Age-Related Changes in Temporal Binding Involving Auditory and Vestibular Inputs.

Maintaining balance involves the combination of sensory signals from the visual, vestibular, proprioceptive, and auditory systems. However, physical and biological constraints ensure that these signals are perceived slightly asynchronously. The brain only recognizes them as simultaneous when they occur within a period of time called the temporal binding window (TBW). Aging can prolong the TBW, leading to temporal uncertainty during multisensory integration. This effect might contribute to imbalance in the elderly but has not been examined with respect to vestibular inputs. Here, we compared the vestibular-related TBW in 13 younger and 12 older subjects undergoing 0.5 Hz sinusoidal rotations about the earth-vertical axis. An alternating dichotic auditory stimulus was presented at the same frequency but with the phase varied to determine the temporal range over which the two stimuli were perceived as simultaneous at least 75% of the time, defined as the TBW. The mean TBW among younger subjects was 286 ms (SEM ± 56 ms) and among older subjects was 560 ms (SEM ± 52 ms). TBW was related to vestibular sensitivity among younger but not older subjects, suggesting that a prolonged TBW could be a mechanism for imbalance in the elderly person independent of changes in peripheral vestibular function.

Comparative utility of vestibular function tests in patients with peripheral and central vestibular dysfunction.

Background: Bithermal caloric irrigation, video head impulse test (vHIT), and rotational testing are commonly used to assess peripheral vestibular function, but the relative clinical utility of each test in differentiating patients with peripheral vestibulopathy is debated. Objectives: To determine whether (1) the combination of two or more vestibular tests enhances diagnostic utility over a single test; (2) abnormal test results on vestibular tests correlate with one another. Methods: Retrospective analysis of data collected from multidisciplinary vestibular clinics at two academic medical centers from 2016 to 2022. Results: 150 patients (54.10 ± 15.09 years, 88 females) were included. No individual test was significantly better at predicting the presence of peripheral vestibular damage (p > 0.05). vHIT test results improved significantly when combined with either the caloric test (p = 0.007) or rotary chair test (p = 0.039). Caloric and rotational testing had high sensitivity (74.65% and 76.06%, respectively) and specificity (83.54% and 78.48%, respectively). vHIT demonstrated excellent specificity (89.87%) but poor sensitivity (47.89%). Caloric, vHIT, and rotary chair tests results did not correlate with one another (p > 0.05). Conclusions: Vestibular function tests have comparable diagnostic utility, yet each offers unique advantages. Caloric and rotational testing may be best suited for screening peripheral damage and vHIT may function ideally as a confirmatory test.

Vestibular damage affects the precision and accuracy of navigation in a virtual visual environment.

Vestibular information is available to the brain during navigation, as are the other self-generated (idiothetic) and external (allothetic) sensorimotor cues that contribute to central estimates of position and motion. Rodent studies provide strong evidence that vestibular information contributes to navigation but human studies have been less conclusive. Furthermore, sex-based differences have been described in human navigation studies performed with the head stationary, a situation where dynamic vestibular (and other idiothetic) information is absent, but sex differences in the utilization of vestibular information have not been described. Here, we studied men and women with severe bilateral vestibular damage as they navigated through a visually barren virtual reality environment and compared their performance to normal men and women. Two navigation protocols were employed, which either activated dynamic idiothetic cues ('dynamic task', navigate by turning, walking in place) or eliminated them ('static task', navigate with key presses, head stationary). For both protocols, we employed a standard 'triangle completion task' in which subjects moved to two visual targets in series and then were required to return to their perceived starting position without localizing visual information. The angular and linear 'accuracy' (derived from response error) and 'precision' (derived from response variability) were calculated. Comparing performance 'within tasks', navigation on the dynamic paradigm was worse in male vestibular-deficient patients than in normal men but vestibular-deficient and normal women were equivalent; on the static paradigm, vestibular-deficient men (but not women) performed better than normal subjects. Comparing performance 'between tasks', normal men performed better on the dynamic than the static paradigm while vestibular-deficient men and both normal and vestibular-deficient women were equivalent on both tasks. Statistical analysis demonstrated that for the angular precision metric, sex had a significant effect on the interaction between vestibular status and the test paradigm. These results provide evidence that humans use vestibular information when they navigate in a virtual visual environment and that men and women may utilize vestibular (and visual) information differently. On our navigation paradigm, men used vestibular information to improve navigation performance, and in the presence of severe vestibular damage, they utilized visual information more effectively. In contrast, we did not find evidence that women used vestibular information while navigating on our virtual task, nor did we find evidence that they improved their utilization of visual information in the presence of severe vestibular damage.

The Next Challenges of Vestibular Implantation in Humans.

Patients with bilateral vestibulopathy suffer from a variety of complaints, leading to a high individual and social burden. Available treatments aim to alleviate the impact of this loss and improve compensatory strategies. Early experiments with electrical stimulation of the vestibular nerve in combination with knowledge gained by cochlear implant research, have inspired the development of a vestibular neuroprosthesis that can provide the missing vestibular input. The feasibility of this concept was first demonstrated in animals and later in humans. Currently, several research groups around the world are investigating prototype vestibular implants, in the form of vestibular implants as well as combined cochlear and vestibular implants. The aim of this review is to convey the presentations and discussions from the identically named symposium that was held during the 2021 MidWinter Meeting of the Association for Research in Otolaryngology, with researchers involved in the development of vestibular implants targeting the ampullary nerves. Substantial advancements in the development have been made. Yet, research and development processes face several challenges to improve this neuroprosthesis. These include, but are not limited to, optimization of the electrical stimulation profile, refining the surgical implantation procedure, preserving residual labyrinthine functions including hearing, as well as gaining regulatory approval and establishing a clinical care infrastructure similar to what exists for cochlear implants. It is believed by the authors that overcoming these challenges will accelerate the development and increase the impact of a clinically applicable vestibular implant.

Vestibular dysfunction in neurofibromatosis type 2-related schwannomatosis.

Neurofibromatosis type 2-related schwannomatosis is a genetic disorder characterized by neurologic tumours, most typically vestibular schwannomas that originate on the vestibulo-cochlear nerve(s). Although vestibular symptoms can be disabling, vestibular function has never been carefully analysed in neurofibromatosis type 2-related schwannomatosis. Furthermore, chemotherapy (e.g. bevacizumab) can reduce tumour volume and improve hearing in neurofibromatosis type 2-related schwannomatosis, but nothing is known about its vestibular effects. In this report, we studied the three primary vestibular-mediated behaviours (eye movements, motion perception and balance), clinical vestibular disability (dizziness and ataxia), and imaging and hearing in eight untreated patients with neurofibromatosis type 2-related schwannomatosis and compared their results with normal subjects and patients with sporadic, unilateral vestibular schwannoma tumours. We also examined how bevacizumab affected two patients with neurofibromatosis type 2-related schwannomatosis. Vestibular schwannomas in neurofibromatosis type 2-related schwannomatosis degraded vestibular precision (inverse of variability, reflecting a reduced central signal-to-noise ratio) but not vestibular accuracy (amplitude relative to ideal amplitude, reflecting the central signal magnitude) and caused clinical disability. Bevacizumab improved vestibular precision and clinical disability in both patients with neurofibromatosis type 2-related schwannomatosis but did not affect vestibular accuracy. These results demonstrate that vestibular schwannoma tumours in our neurofibromatosis type 2-related schwannomatosis population degrade the central vestibular signal-to-noise ratio, while bevacizumab improves the signal-to-noise ratio, changes that can be explained mechanistically by the addition (schwannoma) and suppression (bevacizumab) of afferent neural noise.

Visuospatial Cognitive Dysfunction in Patients with Vestibular Loss.

OBJECTIVE: To characterize visuospatial and nonvisuospatial cognitive domains affected by vestibular loss and determine whether patient-reported outcomes measures (PROMs) correlate with performance on neuropsychological tests. STUDY DESIGN: Cross-sectional study. SETTING: University-based tertiary medical center. PATIENTS: Sixty-nine age-matched subjects: 25 patients with bilateral vestibular loss (BVL), 14 patients with unilateral vestibular loss (UVL), and 30 normal controls (NC). INTERVENTIONS: Neuropsychological tests used to assess visuospatial and auditory short-term and working memory, number magnitude representation, executive function, and attention. Validated PROMs used to evaluate quality of life and subjective cognitive impairment. MAIN OUTCOME MEASURES: Performance on neuropsychological tests and scores on PROM surveys. RESULTS: BVL and UVL patients performed significantly worse than NC subjects on tasks requiring visuospatial representation compared with NC subjects ( p < 0.01). BVL patients demonstrated decreased performance on spatial representation tasks compared with UVL and NC subjects ( p < 0.05 and p < 0.05, respectively). All subject groups performed similarly on tasks assessing nonvisuospatial cognitive domains, such as auditory short-term and working memory, executive function, and attention. PROMs did not seem to correlate with performance on neuropsychological tasks. CONCLUSION: Patients with vestibular loss exhibit impairments in tasks requiring visuospatial representation but perform similarly to NC subjects in tasks of auditory working memory, executive function, or attention. Currently available questionnaires may be insufficient to screen patients for cognitive deficits.

Evidence for cognitive impairment in patients with vestibular disorders.

OBJECTIVE:  Extensive animal research has shown that vestibular damage can be associated with cognitive deficits. More recently, new evidence has emerged linking vestibular disorders to cognitive impairment in humans. Herein, we review contemporary research on the pathophysiology of cognitive-vestibular interactions and discuss its emerging clinical relevance. DATA SOURCES: PubMed, Embase, and Cochrane databases. REVIEW METHODS: A systematic literature search was performed with combinations of search terms: "cognition," "cognitive impairment," "chronic fatigue," "brain fog," "spatial navigation," "attention," "memory," "executive function," "processing speed," and "vestibular hypofunction." Relevant articles were considered for inclusion, including basic and clinical studies, case series, and major reviews. CONCLUSIONS: Patients with vestibular disorders can demonstrate long-term deficits in both spatial and nonspatial cognitive domains. The underlying mechanism(s) linking the vestibular system to cognitive function is not well characterized, but several neuro-biologic correlates have been identified. Additional screening tools are required to identify individuals at risk for cognitive impairment, and further research is needed to determine whether treatment of vestibular dysfunction has the capacity to improve cognitive function. IMPLICATIONS FOR PRACTICE: Physicians should be aware of emerging data supporting the presence of cognitive deficits in patients with vestibular disorders. Prevention and treatment of long-term cognitive deficits may be possible through screening and rehabilitation.

How Peripheral Vestibular Damage Affects Velocity Storage: a Causative Explanation.

Velocity storage is a centrally-mediated mechanism that processes peripheral vestibular inputs. One prominent aspect of velocity storage is its effect on dynamic responses to yaw rotation. Specifically, when normal human subjects are accelerated to constant angular yaw velocity, horizontal eye movements and perceived angular velocity decay exponentially with a time constant circa 15-30 s, even though the input from the vestibular periphery decays much faster (~ 6 s). Peripheral vestibular damage causes a time constant reduction, which is useful for clinical diagnoses, but a mechanistic explanation for the relationship between vestibular damage and changes in these behavioral dynamics is lacking. It has been hypothesized that Bayesian optimization determines ideal velocity storage dynamics based on statistics of vestibular noise and experienced motion. Specifically, while a longer time constant would make the central estimate of angular head velocity closer to actual head motion, it may also result in the accumulation of neural noise which simultaneously degrades precision. Thus, the brain may balance these two effects by determining the time constant that optimizes behavior. We applied a Bayesian optimal Kalman filter to determine the ideal velocity storage time constant for unilateral damage. Predicted time constants were substantially lower than normal and similar to patients. Building on our past work showing that Bayesian optimization explains age-related changes in velocity storage, we also modeled interactions between age-related hair cell loss and peripheral damage. These results provide a plausible mechanistic explanation for changes in velocity storage after peripheral damage. Results also suggested that even after peripheral damage, noise originating in the periphery or early central processing may remain relevant in neurocomputations. Overall, our findings support the hypothesis that the brain optimizes velocity storage based on the vestibular signal-to-noise ratio.

The predictive power of geographic health care utilization for unintentional fatal fall rates.

BACKGROUND: Falls are the leading cause of fatal and nonfatal injuries among adults over 65 years old. The increase in fall mortality rates is likely multifactorial. With a lack of key drivers identified to explain rising rates of death from falls, accurate predictive modelling can be challenging, hindering evidence-based health resource and policy efforts. The objective of this work is to examine the predictive power of geographic utilization and longitudinal trends in mortality from unintentional falls amongst different demographic and geographic strata. METHODS: This is a nationwide, retrospective cohort study using the United States Centers for Disease Control (CDC) Web-based Injury Statistics Query and Reporting System (WISQARS) database. The exposure was death from an unintentional fall as determined by the CDC. Outcomes included aggregate and trend crude and age-adjusted death rates. Health care utilization, reimbursement, and cost metrics were also compared. RESULTS: Over 2001 to 2018, 465,486 total deaths due to unintentional falls were recorded with crude and age-adjusted rates of 8.42 and 7.76 per 100,000 population respectively. Comparing age-adjusted rates, males had a significantly higher age-adjusted death rate (9.89 vs. 6.17; p <  0.00001), but both male and female annual age-adjusted mortality rates are expected to rise (Male: + 0.25 rate/year, R2= 0.98; Female: + 0.22 rate/year, R2= 0.99). There were significant increases in death rates commensurate with increasing age, with the adults aged 85 years or older having the highest aggregate (201.1 per 100,000) and trending death rates (+ 8.75 deaths per 100,000/year, R2= 0.99). Machine learning algorithms using health care utilization data were accurate in predicting geographic age-adjusted death rates. CONCLUSIONS: Machine learning models have high accuracy in predicting geographic age-adjusted mortality rates from health care utilization data. In the United States from 2001 through 2018, adults aged 85+ years carried the highest death rate from unintentional falls and this rate is forecasted to accelerate.

Imbalance and dizziness caused by unilateral vestibular schwannomas correlate with vestibulo-ocular reflex precision and bias.

Imbalance and dizziness are disabling symptoms for many patients with vestibular schwannomas (VS) but symptom severity typically does not correlate with the vestibulo-ocular reflex (VOR) amplitude-based metrics used to assess peripheral vestibular damage. In this study, we tested the hypothesis that imbalance and dizziness in patients with VS relate to VOR metrics that are not based on response amplitude. Twenty-four patients with unilateral, sporadic VS tumors were studied, and objective (balance) and subjective (dizziness) vestibular dysfunction was quantified. The VOR was tested using two yaw-axis motion stimuli, low-frequency en-bloc sinusoidal, and high-frequency head-on-body impulsive rotations. Imbalance correlated with VOR precision (the inverse of the trial-to-trial variability) and with low-frequency VOR dynamics (quantified with the time constant), and these two metrics were also strongly correlated. Dizziness correlated with the VOR bias caused by an imbalance in static central vestibular tone, but not with dynamic VOR metrics. VOR accuracy (mean response amplitude relative to the ideal response) was not correlated with the severity of imbalance or dizziness or with measures of VOR precision or time constant. Imbalance in patients with VS, therefore, scales with VOR precision and time constant, both of which appear to reflect the central vestibular signal-to-noise ratio, but not with VOR slow-phase accuracy, which is based on the magnitude of the central vestibular signals. Dizziness was related to the presence of a static central tone imbalance but not to any VOR metrics, suggesting that abnormal perception in VS may be affected by factors that are not captured by yaw-axis VOR measurements.NEW & NOTEWORTHY The severity of symptoms associated with unilateral vestibular schwannomas (VS) is poorly correlated with standard yaw-axis vestibulo-ocular reflex (VOR) metrics that are based on response amplitude. In this study, we show that the balance and perceptual dysfunction experienced by patients with VS scales with VOR metrics that capture information about the central signal-to-noise ratio (balance) and central static tone (dizziness), but are not correlated with the VOR gain, which reflects central signal amplitude.

Gait Difficulties and Postural Instability in Adrenoleukodystrophy.

Background: Gait and balance difficulties are among the most common clinical manifestations in adults with X-linked adrenoleukodystrophy, but little is known about the contributions of sensory loss, motor dysfunction, and postural control to gait dysfunction and fall risk. Objective: To quantify gait and balance deficits in both males and females with adrenoleukodystrophy and evaluate how environmental perturbations (moving surfaces and visual surrounds) affect balance and fall risk. Methods: We assessed sensory and motor contributions to gait and postural instability in 44 adult patients with adrenoleukodystrophy and 17 healthy controls using three different functional gait assessments (25 Foot Walk test, Timed Up and Go, and 6 Minute Walk test) and computerized dynamic posturography. Results: The median Expanded Disability Status Scale score for the patient cohort was 3.0 (range 0.0-6.5). Both males and females with adrenoleukodystrophy showed impairments on all three functional gait assessments relative to controls (P < 0.001). Performance on walking tests and Expanded Disability Status Scale scores correlated with incidence of falls on computerized dynamic posturography, with the 25 Foot Walk being a moderately reliable predictor of fall risk (area under the ROC curve = 0.7675, P = 0.0038). Conclusion: We demonstrate that gait difficulties and postural control deficits occur in patients with adrenoleukodystrophy, albeit at an older age in females. Postural deficits were aggravated by eyes closed and dynamic conditions that rely on vestibular input, revealing challenges to the interplay of motor, sensory and vestibular circuitry in adrenoleukodystrophy.

An Implanted Vestibular Prosthesis Improves Spatial Orientation in Animals with Severe Vestibular Damage.

Gravity is a pervasive environmental stimulus, and accurate graviception is required for optimal spatial orientation and postural stability. The primary graviceptors are the vestibular organs, which include angular velocity (semicircular canals) and linear acceleration (otolith organs) sensors. Graviception is degraded in patients with vestibular damage, resulting in spatial misperception and imbalance. Since minimal therapy is available for these patients, substantial effort has focused on developing a vestibular prosthesis or vestibular implant (VI) that reproduces information normally provided by the canals (since reproducing otolith function is very challenging technically). Prior studies demonstrated that angular eye velocity responses could be driven by canal VI-mediated angular head velocity information, but it remains unknown whether a canal VI could improve spatial perception and posture since these behaviors require accurate estimates of angular head position in space relative to gravity. Here, we tested the hypothesis that a canal VI that transduces angular head velocity and provides this information to the brain via motion-modulated electrical stimulation of canal afferent nerves could improve the perception of angular head position relative to gravity in monkeys with severe vestibular damage. Using a subjective visual vertical task, we found that normal female monkeys accurately sensed the orientation of the head relative to gravity during dynamic tilts, that this ability was degraded following bilateral vestibular damage, and improved when the canal VI was used. These results demonstrate that a canal VI can improve graviception in vestibulopathic animals, suggesting that it could reduce the disabling perceptual and postural deficits experienced by patients with severe vestibular damage.SIGNIFICANCE STATEMENT Patients with vestibular damage experience impaired vision, spatial perception, and balance, symptoms that could potentially respond to a vestibular implant (VI). Anatomic features facilitate semicircular canal (angular velocity) prosthetics but inhibit approaches with the otolith (linear acceleration) organs, and canal VIs that sense angular head velocity can generate compensatory eye velocity responses in vestibulopathic subjects. Can the brain use canal VI head velocity information to improve estimates of head orientation (e.g., head position relative to gravity), which is a prerequisite for accurate spatial perception and posture? Here we show that a canal VI can improve the perception of head orientation in vestibulopathic monkeys, results that are highly significant because they suggest that VIs mimicking canal function can improve spatial orientation and balance in vestibulopathic patients.

Effects of vestibular neurectomy and neural compensation on head movements in patients undergoing vestibular schwannoma resection.

The vestibular system is vital for maintaining balance and stabilizing gaze and vestibular damage causes impaired postural and gaze control. Here we examined the effects of vestibular loss and subsequent compensation on head motion kinematics during voluntary behavior. Head movements were measured in vestibular schwannoma patients before, and then 6 weeks and 6 months after surgical tumor removal, requiring sectioning of the involved vestibular nerve (vestibular neurectomy). Head movements were recorded in six dimensions using a small head-mounted sensor while patients performed the Functional Gait Assessment (FGA). Kinematic measures differed between patients (at all three time points) and normal subjects on several challenging FGA tasks, indicating that vestibular damage (caused by the tumor or neurectomy) alters head movements in a manner that is not normalized by central compensation. Kinematics measured at different time points relative to vestibular neurectomy differed substantially between pre-operative and 6-week post-operative states but changed little between 6-week and > 6-month post-operative states, demonstrating that compensation affecting head kinematics is relatively rapid. Our results indicate that quantifying head kinematics during self-generated gait tasks provides valuable information about vestibular damage and compensation, suggesting that early changes in patient head motion strategy may be maladaptive for long-term vestibular compensation.

Self-motion perception is sensitized in vestibular migraine: pathophysiologic and clinical implications.

Vestibular migraine (VM) is the most common cause of spontaneous vertigo but remains poorly understood. We investigated the hypothesis that central vestibular pathways are sensitized in VM by measuring self-motion perceptual thresholds in patients and control subjects and by characterizing the vestibulo-ocular reflex (VOR) and vestibular and headache symptom severity. VM patients were abnormally sensitive to roll tilt, which co-modulates semicircular canal and otolith organ activity, but not to motions that activate the canals or otolith organs in isolation, implying sensitization of canal-otolith integration. When tilt thresholds were considered together with vestibular symptom severity or VOR dynamics, VM patients segregated into two clusters. Thresholds in one cluster correlated positively with symptoms and with the VOR time constant; thresholds in the second cluster were uniformly low and independent of symptoms and the time constant. The VM threshold abnormality showed a frequency-dependence that paralleled the brain stem velocity storage mechanism. These results support a pathogenic model where vestibular symptoms emanate from the vestibular nuclei, which are sensitized by migraine-related brainstem regions and simultaneously suppressed by inhibitory feedback from the cerebellar nodulus and uvula, the site of canal-otolith integration. This conceptual framework elucidates VM pathophysiology and could potentially facilitate its diagnosis and treatment.

Relationship between vestibular sensitivity and multisensory temporal integration.

A single event can generate asynchronous sensory cues due to variable encoding, transmission, and processing delays. To be interpreted as being associated in time, these cues must occur within a limited time window, referred to as a "temporal binding window" (TBW). We investigated the hypothesis that vestibular deficits could disrupt temporal visual-vestibular integration by determining the relationships between vestibular threshold and TBW in participants with normal vestibular function and with vestibular hypofunction. Vestibular perceptual thresholds to yaw rotation were characterized and compared with the TBWs obtained from participants who judged whether a suprathreshold rotation occurred before or after a brief visual stimulus. Vestibular thresholds ranged from 0.7 to 16.5 deg/s and TBWs ranged from 13.8 to 395 ms. Among all participants, TBW and vestibular thresholds were well correlated ( R2 = 0.674, P < 0.001), with vestibular-deficient patients having higher thresholds and wider TBWs. Participants reported that the rotation onset needed to lead the light flash by an average of 80 ms for the visual and vestibular cues to be perceived as occurring simultaneously. The wide TBWs in vestibular-deficient participants compared with normal functioning participants indicate that peripheral sensory loss can lead to abnormal multisensory integration. A reduced ability to temporally combine sensory cues appropriately may provide a novel explanation for some symptoms reported by patients with vestibular deficits. Even among normal functioning participants, a high correlation between TBW and vestibular thresholds was observed, suggesting that these perceptual measurements are sensitive to small differences in vestibular function. NEW & NOTEWORTHY While spatial visual-vestibular integration has been well characterized, the temporal integration of these cues is not well understood. The relationship between sensitivity to whole body rotation and duration of the temporal window of visual-vestibular integration was examined using psychophysical techniques. These parameters were highly correlated for those with normal vestibular function and for patients with vestibular hypofunction. Reduced temporal integration performance in patients with vestibular hypofunction may explain some symptoms associated with vestibular loss.

Bayesian optimal adaptation explains age-related human sensorimotor changes.

The brain uses information from different sensory systems to guide motor behavior, and aging is associated with simultaneous decline in the quality of sensory information provided to the brain and deterioration in motor control. Correlations between age-dependent decline in sensory anatomical structures and behavior have been demonstrated in many sensorimotor systems, and it has recently been suggested that a Bayesian framework could explain these relationships. Here we show that age-dependent changes in a human sensorimotor reflex, the vestibuloocular reflex, are explained by a Bayesian optimal adaptation in the brain occurring in response to death of motion-sensing hair cells. Specifically, we found that the temporal dynamics of the reflex as a function of age emerge from ( r = 0.93, P < 0.001) a Kalman filter model that determines the optimal behavioral output when the sensory signal-to-noise characteristics are degraded by death of the transducers. These findings demonstrate that the aging brain is capable of generating the ideal and statistically optimal behavioral response when provided with deteriorating sensory information. While the Bayesian framework has been shown to be a general neural principle for multimodal sensory integration and dynamic sensory estimation, these findings provide evidence of longitudinal Bayesian processing over the human life span. These results illuminate how the aging brain strives to optimize motor behavior when faced with deterioration in the peripheral and central nervous systems and have implications in the field of vestibular and balance disorders, as they will likely provide guidance for physical therapy and for prosthetic aids that aim to reduce falls in the elderly. NEW & NOTEWORTHY We showed that age-dependent changes in the vestibuloocular reflex are explained by a Bayesian optimal adaptation in the brain that occurs in response to age-dependent sensory anatomical changes. This demonstrates that the brain can longitudinally respond to age-related sensory loss in an ideal and statistically optimal way. This has implications for understanding and treating vestibular disorders caused by aging and provides insight into the structure-function relationship during aging.

An Engineering Model to Test for Sensory Reweighting: Nonhuman Primates Serve as a Model for Human Postural Control and Vestibular Dysfunction.

Quantitative animal models are critically needed to provide proof of concept for the investigation of rehabilitative balance therapies (e.g., invasive vestibular prostheses) and treatment response prior to, or in conjunction with, human clinical trials. This paper describes a novel approach to modeling the nonhuman primate postural control system. Our observation that rhesus macaques and humans have even remotely similar postural control motivates the further application of the rhesus macaque as a model for studying the effects of vestibular dysfunction, as well as vestibular prosthesis-assisted states, on human postural control. Previously, system identification methodologies and models were only used to describe human posture. However, here we utilized pseudorandom, roll-tilt balance platform stimuli to perturb the posture of a rhesus monkey in normal and mild vestibular (equilibrium) loss states. The relationship between rhesus monkey trunk sway and platform roll-tilt was determined via stimulus-response curves and transfer function results. A feedback controller model was then used to explore sensory reweighting (i.e., changes in sensory reliance), which prevented the animal from falling off of the tilting platform. Conclusions involving sensory reweighting in the nonhuman primate for a normal sensory state and a state of mild vestibular loss led to meaningful insights. This first-phase effort to model the balance control system in nonhuman primates is essential for future investigations toward the effects of invasive rehabilitative (balance) technologies on postural control in primates, and ultimately, humans.

Postural compensation strategy depends on the severity of vestibular damage.

The purpose of this study was to investigate the effects of various levels of vestibular function on balance in two, free-standing rhesus monkeys. We hypothesized that postural control strategy depended on the severity of vestibular damage. More specifically, that increased muscle stiffness (via short-latency mechanisms) was adequate to compensate for mild damage, but long-latency mechanisms must be utilized for more severe vestibular damage. One animal was studied for pre-ablated and mild vestibular dysfunction states, while a second animal was studied in a pre-ablated and severe vestibular dysfunction state. The vestibulo-ocular reflex (VOR), an eye movement reflex directly linked to vestibular function, was used to quantify the level of vestibular damage. A postural feedback controller model, previously only used for human studies, was modified to interpret non-human primate postural responses (differences observed in the measured trunk roll) for these three levels of vestibular function. By implementing a feedback controller model, we were able to further interpret our empirical findings and model results were consistent with our above hypothesis. This study establishes a baseline for future studies of non-human primate posture.

Vestibular implants studied in animal models: clinical and scientific implications.

Damage to the peripheral vestibular system can result in debilitating postural, perceptual, and visual symptoms. A potential new treatment for this clinical problem is to replace some aspects of peripheral vestibular function with an implant that senses head motion and provides this information to the brain by stimulating branches of the vestibular nerve. In this review I consider animal studies performed at our institution over the past 15 years, which have helped elucidate how the brain processes information provided by a vestibular (semicircular canal) implant and how this information could be used to improve the problems experienced by patients with peripheral vestibular damage.