Bernard eCohen

Gay R Holstein

Sergei B Yakushin

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Frontiers in Neurology

WHAT DOES GALVANIC VESTIBULAR STIMULATION ACTUALLY ACTIVATE?

Bernard Cohen

Sergei B. Yakushin

Gay R. Holstein

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What does galvanic vestibular stimulation actually activate?
Bernard Cohen1*, Sergei B. Yakushin1 and Gay R. Holstein1,2,3
1 Department of Neurology, Mount Sinai School of Medicine, New York, NY, USA
2 Department of Neuroscience, Mount Sinai School of Medicine, New York, NY, USA
3 Department of Anatomy/Functional Morphology, Mount Sinai School of Medicine, New York, NY, USA
*Correspondence: bernard.cohen@mssm.edu
Luigi Galvani spent 20 years conduct-
ing experiments to demonstrate electrical 
conductivity of nerves and muscles before 
publishing his major treatise on the subject 
in 1791 (Galvani, 1791). His personal friend 
and professional nemesis Count Alessandro 
Volta held a respectful but opposing view, 
that nerve and muscle tissues simply serve 
as passive conductors, and he built the first 
“voltaic” battery in an attempt to prove his 
point. Ultimately it appears that they were 
both partially correct, and the same bio-
electric potentials sought by Galvani and 
debunked by Volta continue to be used in 
present day because they are an easy, non-
invasive approach to activate the vestibular 
nerve(s). Yet, debate continues in contem-
porary medicine and science regarding the 
exact effect of galvanic stimulation on the 
nervous system.
Galvanic vestibular stimulation (GVS) 
has been used to activate fibers of the ves-
tibular nerve in humans and experimental 
animals by applying 0.1–4 mA DC currents 
through the skin over the mastoid processes 
(for reviews, see Fitzpatrick and Day, 2004; 
Curthoys, 2009). Steps of current are used 
most often, causing continuous activation 
of the entire vestibular nerve, particularly 
those fibers with irregular spontaneous fir-
ing rates (Goldberg et al., 1984; Minor and 
Goldberg, 1991). This stimulation excites 
a wide range of central vestibular neurons, 
including those related to both the semicir-
cular canals and the otolith organs (Wilson 
et al., 1979; Peterson et al., 1980; Ezure et al., 
1983; Courjon et al., 1987). However, despite 
this non-selective activation, it appears that 
only otolith-related behavioral responses 
are induced. Human subjects experience 
sensations of rocking or pitching, head 
and/or body tilt, and have ocular torsion 
– all characteristics of otolith system activa-
tion (Zink et al., 1997; Watson et al., 1998; 
Séverac Cauquil et al., 2003; Macdougall 
et al., 2005; Bent et al., 2006). They do not 
experience sensations of rotation and do 
not display ocular  nystagmus, which would 
occur if the semicircular canals were con-
tinuously stimulated (Mach, 1875; Cohen 
et al., 1965; Guedry, 1974). This apparent 
paradox has engendered considerable con-
troversy: does GVS primarily or exclusively 
activate the otolith system, or does it acti-
vate both the otolith and semicircular canal 
systems equivalently?
The preponderance of physiological data 
support the view that GVS is primarily an 
otolithic stimulus. A variant of GVS utiliz-
ing binaurally applied sinusoidal currents 
(sinusoidal GVS, sGVS) was introduced by 
Macefield and colleagues (Bent et al., 2006; 
Grewal et al., 2009; James and Macefield, 
2010; James et al., 2010), and has proven to 
be a potent technique for inducing muscle 
sympathetic nerve activity (MSNA) in the 
legs of humans. MSNA causes peripheral 
vasoconstriction, which maintains adequate 
blood supply to the brain upon standing. 
This orthostatic response is clearly associ-
ated with the otolith system (Yates, 1992; 
Woodring et al., 1997; Kerman et al., 2003). 
When sGVS is applied to anesthetized rats, 
it can also induce sudden decreases in 
blood pressure and heart rate that resem-
ble human vasovagal syncope (Cohen et al., 
2011). Similar sustained drops in blood 
pressure have been shown in alert and anes-
thetized rats after linear acceleration (Zhu 
et al., 2007). sGVS also evokes frequency-
dependent postural sway in standing sub-
jects, further supporting the idea that the 
stimulus primarily activates the otolith 
system (Lau et al., 2003).
Functional anatomical studies have also 
contributed to the controversy regarding 
the neural effect(s) of GVS. These investi-
gations have utilized GVS to induce acti-
vation of the immediate early gene c-fos, 
and to visualize its protein product c-Fos, 
which accumulates in the nuclei of acti-
vated neurons. Steps of GVS applied uni-
laterally to rodents result in bilateral c-Fos 
expression near the ventricular wall in the 
medial vestibular nucleus (MVN), with 
muted expression in the inferior vestibular 
nucleus (IVN) and no c-Fos accumulation 
in the superior or lateral vestibular nuclei 
(SVN and LVN, respectively; Kaufman and 
Perachio, 1994; Marshburn et al., 1997; 
Abe et al., 2009). In this Frontiers Special 
Topic, Holstein and colleagues report that 
sGVS in rats results in c-Fos accumulation 
in some neurons in caudal IVN, in cells 
of the parasolitary nucleus, in neurons 
throughout MVN, and in cells located in a 
small medial wedge in caudal SVN. There 
were no activated neurons in the portions 
of the vestibular nuclear complex (VNC) 
that participate directly in the horizontal 
and vertical vestibulo-ocular reflexes, or 
the vestibulo-spinal postural reflexes. These 
studies reflect the same apparent contra-
diction evident in human physiological 
investigations: if GVS activates the entire 
vestibular nerve, why are activated neurons 
restricted to non-vestibulo-ocular and ves-
tibulo-spinal regions?
The most likely explanation for this dis-
crepancy derives from a report by Courjon 
et al. (1987) in which a wide variety of cen-
tral vestibular neurons were activated by 
galvanic stimulation. Units that responded 
to rotation promptly habituated, while 
those units that were non-responsive to 
rotation, which were presumably otolith 
units, continued to fire in response to GVS. 
We propose that this canal-specific response 
habituation underlies the apparent incon-
sistency between the global vestibular acti-
vation by GVS and the otolith-predominant 
neural and behavioral responses. Moreover, 
the c-Fos localization findings can be fur-
ther interpreted in this light, since c-Fos 
protein is not manifest in neurons that are 
tonically inhibited (Chan and Sawchenko, 
1994). Many vestibular neurons that par-
ticipate in vestibulo-ocular and vestibulo-
spinal reflexes receive formidable direct 
inhibition from cerebellar Purkinje cells 
and/or inhibitory commissural and intra-
VNC fibers (for review, see Holstein, 2011). 
These neurons are not likely to express c-Fos 
protein, even though they may initially be 
www.frontiersin.org January 2012 | Volume 2 | Article 90 | 1
OpiniOn Article
published: 06 January 2012
doi: 10.3389/fneur.2011.00090
activated by sGVS. Further still, while neu-
rons that receive predominantly excitatory 
input and some cells under conditions of 
release from tonic inhibition show c-Fos 
expression in response to appropriate 
stimuli, other disinhibited neurons do not 
express c-Fos induction (for review, see 
Kovács, 2008), and c-Fos is rarely observed 
in large motor neurons of the brainstem 
(Chan and Sawchenko, 1994). As a result, 
vestibulo-ocular, vestibulo-spinal, and ves-
tibulo-colic motor neurons present in sub-
regions of the VNC should not be expected 
to accumulate c-Fos protein. On the basis of 
this analysis, we conclude that while sGVS 
does indeed activate the entire vestibular 
nerve, only the otolith system expresses a 
persistent behavioral and neural response 
due to the habituation of the canal-related 
units and the attendant inhibition of ves-
tibular neuronal populations. It is likely that 
the habituation of the semicircular canal 
induced activity originates in the cerebel-
lum, but this remains to be determined.
Acknowledgments
The research underlying this opinion article 
was supported by NIH grants DC008846 
(Gay R. Holstein), DC004996 (Sergei B. 
Yakushin), and Core Center DC05204 
(Bernard Cohen).
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Received: 08 December 2011; accepted: 21 December 2011; 
published online: 06 January 2012.
Citation: Cohen B, Yakushin SB and Holstein GR (2012) 
What does galvanic vestibular stimulation actually activate? 
Front. Neur. 2:90. doi: 10.3389/fneur.2011.00090
This article was submitted to Frontiers in Neuro-otology, a 
specialty of Frontiers in Neurology.
Copyright © 2012 Cohen, Yakushin and Holstein. This is 
an open-access article distributed under the terms of the 
Creative Commons Attribution Non Commercial License, 
which permits non-commercial use, distribution, and repro-
duction in other forums, provided the original authors and 
source are credited.
Frontiers in Neurology | Neuro-otology  January 2012 | Volume 2 | Article 90 | 2
Cohen et al. Galvanic vestibular stimulation effects


What Does Galvanic Vestibular Stimulation Actually Activate?

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What Does Galvanic Vestibular Stimulation Actually Activate?

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