Modulation of the central vestibular networks through aging and high-strength magnetic fields

The importance of the vestibular system usually goes unnoticed in our daily lives and its significance is only experienced by patients suffering from vestibular diseases. The vestibular system is essential for orientation in space, and perception of motion, as well as keeping balance, and maintaining stable visual perception while moving in a three-dimensional world. Functional imaging has long been used to study the multisensory vestibular network in healthy subjects, as well as in patients with diseases of the vestibular system. The majority of these previous studies sought to associate brain areas with vestibular processing, by evaluating increases or decreases in blood-oxygen-level dependent signal (BOLD-signal) during application of artificial vestibular stimulations. However, many basic network properties of the multisensory vestibular cortical network still remain unknown. Since it is now possible to infer networks from functional connectivity analysis, that associates areas into networks based on their spatiotemporal signal behavior, a few of the remaining questions can be addressed. The dynamics of the vestibular networks and other co-activated networks in regard to the processing of a multisensory stimulation remain largely unknown. Do subjects of different ages respond differently to a vestibular challenge? Furthermore, a new form of vestibular stimulation, termed magnetic vestibular stimulation (MVS), has recently been discovered. It occurs in strong magnetic fields (≥1.5 tesla), that are commonly used in functional magnetic resonance imaging (fMRI), and raises questions about a possible modulation of vestibular networks during fMRI, potentially biasing functional neuroimaging results. The purpose of this thesis is to develop suggestions for studying the multisensory vestibular network and the influence of vestibular modulations on resting-state networks with fMRI. The focus lies on basic scientific investigations of (1) the influence of aging on the ability of subjects to respond to a challenge of the multisensory vestibular network and (2) the modulatory influence of magnetic fields (the MR environment) on functional imaging and resting-state networks in general. To this end, we carried out two studies. The first study was a cross-sectional aging study investigating the modulation of vestibular, somatosensory and motor networks in healthy adults (N=39 of 45 in total, age 20 to 70 years, 17 males). We used galvanic vestibular stimulation (GVS) to stimulate all afferences of the peripheral vestibular end organs or vestibular nerve in order to activate the entire multisensory vestibular network, as age-associated changes might be specific to sensory processing. We also controlled for changes of the motor network, structural fiber integrity (fractional anisotropy – FA), and volume changes to simultaneously compare the effects of aging across structure and function. The second study investigated the influence of the static magnetic field of the MR environment in a group of healthy subjects (N=27 of 30 in total, age 21 to 38 years, 19 females), as it was recently shown that a strong magnetic field produces a vestibular imbalance in healthy subjects. We examined MVS at field strengths of 1.5 tesla and 3 tesla. The associated spontaneous nystagmus, the scaling of the nystagmus’ slow phase velocity (SPV) across field strengths, the between subject variance of the SPV were analysed, and the analogous scaling relationship was identified in the modulation of resting-state network amplitudes, like the default mode network (DMN), between 1.5 tesla and 3 tesla to reveal its effect on fMRI results. Aging and MVS modulated networks associated with vestibular function and resting-state networks known for vestibular interactions. The results from our aging study imply that the dynamics of vestibular networks is limited by the influence of aging even in healthy adults without any noticeable vestibular deficit. Vestibular networks show a decline of functional connectivity with age and an increase of temporal variability (in excess of stimulation induced changes) with age. In contrast somatosensory and motor networks did not show any significant linear relationship with age or any significant changes between the youngest and oldest participants. Age-associated structural changes (gray matter volume changes or structural connectivity changes) did not explain the decline in functional connectivity or increase in temporal variability. Furthermore, stimulation thresholds did not change with age (nor did they correlate with the functional connectivity amplitudes or temporal variability), indicating that the age-associated changes that were found for the vestibular network, were not dependent on peripheral decline, as GVS is thought to directly stimulate the vestibular nerve. The results from our study of the influence of the static magnetic field of the MR environment showed that MVS was already present at a field strength of 1.5 tesla, as evident from the induced nystagmus, indicating a state of vestibular imbalance. Furthermore, MVS scaled linearly with field strength between 1.5 tesla and 3 tesla, and identified the effects of MVS in the scaling of functional resting-state network fluctuations, showing that MVS does indeed influence resting-state networks due to vestibular imbalance. Specifically, MVS does influence DMN resting-state network dynamics in accordance with the predicted scaling of MVS based on the Lorentz-force model for MVS. These results taken together not only imply that subjects were in a vestibular state of imbalance, but also that the extent and direction of the state of imbalance showed more variance between subjects with increasing field strength. In summary, the following suggestions for vestibular research can be delineated to extend the kind of questions that can be answered by functional MRI experiments and to improve these investigations for the benefit of clinically relevant research of healthy controls and patients. Regarding the influence of age, we suggest that researchers comparing patients with vestibular deficits and healthy controls should separate the age-matched group into age-strata (non-overlapping subgroups with different age spans, e.g. 20-40 years, 40-60 years and above 60 years of age). Each stratum should be compared and interpreted separately given that different age-groups have different levels of vestibular network dynamics available for compensation (or responding to a challenge). This is particularly relevant when patients show a wide age-distribution, e.g. in the case of vestibular neuritis patients. With respect to the influence of magnetic fields, we suggest that MVS should be seen as a new way of manipulating networks that either process vestibular information or show vestibular interactions, by using strong magnetic fields (≥1.5 tesla), as commonly used in MRI. The potential of modulating vestibular influences on networks via MVS lies in being able to induce or manipulate vestibular imbalances. In the healthy this can be used to create states that are similar to the diseased state, but without peripheral or central lesions. In patients this will allow to extend or reduce vestibular imbalances. In both cases this can be done while performing functional MRI simply by using the magnetic field of the MRI scanner and adjusting the head position of the subject in question. In studies that need to avoid vestibular perturbations MVS should be controlled by adjusting the head position of the subject and measuring the resulting eye movements. This should then be seen as an effort to remove unwanted variance, i.e., as an effort to homogenize the group, and achieve better statistical results due to less (uncontrolled) MVS interference that increases bias and variance with increasing field strength. In summary, these suggestions result in three short questions that researchers could ask themselves when thinking about vestibular research projects in the future. Age-grouping: “Is the response to a challenge different for younger adults than older adults, i.e., does each age-group compensate differently?” MVS modulation: “Can a manipulation of the imbalance state of our subjects with MVS help us to reveal more about the vestibular network’s response to a challenge or should we avoid interference by MVS in the imbalance state of our subjects?” Sensitivity: “Is the measure that I want to use sensitive enough to show the differences that I am looking for?” Connectivity and temporal variability might be sensitive enough, but many clinical tests might not be sufficient

Modulation of the central vestibular networks through aging and high-strength magnetic fields

The importance of the vestibular system usually goes unnoticed in our daily lives and its significance is only experienced by patients suffering from vestibular diseases. The vestibular system is essential for orientation in space, and perception of motion, as well as keeping balance, and maintaining stable visual perception while moving in a three-dimensional world. Functional imaging has long been used to study the multisensory vestibular network in healthy subjects, as well as in patients with diseases of the vestibular system. The majority of these previous studies sought to associate brain areas with vestibular processing, by evaluating increases or decreases in blood-oxygen-level dependent signal (BOLD-signal) during application of artificial vestibular stimulations. However, many basic network properties of the multisensory vestibular cortical network still remain unknown. Since it is now possible to infer networks from functional connectivity analysis, that associates areas into networks based on their spatiotemporal signal behavior, a few of the remaining questions can be addressed. The dynamics of the vestibular networks and other co-activated networks in regard to the processing of a multisensory stimulation remain largely unknown. Do subjects of different ages respond differently to a vestibular challenge? Furthermore, a new form of vestibular stimulation, termed magnetic vestibular stimulation (MVS), has recently been discovered. It occurs in strong magnetic fields (≥1.5 tesla), that are commonly used in functional magnetic resonance imaging (fMRI), and raises questions about a possible modulation of vestibular networks during fMRI, potentially biasing functional neuroimaging results. The purpose of this thesis is to develop suggestions for studying the multisensory vestibular network and the influence of vestibular modulations on resting-state networks with fMRI. The focus lies on basic scientific investigations of (1) the influence of aging on the ability of subjects to respond to a challenge of the multisensory vestibular network and (2) the modulatory influence of magnetic fields (the MR environment) on functional imaging and resting-state networks in general. To this end, we carried out two studies. The first study was a cross-sectional aging study investigating the modulation of vestibular, somatosensory and motor networks in healthy adults (N=39 of 45 in total, age 20 to 70 years, 17 males). We used galvanic vestibular stimulation (GVS) to stimulate all afferences of the peripheral vestibular end organs or vestibular nerve in order to activate the entire multisensory vestibular network, as age-associated changes might be specific to sensory processing. We also controlled for changes of the motor network, structural fiber integrity (fractional anisotropy – FA), and volume changes to simultaneously compare the effects of aging across structure and function. The second study investigated the influence of the static magnetic field of the MR environment in a group of healthy subjects (N=27 of 30 in total, age 21 to 38 years, 19 females), as it was recently shown that a strong magnetic field produces a vestibular imbalance in healthy subjects. We examined MVS at field strengths of 1.5 tesla and 3 tesla. The associated spontaneous nystagmus, the scaling of the nystagmus’ slow phase velocity (SPV) across field strengths, the between subject variance of the SPV were analysed, and the analogous scaling relationship was identified in the modulation of resting-state network amplitudes, like the default mode network (DMN), between 1.5 tesla and 3 tesla to reveal its effect on fMRI results. Aging and MVS modulated networks associated with vestibular function and resting-state networks known for vestibular interactions. The results from our aging study imply that the dynamics of vestibular networks is limited by the influence of aging even in healthy adults without any noticeable vestibular deficit. Vestibular networks show a decline of functional connectivity with age and an increase of temporal variability (in excess of stimulation induced changes) with age. In contrast somatosensory and motor networks did not show any significant linear relationship with age or any significant changes between the youngest and oldest participants. Age-associated structural changes (gray matter volume changes or structural connectivity changes) did not explain the decline in functional connectivity or increase in temporal variability. Furthermore, stimulation thresholds did not change with age (nor did they correlate with the functional connectivity amplitudes or temporal variability), indicating that the age-associated changes that were found for the vestibular network, were not dependent on peripheral decline, as GVS is thought to directly stimulate the vestibular nerve. The results from our study of the influence of the static magnetic field of the MR environment showed that MVS was already present at a field strength of 1.5 tesla, as evident from the induced nystagmus, indicating a state of vestibular imbalance. Furthermore, MVS scaled linearly with field strength between 1.5 tesla and 3 tesla, and identified the effects of MVS in the scaling of functional resting-state network fluctuations, showing that MVS does indeed influence resting-state networks due to vestibular imbalance. Specifically, MVS does influence DMN resting-state network dynamics in accordance with the predicted scaling of MVS based on the Lorentz-force model for MVS. These results taken together not only imply that subjects were in a vestibular state of imbalance, but also that the extent and direction of the state of imbalance showed more variance between subjects with increasing field strength. In summary, the following suggestions for vestibular research can be delineated to extend the kind of questions that can be answered by functional MRI experiments and to improve these investigations for the benefit of clinically relevant research of healthy controls and patients. Regarding the influence of age, we suggest that researchers comparing patients with vestibular deficits and healthy controls should separate the age-matched group into age-strata (non-overlapping subgroups with different age spans, e.g. 20-40 years, 40-60 years and above 60 years of age). Each stratum should be compared and interpreted separately given that different age-groups have different levels of vestibular network dynamics available for compensation (or responding to a challenge). This is particularly relevant when patients show a wide age-distribution, e.g. in the case of vestibular neuritis patients. With respect to the influence of magnetic fields, we suggest that MVS should be seen as a new way of manipulating networks that either process vestibular information or show vestibular interactions, by using strong magnetic fields (≥1.5 tesla), as commonly used in MRI. The potential of modulating vestibular influences on networks via MVS lies in being able to induce or manipulate vestibular imbalances. In the healthy this can be used to create states that are similar to the diseased state, but without peripheral or central lesions. In patients this will allow to extend or reduce vestibular imbalances. In both cases this can be done while performing functional MRI simply by using the magnetic field of the MRI scanner and adjusting the head position of the subject in question. In studies that need to avoid vestibular perturbations MVS should be controlled by adjusting the head position of the subject and measuring the resulting eye movements. This should then be seen as an effort to remove unwanted variance, i.e., as an effort to homogenize the group, and achieve better statistical results due to less (uncontrolled) MVS interference that increases bias and variance with increasing field strength. In summary, these suggestions result in three short questions that researchers could ask themselves when thinking about vestibular research projects in the future. Age-grouping: “Is the response to a challenge different for younger adults than older adults, i.e., does each age-group compensate differently?” MVS modulation: “Can a manipulation of the imbalance state of our subjects with MVS help us to reveal more about the vestibular network’s response to a challenge or should we avoid interference by MVS in the imbalance state of our subjects?” Sensitivity: “Is the measure that I want to use sensitive enough to show the differences that I am looking for?” Connectivity and temporal variability might be sensitive enough, but many clinical tests might not be sufficient

Beyond binary parcellation of the vestibular cortex - A dataset

The data-set presented in this data article is supplementary to the original publication, doi:10.1016/j.neuroimage.2018.05.018 (Kirsch et al., 2018). Named article describes handedness-dependent organizational patterns of functional subunits within the human vestibular cortical network that were revealed by functional magnetic resonance imaging (fMRI) connectivity parcellation. 60 healthy volunteers (30 left-handed and 30 right-handed) were examined on a 3T MR scanner using resting state fMRI. The multisensory (non-binary) nature of the human (vestibular) cortex was addressed by using masked binary and non-binary variations of independent component analysis (ICA). The data have been made publicly available via github (https://github.com/RainerBoegle/BeyondBinar yParcellationData). (C) 2019 The Authors. Published by Elsevier Inc

Visuospatial cognition in acute unilateral peripheral vestibulopathy

BackgroundThis study aims to investigate the presence of spatial cognitive impairments in patients with acute unilateral peripheral vestibulopathy (vestibular neuritis, AUPV) during both the acute phase and the recovery phase.MethodsA total of 72 AUPV patients (37 with right-sided AUPV and 35 with left-sided AUPV;aged 34-80 years, median 60.5;39 males, 54.2%) and 35 healthy controls (HCs;aged 43-75 years, median 59;20 males, 57.1%) participated in the study. Patients underwent comprehensive neurotological assessments, including video-oculography, video head impulse and caloric tests, ocular and cervical vestibular-evoked myogenic potentials, and pure-tone audiometry. Additionally, the Visual Object and Space Perception (VOSP) battery was used to evaluate visuospatial perception, while the Block design test and Corsi block-tapping test assessed visuospatial memory within the first 2 days (acute phase) and 4 weeks after symptom onset (recovery phase).ResultsAlthough AUPV patients were able to successfully perform visuospatial perception tasks within normal parameters, they demonstrated statistically worse performance on the visuospatial memory tests compared to HCs during the acute phase. When comparing right versus left AUPV groups, significant decreased scores in visuospatial perception and memory were observed in the right AUPV group relative to the left AUPV group. In the recovery phase, patients showed substantial improvements even in these previously diminished visuospatial cognitive performances.ConclusionAUPV patients showed different spatial cognition responses, like spatial memory, depending on the affected ear, improving with vestibular compensation over time. We advocate both objective and subjective visuospatial assessments and the development of tests to detect potential cognitive deficits after unilateral vestibular impairments

Structural reorganization of the cerebral cortex after vestibulo-cerebellar stroke

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

Global multisensory reorganization after vestibular brain stem stroke

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

Visuospatial cognition in acute unilateral peripheral vestibulopathy

BackgroundThis study aims to investigate the presence of spatial cognitive impairments in patients with acute unilateral peripheral vestibulopathy (vestibular neuritis, AUPV) during both the acute phase and the recovery phase.MethodsA total of 72 AUPV patients (37 with right-sided AUPV and 35 with left-sided AUPV; aged 34–80 years, median 60.5; 39 males, 54.2%) and 35 healthy controls (HCs; aged 43–75 years, median 59; 20 males, 57.1%) participated in the study. Patients underwent comprehensive neurotological assessments, including video-oculography, video head impulse and caloric tests, ocular and cervical vestibular-evoked myogenic potentials, and pure-tone audiometry. Additionally, the Visual Object and Space Perception (VOSP) battery was used to evaluate visuospatial perception, while the Block design test and Corsi block-tapping test assessed visuospatial memory within the first 2 days (acute phase) and 4 weeks after symptom onset (recovery phase).ResultsAlthough AUPV patients were able to successfully perform visuospatial perception tasks within normal parameters, they demonstrated statistically worse performance on the visuospatial memory tests compared to HCs during the acute phase. When comparing right versus left AUPV groups, significant decreased scores in visuospatial perception and memory were observed in the right AUPV group relative to the left AUPV group. In the recovery phase, patients showed substantial improvements even in these previously diminished visuospatial cognitive performances.ConclusionAUPV patients showed different spatial cognition responses, like spatial memory, depending on the affected ear, improving with vestibular compensation over time. We advocate both objective and subjective visuospatial assessments and the development of tests to detect potential cognitive deficits after unilateral vestibular impairments

Quelle stratégie de communication mettre en place pour augmenter la valeur perçue du Gardasil® en Europe ?

LYON1-BU Santé (693882101) / SudocSudocFranceF

Investigating the vestibular system using modern imaging techniques – A review on the available stimulation and imaging methods

The vestibular organs, located in the inner ear, sense linear and rotational acceleration of the head and itsposition relative to the gravitationalfield of the earth. These signals are essential for many fundamental skillssuch as the coordination of eye and head movements in the three-dimensional space or the bipedal locomotion ofhumans. Furthermore, the vestibular signals have been shown to contribute to higher cognitive functions such asnavigation. As the main aim of the vestibular system is the sensation of motion it is a challenging system to bestudied in combination with modern imaging methods. Over the last years various different methods were usedfor stimulating the vestibular system. These methods range from artificial approaches like galvanic or caloricvestibular stimulation to passive full body accelerations using hexapod motion platforms, or rotatory chairs. Inthefirst section of this review we provide an overview over all methods used in vestibular stimulation incombination with imaging methods (fMRI, PET, E/MEG, fNIRS). The advantages and disadvantages of everymethod are discussed, and we summarize typical settings and parameters used in previous studies. In the secondsection the role of the four imaging techniques are discussed in the context of vestibular research and theirpotential strengths and interactions with the presented stimulation methods are outlined