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Zubko, Olga, Wilkinson, David T., Langston, Deborah and Sakel, Mohamed
(2013) The effect of repeated sessions of galvanic vestibular stimulation
on target cancellation in visuo-spatial neglect: Preliminary evidence from
two cases. Brain Injury, 27 (5). pp. 613-619. ISSN 1362–301X.

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The effect of repeated sessions of galvanic vestibular stimulation
on target cancellation in visuo-spatial neglect:
Preliminary evidence from two cases

	
  

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Abstract
Objective: In recent years it has emerged that the attentional disorder of visuospatial neglect can be overcome via artificial stimulation of the balance system. One
means of achieving this is via galvanic vestibular stimulation (GVS), a simple
procedure in which tiny, electrical currents are discharged to the part of the scalp
overlying the vestibular nerves. Attempts to remediate neglect with GVS have
utilised only a single session of stimulation, and although this can induce
spontaneous recovery, symptoms resurface soon after stimulation. Here we
assessed whether repeated sessions induce longer carry-over.

Methods: Two individuals diagnosed with neglect post-stroke received five days of
sub-sensory, left anodal GVS. Performance was assessed via the letter and star
cancellation tasks of the Behavioural Inattention Test on four occasions; three days
before the start of stimulation, on the first and last day of stimulation, and three-days
after stimulation.

Results: Analyses of variance indicated that both participants missed significantly
fewer targets in both tasks on the fifth day of stimulation compared to baseline. More
so, this improvement was still evident at follow-up three days later.

Conclusion: The results strengthen the need for a larger, sham-controlled trial to
establish whether repeated GVS provides lasting relief from neglect.

	
  

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Introduction
Visuo-spatial neglect is a disabling, neurological condition commonly acquired
through stroke, and is characterised by an impaired ability to respond to visual
stimuli presented in contralesional space. The condition most frequently occurs
following a lesion to the right hemisphere, inducing a tendency to collide with leftsided objects and ignore people who approach from the left [1]. Neglect is a poor
prognostic indicator of general functional recovery after stroke, extending length of
hospital stay [2], and impacting functional independence post-discharge [3]. Although
relatively common in right hemisphere stroke, the condition persists in approximately
20% of stroke survivors [4]. Unfortunately, the most widely practiced treatment for
neglect, visual scanning therapy, is of limited efficacy [5]. More promising treatments
are, however, beginning to emerge (see [6]), one of which is galvanic vestibular
stimulation (GVS).
GVS modulates the firing rates of the vestibular nerves via the delivery of
small-amplitude current (~1mA-2mA) to the overlying mastoid processes [7]. The
brain interprets this modulation as a natural head movement, which in turn elicits a
variety of cortical and subcortical compensatory responses. Neuroimaging indicates
that GVS increases blood flow [8], and electrical power spectra [9] in those temporalparietal and frontal regions of brain typically damaged in neglect. Such increases
may be important for subsequent cognitive restoration and behavioural improvement
[10]. At the psychological level, Karnath [11] has proposed that the central
transformation that converts sensory input co-ordinates into an egocentric, bodycentered co-ordinate system is systematically skewed in neglect, resulting in a
horizontal deviation of the spatial reference frame to the ipsilesional side. The idea
behind sensory stimulation is that by artificially boosting sensory inputs from the

	
  

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neglected side, a correctional spatial bias is induced that runs counter to the
rightward shift imposed by neglect [12]. That is, the existing spatial imbalance is
eliminated by adding a new one of opposite magnitude.
Several research groups have shown that a single session of GVS can
spontaneously reduce aspects of the neglect syndrome [13-15]. This observation
builds on the longstanding finding that caloric vestibular stimulation, an allied method
that modulates peripheral vestibular activity via thermal as opposed to electric
waveforms but in a less controlled and tolerated manner, can produce dramatic and
spontaneous relief from neglect [16,17]. A key drawback of vestibular stimulation is,
however, that its effect on neglect seems to recede only minutes or hours after
stimulation is withdrawn. To hold relevance to rehabilitative practice, the duration of
carry-over must somehow be increased.
One clue to how longer carry-over might be achieved is apparent from the
broader neuro-stimulation literature which indicates that persistent cognitive change
tends to follow from repeated treatment sessions [18-20], a result that chimes with
the idea that underlying neuro-plastic change relies on multiple stimulus exposures
[21]. For example, Schindo and colleagues [18] showed that 6 daily sessions of
transcranial magnetic stimulation (TMS) induced recovery from neglect that was still
evident 6 weeks later. More widely, Kleinjung et al. [19] showed that 5 consecutive
days of TMS led to a significant reduction of tinnitus for 6 months in 14 patients,
while Naeser et al. [20] showed that 10 daily TMS sessions generated a 2 month
improvement in picture naming in stable, chronic aphasic patients 3-6 months poststroke. Although these findings give reason to explore the effects of long-term TMS
in neglect patients, we should perhaps point out that GVS currently affords several
advantages. Unlike TMS, GVS is delivered to a single, easily identifiable scalp

	
  

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location (the mastoids), and relies on a small, battery-driven constant current
generator that is lighter, portable and easier to operate by nurses and carers.
Although strict safety protocols must be followed during GVS, these are less
stringent and inclusive of more patient groups than those that accompany TMS [22].
As might be expected, the hardware needed to deliver TMS is relatively expensive,
currently costing at least four or five times more than an off-the-shelf DC stimulator
suitable for GVS. As a consequence, GVS may be a more viable tool for some
developing healthcare economies.
In this small pilot study, we therefore assessed whether five consecutive daily
sessions of GVS could induce an improvement in visual neglect that was still evident
3 days later. We chose a 3 day follow-up period because the aim was to simply show
that it is possible to induce carry-over beyond just a few hours. If such carry-over
could be shown then there would be reason to move ahead with a larger, properly
controlled trial that more systematically investigated the effect of treatment repetition
on carry-over. To assess change, we administered the letter and star cancellation
tasks of the Behavioural Inattention Test (BIT) [23]. We chose these tests because
they are highly sensitive to neglect [24], and because they emphasise the need for
spatial exploration, an ability that runs to the heart of many daily activities.

Methods
Participant characteristics
Patient B.W, female, aged 61, suffered a right middle cerebral artery infarct (see
figure 1a) 8 weeks prior to study enrolment and was still residing in hospital at the
time of testing. On admission, she experienced severe left hemiparesis with no

	
  

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active movement in her upper and lower left limbs, left facial palsy and dysphagia.
The presence of left inattention was notable throughout administration of the NIH
Stroke Scale [25] and although this was later shown to impact her reading and
writing skills, no specific communication impairment was detected by the speech and
language therapist. Pain sensation was normal, but touch, temperature and position
sense were reduced. During eligibility screening, she scored 48/146 (normative cutoff = 129) on the conventional tests of the BIT, and often failed to respond when
addressed from the left during daily ward routine. At the time of screening, muscle
tone was increased in her left upper and lower limbs. Her MRC muscle power score
was 0/5 in her left arm and 4/5 in her left leg. Upper and lower limb reflexes were
especially brisk on the left side. A few days prior she scored 10 for anxiety and 10 for
depression on the Hospital Anxiety and Depression Scale [26], suggestive of a mild
mood disorder.

Patient S.M, male, aged 59, presented at admission with evidence of a right middle
cerebral artery infarct with midline shift (see figure 1b) and underwent an emergency
decompressive craniotomy. He showed a dense left hemiplegia and suffered a loss
of sensation throughout his left side. Administration of the NIH Stroke Scale
confirmed a florid, left-sided, personal and peri-personal neglect, which in turn
impacted sitting balance and posture. Formal perimetry conducted shortly after
revealed a left, homonymous hemianopia, although this was not reassessed at the
time of study enrolment. No communication or swallowing difficulties were observed
by the speech and language therapist. At the time of study enrolment, 38 months
post-onset, S.M. was living semi-independently at home and scored 79/146 on the
conventional tests of the BIT. He also produced an MRC muscle power score of 0/5

	
  

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in his left arm and 4/5 in his left leg, and showed continued evidence of a mild, upper
motor neuron-type left facial weakness.

Figure 1 about here
Behavioural Protocol
Both participants performed the letter and star cancellation sub-tests of the BIT on 4
separate occasions: 3 days before stimulation, on the first and last day of
stimulation, and then 3 days later. During administration, the test sheets were placed
in front of the participant on a desk, and aligned with the mid-sagittal plane. The
experimenter sat directly opposite. On those days when stimulation was
administered, participants performed the tests during (as opposed to after GVS).
Both participants gave written informed consent prior to study commencement, and
remained in good humour throughout. The study was approved by an NHS Research
Ethics committee and conducted in accordance with the 1964 Declaration of
Helsinki.

Stimulation Protocol
GVS was administered by applying bipolar current through a pair of 5.1cm x 10.2cm
carbon-rubber, self-adhesive electrodes, placed over the mastoid processes. To
ensure complete electrical contact with the electrodes, the skin surrounding the
mastoids was cleansed with an alcohol wipe and conductive gel was coated on the
underside of the electrodes. The anode was placed over the left mastoid and the
cathode over the right mastoid. The electrodes were connected to a Magstim Eldith
Transcranial DC Stimulator Plus™ device which discharged current at 90% of
cutaneous sensory threshold (1mA for participant S.M and 1.5mA for participant

	
  

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B.W.) for a period of 20 minutes on each of the 5 consecutive days. (Sensory
threshold was determined prior to the baseline session using the staircase procedure
described by Wilkinson et al. [27]). Participants were subsequently encouraged to
report any unusual sensation such as itching/tingling behind the ears, but neither did.
The participants wore the electrodes in the baseline but not follow-up session.

Results
The number of missed targets in the letter and star cancellation tasks were analysed
separately for each participant using one-way ANOVAs (Session: Pre-GVS, GVS-1,
GVS-5, Post-GVS). Post hoc pairwise comparisons were performed using the Tukey
HSD test (α=0.05).
Participant B.W.
See figure 2a for a graph showing B.W.’s mean errors and figure 3 for reproductions
of her cancellation performance.

Star cancellation: A one-way ANOVA revealed a significant effect of Session (F (3,
215) = 8.4, p < 0.01). Post hoc comparisons showed that B.W. missed fewer targets
in the GVS-5 and post-GVS sessions compared to the pre-GVS session. Fewer
targets were also missed in the GVS-5 and post-GVS sessions compared to the
GVS-1 session. As can be seen from figure 2a, these reductions in the number of
missed targets reflected a greater sensitivity to those appearing on the left-hand
side, a pattern that is repeated in all datasets reported below. No other significant
differences were found (ps > 0.82).

	
  

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Letter cancellation: A one-way ANOVA again revealed a main effect of Session (F(3,
159) = 49.1, p < 0.01). Post hoc comparisons revealed that, as with the star
cancellation, B.W. missed fewer letters in the GVS-5 and post-GVS sessions
compared to the pre-GVS session. BW was also more accurate in the GVS-5 and
post-GVS sessions compared to the GVS-1 sessions. No other effects were
significant (ps > 0.42).
Figures 2 and 3 about here
Participant S.M.
See figure 2b for a graph showing S.M.’s mean errors and figure 4 for reproductions
of his cancellation performance.

Star cancellation: A one-way ANOVA showed the main effect of Session to be
reliable (F (3, 215) = 16.0, p < 0.01). The Tukey HSD test indicated that S.M. missed
significantly more targets in the pre-GVS session compared to all other sessions.
S.M. also missed more targets in the first GVS session compared to the post-GVS
session. No other differences were significant (ps > 0.07).

Letter cancellation: As with star cancellation, a one-way ANOVA indicated a
significant main effect of Session (F (3, 159) = 7.1, p < 0.01). Post hoc comparisons
showed that S.M. missed fewer targets in the GVS-5 and post-GVS sessions
compared to the pre-GVS session. No other differences were significant (ps > 0.2).
Figure 4 about here

	
  

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Discussion
Previous studies have shown that a single session of vestibular stimulation can
improve performance on tests of unilateral neglect [13-15]. However, the duration of
improvement has remained uncertain, either because it has not been measured or
because it has fallen away after just a few hours. Here we wanted to establish
whether it was possible to prolong carry-over to a period of days rather than hours.
Given the general notion that lasting neuro-plastic change is most likely to occur
following multiple stimulus exposures [21], we administered five daily sessions and
then tested for carry-over 3 days later. Compared to the baseline, both neglect
participants showed a significant improvement in their star and letter cancellation
performance after 5 days of stimulation. Consistent with a cumulative effect, the level
of improvement on the fifth day was generally greater than that seen on the first.
Most important, the level of performance seen at day 5 was still apparent 3 days
after stimulation was stopped. In the case of participant S.M., the number of targets
missed at baseline had diminished by 37% at follow-up (37%-0%) for star
cancellation and by 25% (30% to 5%) for letter cancellation. In the case of participant
B.W., the number of targets missed at baseline had diminished by 35% at follow-up
(85% to 50%) for star cancellation and by 70% (90% to 20%) for letter cancellation.
These data are important because they indicate that GVS may be able to induce
long-term relief from neglect. Given that neither participant showed ill-effect, these
data also confirm our earlier report that 5 days of stimulation are well-tolerated [28].
On a cautionary note, we point out that that in the absence of a sham
condition, it is not possible to discount the effects of natural recovery, practice and/or
placebo. That said, participants wore the electrodes during the baseline session, so
if there was a strong placebo effect then one might have expected little change from

	
  

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baseline to actual stimulation (note that all stimulation was sub-sensory). Given that
both participants, especially S.M., had showed a relatively stable neglect for weeks
prior to testing, we are reluctant to believe that the sudden change in cancellation
performance simply reflected natural recovery. Finally, cancellation tests have shown
good test-retest reliability, especially in more severe cases of neglect such as those
assessed here [29]. Although these considerations lend a degree of confidence to
the current findings, a larger, properly controlled trial is now needed for both
confirmatory purposes and to determine whether there is transfer to activities of daily
living. For the time being, we wish to highlight the potential, albeit often underplayed,
contribution of GVS to neglect rehabilitation.

	
  

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Acknowledgements
We thank B.W. and S.M for their patient assistance throughout the study.

	
  

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Declaration of Interest
The authors report no declarations of interest.

	
  

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Figure Captions
Figure 1. Participant CT Scans. (a) Selected axial sections of Participant B.W.’s
brain lesion, showing a large ill-defined wedge shaped area of low attenuation within
the right frontal, parietal, and temporal lobes with deep white matter extension into
the ipsilateral basal ganglia. The right middle cerebral artery is hyperdense
compared to the contralateral side in keeping with the ‘dense artery sign’ of an acute
MCA thrombus. There is sulcal effacement and loss of normal gyral patterns. A mass
effect partially effaces the right ventricle with an anterior horn predominance, causing
a midline shift of 6mm. (b) Selected sections of Participant S.M.’s brain lesion,
showing gliosis and porencephaly in the right middle cerebral artery territory
including all of its segments, with dilatation of the ipsilateral ventricle. There is also
evidence of a small, hyperdense extra axial collection with a maximum depth of
8.5mm, consistent with a subdural haemotoma following craniotomy.
Figure 2. Percentage of targets omitted in the star and cancellation tasks for
Participants (a) B.W. and (b) S.M.

Figure 3. Spatial distribution of target omissions produced by Participant B.W.
Missed targets are highlighted via either a circle (in the star cancellation task) or
rectangle (in the letter cancellation task).

Figure 4 Spatial distribution of target omissions produced by Participant S.M. Missed
targets are highlighted via either a circle (star cancellation task) or rectangle (letter
cancellation task).

	
  

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