Effect of Different Stimulus Configurations On The Visual Evoked Potential

Doc Ophthalmol
DOI 10.1007/s10633-012-9319-0
ORIGINAL RESEARCH ARTICLE
Effect of different stimulus configurations on the visual

evoked potential (VEP)
Naveen K. Yadav Diana P. Ludlam
Kenneth J. Ciuffreda
Received: 15 August 2011 / Accepted: 2 March 2012

Springer-Verlag 2012
Abstract The purpose of this study was to assess

changes in the response profile of the pattern visual
evoked potential (VEP) using three stimulus configurations simulating visual-field scotomas: central
circular and central blank fields increasing incrementally in diameter from 1 to 15, hemi-field, and
quadrant patterns. Five visually normal adult subjects
(ages 2268 years) were tested binocularly at 1 m for
each stimulus configuration on 5 separate days. A
checkerboard test pattern (64 9 64 black-and-white
checks, 85 % contrast, 64 cd/m2 luminance, 20 s of
stimulus duration, 2-Hz temporal frequency) was used.
The group mean VEP amplitude increased in a linear
manner with increase in the central circular diameter
(y = 0.805x ? 2.00; r = 0.986) and decrease in central blank field diameter (y = -0.769x ? 16.22;
r = 0.987). There was no significant change in latency
in nearly all cases. The group mean coefficient of
variability results indicated that the VEP amplitude
was repeatable for the different stimulus configurations. The finding of VEP response linearity for the
circular stimulus fields, and repeatability for all
stimulus configurations, suggests that the clinician
may be able to use the VEP technique with the
suggested test patterns as a rapid and simple tool for
N. K. Yadav (&) D. P. Ludlam K. J. Ciuffreda

Department of Biological and Vision Sciences, SUNY
State College of Optometry, 33 West 42nd Street,
New York, NY 10036, USA
e-mail: nyadav@sunyopt.edu
objective assessment for several types of visual-field

defects for a range of abnormal visual conditions and
special populations.
Keywords Visual evoked potential (VEP)
VEP amplitude VEP latency Visual fields
Linearity Repeatability
Introduction
Visual-field testing is used to assess the integrity and
functionality of the retinal and early afferent visual
pathways. For example, it is used to detect and monitor
the progression of visual-field loss in a range of ocular
and/or neurological diseases, such as glaucoma,
macular degeneration, retinitis pigmentosa (RP),
acquired brain injury (ABI), Parkinsons disease, and
Alzheimers disease [1, 2]. However, in many cases,
assessment of the visual field is considered to be
unreliable with poor repeatability [3, 4]. In addition, it
is a subjective, time-consuming method. Due to these
potential problems, conventional visual-field testing
has often been called into question. Furthermore,
special populations with cognitive impairment (e.g.,
ABI) frequently have difficulty performing well with
conventional subjective approaches to visual-field
testing [5]. These individuals may not understand the
task and/or remember the instructions. In addition,
they may have limitations due to attentional deficits
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(e.g., in Alzheimers disease, ADHD, and ABI).

Moreover, those having fixational eye movement
deficits cannot maintain accurate central fixation for
a sufficient period of time during visual-field testing
(e.g., 510 min), thus biasing the findings and/or
increasing response variability.
Studies have been conducted to investigate the
important issues of repeatability and reliability of
clinical visual-field testing. Newkirk et al. [3] and Katz
and Sommer [4] assessed visual-field repeatability in
normal individuals and in those with glaucoma using
automated perimetry. They assessed three factors:
false-positive rate, false-negative rate, and the number
of fixational losses. The higher the number, the poorer
was the test repeatability and reliability. These latter
two aspects are essential in the proper diagnosis and
monitoring of the progression of ocular and neurological diseases producing visual-field defects. All three
values were higher than normal limits in both groups,
thus suggesting poor repeatability and lack of good
reliability of the correlated visual-field testing. Katz
and Sommer [4] found unreliable visual fields in 41 %
of the normal and 67 % of glaucomatous patients, all
of which were attributed to fixational problems.
Lastly, in a related study by Asman et al. [6], they
too found that abnormal fixation resulted in increased
difficulty in detecting the visual-field loss, as well as
increased threshold variability.
The visual evoked potential (VEP) method circumvents to a considerable extent all of the above potential
problems involved in conventional visual-field testing.
The conventional VEP test paradigm is an objective,
rapid, repeatable, and non-invasive method to quantify
the integrity and functionality of the retinal and the
early afferent visual-cortical pathways [7, 8]. Furthermore, it provides global real-time information as to the
patients performance (i.e., assessing VEP amplitude
and latency as the averaged responses dynamically
summate over time) for the specific stimulus pattern.
Moreover, the objective VEP information can be used
to correlate with, and corroborate, the conventional
subjective psychophysical results of a clinical visualfield assessment [9].
Several studies have used a high-contrast central
stimulus of progressively increasing size to assess
changes in the VEP response in visually normal
individuals to simulated visual-field defects in the
central field and near retinal periphery. Circular
stimulus field sizes ranged from 1.25 to 15, whereas
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square stimulus field sizes ranged from 2 to 24, with

a full complement of check sizes (680 min arc).
Some of the studies found a nearly linear response
profile [1013], whereas others found a clear nonlinear VEP response profile [14, 15]. Thus, the
findings of these earlier studies were equivocal.
Second, and of critical importance, none of these
studies assessed repeatability in their test populations.
Lastly, effect on response latency was not considered
in any of the investigations.
Several studies have used a central blank field of
progressively increasing size surrounded by a highcontrast checkerboard stimulus to assess changes in
the VEP response in visually normal individuals to
simulated central visual-field defects. Circular blank
field sizes ranged from 1.25 to 15, whereas square
blank field sizes ranged from 2 to 24, with a full
complement of check sizes (680 min arc). Some of
the studies found a nearly linear response profile
[1113, 16], whereas others found a clear non-linear
VEP response profile [14]. Thus, the findings of these
earlier studies were equivocal. Furthermore, only one
study assessed the effect on response latency [16]; it
remained constant for the range of field sizes tested.
Again, and of critical importance, none of these
studies assessed repeatability in their test populations.
Two studies have investigated the effect of simulated hemi-field and quadrant visual-field stimulus
configurations on the VEP response in visually normal
subjects using high-contrast, checkerboard patterns.
Orban and Muller [17] assessed the effect of simulated
hemi-field defects (temporal, nasal) on the VEP
amplitude. For each stimulus configuration, the VEP
amplitudes were lower than the full-field response,
which is expected as these former patterns stimulated
fewer cones and overall retinal area as compared to the
latter condition. They also found that summation of
the individual nasal and temporal hemi-fields amplitude was larger than that found for the full field.
However, they attributed this to an artifact due to
variable fixation on the stimulus border. Lan et al. [18]
compared the VEP amplitude between full-field and
simulated quadrant visual-field defects (lower temporal, lower nasal, upper temporal, and upper nasal). The
full-field response was larger when compared with the
responsivity of the quadrant fields, again as expected.
They found a difference in the VEP amplitude
between the lower and upper quadrant fields: the
lower temporal and nasal field amplitudes were larger
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than the upper temporal and nasal ones. Lan et al. [18]
attributed this response inequality to asymmetry in the
retinal ganglion cell distribution and/or the retinocortical pathway. However, neither of these studies
assessed latency or tested repeatability.
Thus, given the aforementioned critical gaps in
these earlier pioneering experiments, the purpose of
the present study was to assess quantitatively and more
comprehensively the response characteristics, and
repeatability, for a range of electronically generated
stimulus configurations on both the amplitude and
latency of the pattern VEP in visually normal adults.
Stimulus configurations included circular, hemi-field,
and quadrant patterns that simulated visual-field
defects. The goal was to determine the feasibility of
using the VEP technique with these specific stimulus
patterns as a form of objective visual-field testing in
patients having visual-field deficits.
Methods
Subjects
Nine visually normal adults participated in the study
comprising students and faculty at the college. Five
subjects participated in each of the three experiments.
The nine subjects were distributed between the three
experiments as follows: one subject participated in all
three experiments, four subjects participated in experiment # 1 and 3, and the remaining four subjects
participated only in experiment # 2. Subjects had a
mean age of 31.1 years (SD = 14.2), with a range
from 22 to 68 years. They had best corrected visual
acuity of 20/20 at distance and at near in each eye.
Exclusion criteria were the presence of binocular
vision anomalies, such as constant strabismus and
amblyopia, or any ocular, systemic, and/or neurological disease. The study was approved by the institutional review board at the SUNY, State College of
Optometry. Written informed consent was obtained
from all subjects.
presentation and a display monitor for online viewing

by the experimenter, as well as a computer for
stimulus generation and graphical display. This system is available commercially and has been approved
by the FDA. It is used in several pediatric clinics, as
well as adult medical and optometric practices [8, 19].
The stimulus was presented on the 1700 LCD display
monitor with a refresh rate of 75 Hz. Three Grass
(Grass Technologies, Astro-Med, Inc., West Warwick,
RI, USA) gold cup electrodes of 1 cm in diameter (one
active, one reference, and one ground) were used for
the recordings.
Stimulus
A standard full-field 64 9 64 (17 H 9 15 V)
checkerboard pattern (20.6 min arc check size at 1
meter) comprising black-and-white checks was used
as the comparison stimulus for experiment 3, as well
as baseline testing to assess normalcy of response in all
of the experimental conditions (Fig. 1). The patterned
stimuli for all experiments had a Michelson contrast of
85 % and mean luminance of 64 cd/m2. During the
recordings, the checkerboard pattern was modulated at
a temporal frequency of 2 Hz (four reversals per
second) for a 20-s duration. A small (0.25 deg radius),
red, rotating central fixation target was present to
control central fixation and maintain visual attention.
The VEP amplitude and latency were assessed for
each of the three experiments involving different
stimulus configurations:
Experiment 1 The VEP amplitude and latency were
assessed for a central circular stimulus increasing
17o
15o
Apparatus
The Diopsys NOVA-TR system (Diopsys, Inc., Pine
Brook, New Jersey, USA) was used to generate a
checkerboard pattern stimulus and analyze the VEP
data. It consisted of a test monitor for stimulus
Fig. 1 Standard full-field checkerboard pattern stimulus. Not

drawn to scale
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incrementally in diameter from 1 to 15, i.e., 1, 2,

4, 6, 8, 12, 15 (Fig. 2).
assessed for a central circular blank field increasing
incrementally in diameter from 1 to 15, i.e., 1, 2,
4, 6, 8, 12, 15 (Fig. 3).
assessed for simulated hemi-field (right, left) and
quadrant (upper right, upper left, lower right, lower
left) visual-field defects (Fig. 4), which were compared with the standard full-field (17 H 9 15 V)
stimulus (Fig. 1).
Procedures
Electrode placement
The VEP amplitude and latency were recorded from
over the primary visual cortex (V1). The electrode
placement was slightly modified from the International 10/20 system [20], as suggested by the manufacturer. This electrode placement was used to reduce
test preparation time in clinical populations. After
thorough cleaning of the scalp, the central active
channel electrode was placed at the Oz position, which

was 2.5 cm above the inion, the reference electrode
was placed at the Fz position, which was approximately 10 % of the distance from the nasion to inion,
and the ground electrode was placed at the Fp2
position, which was on the right side of the forehead. A
head band was used to keep the electrodes firmly
positioned on the scalp.
Recordings
Each electrode had an impedance of B5 K ohm, per
the standards of the International Society for Clinical
Electrophysiology of Vision (ISCEV) [7]. An amplification factor of 10 K was used to increase the analog
signals. A bandpass filter (0.5100 Hz) was used to
filter any noise. An artifact detector was used to
eliminate artifacts in the EEG signals produced by
such factors as blinks and gaze shifts. Furthermore,
based on our experience with this system, up to five
artifacts were allowed to be present before rejecting
any record; more than five artifacts typically produced
noise and increased variability in the response profile.
In addition, an artificat rejection algorithm was used in
the DIOPSYS system to assess the digitized response
Fig. 2 Central circular stimulus increasing incrementally in diameter from 1 to 15, i.e., 1, 2, 4, 6, 8, 12, 15. Not drawn to scale
Fig. 3 Central blank field

diameter increasing
incrementally from 1 to
15, i.e., 1, 2, 4, 6, 8,
12, 15. Not drawn to scale
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Right visual-field defect
Upper right visual-field defect
Upper left visual-field defect
Left visual-field defect
Lower right visual-field defect
Lower left visual-field defect
Fig. 4 Simulated hemianopic and quadrant visual-field defects. Not drawn to scale
to the stimulus. This algorithm checks the sampled

data to ascertain if the maximum amplitude has been
maintained over consecutive samples during the trial.
Following electrode placement, the subjects were
requested to gaze carefully at the central fixation target
on the monitor positioned at eye level along the
midline. A test distance of 1 m was used. The VEP
measurements were obtained binocularly with refractive correction in place. Testing was performed in a
darkened room (38 lux) with natural pupils. Subjects
were provided 5 min of rest periods between the
different test conditions, as needed.
Two trials per test condition were obtained. Subjects were tested five times for each stimulus
configuration on each of 5 different days in a

counterbalanced manner within each experiment.
The repeatability was performed to assess the VEP
response variability for each stimulus configuration
across subjects and days. The difference between the
VEP amplitude at N75 and at P100 latency (delta) was
used to define the VEP amplitude (Fig. 5). For most
conditions, an automated algorithm developed by
DIOPSYS system was used for response identification. However, for the two smallest stimuli in experiment 1 (i.e., 1 and 2) and 2 (i.e., 12 and 15), where
the peak response amplitude was very small, the cursor
was placed at the N75 and P100 peaks to assess the
amplitude response difference. This method helped to
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Fig. 5 Typical VEP waveform showing amplitude (lV) and latency at N75-P100 (ms) for the standard full-field stimulus. Crosses are
placed at the response peak (P100) and trough (N75). Time scale is 400 ms. Amplitude is autoscaled by the computer software
reduce observer bias regarding peak-to-trough specification, as these standard temporal reference points
were always used. The individual and group mean
VEP amplitudes and latencies for each stimulus
configuration were used for the analysis. Data were
analyzed using GraphPad Prism 5 software.
Results
Experiment 1
The VEP amplitude and latency were assessed for the
central circular stimulus.
VEP amplitude
The results revealed a linear increase in the mean VEP
amplitude with increase in the central circular stimulus
diameter in each of the five subjects (Fig. 6ae). A
similar trend was evident in the group data (Fig. 6f).
Linear regression analysis was used to assess the
slope, which ranged from ?0.56 to ?1.07 across the
five subjects. The mean group slope was ?0.80
0.06 SEM. The correlation coefficient values across the
five subjects ranged from ?0.97 to ?0.99. The group
mean (n = 5) correlation coefficient value was ?0.98.
The correlation was significantly different for each
individual subject and also for the group mean
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(p \ 0.05). Slopes estimated for each subject, as well

as for the group mean, were significantly different from
zero (t test, p \ 0.05). A one-way analysis of variance
(ANOVA) was performed on the group mean for the
factor of stimulus diameter. It revealed a significant
effect of stimulus diameter on the VEP amplitude [F(6,
28) = 16.29, p = 0.0001]; response amplitude progressively increased as the central field stimulus
diameter increased. The post hoc Tukey test results
are summarized in Table 1 for the significant comparisons. Several significant differences were found.
In addition, more detailed analyses were performed
in each subject, for each stimulus configuration and
test session, with respect to VEP amplitude. As
performed on the group and individual data above,
linear regression was used, and the slope values were
assessed. If the slope was statistically equal to zero,
then the values obtained over the five sessions would
of necessity be deemed similar, and hence repeatable.
In contrast, if the slope was not statistically equal to
zero, then the values obtained over the five test
sessions would of necessity be deemed dissimilar, and
hence not repeatable. In all cases for experiment 1, the
slopes were not significantly different from zero
(p [ 0.05).
In addition, a repeated-measures, two-way
ANOVA was performed in each subject for the factors
of stimulus size and test session, in conjunction with
the Bonferroni post hoc test. With regard to the factor
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Subject - 1(S1)
y = 1.076 x + 1.34
r = 0.987
(B)
Mean Amplitude (microvolts)
(A) 25
20
15
10
0
1 2
12
25
Subject - 2 (S2)
r = 0.962
20
15
10
15 FF
1 2
Subject - 3 (S3) y = 1.02 x + 3.57

r = 0.992
(D)
25
20
15
10
0
6
12
25
12
15 FF
Subject - 4 (S4)
y = 0.794 x + 1.01
r = 0.978
20
15
10
15 FF
Subject - 5 (S5)
y = 0.561 x + 1.70
r = 0.977
20
15
10
1 2
12
15 FF
Stimulus Diameter (degrees)
(F)
25
(E)
0
1 2
25
(C)
y = 0.571 x + 2.41
Mean Group (n=5)
y = 0.805 x + 2.00
r = 0.986
20
15
10
0
1 2
12
15 FF

Fig. 6 Experiment 1: Plots ae present increasing stimulus
diameter () versus mean 1 SD VEP amplitude (microvolts)
for subjects S1, S2, S3, S4 and S5, respectively, as well as
1 2
12
15 FF

related linear regressions. Plot f presents the group data
(n = 5) 1 SEM VEP amplitude (microvolts) and related
linear regression. FF represents full field
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Table 1 Experiment 1: post hoc Tukey test significant findings (p \ 0.05 = *) with increase in central stimulus diameter
Experiment 2
Stimulus diameter ()

central blank stimulus.
Stimulus diameter ()
6
12
15
VEP amplitude
The results revealed a linear decrease in the mean VEP
amplitude with increase in central blank field diameter
in each of the five subjects (Fig. 8ae). A similar trend
was evident in the group data (Fig. 8f). Linear
regression analysis was used to assess the slope,
which ranged from -0.92 to -0.59 across the five
subjects. The mean group slope was -0.76 0.05
SEM. The correlation coefficient values across the five
subjects ranged from ?0.92 to ?0.99. The mean group
correlation coefficient value was ?0.98. The correlation was significantly different for each individual
subject and also for the group mean (p \ 0.05). Slopes
estimated for each subject, as well as for the mean
group, were significantly different from zero (t test,
p \ 0.05). A one-way ANOVA was performed on the
mean group for the factor of stimulus diameter. It
revealed a significant effect of stimulus diameter on
the VEP amplitude [F(6, 28) = 40.89, p = 0.0001];
response amplitude progressively decreased as the
blank field stimulus diameter increased. The post hoc
Tukey test results are summarized in Table 3 for the
significant comparisons.
of test session, none of the multiple comparisons were

significant (p [ 0.05). In contrast, with regard to the
factor of stimulus size, all of the multiple comparisons
were significant (p \ 0.05). There was no interaction
(p [ 0.05).
The coefficient of variability (COV = standard
deviation/response mean amplitude) of the VEP
amplitude was calculated for each subject for each
stimulus diameter (Table 2). The results revealed that
the COV decreased as stimulus diameter increased;
the smaller the value, the lesser was the variability.
The group mean range of the COV was from ?16 to
31 %.
Latency (N75-P100)
Figure 7ae presents the latency values at N75 and
P100 (ms) with increase in stimulus diameter in each
of the five subjects. The mean group latency values are
presented in Fig. 7f. A one-way ANOVA was performed for the factor of stimulus diameter. The results
revealed that the group mean latency at N75 [F(6,
28) = 0.99, p = 0.44] and at P100 [F(6, 28) = 1.17,
p = 0.35] was not significantly different for any of the
stimulus diameters.
Table 2 Experiment 1:
coefficient of variability
(COV, %) for the five
subjects with increase in
central stimulus diameter
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Stimulus
diameter
()
Subject 1
COV
Subject 2
COV
Subject 3
COV
Subject 4
COV
Subject 5
COV
Group
Mean
COV
26
23
28
37
40
31
41
29
30
27
17
29
30
20
28
23
22
13
19
19
21
16
12
11
12
23
14
14
12
11
15
16
16
14
14
15
13
15
17
19
16
16
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150
Mean Latency P 100
Subject - 1(S1)
Mean Latency N 75
130
110
90
70
(B)
150
Mean Latency (N 75 - P 100 ms)
(A)
Subject - 2(S2)
Mean Latency N 75
130
110
90
70
50
50
1 2
12
15 FF
1 2
Mean Latency N 75
130
110
90
70
50
1 2
12
(D)
Mean Latency P100
Subject - 3 (S3)
150
12
15 FF
Mean Latency P 100

Mean Latency N 75
Subject - 4(S4)
130
110
90
70
50
1 2
15 FF
12
15 FF
(E)
(F)
150
Mean Latency P 100
Subject - 5(S5)
Mean Latency N 75
130
110
90
70
50
1 2
12
15 FF

Fig. 7 Experiment 1: Plots ae present increasing stimulus
diameter () versus mean 1 SD VEP latency at N 75 and P 100
(ms) for subjects S1, S2, S3, S4 and S5, respectively. Plot
150
(C)
150
Mean Latency P 100
Mean Group (n=5)
Mean Latency P 100

Mean Latency N 75
1 2
12
130
110
90
70
50
4
15 FF

f presents the group data (n = 5) 1 SEM VEP latency at N
75P 100 (ms). FF represents full field
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25
y = - 0.835 x + 18.78
r = 0.983
Subject - 1(S1)
(B)
20
15
10
20
15
10
0
FF 1
12
15
FF
Central Blank Field Diameter (deg.)

25
(D) 25
y = - 0.746 x + 14.84
r = 0.969
Subject - 3(S3)
20
15
10
12
12
15
y = - 0.599 x + 13.76
r = 0.991
15
10
15
FF 1
Subject - 5(S5)
(F)
y = - 0.926 x + 17.78
r = 0.986
20
15
10
12
15
Subject - 4 (S4)

25
Group Mean (n=5) y = - 0.769 x + 16.22

r = 0.987
20
15
10
0
FF 1
12
15

Fig. 8 Experiment 2: Plots ae presents increasing central
blank field diameter () versus mean 1 SD VEP amplitude
(microvolts) for subjects S1, S2, S3, S4 and S5, respectively, as
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0
FF 1
25
20
(E)
(C)
y = - 0.737 x + 15.95
r = 0.927
Subject - 2(S2)
25
(A)
FF
12
15

well as related linear regressions. Plot f presents the group data
(n = 5) 1 SEM VEP amplitude (microvolts) and related
linear regression. FF represents full field
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of necessity be deemed similar and hence repeatable.

(p [ 0.05).
In addition, a repeated-measures, two-way ANOVA
was performed in each subject for the factors of
stimulus size and test session, in conjunction with the
Bonferroni post hoc test. With regard to the factor of
test session, none of the multiple comparisons were
significant (p [ 0.05). In contrast, with regard to the
factor of stimulus size, all of the multiple comparisons
were significant (p \ 0.05). There was no interaction
(p [ 0.05).
The COV of the VEP amplitude was calculated in
each subject for each stimulus diameter (Table 4). The
results revealed that the COV increased as central
blank field diameter increased. The group mean range
of the COV was from ?7 % to ?32 %.
Table 3 Experiment 2: post hoc Tukey test significant findings (p \ 0.05 = *) with increase in central blank field
diameter
Central blank field
diameter ()
1
12
6
8
Table 4 Experiment 2:
coefficient of variability
(COV, %) for the five
subjects with increase in
central blank field diameter
15
Figure 9ae presents the VEP latency values at N75

and P100 (ms) for increasing central blank field
diameter in the individual subjects. The mean group
latency values are shown in Fig. 9f. A one-way
ANOVA was performed for the factor of stimulus
diameter. The results revealed that the group mean
latency at N75 [F(6, 28) = 4.45, p = 0.0028] and at
P100 [F(6, 28) = 5.64, p = 0.0006] was significantly
different for the factor of stimulus diameter. The post
hoc Tukey test results at N75 and P100 (ms) latency
are summarized in Tables 5 and 6 showing the
significant comparisons. Tukey test results revealed
that at N75, the 15 central blank field diameter was
significantly different from the 1, 2, 4, 6, 8
patterns. Similar trends were found for the P100
component, except that the 1 central blank field
diameter was also significantly different from 12.
Experiment 3
simulated hemi-field (right, left) and quadrant (upper
right, upper left, lower right, lower left) visual-field
defects.
VEP amplitude
Central blank field diameter ()

4
Latency (N75-P100)
For the simulated hemi- and quadrant visual-field

defects, the VEP amplitude was greater for the
simulated quadrant than for the hemi-field defect in
each of the five subjects (Fig. 10ae). A similar trend
was evident in the group data (Fig. 10f). A one-way
ANOVA performed on the mean group for the factor
of type of simulated visual-field defect revealed no
Central blank field

diameter ()
Subject 1
COV
Subject 2
COV
Subject 3
COV
Subject 4
COV
Subject 5
COV
Group
Mean
COV
15
20
24
36
55
27
32
12
41
27
42
21
28
32
19
16
50
23
19
25
11
11
17
10
13
12
11
11
10
13
12
10
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150
Mean Latency P 100

Mean Latency N 75
Subject - 1(S1)
130
110
90
70
(B)
(A)
150
130
110
90
70
50
50
FF 1
12
FF 1
15
Mean Latency P 100

Mean Latency N 75
Subject - 3(S3)
130
110
90
70
(D)
150
150
12
15
Mean Latency P 100

Mean Latency N 75
Subject - 4(S4)
130
110
90
70
50
FF 1
50
FF 1
12
15
150
12
15
(F)
Mean Latency P 100
Mean Latency N 75
Subject - 5 (S5)
130
110
90
70
50
150
Mean Latency P 100

Mean Latency N 75
Group Mean (n=5)
130
110
90
70
50
FF 1
12
15

Fig. 9 Experiment 2: Plots ae present increasing central blank
field diameter () versus mean 1 SD VEP latency at N 75 and
P 100 (ms) for subjects S1, S2, S3, S4 and S5, respectively. Plot
123
(E)
(C)
Mean Latency P 100

Mean Latency N 75
Subject - 2(S2)
FF
12
15

f presents the group data (n = 5) 1 SEM VEP latency at N
75P 100 (ms). FF represents full field
Doc Ophthalmol
Table 5 Experiment 2: post hoc Tukey test significant findings (p \ 0.05 = *) for latency at N75 (ms) for increase in
Central blank
field diameter ()
Central blank
field diameter ()
15
2
4
*
*
Table 6 Experiment 2: post hoc Tukey test significant findings (p \ 0.05 = *) for latency at P100 (ms) for increase in
Central blank
field diameter ()
Central blank
field diameter ()

(p [ 0.05).
The mean COV was 15 % for the full field, which
was lower than either the hemi-field (right and
left = 24 and 22 %, respectively) or quadrant (upper
right, upper left, lower right, and lower left = 19, 17,
17, and 19 %, respectively) visual-field defects. The
average effect of these simulated visual-field defects
on the VEP amplitude was assessed, i.e., hemi-field
(right ? left/2) and quadrant field (upper right ?
upper left ? lower right ? lower left/4) (Fig. 11).
T test results revealed that average hemi-field response
was significantly different and smaller than the
average of the quadrant fields responses [t(4) = 3.18,
p = 0.01], and furthermore that the average simulated
hemi-field defect was significantly different from the
full-field findings [t(5) = 2.05, p = 0.04].
12
15
Latency (N75-P100)
Figure 12ae presents the VEP latency at N75 and

P100 (ms) for the simulated hemi- and quadrant
visual-field defects in the individual subjects. The
mean group latency values are presented in Fig. 12f. A
one-way ANOVA was performed for the factor of type
of simulated visual-field defect. The results revealed
that the mean latency at N75 [F(6, 28) = 0.06,
p = 0.99] and at P100 [F(6, 28) = 0.27, p = 0.94]
was not significantly different for any of the simulated
field defects.
2
4
*
*
significant effect on the VEP amplitude [F(6,

28) = 2.31, p = 0.06], although a trend was suggested. A one-way ANOVA performed on the mean
group for the factor of the quadrant only simulated
visual-field defect (upper right, upper left, lower right,
and lower left) revealed no significant effect on VEP
amplitude [F(3, 16) = 0.20, p = 0.89]. The COV of
the VEP amplitude was calculated in each subject for
each hemi- and quadrant-simulated visual-field defect
(Table 7).
of necessity be deemed similar, and hence repeatable.
Discussion
The results of the present study have demonstrated a
relatively linear VEP response profile to changes in
test target diameter for both the central circular and the
central blank fields. Some of the earlier studies found
either a nearly linear or clear non-linear response
profile with either of the aforementioned stimulus
configurations. However, some of these earlier studies
plotted the VEP response amplitude profile in relation
to its stimulus area (cm2), rather than its stimulus
diameter (cm) [10, 14, 15] as was done in the present
investigation. Thus, a non-linear response profile
might in fact be expected in these earlier area-based
studies. Rover et al. [15] stated that due to the nonlinear VEP response they found with increase in
stimulus area, it would not be possible to conceptualize
123
Doc Ophthalmol
25
(B)
Subject - 1(S1)
(A)
20
15
10
25
Subject - 2(S2)
20
15
10
0
RH
LH
LUQ
RUQ
LUQ
RUQ
RH
FF
30
(D)
Subject - 3(S3)
(C)
25
20
15
10
5
0
25
LH
LUQ RUQ LLQ RLQ
RUQ
FF
15
10
RH
LH
LUQ
RUQ
LLQ
RLQ
FF
Simulated Field Defects

25
Mean Group (n=5)
Subject - 5(S5)
LUQ
20
FF
(F)
20
15
10
20
15
10
0
RH
LH
LUQ
RUQ
LLQ
RLQ
FF

Fig. 10 Experiment 3: Plots ae present simulated visual field
defects versus mean 1 SD VEP amplitude (microvolts) for
subjects S1, S2, S3, S4 and S5, respectively. Plot f presents the
group data (n = 5) 1 SEM VEP amplitude in microvolts. RH,
123
RUQ
Subject - 4(S4)

25
LUQ
RH
(E)
LH
RH
LH
LUQ
RUQ
LLQ
RLQ
FF

LH, LUQ, RUQ, LLQ, RLQ, and FF represent right hemi-field,
left hemi-field, left upper quadrant, right upper quadrant, left
lower quadrant, right lower quadrant, and full field, respectively
Doc Ophthalmol
Table 7 Experiment 3: coefficient of variability (COV, %) for the five subjects with simulated hemi and quadrant visual field
Field defects
Subject 1
COV
Subject 2
COV
Subject 3
COV
Subject 4
COV
Subject 5
COV
Group
Mean
COV
Right hemi-field
25
22
26
15
33
24
Left hemi-field
15
21
37
15
23
22
LUQ
19
11
22
18
25
19
RUQ
18
32
18
11
17
LLQ
28
15
17
16
17
RLQ
Full field
21
21
35
12
19
10
14
19
11
20
15
Half-field
25
Quadrant-field
Full-field
20
15
10
0
Half-field
Quadrant-field
Full-field
Visual-Field Test Condition

Fig. 11 Visual-field test condition versus mean response
amplitude in microvolts. Plotted is the mean ?1 SEM (n = 5)
and develop the VEP as an objective clinical screening

test to detect visual-field defects in ocular disease
conditions; it would be too complicated for all but the
research environment. Linearity of the VEP response
found in the present study as assessed and compared
statistically using the parameters of stimulus diameter
per se, however, provides a way by which the VEP
method can be more readily and easily adapted
clinically to assess visual-field defects in individual
patients. For example, in a patient having only a small
central region (e.g., 8 diameter) of healthy retina, the
initial linear VEP response profile would begin to
exhibit a non-linear, saturation-like effect, and
hence to flatten, as the VEP stimulus exceeded
this diameter (see later, Discussion). Thus, as used in
the present study, VEP may provide an important
objective means of assessing the degree and type of

visual-field defects in the future in specific ocular
disease conditions, such as glaucoma, macular degeneration, and RP, especially when there is conventional
visual-field test uncertainty and/or conflicting results.
In the present study, the correlation coefficient
values were preliminarily assessed using both linear
and exponential fits. The linear fit always provided a
slightly higher correlation than the exponential fit
(e.g., 0.992 vs. 0.953). Therefore, the linear fit
provided a better mathematical description of the
overall response function, at least up to the retinal
eccentricity tested in the present study. If one were to
test further in the retinal periphery, it is likely that the
exponential fit would be equal or perhaps even better.
However, despite the best fit statistically being linear
in nature, the data profile suggests some degree of
response non-linearity prior to the maximum stimulus
diameter tested of 15. Thus, it is especially important
for the clinician to exercise caution in using the
proposed protocol to assess the presence and/or degree
of peripheral visual field impairment in a patient with
respect to its departure from the 1:1 line. There are
possible three scenarios as shown in Fig. 13: first, in
the patient not having any visual field defect, the
predicted response will lie within the gray region, that
is, below the 1:1 line. Second, and in contrast, in the
case of a patient with an absolute scotoma, the change
in response over the affected visual field region will
effectively be zero, thus reflecting complete/full
(hard) response saturation. Third, in the case of a
patient with a relative scotoma, the change in response
over the affected visual field region will be present, but
reduced as compared to a normal patient, thus
reflecting partial (soft) response saturation. It is in
this last scenario that the clinician must be especially
123
Doc Ophthalmol
(A)
(B)
Mean Latency P 100
Subject - 1(S1)
Mean Latency N 75
140
130
120
110
100
90
80
70
60
150
150
Subject - 2(S2)
130
120
110
100
90
80
70
60
50
50
RH
LH
LUQ
RUQ
LLQ
RLQ
RH
FF
Mean Latency P 100

Mean Latency N 75
140
130
120
110
100
90
80
70
60
50
RH
LH
LUQ
RUQ
LLQ
RLQ
150
Subject - 4(S4)
130
120
110
100
90
80
70
60
50
RH
FF
(F)
Subject - 5(S5)
Mean Latency P 100

Mean Latency N 75
140
130
120
110
100
90
80
70
60
LUQD RUQD LLQD RLQD
FF
150
Mean Latency P 100

Mean Latency N 75
Group mean (n=5)
140
130
120
110
100
90
80
70
60
50
50
RH
LH
LUQ
RUQ
LLQ
RLQ
123
LH

150
Mean Latency P 100

Mean Latency N 75
140
(E)
FF
(D)
Subject - 3(S3)
150
LH LUQD RUQD LLQD RLQD
(C)
Mean Latency P 100

Mean Latency N 75
140
FF
RH
LH
LUQ
RUQ
LLQ
RLQ
FF
Doc Ophthalmol
defects versus mean 1 SD VEP latency at N 75 and P 100 in

milliseconds (ms) for subjects S1, S2, S3, S4 and S5,
respectively. Plot f presents the group data (n = 5) 1 SEM
VEP latency at N 75 and P 100 in milliseconds (ms). RH, LH,
LUQ, RUQ, LLQ, RLQ, and FF represent right hemi-field, left
hemi-field, left upper quadrant, right upper quadrant, left lower
quadrant, right lower quadrant and full field, respectively
Total Increase in Cumulative Cone

2
Number (x1000/mm )
b Fig. 12 Experiment 3: Plots ae present simulated visual field
y = 5.99x + 193
300
r 2 = 0.913
r = 0.955
250
200
150
0
10
15
Fig. 14 Relationship between total cumulative increase in cone

number (X 1,000/mm2) and mean VEP amplitude (microvolts)
with increase in stimulus diameter
Fig. 13 Plot schematically representing the three possible

response profiles (normal, partial saturation, and complete
saturation) for stimulus diameter () and relative amplitude per
experiment 1, along with the 1:1 line
astute and observant: a small and normal partial

saturation response must be differentiated from cases
of slightly greater but abnormal partial saturation. It
may require additional test repetitions to segregate
these two latter ensemble responses.
The relatively linear VEP response profile was
likely due to the cumulative change in total cone
number (i.e., the integration/summation in total cone
number with changes in test stimulus area) with
increase in either the central circular or the central
blank field diameter stimulation, respectively, at least
for the range of retinal eccentricities tested. This is
suggested by the significant correlation presented in
Fig. 14 between these two parameters. To construct
this graph, the mean VEP amplitude for each eccentricity tested in Experiment 1 was plotted against the
total increase in cumulative cone number. For example, in Experiment 1, the VEP amplitude progressively
and significantly increased with increase in cumulative mean cone number (r = 0.95) per Osterbergs
[21] human retinal topographic findings. It accounted
for over 90 % of the variance. This relationship also

confirms that the VEP is a cone-mediated response.
Furthermore, the present finding is consistent with the
speculation of Meredith and Celesia [22], namely that
the VEP amplitude is related to the density of the
retinal cone photoreceptors.
None of the earlier studies assessed repeatability of
the VEP response, which includes both amplitude and
latency, for the present array of different stimulus
configurations. The results of the present study
revealed that the VEP linear response was highly
repeatable for the simulated circular, hemi-field, and
quadrant visual-field defects in each subject. The COV
values for the different stimulus configurations provided additional evidence regarding repeatability of
the VEP amplitude responsivity and resultant overall
profile, as these values were consistently relatively
low [8]. Similarly, the VEP latency (N75-P100 ms)
values remained relatively constant for nearly all of
the stimulus configurations, with the exception of the
12 and 15 central blank field diameters, which
revealed increased latency. This finding may be due to
the lower signal-to-noise ratio when the aggregate
cone stimulation was minimal with those very peripheral-only stimuli. The notion of high repeatability, in
conjunction with the aforementioned finding of relatively good linearity, support the concept of using the
VEP as an objective indicator of visual-field dysfunction, as has been suggested and tested to some degree
in earlier studies [9, 2329].
123
Doc Ophthalmol
There was response differentiation for the hemianopic and quadrant stimulus configurations when
compared with the standard full-field stimulus. The
VEP amplitude was lower for the simulated hemianopic defect as compared to the simulated quadrant
defect and the full-field stimulus, as would be
expected due to reduced area of overall cone stimulation. Thus, the results of the present study revealed
that the conventional VEP may be a feasible objective
future tool to assess hemi- and quadrant visual-field
defects in different ocular and neurological conditions
in individual patients.
The question of possible luminance effects on the
data is both interesting and important. There were no
luminance changes/compensations made to the various stimulus patterns used during testing in the present
experiment. The blank areas had very low luminance
(1.27 cd/m2). This was purposely done to best simulate that which would be found in a clinic patient, for
example, a patient with dense hemianopia (i.e.,
absolute scotoma as frequently found in stroke). Thus,
while the overall retinal luminance would be different
when averaged over the entire 15V 9 17H region of
the retina (as well as the stimulus display), it would not
change for the local retinal region under investigation
and being tested. For example, in Experiment 3 using
the hemianopic configuration, 50 % of the test field
would have very low luminance, whereas the other
50 % would have the specified luminance of 64 cd/m2.
Thus, the average luminance combined over the two
half-field would be approximately 32 cd/m2, with 0.3
log unit difference. In the only study directly relevant
to the present investigation [30], VEP amplitude and
latency were assessed under two relatively extreme
luminance conditions: 55 cd/m2 and 0.76 cd/m2, a
1.86 log unit difference. They found an average
reduction in amplitude (but not latency) of approximately 35 % under the lower luminance condition as
compared with the higher one. However, both the
average (32 cd/m2) and local (64 cd/m2) luminance levels used in the present investigation were
much less extreme and similar to each other, as
compared to the two levels used by Brannan et al. [30].
Lastly, we performed five VEP repetitions on one
experienced subject used in the present study monocularly, using our standard full-field array with and
without a 0.3-ND filter, which reduced the stimulus
luminance by 50 %. There was no significant change
in the VEP amplitude. Thus, based on the above
123
information, we believe that any possible changes in

test field luminance did not have an effect on the data.
There have been several previous studies which in
fact have used the VEP technique to assess visual-field
defects objectively for a limited range of stimuli [23,
2527, 3133]. However, most used a focal flash
stimulus rather than the pattern reversal approach
[3133]. The latter is more effective in detecting
visual-field defects [23, 2527]. Furthermore, results
of many of these earlier studies were limited by the
techniques used to measure the VEP amplitude, which
resulted in lower signal-to-noise ratios and longer test
times [3133]. Therefore, Bradnam et al. [9] performed an investigation which attempted to overcome
these two limitations. They used an adaptive noise
canceling method to measure the VEP response, and a
test duration of only 2 min. Nine patients with hemiand quadrant visual field defects due to different
pathological conditions were assessed using the
pattern VEP (check size = 90 min of arc, temporal
frequency = 3.85 Hz, contrast = 99 %, luminance =
20 cd/m2). Bradnam et al. [9] confirmed the presence
of visual-field defects using the objective VEP technique, as well as corroborated the findings with
subjective perimetry, which were in reasonable agreement. In addition, the results and concepts put forth in
the present study regarding use of the VEP method to
detect visual-field defects are consistent with a series
of studies performed by the Harding group in clinical
populations [3437]. They found that the VEP technique provided reliable results in both children and
adults with epilepsy. Lastly, increased use of the
multifocal VEP (mfVEP) technique in the future
should further help to improve resolution and specificity of visual-field dysfunction in these populations
[38, 39], perhaps in conjunction with conventional
visual field testing and/or the objective VEP approach
described in the present paper.
We are enthusiastic about the potential use of the
VEP to assess visual field dysfunctions in a range of
diagnostic groups. However, special consideration
may need to be exercised at times. First, all testing in
the present experiments was performed binocularly,
with binocular summation resulting in a 26 % increase
in amplitude over that found monocularly [40]. Since
most of the clinical testing for which the proposed
stimulus configurations will be employed will be
performed with monocular testing of each eye,
the resultant reduced VEP amplitude will make
Doc Ophthalmol
differentiation for the various test fields somewhat

more difficult. Thus, more trials may be needed to
make a differential diagnosis. Second, in patients with
fixational abnormalities (e.g., saccadic intrusions),
more trials may be required to obtain reliable
responses. Third, in cases where the visual field defect
may be relatively mild in the retinal periphery, addition
test repetitions may be required to differentiate
between normal and abnormal partial response
saturation effects.
7.
8.
9.
10.
Conclusions
The results of the present study presented several new
and important results. First, response linearity was a
consistent finding, which was equivocal in the previous studies. Second, repeatability was found, which
has never been so comprehensively tested in the past.
Third, such a wide array of stimulus configurations has
not been tested in the same visually normal population.
These findings pave the way for increased clinical
utility of the VEP and the suggested stimulus patterns,
especially as a rapid and new tool for objective
assessment of visual-field dysfunction for a range of
abnormal visual conditions and special populations
(e.g., young children, cognitively impaired) in the near
future.
Acknowledgments We thank DIOPSYS Inc., Pine Brook,
New Jersey, USA for providing the test system.
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Effect of Different Stimulus Configurations On The Visual Evoked Potential

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Effect of Different Stimulus Configurations On The Visual Evoked Potential

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ORIGINAL RESEARCH ARTICLE

Effect of different stimulus configurations on the visual

Received: 15 August 2011 / Accepted: 2 March 2012

Abstract The purpose of this study was to assess

N. K. Yadav (&) D. P. Ludlam K. J. Ciuffreda

objective assessment for several types of visual-field

(e.g., in Alzheimers disease, ADHD, and ABI).

square stimulus field sizes ranged from 2 to 24, with

presentation and a display monitor for online viewing

Fig. 1 Standard full-field checkerboard pattern stimulus. Not

incrementally in diameter from 1 to 15, i.e., 1, 2,

channel electrode was placed at the Oz position, which

Fig. 3 Central blank field

Right visual-field defect

Upper right visual-field defect

Upper left visual-field defect

Left visual-field defect

Lower right visual-field defect

Lower left visual-field defect

to the stimulus. This algorithm checks the sampled

configuration on each of 5 different days in a

(p \ 0.05). Slopes estimated for each subject, as well

Mean Amplitude (microvolts)

Subject - 3 (S3) y = 1.02 x + 3.57

Mean Amplitude (microvolts)

Stimulus Diameter (degrees)

Mean Amplitude (microvolts)

Stimulus Diameter (degrees)

Stimulus Diameter (degrees)

Stimulus Diameter (degrees)

Mean Group (n=5)

Stimulus Diameter (degrees)

Stimulus Diameter (degrees)

The VEP amplitude and latency were assessed for the

of test session, none of the multiple comparisons were

Mean Latency P 100

Mean Latency (N 75 - P 100 ms)

Mean Latency (N 75 - P 100 ms)

Stimulus Diameter (degrees)

Mean Latency (N 75 - P 100 ms)

Mean Latency P100

Mean Latency P 100

Stimulus Diameter (degrees)

Stimulus Diameter (degrees)

Mean Latency P 100

Stimulus Diameter (degrees)

Mean Latency (N 75 - P 100 ms)

Mean Latency (N 75 - P 100 ms)

Stimulus Diameter (degrees)

Mean Latency P 100

Mean Group (n=5)

Mean Latency P 100

Stimulus Diameter (degrees)

Central Blank Field Diameter (deg.)

Central Blank Field Diameter (deg.)

Mean Amplitude (microvolts)

Mean Amplitude (microvolts)

Central Blank Field Diameter (deg.)

Group Mean (n=5) y = - 0.769 x + 16.22

Central Blank Field Diameter (deg.)

Central Blank Field Diameter (deg.)

Mean Amplitude (microvolts)