Effects of galvanic vestibular stimulation on resting state brain activity in patients with bilateral vestibulopathy

We examined the effect of galvanic vestibular stimulation (GVS) on resting state brain activity using fMRI (rs‐fMRI) in patients with bilateral vestibulopathy. Based on our previous findings, we hypothesized that GVS, which excites the vestibular nerve fibers, (a) increases functional connectivity in temporoparietal regions processing vestibular signals, and (b) alleviates abnormal visual–vestibular interaction. Rs‐fMRI of 26 patients and 26 age‐matched healthy control subjects was compared before and after GVS. The stimulation elicited a motion percept in all participants. Using different analyses (degree centrality, DC; fractional amplitude of low frequency fluctuations [fALFF] and seed‐based functional connectivity, FC), group comparisons revealed smaller rs‐fMRI in the right Rolandic operculum of patients. After GVS, rs‐fMRI increased in the right Rolandic operculum in both groups and in the patients' cerebellar Crus 1 which was related to vestibular hypofunction. GVS elicited a fALFF increase in the visual cortex of patients that was inversely correlated with the patients' rating of perceived dizziness. After GVS, FC between parietoinsular cortex and higher visual areas increased in healthy controls but not in patients. In conclusion, short‐term GVS is able to modulate rs‐fMRI in healthy controls and BV patients. GVS elicits an increase of the reduced rs‐fMRI in the patients' right Rolandic operculum, which may be an important contribution to restore the disturbed visual–vestibular interaction. The GVS‐induced changes in the cerebellum and the visual cortex were associated with lower dizziness‐related handicaps in patients, possibly reflecting beneficial neural plasticity that might subserve visual–vestibular compensation of deficient self‐motion perception.     

Noisy galvanic vestibular stimulation improves vestibular perception in bilateral vestibulopathy

Journal of Neurology - Patients with bilateral vestibulopathy (BVP) suffer from impaired vestibular motion perception that is linked to deficits in spatial memory and navigation. To examine the...     

Noisy vestibular stimulation improves vestibulospinal function in patients with bilateral vestibulopathy

Objectives

To examine the mechanism underlying previously reported ameliorating effects of noisy galvanic vestibular stimulation (GVS) on balance performance in patients with bilateral vestibulopathy (BVP) and determine those patients (incomplete versus complete vestibular loss) that might benefit from this intervention.

Methods

Vestibulospinal reflex thresholds were determined in 12 patients with BVP [2 with complete loss (cBVP) and 10 with residual function (rBVP)]. Patients were stimulated with 1 Hz sinusoidal GVS of increasing amplitudes (0–1.9 mA). Coherence between GVS input and stimulation-induced body motion was determined and psychometric function fits were subsequently used to determine individual vestibulospinal reflex thresholds. The procedure was repeated with an additional application of imperceptible white noise GVS (nGVS).

Results

All patients with rBVP but none with cBVP exhibited stimulation-induced vestibulospinal reflex responses with a mean threshold level of 1.26?±?0.08 mA. Additional nGVS resulted in improved processing of weak subthreshold vestibular stimuli (p?=?0.015) and thereby effectively decreased the vestibulospinal threshold in 90% of patients with rBVP (mean reduction 17.3?±?3.9%; p?<?0.001).

Conclusion

The present findings allow to identify the mechanism by which nGVS appears to stabilize stance and gait performance in patients with BVP. Accordingly, nGVS effectively lowers the vestibular threshold to elicit balance-related reflexes that are required to adequately regulate postural equilibrium. This intervention is only effective in the presence of a residual vestibular functionality, which, however, applies for the majority of patients with BVP. Low-intensity noise stimulation thereby provides a non-invasive treatment option to optimize residual vestibular resources in BVP.

     

Asymmetry of balance responses to monaural galvanic vestibular stimulation in subjects with vestibular schwannoma

ObjectiveWe investigated the potential of galvanic vestibular stimulation (GVS) to quantify lateralised asymmetry of the vestibulospinal pathways by measuring balance responses to monaural GVS in 10 subjects with vestibular schwannoma and 22 healthy control subjects.MethodsSubjects standing without vision were stimulated with 3 s, 1 mA direct current stimuli delivered monaurally. The mean magnitude and direction of the evoked balance responses in the horizontal plane were measured from ground-reaction forces and from displacement and velocity of the trunk. Vestibular-evoked myogenic potentials (VEMPs) to 500 Hz air and bone-conducted tones were also recorded.ResultsIn healthy subjects, the magnitudes of the force, velocity and displacement responses were not significantly different for left compared to right ear stimulation. Their individual asymmetry ratios were always <30%. Subjects with vestibular schwannoma had significantly smaller force, velocity and displacement responses to stimulation of the affected compared with non-affected ear. Their mean asymmetry ratios were significantly elevated for all three measures (41.2 ± 10.3%, 40.3 ± 15.1% and 21.9 ± 14.6%).ConclusionsAsymmetry ratios of balance responses to monaural GVS provide a quantitative and clinically applicable lateralising test of the vestibulospinal pathways.SignificanceThis method offers a more clinically relevant measure of standing balance than existing vestibular function tests which assess only vestibuloocular and vestibulocollic pathways.     

The effect of galvanic vestibular stimulation on postural response of Down syndrome individuals on the seesaw

In order to better understand the role of the vestibular system in postural adjustments on unstable surfaces, we analyzed the effects of galvanic vestibular stimulation (GVS) on the pattern of muscle activity and joint displacements (ankle knee and hip) of eight intellectually normal participants (control group - CG) and eight control group individuals with Down syndrome (DS) while balancing on seesaws of different heights. The CG individuals adopted a pattern of muscle activation characterized by alternation between ankle agonist and antagonist muscles. The individuals with DS adopted a pattern of muscle co-contraction. The GVS affected neither the ability of CG individuals to maintain balance nor their pattern of muscle contraction. On the other hand, the individuals with DS showed greater sensitivity to GVS while balancing on a seesaw and were not able to select the appropriate motor strategy to efficiently balance and compensate the effects of GVS. These increased vestibular sensitivities observed in individuals with DS can reflect deficits in the proprioceptive system.     

Serum antibodies against membranous labyrinth in patients with „idiopathic“ bilateral vestibulopathy

To investigate the possibility of an autoimmune mechanism in idiopathic bilateral vestibulopathy (IBV), we screened patients’ sera for antibodies against inner ear structures. IgG antibodies against membranous labyrinth (ampulla, semicircular canals, saccule and utricle) were detected in 8 of 12 patients by immunofluorescence on rat inner ear cryosections. All but one serum of 22 healthy controls and the sera of 6 patients with known autoimmune disorders showed only background staining. Low-titre anti-nuclear IgM antibodies were present in three control sera and one IBV serum. High-titre anti-nuclear IgM was found in a patient with lupus erythematosus and in one with scleroderma. Anti-nuclear IgM was not organ-specific. No human serum used contained detectable anti-vascular preformed antibodies. Cross-reactivity to sections of liver, kidney, cornea, brain and skeletal muscle was absent. Double-staining for IgG and F-actin, the primary constituent of hair cell cilia, did not show predominant Ig-coating of sensory hair cells. Immunosuppressive therapy in 3 IBV patients did not improve the disorder, probably owing to irreversible loss of sensory and neural structures. These data suggest that the bulk of anti-labyrinthine autoantibodies may be an epiphenomenon, yet a small subgroup of organ-specific autoantibodies may synergize with a cellular response in the development of vestibular lesions. Received: 7 July 1997 Received in revised form: 25 September 1997 Accepted: 20 October 1997     

Responses of primary vestibular neurons to galvanic vestibular stimulation (GVS) in the anaesthetised guinea pig

Previous studies in humans and animals which have shown that DC galvanic vestibular stimulation (GVS) induces horizontal and torsional eye movements have been interpreted as being due to a preferential activation of primary vestibular afferents innervating the horizontal semicircular canals and otoliths by GVS. The present study sought to determine in guinea pigs whether GVS does indeed selectively activate primary horizontal canal and otolith afferents. Constant-current GVS was passed between electrodes implanted in the tensor-tympani muscle of each middle ear or between electrodes on the skin over the mastoid. During this stimulation, responses from single primary vestibular neurons were recorded extracellularly by glass microelectrodes in Scarpa's ganglion. Afferents from all vestibular sensory regions were activated by both surface and tensor-tympani galvanic stimulation. Tensor tympani GVS was approximately 10 times more effective than surface GVS. At larger current intensities irregularly discharging afferents showed an asymmetrical response: cathodal stimulation resulted in a larger change in firing (increase) than anodal stimulation (decrease), whereas regularly discharging afferents responded symmetrically to the two polarities of GVS. Across all afferents tuned for different types of natural vestibular stimulation, neuronal sensitivity for GVS was found to increase with discharge variability (as indexed by CV*). Anterior canal afferents showed a slightly higher sensitivity than afferents from other vestibular sensory regions. Hence, the present study concluded that GVS activates primary vestibular afferents innervating all sensory regions in a uniform fashion. Therefore, the specific pattern of GVS-induced eye movements reported in previous studies are not due to differential sensitivity between different vestibular sensory regions, but are likely to reflect an involvement of central processing.     

Effect of noisy galvanic vestibular stimulation on center of pressure sway of static standing posture

Background

The vestibular system is involved in the control of standing balance. Galvanic vestibular stimulation (GVS) is a noninvasive technique that can stimulate the vestibular system. In recent years, noisy GVS (nGVS) using noise current stimulation has been attempted, but it has not been clarified whether it affects postural sway in open-eye standing.

Locomotion speed determines gait variability in cerebellar ataxia and vestibular failure

Temporal gait variability is a critical parameter in patients with balance problems. Increased magnitude of temporal gait variability corresponds to a higher risk of falls. The purpose of this study was to investigate the influence of walking speed on temporal stride-to-stride variability in patients with cerebellar and vestibular deficits. A GAITRite system was used to analyze the gait of 40 patients with cerebellar ataxia, 22 patients with bilateral vestibular failure, and 51 healthy subjects over the entire range of the individual's speed capacity. The coefficient of variability of stride time was calculated for each walk. Temporal gait variability was increased in cerebellar patients and vestibular patients. The magnitude of this variability depended on walking speed in a disease-specific manner. In patients with cerebellar ataxia, variability was increased during slow (8.4 ± 5.3%, P < .01) and fast (7.9 ± 6.4%, P < .01) walking speed but was normal during preferred walking speed. This resulted in a speed-related U-shaped function of stride-time variability. Patients with vestibular failure had increased variability during slow walking (9.9 ± 4.3%, P < .01). During walking with medium and fast walking speed, stride time variability was normal. Minimal temporal gait variability appears to be attractive for the locomotor system in cerebellar patients because these patients preferred to walk at a velocity associated with minimal stride-time variability. In contrast to previous studies, vestibular patients accelerate rather than decelerate gait to achieve dynamic stability. This may be explained by reduced sensory integration during fast locomotion.     

Stochastic resonance in the human vestibular system – Noise-induced facilitation of vestibulospinal reflexes

Background

There is strong evidence that the presence of noise can enhance information processing in sensory systems via stochastic resonance (SR).

Ocular torsion responses to electrical vestibular stimulation in vestibular schwannoma

Objectives

We determined if eye movements evoked by Electrical Vestibular Stimulation (EVS) can be used to detect vestibular dysfunction in patients with unilateral vestibular schwannoma (VS).

Hippocampal gray matter volume in bilateral vestibular failure

Bilateral vestibular failure (BVF) is a severe chronic disorder of the labyrinth or the eighth cranial nerve characterized by unsteadiness of gait and disabling oscillopsia during head movements. According to animal data, vestibular input to the hippocampus is proposed to contribute to spatial memory and spatial navigation. Except for one seminal study showing the association of impaired spatial navigation and hippocampal atrophy, patient data in BVF are lacking. Therefore, we performed a voxel‐wise comparison of the hippocampal gray matter volume (GMV) in a clinically representative sample of 27 patients with incomplete BVF and 29 age‐ and gender‐matched healthy controls to test the hypothesis of hippocampal atrophy in BVF. Although the two groups did not generally differ in their hippocampal GMV, a reduction of GMV in the bilateral hippocampal CA3 region was significantly correlated with increased vestibulopathy‐related clinical impairment. We propose that GMV reduction in the hippocampus of BVF patients is related to the severity of vestibular‐induced disability which is in line with combined hippocampal atrophy and disorders of spatial navigation in complete vestibular deafferentation due to bilateral nerve section. Clinically, however, the most frequent etiologies of BVF cause incomplete lesions. Accordingly, hippocampus atrophy and deficits in spatial navigation occur possibly less frequently than previously suspected. Hum Brain Mapp 37:1998–2006, 2016. © 2016 Wiley Periodicals, Inc .     

Caloric vestibular stimulation and postural control in patients with spatial neglect following stroke

The impact of spatial neglect remains a substantial challenge to patients undergoing rehabilitation following stroke. Beyond the relatively well-described implications for visuospatial function, neglect is increasingly shown to have a negative impact on the wider aspects of sensori-motor performance with corresponding implications for activities including gait and balance. Caloric vestibular stimulation (CVS) administered to the contralesional ear has previously been shown to improve performance in patients with spatial neglect. Here, in Experiment One, we investigated the effect of CVS on clinical measures of spatial neglect and postural control in three groups of patients following stroke; left brain damaged patients (LBD, n?=?6), right brain damaged patients without neglect (RBD–, n?=?6), and right brain damaged patients with neglect (RBD+?, n?=?6). While post-stimulation scores demonstrated an improvement for participants with spatial neglect, further analysis of postural scores indicated that improvement was selective for asymmetrical activities, with symmetrical activities remaining unchanged. We interpret these results with reference to the related problem of extinction which predicts that activities demanding synchronous bilateral activity (symmetrical activities) would cause greater difficulties for patients with neglect. In Experiment Two, we tested a further six RBD+ patients on the same measures following CVS to the ipsilesional (right) ear. There was no significant improvement in perceptual or postural scores. Our findings are supportive of previous studies that demonstrate improvement in perception and movement for patients with spatial neglect following contralesional CVS and suggest that these improvements may have clinical benefits.     

Galvanic vestibular stimulation reduces the pathological rightward line bisection error in neglect-a sham stimulation-controlled study

Patients with right hemisphere lesions often show left spatial neglect and the typical rightward deviation in horizontal line bisection. Previous studies have shown that sensory stimulation modulates line bisection. A less well-known but promising sensory stimulation method is galvanic vestibular stimulation (GVS). This non-invasive technique leads to activation of the vestibular cortices and adjacent cortical areas in the temporo-parietal cortex via polarization effects of the vestibular nerves. This is accomplished by application of weak direct currents, delivered by two electrodes attached to the mastoids. Despite the relative benefits of GVS its effects on line bisection have not yet been studied in neglect patients. Thus, the present study investigated the impact of GVS on performance in a modified line bisection task in right-brain damaged patients with versus without leftsided visual neglect. In neglect patients, but not in control patients, left-cathodal and right-cathodal GVS significantly reduced the rightward line bisection error as compared to Baseline (without GVS) and sham stimulation. A larger decrease of the rightward line bisection error was observed during right-cathodal GVS. Sham stimulation showed no specific effects on line bisection. The beneficial effects of GVS might be due to activation of preserved structures of the lesioned right posterior parietal cortex which is known to be involved in line bisection.     

Galvanic vestibular stimulation impairs cell proliferation and neurogenesis in the rat hippocampus but not spatial memory

Galvanic vestibular stimulation (GVS) is a method of activating the peripheral vestibular system using direct current that is widely employed in clinical neurological testing. Since movement is recognized to stimulate hippocampal neurogenesis and movement is impossible without activation of the vestibular system, we speculated that activating the vestibular system in rats while minimizing movement, by delivering GVS under anesthesia, would affect hippocampal cell proliferation and neurogenesis, and spatial memory. Compared with the sham control group, the number of cells incorporating the DNA replication marker, bromodeoxyuridine (BrdU), was significantly reduced in the bilateral hippocampi in both the cathode left‐anode right and cathode right‐anode left stimulation groups (P ≤ 0.0001). The majority of the BrdU^+ve cells co‐expressed Ki‐67, a marker for the S phase of the cell cycle, suggesting that these BrdU^+ve cells were still in the cell cycle; however, there was no significant difference in the degree of co‐labeling between the two stimulation groups. Single labeling for doublecortin (DCX), a marker of immature neurons, showed that while there was no significant difference between the different groups in the number of DCX^+ve cells in the right dentate gryus, in the left dentate gyrus there was a significant decrease in the cathode left‐anode right group compared with the sham controls (P ≤ 0.03). Nonetheless, when animals were tested in place recognition, object exploration and Morris water maze tasks, there were no significant differences between the GVS groups and the sham controls. These results suggest that GVS can have striking effects on cell proliferation and possibly neurogenesis in the hippocampus, without affecting spatial memory. © 2014 Wiley Periodicals, Inc.     

Precision of perceived direction of gravity in partial bilateral vestibulopathy correlates with residual utricular function

Objective

Gait imbalance in patients with bilateral-vestibular-deficiency (BVD) was linked to increased variability in perceived direction of gravity while upright. We hypothesized this to be true also when roll-tilted. Moreover, as utricular input is essential for spatial orientation, we predicted the variability of perceived vertical to correlate inversely with utricular function.

Acoustic, mechanical and galvanic stimulation modes elicit ocular vestibular-evoked myogenic potentials

ObjectiveThis study compared the characteristic parameters of ocular vestibular-evoked myogenic potentials (oVEMPs) elicited by the air-conducted sound (ACS) and bone-conducted vibration (BCV) stimulation modes as well as the galvanic vestibular stimulation (GVS) mode.DesignFifteen healthy subjects underwent oVEMP tests using ACS (127 dBSPL), BCV (142 dB force level), and GVS (5 mA) modes. The response rate, latencies of nI and pI, nI–pI interval and amplitude were measured for each mode and compared among modes.ResultsAll 15 healthy subjects (30 ears) had 100% response rates in both BCV- and GVS–oVEMPs, exhibiting a response rate significantly higher than 80% in ACS–oVEMPs. The mean nI latency was the shortest in the GVS mode, followed by BCV and then ACS modes. The variation among the latencies of the three modes was significant. Likewise, the mean nI–pI amplitudes in ACS-, BCV- and GVS modes varied significantly. However, the mean nI–pI interval did not differ significantly among the three modes.ConclusionsAmong the ACS (127 dBSPL), BCV (142 dB force level), and GVS (5 mA) modes, the BCV mode yields a 100% response rate and the largest nI–pI amplitude of oVEMPs.SignificanceThe oVEMPs in ACS and GVS modes may help to differentiate the saccular from the retro-saccular lesions. If ACS–oVEMPs are normal, then oVEMPs in BCV and GVS modes can distinguish between utricular and retro-utricular disorders. Restated, oVEMPs in ACS, BCV, and GVS modes may promote the topographical delineation of the lesion site of the otolithic–ocular reflex pathway.     

Postoperative gait deterioration after bilateral subthalamic nucleus stimulation in Parkinson's disease

Deep brain stimulation of the subthalamic nuclei (STN) is a good therapeutic option to reduce dyskinesias and improve appendicular motor signs in well‐selected patients with advanced Parkinson's disease (PD). Concerns about long‐term adverse effects play an increasingly role in the decision whether or not to refer patients for this treatment. Worsening of gait as a consequence of STN stimulation for PD has been described, but may be under‐recognized in clinical practice. The aim of this study was to evaluate the effects of STN stimulation on gait relative to global outcome in a group of consecutively operated patients. For this purpose, we used a standardized patient questionnaire that asked about global outcome and specific effects on gait, as experienced both 6 months postoperatively and currently (at the time of completing the questionnaire; mean: 2.7 +/? 1.1 years). A delayed worsening of gait after bilateral STN stimulation was experienced by a considerable proportion of patients (42% of subjects, for gait in the OFF phase), and this was apparently relatively “selective” because their global outcome scores continued to be improved. These findings highlight the presence of a hitherto poorly recognized long‐term complication of bilateral STN stimulation. Further systematic studies are required to pinpoint the clinical and surgical determinants of this late gait deterioration. © 2008 Movement Disorder Society     

GABAergic inhibitory response of locus coeruleus neurons to caloric vestibular stimulation in rats

We examined the effects of caloric vestibular stimulation on the neuronal activity of the locus coeruleus (LC) in urethane-anesthetized rats. The middle ear cavity was irrigated with hot (44°C) or cold (30°C) water through a polyethylene tube. Most neurons (hot water: 76%, ; cold water: 90%, ) exhibited suppression of neuronal discharge in response to caloric stimulation. The suppression of LC neuronal discharge following caloric stimulation occurred with a long latency (approximately 80 s), and lasted a long period of time (approximately 3 min). Neither caloric stimulation of the auricle, nor irrigation of the middle ear with water at 37°C, nor caloric stimulation of the middle ear after labyrinthectomy inhibited LC neuronal discharge. The caloric stimulation-induced LC neuronal inhibition was significantly attenuated by the intravenous injection of picrotoxin and by the iontophoretic application of bicuculline methiodide. These findings indicate that the predominant effect of caloric vestibular stimulation on LC neuronal discharge is inhibitory, and that the caloric stimulation-induced LC neuronal inhibition is mediated by GABAA receptors located on the membrane of LC neurons. It is suggested that the suppressed activity of noradrenergic LC neurons is involved in the vestibulo-autonomic reflex.