related cells. Although sparse, the projections of the utricle to the flocculus/ventral paraflocculus suggest a potential convergence with floccular projection inputs from the vestibular brainstem that have been implicated in vestibulo‐ocular motor learning. J. Comp. Neurol. 466:31–47, 2003.

Compensation of horizontal canal related activity in the medial vestibular nucleus following unilateral labyrinth ablation in the decerebrate gerbil

The spontaneous activity and dynamic responses to sinusoidal horizontal head angular acceleration of type II horizontal semicircular canal related neurons in the medial vestibular nucleus (MVN) were recorded bilaterally in decerebrate Mongolian gerbils (Meriones unguiculatus) under three experimental conditions: normal labyrinths intact, acutely following unilateral labyrinthine lesion, and four to seven weeks following labyrinthine lesion. The number of type II neurons detected contralateral to the lesion was greatly reduced both in the acutely hemilabyrinthectomized animals and following compensation. The gain of the responses was depressed bilaterally acutely following the lesion. A greater reduction in response gain was noted in cells contralateral to the lesion. The gain of the contralateral type II responses increased with time such that in the compensated animal bilaterally symmetric gains were recorded. While the significant changes which occur in the gain of type II neurons with recovery from peripheral vestibular lesions can largely be attributed to type I neurons on the other side of the midline, changes in type I neurons were not entirely reflected in the type II population. The spontaneous activity of type II neurons did not undergo any significant changes following the labyrinthine lesion. We present a model utilizing the dynamic responses to estimate the functional recovery of commissural connections in compensated animals. The overall gain of the contralateral type I to ipsilateral type I commissural polysynaptic pathway appears to improve, while the efficacy in the reverse direction remains depressed, suggesting that modifications in commissural connections, particularly involving the type II to type I connections within the MVN on the injured side, mediate aspects of behavioral recovery.SummaryThe spontaneous activity and dynamic responses to two frequencies (1.3 and 0.13 Hz) of sinusoidal angular horizontal head acceleration of type I neurons in the medial vestibular nucleus were recorded bilaterally in decerebrate Mongolian gerbils (Meriones unguiculatus) under three experimental conditions; normal labyrinth intact, acutely following unilateral labyrinthine lesion, and four to seven weeks following labyrinthine lesion. The mean spontaneous activity and number of detected type I neurons decreased immediately ipsilateral to the lesion but recovered significantly with time. In contrast, spontaneous activity on the contralateral side increased during compensation following hemilabyrinthectomy. The mean response gains at both frequencies of head oscillation were depressed bilaterally and asymmetrically acutely following the lesion such that the response gain of cells on the intact side exceeded that of the neurons recorded on the injured side. After compensation the number of detected type I neurons on the side ipsilateral to the injury increased but remained below normal levels. The mean gains remained depressed but became symmetric with compensation as a result of improvement in the response of ipsilateral neurons. The phase of responses were significantly advanced in the compensated animals. Although response gain is not fully restored, the linearity of the dynamic modulation in compensated animals is improved as evidenced by a continuous modulation of the increased spontaneous activity of neurons contralateral to the hemilabyrinthectomy. It is proposed that this effect is related to the concurrent improvement in the linearity of the horizontal vestibulo-ocular response. Electrical cathodal polarization of the vestibular nerve ipsilateral to the ablated labyrinth was utilized to investigate the relationship between recovery of spontaneous activity and dynamic function. Acutely following hemilabyrinthectomy, cathodal polarization restored activity in second-order type I neurons to near normal levels but their response gain to head rotation remained depressed. Similar galvanic stimulation in compensated animals also elevated ipsilateral spontaneous activity. As in the acute preparation, such stimulation did not modify the response gain or phase. Thus, the improvement in response of type I neurons in the compensated gerbil was not a direct consequence of restoration of spontaneous activity on the side of the injury.

Sensory Convergence Solves a Motion Ambiguity Problem

Our inner ear is equipped with a set of linear accelerometers, the otolith organs, that sense the inertial accelerations experienced during self-motion. However, as Einstein pointed out nearly a century ago, this signal would by itself be insufficient to detect our real movement, because gravity, another form of linear acceleration, and self-motion are sensed identically by otolith afferents. To deal with this ambiguity, it was proposed that neural populations in the pons and midline cerebellum compute an independent, internal estimate of gravity using signals arising from the vestibular rotation sensors, the semicircular canals. This hypothesis, regarding a causal relationship between firing rates and postulated sensory contributions to inertial motion estimation, has been directly tested here by recording neural activities before and after inactivation of the semicircular canals. We show that, unlike cells in normal animals, the gravity component of neural responses was nearly absent in canal-inactivated animals. We conclude that, through integration of temporally matched, multimodal information, neurons derive the mathematical signals predicted by the equations describing the physics of the outside world.

Central projections of the vestibular nerve: a review and single fiber study in the Mongolian gerbil

The primary purpose of this article is to review the anatomy of central projections of the vestibular nerve in amniotes. We also report primary data regarding the central projections of individual horseradish peroxidase (HRP)-filled afferents innervating the saccular macula, horizontal semicircular canal ampulla, and anterior semicircular canal ampulla of the gerbil. In total, 52 characterized primary vestibular afferent axons were intraaxonally injected with HRP and traced centrally to terminations. Lateral and anterior canal afferents projected most heavily to the medial and superior vestibular nuclei. Saccular afferents projected strongly to the spinal vestibular nucleus, weakly to other vestibular nuclei, to the interstitial nucleus of the eighth nerve, the cochlear nuclei, the external cuneate nucleus, and nucleus y. The current findings reinforce the preponderance of literature. The central distribution of vestibular afferents is not homogeneous. We review the distribution of primary afferent terminations described for a variety of mammalian and avian species. The tremendous overlap of the distributions of terminals from the specific vestibular nerve branches with one another and with other sensory inputs provides a rich environment for sensory integration.

Endoscopic treatment of juvenile nasopharyngeal angiofibroma

Traditional treatment of juvenile nasopharyngeal angiofibromas (JNAs) has included open surgical approaches for the majority of tumors. At the University of Washington Medical Center (UWMC), endoscopic techniques have been used for the removal of some small JNAs. This report describes the institutional experience in treating these tumors. The medical records of 15 patients at UWMC treated over a 15-year period for JNA were reviewed. Three patients were treated only by an endoscopic approach, and one patient had a combined endoscopic and open procedure. All three of the patients treated only by the endoscopic approach were disease free with a minimum of 24 months follow up. The one patient treated with a combined endoscopic and open approach had recurrence of disease. Endoscopic removal after embolization effectively treated three patients with early stage JNAs. Indications for this procedure are discussed.

Implantation of the Semicircular Canals with Preservation of Hearing and Rotational Sensitivity: a vestibular neurostimulator suitable for clinical research

Hypothesis It is possible to implant a stimulating electrode array in the semicircular canals without damaging rotational sensitivity or hearing. The electrodes will evoke robust and precisely controlled eye movements. Background A number of groups are attempting to develop a neural prosthesis to ameliorate abnormal vestibular function. Animal studies demonstrate that electrodes near the canal ampullae can produce electrically evoked eye movements. The target condition of these studies is typically bilateral vestibular hypofunction. Such a device could potentially be more widely useful clinically and would have a simpler roadmap to regulatory approval if it produced minimal or no damage to the native vestibular and auditory systems. Methods An electrode array was designed for insertion into the bony semicircular canal adjacent to the membranous canal. It was designed to be sufficiently narrow so as to not compress the membranous canal. The arrays were manufactured by Cochlear, Ltd., and linked to a Nucleus Freedom receiver/stimulator. Seven behaviorally trained rhesus macaques had arrays placed in 2 semicircular canals using a transmastoid approach and “soft surgical” procedures borrowed from Hybrid cochlear implant surgery. Postoperative vestibulo-ocular reflex was measured in a rotary chair. Click-evoked auditory brainstem responses were also measured in the 7 animals using the contralateral ear as a control. Results All animals had minimal postoperative vestibular signs and were eating within hours of surgery. Of 6 animals tested, all had normal postoperative sinusoidal gain. Of 7 animals, 6 had symmetric postoperative velocity step responses toward and away from the implanted ear. The 1 animal with significantly asymmetric velocity step responses also had a significant sensorineural hearing loss. One control animal that underwent canal plugging had substantial loss of the velocity step response toward the canal-plugged ear. In 5 animals, intraoperative electrically evoked vestibular compound action potential recordings facilitated electrode placement. Postoperatively, electrically evoked eye movements were obtained from electrodes associated with an electrically evoked vestibular compound action potential wave form. Hearing was largely preserved in 6 animals and lost in 1 animal. Conclusion It is possible to implant the vestibular system with prosthetic stimulating electrodes without loss of rotational sensitivity or hearing. Because electrically evoked eye movements can be reliably obtained with the assistance of intraoperative electrophysiology, it is appropriate to consider treatment of a variety of vestibular disorders using prosthetic electrical stimulation. Based on these findings, and others, a feasibility study for the treatment of human subjects with disabling Ménière’s disease has begun.

Central projections of the utricular nerve in the gerbil.

The central projections of primary afferent fibers in the utricular nerve, which convey linear head acceleration signals to neurons in the brainstem and cerebellum, are not completely defined. The purpose of this investigation was twofold: 1) to define the central projections of the gerbil utricular afferents by injecting horseradish peroxidase (HRP) and biotinylated dextran amine (BDA) into the utricular macula; and 2) to investigate the projections of individual utricular afferents by injecting HRP intracellularly into functionally identified utricular neurons. We found that utricular afferents in the gerbil projected to all divisions of the vestibular nuclear complex, except the dorsal lateral vestibular nucleus. In addition, terminals were observed in the interstitial nucleus of the eighth nerve, nucleus Y, external cuneate nucleus, and lobules I, IV, V, IX, and X of the cerebellar vermis. No projections appeared in the flocculus or paraflocculus. Fibers traversed the medial and intermediate cerebellar nuclei, but terminals appeared only occasionally. Individual utricular afferents collateralize extensively, projecting to much of the brainstem area innervated by the whole of the utricular nerve. This study did not produce complete filling of individual afferent collateral projections into the cerebellar cortex. J. Comp. Neurol. 452:11–23, 2002.

Impact of radiotherapy on laryngeal cancer survival: a population-based study of 13,808 US patients.

Radiotherapy with its advantage of organ preservation has been used to treat laryngeal cancer (LC) for several decades. However, the impact of radiation on overall survival (OS) in a large population‐based study has not been evaluated to date.

Distribution and time course of hair cell regeneration in the pigeon utricle

Vestibular and cochlear regeneration following ototoxic insult from aminoglycoside antibiotics has been well documented, particularly in birds. In the present study, intraotic application of a 2 mg streptomycin paste was used to achieve complete vestibular hair cell destruction in pigeons (Columba livia) while preserving regenerative ability. Scanning electron microscopy was used to quantify hair cell density longitudinally during regeneration in three different utricular macula locations, including the striola, central and peripheral regions. The utricular epithelium was void of stereocilia (indicating hair cell loss) at 4 days after intraotic treatment with streptomycin. At 2 weeks the stereocilia began to appear randomly and mostly in an immature form. However, when present most kinocilia were polarized toward the developing striola. Initially, regeneration occurred more rapidly in the central and peripheral regions of the utricle as compared to the striola. As regeneration proceeded from 2 to 12 weeks, hair cell density in the striola region equaled the density noted in the central and peripheral regions. At 24 weeks, hair cell density of the central and peripheral regions was equal to normal values, however the striola region had a slightly greater hair cell density than that observed for normal animals.