Vestibular, locomotor, and vestibulo-autonomic research: 50 years of collaboration with Bernard Cohen

My collaboration on the vestibulo-ocular reflex with Bernard Cohen began in 1972. Until 2017, this collaboration included studies of saccades, quick phases of nystagmus, the introduction of the concept of velocity storage, the relationship of velocity storage to motion sickness, primate and human locomotion, and studies of vasovagal syncope. These studies have elucidated the functioning of the vestibuloocular reflex, the locomotor system, the functioning of the vestibulo-sympathetic reflex, and how blood pressure and heart rate are controlled by the vestibular system. Although it is virtually impossible to review all the contributions in detail in a single paper, this article traces a thread of modeling that I brought to the collaboration, which, coupled with Bernie Cohen’s expertise in vestibular and sensory-motor physiology and clinical insights, has broadened our understanding of the role of the vestibular system in a wide range of sensory-motor systems. Specifically, the paper traces how the concept of a relaxation oscillator was used to model the slow and rapid phases of ocular nystagmus. Velocity information that drives the slow compensatory eye movements was used to activate the saccadic system that resets the eyes, giving rise to the relaxation oscillator properties and simulated nystagmus as well as predicting the types of unit activity that generated saccades and nystagmic beats. The slow compensatory component of ocular nystagmus was studied in depth and gave rise to the idea that there was a velocity storage mechanism or integrator that not only is a focus for visual-vestibular interaction but also codes spatial orientation relative to gravity as referenced by the otoliths. Velocity storage also contributes to motion sickness when there are visual-vestibular as well as orientation mismatches in velocity storage. The relaxation oscillator concept was subsequently used to model the stance and swing phases of locomotion, how this impacted head and eye movements to maintain gaze in the direction of body motion, and how these were affected by Parkinson’s disease. Finally, the relaxation oscillator was used to elucidate the functional form of the systolic and diastolic beats during blood pressure and how vasovagal syncope might be initiated by cerebellar-vestibular malfunction.

Altered visual population receptive fields in human albinism

1AbstractAlbinism is a congenital disorder where misrouting of the optic nerves at the chiasm gives rise to abnormal visual field representations in occipital cortex. In typical human development, the left occipital cortex receives retinal input predominantly from the right visual field, and vice-versa. In albinism, there is a more complete decussation of optic nerve fibers at the chiasm, resulting in partial representation of the temporal hemiretina (ipsilateral visual field) in the contralateral hemisphere. In this study, we characterize the receptive field properties for these abnormal representations by conducting detailed fMRI population receptive field mapping in a rare subset of participants with albinism and no ocular nystagmus. We find a nasal bias for receptive field positions in the abnormal temporal hemiretina representation. In addition, by modelling responses to bilateral visual field stimulation in the overlap zone, we found evidence in favor of discrete unilateral receptive fields, suggesting a conservative pattern of spatial selectivity in the presence of abnormal retinal input.HighlightsWe characterized population receptive fields in albinotic participants with no ocular nystagmusConfirmed overlapping representations of left and right visual fields in cortexDetected nasal bias in receptive field location for temporal hemiretina representationEvidence in favor of discrete unilateral receptive fields and against double coding

Wernicke’s encephalopathy and central pontine myelinolysis in hyperemesis gravidarum

ABSTRACTA pregnant woman, who had been suffering from hyperemesis gravidarum, presented with alteration of consciousness, ocular nystagmus and ataxia. Magnetic Resonance Imaging of the brain showed typical findings of Wernicke’s encephalopathy and central pontine myelinolysis. The clinical features responded dramatically to thiamine supplementation.

Biomechanics of horizontal canal benign paroxysmal positional vertigo

Horizontal canal (HC) benign paroxysmal positional vertigo (HC-BPPV) is a vestibular disorder characterized by bouts of horizontal ocular nystagmus induced during reorientation of the head relative to gravity. The present report addresses the application of a morphologically descriptive 3-canal biomechanical model of the human membranous labyrinth to study gravity-dependent semicircular canal responses during this condition. The model estimates dynamic cupular and endolymph displacements elicited during HC-BPPV provocative diagnostic maneuvers and canalith repositioning procedures (CRPs). The activation latencies in response to an HC-BPPV provocative diagnostic test were predicted to vary depending upon the initial location of the canalith debris (e.g. within the HC lumen vs. in the ampulla). Results may explain why the onset latency of ocular nystagmus evoked by the Dix-Hallpike provocative maneuver for posterior canal BPPV are typically longer than the latencies evoked by analogous tests for HC-BPPV. The model was further applied to assess the efficacy of a 360°-rotation CRP for the treatment of canalithiasis HC-BPPV.

Role of irregular otolith afferents in the steady-state nystagmus during off-vertical axis rotation

1. During constant velocity off-vertical axis rotations (OVAR) in the dark a compensatory ocular nystagmus is present throughout rotation despite the lack of a maintained signal from the semicircular canals. Lesion experiments and canal plugging have attributed the steady-state ocular nystagmus during OVAR to inputs from the otolith organs and have demonstrated that it depends on an intact velocity storage mechanism. 2. To test whether irregularly discharging otolith afferents play a crucial role in the generation of the steady-state eye nystagmus during OVAR, we have used anodal (inhibitory) currents bilaterally to selectively and reversibly block irregular vestibular afferent discharge. During delivery of DC anodal currents (100 microA) bilaterally to both ears, the slow phase eye velocity of the steady-state nystagmus during OVAR was reduced or completely abolished. The disruption of the steady-state nystagmus was transient and lasted only during the period of galvanic stimulation. 3. To distinguish a possible effect of ablation of the background discharge rates of irregular vestibular afferents on the velocity storage mechanism from specific contributions of the dynamic responses from irregular otolith afferents to the circuit responsible for the generation of the steady-state nystagmus, bilateral DC anodal galvanic stimulation was applied during optokinetic nystagmus (OKN) and optokinetic afternystagmus (OKAN). No change in OKN and OKAN was observed.(ABSTRACT TRUNCATED AT 250 WORDS)