Response characteristics of vestibular evoked myogenic potentials recorded over splenius capitis in young adults and adolescents.

BACKGROUND AND OBJECTIVES: Examine vestibular evoked myogenic potential (VEMP) responses recorded from surface electrodes over Splenius Capitis (SPC) in a seated position. SPECIFIC AIMS: (1) validate response characteristics of VEMP recordings from surface electrodes over Sternocleidomastoid (SCM) and over SCP and (2) assess age effects on responses in adolescents and young adults. MATERIALS AND METHODS: Simultaneous surface VEMP was recorded bilaterally from electrodes placed over the dorsal neck musculature at a location known from previous work to record from SPC in 15 healthy participants during trials with head rotation toward and away from the stimulated ear. VEMP was also recorded from electrodes over SCM, ipsilateral to the stimulus ear, in the same participants in a supine, head lift/turn position. RESULTS: Response amplitudes significantly increased with contraction strength and decreased with age. Participants were able to maintain sufficient contraction strength (amplitude) with head rotation to reliably measure over SPC. Normalized response amplitudes measured from electrodes over contralateral SPC were largest with head rotation contralateral to the stimulus ear. Normalized amplitudes and peak latencies were comparable to the same measures from SCM obtained in supine, head lift/turn position. CONCLUSIONS: Otolith generated myogenic responses can be recorded seated from electrodes over the dorsal neck with head rotation contralateral to the stimulus ear. In this position, contralateral recordings are consistent with responses known from previous work to arise from SPC; ipsilateral recordings may include crosstalk from activated muscles nearby, including ipsilateral SCM. Overall, techniques targeting contralateral SPC during contralateral head turn may provide additional methods of recording VEMPs.

Response characteristics of vestibular evoked myogenic potentials recorded over splenius capitis in young adults and adolescents

Background and objectives: Examine vestibular evoked myogenic potential (VEMP) responses recorded from surface electrodes over Splenius Capitis (SPC) in a seated position. Specific aims: (1) validate response characteristics of VEMP recordings from surface electrodes over Sternocleidomastoid (SCM) and over SCP and (2) assess age effects on responses in adolescents and young adults. Materials and methods: Simultaneous surface VEMP was recorded bilaterally from electrodes placed over the dorsal neck musculature at a location known from previous work to record from SPC in 15 healthy participants during trials with head rotation toward and away from the stimulated ear. VEMP was also recorded from electrodes over SCM, ipsilateral to the stimulus ear, in the same participants in a supine, head lift/turn position. Results: Response amplitudes significantly increased with contraction strength and decreased with age. Participants were able to maintain sufficient contraction strength (amplitude) with head rotation to reliably measure over SPC. Normalized response amplitudes measured from electrodes over contralateral SPC were largest with head rotation contralateral to the stimulus ear. Normalized amplitudes and peak latencies were comparable to the same measures from SCM obtained in supine, head lift/turn position. Conclusions: Otolith generated myogenic responses can be recorded seated from electrodes over the dorsal neck with head rotation contralateral to the stimulus ear. In this position, contralateral recordings are consistent with responses known from previous work to arise from SPC; ipsilateral recordings may include crosstalk from activated muscles nearby, including ipsilateral SCM. Overall, techniques targeting contralateral SPC during contralateral head turn may provide additional methods of recording VEMPs.(AU)

Antecedentes y objetivos: Examinamos las respuestas de los potenciales evocados miogénicos vestibulares (PEMV) recogidas de los electrodos de superficie sobre el músculo esplenio (ME) en posición sentada. Objetivos específicos: 1) validar las características de los registros de la respuesta de los PEMV recogidos de los electrodos de superficie sobre el músculo esternocleidomastoideo (SCM) y el ME, y 2) evaluar los efectos de la edad en adolescentes y adultos jóvenes. Materiales y métodos: Se registraron simultáneamente los PEMV bilaterales de los electrodos situados en la musculatura dorsal del cuello, en un sitio conocido de un estudio anterior para obtener registros del ME en 15 participantes sanos durante los ensayos, con rotación de cabeza hacia y fuera del oído estimulado. También se registraron los PEMV de los electrodos situados sobre el SCM, en posición ipsilateral al oído estimulado, en los mismos participantes, en posición supina y con elevación/giro de cabeza. Resultados: Las amplitudes de la respuesta se incrementaron significativamente con la fuerza de la contracción y disminuyeron con la edad. Los participantes fueron capaces de mantener suficiente fuerza de contracción (amplitud) con la rotación de cabeza, para realizar mediciones fiables sobre el ME. Las amplitudes de la respuesta normalizada medidas en los electrodos sobre el ME contralateral fueron mayores con la rotación de cabeza contralateral al oído estimulado. Las amplitudes normalizadas y las latencias máximas fueron comparables a las mismas medidas del SCM obtenidas en posición supina, y elevación/giro de cabeza. Conclusiones: Las respuestas miogénicas generadas por otolitos pueden registrarse en posición sentada a partir de los electrodos situados en la parte dorsal del cuello, contralateral al oído estimulado. En esta posición, los registros contralaterales son coherentes con las respuestas conocidas de un estudio previo, derivadas del ME; los registros ipsilaterales pueden incluir interferencias de los músculos activados cercanos, incluyendo el SCM ipsilateral. En general, las técnicas centradas en el ME contralateral durante el giro de cabeza contralateral pueden aportar métodos adicionales de registro de los PEMV.(AU)

Stochastic and sinusoidal electrical stimuli increase the irregularity and gain of Type A and B medial vestibular nucleus neurons, in vitro.

Galvanic vestibular stimulation (GVS) has been shown to improve vestibular function potentially via stochastic resonance, however, it remains unknown how central vestibular nuclei process these signals. In vivo work applying electrical stimuli to the vestibular apparatus of animals has shown changes in neuronal discharge at the level of the primary vestibular afferents and hair cells. This study aimed to determine the cellular impacts of stochastic, sinusoidal, and stochastic + sinusoidal stimuli on individual medial vestibular nucleus (MVN) neurons of male and female C57BL/6 mice. All stimuli increased the irregularity of MVN neuronal discharge, while differentially affecting neuronal gain. This suggests that the heterogeneous MVN neuronal population (marked by differential expression of ion channels), may influence the impact of electrical stimuli on neuronal discharge. Neuronal subtypes showed increased variability of neuronal firing, where Type A and B neurons experienced the largest gain changes in response to stochastic and sinusoidal stimuli. Type C neurons were the least affected regarding neuronal firing variability and gain changes. The membrane potential (MP) of neurons was altered by sinusoidal and stochastic + sinusoidal stimuli, with Type B and C neuronal MP significantly affected. These results indicate that GVS-like electrical stimuli impact MVN neuronal discharge differentially, likely as a result of heterogeneous ion channel expression.

Response characteristics of vestibular evoked myogenic potentials recorded over splenius capitis in young adults and adolescents.

BACKGROUND AND OBJECTIVES: Examine vestibular evoked myogenic potential (VEMP) responses recorded from surface electrodes over Splenius Capitis (SPC) in a seated position. SPECIFIC AIMS: (1) validate response characteristics of VEMP recordings from surface electrodes over Sternocleidomastoid (SCM) and over SCP and (2) assess age effects on responses in adolescents and young adults. MATERIALS AND METHODS: Simultaneous surface VEMP was recorded bilaterally from electrodes placed over the dorsal neck musculature at a location known from previous work to record from SPC in 15 healthy participants during trials with head rotation toward and away from the stimulated ear. VEMP was also recorded from electrodes over SCM, ipsilateral to the stimulus ear, in the same participants in a supine, head lift/turn position. RESULTS: Response amplitudes significantly increased with contraction strength and decreased with age. Participants were able to maintain sufficient contraction strength (amplitude) with head rotation to reliably measure over SPC. Normalized response amplitudes measured from electrodes over contralateral SPC were largest with head rotation contralateral to the stimulus ear. Normalized amplitudes and peak latencies were comparable to the same measures from SCM obtained in supine, head lift/turn position. CONCLUSIONS: Otolith generated myogenic responses can be recorded seated from electrodes over the dorsal neck with head rotation contralateral to the stimulus ear. In this position, contralateral recordings are consistent with responses known from previous work to arise from SPC; ipsilateral recordings may include crosstalk from activated muscles nearby, including ipsilateral SCM. Overall, techniques targeting contralateral SPC during contralateral head turn may provide additional methods of recording VEMPs.

Summating potentials from the utricular macula of anaesthetized guinea pigs.

The Summating Potential (SP) was first recorded in the cochlea in the 1950s and represents an objective measure of cochlear hair cell function, in vivo. Despite being a regular tool in hearing research, a similar response has not yet been recorded from the vestibular system. This is mainly due to the lack of experimental techniques available to record electrical vestibular hair cell responses in isolation from the much larger cochlear potentials. Here we demonstrate the first recordings of the vestibular SP, evoked by Bone-Conducted Vibration (BCV) and Air-Conducted Sound (ACS) stimuli, in anaesthetized guinea pigs. Field potential measurements were taken from the basal surface of the utricular macula, and from the facial nerve canal following surgical or chemical ablation of the cochlea. SPs were evoked by stimuli with frequencies above ~200 Hz, and only with moderate to high intensity (~0.005-0.05 g) BCV and ACS (~120-140 dB SPL). Neural blockade abolished the Vestibular short-latency Evoked Potential (VsEP) and Vestibular Nerve Neurophonic (VNN) from the facial nerve canal recordings but did not abolish the vestibular SP nor the vestibular microphonic. Importantly, the vestibular SP was irreversibly abolished from the utricle and facial nerve canal recordings following local gentamicin application, highlighting its hair cell origin. This is the first study to record the Summating Potential from the mammalian vestibular system, in vivo, providing a novel research tool to assess vestibular hair cell function during experimental manipulations and animal models of disease.

K369I Tau Mice Demonstrate a Shift Towards Striatal Neuron Burst Firing and Goal-directed Behaviour.

Pathological forms of the microtubule-associated protein tau are involved in a large group of neurodegenerative diseases named tauopathies, including frontotemporal lobar degeneration (FTLD-tau). K369I mutant tau transgenic mice (K3 mice) recapitulate neural and behavioural symptoms of FTLD, including tau aggregates in the cortex, alterations to nigrostriatum, memory deficits and parkinsonism. The aim of this study was to further characterise the K3 mouse model by examining functional alterations to the striatum. Whole-cell patch-clamp electrophysiology was used to investigate the properties of striatal neurons in K3 mice and wildtype controls. Additionally, striatal-based instrumental learning tasks were conducted to assess goal-directed versus habitual behaviours (i.e., by examining sensitivity to outcome devaluation and progressive ratios). The K3 model demonstrated significant alterations in the discharge properties of striatal neurons relative to wildtype mice, which manifested as a shift in neuronal output towards a burst firing state. K3 mice acquired goal-directed responding faster than control mice and were goal-directed at test unlike wildtype mice, which is likely to indicate reduced capacity to develop habitual behaviour. The observed pattern of behaviour in K3 mice is suggestive of deficits in dorsal lateral striatal function and this was supported by our electrophysiological findings. Thus, both the electrophysiological and behavioural alterations indicate that K3 mice have early deficits in striatal function. This finding adds to the growing literature which indicate that the striatum is impacted in tau-related neuropathies such as FTLD, and further suggests that the K3 model is a unique mouse model for investigating FTLD especially with striatal involvement.

Stochastic Noise Application for the Assessment of Medial Vestibular Nucleus Neuron Sensitivity In Vitro.

Galvanic vestibular stimulation (GVS) has been shown to improve balance measures in individuals with balance or vestibular impairments. This is proposed to be due to the stochastic resonance (SR) phenomenon, which is defined as application of a low-level/subthreshold stimulus to a non-linear system to increase detection of weaker signals. However, it is still unknown how SR exhibits its positive effects on human balance. This is one of the first demonstrations of the effects of sinusoidal and stochastic noise on individual neurons. Using whole-cell patch clamp electrophysiology, sinusoidal and stochastic noise can be applied directly to individual neurons in the medial vestibular nucleus (MVN) of C57BL/6 mice. Here we demonstrate how to determine the threshold of MVN neurons in order to ensure the sinusoidal and stochastic stimuli are subthreshold and from this, determine the effects that each type of noise has on MVN neuronal gain. We show that subthreshold sinusoidal and stochastic noise can modulate the sensitivity of individual neurons in the MVN without affecting basal firing rates.

Splenius capitis: sensitive target for the cVEMP in older and neurodegenerative patients.

BACKGROUND: The vestibular evoked myogenic potential (VEMP) is a technique used to assess vestibular function. Cervical VEMPs (cVEMPs) are obtained conventionally from the sternocleidomastoid (SCM) muscle; however, the dorsal neck muscle splenius capitis (SPL) has also been shown to be a reliable target alongside the SCM in young subjects. OBJECTIVE: This study aimed to compare cVEMPs from the SCM and SPL in two positions across young, older, and Parkinson's disease (PD) patients. METHOD: Experiments were carried out using surface EMG electrodes placed over the SCM and SPL. cVEMPs were measured using a 30 s, 126 dB sound stimulus with 222 individual tone bursts, while subjects were in a supine and head-turned posture (also known as the head elevation method), and in a seated head-turned posture. RESULTS: When comparing cVEMPs across positions, the incidence of supine and seated SCM-cVEMPs diminished significantly in older and PD patients in comparison with young subjects. However, no statistically significant differences in incidences were found in seated SPL-cVEMPs when comparing young, older and PD patients. SPL-cVEMPs were present significantly more often than seated SCM-cVEMPs in PD patients. CONCLUSIONS: SPL-cVEMPs are not altered to the same extent that SCM-cVEMPs are by aging and disease and its addition to cVEMP testing may reduce false-positive tests for vestibulopathy.

Animal Models of Vestibular Evoked Myogenic Potentials: The Past, Present, and Future.

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.

Corrigendum: Reviewing the Role of the Efferent Vestibular System in Motor and Vestibular Circuits.

[This corrects the article on p. 552 in vol. 8, PMID: 28824449.].

Reviewing the Role of the Efferent Vestibular System in Motor and Vestibular Circuits.

Efferent circuits within the nervous system carry nerve impulses from the central nervous system to sensory end organs. Vestibular efferents originate in the brainstem and terminate on hair cells and primary afferent fibers in the semicircular canals and otolith organs within the inner ear. The function of this efferent vestibular system (EVS) in vestibular and motor coordination though, has proven difficult to determine, and remains under debate. We consider current literature that implicate corollary discharge from the spinal cord through the efferent vestibular nucleus (EVN), and hint at a potential role in overall vestibular plasticity and compensation. Hypotheses range from differentiating between passive and active movements at the level of vestibular afferents, to EVS activation under specific behavioral and environmental contexts such as arousal, predation, and locomotion. In this review, we summarize current knowledge of EVS circuitry, its effects on vestibular hair cell and primary afferent activity, and discuss its potential functional roles.

Splenius capitis is a reliable target for measuring cervical vestibular evoked myogenic potentials in adults.

The cervical vestibular evoked myogenic potential (cVEMP) is a common and simple test of vestibulospinal reflex patency. In the clinic, cVEMPs are measured in response to loud sounds from the sternocleidomastoid (SCM) on the ventral neck, as subjects maintain an uncomfortable head posture needed to recruit SCM. Here we characterize the cVEMP in a dorsal neck turner (splenius capitis; SPL), and compare it with the SCM cVEMP. cVEMPs were recorded simultaneously via surface electromyography from SCM and SPL from 17 healthy subjects in a variety of postures, including head-turned postures adopted while either seated or standing, and the clinical posture. Like the SCM cVEMP recorded ipsilateral to the side of sound stimulation, the cVEMP on the contralateral SPL (synergistic with ipsilateral SCM) was characterized by a biphasic wave of muscle activity that began at ~ 13 ms. cVEMP reliability was higher on SPL vs. SCM in standing postures (chi-squared; P < 0.05), and equivalent results were obtained from SPL in a standing or seated posture. In 9 of the 17 subjects, we also obtained bilateral intramuscular (IM) recordings from SPL at the same time as the surface recordings. In these subjects, the initial surface response in SPL was associated with a consistent decrease in multi-unit IM SPL activity. Overall, these results demonstrate that SPL recordings offer a complimentary target for cVEMP assessments. The expression of SPL cVEMPs in simple head-turned postures may also improve the utility of cVEMP testing for vestibular assessment in children, the elderly, or non-compliant.

Motor Performance is Impaired Following Vestibular Stimulation in Ageing Mice.

UNLABELLED: Balance and maintaining postural equilibrium are important during stationary and dynamic movements to prevent falls, particularly in older adults. While our sense of balance is influenced by vestibular, proprioceptive, and visual information, this study focuses primarily on the vestibular component and its age-related effects on balance. C57Bl/6J mice of ages 1, 5-6, 8-9 and 27-28 months were tested using a combination of standard (such as grip strength and rotarod) and newly-developed behavioral tests (including balance beam and walking trajectory tests with a vestibular stimulus). In the current study, we confirm a decline in fore-limb grip strength and gross motor coordination as age increases. We also show that a vestibular stimulus of low frequency (2-3 Hz) and duration can lead to age-dependent changes in balance beam performance, which was evident by increases in latency to begin walking on the beam as well as the number of times hind-feet slip (FS) from the beam. Furthermore, aged mice (27-28 months) that received continuous access to a running wheel for 4 weeks did not improve when retested. Mice of ages 1, 10, 13 and 27-28 months were also tested for changes in walking trajectory as a result of the vestibular stimulus. While no linear relationship was observed between the changes in trajectory and age, 1-month-old mice were considerably less affected than mice of ages 10, 13 and 27-28 months. CONCLUSION: this study confirms there are age-related declines in grip strength and gross motor coordination. We also demonstrate age-dependent changes to finer motor abilities as a result of a low frequency and duration vestibular stimulus. These changes showed that while the ability to perform the balance beam task remained intact across all ages tested, behavioral changes in task performance were observed.

Vestibular Interactions in the Thalamus.

It has long been known that the vast majority of all information en route to the cerebral cortex must first pass through the thalamus. The long held view that the thalamus serves as a simple hi fidelity relay station for sensory information to the cortex, however, has over recent years been dispelled. Indeed, multiple projections from the vestibular nuclei to thalamic nuclei (including the ventrobasal nuclei, and the geniculate bodies)- regions typically associated with other modalities- have been described. Further, some thalamic neurons have been shown to respond to stimuli presented from across sensory modalities. For example, neurons in the rat anterodorsal and laterodorsal nuclei of the thalamus respond to visual, vestibular, proprioceptive and somatosensory stimuli and integrate this information to compute heading within the environment. Together, these findings imply that the thalamus serves crucial integrative functions, at least in regard to vestibular processing, beyond that imparted by a "simple" relay. In this mini review we outline the vestibular inputs to the thalamus and provide some clinical context for vestibular interactions in the thalamus. We then focus on how vestibular inputs interact with other sensory systems and discuss the multisensory integration properties of the thalamus.

Efferent Vestibular Neurons Show Homogenous Discharge Output But Heterogeneous Synaptic Input Profile In Vitro.

Despite the importance of our sense of balance we still know remarkably little about the central control of the peripheral balance system. While previous work has shown that activation of the efferent vestibular system results in modulation of afferent vestibular neuron discharge, the intrinsic and synaptic properties of efferent neurons themselves are largely unknown. Here we substantiate the location of the efferent vestibular nucleus (EVN) in the mouse, before characterizing the input and output properties of EVN neurons in vitro. We made transverse serial sections through the brainstem of 4-week-old mice, and performed immunohistochemistry for calcitonin gene-related peptide (CGRP) and choline acetyltransferase (ChAT), both expressed in the EVN of other species. We also injected fluorogold into the posterior canal and retrogradely labelled neurons in the EVN of ChAT:: tdTomato mice expressing tdTomato in all cholinergic neurons. As expected the EVN lies dorsolateral to the genu of the facial nerve (CNVII). We then made whole-cell current-, and voltage-clamp recordings from visually identified EVN neurons. In current-clamp, EVN neurons display a homogeneous discharge pattern. This is characterized by a high frequency burst of action potentials at the onset of a depolarizing stimulus and the offset of a hyperpolarizing stimulus that is mediated by T-type calcium channels. In voltage-clamp, EVN neurons receive either exclusively excitatory or inhibitory inputs, or a combination of both. Despite this heterogeneous mixture of inputs, we show that synaptic inputs onto EVN neurons are predominantly excitatory. Together these findings suggest that the inputs onto EVN neurons, and more specifically the origin of these inputs may underlie EVN neuron function.

Near infrared (NIr) light increases expression of a marker of mitochondrial function in the mouse vestibular sensory epithelium.

Strategies for attenuating decline in balance function with increasing age are predominantly focused on physical therapies including balance tasks and exercise. However, these approaches do not address the underlying causes of balance decline. Using mice, the impact of near infrared light (NIr) on the metabolism of cells in the vestibular sensory epithelium was assessed. Data collected shows that this simple and safe intervention may protect these vulnerable cells from the deleterious effects of natural aging. mRNA was extracted from the isolated peripheral vestibular sensory epithelium (crista ampullaris and utricular macula) and subsequently transcribed into a cDNA library. This library was then probed for the expression of ubiquitous antioxidant (SOD-1). Antioxidant gene expression was then used to quantify cellular metabolism. Using transcranial delivery of NIr in young (4 weeks) and older (8-9 months) mice, and a brief treatment regime (90 sec/day for 5 days), this work suggests NIr alone may be sufficient to improve mitochondrial function in the vestibular sensory epithelium. Since there are currently no available, affordable, non-invasive methods of therapy to improve vestibular hair cell function, the application of external NIr radiation provides a potential strategy to counteract the impact of aging on cellular metabolism inthe vestibular sensory epithelium.

Behavioral assessment of the aging mouse vestibular system.

Age related decline in balance performance is associated with deteriorating muscle strength, motor coordination and vestibular function. While a number of studies show changes in balance phenotype with age in rodents, very few isolate the vestibular contribution to balance under either normal conditions or during senescence. We use two standard behavioral tests to characterize the balance performance of mice at defined age points over the lifespan: the rotarod test and the inclined balance beam test. Importantly though, a custom built rotator is also used to stimulate the vestibular system of mice (without inducing overt signs of motion sickness). These two tests have been used to show that changes in vestibular mediated-balance performance are present over the murine lifespan. Preliminary results show that both the rotarod test and the modified balance beam test can be used to identify changes in balance performance during aging as an alternative to more difficult and invasive techniques such as vestibulo-ocular (VOR) measurements.