Galvanic vestibular stimulation: from basic concepts to clinical applications.

Galvanic vestibular stimulation (GVS) plays an important role in the quest to understand sensory signal processing in the vestibular system under normal and pathological conditions. It has become a highly relevant tool to probe neuronal computations and to assist in the differentiation and treatment of vestibular syndromes. Following its accidental discovery, GVS became a diagnostic tool that generates eye movements in the absence of head/body motion. With the possibility to record extracellular and intracellular spikes, GVS became an indispensable method to activate or block the discharge in vestibular nerve fibers by cathodal and anodal currents, respectively. Bernie Cohen, in his attempt to decipher vestibular signal processing, has used this method in a number of hallmark studies that have added to our present knowledge, such as the link between selective electrical stimulation of semicircular canal nerves and the generation of directionally corresponding eye movements. His achievements paved the way for other major milestones including the differential recruitment order of vestibular fibers for cathodal and anodal currents, pronounced discharge adaptation of irregularly firing afferents, potential activation of hair cells, and fiber type-specific activation of central circuits. Previous disputes about the structural substrate for GVS are resolved by integrating knowledge of ion channel-related response dynamics of afferents, fiber type-specific innervation patterns, and central convergence and integration of semicircular canal and otolith signals. On the basis of solid knowledge of the methodology, specific waveforms of GVS are currently used in clinical diagnosis and patient treatment, such as vestibular implants and noisy galvanic stimulation.

Galvanic Vestibular Stimulation: Cellular Substrates and Response Patterns of Neurons in the Vestibulo-Ocular Network.

UNLABELLED: Galvanic vestibular stimulation (GVS) uses modulated currents to evoke neuronal activity in vestibular endorgans in the absence of head motion. GVS is typically used for a characterization of vestibular pathologies; for studies on the vestibular influence of gaze, posture, and locomotion; and for deciphering the sensory-motor transformation underlying these behaviors. At variance with the widespread use of this method, basic aspects such as the activated cellular substrate at the sensory periphery or the comparability to motion-induced neuronal activity patterns are still disputed. Using semi-intact preparations of Xenopus laevis tadpoles, we determined the cellular substrate and the spatiotemporal specificity of GVS-evoked responses and compared sinusoidal GVS-induced activity patterns with motion-induced responses in all neuronal elements along the vestibulo-ocular pathway. As main result, we found that, despite the pharmacological block of glutamatergic hair cell transmission by combined bath-application of NMDA (7-chloro-kynurenic acid) and AMPA (CNQX) receptor blockers, GVS-induced afferent spike activity persisted. However, the amplitude modulation was reduced by ∼30%, suggesting that both hair cells and vestibular afferent fibers are normally recruited by GVS. Systematic alterations of electrode placement with respect to bilateral semicircular canal pairs or alterations of the bipolar stimulus phase timing yielded unique activity patterns in extraocular motor nerves, compatible with a spatially and temporally specific activation of vestibulo-ocular reflexes in distinct planes. Despite the different GVS electrode placement in semi-intact X. laevis preparations and humans and the more global activation of vestibular endorgans by the latter approach, this method is suitable to imitate head/body motion in both circumstances. SIGNIFICANCE STATEMENT: Galvanic vestibular stimulation is used frequently in clinical practice to test the functionality of the sense of balance. The outcome of the test that relies on the activation of eye movements by electrical stimulation of vestibular organs in the inner ear helps to dissociate vestibular impairments that cause vertigo and imbalance in patients. This study uses an amphibian model to investigate at the cellular level the underlying mechanism on which this method depends. The outcome of this translational research unequivocally revealed the cellular substrate at the vestibular sensory periphery that is activated by electrical currents, as well as the spatiotemporal specificity of the evoked eye movements, thus facilitating the interpretation of clinical test results.