Effects of perceptible and imperceptible galvanic vestibular stimulation on the postural control of patients with bilateral vestibulopathy.

Galvanic vestibular stimulation (GVS) has increasingly been used to stimulate the vestibular system in health and disease. While perceptible supra-threshold GVS destabilizes postural control in healthy control (HC) subjects, imperceptible 'noisy' GVS (nGVS) is reported to improve postural control in patients with bilateral vestibulopathy (BV) and therapeutic devices using nGVS are currently under development. We questioned (1) whether perceptible GVS destabilizes postural control of BV patients, expecting any effect to be smaller than in healthy subjects due to the patients' vestibulopathy, and (2) whether imperceptible nGVS improves postural control in comparison to an active sham stimulus in context-dependent conditions, hypothesizing that it fades off once postural control becomes more challenging with respect to its sensory (standing on foam) or cognitive (dual task) complexity. We tested postural responses of 30 BV patients to bimastoidal perceptible (lowGVS, highGVS) or imperceptible (nGVS, sham, noGVS) GVS in comparison to 24 age-matched HC. Perceptible GVS intensities were applied according to the participants' individual motion perception thresholds. Postural sway speed (PSS) was analyzed in a 4-factorial experimental design with the factors group (BV, HC), vision (eyes open/closed), condition (baseline, proprioception, cognition) and stimulation (noGVS, sham, nGVS, lowGVS, highGVS). With eyes open (EO), there were no group-related PSS differences in the baseline and cognition condition in response to either stimulations. With EO on foam and with eye closed (EC) in all conditions, patients showed larger PSS than HC, irrespective of the stimulation type. PSS differed with GVS intensities within each group but not between the groups. PSS under nGVS on EC was only smaller in patients when compared to perceptible GVS, but it was not different from noGVS or sham stimulation. Moreover, this nGVS effect was only found in the baseline but not in the more challenging dual task and foam condition. Almost half of the patients showed higher individual thresholds of motion perception of GVS compared to HC. Interestingly, this high-threshold subgroup showed significantly larger PSS with EC as compared to HC and the low-threshold patient subgroup, although both patient subgroups did not differ in vestibular parameters. We conclude, first, that perceptible GVS is able to destabilize BV patients similarly to HC subjects, suggesting sufficient vestibular afferent processing of GVS during vestibulo-spinal postural control. Second, the effect of the hitherto observed improved postural control by nGVS appears to be small during more demanding postural control conditions (foam, cognitive distraction) that are closer to the patients' everyday life, when active sham stimuli are used as control stimuli. These findings underline the meaning of active control conditions when the efficacy of nGVS is tested, e.g. in portable GVS devices in the attempt to improve postural control in BV patients. However, differential GVS effects on vestibulo-perceptional and vestibulo-spinal thresholds should be taken into account. Finally, our data suggest that individual motion perception thresholds for GVS could potentially serve as a predictor of postural control safety and falling risk in BV.

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.

Increased brain responsivity to galvanic vestibular stimulation in bilateral vestibular failure.

In this event-related functional magnetic resonance imaging (fMRI) study we investigated how the brain of patients with bilateral vestibular failure (BVF) responds to vestibular stimuli. We used imperceptible noisy galvanic vestibular stimulation (GVS) and perceptible bi-mastoidal GVS intensities and related the corresponding brain activity to the evoked motion perception. In contrast to caloric irrigation, GVS stimulates the vestibular organ at its potentially intact afferent nerve site. Motion perception thresholds and cortical responses were compared between 26 BVF patients to 27 age-matched healthy control participants. To identify the specificity of vestibular cortical responses we used a parametric design with different stimulus intensities (noisy imperceptible, low perceptible, high perceptible) allowing region-specific stimulus response functions. In a 2 × 3 flexible factorial design all GVS-related brain activities were contrasted with a sham condition that did not evoke perceived motion. Patients had a higher motion perception threshold and rated the vestibular stimuli higher than the healthy participants. There was a stimulus intensity related and region-specific increase of activity with steep stimulus response functions in parietal operculum (e.g. OP2), insula, superior temporal gyrus, early visual cortices (V3) and cerebellum while activity in the hippocampus and intraparietal sulcus did not correlate with vestibular stimulus intensity. Using whole brain analysis, group comparisons revealed increased brain activity in early visual cortices (V3) and superior temporal gyrus of patients but there was no significant interaction, i.e. stimulus-response function in these regions were still similar in both groups. Brain activity in these regions during (high)GVS increased with higher dizziness-related handicap scores but was not related to the degree of vestibular impairment or disease duration. nGVS did not evoke cortical responses in any group. Our data indicate that perceptible GVS-related cortical responsivity is not diminished but increased in multisensory (visual-vestibular) cortical regions despite bilateral failure of the peripheral vestibular organ. The increased activity in early visual cortices (V3) and superior temporal gyrus of BVF patients has several potential implications: (i) their cortical reciprocal inhibitory visuo-vestibular interaction is dysfunctional, (ii) it may contribute to the visual dependency of BVF patients, and (iii) it needs to be considered when BVF patients receive peripheral vestibular stimulation devices, e.g. vestibular implants or portable GVS devices. Imperceptible nGVS did not elicit cortical brain responses making it unlikely that the reported balance improvement of BVF by nGVS is mediated by cortical mechanisms.