ABSTRACT
Introduction: Cervical vestibular evoked myogenic potentials (cVEMPs) provide an objective measure of the integrity of the sacculo-collic pathway leading to their widespread use as a clinical tool in the diagnostic vestibular test battery. Though the application of cVEMPs in preclinical models to assess vestibular function, as performed in relevant clinical populations, remains limited. The present study aimed to establish a rodent model of cVEMP with standardized methods and protocols, examine the neural basis of the responses, and characterize and validate important features for interpretation and assessment of vestibular function. Methods: We compared air-conducted sound (ACS)-evoked VEMPs from the sternocleidomastoid muscles in naïve Brown Norway rats. A custom setup facilitated repeatable and reliable measurements which were carried out at multiple intensities with ACS between 1 and 16 kHz and over 7 days. The myogenic potentials were identified by the presence of a positive (P1)-negative (N1) waveform at 3-5 ms from the stimulus onset. Threshold, amplitude, and latency were compared with intensity- and frequency-matched responses within and between animals. Results: cVEMP responses were repeatedly evoked with stimulus intensities between 50-100 dB SPL with excellent test-retest reliability and across multiple measurements over 7 days for all frequencies tested. Suprathreshold, cVEMP responses at 90 dB SPL for 6-10 kHz stimuli demonstrated significantly larger amplitudes (p < 0.01) and shorter latencies (p < 0.001) compared to cVEMP responses for 1-4 kHz stimuli. Latency of cVEMP showed sex-dependent variability, but no significant differences in threshold or amplitude between males and females was observed. Discussion: The results provide a replicable and reliable setup, test protocol, and comprehensive characterization of cVEMP responses in a preclinical model which can be used in future studies to elucidate pathophysiological characteristics of vestibular dysfunctions or test efficacy of therapeutics.
ABSTRACT
Although vestibular anatomy was described in the Renaissance period, research in vestibular physiology began in the 1820s and was spearheaded by Purkinje and Flourens. This was subsequently expanded by Ménière, Helmholtz, Goltz, Mach, Breuer, Ewald, and Hogyes, who are regarded as the early pioneers in research on vestibular physiology in the 19th century. The relationship of endolymphatic flow and semicircular canal function is termed the Mach-Breuer hypothesis. What is less well known is that a Scottish chemist, Alexander Crum Brown, arrived at similar conclusions as Mach and Breuer at the same time quite independently. In fact, he pioneered several concepts in vestibular physiology that included pairing of semicircular canals for function, the vestibular pathway, optic fixation elimination in vestibular experimentation, the theory of motion intolerance, and study in deaf mutes for insights into vestibular pathology and vestibular compensation. This article is a tribute to this forgotten pioneer in vestibular research.
Subject(s)
Otolaryngology/history , Vestibular Diseases/history , History, 19th Century , History, 20th Century , Humans , Scotland , Vestibular Diseases/physiopathologyABSTRACT
Vestibular-evoked myogenic potentials (VEMPs) provide a simple and cost-effective means to assess the patency of vestibular reflexes. VEMP testing constitutes a core screening method in a clinical battery that probes vestibular function. The confidence one has in interpreting the results arising from VEMP testing is linked to a fundamental understanding of the underlying functional anatomy and physiology. In this review, we will summarize the key role that studies across a range of animal models have fulfilled in contributing to this understanding, covering key findings regarding the mechanisms of excitation in the sensory periphery, the processing of sensory information in central networks, and the distribution of reflexive output to the motor periphery. Although VEMPs are often touted for their simplicity, work in animals models have emphasized how vestibular reflexes operate within a broader behavioral and functional context, and as such vestibular reflexes are influenced by multisensory integration, governed by task demands, and follow principles of muscle recruitment. We will conclude with considerations of future questions, and the ways in which studies in current and emerging animal models can contribute to further use and refinement of this test for both basic and clinical research purposes.
ABSTRACT
CONCLUSION: The developed software (HITCal) may be a useful tool in the analysis and measurement of the saccadic video head impulse test (vHIT) responses and with the experience obtained during its use the authors suggest that HITCal is an excellent method for enhanced exploration of vHIT outputs. OBJECTIVE: To develop a (software) method to analyze and explore the vHIT responses, mainly saccades. METHODS: HITCal was written using a computational development program; the function to access a vHIT file was programmed; extended head impulse exploration and measurement tools were created and an automated saccade analysis was developed using an experimental algorithm. For pre-release HITCal laboratory tests, a database of head impulse tests (HITs) was created with the data collected retrospectively in three reference centers. This HITs database was evaluated by humans and was also computed with HITCal. RESULTS: The authors have successfully built HITCal and it has been released as open source software; the developed software was fully operative and all the proposed characteristics were incorporated in the released version. The automated saccades algorithm implemented in HITCal has good concordance with the assessment by human observers (Cohen's kappa coefficient = 0.7).