Cognition in vestibular disorders: state of the field, challenges, and priorities for the future

Vestibular disorders are prevalent and debilitating conditions of the inner ear and brain which affect balance, coordination, and the integration of multisensory inputs. A growing body of research has linked vestibular disorders to cognitive problems, most notably attention, visuospatial perception, spatial memory, and executive function. However, the mechanistic bases of these cognitive sequelae remain poorly defined, and there is a gap between our theoretical understanding of vestibular cognitive dysfunction, and how best to identify and manage this within clinical practice. This article takes stock of these shortcomings and provides recommendations and priorities for healthcare professionals who assess and treat vestibular disorders, and for researchers developing cognitive models and rehabilitation interventions. We highlight the importance of multidisciplinary collaboration for developing and evaluating clinically relevant theoretical models of vestibular cognition, to advance research and treatment

Cognition in vestibular disorders: state of the field, challenges, and priorities for the future

Vestibular disorders are prevalent and debilitating conditions of the inner ear and brain which affect balance, coordination, and the integration of multisensory inputs. A growing body of research has linked vestibular disorders to cognitive problems, most notably attention, visuospatial perception, spatial memory, and executive function. However, the mechanistic bases of these cognitive sequelae remain poorly defined, and there is a gap between our theoretical understanding of vestibular cognitive dysfunction, and how best to identify and manage this within clinical practice. This article takes stock of these shortcomings and provides recommendations and priorities for healthcare professionals who assess and treat vestibular disorders, and for researchers developing cognitive models and rehabilitation interventions. We highlight the importance of multidisciplinary collaboration for developing and evaluating clinically relevant theoretical models of vestibular cognition, to advance research and treatment

Reliability of the Dynamic Gait Index in Vestibular Disorders

The purpose of this study was to examine the inter-rater and intra-rater reliability of the Dynamic Gait Index (DGI) when used with patients with vestibular disorders. Subjects included 30 patients aged 27-88 years, with vestibular disorders, who were referred for vestibular rehabilitation. Subjects\u27 performance on the DGI was concurrently rated by two physical therapists experienced in vestibular rehabilitation to determine inter-rater reliability. To determine intra-rater reliability each subject repeated the DGI one-hour later. Percent agreement and kappa statistics were calculated for individual DGI items. Kappa statistics for individual items were averaged to yield a composite kappa score of the DGI. Total DGI scores were evaluated for inter-rater and intra-rater reliability using Spearman rank order correlation coefficient. Inter-rater reliability of individual DGI items varied from poor to excellent based on kappa values. Composite kappa values demonstrated good overall inter-rater reliability of total DGI scores. Spearman Rho demonstrated excellent correlation between total DGI scores of both raters. Intra-rater reliability of individual items varied from fair to excellent based on kappa values. Composite kappa values demonstrated good overall intra-rater reliability of DGI. Fair but significant correlation was demonstrated between total DGI scores using Spearman Rho. It was concluded that the Dynamic Gait Index demonstrated only fair inter- and intra-rater reliability when used with subjects with vestibular disorders

The Effect of Vibrotactile Feedback on Healthy People and People with Vestibular Disorders during Dual-task Conditions

Vibrotactile feedback (VTF) has been shown to improve balance performance in healthy people and people with vestibular disorders in a single-task experimental condition. However, typical balance activities occur in a multi-task environment. Dual-task performance can degrade with age and in people with vestibular disorders. It is unclear if the ability to use VTF might be affected by dual-task conditions in different age groups and people with vestibular disorders. The purposes of this dissertation are to investigate in healthy young and older adults, and people with vestibular disorders: 1) balance performance in a dual-task paradigm under various sensory conditions while using VTF, 2) reaction time during dual-task performance under different sensory conditions while using VTF, and 3) the effect of testing duration and visit on VTF use. Three study visits were included in this dissertation study: one screening visit and two experimental visits. Twenty younger and twenty older subjects were recruited in the first study to determine if VTF was affected by age. Seven people with unilateral vestibular hypofunction (UVH) and seven age-matched controls were recruited in the second study to investigate the effect of vestibular dysfunction. The results showed that young and older adults use VTF differently, depending on the underlying sensory integration balance task. Older adults increased postural sway during fixed platform conditions, but both young and older adults decreased postural sway during sway-referenced platform conditions. Reaction times on the secondary cognitive tasks increased more while using the VTF in older adults compared with young adults. This finding suggested that using VTF requires greater attention in older adults. The trial duration and visit also affected postural sway performance while VTF was applied. Similar postural sway results were found when comparing people with UVH and age-matched controls. However, no group difference was found between people with UVH and age-matched controls in the magnitude of postural sway, which suggested that people with UVH were able to use VTF under dual-task conditions similar to normal adults. Our data also indicated that people with UVH require more attentional resources to perform secondary cognitive tasks while using VTF

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

Doctor of Philosophy in Rehabilitation Science

dissertationMultiple Sclerosis (MS) is a chronic, neurological disorder characterized by imbalance and falls. Accurate perception and integration of three sensory inputs - the vestibular, vision, and somatosensory, is critical to produce human gaze and posture orientation. In MS, demyelination of pathways within the brainstem and cerebellum adversely affect gaze and postural stability. However, the deficits and the psychometric properties of these measures remain less examined. Moreover, the benefits of training on gaze and postural stability are unknown in MS. This study examined the deficits in gaze stability, dynamic balance, and self-report measures in persons with MS as compared to controls; assessed the test-retest reliability and response stability of gaze stability, postural sway, and dynamic balance tests; and investigated the effects of training on gaze stability, galvanic-induced postural sway, dynamic balance, and self-report measures in persons with MS. We hypothesized that persons with MS will demonstrate deficits in gaze and postural stability; that study measures will demonstrate moderate to good reliability and acceptable response stability; and that persons with MS will demonstrate significant improvements after training. Nineteen persons with MS at fall-risk and 14 controls were recruited and the assessments were carried out on 2 occasions. The participants then completed a 2-week training followed by re-assessments. Persons with MS demonstrated significant differences in the gaze stability, dynamic balance, and self-report measures versus controls. In addition, significant inter-relationships were found. The majority of gaze stabilization measures demonstrated moderate while the postural sway and dynamic balance measures showed good reliability. The aVOR gain, FGA, and FSST showed SEM % <20 and MDD95% <20, suggesting acceptable response stability. After training, gaze stability was achieved by recruiting substitutive oculomotor strategies whereas postural stability was achieved by sway response adaptations. Consistent improvements in dynamic balance and self-report measures suggest clinically meaningful changes. Taken together, these findings support the study hypothesis and suggest that significant deficits in gaze and posture may be present in persons with MS. This highlights the utility of these assessments in fall-risk evaluations in persons with MS. Moreover, the different strategical mechanisms for improvements after training suggest the clinical value of a focused training intervention

The feasibility of standardized cognitive assessments for vestibular patients

Vestibular dysfunction, or impairments in the inner ear and/or brain structures that process sensory information and help control balance, has a high correlation with cognitive deficits, or problems with mental processes. This relationship negatively affects daily activities and quality of life in persons that live with vestibular dysfunction. Though there is sufficient research proving the relationship, few studies have applied that information in ways to better help the population with vestibular dysfunction. The purpose of this study was to assess the feasibility of a cognitive assessment battery (a set of correlated assessments delivered in one session) tailored to measuring performance in the specific cognitive domains that are affected by vestibular dysfunction, and to determine its practicality for clinical and research use. A thorough review of the literature was conducted to determine which tests exist that assess the specific cognitive domains that may be affected by vestibular disorders: attention, memory, executive function, language, visuospatial skills. The Cognitive Linguistic Quick Test (CLQT) was found to be the most appropriate, as it measures performance in these domains. In order to determine the practicality of the assessment, the CLQT was administered to a college population and an older population who were tested and found to have no vestibular abnormalities. The use of a validated objective measurement tool will improve the quality of research and the ability of clinicians to identify and address cognitive deficits and measure treatment effectiveness in vestibular patients

Gaze stabilization test: reliability, response stability, performance of healthy subjects and patients with concussion

Gaze stabilization test (GST) and dynamic visual acuity (DVA) test are functional measures of the vestibulo-ocular reflex which helps to maintain clear vision during head movement. The purposes of this dissertation were threefold; first the reliability of GST and DVA test were examined. Twenty-nine patients with vestibular disease were tested repeatedly using the computerized InVision™ test. Results showed that the reliability of the tests were fair to poor with the DVA reliability better than the GST and the within-session reliability better than between-session reliability. In the second Aim, the goal was to obtain better understanding of the effect of optotype (the letter E) parameters on subjects' performance. The performance of twenty-one healthy young subjects on the GST was examined over a range of optotype sizes and presentation times. Results showed that the optotype parameters had a significant effect on subjects' performance with only one combination in which most healthy subjects were able to accomplish fast head velocities while being able to identify the optotype correctly. An optotype that is 0.30 logMAR above a subject's static vision and presented for 40 msec longer than minimum presentation time is recommended for future testing. Lastly, the preferred combination from the second Aim was used to examine the performance of twenty-two young patients following concussion and compare it with the healthy subjects from Aim 2. Correlations between patients' performance on the GST and their scores on tests commonly used following concussion were also examined. Results showed no significant differences between the performance of patients and that of healthy subjects on the GST. Also, there were no significant correlations between the GST and other measures used following concussion. Results show that the protocol used for the GST needed refinement. Special consideration is to be given to the optotype parameters used since these were found to significantly influence performance. The lack of significant differences between patients following concussion and healthy subjects could be due to the inclusion of all patients following concussion without objective evidence of vestibular involvement. Future studies should use specific optotype parameters and include patients following concussion with evidence of vestibular dysfunction