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Combining magnetic resonance imaging (MRI) sequences that permit the determination of vestibular nerve angulation (NA = change of nerve caliber or direction), structural nerve integrity via diffusion tensor imaging (DTI), and exclusion of endolymphatic hydrops (ELH) via delayed gadolinium-enhanced MRI of the inner ear (iMRI) could increase the diagnostic accuracy in patients with vestibular paroxysmia (VP). Thirty-six participants were examined, 18 with VP (52.6 ± 18.1 years) and 18 age-matched with normal vestibulocochlear testing (NP 50.3 ± 16.5 years). This study investigated whether (i) NA, (ii) DTI changes, or (iii) ELH occur in VP, and (iv) to what extent said parameters relate. Methods included vestibulocochlear testing and MRI data analyses for neurovascular compression (NVC) and NA verification, DTI and ELS quantification. As a result, (i) NA increased NVC specificity. (ii) DTI structural integrity was reduced on the side affected by VP (p < 0.05). (iii) 61.1% VP showed mild ELH and higher asymmetry indices than NP (p > 0.05). (iv) "Disease duration" and "total number of attacks" correlated with the decreased structural integrity of the affected nerve in DTI (p < 0.001). NVC distance within the nerve's root-entry zone correlated with nerve function (Roh = 0.72, p < 0.001), nerve integrity loss (Roh = - 0.638, p < 0.001), and ELS volume (Roh = - 0.604, p < 0.001) in VP. In conclusion, this study is the first to link eighth cranial nerve function, microstructure, and ELS changes in VP to clinical features and increased vulnerability of NVC in the root-entry zone. Combined MRI with NVC or NA verification, DTI and ELS quantification increased the diagnostic accuracy at group-level but did not suffice to diagnose VP on a single-subject level due to individual variability and lack of diagnostic specificity., (© 2022. The Author(s).)

Background: Naturalistic head accelerations can be used to elicit vestibular evoked potentials (VestEPs). These potentials allow for analysis of cortical vestibular processing and its multi-sensory integration with a high temporal resolution., Methods: We report the results of two experiments in which we compared the differential VestEPs elicited by randomized translations, rotations, and tilts in healthy subjects on a motion platform., Results: An event-related potential (ERP) analysis revealed that established VestEPs were verifiable in all three acceleration domains (translations, rotations, tilts). A further analysis of the VestEPs showed a significant correlation between rotation axes (yaw, pitch, roll) and the amplitude of the evoked potentials. We found increased amplitudes for rotations in the roll compared to the pitch and yaw plane. A distributed source localization analysis showed that the activity in the cingulate sulcus visual (CSv) area best explained direction-dependent amplitude modulations of the VestEPs, but that the same cortical network (posterior insular cortex, CSv) is involved in processing vestibular information, regardless of the motion direction., Conclusion: The results provide evidence for an anisotropic, direction-dependent processing of vestibular input by cortical structures. The data also suggest that area CSv plays an integral role in ego-motion perception and interpretation of spatial features such as acceleration direction and intensity.

Background and Purpose: We aimed to delineate common principles of reorganization after infarcts of the subcortical vestibular circuitry related to the clinical symptomatology. Our hypothesis was that the recovery of specific symptoms is associated with changes in distinct regions within the core vestibular, somatosensory, and visual cortical and subcortical networks., Methods: We used voxel- and surface-based morphometry to investigate structural reorganization of subcortical and cortical brain areas in 42 patients with a unilateral, subcortical infarct with vestibular and ocular motor deficits in the acute phase. The patients received structural neuroimaging and clinical monitoring twice (acute phase and after 6 months) to detect within-subject changes over time., Results: In patients with vestibular signs such as tilts of the subjective visual vertical (SVV) and ocular torsion in the acute phase, significant volumetric increases in the superficial white matter around the parieto-opercular (retro-)insular vestibular cortex (PIVC) were found at follow-up. In patients with SVV tilts, spontaneous nystagmus, and rotatory vertigo in the acute phase, gray matter volume decreases were located in the cerebellum and the visual cortex bilaterally at follow-up. Patients with saccade pathology demonstrated volumetric decreases in cerebellar, thalamic, and cortical centers for ocular motor control., Conclusions: The findings support the role of the PIVC as the key hub for vestibular processing and reorganization. The volumetric decreases represent the reciprocal interaction of the vestibular, visual, and ocular motor systems during self-location and egomotion detection. A modulation in vestibular and ocular motor as well as visual networks was induced independently of the vestibular lesion site., (© 2022 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Objective: Structural reorganization following cerebellar infarcts is not yet known. This study aimed to demonstrate structural volumetric changes over time in the cortical vestibular and multisensory areas (i.e., brain plasticity) after acute cerebellar infarcts with vestibular and ocular motor symptoms. Additionally, we evaluated whether structural reorganization in the patients topographically correlates with cerebello-cortical connectivity that can be observed in healthy participants., Methods: We obtained high-resolution structural imaging in seven patients with midline cerebellar infarcts at two time points. These data were compared to structural imaging of a group of healthy age-matched controls using voxel-based morphometry (2×2 ANOVA approach). The maximum overlap of the infarcts was used as a seed region for a separate resting-state functional connectivity analysis in healthy volunteers., Results: Volumetric changes were detected in the multisensory cortical vestibular areas around the parieto-opercular and (retro-) insular cortex. Furthermore, structural reorganization was evident in parts of the frontal, temporal, parietal, limbic, and occipital lobes and reflected functional connections between the main infarct regions in the cerebellum and the cerebral cortex in healthy individuals., Conclusions: This study demonstrates structural reorganization in the parieto-opercular insular vestibular cortex after acute vestibulo-cerebellar infarcts. Additionally, the widely distributed structural reorganization after midline cerebellar infarcts provides additional in vivo evidence for the multifaceted contribution of cerebellar processing to cortical functions that extend beyond vestibular or ocular motor function., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Strong static magnetic fields, as used in magnetic resonance imaging (MRI), stimulate the vestibular inner ear leading to a state of imbalance within the vestibular system that causes nystagmus. This magnetic vestibular stimulation (MVS) also modulates fluctuations of resting-state functional MRI (RS-fMRI) networks. MVS can be explained by a Lorentz force model, indicating that MVS is the result of the interaction of the static magnetic field strength and direction (called "B0 magnetic field" in MRI) with the inner ear's continuous endolymphatic ionic current. However, the high variability between subjects receiving MVS (measured as nystagmus slow-phase velocity and RS-fMRI amplitude modulations) despite matching head position, remains to be explained. Furthermore, within the imaging community, an "easy-to-acquire-and-use" proxy accounting for modulatory MVS effects in RS-fMRI fluctuations is needed. The present study uses MRI data of 60 healthy volunteers to examine the relationship between RS-fMRI fluctuations and the individual orientation of inner-ear anatomy within the static magnetic field of the MRI. The individual inner-ear anatomy and orientation were assessed via high-resolution anatomical CISS images and related to fluctuations of RS-fMRI networks previously associated with MVS. More specifically, we used a subject-specific proxy for MVS (pMVS) that corresponds to the orientation of the individual inner-ear anatomy within the static magnetic field direction (also called "z-direction" in MR imaging). We found that pMVS explained a considerable fraction of the total variance in RS-fMRI fluctuations (for instance, from 11% in the right cerebellum up to 36% in the cerebellar vermis). In addition to pMVS, we examined the angle of Reid's plane, as determined from anatomical imaging as an alternative and found that this angle (with the same sinus transformation as for pMVS) explained considerably less variance, e.g., from 2 to 16%. In our opinion, an excess variability due to MVS should generally be addressed in fMRI research analogous to nuisance regression for movement, pulsation, and respiration effects. We suggest using the pMVS parameter to deal with modulations of RS-fMRI fluctuations due to MVS. MVS-induced variance can easily be accounted by using high-resolution anatomical imaging of the inner ear and including the proposed pMVS parameter in fMRI group-level analysis.

Objective: Patients with acute central vestibular syndrome suffer from vertigo, spontaneous nystagmus, postural instability with lateral falls, and tilts of visual vertical. Usually, these symptoms compensate within months. The mechanisms of compensation in vestibular infarcts are yet unclear. This study focused on structural changes in gray and white matter volume that accompany clinical compensation., Methods: We studied patients with acute unilateral brain stem infarcts prospectively over 6 months. Structural changes were compared between the acute phase and follow-up with a group of healthy controls using voxel-based morphometry., Results: Restitution of vestibular function following brain stem infarcts was accompanied by downstream structural changes in multisensory cortical areas. The changes depended on the location of the infarct along the vestibular pathways in patients with pathological tilts of the SVV and on the quality of the vestibular percept (rotatory vs graviceptive) in patients with pontomedullary infarcts. Patients with pontomedullary infarcts with vertigo or spontaneous nystagmus showed volumetric increases in vestibular parietal opercular multisensory and (retro-) insular areas with right-sided preference. Compensation of graviceptive deficits was accompanied by adaptive changes in multiple multisensory vestibular areas in both hemispheres in lower brain stem infarcts and by additional changes in the motor system in upper brain stem infarcts., Interpretation: This study demonstrates multisensory neuroplasticity in both hemispheres along with the clinical compensation of vestibular deficits following unilateral brain stem infarcts. The data further solidify the concept of a right-hemispheric specialization for core vestibular processing. The identification of cortical structures involved in central compensation could serve as a platform to launch novel rehabilitative treatments such as transcranial stimulations., (© 2020 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

The vestibular organs, located in the inner ear, sense linear and rotational acceleration of the head and its position relative to the gravitational field of the earth. These signals are essential for many fundamental skills such as the coordination of eye and head movements in the three-dimensional space or the bipedal locomotion of humans. Furthermore, the vestibular signals have been shown to contribute to higher cognitive functions such as navigation. As the main aim of the vestibular system is the sensation of motion it is a challenging system to be studied in combination with modern imaging methods. Over the last years various different methods were used for stimulating the vestibular system. These methods range from artificial approaches like galvanic or caloric vestibular stimulation to passive full body accelerations using hexapod motion platforms, or rotatory chairs. In the first section of this review we provide an overview over all methods used in vestibular stimulation in combination with imaging methods (fMRI, PET, E/MEG, fNIRS). The advantages and disadvantages of every method are discussed, and we summarize typical settings and parameters used in previous studies. In the second section the role of the four imaging techniques are discussed in the context of vestibular research and their potential strengths and interactions with the presented stimulation methods are outlined., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Current evidence points towards a vestibular cortex that involves a multisensory bilateral temporo-parietal-insular network with a handedness-dependent hemispheric lateralization. This study aimed to identify handedness-dependent organizational patterns of (lateralized and non-lateralized) functional subunits within the human vestibular cortex areas. 60 healthy volunteers (30 left-handed and 30 right-handed) were examined on a 3T MR scanner using resting state functional MRI (fMRI). The data was analyzed in four major steps using a functional connectivity based parcellation (fCBP) approach: (1) independent component analysis (ICA) on a whole brain level to identify different resting state networks (RSN); (2) creation of a vestibular informed mask from four whole brain ICs that included reference coordinates of the vestibular network extracted from meta-analyses of vestibular neuroimaging experiments; (3) Re-ICA confined to the vestibular informed mask; (4) cross-correlation of the activated voxels within the vestibular subunits (parcels) to each other (P-to-P) and to the whole-brain RSN (P-to-RSN). This approach disclosed handedness-dependency, inter-hemispheric symmetry, the scale of connectedness to major whole brain RSN and the grade of spatial overlap of voxels within parcels (common/unique) as meaningful discriminatory organizational categories within the vestibular cortex areas. This network consists of multiple inter-hemisphere symmetric (not lateralized), well-connected (many RSN-assignments) multisensory areas (or hubs; e.g., superior temporal gyrus, temporo-parietal intersection) organized around an asymmetric (lateralized, "dominant") and functionally more specialized (few RSN-assignments) core region in the parieto-insular cortex. The latter is in the middle, posterior and inferior insula. In conclusion, the bilateral cortical vestibular network contains not only a handedness-dependent lateralized central region concentrated in the right hemisphere in right-handers and left hemisphere in left-handers, but also surrounding inter-hemisphere symmetric multisensory vestibular areas that seem to be functionally influenced by their neighboring sensory systems (e.g., temporo-parietal intersection by the visual system). One may speculate that the development of an asymmetrical organized vestibular subsystem reflects a more recent phylogenetic evolution of various multisensory vestibular functions. The right hemispheric dominance of spatial orientation and its disorders, spatial neglect and pusher syndrome, may serve as examples., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Multisensory convergence and sensorimotor integration are important aspects for the mediation of higher vestibular cognitive functions at the cortical level. In contrast to the integration of vestibulo-visual or vestibulo-tactile perception, much less is known about the neural mechanism that mediates the integration of vestibular-otolith (linear acceleration/translation/gravity detection) and auditory processing. Vestibular-otolith and auditory afferents can be simultaneously activated using loud sound pressure stimulation, which is routinely used for testing cervical and ocular vestibular evoked myogenic potentials (VEMPs) in clinical neurotological testing. Due to the simultaneous activation of afferents there is always an auditory confound problem in fMRI studies of the neural topology of these systems. Here, we demonstrate that the auditory confounding problem can be overcome in a novel way that does not require the assumption of simple subtraction and additionally allows detection of non-linear changes in the response due to vestibular-otolith interference. We used a parametric sound pressure stimulation design that took each subject's vestibular stimulation threshold into account and analyzed for changes in BOLD-response below and above vestibular-otolith threshold. This approach helped to investigate the functional neuroanatomy of sound-induced auditory and vestibular integration using functional magnetic resonance imaging (fMRI). Results revealed that auditory and vestibular convergence are contained in overlapping regions of the caudal part of the superior temporal gyrus (STG) and the posterior insula. In addition, there are regions that were responsive only to suprathreshold stimulations, suggesting vestibular (otolith) signal processing in these areas. Based on these parametric analyses, we suggest that the caudal part of the STG and posterior insula could contain areas of vestibular contribution to auditory processing, i.e., higher vestibular cortices that provide multisensory integration that is important for tasks such as spatial localization of sound., (Copyright © 2018 Elsevier Inc. All rights reserved.)

In the elderly, major complaints include dizziness and an increasing number of falls, possibly related to an altered processing of vestibular sensory input. In this study, we therefore investigate age-related changes induced by processing of vestibular sensory stimulation. While previous functional imaging studies of healthy aging have investigated brain function during task performance or at rest, we used galvanic vestibular stimulation during functional MRI in a task-free sensory stimulation paradigm to study the effect of healthy aging on central vestibular processing, which might only become apparent during stimulation processing. Since aging may affect signatures of brain function beyond the BOLD-signal amplitude-such as functional connectivity or temporal signal variability--we employed independent component analysis and partial least squares analysis of temporal signal variability. We tested for age-associated changes unrelated to vestibular processing, using a motor paradigm, voxel-based morphometry and diffusion tensor imaging. This allows us to control for general age-related modifications, possibly originating from vascular, atrophic or structural connectivity changes. Age-correlated decreases of functional connectivity and increases of BOLD--signal variability were associated with multisensory vestibular networks. In contrast, no age-related functional connectivity changes were detected in somatosensory networks or during the motor paradigm. The functional connectivity decrease was not due to structural changes but to a decrease in response amplitude. In synopsis, our data suggest that both the age-dependent functional connectivity decrease and the variability increase may be due to deteriorating reciprocal cortico-cortical inhibition with age and related to multimodal vestibular integration of sensory inputs.

Vestibular-evoked myogenic potentials (VEMPs) are frequently used in the clinical diagnosis and research of vertigo syndromes. Altered latencies or amplitudes are typically interpreted as an indication of disturbance in the processing of vestibular stimuli along the otolithic pathways. Correct interpretation, however, can be difficult as VEMP amplitudes can vary greatly across subjects and across laboratories, likely because they are very sensitive to measurement conditions. Here, we attempted to quantify the impact of examiner differences on VEMP data. We collected data from 1,038 people using eight different experimental examiners, and investigated the effect of examiner on VEMP latencies and amplitudes. We found that the examiner collecting the data had a strong effect on outcome measures with significant differences (p < 0.001) in cVEMP and oVEMP latencies and in oVEMP amplitudes. No significant differences between examiners were found for the cVEMP amplitudes. When we compared the healthy and pathological sides of patients with a clinically diagnosed unilateral disease, no significant differences between sides were found. Given our results and the results reported in the literature, we conclude that the signal features of VEMPs are very sensitive to variables that may be influenced by the examiner. The field should therefore work on a better standard for VEMP recordings.