Variation between individuals in sensorimotor feedback control of standing balance.

We examined intersubject variation in human balance, focusing on sensorimotor feedback. Our central hypothesis was that intersubject variation in balance characteristics arises from differences in central sensorimotor processing. Our second hypothesis was that similar sensorimotor feedback mechanisms are used for sagittal and frontal balance. Twenty-one adults stood on a continuously rotating platform with their eyes closed in the sagittal or frontal plane. Plant dynamics (mass, height, and inertia) and feedback control were included in a model of sensory weight, neural time delays, and sensory-to-motor scaling (stiffness, damping, and integral gains). Sway metrics [root-mean-square (RMS) sway and velocity] were moderately correlated between planes of motion (RMS: R = 0.66-0.69 and RMS velocity: R = 0.53-0.58). Sensory weight and integral gain exhibited the highest correlations between the plane of motion (R = 0.59 for sensory weight and R = 0.75 for integral gain during large stimuli). Compared with other subjects, people who adopted a high vestibular weight or large integral gain in one condition did so across all tests. Intersubject variation in sensory weight, stiffness, and integral gain were significantly associated with intersubject variation in RMS sway whereas sensory weight and time delay were the strongest significant predictors of RMS velocity. Multiple linear regression showed that intersubject variation in sway metrics was predicted better by intersubject variation in central feedback mechanisms vs. plant dynamics. Together, results supported the first hypothesis and partially supported the second hypothesis because only a subset of feedback processes was moderately or strongly correlated (mostly during large surface tilts) between planes of motion.NEW & NOTEWORTHY This study details naturally occurring intersubject variation in healthy adults' balance control. Experimental surface tilts evoked postural sway and sensorimotor modeling defined feedback control parameters. We determined the relation between intersubject variation in feedback control (vestibular and proprioceptive reliance, neural time delay, sensory-to-motor scaling) and intersubject variation in postural sway between planes of motion and between stimulus amplitudes.

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.

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.

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.

The role of vestibular cues in postural sway.

Controlling posture requires continuous sensory feedback about body motion and orientation, including from the vestibular organs. Little is known about the role of tilt vs. translation vs. rotation vestibular cues. We examined whether intersubject differences in vestibular function were correlated with intersubject differences in postural control. Vestibular function was assayed using vestibular direction-recognition perceptual thresholds, which determine the smallest motion that can be reliably perceived by a subject seated on a motorized platform in the dark. In study A, we measured thresholds for lateral translation, vertical translation, yaw rotation, and head-centered roll tilts. In study B, we measured thresholds for roll, pitch, and left anterior-right posterior and right anterior-left posterior tilts. Center-of-pressure (CoP) sway was measured in sensory organization tests (study A) and Romberg tests (study B). We found a strong positive relationship between CoP sway and lateral translation thresholds but not CoP sway and other thresholds. This finding suggests that the vestibular encoding of lateral translation may contribute substantially to balance control. Since thresholds assay sensory noise, our results support the hypothesis that vestibular noise contributes to spontaneous postural sway. Specifically, we found that lateral translation thresholds explained more of the variation in postural sway in postural test conditions with altered proprioceptive cues (vs. a solid surface), consistent with postural sway being more dependent on vestibular noise when the vestibular contribution to balance is higher. These results have potential implications for vestibular implants, balance prostheses, and physical therapy exercises.NEW & NOTEWORTHY Vestibular feedback is important for postural control, but little is known about the role of tilt cues vs. translation cues vs. rotation cues. We studied healthy human subjects with no known vestibular pathology or symptoms. Our findings showed that vestibular encoding of lateral translation correlated with medial-lateral postural sway, consistent with lateral translation cues contributing to balance control. This adds support to the hypothesis that vestibular noise contributes to spontaneous postural sway.

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.

Human manual control precision depends on vestibular sensory precision and gravitational magnitude.

Precise motion control is critical to human survival on Earth and in space. Motion sensation is inherently imprecise, and the functional implications of this imprecision are not well understood. We studied a "vestibular" manual control task in which subjects attempted to keep themselves upright with a rotational hand controller (i.e., joystick) to null out pseudorandom, roll-tilt motion disturbances of their chair in the dark. Our first objective was to study the relationship between intersubject differences in manual control performance and sensory precision, determined by measuring vestibular perceptual thresholds. Our second objective was to examine the influence of altered gravity on manual control performance. Subjects performed the manual control task while supine during short-radius centrifugation, with roll tilts occurring relative to centripetal accelerations of 0.5, 1.0, and 1.33 GC (1 GC = 9.81 m/s2). Roll-tilt vestibular precision was quantified with roll-tilt vestibular direction-recognition perceptual thresholds, the minimum movement that one can reliably distinguish as leftward vs. rightward. A significant intersubject correlation was found between manual control performance (defined as the standard deviation of chair tilt) and thresholds, consistent with sensory imprecision negatively affecting functional precision. Furthermore, compared with 1.0 GC manual control was more precise in 1.33 GC (-18.3%, P = 0.005) and less precise in 0.5 GC (+39.6%, P < 0.001). The decrement in manual control performance observed in 0.5 GC and in subjects with high thresholds suggests potential risk factors for piloting and locomotion, both on Earth and during human exploration missions to the moon (0.16 G) and Mars (0.38 G). NEW & NOTEWORTHY The functional implications of imprecise motion sensation are not well understood. We found a significant correlation between subjects' vestibular perceptual thresholds and performance in a manual control task (using a joystick to keep their chair upright), consistent with sensory imprecision negatively affecting functional precision. Furthermore, using an altered-gravity centrifuge configuration, we found that manual control precision was improved in "hypergravity" and degraded in "hypogravity." These results have potential relevance for postural control, aviation, and spaceflight.

Human perception of whole body roll-tilt orientation in a hypogravity analog: underestimation and adaptation.

Overestimation of roll tilt in hypergravity ("G-excess" illusion) has been demonstrated, but corresponding sustained hypogravic conditions are impossible to create in ground laboratories. In this article we describe the first systematic experimental evidence that in a hypogravity analog, humans underestimate roll tilt. We studied perception of self-roll tilt in nine subjects, who were supine while spun on a centrifuge to create a hypogravity analog. By varying the centrifuge rotation rate, we modulated the centripetal acceleration (GC) at the subject's head location (0.5 or 1 GC) along the body axis. We measured orientation perception using a subjective visual vertical task in which subjects aligned an illuminated bar with their perceived centripetal acceleration direction during tilts (±11.5-28.5°). As hypothesized, based on the reduced utricular otolith shearing, subjects initially underestimated roll tilts in the 0.5 GC condition compared with the 1 GC condition (mean perceptual gain change = -0.27, P = 0.01). When visual feedback was given after each trial in 0.5 GC, subjects' perceptual gain increased in approximately exponential fashion over time (time constant = 16 tilts or 13 min), and after 45 min, the perceptual gain was not significantly different from the 1 GC baseline (mean gain difference between 1 GC initial and 0.5 GC final = 0.16, P = 0.3). Thus humans modified their interpretation of sensory cues to more correctly report orientation during this hypogravity analog. Quantifying the acute orientation perceptual learning in such an altered gravity environment may have implications for human space exploration on the moon or Mars. NEW & NOTEWORTHY Humans systematically overestimate roll tilt in hypergravity. However, human perception of orientation in hypogravity has not been quantified across a range of tilt angles. Using a centrifuge to create a hypogravity centripetal acceleration environment, we found initial underestimation of roll tilt. Providing static visual feedback, perceptual learning reduced underestimation during the hypogravity analog. These altered gravity orientation perceptual errors and adaptation may have implications for astronauts.

Perceptual precision of passive body tilt is consistent with statistically optimal cue integration.

When making perceptual decisions, humans have been shown to optimally integrate independent noisy multisensory information, matching maximum-likelihood (ML) limits. Such ML estimators provide a theoretic limit to perceptual precision (i.e., minimal thresholds). However, how the brain combines two interacting (i.e., not independent) sensory cues remains an open question. To study the precision achieved when combining interacting sensory signals, we measured perceptual roll tilt and roll rotation thresholds between 0 and 5 Hz in six normal human subjects. Primary results show that roll tilt thresholds between 0.2 and 0.5 Hz were significantly lower than predicted by a ML estimator that includes only vestibular contributions that do not interact. In this paper, we show how other cues (e.g., somatosensation) and an internal representation of sensory and body dynamics might independently contribute to the observed performance enhancement. In short, a Kalman filter was combined with an ML estimator to match human performance, whereas the potential contribution of nonvestibular cues was assessed using published bilateral loss patient data. Our results show that a Kalman filter model including previously proven canal-otolith interactions alone (without nonvestibular cues) can explain the observed performance enhancements as can a model that includes nonvestibular contributions.NEW & NOTEWORTHY We found that human whole body self-motion direction-recognition thresholds measured during dynamic roll tilts were significantly lower than those predicted by a conventional maximum-likelihood weighting of the roll angular velocity and quasistatic roll tilt cues. Here, we show that two models can each match this "apparent" better-than-optimal performance: 1) inclusion of a somatosensory contribution and 2) inclusion of a dynamic sensory interaction between canal and otolith cues via a Kalman filter model.

Dynamics of individual perceptual decisions.

Perceptual decision making is fundamental to a broad range of fields including neurophysiology, economics, medicine, advertising, law, etc. Although recent findings have yielded major advances in our understanding of perceptual decision making, decision making as a function of time and frequency (i.e., decision-making dynamics) is not well understood. To limit the review length, we focus most of this review on human findings. Animal findings, which are extensively reviewed elsewhere, are included when beneficial or necessary. We attempt to put these various findings and data sets, which can appear to be unrelated in the absence of a formal dynamic analysis, into context using published models. Specifically, by adding appropriate dynamic mechanisms (e.g., high-pass filters) to existing models, it appears that a number of otherwise seemingly disparate findings from the literature might be explained. One hypothesis that arises through this dynamic analysis is that decision making includes phasic (high pass) neural mechanisms, an evidence accumulator and/or some sort of midtrial decision-making mechanism (e.g., peak detector and/or decision boundary).

Determining thresholds using adaptive procedures and psychometric fits: evaluating efficiency using theory, simulations, and human experiments.

When measuring thresholds, careful selection of stimulus amplitude can increase efficiency by increasing the precision of psychometric fit parameters (e.g., decreasing the fit parameter error bars). To find efficient adaptive algorithms for psychometric threshold ("sigma") estimation, we combined analytic approaches, Monte Carlo simulations, and human experiments for a one-interval, binary forced-choice, direction-recognition task. To our knowledge, this is the first time analytic results have been combined and compared with either simulation or human results. Human performance was consistent with theory and not significantly different from simulation predictions. Our analytic approach provides a bound on efficiency, which we compared against the efficiency of standard staircase algorithms, a modified staircase algorithm with asymmetric step sizes, and a maximum likelihood estimation (MLE) procedure. Simulation results suggest that optimal efficiency at determining threshold is provided by the MLE procedure targeting a fraction correct level of 0.92, an asymmetric 4-down, 1-up staircase targeting between 0.86 and 0.92 or a standard 6-down, 1-up staircase. Psychometric test efficiency, computed by comparing simulation and analytic results, was between 41 and 58% for 50 trials for these three algorithms, reaching up to 84% for 200 trials. These approaches were 13-21% more efficient than the commonly used 3-down, 1-up symmetric staircase. We also applied recent advances to reduce accuracy errors using a bias-reduced fitting approach. Taken together, the results lend confidence that the assumptions underlying each approach are reasonable and that human threshold forced-choice decision making is modeled well by detection theory models and mimics simulations based on detection theory models.

Visual and vestibular perceptual thresholds each demonstrate better precision at specific frequencies and also exhibit optimal integration.

Prior studies show that visual motion perception is more precise than vestibular motion perception, but it is unclear whether this is universal or the result of specific experimental conditions. We compared visual and vestibular motion precision over a broad range of temporal frequencies by measuring thresholds for vestibular (subject motion in the dark), visual (visual scene motion) or visual-vestibular (subject motion in the light) stimuli. Specifically, thresholds were measured for motion frequencies spanning a two-decade physiological range (0.05-5 Hz) using single-cycle sinusoidal acceleration roll tilt trajectories (i.e., distinguishing left-side down from right-side down). We found that, while visual and vestibular thresholds were broadly similar between 0.05 and 5.0 Hz, each cue is significantly more precise than the other at certain frequencies. Specifically, we found that 1) visual and vestibular thresholds were indistinguishable at 0.05 Hz and 2 Hz (i.e., similarly precise); 2) visual thresholds were lower (i.e., vision more precise) than vestibular thresholds between 0.1 Hz and 1 Hz; and 3) visual thresholds were higher (i.e., vision less precise) than vestibular thresholds above 2 Hz. This shows that vestibular perception can be more precise than visual perception at physiologically relevant frequencies. We also found that sensory integration of visual and vestibular information is consistent with static Bayesian optimal integration of visual-vestibular cues. In contrast with most prior work that degraded or altered sensory cues, we demonstrated static optimal integration using natural cues.

Whole body motion-detection tasks can yield much lower thresholds than direction-recognition tasks: implications for the role of vibration.

Earlier spatial orientation studies used both motion-detection (e.g., did I move?) and direction-recognition (e.g., did I move left/right?) paradigms. The purpose of our study was to compare thresholds measured with motion-detection and direction-recognition tasks on a standard Moog motion platform to see whether a substantial fraction of the reported threshold variation might be explained by the use of different discrimination tasks in the presence of vibrations that vary with motion. Thresholds for the perception of yaw rotation about an earth-vertical axis and for interaural translation in an earth-horizontal plane were determined for four healthy subjects with standard detection and recognition paradigms. For yaw rotation two-interval detection thresholds were, on average, 56 times smaller than two-interval recognition thresholds, and for interaural translation two-interval detection thresholds were, on average, 31 times smaller than two-interval recognition thresholds. This substantive difference between recognition thresholds and detection thresholds is one of our primary findings. For motions near our measured detection threshold, we measured vibrations that matched previously established vibration thresholds. This suggests that vibrations contribute to whole body motion detection. We also recorded yaw rotation thresholds on a second motion device with lower vibration and found direction-recognition and motion-detection thresholds that were not significantly different from one another or from the direction-recognition thresholds recorded on our Moog platform. Taken together, these various findings show that yaw rotation recognition thresholds are relatively unaffected by vibration when moderate (up to ≈ 0.08 m/s(2)) vibration cues are present.

Your Vestibular Thresholds May Be Lower Than You Think: Cognitive Biases in Vestibular Psychophysics.

PURPOSE: Recently, there has been a surge of interest in measuring vestibular perceptual thresholds, which quantify the smallest motion that a subject can reliably perceive, to study physiology and pathophysiology. These thresholds are sensitive to age, pathology, and postural performance. Threshold tasks require decisions to be made in the presence of uncertainty. Since humans often rely on past information when making decisions in the presence of uncertainty, we hypothesized that (a) perceptual responses are affected by their preceding trial; (b) perceptual responses tend to be biased opposite of the "preceding response" because of cognitive biases but are not biased by the "preceding stimulus"; and (c) when fits do not account for this cognitive bias, thresholds are overestimated. To our knowledge, these hypotheses are unaddressed in vestibular and direction-recognition tasks. CONCLUSIONS: Results in normal subjects supported each hypothesis. Subjects tended to respond opposite of their preceding response (not the preceding stimulus), indicating a cognitive bias, and this caused an overestimation of thresholds. Using an enhanced model (MATLAB code provided) that considered these effects, average thresholds were lower (5.5% for yaw, 7.1% for interaural). Since the results indicate that the magnitude of cognitive bias varies across subjects, this enhanced model can reduce measurement variability and potentially improve the efficiency of data collection.

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.

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.

A distributed, dynamic, parallel computational model: the role of noise in velocity storage.

Networks of neurons perform complex calculations using distributed, parallel computation, including dynamic "real-time" calculations required for motion control. The brain must combine sensory signals to estimate the motion of body parts using imperfect information from noisy neurons. Models and experiments suggest that the brain sometimes optimally minimizes the influence of noise, although it remains unclear when and precisely how neurons perform such optimal computations. To investigate, we created a model of velocity storage based on a relatively new technique--"particle filtering"--that is both distributed and parallel. It extends existing observer and Kalman filter models of vestibular processing by simulating the observer model many times in parallel with noise added. During simulation, the variance of the particles defining the estimator state is used to compute the particle filter gain. We applied our model to estimate one-dimensional angular velocity during yaw rotation, which yielded estimates for the velocity storage time constant, afferent noise, and perceptual noise that matched experimental data. We also found that the velocity storage time constant was Bayesian optimal by comparing the estimate of our particle filter with the estimate of the Kalman filter, which is optimal. The particle filter demonstrated a reduced velocity storage time constant when afferent noise increased, which mimics what is known about aminoglycoside ablation of semicircular canal hair cells. This model helps bridge the gap between parallel distributed neural computation and systems-level behavioral responses like the vestibuloocular response and perception.

Spatial and temporal properties of eye movements produced by electrical stimulation of semicircular canal afferents.

To investigate the characteristics of eye movements produced by electrical stimulation of semicircular canal afferents, we studied the spatial and temporal features of eye movements elicited by short-term lateral canal stimulation in two squirrel monkeys with plugged lateral canals, with the head upright or statically tilted in the roll plane. The electrically induced vestibuloocular reflex (eVOR) evoked with the head upright decayed more quickly than the stimulation signal provided by the electrode, demonstrating an absence of the classic velocity storage effect that improves the dynamics of the low-frequency VOR. When stimulation was provided with the head tilted in roll, however, the eVOR decayed more rapidly than when the head was upright, and a cross-coupled vertical response developed that shifted the eye's rotational axis toward alignment with gravity. These results demonstrate that rotational information provided by electrical stimulation of canal afferents interacts with otolith inputs (or other graviceptive cues) in a qualitatively normal manner, a process that is thought to be mediated by the velocity storage network. The observed interaction between the eVOR and graviceptive cues is of critical importance for the development of a functionally useful vestibular prosthesis. Furthermore, the presence of gravity-dependent effects (dumping, spatial orientation) despite an absence of low-frequency augmentation of the eVOR has not been previously described in any experimental preparation.

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.

Vestibular Precision at the Level of Perception, Eye Movements, Posture, and Neurons.

Precision and accuracy are two fundamental properties of any system, including the nervous system. Reduced precision (i.e., imprecision) results from the presence of neural noise at each level of sensory, motor, and perceptual processing. This review has three objectives: (1) to show the importance of studying vestibular precision, and specifically that studying accuracy without studying precision ignores fundamental aspects of the vestibular system; (2) to synthesize key hypotheses about precision in vestibular perception, the vestibulo-ocular reflex, posture, and neurons; and (3) to show that groups of studies that are thoughts to be distinct (e.g., perceptual thresholds, subjective visual vertical variability, neuronal variability) are actually "two sides of the same coin" - because the methods used allow results to be related to the standard deviation of a Gaussian distribution describing the underlying neural noise. Vestibular precision varies with age, stimulus amplitude, stimulus frequency, body orientation, motion direction, pathology, medication, and electrical/mechanical vestibular stimulation, but does not vary with sex. The brain optimizes precision during integration of vestibular cues with visual, auditory, and/or somatosensory cues. Since a common concern with precision metrics is time required for testing, we describe approaches to optimize data collection and provide evidence that fatigue and session effects are minimal. Finally, we summarize how precision is an individual trait that is correlated with clinical outcomes in patients as well as with performance in functional tasks like balance. These findings highlight the importance of studying vestibular precision and accuracy, and that knowledge gaps remain.