Unilateral Vestibular Damage Research Articles

Advanced progress of vestibular compensation in vestibular neural networks.

Vestibular compensation is the natural process of recovery that occurs with acute peripheral vestibular lesion. Here, we summarize the current understanding of the mechanisms underlying vestibular compensation, focusing on the role of the medial vestibular nucleus (MVN), the central hub of the vestibular system, and its associated neural networks. The disruption of neural activity balance between the bilateral MVNs underlies the vestibular symptoms after unilateral vestibular damage, and this balance disruption can be partially reversed by the mutual inhibitory projections between the bilateral MVNs, and their top-down regulation by other brain regions via different neurotransmitters. However, the detailed mechanism of how MVN is involved in vestibular compensation and regulated remains largely unknown. A deeper understanding of the vestibular neural network and the neurotransmitter systems involved in vestibular compensation holds promise for improving treatment outcomes and developing more effective interventions for vestibular disorders.

Clinical vestibular testing assessed with machine-learning algorithms.

Dizziness and imbalance are common clinical problems, and accurate diagnosis depends on determining whether damage is localized to the peripheral vestibular system. Vestibular testing guides this determination, but the accuracy of the different tests is not known. To determine how well each element of the vestibular test battery segregates patients with normal peripheral vestibular function from those with unilateral reductions in vestibular function. Retrospective analysis of vestibular test batteries in 8080 patients. Clinical medical records were reviewed for a subset of individuals with the reviewers blinded to the vestibular test data. A group of machine-learning classifiers were trained using vestibular test data from persons who were "manually" labeled as having normal vestibular function or unilateral vestibular damage based on a review of their medical records. The optimal trained classifier was then used to categorize patients whose diagnoses were unknown, allowing us to determine the information content of each element of the vestibular test battery. The information provided by each element of the vestibular test battery to segregate individuals with normal vestibular function from those with unilateral vestibular damage. The time constant calculated from the rotational test ranked first in information content, and measures that were related physiologically to the rotational time constant were 10 of the top 12 highest-ranked variables. The caloric canal paresis ranked eighth, and the other elements of the test battery provided minimal additional information. The sensitivity of the rotational time constant was 77.2%, and the sensitivity of the caloric canal paresis was 59.6%; the specificity of the rotational time constant was 89.0%, and the specificity of the caloric canal paresis was 64.9%. The diagnostic accuracy of the vestibular test battery increased from 72.4% to 93.4% when the data were analyzed with the optimal machine-learning classifier. Rotational testing should be considered the primary test to diagnose unilateral peripheral vestibular damage in patients with dizziness or imbalance. Most physicians, however, continue to rely on caloric tests to guide their diagnoses. Our results support a significant shift in the approach used to determine diagnoses in patients with vestibular symptoms.

Examination and Treatment of Patients With Unilateral Vestibular Damage, With Focus on the Musculoskeletal System: A Case Series

Persistent dizziness and balance problems have been reported in some patients with unilateral vestibular pathology. The purpose of this case series was to address the examination and treatment of musculoskeletal dysfunction in patients with unilateral vestibular hypofunction. The musculoskeletal system was evaluated with the Global Physiotherapy Examination, dynamic balance was measured during walking with triaxial accelerometers positioned on the lower and upper trunk, and symptoms and functional limitations were assessed with standardized self-report measures. The 4 included patients had symptoms of severe dizziness that had lasted more than 1 year after the onset of vestibular dysfunction and a moderate level of perceived disability. Musculoskeletal abnormalities typically included postural misalignment, restricted abdominal respiration, restricted trunk movements, and tense muscles of the upper trunk and neck. The patients attended a modified vestibular rehabilitation program consisting of body awareness exercises addressing posture, movements, and respiration. After the intervention, self-reported symptoms and perceived disability improved. Improvements in mobility and positive physical changes were found in the upper trunk and respiratory movements. The attenuation of mediolateral accelerations (ie, body oscillations) in the upper trunk changed; a relatively more stable upper trunk and a concomitantly more flexible lower trunk were identified during walking in 3 patients. The recovery process may be influenced by self-inflicted rigid body movements and behavior strategies that prevent compensation. Addressing physical dysfunction and enhancing body awareness directly and dizziness indirectly may help patients with unilateral vestibular hypofunction break a self-sustaining cycle of dizziness and musculoskeletal problems. Considering the body as a functional unit and including both musculoskeletal and vestibular systems in examination and treatment may be important.

Intrinsic Neuronal Excitability: A Role in Homeostasis and Disease

Intrinsic Neuronal Excitability: A Role in Homeostasis and Disease

Type B GABA receptors contribute to the restoration of balance during vestibular compensation in mice

Following unilateral vestibular damage (UVD), vestibular compensation restores both static and dynamic vestibular reflexes. The cerebellar cortex provides powerful GABAergic inhibitory input to the vestibular nuclei which is necessary for compensation. Metabotropic GABA type B (GABA B) receptors in the vestibular nuclei are thought to be involved. However, the contribution of GABA B receptors may differ between static and dynamic compensation. We tested static and dynamic postural reflexes and gait in young mice, while they compensated for UVD caused by injection of air into the vestibular labyrinth. The effects of an agonist (baclofen), an antagonist (CGP56433A) and a positive allosteric modulator (CGP7930) of the GABA B receptor were evaluated during compensation. Static postural reflexes recovered very rapidly in our model, and baclofen slightly accelerated recovery. However, CGP56433A significantly impaired static compensation. Dynamic reflexes were evaluated by balance-beam performance and by gait; both showed significant decrements following UVD and performance improved over the next 2 days. Both CGP56433A and baclofen temporarily impaired the ability to walk on a balance beam after UVD. Two days later, there were no longer any significant effects of drug treatments on balance-beam performance. Baclofen slightly accelerated the recovery of stride length on a flat surface, but CGP7930 worsened the gait impairment following UVD. Using immunohistochemistry, we confirmed that GABA B receptors are abundantly expressed on the vestibulospinal neurons of Deiters in mice. Our results suggest that GABA B receptors contribute to the compensation of static vestibular reflexes following unilateral peripheral damage. We also conclude that impairment of the first stage of compensation, static recovery, does not necessarily result in an impairment of dynamic recovery in the long term.

Modulation of Memory by Vestibular Lesions and Galvanic Vestibular Stimulation

For decades it has been speculated that there is a close association between the vestibular system and spatial memories constructed by areas of the brain such as the hippocampus. While many animal studies have been conducted which support this relationship, only in the last 10 years have detailed quantitative studies been carried out in patients with vestibular disorders. The majority of these studies suggest that complete bilateral vestibular loss results in spatial memory deficits that are not simply due to vestibular reflex dysfunction, while the effects of unilateral vestibular damage are more complex and subtle. Very recently, reports have emerged that sub-threshold, noisy galvanic vestibular stimulation can enhance memory in humans, although this has not been investigated for spatial memory as yet. These studies add to the increasing evidence that suggests a connection between vestibular sensory information and memory in humans.

Adaptive rescaling of central sensorimotor signals is preserved after unilateral vestibular damage

Adaptive rescaling is a widespread phenomenon that dynamically adjusts the input–output relationship of a sensory system in response to changes in the ambient stimulus conditions. Rescaling has been described in the central vestibular neurons of normal cats. After recovery from unilateral vestibular damage, the vestibulo-ocular reflex (VOR) remains nonlinear for rotation toward the damaged side. Therefore, rescaling in the VOR pathway may be especially important after damage. Here, we demonstrate that central vestibular neurons adjust their input–output relationships depending on the input velocity range, suggesting that adaptive rescaling is preserved after vestibular damage and can contribute to the performance of the VOR. We recorded from isolated vestibular neurons in alert cats that had recovered from unilateral vestibular damage. The peak velocity of 1-Hz sinusoidal rotation was varied from 10 to 120°/s and the sensitivities and dynamic ranges of vestibular neurons were measured. Most neuronal responses showed significant nonlinearities even at the lowest peak velocity that we tested. Significant rescaling was seen in the responses of neurons both ipsilateral and contralateral to chronic unilateral damage. On the average, when the peak rotational velocity increased by a factor of 8, the average sensitivity to rotation decreased by roughly a factor of 2. Rescaling did not depend on eye movement signals. Our results suggest that the dynamic ranges of central neurons are extended by rescaling and that, after vestibular damage, adaptive rescaling may act to reduce nonlinearities in the response of the VOR to rotation at high speeds.

Nitric oxide synthase and arginase expression changes in the rat perirhinal and entorhinal cortices following unilateral vestibular damage: A link to deficits in object recognition?

Previous studies have shown that peripheral vestibular damage causes long-term neurochemical changes in the hippocampus which may be related to spatial memory deficits. Since recent studies have also demonstrated deficits in non-spatial object recognition memory following vestibular lesions, the aim of the present study was to extend these investigations into the perirhinal cortex (PRC), which is known to be important for object recognition, and the related entorhinal cortex (EC). We examined the effects of unilateral vestibular deafferentation (UVD) on the expression of four enzymes associated with neuronal plasticity, neuronal nitric oxide synthase (nNOS), endothelial nitric oxide synthase (eNOS), arginase I and arginase II (AI and II), in the rat EC and PRC using Western blotting. Tissue was collected at 10 hs, 50 hs and 2 weeks post-UVD. In the EC and PRC, nNOS protein expression decreased on the contralateral side at 2 weeks post-UVD but not before. At the same time, eNOS protein expression increased in both regions on the contralateral side. In the EC, AII protein expression increased on the ipsilateral side at 2 weeks post-UVD. In the PRC, AI increased and decreased on the contralateral and ipsilateral sides (respectively) at 2 weeks post-UVD. AII showed a bilateral increase in the PRC at 2 weeks post-UVD. These results demonstrate changes in NOS and arginase protein expression in the PRC and EC following UVD, which are unlikely to be due to the initial severity of the vestibular syndrome because they develop well after vestibular compensation has taken place. Neurochemical changes in these regions of the medial temporal lobe may be implicated in the development of object recognition deficits that contribute to cognitive dysfunction following peripheral vestibular damage.

Long-term changes in hippocampal n-methyl- d-aspartate receptor subunits following unilateral vestibular damage in rat

Previous studies have indicated that damage to the peripheral vestibular system results in dysfunction of hippocampal place cells and an impairment of spatial learning and memory. The aim of this study was to determine whether lesions of one vestibular labyrinth (unilateral vestibular deafferentation, UVD) result in changes in the expression of the NR1 and NR2A subunits of the N-methyl- d-aspartate (NMDA) receptor, and the GluR2 subunit of the α-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor, in subregions of the rat hippocampus (CA1, CA2/3 and the dentate gyrus) at 10 h or 2 weeks following UVD. Compared with sham surgery controls and anaesthetic controls, the expression of the NR1 subunit was significantly reduced in the ipsilateral CA2/3 region at 2 weeks post-UVD. The expression of the NR2A subunit was also significantly reduced in the ipsilateral CA2/3 and, to a smaller extent, in the contralateral CA2/3 region, at 2 weeks post-UVD. The only other change in NR2A expression was an increase in the ipsilateral CA1 at 10 h post-UVD. No other changes in NR1, NR2A or GluR2 expression were observed in any hippocampal subregion, at any time point, or in cortical tissue at any time point. These results suggest that UVD may result in long-term changes in NMDA receptor subunit expression in the rat hippocampus.

Unilateral inner ear damage results in lasting changes in hippocampal CA1 field potentials in vitro.

We investigated the effects of a surgical lesion of one vestibular inner ear (unilateral vestibular damage [UVD]) on the field potential responses of CA1 neurons in vitro. Hippocampal slices were removed from rats at 4-6 weeks or 5-6 months post-UVD, and the field responses of CA1 neurons to electrical stimulation of the Schaffer collateral commissural pathway were analyzed. Compared with slices from sham and naive control animals, slices from UVD animals at 5-6 months post-UVD exhibited decreases in the population spike amplitude, the somal field excitatory postsynaptic potential (sfEPSP) slope, and the field EPSP (fEPSP) slope. For the population spike amplitude and fEPSP slope, this effect was observed in both CA1 ipsilateral and contralateral to the UVD. On both the ipsilateral and contralateral sides, paired-pulse testing showed increases in paired-pulse inhibition at the shortest interstimulus intervals (ISIs), with increases in paired-pulse facilitation at longer ISIs. This study provides the first evidence that peripheral vestibular damage can produce long-term changes in hippocampal electrophysiological activity in vitro.

Changes in brainstem calcitonin gene-related peptide after VIIth and VIIIth cranial nerve lesions in guinea pig

The present study investigated the effect of seventh and eighth cranial nerve lesions on the prominence of calcitonin gene-related peptide in the hypoglossal (XII), facial (VII), abducens (VI), and oculomotor (III) cranial nerve nuclei. Guinea pigs were anesthetized and subjected to unilateral cochlear removal, vestibular end organ ablation, and seventh nerve transection. After a survival period ranging from 4 h to 5 days, each animal was anesthetized and perfused intracardially. Frozen sections were collected through the brainstem and stained immunohistochemically for calcitonin gene-related peptide using a polyclonal antibody with the Vectastain ABC kit and protocol. Positive cells were counted in each nucleus bilaterally and analyzed for side to side differences. Nuclei XII and III showed no significant difference in the numbers of cells staining positively for calcitonin gene-related peptide between the ipsilateral and the contralateral sides to the lesion. However, nuclei VII and VI showed elevated numbers ipsilateral to the lesion on some days, but not all. For VII, there was no significant difference before 24 h, but there were significant differences 1–5 days after the lesion. Similarly, in VI, there was no difference before 24 h, but differences were significant beginning with day 1 and continuing through day 3, and finally disappearing by day 4. Changes in the numbers of CGRP positive cells in VII measurable 24 h after the lesion and continuing for at least 5 days afterward indicate a central nervous system retrograde response to peripheral motor nerve injury. However, since no peripheral damage occurred to any structure other than those related to VII and VIII, increased numbers of calcitonin gene-related peptide positive cells in VI indicates the presence of a separate mediating mechanism. We believe this increase may be due, not to the direct loss of a peripheral nerve as in the case of VII, but instead, to an indirect motor stimulation of the eye muscles (indicated by nystagmus) that accompanies unilateral vestibular damage. Thus, while the central CGRP response in VII is activated by a retrograde neuronal mechanism, the central calcitonin gene-related peptide response in VI is activated by an anterorade transsynaptic neuronal mechanism.

Vestibular compensation without brainstem commissures in the guinea pig

The rapid recovery from the postural and ocular motor asymmetries produced by unilateral vestibular damage (vestibular compensation) has been presented as an example of plasticity in the central nervous system. A recent model (J. Neurophysiol., 51 (1984) 242–259) has identified the fibers joining the two vestibular nuclei in the brainstem (the vestibular commissures) as the site of the plastic changes. We report that in guinea pigs, compensation of postural symptoms still occurs after sectioning these commissural fibers. We suggest that a number of mechanisms may be responsible for vestibular compensation, including some which are independent of the vestibular commissures.

On the role of vestibulo-ocular reflex plasticity in recovery after unilateral peripheral vestibular lesions.

Although adaptive plasticity is a well-known feature of the vestibulo-ocular reflex (VOR), deficits in VOR performance after unilateral labyrinthectomy are poorly compensated in a large percentage of cats. To assess whether VOR plastic capabilities are affected by labyrinthectomy, forced oscillation in front of a patterned surround was imposed in unilaterally labyrinthectomized cats. This experimental paradigm has been shown to be very effective in inducing adaptive VOR gain changes in intact animals. We demonstrate that plasticity of VOR gain is still present both in acute and chronic stages following vestibular lesions. By contrast, forced oscillation did not significantly alter the lesion-induced asymmetry of responses. We conclude that VOR gain control mechanisms are not used to their fullest possible extent in a large percentage of animals suffering unilateral vestibular damage.

Tonic cervical influences on eye nystagmus following hemilabyrinthectomy: immediate and plastic effects

In intact guinea pigs a passive horizontal rotation of the body about the fixed head induces compensatory ocular movements (cervico-ocular reflex). When the static neck deviation is maintained, a significant ocular displacement is observed. In acutely hemilabyrinthectomized animals, static body deviation towards the lesion side tonically alters eyenystagmus. It affects slow phase eye velocity and quick phase amplitude and frequency causing the eye to reach a less eccentric orbital position. Apart from such immediate influences, a plastic effect on eye nystagmus abatement is induced. In the animals restrained with no body-on-head deviation, abatement of nystagmus is delayed with respect to the animals restrained with 35° body deviation towards the lesion side. Thus the head position signal is not only a contributing factor for the correction of postural deficits but also influences the time course of the ocular balancing process following unilateral vestibular damage.

Effect of vestibular nerve section on torsion and on evoked rotatory movements

The effect of acute and chronic section of the vestibular nerves, unilateral and bilateral, was measured on spontaneous torsion and on rotation elicited by electrical stimulation of the region of the zona incerta. In cats prepared as encéphales isolés, acute section of the vestibular nerve was followed by persistent spontaneous clockwise torsion of both eyes. This torsion was partially corrected for the right eye, and over-corrected for the left eye, following acute section of the right vestibular nerve. Rotational movements of both eyes could be elicited upon stimulation of left or right zona incerta or interstitial nucleus before and after unilateral and bilateral vestibular damage. Head rotation was elicited by stimulation of left and right zona incerta through electrodes implanted chronically in eight cats. Following unilateral section of the vestibular nerve, an enduring head tilt toward the side of the lesion was observed. In spite of this spontaneous tilt, stimulation of either incertal site still elicited head rotation comparable in extent to that seen upon control stimulation. Section of the other vestibular nerve in five of the cats resulted in correction or over-correction of the spontaneous head tilt. Stimulation of either incertal site was still capable of evoking head rotation, though this was less coordinated and more variable in threshold and extent than that seen before or after unilateral vestibular damage. Thus although vestibular nerves contribute to maintenance of posture and provide muscle tone, rotatory movements can be performed even after chronic bilateral vestibular nerve section.