Watching the Effects of Gravity. Vestibular Cortex and the Neural Representation of “Visual” Gravity

Gravity is a physical constraint all terrestrial species have adapted to through evolution. Indeed, gravity effects are taken into account in many forms of interaction with the environment, from the seemingly simple task of maintaining balance to the complex motor skills performed by athletes and dancers. Graviceptors, primarily located in the vestibular otolith organs, feed the Central Nervous System with information related to the gravity acceleration vector. This information is integrated with signals from semicircular canals, vision, and proprioception in an ensemble of interconnected brain areas, including the vestibular nuclei, cerebellum, thalamus, insula, retroinsula, parietal operculum, and temporo-parietal junction, in the so-called vestibular network. Classical views consider this stage of multisensory integration as instrumental to sort out conflicting and/or ambiguous information from the incoming sensory signals. However, there is compelling evidence that it also contributes to an internal representation of gravity effects based on prior experience with the environment. This a priori knowledge could be engaged by various types of information, including sensory signals like the visual ones, which lack a direct correspondence with physical gravity. Indeed, the retinal accelerations elicited by gravitational motion in a visual scene are not invariant, but scale with viewing distance. Moreover, the “visual” gravity vector may not be aligned with physical gravity, as when we watch a scene on a tilted monitor or in weightlessness. This review will discuss experimental evidence from behavioral, neuroimaging (connectomics, fMRI, TMS), and patients’ studies, supporting the idea that the internal model estimating the effects of gravity on visual objects is constructed by transforming the vestibular estimates of physical gravity, which are computed in the brainstem and cerebellum, into internalized estimates of virtual gravity, stored in the vestibular cortex. The integration of the internal model of gravity with visual and non-visual signals would take place at multiple levels in the cortex and might involve recurrent connections between early visual areas engaged in the analysis of spatio-temporal features of the visual stimuli and higher visual areas in temporo-parietal-insular regions.

Vestibular Influence on Vertebrate Skeletal Symmetry and Body Shape

Vestibular endorgans in the vertebrate inner ear form the principal sensors for head orientation and motion in space. Following the evolutionary appearance of these organs in pre-vertebrate ancestors, specific sensory epithelial patches, such as the utricle, which is sensitive to linear acceleration and orientation of the head with respect to earth’s gravity, have become particularly important for constant postural stabilization. This influence operates through descending neuronal populations with evolutionarily conserved hindbrain origins that directly and indirectly control spinal motoneurons of axial and limb muscles. During embryogenesis and early post-embryonic periods, bilateral otolith signals contribute to the formation of symmetric skeletal elements through a balanced activation of axial muscles. This role has been validated by removal of otolith signals on one side during a specific developmental period in Xenopus laevis tadpoles. This intervention causes severe scoliotic deformations that remain permanent and extend into adulthood. Accordingly, the functional influence of weight-bearing otoconia, likely on utricular hair cells and resultant afferent discharge, represents a mechanism to ensure a symmetric muscle tonus essential for establishing a normal body shape. Such an impact is presumably occurring within a critical period that is curtailed by the functional completion of central vestibulo-motor circuits and by the modifiability of skeletal elements before ossification of the bones. Thus, bilateral otolith organs and their associated sensitivity to head orientation and linear accelerations are not only indispensable for real time postural stabilization during motion in space but also serve as a guidance for the ontogenetic establishment of a symmetric body.

Objective vestibular function changes in children following cochlear implantation

BACKGROUND: To date, systematically objective evaluations of vestibular function in children with cochlear implantation (CI) have been conducted sparsely, especiallyin children with large vestibular aqueduct syndrome (LVAS). OBJECTIVE: Our goal was to investigate the function of all five vestibular end-organs pre- and post-cochlear implantation in children with LVAS and normal CT. METHODS: In this retrospective cohort study, 34 children (age 4–17 years) with bilateral profound sensorineural hearing loss (SNHL) undergoing unilateral CI were included. Participants included 18 (52.9%) children with LVAS. Objective modalities to evaluate vestibular function included the caloric test, cervical vestibular-evoked myogenic potentials (cVEMP), ocular vestibular-evoked myogenic potentials (oVEMP), and video head impulse test (vHIT). All measurements were performed before surgery and 9 months after surgery. RESULTS: Mean age at CI was 8.1±3.7 years. Caloric testing showed hypofunction in 38.2%of cases before implantation and in 50%after (p > 0.05). We found a significant increase of overall abnormality rate in cVEMP and oVEMP from pre- to post-CI (p < 0.05). In all three semicircular canals tested by vHIT, there were no statistically significant mean gain changes (p > 0.05). Higher deterioration rates in cVEMP (53.3%) and oVEMP (52.0%) after surgery were observed (p < 0.05). In children with LVAS, cVEMP revealed a higher deterioration rate than superior semicircular canal (SSC) and posterior semicircular canal (PSC) (p < 0.05). In children with normal CT, the deterioration rates in VEMPs were both higher than those in vHIT (p < 0.05). CONCLUSIONS: In general, the otolith organs were the most affected peripheral vestibular sensors in children after cochlear implantation. The variations in otolith function influenced by CI were different between children with LVAS and normal CT. We recommend the use of this vestibular function test battery for children with cochlear implantation.

Calcium functional imaging with high-resolution CT in the inner ear

Although the otolith and otolith organs correlate with vertigo and instability, there is no method to investigate them without harmful procedures. We will create the technique for 3D microanatomical images of them, and investigate the in vivo internal state and metabolisms. The otolith and otolith organs images were reconstructed from a texture synthesis algorithm under the skull volume rendering algorithm using a cutting-plane method. The utricular macula was elongated pea-shaped. The saccular macula was almost bud-shaped. The changes in the amount of CaCO3 in the maculae and the endolymphatic sac showed various morphologies, reflecting the balance status of each subject. Both shapes and volumes were not always constant depending on time. In Meniere’s disease (MD), the saccular macula was larger and the utricular macula was smaller. In benign paroxysmal positional vertigo (BPPV), the otolith increased in the utricular macula but did not change much in the saccular macula. The saccule, utricle, and endolymphatic sac were not constantly shaped according to their conditions. These created 3D microanatomical images can allow detailed observations of changes in physiological and biological information. This imaging technique will contribute to our understanding of pathology and calcium metabolism in the in vivo vestibulum.

Pulsed Infrared Stimulation of Vertical Semicircular Canals Evokes Cardiovascular Changes in the Rat

A variety of stimuli activating vestibular end organs, including sinusoidal galvanic vestibular stimulation, whole body rotation and tilt, and head flexion have been shown to evoke significant changes in blood pressure (BP) and heart rate (HR). While a role for the vertical semicircular canals in altering autonomic activity has been hypothesized, studies to-date attribute the evoked BP and HR responses to the otolith organs. The present study determined whether unilateral activation of the posterior (PC) or anterior (AC) semicircular canal is sufficient to elicit changes in BP and/or HR. The study employed frequency-modulated pulsed infrared radiation (IR: 1,863 nm) directed via optical fibers to PC or AC of adult male Long-Evans rats. BP and HR changes were detected using a small-animal single pressure telemetry device implanted in the femoral artery. Eye movements evoked during IR of the vestibular endorgans were used to confirm the stimulation site. We found that sinusoidal IR delivered to either PC or AC elicited a rapid decrease in BP and HR followed by a stimulation frequency-matched modulation. The magnitude of the initial decrements in HR and BP did not correlate with the energy of the suprathreshold stimulus. This response pattern was consistent across multiple trials within an experimental session, replicable, and in most animals showed no evidence of habituation or an additive effect. Frequency modulated electrical current delivered to the PC and IR stimulation of the AC, caused decrements in HR and BP that resembled those evoked by IR of the PC. Frequency domain heart rate variability assessment revealed that, in most subjects, IR stimulation increased the low frequency (LF) component and decreased the high frequency (HF) component, resulting in an increase in the LF/HF ratio. This ratio estimates the relative contributions of sympathetic nervous system (SNS) and parasympathetic nervous system (PNS) activities. An injection of atropine, a muscarinic cholinergic receptor antagonist, diminished the IR evoked changes in HR, while the non-selective beta blocker propranolol eliminated changes in both HR and BP. This study provides direct evidence that activation of a single vertical semicircular canal is sufficient to activate and modulate central pathways that control HR and BP.

EMX2-GPR156-Gαi reverses hair cell orientation in mechanosensory epithelia

Hair cells detect sound, head position or water movements when their mechanosensory hair bundle is deflected. Each hair bundle has an asymmetric architecture that restricts stimulus detection to a single axis. Coordinated hair cell orientations within sensory epithelia further tune stimulus detection at the organ level. Here, we identify GPR156, an orphan GPCR of unknown function, as a critical regulator of hair cell orientation. We demonstrate that the transcription factor EMX2 polarizes GPR156 distribution, enabling it to signal through Gαi and trigger a 180° reversal in hair cell orientation. GPR156-Gαi mediated reversal is essential to establish hair cells with mirror-image orientations in mouse otolith organs in the vestibular system and in zebrafish lateral line. Remarkably, GPR156-Gαi also instructs hair cell reversal in the auditory epithelium, despite a lack of mirror-image organization. Overall, our work demonstrates that conserved GPR156-Gαi signaling is integral to the framework that builds directional responses into mechanosensory epithelia.

The Importance of Being in Touch

This paper describes a series of studies resulting from the finding that when free floating in weightless conditions with eyes closed, all sense of one's spatial orientation with respect to the aircraft can be lost. But, a touch of the hand to the enclosure restores the sense of spatial anchoring within the environment. This observation led to the exploration of how light touch of the hand can stabilize postural control on Earth even in individuals lacking vestibular function, and can override the effect of otherwise destabilizing tonic vibration reflexes in leg muscles. Such haptic stabilization appears to represent a long loop cortical reflex with contact cues at the hand phase leading EMG activity in leg muscles, which change the center of pressure at the feet to counteract body sway. Experiments on dynamic control of balance in a device programmed to exhibit inverted pendulum behavior about different axes and planes of rotation revealed that the direction of gravity not the direction of balance influences the perceived upright. Active control does not improve the accuracy of indicating the upright vs. passive exposure. In the absence of position dependent gravity shear forces on the otolith organs and body surface, drifting and loss of control soon result and subjects are unaware of their ongoing spatial position. There is a failure of dynamic path integration of the semicircular canal signals, such as occurs in weightless conditions.

Two functionally distinct Purkinje cell populations implement an internal model within a single olivo-cerebellar loop

Olivo-cerebellar loops, where anatomical patches of the cerebellar cortex and inferior olive project one onto the other, form an anatomical unit of cerebellar computation. Here, we investigated how successive computational steps map onto olivo-cerebellar loops. Lobules IX-X of the cerebellar vermis, i.e. the nodulus and uvula, implement an internal model of the inner ear's graviceptor, the otolith organs. We have previously identified two populations of Purkinje cells that participate in this computation: Tilt-selective cells transform egocentric rotation signals into allocentric tilt velocity signals, to track head motion relative to gravity, and translation-selective cells encode otolith prediction error. Here we show that, despite very distinct simple spike response properties, both types of Purkinje cells emit complex spikes that are proportional to sensory prediction error. This indicates that both cell populations comprise a single olivo-cerebellar loop, in which only translation-selective cells project to the inferior olive. We propose a neural network model where sensory prediction errors computed by translation-selective cells are used as a teaching signal for both populations, and demonstrate that this network can learn to implement an internal model of the otoliths.

Visually Induced Roll Circular Vection: Do Effects of Stimulation Velocity Differ for Supine and Upright Participants?

Visually induced circular vection (CV) has been the subject of a wide range of functional brain and behavioral research. Participants in MRI or PET studies on CV were mostly in a supine viewing position, while participants in behavioral studies on CV were mostly in an upright viewing position. This study examines the effects of viewing positions (upright and supine) on roll CV reported by 16 participants while watching random dots (92 × 60 degrees field-of-view) rotating at different angular velocities (2, 4, 8, 16, 32, 64 deg/s) for 30 s. Viewing positions affected roll CV durations differently depending on the stimulation velocities. At slower velocities (2, 4, and 8 deg/s), participants exhibited significantly longer roll CV sensations when they were sitting in an upright position as opposed to lying in a supine position. The onset of roll CV was also significantly earlier with participants in an upright position despite similar roll CV intensities in both viewing positions. Significant two-way interactions between effects of viewing positions and dot rotating velocities for some conditions were noted. Consistency between current findings and the hypothesis predicting a weaker roll CV in upright positions based upon perceived gravity by the otolith organs is discussed.

Sound generation in zebrafish with Bio-Opto-Acoustics

Hearing is a crucial sense in underwater environments for communication, hunting, attracting mates, and detecting predators. However, the tools currently used to study hearing are limited, as they cannot controllably stimulate specific parts of the auditory system. To date, the contributions of hearing organs have been identified through lesion experiments that inactivate an organ, making it difficult to gauge the specific stimuli to which each organ is sensitive, or the ways in which inputs from multiple organs are combined during perception. Here, we introduce Bio-Opto-Acoustic (BOA) stimulation, using optical forces to generate localized vibrations in vivo, and demonstrate stimulation of the auditory system of zebrafish larvae with precise control. We use a rapidly oscillated optical trap to generate vibrations in individual otolith organs that are perceived as sound, while adjacent otoliths are either left unstimulated or similarly stimulated with a second optical laser trap. The resulting brain-wide neural activity is characterized using fluorescent calcium indicators, thus linking each otolith organ to its individual neuronal network in a way that would be impossible using traditional sound delivery methods. The results reveal integration and cooperation of the utricular and saccular otoliths, which were previously described as having separate biological functions, during hearing.