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.

[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.

Unreliable association between self-reported sense of direction and peripheral vestibular function.

BACKGROUND: Uni- or bilateral peripheralvestibular impairment causes objective spatial orientation deficits, which can be measured using pen-and-paper-tests or sensorimotor tasks (navigation or pointing). For patients' subjective orientation abilities, questionnaires are commonly used (e.g., Santa Barbara sense of direction scale [SBSODS]). However, the relationship between subjective assessment of spatial skills and objective vestibular function has only been scarcely investigated. METHODS: A total of 177 patients (mean age 57.86 ± 17.53 years, 90 females) who presented in our tertiary Center for Vertigo and Balance Disorders underwent neuro-otological examinations, including bithermal water calorics, video head impulse test (vHIT), and testing of the subjective visual vertical (SVV), and filled out the SBSODS (German version). Correlation analyses and linear multiple regression model analyses were performed between vestibular test results and self-assessment scores. Additionally, groupwise vestibular function for patients with low, average, and high self-report scores was analyzed. RESULTS: Forty-two patients fulfilled the diagnostic criteria for bilateral vestibulopathy, 93 for chronic unilateral vestibulopathy (68 unilateral caloric hypofunction and 25 isolated horizontal vestibulo-ocular reflex deficits), and 42 patients had normal vestibular test results. SBSODS scores showed clear sex differences with higher subjective skill levels in males (mean score males: 4.94 ± 0.99, females 4.40 ± 0.94; Student's t-test: t-3.78, p < .001***). No stable correlation between objective vestibular function and subjective sense of spatial orientation was found. A multiple linear regression model could not reliably explain the self-reported variance. The three patient groups with low, average, and high self-assessment-scores showed no significant differences of vestibular function. CONCLUSION: Self-reported assessment of spatial orientation does not robustly correlate with objective peripheral vestibular function. Therefore, other methods of measuring spatial skills in real-world and virtual environments are required to disclose orientation deficits due to vestibular hypofunction.

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.

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.

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.

Appraisal of the signal-to-noise-ratio of uni- and bipolar recordings of ocular vestibular evoked myogenic potentials.

Ocular vestibular evoked myogenic potentials (oVEMPs) are a non-invasive method to investigate otolith function mediated via the superior vestibular nerve. However, the herein used recordings and protocols may alter within different studies. In particular the diverging use of electrode configuration regarding polarity or even electrode position varies across studies. Therefore, a systematic analysis and appraisal of the different electrode configuration seems mandatory. In this study we compared the quality of uni- and bipolar recordings based on the signal to noise ratio (SNR). We recoded oVEMPs using a uni- and bipolar electrode configuration simultaneously and compared the recorded amplitudes and latencies and calculated the SNR. The amplitudes recorded by the unipolar configurations were significantly (p < 0.01) increased compared to the bipolar configuration. However, the SNR of the bipolar setup was significantly better (p < 0.05) when compared to the unipolar setup. Additionally, we estimated a transfer function that enabled a comparison of uni- and bipolar recordings. To conclude, the variety of setups used for oVEMP recording hinder a comparison of results and unipolar electrode configurations have clear disadvantages.