A new rehabilitation method is presented for rebalancing the vestibular system in patients with asymmetric responses, which consists of unidirectional rotations toward the weaker side. By directly modifying the vestibular pathway rather than enhancing the multisensory aspects of compensation, asymmetry can be normalized within 1-2 sessions and show lasting effects.
The vestibular system provides information about head movement and mediates reflexes that contribute to balance control and gaze stabilization during daily activities. Vestibular sensors are located in the inner ear on both sides of the head and project to the vestibular nuclei in the brainstem. Vestibular dysfunction is often due to an asymmetry between input from the two sides. This results in asymmetrical neural inputs from the two ears, which can produce an illusion of rotation, manifested as vertigo. The vestibular system has an impressive capacity for compensation, which serves to rebalance how asymmetrical information from the sensory end organs on both sides is processed at the central level. To promote compensation, various rehabilitation programs are used in the clinic; however, they primarily use exercises that improve multisensory integration. Recently, visual-vestibular training has also been used to improve the vestibulo-ocular reflex (VOR) in animals with compensated unilateral lesions. Here, a new method is introduced for rebalancing the vestibular activity on both sides in human subjects. This method consists of five unidirectional rotations in the dark (peak velocity of 320°/s) toward the weaker side. The efficacy of this method was shown in a sequential, double-blinded clinical trial in 16 patients with VOR asymmetry (measured by the directional preponderance in response to sinusoidal rotations). In most cases, VOR asymmetry decreased after a single session, reached normal values within the first two sessions in one week, and the effects lasted up to 6 weeks. The rebalancing effect is due to both an increase in VOR response from the weaker side and a decrease in response from the stronger side. The findings suggest that unidirectional rotation can be used as a supervised rehabilitation method to reduce VOR asymmetry in patients with longstanding vestibular dysfunction.
Vestibular dysfunction is a common disorder with a prevalence of ~35% in adults above 40 years old1. Most vestibular disorders result in an asymmetry between input from both sides, resulting in an illusion of rotation called vertigo. In the absence of normal vestibular function, even simple daily activities can be challenging. Vestibular dysfunction is often quantified by the vestibulo-ocular reflex (VOR). During natural activities, such as walking or running, the VOR moves the eyes in the opposite direction and with the same velocity as head movement. This reflex has a short latency of ~5 ms, and it is mediated in the horizontal plane through a simple, three-neuron arc2. The information travels from vestibular receptors to the vestibular nuclei, then to the abducens motor neurons. These eye movements result in stabilization of horizontal gaze during daily activities. The symmetry of the VOR in response to clockwise and counterclockwise rotations is an important test of vestibular function.
Unilateral vestibular dysfunction produces central compensatory changes and centrally driven peripheral changes to overcome defective asymmetric VOR and resulting vestibular imbalance. Even after permanent vestibular lesions, such as a unilateral vestibular neurectomy, the vertigo and accompanying symptoms improve over a short period (days to weeks) of time. Due to this ability, the vestibular system has been a model for studying adaptation and compensation in neural pathways. It has been previously shown3 that changes in central vestibular pathways can be implemented by a unidirectional rotation based on a hypothesis proposed by one of the authors (N.R.) about 20 years ago. Other studies have also shown compensatory changes in different parts of the sensory pathway, including the vestibular nuclei (VN)4,5,6,7,8, commissural pathways between the VN on both sides9, cerebellar inputs10, and the vestibular periphery11. These compensatory changes result in a new balance in the activity of VN neurons on both sides.
Despite the impressive ability of the vestibular system to compensate for asymmetric inputs from the two ears, research has shown that responses to fast movements are never fully compensated12,13. It is now known that natural vestibular compensation does not use the full capacity of the system, and the compensated VOR response can be improved in animals that have participated in visual-vestibular training14,15. It has long been known that vestibular rehabilitation exercises improve the compensation in patients with chronic imbalance problems by enhancing the (non-vestibular) multisensory nature of balance control16,17,18,19,20,21. The goal of these vestibular rehabilitation exercises is to use physiological or behavioral approaches to improve symptoms as well as a patient's quality of life and independence22,23.
Described herein is a rehabilitation method that uses unidirectional rotations toward the "weaker" side (Figure 1A). The basic idea for this method comes from Hebbian plasticity, in which neural connections become stronger when they are stimulated. This method specifically modifies vestibular inputs rather than enhancing multisensory integration, which is the basis for other vestibular rehabilitation exercises. Previous research has shown that unidirectional rotations decreases VOR asymmetry in 1-2 sessions in patients with unilateral vestibular dysfunction3. This effect was mainly due to an increase in the activity of the side with a lower response (LR), as well as a slight decrease in the activity of the side with a higher response (HR). This change is most likely mediated by modifications in the central pathways (e.g., strengthening of afferent pathways, such as VN connections or changes in commissural inputs). In effect, this technique may be used as a supervised method for vestibular rehabilitation in those with longstanding vestibular asymmetry.
The data presented here and previously published3 were obtained by studies carried out in accordance with the recommendations of the Ethics Committee of Shahid Beheshti University of Medical Sciences, Tehran, Iran and a protocol that was approved by the Institutional Review Board of the University.
1. Participant screening and preparation
2. Measurement of the vestibulo-ocular reflex (VOR)
3. Unidirectional rotation stimulus
4. Experiment design
5. Sessions details
Short-term effects of the unidirectional rotation were evaluated by measuring the VOR with a 0.2 Hz (40°/s) sinusoidal rotation test at 70 min after rehabilitation3. Figure 2 shows the peak eye velocities during the VOR responses to rotations in the two directions (Figure 2A) and the change in the DP (Figure 2B). Following unidirectional rotation, the response to rotations in the direction of the side with the lower response (LR) was increased, and the response to rotations in the opposite direction (the direction with the stronger response [HR]) decreased, resulting in decreases in VOR asymmetry and DP value. It should be noted that the phase of the response was not calculated in the current study since subjects had asymmetric VOR responses and the VOR phase is known to be a sensitive measure in compensated patients with normal symmetric gains, specially at low frequencies of rotation26,29,30,31.
Exposing subjects to the unidirectional rotation during multiple sessions further decreased the DP value. The effect of this rehabilitation was retained between sessions (Figure 2C), and the cumulative effect resulted in most subjects having a normal DP after only two sessions. Similar to the short-term effect, the improvement in DP was the result of an increase in VOR responses for rotations toward the LR side and decrease in VOR responses during rotations toward the HR side3.
Figure 1: Unidirectional rotation decreases asymmetry between the two sides. (A) Schematic showing the hypothesis behind the unidirectional rotation. Stimulation of the side with lower response (LR) and inhibition of the side with the higher response (HR, red arrows) will result in a change in commissural inputs as well as direct afferent inputs. This results in an increase in the response of LR neurons and decrease in the asymmetry between the two sides (black arrows). (B) Experimental design and rotational paradigms. Please click here to view a larger version of this figure.
Figure 2: Short-term and long-term effect of the unidirectional rotation. (A) In the first session and 70 min after unidirectional rotation, peak eye velocity (°/s) showed a 14% increase in response to rotations toward the side with lower response (LR) and 16% decrease for rotations toward the side with higher response (HR, n = 16). Although these changes were not statistically significant (for LR: 25.0 ± 2.2 vs. 26.75 ± 5.3 °/s, paired Student's t-test, p = 0.23; for HR: 35.0 ± 3.6 vs. 26.0 ± 4.4 °/s, paired Student's t-test, p = 0.15), they resulted in a decrease in overall asymmetry. Error bars represent SEM. (B) Corresponding DP values decreased significantly (paired Student's t-test, p = 0.0006) and reached normal values. Error bars represent SEM. (C) The effect of the unidirectional rotation stayed for a longer time period and was cumulative. Pre-session values were measured before rehabilitation in a session and post-session values were measured 70 min after rehabilitation in that session. Negative DP values indicate reversal of the direction of asymmetry compared to the beginning of the study. Sessions are comparable to the Figure 1B schematic. Error bars represent SEM. This figure has been modified from Sadeghi et al.3. Please click here to view a larger version of this figure.
The rehabilitation method presented here consists of repeated unidirectional rotations in the dark toward the less responsive (LR) side in patients with vestibular imbalance and VOR asymmetry. Most rehabilitation techniques enhance multisensory integration in order to improve balance16,17,18,19,20. The method presented here targets the vestibular pathway, and its effects may be explained by a response increase in the VN on the LR side and a decrease in VN response on the HR side. These effects may be mediated at the afferent VN synapse due to the unidirectional stimulation of the sensors and nerves on the LR side and simultaneous decrease on the HR side. It may also affect VN activity through changes in the commissural inputs, which are known to play an important role in vestibular compensation9. Regardless of the mechanism, this method provides an effective way for decreasing asymmetry in responses of the two sides.
Previous studies have shown that repeated rotations could result in habituation of responses in normal animals and humans32,33,34,35,36,37. While this appears to be in contrast with these results, the conditions are different when the system is compensating for an asymmetry. Furthermore, a critical step in the design of the unidirectional rotation is to have a very slow deceleration in order to avoid stimulation of the other side. None of the previous studies have used such asymmetric stimulation.
It was found here that most subjects showed normal DP after two sessions3. This suggests that patients should be evaluated after two sessions to determine their progress and plan for future sessions. Furthermore, it is not known whether changes in DP are correlated with changes in subjective perceptions of retinal slippage. Future studies are required to evaluate this relationship using standardized vestibular/balance questionnaires before and after unidirectional-rotation sessions. Finally, a change in VOR asymmetry was only evaluated at lower frequencies of rotation (0.2 Hz). 1) The effects of this treatment on VOR phase or 2) whether or not this improvement transfers to higher frequencies of rotation or to the vestibulo-spinal pathways requires further investigation.
It is well-known that customized and supervised exercises provide better results in patients compared to unsupervised exercises that can be performed at home38,39,40,41,42,43. Here, to perform the unidirectional rotations, an expensive rotary chair is used that limits the use of this method. However, two important parameters for successful unidirectional rotation are a relatively high peak velocity during acceleration and a slow deceleration, which can be achieved by any rotating chair to which the patient can be securely attached using a trained partner to perform the asymmetrical rotation, or through the use of tele-health approaches. If confirmed by future studies, alternative low-tech approaches may provide a far less expensive alternative for performing this vestibular rehabilitation service.
Overall, in this preliminary study, unidirectional rotation provides an effective way for reducing VOR asymmetry in patients, even in the compensated stage. The results show that this method may be used as an effective supervised method for vestibular rehabilitation even in patients with longstanding vestibular dysfunction.
The authors have nothing to disclose.
N. R. was supported by a research fund from Shahid Beheshti University of Medical Sciences and Health Services. S. G. S. was supported by NIDCD R03 DC015091 grant.
VEST operating and analysis software | NeuroKinetics | ||
Electronystagmograph | Nicolet | Spirit Model 1992 | Equipment used for collecting the data presented in the Results section |
I-Portal NOTC (Neurotologic Test Center) | NeuroKinetics | Equipment shown for current studies and shown in the movie |