Original Research

Combining Visual Rehabilitative Training and
Noninvasive Brain Stimulation to Enhance Visual
Function in Patients With Hemianopia: A
Comparative Case Study
Ela B. Plow, PhD, PT, Souzana N. Obretenova, BA, Mark A. Halko, PhD,
Sigrid Kenkel, Dipl Psych, Mary Lou Jackson, MD, Alvaro Pascual-Leone, MD, PhD,
Lotfi B. Merabet, OD, PhD
Objective: To standardize a protocol for promoting visual rehabilitative outcomes in
post-stroke hemianopia by combining occipital cortical transcranial direct current stimulation (tDCS) with Vision Restoration Therapy (VRT).
Design: A comparative case study assessing feasibility and safety.
Setting: A controlled laboratory setting.
Patients: Two patients, both with right hemianopia after occipital stroke damage.
Methods and Outcome Measurements: Both patients underwent an identical VRT
protocol that lasted 3 months (30 minutes, twice a day, 3 days per week). In patient 1,
anodal tDCS was delivered to the occipital cortex during VRT training, whereas in patient 2
sham tDCS with VRT was performed. The primary outcome, visual field border, was defined
objectively by using high-resolution perimetry. Secondary outcomes included subjective
characterization of visual deficit and functional surveys that assessed performance on
activities of daily living. For patient 1, the neural correlates of visual recovery were also
investigated, by using functional magnetic resonance imaging.
Results: Delivery of combined tDCS with VRT was feasible and safe. High-resolution
perimetry revealed a greater shift in visual field border for patient 1 versus patient 2. Patient
1 also showed greater recovery of function in activities of daily living. Contrary to the
expectation, patient 2 perceived greater subjective improvement in visual field despite
objective high-resolution perimetry results that indicated otherwise. In patient 1, visual
function recovery was associated with functional magnetic resonance imaging activity in
surviving peri-lesional and bilateral higher-order visual areas.
Conclusions: Results of preliminary case comparisons suggest that occipital cortical
tDCS may enhance recovery of visual function associated with concurrent VRT through
visual cortical reorganization. Future studies may benefit from incorporating protocol
refinements such as those described here, which include global capture of function, control
for potential confounds, and investigation of underlying neural substrates of recovery.
PM R 2011;3:825-835

INTRODUCTION
Visual impairment that stems from cerebral damage such as stroke greatly impacts upon an
individual’s sense of independence and well-being [1]. Damage to the occipital cortex
and/or the optic radiations results in a deficit within the contralateral half of the visual field
of both eyes. This partial blindness, termed hemianopia [2-4], profoundly affects many
important activities of daily living (ADL), including reading [5,6] and navigating safely
within one’s environment [7-9]. In the majority of cases, patients demonstrate less than 5°
of central visual sparing [10], and complete spontaneous recovery occurs only rarely
[9,11,12]. Given that relatively few therapeutic options exist for this condition, developing
novel rehabilitation strategies to promote the recovery of visual function after cerebral
damage is of great importance [13].
PM&R
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Author affiliations and disclosures are provided at the end of the article.
Disclosure Key can be found on the Table of
Contents and at www.pmrjournal.org
Research support: This work was supported by
an investigator-initiated pilot grant from Novavision VRT Inc. and by the National Institutes of
Health (K23-EY016131 to L.B.M.).
Submitted for publication September 13,
2010; accepted May 26, 2011.

© 2011 by the American Academy of Physical Medicine and Rehabilitation
Vol. 3, 825-835, September 2011
DOI: 10.1016/j.pmrj.2011.05.026

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Multiple lines of evidence from animal and human clinical
studies have highlighted the potential of the brain to reorganize itself within the context of functional recovery after
injury [14-16]. Efforts also have been aimed at identifying
interventions that can leverage and modulate these mechanisms [17-23]. One example emerges from work in motor
recovery after stroke, which demonstrates that repeated systematic training combined with direct invasive electrical
stimulation (delivered to areas of the motor cortex that correspond to the paretic hand) significantly improves functional rehabilitative outcomes [20,24-26]. Similar findings
also have been reported when using adjunctive noninvasive
forms of brain stimulation [21,27-31].
Translating these concepts to the case of hemianopia
requires a visual analog of systematic rehabilitative training.
One possibility is to incorporate computer-based visual
training strategies such as Vision Restoration Therapy (VRT)
(Novavision Inc, Boca Raton, FL). VRT trains patients to
detect repeated presentations of visual stimuli concentrated
within the area between blind and intact visual fields. This
area of residual vision has been referred to as the “transition
zone,” and has been functionally characterized as an area of
suboptimal visual perception that may physiologically correspond to partially surviving neurons associated with damaged visual areas [13,32,33]. By following a daily training
regimen (typically lasting 6 months), a demonstrable expansion in visual field border has been reported [32-38]. Visual
recovery may implicate the reactivation of surviving perilesional areas as well the recruitment of neighboring higherorder visual areas [32,39-42]. Thus, similar to motor recovery, cortical stimulation that targets areas implicated in
repeated systematic training of the affected visual field may
potentiate synaptic and network level neuroplastic changes
and may lead to improved functional outcomes.
Based on these concepts, we developed a comparative case
study protocol designed to test the feasibility and preliminary
efficacy of combining VRT with noninvasive brain stimulation (transcranial direct current stimulation [tDCS]). TDCS
has been gaining considerable interest not only for its ability
to modulate cortical excitability but also for its relative simplicity of implementation and good safety profile [18,43].
Results of previous studies have shown that tDCS delivered
to the occipital cortex can modulate visual perceptual functions, such as contrast sensitivity detection and motion perception [44-46]. We hypothesized that combining VRT with
anodal tDCS (so as to upregulate the excitability of both the
intact and lesioned hemispheres) would potentiate visual
rehabilitative efficacy compared with VRT alone (ie, paired
with sham tDCS).
We also incorporated a series of design refinements specifically aimed to address criticisms raised from previous
studies regarding VRT [47-49]. First, by using online eye
tracking, we investigated whether compensatory eye movements led to the erroneous appearance of visual field expan-

sion [48-50]. Second, we included an ancillary assessment of
visual field (by using a MP-1 microperimeter; NIDEK Technologies, Padova, Italy) to further compare and validate
observed visual field changes after training. Third, we incorporated validated tests to capture associated functional benefits on ADLs. Fourth, we quantified the patients’ own subjective changes in visual field deficit to address reported
discontinuities between quantitative and qualitative outcomes [47,49]. Finally, we incorporated a functional magnetic resonance imaging (fMRI) study to characterize neural
substrates associated with recovery after training [49].

METHODS
Subjects
Patients 1 and 2 (both women, aged 61 and 62 years, respectively) were both diagnosed with right-sided hemianopic
visual field loss resulting from ischemic stroke and were in
the chronic phase of visual recovery [9,11]. Neither patient
presented with any additional confounding visual deficit (eg,
ocular complications), nor was either patient concurrently
involved in another form of rehabilitative training. Neither
presented with any exclusion criteria drawn from safety
guidelines associated with the use of noninvasive brain stimulation [51-53]. Briefly, this included the following: (1)
history or familial history of seizure disorder; (2) metallic,
mechanical, or magnetic implant in the head or body; and (3)
chronic use of neurostimulants, anticonvulsants, or antidepressants.
Patient 1 was randomly assigned to receive VRT combined
with active tDCS, whereas patient 2 received VRT combined
with sham tDCS (Figure 1). Experimental blinding was implemented at the level of patients and the individuals who
were assessing visual field outcomes. Both patients provided
written informed consent, and the study was approved by the
institutional review board of the Beth Israel Deaconess Medical Center, Boston, Massachusetts.

Interventions
VRT. The study was conducted in a controlled laboratory
environment, which allowed for the standardization of the
training environment and the opportunity to continually
monitor and provide feedback on progress. A contracted VRT
training regimen that lasted 3 months was used (ie, 2 halfhour sessions per day, 3 days per week for a total of 36
hours), which corresponded to approximately one-fourth of
the typical schedule used in previous VRT studies (ie, 6
months, for a total of 144 hours) [32,33,35]. After comprehensive neurologic and ophthalmologic examinations, the
patients’ visual field function was assessed to characterize
progress and also to guide the spatial parameters of customized VRT (see below for details).

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Figure 1. Overview of study design. Potential study participants are evaluated for eligibility based on predetermined inclusion and
exclusion criteria. Baseline (pretest) measures of performance are obtained, including objective, subjective, and functional
outcomes as well as a baseline fMRI. Participants are randomized to either VRT and active tDCS or VRT and sham stimulation, after
which they undergo a 3-month visual rehabilitation program. Outcome measures of performance are again reassessed at monthly
intervals and at the end (post-test). fMRI, functional magnetic resonance imaging; HRP, high-resolution perimetry; IVI, Impact of
Vision Impairment; tDCS, transcranial direct current stimulation; VFQ, Visual Functional Questionnaire; VRT, Vision Restoration
Therapy; MNREAD, Minnesota Low-Vision Reading Test.

During training, the patient was seated in front of a 15-in
liquid crystal display monitor and at a constant viewing
distance of 30 cm with the head supported comfortably in a
chin rest (Figure 2). The patient was instructed to fixate with
both eyes on a central target presented on the monitor
(appropriate spectacle correction was used when necessary).
During one 30-minute training session, 500 light stimuli
were presented, primarily concentrated within the transition

Figure 2. Experimental setup. The patient is seated in front of a
computer monitor and instructed to fixate on a central target
while responding (by using a response button) to the detection
of visual stimuli presented. An eye-tracking camera monitors
eye position throughout the experimental session. The stimulation montage consists of 2 electrodes connected to the
transcranial direct current stimulation (tDCS) device. The anodal electrode is placed over the occipital pole (Oz), and the
cathodal electrode is placed over the vertex (Cz).

zone v (see primary outcome measure: visual field assessment
for details). Each stimulus appeared for 2000 milliseconds,
from low to high luminance (⬍1-50 cd/m2) in a stepwise
manner. The patient was instructed to respond as quickly as
possible with a key press upon detecting the peripheral
stimulus. As a built-in fixation monitoring strategy, the patient also was required to detect a color change of the fixation
target within 750 milliseconds, presented at random intervals (for more details regarding the specifics of the VRT
protocol, see Poggel et al [54]).
tDCS. tDCS was delivered by using 2 electrode sponges
(5 ⫻ 7 cm, soaked in 0.9% saline solution) connected to a
battery-operated unit that delivered continuous current
(IOMED Inc, Salt Lake City, UT). Based on the 10-20 International EEG Coordinate System, the anode was placed overlying the Oz position, with the intention of stimulating the
occipital cortex bilaterally, and the reference (cathode) was
placed over Cz (vertex). The electrodes were secured in place
by using nonlatex rubber straps (Figure 2). When a tDCS unit
is turned on, current is slowly ramped up until the target
current level is reached. During this initial period (approximately 30 seconds), subjects will typically report a tingling or
itching sensation beneath the surface of the anode. The
sensation subsides shortly thereafter (by habituation) and
remains below the threshold of detection. This fact is exploited for the purposes of experimental blinding [18,52,55].
Specifically, in patient 1, once the current was ramped up to
the target 2 mA/min, it was sustained throughout the duration of VRT training. For patient 2, the current was ramped
down (to zero) after initial habituation. Thus, both patients
remained unaware as to whether they were receiving active or

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sham tDCS. Effective blinding was further verified at the exit
interview.

Outcome Measures
Outcomes were assessed at baseline (pretest) and at monthly
intervals until completion of the 3-month training period
(post-test), unless noted otherwise.
Primary Outcome Measure: Visual Field Assessment. Visual fields were assessed by using high-resolution
perimetry (HRP) (described in detail previously [33,56]),
which is believed to correlate with more typical clinical visual
field assessments [56]. As with standard automated perimetry, the patients were instructed to maintain fixation on a
central target. Visual stimuli were randomly presented at
suprathreshold intensity (luminance 95 cd/m2) within the
entire testing area (spanning 43°⫻ 32° within an imaginary
grid of 19 ⫻ 15 cells, each cell subtending 2°). The patients
reported target detection by using a key press. Fixation
monitoring strategy was similar to that used in VRT.
The final visual field map was generated by overlaying the
results of 3 separate, consecutive tests. Intertest reliability
was verified by consistent performance in stimulus detection,
fixation performance, and false-positive rates. The composite
visual field map comprised intact regions (areas where stimuli were detected on all 3 tests), blind (regions never detected), and transition zone (stimuli were detected on only
one or 2 tests) (Figure 3). By convention, the visual field
border was defined as the average horizontal distance between the central vertical meridian and the medial edge of
2 consecutive blind cells along each row in the imaginary
grid [36].

Figure 3. Assessment of the visual field by using high-resolution
perimetry. The results of 3 separate suprathreshold perimetry
tests are overlaid to generate a composite map that identifies
the intact field, the blind field, and the transition zone of the
visual field. The transition zone is further subdivided into regions
where stimuli are detected once (33% probability) or twice
(66% probability).

Secondary Outcome Measures.
● Functional Outcome Measures (Reading and ADLs): Func-

tional outcomes of performance included the Impact of Vision Impairment (IVI) [57,58] and Veterans Affairs
Low Vision-Visual Functional Questionnaire (LV-VFQ)
[59,60]. Responses were rated by using a Likert-type scale
(with 0 indicating “not affected” to 5 indicating “cannot do
it at all” for the IVI; and 1 indicating “not difficult at all” to
4 indicating “impossible” for the LV-VFQ). Reading performance was assessed at pretest and post-test by using the
Minnesota Low-Vision Reading Test (MNREAD) standardized test for reading speed (medium print size, 2M print
size equivalent to 0.7 logarithm of the Minimum Angle of
Resolution [logMAR]) [61] and was expressed in words per
minute (wpm).
● Subjective drawings of the affected hemifield: To characterize a subjective visual field, the patients were instructed
to fixate on a central target on a 9 ⫻ 12-in sheet of graph
paper (similar in design to an Amsler grid) at a viewing
distance of 40 cm. The patients then indicated the location
of the intact visual border, and the drawings were then
digitized and converted into dichotomous black and white
figures with preserved aspect ratio [62]. The area of affected vision (represented by regions in black on digital
images) was then calculated by using customized software
(version 4.0.2; Scion, Frederick, MD).
Ancillary Visual Field Assessment. As an ancillary
outcome measure, visual field performance was assessed at
pretest and at post-test by using a NIDEK microperimeter
(MP-1). This device is gaining acceptance within the clinical
community and allows luminance-based thresholded microperimetry with fixation tracking [63] using retinal fundus
landmarks and false-positive rate measures [64,65]. The
NIDEK MP-1 testing grid covered a circular area within
central 20°, and a luminance-thresholded approach using a
4-2 strategy was used. Within the affected visual field, stimulus locations were categorized as “blind” (0-6 dB), “transition” (7-12 dB), and “intact” (13-20 dB) based on predefined
thresholds of luminance of detection [64].
Eye Movement Tracking. In addition to fixation monitoring built into the HRP system, we incorporated an independent measure of fixation performance by using a 2-dimensional infrared eye tracking device (Applied Science
Laboratories, Bedford, MA). Tracking ocular pupillary and
corneal reflections at a sampling frequency of 60 Hz (expressed in Cartesian coordinates) [66] allowed for online
quantification of fixation performance during training and
visual field testing. The “fixation moment” was defined as the
instance in which the central gaze remained within 0.5° of a
prior location for more than 12 milliseconds. The percentage
time for which fixation moment was within the central 1° and
2° radius was then calculated.

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Functional Neuroimaging. fMRI has been used extensively in cognitive neuroscience and clinical neurology for its
ability to localize brain activity [67-69]. Previous VRT studies
have used fMRI to characterize patterns of neural activation
with regard to the initial phases of VRT training [34] and with
visual tasks designed for visual cortex mapping [34,70].
Here, we incorporated fMRI to identify patterns of activation
associated with recovery of function.
The fMRI data were collected at baseline and at post-test
for patient 1 (data could not be obtained for patient 2).
Imaging parameters included blood oxygen level– dependent
signal fMRI collected by using a whole-body Philips Achieva
Intera 3T scanner equipped with an 8-channel SENSE head
coil (Philips Medical Systems, Bothell, WA) and coregistered
to the same-session high-resolution anatomical images. Analysis of functional data was performed to generate statistical
fMRI activation maps by using the Brain Voyager QX 1.9
analysis software package (Brain Innovation, Maastricht, the
Netherlands). Standard techniques for data preprocessing
and analyses were used and have been previously described
elsewhere [71].
By using a standard block design with alternating conditions of visual task and rest, stimuli were presented in the
intact, blind, or the transition zone regions. The patient was
required to detect and discriminate (1) the orientation of
Gabor grating patches, and (2) the motion direction of random dot kinetograms. The patient responded with a key
press to indicate whether the orientation of the gratings or the
direction of moving dots was the same or different from that
in the previous display. The position of stimuli was based on
the HRP visual field map obtained at pretest and remained
constant between baseline and post-test fMRI scanning sessions. These 2 stimuli were selected for their ability to activate
lower-order (eg, primary visual cortex, V1) and higher-order
(eg, hMT⫹/V5) visual areas, respectively [72].

RESULTS
With regard to safety, neither patient experienced any complication or adverse event associated with the combined
tDCS and VRT intervention. Furthermore, experimental
blinding regarding active or sham delivery of tDCS was
maintained and confirmed during the patient exit interview.
Exit interviewing revealed that patient 1 believed that she
received sham treatment, whereas patient 2 reported that she
received real stimulation (note that these are the opposite
conditions from those to which the patients were relegated).
Preliminary comparative findings were in agreement with
our initial hypothesis. Specifically, HRP revealed a greater
expansion in visual field border in patient 1 as well as
recovery of the visual field that occurred within the periphery
and extended toward the center (Figure 4). Ancillary visual
field testing with the NIDEK MP-1 was in agreement with the
HRP results. In patient 1, blind stimulus locations converted

Figure 4. Changes in high-resolution perimetry (HRP) (top row)
and subjective (bottom row) visual fields in 2 study participants.
When comparing HRP assessments at pretest and post-test,
patient 1 (Vision Restoration Therapy [VRT] and active transcranial direct current stimulation [tDCS]) shows a 3.55° expansion in her central visual field as well as a 4° shift inward from
the periphery (lower right quadrant). Patient 2 (VRT and sham
tDCS) shows a 0.9° expansion centrally. Contrary to HRP findings, a larger expansion in subjective visual field was reported
by patient 2 (a change in the affected field of 53.75 cm2)
compared with patient 1 (a change of 24.14 cm2) after
training.

to transition zone (primarily in the inferior peripheral quadrant), whereas in patient 2, less visual field expansion was
observed, with correspondingly fewer transition zone locations becoming intact (primarily in the macular region). Both

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associated with the Gabor orientation task (albeit less robust)
also was observed (data not shown).

DISCUSSION

Figure 5. Online eye tracking trace from patient 1 (right
hemianopia). Horizontal deviation of eye position (in visual
field angle in degrees) from central fixation (marked at 0 on
the x-axis) is shown during a continuous 40-minute trace captured during high-resolution perimetry (HRP) testing (sampled
at 60 Hz). On average, the patient spends more than 95% of
the time within ⫾1° of central fixation (shaded area).

patients maintained eye fixation within 2° of the central
target 95% of the time (Figure 5). Quantitative secondary
outcome measures, including IVI, LV-VFQ, and MNREAD
reaffirmed that patient 1 received greater functional benefit
after combined VRT and tDCS training. Patient 1 demonstrated considerable improvement on the IVI (from 48 to 4)
and LV-VFQ (from 26 to 24) compared with patient 2 (from
22 to 14 and from 26 to 28, respectively). Similarly, improvement on MNREAD, which evaluates the reading ability for a
medium print size (2M), was greater in patient 1 (150 to 200
wpm) versus patient 2 (200 to 150 wpm). Contrary to
objective visual field results, patient 2 reported a greater
subjective improvement in visual field recovery (Figure 4).
Finally, fMRI data obtained with patient 1 revealed differential patterns of activation after training (Figure 6). Taskrelated activation associated with motion discrimination in
the intact and blind fields remained largely contralesional
and implicated the motion-processing area hMT⫹/V5. However, motion discrimination in the transition zone was associated with a larger network of activation, including perilesional primary visual areas as well as V2/V3 and hMT⫹/V5
(Figure 6) following training. A similar pattern of activation

In the present comparative case study, we have contrasted
the effects of combining systematic visual rehabilitative training and noninvasive brain stimulation with training alone in
improving visual functional outcomes in hemianopia. To our
knowledge, this study represents the first attempt within the
visual rehabilitation arena to replicate previous concepts
drawn from stroke motor recovery.
Visual rehabilitative training (provided by VRT) combined with tDCS targeting the occipital cortex bilaterally
enhanced visual field function to a greater degree than VRT
alone. Besides assessing feasibility, the present case study
protocol allowed us to incorporate study design refinements
to help establish the foundation for more rigorous investigations in the future. Carried out in a controlled laboratory
environment, we monitored the influence of potential confounds, such as ambient conditions and compensatory eye
movements [48-50]. Regarding the latter point, we found
that both patients were able to maintain accurate fixation
throughout training and testing. Kasten et al [73] similarly
concluded that improvements that resulted from VRT were
not artifacts of compensatory eye movements (when using
recordings for 3.5 minutes). Implementing online fixation
monitoring for longer duration (as in the present report) has
helped address previous concerns regarding the role of eye
movements in visual field recovery (for further discussion,
see Trauzettel-Klosinski and Reinhard [74]).
To compare and further characterize visual field recovery
outcomes, we incorporated secondary perimetry assessment
by using the NIDEK MP-1. Qualitatively, regional changes in
the visual field were similar between NIDEK MP-1 and HRP.
Although previous reports similarly suggest concordance
between clinical perimetry and HRP [54,56], establishing
quantitative agreement and clear correlations still requires
further investigation [13,36].
Rehabilitative success has been operationalized by using
objective measures that characterize visual field changes. To
help capture functional changes, we also assessed reading
performance (MNREAD) as well as standardized self-report
questionnaires (IVI and VFQ). We found that increased
visual field expansion was associated with improved performance of ADLs. Incorporating advanced methods of analyzing questionnaire-based functional assessments such as the
Rasch analysis [75] may help to further characterize changes
in visual function more accurately.
Interestingly, by studying both objective perimetry and
subjective perception of visual field, we observed an apparent
discontinuity between the two. This objective–subjective disconnect has been previously reported [47,49]. It is interesting to
note that both patients reported that their tDCS status (ie, real or

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Post Training

Intact

A

Baseline

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Dot Kinetogram

transition

blind

Blind

intact

B

Transition

-2

R

R

Figure 6. Functional neuroimaging results. (A) Visual stimuli used in the study include random dot kinetograms and Gabor patches (not
shown). Behavioral performance on a direction-discrimination task is assessed with stimuli presented in either the intact field, the blind
field, or the transition zone (as shown). (B) Structural magnetic resonance image (sagittal view) of patient 1 (Vision Restoration Therapy
and active transcranial direct current stimulation), showing location of occipital lesion in the left hemisphere. The horizontal line illustrates
the location of the axial slice shown in (C). (C) Visual motion perception–related activation as a function of stimulus location before and
after training. When the visual stimulus is located in the intact visual field, activation within the contralateral area of V5/hMT⫹ is observed
and is comparable at baseline and after training (black arrow). In the blind field, note the bilateral activation of V5/hMT⫹ in both the
contralateral (white arrow) and ipsilateral visual (black arrow) at both baseline and after training. Finally, task performance with the visual
stimulus presented in the transition zone at baseline is associated with bilateral V5/hMT⫹ activation as well as peri-lesional activation
(dotted circle). Post-training activation related to visual motion perception in the transition zone, showing again bilateral activation of
V5/hMT⫹ but now a greater spread of activation within the occipital pole. The threshold for significance was set at P ⬍ .05. A similar
pattern of activation was observed with the Gabor patch visual stimulus, albeit with less robust activation.

sham) was opposite to what they actually received. Therefore,
this disconnect may be related to their own expectations of
outcome, or may reflect subjective differences in the functional
relevance afforded to different regions of the visual field (eg,
central visual versus peripheral sparing) [62]. Certainly, this
issue confirms the need for accurate and reliable methods to
assess visual function and the value of incorporating experimental blinding to help validate findings.
In an effort to elucidate recovery-associated mechanisms
implicated in visual function recovery, we incorporated a
neuroimaging component for patient 1 (VRT with active
tDCS). After training, task-dependent and visual field loca-

tion–specific reorganization implicated peri-lesional as well
as bilateral higher-order visual areas. Although we cannot
disentangle the contributory effects of VRT from tDCS, this
widespread activation is in line with the view that visual
recovery potentially reactivates surviving visual areas [32,3942], a finding that is analogous to comparative work in
post-stroke motor recovery [76-78]. The preliminary nature
of these results warrants caution in interpretation. Incorporating additional specialized techniques and methods of analysis, such as tractography and functional connectivity, could
further help to establish a relationship between cortical activity, neural pathways, and functional outcomes.

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The potential neurophysiological mechanisms that underlie the combined benefit provided by VRT and tDCS remain
unclear. Mechanisms may include increased neuronal excitability [29], induction of long-term potentiation [79-81], and
functional reorganization of cortical maps [24], as well as
increases in neuronal density [25,82].
At this juncture, it is difficult to surmise the impact of the
electrode configuration of tDCS chosen for the present study
in facilitating visual rehabilitative outcomes. Certainly, a
variety of stimulation montages could have been used. However, because there was no a priori evidence that selective stimulation of either the lesioned or intact hemisphere would lead to
a greater effect, we opted for a montage similar to previous
studies that demonstrated that anodal stimulation delivered
bilaterally to the occipital pole modulates a variety of neurophysiological outcomes, including phosphene thresholds and
visual evoked potentials [46,83-85]. Interestingly, results of
compartment-based current density modeling suggest that lesioned areas of the brain create an electrical shunt (due to the
presence of cerebral spinal fluid), which affects the overall
distribution of current between lesioned and nonlesioned areas
[86,87]. Thus, it is possible that with the montage used here,
peri-lesioned areas received preferentially greater current density by virtue of injury-related morphologic changes.
The greatest limitation of the study stems from the fact that we
present results from only a single paired case study. Thus, our
ability to generalize further from these observations is certainly
limited. For example, although the combination of VRT and tDCS
appeared to promote greater visual field recovery, differences in
baseline visual deficits also could potentially lead to these same
observations. It is possible that greater areas of residual vision
present in patient 1 (ie, the size of the transition zone and the
presence of peripheral islands of vision) could have been associated
factors leading to greater visual field improvement from training.
Indeed, the size of the transition zone has been reported to be an
important predictor of overall visual field recovery [38,41,54].
Certainly, a larger randomized clinical trial is required not only to
confirm these preliminary findings but also to help disentangle
these multifactorial issues related to recovery and further validate
the study design approach described here.
Finally, these preliminary findings hold promise not only
from a functional outcomes perspective but also in terms of
time and potential cost. Several groups have been pursuing
computer-based training strategies [33,88-91] as well as
novel cross-modal sensory approaches [92], and preliminary
results have been encouraging. As with VRT, these strategies
require thousands of repeated trials delivered over many
months of training before beneficial effects are achieved. It is
worthy of note that, in this study, a contracted training regimen
was used (ie, one-fourth in the duration of the standard clinical
paradigm). Yet, comparable changes in the visual field were
possible (compared with the outcomes from previous studies of
VRT), which suggests that combined stimulation may provide
increased functional benefit and/or an acceleration of desired

outcome achievement, either of which would be highly desirable from a rehabilitative standpoint.

CONCLUSIONS
We present a comparative case study as well as feasibility and
safety findings that describe the effects of combined visual
rehabilitation (provided by VRT) with a form of noninvasive
brain stimulation (tDCS) in patients with heminanopic visual
field loss. Preliminary results are consistent with the hypothesis that the combination of visual rehabilitative training and
noninvasive brain stimulation leads to an increase in functional visual recovery compared with visual rehabilitation
alone. A larger randomized clinical trial is required to confirm these preliminary findings as well as to help uncover the
potential neural correlates of functional recovery.

ACKNOWLEDGMENTS
We thank Dorothe Poggel, Felipe Fregni, Nurhan Torun, and
Joseph F. Rizzo for helpful advice while carrying out this
project and in preparation of this article.

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Footnotes Continued From Page 825.

M.A.H. The Berenson-Allen Center for Noninvasive Brain Stimulation, Department of
Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA
Disclosure: nothing to disclose

E.B.P. The Berenson-Allen Center for Noninvasive Brain Stimulation, Department of
Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA;
Department of Biomedical Engineering, Lerner Research Institute, Physical Medicine and
Rehabilitation, The Cleveland Clinic Foundation, Cleveland, OH
Disclosure: 9, Postdoctoral Fellow on investigator-initiated grant from Novavision
S.N.O. The Berenson-Allen Center for Noninvasive Brain Stimulation, Department of
Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA
Disclosure: nothing to disclose

S.K. NovaVision Zentrum für Sehtherapie (Center for Vision Therapy), Magdeburg,
Germany
Disclosure: 6B, NovaVision
M.L.J. Vision Rehabilitation Center, Massachusetts Eye and Ear Infirmary, Harvard
Medical School, Boston, MA
Disclosure: 7B, Optelec USA

PM&R

A.P.-L. The Berenson-Allen Center for Noninvasive Brain Stimulation, Department of
Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA;
Instituto Guttmann de Neurorrehabilitacióon, Universidad Autónoma de Barcelona,
Badalona, Spain
Disclosure: 2A, scientific and medical advisory board of Novavision VRT Inc, Starlab,
Neosync, Neuronix; 7, grant from Nexstim and equipment support

Vol. 3, Iss. 9, 2011

835

L.B.M. The Berenson-Allen Center for Noninvasive Brain Stimulation, Department of
Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA;
Vision Rehabilitation Center, Massachusetts Eye and Ear Infirmary, Harvard Medical
School, 243 Charles St, Boston, MA 02114. Address correspondence to: L.B.M.; e-mail:
lotfi_merabet@meei.harvard.edu
Disclosure: 9, investigator-initiated grant from NovaVision VTR