US20190232113A1 | 2019-08-01 | |||
US7933654B2 | 2011-04-26 | |||
US8092355B2 | 2012-01-10 | |||
US20190015035A1 | 2019-01-17 | |||
US11273344B2 | 2022-03-15 |
CLAIMS What is claimed is: 1. A vestibular training device for improving vestibular function and balance and reducing fall risk of a subject, the vestibular training device comprising: a motion platform configured to support the subject thereon and to execute a set of discrete motions; one or more input devices configured to enable the subject to provide responses to the motions executed by the motion platform; one or more feedback devices configured to provide the subject with feedback indicative of whether the responses are correct or incorrect; and a controller in communication with the motion platform, the one or more input devices, and the one or more feedback devices, wherein the controller is configured to: cause the motion platform to execute a first motion; receive, via the one or more input devices, a first response indicative of the subject’s perception of the first motion; cause the one or more feedback devices to provide first feedback indicative of whether the first response is correct or incorrect; and determine a second motion based at least in part on the first response; and cause the motion platform to execute the second motion. 2. The vestibular training device of claim 1, wherein the controller is further configured to: receive, via the one or more input devices, a second response indicative of the subject’s perception of the second motion; cause the one or more feedback devices to provide second feedback indicative of whether the second response is correct or incorrect; determine a third motion based at least in part on the second response; and cause the motion platform to execute the third motion. 3. The vestibular training device of claim 1, wherein the controller is further configured to: receive, via the one or more input devices, a second response indicative of the subject’s perception of the second motion; cause the one or more feedback devices to provide second feedback indicative of whether the second response is correct or incorrect; determine a plurality of additional motions based at least in part on the second response; cause the motion platform to execute the additional motions; receive, via the one or more input devices, a plurality of additional responses indicative of the subject’s perception of the additional motions; cause the one or more feedback devices to provide a plurality of additional feedback indicative of whether the additional responses are correct or incorrect; and determine a threshold of the subject based at least in part on the first response, the second response, and at least part of the additional responses, wherein the threshold is a biomarker for a fall risk of the subject. 4. The vestibular training device of claim 3, wherein the controller is further configured to: determine that one of the additional responses is indicative of a lapse by the subject; and determine the threshold of the subject based at least in part on the first response, the second response, and at least part of the additional responses, while excluding the one of the additional responses indicative of a lapse by the subject. 5. The vestibular training device of claim 4, wherein the controller is further configured to use a standard delete-one jackknife procedure to identify the biggest outlier to determine that the one of the additional responses is indicative of a lapse by the subject. 6. The vestibular training device of claim 5, wherein the controller is further configured to use a standard bootstrap method to estimate sample distribution in order to provide strict statistical criteria to identify outliers. 7. The vestibular training device of claim 3, wherein the controller is further configured to determine confidence in order to improve accuracy and precision of the threshold. 8. The vestibular training device of claim 7, wherein the controller is further configured to determine subsequent motions to be executed by the motion platform based at least in part on the confidence. 9. The vestibular training device of claim 3, wherein the controller is further configured to compare the fall risk of the subject to values from a previously quantified population. 10. The vestibular training device of claim 9, wherein the controller is further configured to: determine that the fall risk of the subject is acceptable when the threshold is below a predetermined percentile for young healthy adults; and determine that training of the subject is recommended when the threshold is above the predetermined percentile. 11. The vestibular training device of claim 10, wherein the predetermined percentile is the 50th percentile for young healthy adults. 12. The vestibular training device of claim 10, wherein the training is perceptual training. 13. The vestibular training device of claim 12, wherein the perceptual training comprises motions individually tailored to improve self-motion perception of the subject. 14. The vestibular training device of claim 12, wherein the perceptual training comprises motions individually tailored to improve self-motion perception of the subject by lowering a self- motion perceptual threshold of the subject. 15. The vestibular training device of claim 12, wherein the perceptual training comprises tilt motions individually tailored to improve self-motion perception of the subject by lowering a tilt self-motion perceptual threshold of the subject. 16. The vestibular training device of claim 15, wherein the perceptual training comprises roll tilt motions individually tailored to lower a roll tilt perceptual threshold of the subject. 17. The vestibular training device of claim 15, wherein the perceptual training comprises pitch tilt motions individually tailored to lower a pitch tilt perceptual threshold of the subject. 18. The vestibular training device of claim 15, wherein the perceptual training comprises simultaneous and synchronous roll and pitch tilt motions individually tailored to lower a roll tilt perceptual threshold and a pitch tilt perceptual threshold of the subject. 19. The vestibular training device of claim 1, wherein the controller is further configured to cause the motion platform to execute each of the discrete motions having a single cycle of sinusoidal acceleration. 20. The vestibular training device of claim 1, wherein the set of discrete motions comprises between 10 and 1000 discrete motions. 21. The vestibular training device of claim 1, wherein the set of discrete motions comprises one or more translational motions. 22. The vestibular training device of claim 1, wherein the set of discrete motions comprises one or more rotational motions. 23. The vestibular training device of claim 1, wherein the set of discrete motions comprises one or more tilt motions. 24. The vestibular training device of claim 1, wherein the set of discrete motions comprises one or more roll tilt motions. 25. The vestibular training device of claim 24, wherein the controller is further configured to cause the motion platform to execute each of the one or more roll tilt motions for a duration between 0.5 seconds and 10 seconds. 26. The vestibular training device of claim 24, wherein the controller is further configured to determine roll tilt perception of the subject. 27. The vestibular training device of claim 24, wherein the controller is further configured to determine a roll tilt threshold of the subject. 28. The vestibular training device of claim 1, wherein the motion platform is configured to support the subject thereon in a seated position. 29. The vestibular training device of claim 1, wherein the motion platform is configured to support the subject thereon in a standing position. 30. The vestibular training device of claim 1, wherein the motion platform is configured to support the subject thereon in a lying-down position. 31. The vestibular training device of claim 1, wherein the discrete motions are individually tailored for the subject to enhance training. 32. The vestibular training device of claim 1, wherein the discrete motions are individually tailored for the subject based at least in part on a previously determined threshold for the subject. 33. The vestibular training device of claim 32, wherein the discrete motions are individually tailored for the subject to be at or near the previously determined threshold for the subject. 34. The vestibular training device of claim 32, wherein the discrete motions are individually tailored for the subject using a standard 2-down/1-up staircase. 35. The vestibular training device of claim 32, wherein the discrete motions are individually tailored for the subject using a standard 3-down/1-up staircase. 36. The vestibular training device of claim 32, wherein the discrete motions are individually tailored for the subject using a standard 4-down/1-up staircase. 37. The vestibular training device of claim 32, wherein the discrete motions are individually tailored for the subject using a maximum likelihood method. 38. The vestibular training device of claim 1, wherein the discrete motions are incrementally changed over the course of a training session. 39. The vestibular training device of claim 38, wherein the discrete motions are changed using a standard 2-down/1-up staircase with asymmetrical step sizes. 40. The vestibular training device of claim 38, wherein the discrete motions are changed using a standard 3-down/1-up staircase with asymmetrical step sizes. 41. The vestibular training device of claim 38, wherein the discrete motions are changed using a standard 4-down/1-up staircase with asymmetrical step sizes. 42. The vestibular training device of claim 1, wherein the one or more input devices comprise one or more handheld devices configured to enable the subject to provide the responses to the motions executed by the motion platform. 43. The vestibular training device of claim 42, wherein the one or more handheld devices comprises a plurality of buttons configured to enable the subject to provide different types of the responses to the motions executed by the motion platform. 44. The vestibular training device of claim 1, wherein the responses are indicative of the subject’s perception of direction of the motions executed by the motion platform. 45. The vestibular training device of claim 1, wherein the one or more feedback devices are configured to provide the subject with auditory feedback indicative of whether the responses are correct or incorrect. 46. The vestibular training device of claim 1, wherein the one or more feedback devices are configured to provide the subject with visual feedback indicative of whether the responses are correct or incorrect. 47. The vestibular training device of claim 1, further comprising a blindfold configured to cover the subject’s eyes during testing or training. 48. The vestibular training device of claim 1, further comprising noise-cancelling headphones configured to emit white noise while the motion platform executes each of the discrete motions. 49. The vestibular training device of claim 1, further comprising a visual display configured to present visual information during testing or training. 50. The vestibular training device of claim 1, further comprising a visual display configured to present visual information immediately following each of the responses provided by the subject. 51. A method for improving vestibular function and balance and reducing fall risk of a subject using a vestibular training device comprising a motion platform configured to support the subject thereon and to execute a set of discrete motions, one or more input devices configured to enable the subject to provide responses to the motions executed by the motion platform, one or more feedback devices configured to provide the subject with feedback indicative of whether the responses are correct or incorrect, and a controller in communication with the motion platform, the one or more input devices, and the one or more feedback devices, the method comprising: causing the motion platform to execute a first motion; receiving, via the one or more input devices, a first response indicative of the subject’s perception of the first motion; causing the one or more feedback devices to provide first feedback indicative of whether the first response is correct or incorrect; determining a second motion based at least in part on the first response; and causing the motion platform to execute the second motion. 52. The method of claim 51, further comprising: receiving, via the one or more input devices, a second response indicative of the subject’s perception of the second motion; causing the one or more feedback devices to provide second feedback indicative of whether the second response is correct or incorrect; determining a third motion based at least in part on the second response; and causing the motion platform to execute the third motion. 53. The method of claim 51, further comprising: receiving, via the one or more input devices, a second response indicative of the subject’s perception of the second motion; causing the one or more feedback devices to provide second feedback indicative of whether the second response is correct or incorrect; determining a plurality of additional motions based at least in part on the second response; causing the motion platform to execute the additional motions; receiving, via the one or more input devices, a plurality of additional responses indicative of the subject’s perception of the additional motions; causing the one or more feedback devices to provide a plurality of additional feedback indicative of whether the additional responses are correct or incorrect; and determining a threshold of the subject based at least in part on the first response, the second response, and at least part of the additional responses, wherein the threshold is a biomarker for a fall risk of the subject. 54. The method of claim 53, further comprising: determining that one of the additional responses is indicative of a lapse by the subject; and determining the threshold of the subject based at least in part on the first response, the second response, and at least part of the additional responses, while excluding the one of the additional responses indicative of a lapse by the subject. 55. The method of claim 54, wherein a standard delete-one jackknife procedure is used to identify the biggest outlier to determine that the one of the additional responses is indicative of a lapse by the subject. 56. The method of claim 55, wherein a standard bootstrap method is used to estimate sample distribution in order to provide strict statistical criteria to identify outliers. 57. The method of claim 53, further comprising determining confidence in order to improve accuracy and precision of the threshold. 58. The method of claim 57, further comprising determining subsequent motions to be executed by the motion platform based at least in part on the confidence. 59. The method of claim 53, further comprising comparing the fall risk of the subject to values from a previously quantified population. 60. The method of claim 59, further comprising: determining that the fall risk of the subject is acceptable when the threshold is below a predetermined percentile for young healthy adults; and determining that training of the subject is recommended when the threshold is above the predetermined percentile. 61. The method of claim 60, wherein the predetermined percentile is the 50th percentile for young healthy adults. 62. The method of claim 60, wherein the training is perceptual training. 63. The method of claim 62, wherein the perceptual training comprises motions individually tailored to improve self-motion perception of the subject. 64. The method of claim 62, wherein the perceptual training comprises motions individually tailored to improve self-motion perception of the subject by lowering a self-motion perceptual threshold of the subject. 65. The method of claim 62, wherein the perceptual training comprises tilt motions individually tailored to improve self-motion perception of the subject by lowering a tilt self- motion perceptual threshold of the subject. 66. The method of claim 65, wherein the perceptual training comprises roll tilt motions individually tailored to lower a roll tilt perceptual threshold of the subject. 67. The method of claim 65, wherein the perceptual training comprises pitch tilt motions individually tailored to lower a pitch tilt perceptual threshold of the subject. 68. The method of claim 65, wherein the perceptual training comprises simultaneous and synchronous roll and pitch tilt motions individually tailored to lower a roll tilt perceptual threshold and a pitch tilt perceptual threshold of the subject. 69. The method of claim 51, further comprising causing the motion platform to execute each of the discrete motions having a single cycle of sinusoidal acceleration. 70. The method of claim 51, wherein the set of discrete motions comprises between 10 and 1000 discrete motions. 71. The method of claim 51, wherein the set of discrete motions comprises one or more translational motions. 72. The method of claim 51, wherein the set of discrete motions comprises one or more rotational motions. 73. The method of claim 51, wherein the set of discrete motions comprises one or more tilt motions. 74. The method of claim 51, wherein the set of discrete motions comprises one or more roll tilt motions. 75. The method of claim 74, further comprising causing the motion platform to execute each of the one or more roll tilt motions for a duration between 0.5 seconds and 10 seconds. 76. The method of claim 74, further comprising determining roll tilt perception of the subject. 77. The method of claim 74, further comprising determining a roll tilt threshold of the subject. 78. The method of claim 51, wherein the subject is supported on the motion platform in a seated position. 79. The method of claim 51, wherein the subject is supported on the motion platform in a standing position. 80. The method of claim 51, wherein the subject is supported on the motion platform in a lying-down position. 81. The method of claim 51, wherein the discrete motions are individually tailored for the subject to enhance training. 82. The method of claim 51, wherein the discrete motions are individually tailored for the subject based at least in part on a previously determined threshold for the subject. 83. The method of claim 82, wherein the discrete motions are individually tailored for the subject to be at or near the previously determined threshold for the subject. 84. The method of claim 82, wherein the discrete motions are individually tailored for the subject using a standard 2-down/1-up staircase. 85. The method of claim 82, wherein the discrete motions are individually tailored for the subject using a standard 3-down/1-up staircase. 86. The method of claim 82, wherein the discrete motions are individually tailored for the subject using a standard 4-down/1-up staircase. 87. The method of claim 82, wherein the discrete motions are individually tailored for the subject using a maximum likelihood method. 88. The method of claim 51, wherein the discrete motions are incrementally changed over the course of a training session. 89. The method of claim 88, wherein the discrete motions are changed using a standard 2- down/1-up staircase with asymmetrical step sizes. 90. The method of claim 88, wherein the discrete motions are changed using a standard 3- down/1-up staircase with asymmetrical step sizes. 91. The method of claim 88, wherein the discrete motions are changed using a standard 4- down/1-up staircase with asymmetrical step sizes. 92. The method of claim 51, wherein the one or more input devices comprise one or more handheld devices configured to enable the subject to provide the responses to the motions executed by the motion platform. 93. The method of claim 92, wherein the one or more handheld devices comprises a plurality of buttons configured to enable the subject to provide different types of the responses to the motions executed by the motion platform. 94. The method of claim 51, wherein the responses are indicative of the subject’s perception of direction of the motions executed by the motion platform. 95. The method of claim 51, wherein the one or more feedback devices are configured to provide the subject with auditory feedback indicative of whether the responses are correct or incorrect. 96. The method of claim 51, wherein the one or more feedback devices are configured to provide the subject with visual feedback indicative of whether the responses are correct or incorrect. 97. The method of claim 51, wherein the subject’s eyes are covered with a blindfold during testing. 98. The method of claim 51, wherein the subject’s eyes are covered with a blindfold during training. 99. The method of claim 51, further comprising emitting white noise, via noise-cancelling headphones positioned on the subject’s ears, while the motion platform executes each of the discrete motions. 100. The method of claim 51, further comprising presenting visual information to the subject, via a visual display, during testing. 101. The method of claim 100, wherein the visual information comprises virtual information. 102. The method of claim 100, wherein the visual information comprises real information. 103. The method of claim 51, further comprising presenting visual information to the subject, via a visual display, during training. 104. The method of claim 103, wherein the visual information comprises virtual information. 105. The method of claim 103, wherein the visual information comprises real information. 106. The method of claim 51, wherein the subject’s eyes are covered with a blindfold during each of the discrete motions executed by the motion platform, the method further comprising presenting visual information to the subject, via a visual display, immediately following each of the responses provided by the subject. |
[0065] Motion stimuli consisted of single cycles of sinusoidal acceleration [(a(t) = ;:
Asin(2π.ft); A = peak accel eration, f= frequency, t = time) with frequency reflecting the inverse of the cycle duration (i.e., 1 Hz =::: 1 second of motion). Peak velocity (vpeak:=: AT/π) and peak displacement (D=AT 2 /2π) are proportional to the peak acceleration (A) (7= cycle duration,/p = displacement). This stimulus is without position, velocity, or acceleration discontinuities and mimics typical head motion stimuli during natural motions. Thresholds were assessed at 0.2 Hz, 0.5 Hz and 1 Hz (i.e., stimuli lasting 5, 2, and 1 second, respectively). 0.2 and 0.5 Hz roll tilt thresholds rely on the integration of concomitant vertical semicircular canal and otolith (predominantly utricle) stimulation, whereas 1 Hz thresholds primarily reflect the precision of the vertical canal signal.
[0066] For each threshold assessment, subjects were tilted about a head-centered naso- occipital axis, such that the rotational axis was located midway between the vestibular labyrinths (Figure 1). Once tilted, the participant was asked to report the direction of tilt using handheld buttons, and then was immediately returned to upright. To mitigate motion after-effects a three second interval was provided between each test motion after the return to upright was complete. A symmetric 4D/1U staircase, in which peak velocity was decreased after four consecutive correct responses and increased after one incorrect response, was used to present stimuli that approach the estimated threshold value; simulations show that the use of a 4D1U staircase for the selection of test stimuli provides a balance between efficiency and precision. Stimulus step size was selected using parameter estimation by sequential testing (PEST) rules. One-hundred motions were completed for each test; while a larger number of trials would yield a more precise estimate of thresholds, prior simulations found only marginal improvements in the precision of threshold estimates when increasing the number of trials above 100.
[0067] The threshold parameter was ultimately determined by fitting the binary responses (e.g, left/right) and stimulus magnitudes (e.g., size and direction of the roll tilt stimulus) to a Gaussian cumulative distribution function. A bias reduced generalized linear model (Matlab brglmfit) with a probit link function was used to minimize the expected underestimation of thresholds introduced by the use of an adaptive sampling scheme. The psychometric function is defined by both the standard deviation, which is the threshold parameter, and mean, which represents the vestibular bias and the offset of the psy chometric function along the abscissa from zero. The threshold parameter, given its direct association with vestibular noise, serves as a primary parameter of interest in this study. [0068] Postural Control [0069] Postural control was quantified using a triaxial force plate (AMTI Accusway) to record the displacement of the center of pressure (CoP) under various quiet stance conditions. These conditions included the standard conditions of the Romberg Test of Standing Balance on Firm and Compliant Support Surfaces with the addition of two conditions (eyes open/closed) assessing tandem stance (heel-to-toe) while on foam (Table 1). Subjects stood with the arms folded and feet in narrow (or tandem) stance for 30 (conditions 1,3,5,6) or 60 (conditions 2,4) seconds. The difference in durations reflects an emphasis on vestibular function, which increases in conditions of eyes closed stance. Thus, the period of testing for such conditions was extended. The primary measure of interest was the root mean square distance (RMSD) of the CoP in the mediolateral plane. The RMSD represents the average magnitude by which the CoP deviates when attempting to maintain a quiet stance; this is effectively the standard deviation of the zero-meaned CoP tracing. For the “vestibular” condition (i.e., condition 4), where subjects stood with eyes closed on a foam surface changes in the mean velocity and mean frequency of the mediolateral CoP were also quantified, as these metrics reflect different aspects of postural control independent from the RMSD. Table 1. Balance test conditions. Participants stood with feet together and arms folded across the chest for conditions 1 through 4; for tandem stance conditions, participants stood heel-to-toe with the dominant foot in front. [0070] Roll Tilt Perceptual Training [0071] The experimental groups performed 1300 trials of roll tilt training over a period of 5 days. The sole difference between the two experimental groups was in the frequency of the training stimulus (0.5 Hz vs. 0.2 Hz). Training was not assessed at 1 Hz (or higher frequencies), as these responses are dominated by canal cues and past evidence suggests learning may be specific for more complex motions which stimulate both the canals and otoliths. The control group only underwent baseline and post-test assessments of thresholds and balance. In contrast to the threshold test conditions, during training the participants were given feedback after each response to indicate whether they were correct or incorrect in their judgement of the motion direction. Feedback was given by unique auditory cues (i.e., a “chime” for correct, and a “buzzer” for incorrect) which were explicitly explained to all training participants before the training protocol. Also, a 2D1U, rather than 4D1U, staircase was used to target a stimulus level that would lead to an accuracy level of 70.1%. This was done to approximate the level of challenge (65% correct) shown previously to induce roll tilt perceptual learning. [0072] The initial stimulus magnitude for the adaptive staircase for each training block (i.e., 100 trials) was modified on the basis of the participant’s previous performance and selected to be 2x the threshold of the previous 100 trial run. In the paradigm used in previous studies the stimulus amplitude was selected based upon an individual’s baseline threshold and held constant; as a result, improvements in roll tilt perception (i.e., lowering thresholds) during the training protocol would be expected to yield a training stimulus that targets a higher level of accuracy or a lesser amount of challenge. For example, a baseline threshold of 1°/s would warrant a training stimulus of 0.38°/s, however, if thresholds were to reduce to 0.5°/s with training, a 0.38°/s stimulus would be expected to yield an accuracy level of 78%. The adaptative 2D1U staircase was selected to instead maintain a consistent level of challenge (i.e., level of accuracy of perceptual judgments) despite the anticipated improvements in performance over the course of training. This staircase approach also forgives inaccuracies (e.g., inherent variability) in pre- training threshold measures. While the experimenter could not be blinded to group assignment in order to administer the correct training stimulus, the threshold protocols and training intervention described above are carried out using custom automated software and thus, are not reliant upon human input, aside from monitoring the testing session; also, perceptual threshold and CoP metrics were computed using automated Matlab programs. [0073] Statistical Analysis [0074] Linear mixed effect models (mixed; Stata v17.0, College Station, TX) were fit to the data to account for the repeated measured design. The main effects of time (baseline, post- test) and group (control, 0.5, 0.2 Hz) were included, as well as their interaction (group by time). Post-hoc comparisons were completed using tests of simple effects (i.e., partial F-tests); multiple comparisons were controlled for by computing Bonferroni corrected p-values. Separate mixed effect models were used for each of three frequencies of baseline thresholds (0.2, 0.5, and 1 Hz), as well as for each balance condition. The degrees of freedom in the mixed effect model were adjusted using the Kroger method to mitigate the increase in Type I error that results from the small sample size and the variability in estimates of the subject specific random effect term. To determine whether the extent of threshold improvement was associated with improvements in balance, the spearman rank correlation was calculated between the change in thresholds and the change in balance performance. Finally, to determine the proportion of subjects in each group who showed a meaningful improvement in thresholds after the intervention, the subjects were also categorized as “responders” or “non-responders.” Simulations have shown that thresholds measured using a 4D1U staircase yield a variability of ~16% (1 SD); a meaningful change was defined as a reduction in thresholds of at least 2 SD (here defined as >32%) from the threshold value measured at baseline. Multivariate logistic regression was used to determine whether the odds of responding favorably to the intervention was affected by age, baseline thresholds, or sex. [0075] Results [0076] Baseline Comparison of Groups [0077] Univariate linear regression models were used to compare the threshold measures (0.2, 0.5, and 1 Hz) and postural sway metrics between each of the three groups at baseline. The 0.5 Hz training group showed significantly higher RMSD in the “eyes open, on foam condition” compared to the control group (p=0.004), otherwise no significant differences were observed between any of the groups for any of the chosen metrics (p>0.05; Table 2).
Table 2. Baseline mean (SD) data is shown and p-values reflect the effect of Group in separate linear mixed effect models. RMS = root mean square displacement, MVEL = mean velocity, MFREQ = mean frequency, EO = eyes open, EC = eyes closed. * = significant at p < 0.05. [0078] Effect of Training on Roll Tilt Thresholds [0079] The control group showed consistent 0.2 Hz thresholds on days 1 and 6 of the study, on average increasing thresholds by 1.5% (p>0.999) The 0.2 Hz training group demonstrated a significant change in 0.2 Hz thresholds (p=0.009) improving an average of 23.8%, as did the 0.5 Hz training group (p=0.046) who improved an average of 19.1% (Table 3; Figure 2). Group assignment modified the effect of time, such that the effect of time was greater for the 0.2 Hz group, compared to the control group (p=0.025). While approaching significance, the effect of time was not significantly different between the 0.5 Hz group and controls (p=0.069). Table 3. Baseline (day 1) and post-test (day 6) thresholds are reported for each group. Average change in thresholds is reported. Bonferroni corrected 95% CI reflects the results of the post-hoc partial F-test comparing the effect of time (day 1 vs. day 6) for each group. [0080] For 0.5 Hz roll tilt thresholds, the control group again showed minimal change in thresholds between days 1 and 6 (p>0.999, average decrease of 4 %). A significant decrease in thresholds was observed for the 0.2 Hz group (p=0.046), but not for the 0.5 Hz group (p=0.074), after correcting for multiple comparisons. The 0.2 Hz group showed an average change of 22.2% compared to 17.7% for the 0.5 Hz group (Table 3; Figure 2). In contrast to the significant interaction seen for 0.2 Hz thresholds, no significant group by time interactions were observed, suggesting that group assignment did not modify the effect of time on 0.5 Hz thresholds, putatively as a result of the variability in the response to treatment within the intervention groups (see below). [0081] For 1 Hz roll tilt thresholds, similar improvements in thresholds were observed for each of the three groups, including the control group; this finding is consistent with previous studies. However, despite a decrease in mean thresholds at day 6 for each group (control = 17.4%, 0.2 Hz = 17.8%, 0.5 Hz = 14.8%), the effect of time was not significant for any of the groups (p>0.05) and no group by time interaction effects were present (p>0.05) (Table 3; Figure 2). [0082] Classifying Treatment Responders [0083] After visualizing the data, clusters of “responders” were observed within both the 0.5 and 0.2 Hz training groups, such that approximately half of the subjects appeared to experience a marked decrease in thresholds, while others show relatively stable performance (Figure 3). To quantify this effect, subjects were categorized as “responders” based upon their percent change in thresholds, using a threshold of 32% as an indicator of a meaningful change. This is based upon prior data showing that thresholds, on average, are expected to vary on a within subject basis by one standard deviation or 16% (e.g., 0.16°/s for a threshold of 1°/s); thus, a cut-off at two standard deviations or 32% was set. For 0.2 Hz thresholds, 50% (5/10) of the 0.2 Hz training group and 30% (3/10) of the 0.5 Hz group were categorized as responders, compared to 0% (0/10) of the control group. Similarly, for 0.5 Hz thresholds, 50% (5/10) of the 0.2 Hz training group and 40% (4/10) of the 0.5 Hz group were categorized as responders, and only 10% (1/10) of the control subjects improved by at least 32% (N=1 with a 36.2% change). This behavior was not observed for 1 Hz roll tilt, where similar changes were seen between all three groups; 10% of the control group, 20% of the 0.2 Hz group, and 20% of the 0.5 Hz group improved by at least 32%. [0084] Table 4 shows the age and baseline thresholds for the “responder” and “non- responder” groups, defined by those who showed an improvement of at least 2 SDs on either 0.2 or 0.5 Hz thresholds. Logistic regression was performed to determine the effect of age, sex, and baseline thresholds on responder status. No significant effects were observed (p>0.05) suggesting that the heterogeneity in treatment responses were due to individual differences in the response to the intervention or due to an unaccounted-for confounding variable (cognition, attention, motivation, etc.); the inclusion of healthy, asymptomatic young adults without a significant medical history favors the former, such that individuals may vary in their “optimal” training stimulus or dosage of training. Table 4. Baseline characteristics of those who improved by at least 2 SD’s on either the 0.2 Hz or 0.5 Hz condition (responders) compared to those who did not (non-responders) amongst those in the training groups (N=20). A logistic regression model was used to determine the effect each characteristic on the odds of being a responder (significance at p <0.05). [0085] Effect of Roll Tilt Adaptation on Balance [0086] The original hypothesis was that the greatest change in balance performance would be observed in the “eyes closed, on foam” condition, where vestibular cues are thought to dominate. The 0.2 Hz group showed an average decrease in sway of 17.16% (p<0.001), and the 0.5 Hz group similarly improved by an average of 20.47% (p<0.001). However, unexpectedly, the control group also improved by a similar amount (15.16%; p<0.001) suggesting improvements were not specific to the training groups. The changes were significant for all three groups without a significant group by time interaction, suggesting that the effects of time were similar for each of the three groups (Figure 4). [0087] In the “eyes open, firm” and the “eyes closed, firm” conditions the RMSD was largely unchanged for both the training groups as well as the control group, with the exception of a non- significant reduction of 12.8% for the 0.5 Hz group in the EC/firm condition (Table 5, Figure 4). In the remaining “eyes open, foam” condition, the 0.5 Hz group showed a significant reduction in sway (p=0.032), averaging a 13.8% decrease following the intervention. Finally, in the “eyes open, on foam in tandem” condition, both the 0.2 and 0.5 Hz groups improved by more than 10%, but the effects were not significant (Table 5, Figure 4). Due to falls, only 7/10 subjects in the 0.5 Hz group and 9/10 in the 0.2 Hz group were analyzed in this fifth condition. Much like roll tilt thresholds, changes in balance performance varied between subjects (Figure 5).
Table 5. Average percent change (positive = increase, negative = decrease) in RMSD for each group in each of the 5 primary balance conditions. Corrected p-values are reported in parentheses and represents the results of the post-hoc test comparing RMSD between days 1 and 6 of the protocol. * = significant at a Bonferroni corrected alpha of 0.05. EO = eyes open, EC = eyes closed. [0088] Given the young, healthy population of interest, a sixth balance condition was included to fully capture any subclinical balance deficits; subjects were asked to stand in tandem, on a foam pad with the eyes closed. Only 5/30 (16.7%) of the participants were able to stand for 30 seconds when given two attempts at the baseline assessment. At follow up, four of these five subjects again completed the balance task, showing an average decrease in ML RMSD of -14.9% (-28.8%, +18.5%, -12.9%, and -36.5% respectively). Interestingly, these four subjects were all in the 0.2 Hz training group and showed an average change of -22.24% in 0.2 Hz thresholds and -35.59% in 0.5 Hz thresholds. In addition, at the follow up assessment, four subjects (control = 2, 0.5Hz = 1, 0.2 Hz=1) who failed this task at baseline were able to stand for at least 30 seconds; this cohort showed an average decrease in 0.2 Hz thresholds of 14.2% (- 54.1% to +24.2%) and 5.13% in 0.5 Hz thresholds (-32.3% to +74.5%) with changes in thresholds varying widely. [0089] Discussion [0090] The data show that 0.2 and 0.5 Hz roll tilt perceptual thresholds can be improved significantly in less than 5 hours of training by using an adaptative roll tilt training stimulus. Additionally, these data show that the training response can be robust; 55% (11/20) of subjects in the training groups improved either 0.2 or 0.5 Hz roll tilt thresholds by at least 2 SDs (i.e., 32%) whereas the control group displayed stable thresholds between days 1 and 6 (1/10 improving by more than 32%). The effect of training on quiet stance postural sway was less robust relative to the effects on vestibular perceptual thresholds, however, a significant reduction in postural sway was observed for the 0.5 Hz group in two of the conditions where proprioceptive cues were degraded (i.e., where vestibular cues are more important for postural stability). [0091] Mechanism of Perceptual Adaptation [0092] The stimulus for adaptation of the VOR is generally considered to be the induction of a “retinal slip” (i.e., movement of a visual image off of the fovea) error signal. The disparity between the visual target and fovea is thought to trigger central visuo-vestibular mechanisms that act to reduce the blurring of vision through the generation of preprogrammed eye movements and compensatory saccades, as well as a modest increase in slow phase eye velocity. In the perceptual adaptation paradigm described here, the training takes place in the dark, and thus, no such retinal slip error could have been provided. As a result, the mechanism underlying adaptation in the perceptual domain requires further study, but, given that the roll tilt training stimuli activate both the canals and otoliths, it is presumed that the underlying adaptation mechanism enhances canal-otolith integration. [0093] In contrast to studies of VOR adaptation, subjects were provided trial by trial feedback on their responses, with the expectation that learning would occur based upon the provided feedback. As a result, incorrect responses yield an error signal related to the conflict between the perceived and actual motion stimulus. The benefit of similar feedback has been established for auditory and visual perceptual training. Although several theories exist to describe the mechanisms underlying the positive effect of feedback on perceptual training, the Augmented Hebbian Reweighting Model (AHRM) has a body of evidence that supports its validity. In general, Hebbian learning describes an experience dependent improvement in performance that occurs secondary to a strengthening of the relevant synaptic connections. The AHRM attributes perceptual learning to a reweighting of the appropriate sensory pathways, such that the strength of synaptic connections within the most efficient channels are strengthened, and the least efficient pathways go unused, and are therefore weakened. [0094] While the provision of a mechanistic explanation for the observed effect is beyond the scope of this study, there are likely shared elements between self-motion perceptual learning in the visual and vestibular domains. Specifically, as vestibular thresholds quantify sensory noise, it is posited that perceptual adaptation may lower thresholds by reweighting the more reliable, or “less noisy”, central vestibular pathways. The absence of frequency specific effects for roll tilt adaptation suggests also a possible shared mechanism yielding improvements in both 0.2 and 0.5 Hz thresholds, motions which both require canal-otolith integration. Modeling efforts, analogous to those utilized in the visual system, should be conducted to provide an explanation for the observed effects. Studies comparing learning in the vestibular motor (i.e., VOR) and perceptual domains are also needed to determine whether characteristics previously shown to induce greater adaptation of the VOR (i.e., retinal slip) can yield similar effects for roll tilt perceptual training. [0095] Roll Tilt Perception and Balance [0096] In a sample of healthy older adults, previous studies showed that 0.2 Hz roll tilt thresholds were a significant predictor of the ability to complete an “eyes closed, on foam” balance task, a categorical analog to the quantitative measure of sway reported here. A subsequent mediation analysis showed that 0.2 Hz roll tilt thresholds mediated 46% of age- related imbalance. Together, these findings suggested that vestibular noise, as quantified by roll tilt thresholds, may contribute to subclinical balance impairment. However, despite the large effect and notable sample size (N=99) of this dataset, correlation cannot prove causation, and thus the supposition of whether vestibular noise “causes” imbalance has yet to be tested. [0097] The data disclosed herein provides evidence that increased vestibular noise may be a potential cause of subclinical balance impairment. This is supported by the finding that the 0.5 Hz roll tilt adaptation intervention led to a significant reduction in postural sway in the “eyes open, on foam” and “eyes closed, on foam” balance conditions. This is consistent with recent data showing that 0.5 Hz roll tilt thresholds display a significant positive correlation with postural sway in the “eyes closed, on foam” condition. [0098] However, despite the reduction in sway, several findings temper the interpretation of this effect. First, the improvement for the 0.5 Hz group was variable, and the magnitude of change in thresholds did not display a significant positive correlation with the change in postural sway (Figure 6; EO/Foam: r = -0.28, p = 0.140, EC/Foam: r = -0.13, p = 0.483). One explanation is that unintended factors (i.e., fatigue, motivation) could have preferentially impacted follow up threshold tests (due to the higher attentional demand), more so than balance assessments, in a subset of participants, yielding changes in balance but not thresholds. In addition, the control group also displayed a significant reduction in sway in the “eyes closed, on foam” condition, suggesting that a portion of the improvement in sway may be related to a learning effect, rather than the roll tilt intervention. The small effect sizes also likely result from the healthy population studied, where both balance and vestibular function were tightly distributed within a normal range. Additional studies should test the effect of roll tilt perceptual training on balance in older adults and/or patients with vestibular loss to determine the effect of improving perception in the presence of overt postural instability. [0099] Comparison to Past Studies [0100] Only one previous study attempted to improve roll tilt perception through a behavioral training paradigm. Previous studies showed that 1800 trials of roll tilt performed over the course of 9 days (9 hours total) led to an average improvement in 0.2 Hz roll tilt thresholds of 33%. The present disclosure shows that 0.2 Hz roll tilt thresholds can be improved with roughly 5 hours of training. The primary means by which training time was reduced was through the use of an adaptive training stimulus, which allowed for reduction of the number of training trials from 1800 to 1300. Additionally, the 0.5 Hz group received circa 3 hours of training as the 0.5 Hz stimulus lasts 2 seconds as compared to 5 seconds for 0.2 Hz. Because the specific dosage (time or repetitions) needed to induce perceptual learning are not fully known, the decreased exposure time for the 0.5 Hz group, compared to 0.2 Hz group, may explain the differences in learning observed. Similarly, the observed change in 0.2 Hz roll tilt thresholds of 23.8% for the 0.2 Hz training group was qualitatively less than was shown in previous studies (33%), suggesting that a higher time of exposure (9 vs. 5 hours) may be beneficial. Additional work is needed to determine the optimal dose of training, including whether the added time for training is worth the marginal difference in training outcomes. [0101] In contrast to a previous study that reported that each of the 10 subjects in its training group showed an improvement in thresholds, a striking feature of the presently disclosed dataset was in the variability in responses to the training protocol. Factors that may explain the likelihood of showing a positive response to the intervention (i.e., a change of >32%) were investigated, but a significant difference in sex, age, or baseline thresholds between the responder and non- responder groups was not identified. One potential explanation is that the non-responders may have simply required additional repetitions compared to the responders. Future studies should determine the appropriate dosage (i.e., both time and repetitions) and whether an individualized intervention dose can be predicted to enable participants to reduce thresholds while avoiding overutilization of training resources. [0102] Alternatively, it is possible that the proposed training intervention may not represent the “optimal” stimulus to induce perceptual learning; being that this is only the second such effort, this is certainly a feasible explanation. The 2D1U staircase, as was used here, targeted a challenging stimulus level where, on average, the subject should be able to perceive the direction of motion 70.7% of the time. Since simply guessing leads to an average accuracy of 50% (i.e., heads or tails judgement), the chosen stimuli were quite challenging and thus led to a sizeable proportion of errors. As a result, some subjects may have benefited from an easier task where they experienced a higher level of success. Individual preferences for success, as compared to challenge, may have also been one of the factors leading the clustering of responders and non-responders. [0103] Finally, a body of literature supports that a visual error signal proves to be critical for inducing adaptation in the vestibulo-ocular reflex. Although the VOR and perceptual mechanisms have been shown to be qualitatively different, it remains possible that due to the shared central vestibular structures (i.e., vestibulo-cerebellum) that vestibular perceptual learning may benefit from a similar visual error signal (i.e., providing visual feedback on whether motion perception judgment is correct). [0104] Implications for Rehabilitation [0105] Existing methods for vestibular rehabilitation focus primarily on the recruitment of extra vestibular strategies to compensate for vestibular loss. In the case of vestibular lesions, these methods are robust and lead to marked improvements in dynamic visual acuity, reductions in dizziness, and improvements in postural control. However, in the presence of progressive sensorimotor changes (e.g., due to aging or neurodegenerative diseases) the availability of viable extra-vestibular sensory cues becomes limited, and thus, may constrain the effectiveness of rehabilitation. The present disclosure describes an intervention that aims to directly improve vestibular function by improving the signal to noise ratio of the self-motion roll tilt estimate, thereby avoiding the reliance on intact visual or proprioceptive cues. [0106] In addition, perceptual symptoms of vestibular loss, namely vertigo and dizziness, have been shown to significantly impact quality of life, yet existing means to manage perceptual symptoms are limited. The repetitive exposure to provocative stimuli (i.e., habituation) is generally effective but requires tolerance of the intentional solicitation of symptoms over the course of weeks or months of training. Perceptual adaptation should be explored as a potential alternative to habituation training given its direct target of self-motion perception alongside a high level of tolerance. [0107] Conclusion [0108] Roll tilt perceptual adaptation led to improvements in perceptual thresholds for 0.2 and 0.5 Hz roll tilt whereas a control group showed stable thresholds. In approximately half of the subjects in the training groups, a robust improvement in roll tilt thresholds (> 32% or 2 SDs) was observed, suggesting that variability exists in response to the training intervention. Among individuals who trained using a 0.5 Hz roll tilt stimulus, a reduction in postural sway in conditions where proprioceptive cues were degraded was observed, suggesting that increased vestibular noise may be a potential cause of increased postural sway in these conditions. [0109] Example [0110] In further studies, a single asymptomatic older adult subject (female, 67 years of age) was recruited to complete the 0.5-Hz training protocol. Relative to the cohort of young adult participants (Table 1), this individual showed elevated 0.5-Hz roll tilt thresholds and increased postural sway in the “eyes closed, on foam” condition. At the post-test assessment, a 51.4% decrease in 0.5-Hz roll tilt thresholds (day 1: 1.4°/s, 95% CI 1.34–1.46; day 6: 0.68°/s, 95% CI 0.66–0.80) and a 31.9% reduction in RMSD during the “eyes closed, on foam” balance task (day 1: 16.1mm; day 6: 11.0 mm) was observed for this older adult participant. Interestingly, at the post-test assessment, the 67-year-old subject’s roll tilt threshold and postural sway were each lower than the mean 0.5-Hz roll tilt threshold (0.74°/s) and RMSD (11.89 mm) values reported at baseline for the young adult subjects with a mean age of 25 years old. Although only a single subject, these data support the prior supposition that changes with training may be greatest for those with elevated baseline postural sway and thresholds. In addition, when reassessed 8 weeks after the post-test assessment, the 67-year-old subject was found to have 0.5-Hz roll tilt thresholds (0.88°/s, 95% CI 0.85–0.90) and RMSD values (14.2 mm) that remained improved relative to her day 1 (pre-test) assessment. Future studies should test the effect of roll tilt perceptual training on balance in larger samples of older adults, as well as in individuals with vestibular loss, to determine the effect of roll tilt perceptual training on overt, rather than subclinical, postural instability. [0111] Although specific embodiments of the disclosure have been described, one of ordinary skill in the art will recognize that numerous other modifications and alternative embodiments are within the scope of the disclosure. For example, while various illustrative implementations and structures have been described in accordance with embodiments of the disclosure, one of ordinary skill in the art will appreciate that numerous other modifications to the illustrative implementations and structures described herein are also within the scope of this disclosure. [0112] Although embodiments have been described in language specific to structural features and/or methodological acts, it is to be understood that the disclosure is not necessarily limited to the specific features or acts described. Rather, the specific features and acts are disclosed as illustrative forms of implementing the embodiments. Conditional language, such as, among others, “can,” “could,” “might,” or “may,” unless specifically stated otherwise, or otherwise understood within the context as used, is generally intended to convey that certain embodiments could include, while other embodiments do not include, certain features, elements, and/or steps. Thus, such conditional language is not generally intended to imply that features, elements, and/or steps are in any way required for one or more embodiments.
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