Evaluation of a multimodal diagnostic algorithm for prediction of cognitive impairment in elderly patients with dizziness.

BACKGROUND: The current diagnostic workup for chronic dizziness in elderly patients often neglects neuropsychological assessment, thus missing a relevant proportion of patients, who perceive dizziness as a subjective chief complaint of a concomitant cognitive impairment. This study aimed to establish risk prediction models for cognitive impairment in chronic dizzy patients based on data sources routinely collected in a dizziness center. METHODS: One hundred patients (age: 74.7 ± 7.1 years, 41.0% women) with chronic dizziness were prospectively characterized by (1) neuro-otological testing, (2) quantitative gait assessment, (3) graduation of focal brain atrophy and white matter lesion load, and (4) cognitive screening (MoCA). A linear regression model was trained to predict patients' total MoCA score based on 16 clinical features derived from demographics, vestibular testing, gait analysis, and imaging scales. Additionally, we trained a binary logistic regression model on the same data sources to identify those patients with a cognitive impairment (i.e., MoCA < 25). RESULTS: The linear regression model explained almost half of the variance of patients' total MoCA score (R2 = 0.49; mean absolute error: 1.7). The most important risk-predictors of cognitive impairment were age (ß = - 0.75), pathological Romberg's sign (ß = - 1.05), normal caloric test results (ß = - 0.8), slower timed-up-and-go test (ß = - 0.67), frontal (ß = - 0.6) and temporal (ß = - 0.54) brain atrophy. The binary classification yielded an area under the curve of 0.84 (95% CI 0.70-0.98) in distinguishing between cognitively normal and impaired patients. CONCLUSIONS: The need for cognitive testing in patients with chronic dizziness can be efficiently approximated by available data sources from routine diagnostic workup in a dizziness center.

A clinical 3D pointing test differentiates spatial memory deficits in dementia and bilateral vestibular failure.

BACKGROUND: Deficits in spatial memory, orientation, and navigation are often neglected early signs of cognitive impairment or loss of vestibular function. Real-world navigation tests require complex setups. In contrast, simple pointing at targets in a three-dimensional environment is a basic sensorimotor ability which provides an alternative measure of spatial orientation and memory at bedside. The aim of this study was to test the reliability of a previously established 3D-Real-World Pointing Test (3D-RWPT) in patients with cognitive impairment due to different neurodegenerative disorders, bilateral vestibulopathy, or a combination of both compared to healthy participants. METHODS: The 3D-RWPT was performed using a static array of targets in front of the seated participant before and, as a transformation task, after a 90-degree body rotation around the yaw-axis. Three groups of patients were enrolled: (1) chronic bilateral vestibulopathy (BVP) with normal cognition (n = 32), (2) cognitive impairment with normal vestibular function (n = 28), and (3) combined BVP and cognitive impairment (n = 9). The control group consisted of age-matched participants (HP) without cognitive and vestibular deficits (n = 67). Analyses focused on paradigm-specific mean angular deviation of pointing in the azimuth (horizontal) and polar (vertical) spatial planes, of the preferred pointing strategy (egocentric or allocentric), and the resulting shape configuration of the pointing array relative to the stimulus array. Statistical analysis was performed using age-corrected ANCOVA-testing with Bonferroni correction and correlation analysis using Spearman's rho. RESULTS: Patients with cognitive impairment employed more egocentric pointing strategies while patients with BVP but normal cognition and HP used more world-based solutions (pBonf 5.78 × 10-3**). Differences in pointing accuracy were only found in the azimuth plane, unveiling unique patterns where patients with cognitive impairment showed decreased accuracy in the transformation tasks of the 3D-RWPT (pBonf < 0.001***) while patients with BVP struggled in the post-rotation tasks (pBonf < 0.001***). Overall azimuth pointing performance was still adequate in some patients with BVP but significantly decreased when combined with a cognitive deficit. CONCLUSION: The 3D-RWPT provides a simple and fast measure of spatial orientation and memory. Cognitive impairment often led to a shift from world-based allocentric pointing strategy to an egocentric performance with less azimuth accuracy compared to age-matched controls. This supports the view that cognitive deficits hinder the mental buildup of the stimulus pattern represented as a geometrical form. Vestibular hypofunction negatively affected spatial memory and pointing performance in the azimuth plane. The most severe spatial impairments (angular deviation, figure frame configuration) were found in patients with combined cognitive and vestibular deficits.

Shape configuration of mental targets representation as a holistic measure in a 3D real world pointing test for spatial orientation.

Deficits in spatial memory are often early signs of neurological disorders. Here, we analyzed the geometrical shape configuration of 2D-projections of pointing performances to a memorized array of spatially distributed targets in order to assess the feasibility of this new holistic analysis method. The influence of gender differences and cognitive impairment was taken into account in this methodological study. 56 right-handed healthy participants (28 female, mean age 48.89 ± 19.35 years) and 22 right-handed patients with heterogeneous cognitive impairment (12 female, mean age 71.73 ± 7.41 years) underwent a previously validated 3D-real-world pointing test (3D-RWPT). Participants were shown a 9-dot target matrix and afterwards asked to point towards each target in randomized order with closed eyes in different body positions relative to the matrix. Two-dimensional projections of these pointing vectors (i.e., the shapes resulting from the individual dots) were then quantified using morphological analyses. Shape configurations in healthy volunteers largely reflected the real-world target pattern with gender-dependent differences (ANCOVA area males vs. females F(1,73) = 9.00, p 3.69 × 10-3, partial η2 = 0.10, post-hoc difference = 38,350.43, pbonf=3.69 × 10-3**, Cohen's d 0.76, t 3.00). Patients with cognitive impairment showed distorted rectangularity with more large-scale errors, resulting in decreased overall average diameters and solidity (ANCOVA diameter normal cognition/cognitive impairment F(1,71) = 9.30, p 3.22 × 10-3, partial η2 = 0.09, post-hoc difference = 31.22, pbonf=3.19 × 10-3**, Cohen's d 0.92, t 3.05; solidity normal cognition/cognitive impairment F(1,71) = 7.79, p 6.75 × 10-3, partial η2 = 0.08, post-hoc difference = 0.07, pbonf=6.76 × 10-3** Cohen's d 0.84, t 2.79). Shape configuration analysis of the 3D-RWPT target array appears to be a suitable holistic measure of spatial performance in a pointing task. The results of this methodological investigation support further testing in a clinical study for differential diagnosis of disorders with spatial memory deficits.

Different approaches to test orientation of self in space: comparison of a 2D pen-and-paper test and a 3D real-world pointing task.

Spatial orientation is based on a complex cortical network with input from multiple sensory systems. It is affected by training, sex and age as well as cultural and psychological factors, resulting in different individual skill levels in healthy subjects. Various neurological disorders can lead to different patterns or specific deficits of spatial orientation and navigation. Accordingly, numerous tests have been proposed to assess these abilities. Here, we compare the results of (1) a validated questionnaire-based self-estimate of orientation/navigation ability (Santa Barbara Sense of Direction Scale, SBSODS) and (2) a validated pen-and-paper two-dimensional perspective test (Perspective Taking Spatial Orientation Test, SOT) with (3) a newly developed test of finger-arm pointing performance in a 3D real-world (3D-RWPT) paradigm using a recently established pointing device. A heterogeneous group of 121 participants (mean age 56.5 ± 17.7 years, 52 females), including 16 healthy volunteers and 105 patients with different vestibular, ocular motor and degenerative brain disorders, was included in this study. A high correlation was found between 2D perspective task and 3D pointing along the horizontal (azimuth) but not along the vertical (polar) plane. Self-estimated navigation ability (SBSODS) could not reliably predict actual performance in either 2D- or 3D-tests. Clinical assessment of spatial orientation and memory should therefore include measurements of actual performance, based on a 2D pen-and-paper test or a 3D pointing task, rather than memory-based questionnaires, since solely relying on the patient's history of self-estimated navigation ability results in misjudgments. The 3D finger-arm pointing test (3D-RWPT) reveals additional information on vertical (polar) spatial performance which goes undetected in conventional 2D pen-and-paper tests. Diseases or age-specific changes of spatial orientation in the vertical plane should not be clinically neglected. The major aim of this pilot study was to compare the practicability and capability of the three tests but not yet to prove their use for differential diagnosis. The next step will be to establish a suitable clinical bedside test for spatial memory and orientation.

Different strategies in pointing tasks and their impact on clinical bedside tests of spatial orientation.

Deficits in spatial memory, orientation, and navigation are often early or neglected signs of degenerative and vestibular neurological disorders. A simple and reliable bedside test of these functions would be extremely relevant for diagnostic routine. Pointing at targets in the 3D environment is a basic well-trained common sensorimotor ability that provides a suitable measure. We here describe a smartphone-based pointing device using the built-in inertial sensors for analysis of pointing performance in azimuth and polar spatial coordinates. Interpretation of the vectors measured in this way is not trivial, since the individuals tested may use at least two different strategies: first, they may perform the task in an egocentric eye-based reference system by aligning the fingertip with the target retinotopically or second, by aligning the stretched arm and the index finger with the visual line of sight in allocentric world-based coordinates similar to using a rifle. The two strategies result in considerable differences of target coordinates. A pilot test with a further developed design of the device and an app for a standardized bedside utilization in five healthy volunteers revealed an overall mean deviation of less than 5° between the measured and the true coordinates. Future investigations of neurological patients comparing their performance before and after changes in body position (chair rotation) may allow differentiation of distinct orientational deficits in peripheral (vestibulopathy) or central (hippocampal or cortical) disorders.

The role of delta and theta oscillations during ego-motion in healthy adult volunteers.

The successful cortical processing of multisensory input typically requires the integration of data represented in different reference systems to perform many fundamental tasks, such as bipedal locomotion. Animal studies have provided insights into the integration processes performed by the neocortex and have identified region specific tuning curves for different reference frames during ego-motion. Yet, there remains almost no data on this topic in humans.In this study, an experiment originally performed in animal research with the aim to identify brain regions modulated by the position of the head and eyes relative to a translational ego-motion was adapted for humans. Subjects sitting on a motion platform were accelerated along a translational pathway with either eyes and head aligned or a 20° yaw-plane offset relative to the motion direction while EEG was recorded.Using a distributed source localization approach, it was found that activity in area PFm, a part of Brodmann area 40, was modulated by the congruency of translational motion direction, eye, and head position. In addition, an asymmetry between the hemispheres in the opercular-insular region was observed during the cortical processing of the vestibular input. A frequency specific analysis revealed that low-frequency oscillations in the delta- and theta-band are modulated by vestibular stimulation. Source-localization estimated that the observed low-frequency oscillations are generated by vestibular core-regions, such as the parieto-opercular region and frontal areas like the mid-orbital gyrus and the medial frontal gyrus.

VOLT: a novel open-source pipeline for automatic segmentation of endolymphatic space in inner ear MRI.

BACKGROUND: Objective and volumetric quantification is a necessary step in the assessment and comparison of endolymphatic hydrops (ELH) results. Here, we introduce a novel tool for automatic volumetric segmentation of the endolymphatic space (ELS) for ELH detection in delayed intravenous gadolinium-enhanced magnetic resonance imaging of inner ear (iMRI) data. METHODS: The core component is a novel algorithm based on Volumetric Local Thresholding (VOLT). The study included three different data sets: a real-world data set (D1) to develop the novel ELH detection algorithm and two validating data sets, one artificial (D2) and one entirely unseen prospective real-world data set (D3). D1 included 210 inner ears of 105 patients (50 male; mean age 50.4 ± 17.1 years), and D3 included 20 inner ears of 10 patients (5 male; mean age 46.8 ± 14.4 years) with episodic vertigo attacks of different etiology. D1 and D3 did not differ significantly concerning age, gender, the grade of ELH, or data quality. As an artificial data set, D2 provided a known ground truth and consisted of an 8-bit cuboid volume using the same voxel-size and grid as real-world data with different sized cylindrical and cuboid-shaped cutouts (signal) whose grayscale values matched the real-world data set D1 (mean 68.7 ± 7.8; range 48.9-92.8). The evaluation included segmentation accuracy using the Sørensen-Dice overlap coefficient and segmentation precision by comparing the volume of the ELS. RESULTS: VOLT resulted in a high level of performance and accuracy in comparison with the respective gold standard. In the case of the artificial data set, VOLT outperformed the gold standard in higher noise levels. Data processing steps are fully automated and run without further user input in less than 60 s. ELS volume measured by automatic segmentation correlated significantly with the clinical grading of the ELS (p < 0.01). CONCLUSION: VOLT enables an open-source reproducible, reliable, and automatic volumetric quantification of the inner ears' fluid space using MR volumetric assessment of endolymphatic hydrops. This tool constitutes an important step towards comparable and systematic big data analyses of the ELS in patients with the frequent syndrome of episodic vertigo attacks. A generic version of our three-dimensional thresholding algorithm has been made available to the scientific community via GitHub as an ImageJ-plugin.

Spectral fingerprints of correct vestibular discrimination of the intensity of body accelerations.

Perceptual decision-making is a complex task that requires multiple processing steps performed by spatially distinct brain regions interacting in order to optimize perception and motor response. Most of our knowledge on these processes and interactions were derived from unimodal stimulations of the visual system which identified the lateral intraparietal area and the posterior parietal cortex as critical regions. Unlike the visual system, the vestibular system has no primary cortical areas and it is associated with separate multisensory areas within the temporo-parietal cortex with the parieto-insular vestibular cortex, PIVC, being the core region. The aim of the presented experiment was to investigate the transition from sensation to perception and to reveal the main structures of the cortical vestibular system involved in perceptual decision-making. Therefore, an EEG analysis was performed in 35 healthy subjects during linear whole-body accelerations of different intensities on a motor-driven motion platform (hexapod). We used a discrimination task in order to judge the intensity of the accelerations. Furthermore, we manipulated the expectation of the upcoming stimulus by indicating the probability (25%, 50%, 75%, 100%) of the motion direction. The analysis of the vestibular evoked potentials (VestEPs) showed that the decision-making process leads to a second positive peak (P2b) which was not observed in previous task-free experiments. The comparison of the estimated neural generators of the P2a and P2b components showed significant activity differences in the anterior cingulus, the parahippocampal and the middle temporal gyri. Taking into account the time courses of the P2 components, the physical properties of the stimuli, and the responses given by the subjects we conclude that the P2b likely reflects the transition from the processing of sensory information to perceptual evaluation. Analyzing the decision-uncertainty reported by the subjects, a persistent divergence of the time courses starting at 188 â€‹ms after the acceleration was found at electrode Pz. This finding demonstrated that meta-cognition by means of confidence estimation starts in parallel with the decision-making process itself. Further analyses in the time-frequency domain revealed that a correct classification of acceleration intensities correlated with an inter-trial phase clustering at electrode Cz and an inter-site phase clustering of theta oscillations over frontal, central, and parietal cortical areas. The sites where the phase clustering was observed corresponded to core decision-making brain areas known from neuroimaging studies in the visual domain.

Modulatory effects of magnetic vestibular stimulation on resting-state networks can be explained by subject-specific orientation of inner-ear anatomy in the MR static magnetic field.

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.

Health-related quality of life and functional impairment in acute vestibular disorders.

BACKGROUND AND PURPOSE: Acute vestibular symptoms have a profound impact on patients' well-being. In this study, health-related quality of life (HRQoL) and functional impairment were investigated prospectively in patients with different peripheral and central vestibular disorders during the acute symptomatic stage to decipher the most relevant underlying factors. METHODS: In all, 175 patients with acute vestibular disorders were categorized as central vestibular (CV, n = 40), peripheral vestibular (PV, n = 68) and episodic vestibular disorders (EV, n = 67). All patients completed scores to quantify generic HRQoL (European Quality of Life Score Five Dimensions Five Levels, EQ-5D-5L) and disease-specific HRQoL (Dizziness Handicap Inventory, DHI). Vestibular-ocular motor signs were assessed by video-oculography, vestibular-spinal control by posturography and verticality perception by measurement of subjective visual vertical. RESULTS: Patients with PV had a poorer HRQoL compared to patients with CV and EV (EQ-5D-5L/DHI: PV, 0.53 ± 0.31/56.1 ± 19.7; CV, 0.66 ± 0.28/43.3 ± 24.0; EV, 0.75 ± 0.24/46.7 ± 21.4). After adjusting for age, gender, cardiovascular risk factors and non-vestibular brainstem/cerebellar dysfunction patients with PV persisted to have poorer generic and disease-specific HRQoL (EQ-5D-5L -0.17, DHI +11.2) than patients with CV. Horizontal spontaneous nystagmus was a highly relevant factor for subgroup differences in EQ-5D-5L and DHI, whilst vertical spontaneous nystagmus, subjective visual vertical and sway path were not. EQ-5D-5L decreased significantly with more intense horizontal subjective visual vertical in CV (rho = -0.57) and PV (rho = -0.5) but not EV (rho = -0.13). CONCLUSIONS: Patients with PV have the highest functional impairment of all patients with acute vestibular disorders. Vestibular-ocular motor disturbance in the yaw plane has more impact than vestibular-spinal or vestibular-perceptive asymmetry in the roll and pitch plane, suggesting that horizontal visual stability is the most critical for HRQoL.

Clinical implications of head-shaking nystagmus in central and peripheral vestibular disorders: is perverted head-shaking nystagmus specific for central vestibular pathology?

BACKGROUND AND PURPOSE: The patterns of head-shaking nystagmus (HSN) aid in differentiation between central and peripheral vestibular disorders, and perverted HSN (pHSN) has been considered a central sign. The aim was to determine the characteristics of HSN in a large number of patients with either peripheral or central vestibular disorders in a dizziness clinic of a university hospital. METHODS: The medical records of 7544 dizzy patients were reviewed during a year and 822 patients with a clinical diagnosis of vestibular disorders were recruited. The findings of spontaneous nystagmus (SN) and HSN in these patients were compared with those of healthy controls (n = 48). RESULTS: A total of 217 of the 822 patients (26.4%) were classified as having a central vestibular disorder, whilst 397 (48.3%) had a peripheral vestibular disorder. In the peripheral vestibular disorder group, SN was observed in 14.1% and HSN in 40.8%, amongst whom 24.1% were the pHSN form. In the central group, SN was observed in 17.5% and HSN in 24.0% of whom 57.7% was pHSN. HSN was more frequently observed in the peripheral vestibular disorder group than in the central group (40.8% vs. 24.0%, P < 0.01). However, the proportion of pHSN was significantly increased in the central group compared to the peripheral vestibular patient group (57.7% vs. 24.1%, P < 0.01). CONCLUSIONS: Since pHSN is not specific for central vestibular disorders, other clinical features should be considered in pursuing a central lesion in patients with pHSN.

Addressing a real-life problem: treatment with intravenous thrombolysis and mechanical thrombectomy in acute stroke patients with an extended time window beyond 4.5 h based on computed tomography perfusion imaging.

BACKGROUND AND PURPOSE: Acute ischemic stroke treatment with intravenous thrombolysis (IVT) is restricted to a time window of 4.5 h after known or presumed onset. Recently, magnetic resonance imaging-guided treatment decision-making in wake-up stroke (WUS) was shown to be effective. The aim of this study was to determine the safety and outcome of IVT in patients with a time window beyond 4.5 h selected by computed tomography perfusion (CTP) imaging. METHODS: We analyzed all consecutive patients last seen well beyond 4.5 h after stroke onset treated with IVT based on CTP between January 2015 and October 2018. CTP was visually assessed to estimate the mismatch between cerebral blood flow and cerebral blood volume maps. Early infarct signs were documented according to Alberta Stroke Program Early CT Score (ASPECTS). Safety data were obtained for mortality and symptomatic intracerebral hemorrhage (sICH). Follow-up was assessed with the modified Rankin Scale (mRS). RESULTS: A total of 70 patients fulfilled the inclusion criteria (mean age ± SD 77.6 ± 11.5 years, 50.0% female). Median National Institutes of Health Stroke Scale score on admission was 8.0 [interquartile range (IQR), 4-14]. The most frequent reasons for an extended time window were WUS (60.0%) and delayed hospital admission (27.1%). Median time from last seen well to IVT was 11.4 h. Median ASPECTS was 10 (IQR, 9-10) and CTP mismatch 90% (IQR, 80%-100%). A total of 24 patients (34.3%) underwent additional mechanical thrombectomy. sICH occurred in four patients (5.7%). At follow-up, 49.3% had an mRS score of 0-2 and 22.4% had an mRS score of 0-1. CONCLUSIONS: In patients presenting in an extended time window beyond 4.5 h, IVT treatment with decision-making based on CTP might be a safe procedure. Further evaluation in clinical trials is needed.

Distorted mental spatial representation of multi-level buildings - Humans are biased towards equilateral shapes of height and width.

A distorted model of a familiar multi-level building with a systematic overestimation of the height was demonstrated earlier in psychophysical and real world navigational tasks. In the current study we further investigated this phenomenon with a tablet-based application. Participants were asked to adjust height and width of the presented buildings to best match their memory of the dimensional ratio. The estimation errors between adjusted and true height-width ratios were analyzed. Additionally, familiarity with respect to in- and outside of the building as well as demographic data were acquired. A total of 142 subjects aged 21 to 90 years from the cities of Bern and Munich were tested. Major results were: (1) a median overestimation of the height of the multi-level buildings of 11%; (2) estimation errors were significantly less if the particular building was unknown to participants; (3) in contrast, the height of tower-like buildings was underestimated; (4) the height of long, flat shaped buildings was overestimated. (5) Further features, such as the architectonical complexity were critical. Overall, our internal models of large multi-level buildings are distorted due to multiple factors including geometric features and memory effects demonstrating that such individual models are not rigid but plastic with consequences for spatial orientation and navigation.

A probabilistic atlas of the human inner ear's bony labyrinth enables reliable atlas-based segmentation of the total fluid space.

Intravenous contrast agent-enhanced magnetic resonance imaging of the endolymphatic space (ELS) of the inner ear permits direct, in-vivo, non-invasive visualization of labyrinthine structures and thus verification of endolymphatic hydrops (ELH). However, current volumetric assessment approaches lack normalization. The aim of this study was to develop a probabilistic atlas of the inner ear's bony labyrinth as a first step towards an automated and reproducible volume-based quantification of the ELS. The study included three different datasets: a source dataset (D1) to build the probabilistic atlas and two testing sets (D2, D3). D1 included 24 right-handed patients (12 females; mean age 51.5 ± 3.9 years) and D2 5 patients (3 female; mean age 48.8 ± 5.01 years) with vestibular migraine without ELH or any measurable vestibular deficits. D3 consisted of five patients (one female; mean age 46 ± 5.2 years) suffering from unilateral Menière's disease and ELH. Data processing comprised three steps: preprocessing using an affine and deformable fusion registration pipeline, computation of an atlas for the left and right inner ear using a label-assisted approach, and validation of the atlas based on localizing and segmenting previously unseen ears. The three-dimensional probabilistic atlas of the inner ear's bony labyrinth consisted of the internal acoustic meatus and inner ears (including cochlea, otoliths, and semicircular canals) for both sides separately. The analyses showed a high level of agreement between the atlas-based segmentation and the manual gold standard with an overlap of 89% for the right ear and 86% for the left ear (measured by dice scores). This probabilistic in vivo atlas of the human inner ear's bony labyrinth and thus of the inner ear's total fluid space for both ears represents a necessary step towards a normalized, easily reproducible and reliable volumetric quantification of the perilymphatic and endolymphatic space in view of MR volumetric assessment of ELH. The proposed atlas lays the groundwork for state-of-the-art approaches (e.g., deep learning) and will be provided to the scientific community.

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/BeyondBinaryParcellationData).

[Neuro-otology: at the borders of ear and brain]. / Neurootologie: Grenzfälle zwischen Ohr und Gehirn.

Vertigo and dizziness are frequent chief complaints in clinical practice. Symptoms may originate from otological, neurological, medical and psychiatric etiologies, which poses an interdisciplinary challenge. Systematic analysis of case history and clinical examination generally allow classification into peripheral-, central- or non-vestibular disorders. The most important criteria for differentiation are the timeline, quality of symptoms, modulating factors and accompanying symptoms. As concerns the clinical examination, the following tests are relevant: head impulse test, test for spontaneous nystagmus, positional nystagmus, central ocular motor signs and the Romberg test. However, neuro-otological disorders with combined peripheral and central vestibular pathology do exist. Occlusion of the anterior inferior cerebellar artery results in ischemia of the labyrinth and cerebellum and therefore causes acute vestibular syndrome and unilateral hearing loss. Repetitive attacks of vertigo or dizziness which are accompanied by ear symptoms and headaches may be due to an overlap syndrome of Menière's disease and vestibular migraine. In this case patients often have to be treated with a dual prophylactic medication to control symptoms. In case of chronic dizziness and instability of gait a subsample of patients may suffer from CANVAS, which is a combination of bilateral vestibulopathy, a cerebellar syndrome and polyneuropathy. Chronic dizziness with signs of peripheral and central vestibular dysfunction can also originate from tumors of the cerebellopontine angle with compression of central structures. In conclusion, the diagnostic algorithm in the workup of patients with vertigo and dizziness should always include tests for peripheral and central vestibular and ocular motor function.

Handedness-dependent functional organizational patterns within the bilateral vestibular cortical network revealed by fMRI connectivity based parcellation.

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.