Hemispheric asymmetry of visual cortical response by means of functional transcranial Doppler.

Abstract

We assessed the visual evoked response and investigated side-to-side differences in mean blood flow velocities (MBFVs) by means of functional transcranial Doppler (fTCD) in 49 right-handed patients with severe internal carotid artery (ICA) stenosis and 30 healthy volunteers, simultaneously in both posterior cerebral arteries (PCAs) using 2 MHz probes, successively in the dark and during the white light stimulation. Statistically significant correlation (P = 0.001) was shown in healthy and in patients (P < 0.05) between MBFV in right PCA in physiological conditions and MBFV in right PCA during the white light stimulation and in the dark. The correlation between MBVF in right PCA and contralateral left PCA was not statistically significant (P > 0.05). The correlation between ipsilateral left PCA was significantly higher than the one with contralateral right PCA (P < 0.05). There is a clear trend towards the lateralisation of the visual evoked response in the right PCA.

Full text

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Hindawi Publishing Corporation
Stroke Research and Treatment
Volume 2012, Article ID 615406, 5 pages
doi:10.1155/2012/615406
Clinical Study
HemisphericAsymmetryof Visual CorticalResponseby Means of
FunctionalTranscranialDoppler
MarinaRoje-Bedekovi´ c, ArijanaLovrenˇ ci´ c-Huzjan,
MarijanaBosnar-Pureti´ c,VesnaˇSeri´ c,andVidaDemarin
University Department of Neurology, Sestre milosrdnice University Hospital, Vinogradska cesta 29, 10 000 Zagreb, Croatia
Correspondence should be addressed to Marina Roje-Bedekovi´ c, mroje@mef.hr
Received 8 June 2011; Revised 30 July 2011; Accepted 21 September 2011
Academic Editor: Carlos A. Molina
Copyright © 2012 Marina Roje-Bedekovi´ c et al.ThisisanopenaccessarticledistributedundertheCreativeCommonsAttribution
License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly
cited.
We assessed the visual evoked response and investigated side-to-side differences in mean blood flow velocities (MBFVs) by means
of functional transcranial Doppler (fTCD) in 49 right-handed patients with severe internal carotid artery (ICA) stenosis and 30
healthy volunteers, simultaneously in both posterior cerebral arteries (PCAs) using 2MHz probes, successively in the dark and
during the white light stimulation. Statistically significant correlation (P = 0.001) was shown in healthy and in patients (P < 0.05)
between MBFV in right PCA in physiological conditions and MBFV in right PCA during the white light stimulation and in the
dark. The correlation between MBVF in right PCA and contralateral left PCA was not statistically significant (P > 0.05). The
correlation between ipsilateral left PCA was significantly higher than the one with contralateral right PCA (P < 0.05). There is a
clear trend towards the lateralisation of the visual evoked response in the right PCA.
1.Introduction
Functional transcranial Doppler (fTCD) studies indicated
that simultaneous bilateral stimulation during a different
visual tasks caused greater blood flow velocities in right
hemisphere in healthy individuals, indicating that it may
identify visual hemispheric dominance [1, 2]. Results of the
studies testing the posterior cerebral circulation using visual
stimuli in patients with severe carotid stenosis and consec-
utively compromised anterior cerebral circulation suggest
the existence of an independent cerebral vascular reserve
capacityoftheposteriorpartofWilliscircle[3–7].Undoubt-
edly, collateral variations in circle of Willis have to be taken
into consideration since they are highly variable [8]. In
patients with carotid occlusive disease collateral flow from
posterior to anterior circulation could be through the pos-
terior communicating artery or via the leptomeningeal col-
laterals. In the first case, the blood flow in the vertebrobasilar
arterysystemisshuntedintotheanteriorcerebralcirculation
before the P2 segment branches leading to a decrease in
the P2 flow velocities, and in the latter it is shunted through
the P2 branch into the leptomeningeal collaterals leading to
an increase resting blood flow velocity in the P2 [9, 10].
Theaimofthisstudywastoassessvisualevokedresponse
in PCA in patients with severe carotid stenosis and com-
promised anterior cerebral circulation, as the most powerful
and fully noninvasive test of cerebral autoregulation, in
vascular territory mostly supplied by posterior circulation,
in order to investigate if flow through the circle of Willis
might result in changes in the blood flow distribution in
the PCA territory. Also, the aim was to investigate side-
to-side differences of simultaneously measured PCAs blood
flow velocities during white light stimulation in patients
with severe carotid disease, in order to establish a possible
functional hemispheric asymmetry of the visual cortex in
patients.
2.Methodology
The study cohort consisted of 49 right-handed patients
(mean age ± SD = 67 ± 8; 37 men), with no eye abnor-

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Table 1: Mean blood flow velocities in posterior cerebral artery at
baseline.
Mean blood flow velocities in posterior cerebral artery (cm/s ±
2SD) at baseline (eyes opened)
Patients
(n = 49)
29.08 ±10.46 25.8 ±7.32
28.65 ±9.58
Healthy
(n = 30)
P
PCA at
baseline
right
left
0.14
0.2125.93 ±8.67
cm/s: centimeters in second.
n: number of patients/healthy subjects.
PCA: posterior cerebral artery.
SD: standard deviation.
malities, with high-grade (70–99%) symptomatic or asymp-
tomatic ICA stenosis (20 right and 19 left ICAs) as measured
by Doppler ultrasonography and 30 healthy volunteers
(mean age ± SD = 67 ± 7; 22 men) with normal ICAs.
The two groups were matched in age (P = 0.91) and sex
(P = 0.52). For the comparison, in the group of healthy
individuals, the proportion of the left and right ICA was
matched to the proportion of left and right ICA in the group
of patients with severe carotid stenosis.
Exclusioncriteriawerelimitedultrasoundtemporalbone
window,detectablestenosisorocclusionofanyofthearteries
of the Willis circle or vertebrobasilar circle by means of TCD,
uncooperative patients (dementia, coma, etc.), heart disease
(atrial fibrillation, myocardial infarction, patent foramen
ovale, atrial septum aneurysm, and mitral valve prolapse),
uncontrolled hypertension, diabetes mellitus, and migraine.
In all patients, the risk factors were under control for
at least one year before the study was performed. None
of the patients used vasoactive medications. Patients had
abstained from alcohol, caffeinated beverages, and smoking,
aswellascertaindrugsthatmayalterbloodpressureorcause
vasodilatation (nitrates, β-blocking agents, calcium channel
blockers, anticoagulants, and vasodilatatory agents) for at
least 24 hours prior to the study.
Carotid artery disease was assessed and defined using
the carotid color Doppler flow imaging (CDFI) and power
Doppler imaging (PDI) according to validated criteria [11].
The intracranial arteries were evaluated by TCD according to
validated criteria [12]. Visual evoked response was obtained
by means of TCD (MultiDop X4 DWL, Elektronische
Systeme GmbH, Sipplingen) using a special application
for evoked flow. It included transtemporal simultaneous
insonationofP1orproximalpartofP2segmentiftheP1was
not able to insonate, of both PCAs while obtaining the signal
away from the probe at the depth of 60–70mm using two
2MHz probes mounted on an individually fitted head band.
The test was performed while patient in a supine position,
in a dark, quiet room, after an accommodation period
of resting and closed eyes for 10 minutes. For the visual
stimuli, a 100W electric bulb was used, located 50cm in
front of the head of the examinee. After the accommodation
period, mean blood flow velocities (MBFVs) in each PCA
were measured, in a dark (closed eyes) and during a
white light stimulation (opened eyes, looking at an electric
bulb). The measurements were performed successively in the
dark and during the white light stimulation, during three
Table 2: Mean blood flow velocities in posterior cerebral artery
during the white light stimulation and in the dark in the group of
healthy subjects.
Mean blood flow velocities in posterior cerebral artery (cm/s ±
2SD)
LightDark
Healthy
(n = 30)
cm/s: centimeters in second.
n: number of healthy subjects.
PCA: posterior cerebral artery.
SD: standard deviation.
Right PCA
Left PCA
29.99 ±9.5
30.56 ±8.34
20.12 ±8.33
21.40 ±7.32
consecutive repetitive periods of 1 minute each. Mean values
of MBFV during a one-minute period with and without
visual stimuli were analyzed. Before the testing, all the
subjects were introduced to the testing method and the
testing measurements were performed before the study mea-
surements in order to establish which subjects were suitable
for the study.
Institutional Ethical Committee approved the study. All
patients signed informed consent.
For statistical analyses, we used statistical program pack-
age Statistica for Windows, Kernel release (5.5) A (StatSoft,
Inc. Tulsa, OK) (StatSoft, Inc. (2000); statistics for Windows
(Computer program manual). Tulsa, OK: StatSoft, Inc.
We used paired Student t-test to compare quantitative
variables between the two groups, t-test for dependent vari-
ables to compare values of repetitive measurements within
the same group and linear regression analyses to analyze
the correlation of quantitative variables.
From nonparametric statistics model, we used Pearson
chi-square test to compare a distribution of qualitative
characteristics of the group. Results with P-values of <0.05
were considered statistically significant.
3.Results
Regarding the symptomatic status, 9 of 49 patients were
symptomatic, at least one year or more before the study was
performed. Concerning the presence and functionality of
the collateral cerebral circulation by TCD before testing for
vasomotor reactivity, the patient’s statuses were as follows:
5 patients had anterior collateral pathway, 17 patients had
developed collateral flow through the ophthalmic arteries
(2 of them were symptomatic), and 4 patients had developed
both anterior collateral pathway and collateral pathway
through the ophthalmic artery (2 of them were symp-
tomatic). With regard to vascular risk factors, 30 patients
had no vascular risk factors, 18 patients had arterial hyper-
tension, 10 had cardiomyopathy, 4 had diabetes mellitus,
6 hypercholesterolaemia, 2 patients were cigarette smokers,
and 1 patient was an alcohol abuser.
There was no difference at baseline between right PCAs
(P = 0.14; Student t-test) and left PCAs (P = 0.21; Student
t-test) between healthy and patients (Table 1).
Table 2 displays the difference in MBFV between dark
and white light stimulation in the group of healthy subjects.

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Table 3: Mean blood flow velocities in posterior cerebral artery during the white light stimulation and in the dark in the group of patients
with severe carotid stenosis.
Mean blood flow velocities in posterior cerebral artery (cm/s ± 2SD)
Light Dark
Patients with severe carotid stenosis (n = 49)
Right PCA
Left PCA
29.88 ±8.6
32.6 ±11.49
21.32 ± 7.08
21.40 ± 7.32
cm/s: centimeters in second.
n: number of patients.
PCA: posterior cerebral artery.
SD: standard deviation.
Table 4: Correlation between internal carotid artery stenosis and mean blood flow velocities in posterior cerebral artery.
Mean blood flow velocities in posterior cerebral artery (cm/s)
Light
Left PCA
0.0546, P = 0.710
−0.008, P = 0.955
Dark
Patients (n = 49)
Stenosis
Right PCA
0.1891, P = 0.193
−0.1092, P = 0.455
Right PCA
0.2009, P = 0.166
−0.072, P = 0.622
Left PCA
0.1349, P = 0.355
−0.0390, P = 0.790
Right ICA
Reft ICA
cm/s: centimeters in second.
n: number of patients.
ICA: internal carotid artery.
PCA: posterior cerebral artery.
MBFV during the white light stimulation and in the dark
in the group of patients with severe carotid stenosis are
displayed in Table 3.
Linear regression analysis showed no statistically signif-
icant correlation between the degree of right ICA stenosis
and MBFV either in any PCA in the dark and during a light
stimulation (Table 4), but there was a trend of negative cor-
relation between the degree of left ICA stenosis and MBFV
both in contralateral PCA as well as in ipsilateral PCA, but
with no statistical significance (Table 4).
In the same time, significant correlation (P = 0.001)
of the measured parameters both during the white light
stimulation and in the dark, regardless of the side of the
measurement, was found in the group of healthy individuals
(Table 5).
In the group of patients with severe carotid stenosis,
correlation between MBFV in left and right PCA at baseline
and MBFV in left and right PCA during the white light
stimulation and in the dark showed statistically significant
correlation (linear regression analyses; P < 0.05) between
MBFV in right PCA at baseline and MBFV in right PCA
during the white light stimulation and in the dark (Table 6).
On the contrary, correlation between MBFV in right PCA at
baseline and contralateral PCA either during the white light
stimulation or in the dark was not statistically significant
(linear regression analyses; P > 0.05) (Table 6). The results
showed the higher flow response under various conditions in
the right PCA compared to the left one.
Analyzing the correlation between MBFV in left PCA
at baseline conditions, statistically significant correlation
between MBFV in both ipsilateral and contralateral PCA,
both during the white light stimulation and in the dark,
was found, but the correlation with ipsilateral side was
significantly higher than with contralateral side (linear
regression analyses; P < 0.05) (Table 6).
Considering the small number of symptomatic patients,
which is not suitable for statistical analyses, and the fact that
theyhadsymptomsatleastoneyearormorebeforethestudy
was performed, we did not find it suitable to separate the
results by symptomatic status. Additionally, the number of
symptomatic patients was too small to be suitable for sepa-
rate analyses regarding the presence and functionality of the
collateral cerebral circulation.
4.Discussion
We found no statistical difference in MBFV at baseline
conditions between right and left PCAs between healthy
subjects and patients. According to our results, a degree of
ICA stenosis does not influence the MBFV in ipsilateral nor
in contralateral PCA, showing that visual evoked response
of the PCA remains similar both on the stenosed and the
unstenosed side of ICAs in the case of more pronounced
metabolic demands of the region and that the degree of ICA
stenosis has no impact, or only exceptionally, on the collat-
eralizing capacity of the PCAs. Those results that are in con-
cordancewiththeresultsofthepreviousstudiesdemonstrate
an independent cerebral posterior circulation mechanism
that compensates very successfully the anterior circulation
insufficiency in severe carotid disease [3–7]. Concerning the
correlation of the ICA stenosis, one of the limitations of our
study was limited number of patients. Another limitation
is that the ICA stenosis might serve as an indicator of
vascular risk since it was shown that patients with increased
risk factors have decreased hemodynamic response due to
functional activation [13]. Our results show that our group
ofpatientswithseverecarotidstenosishadthesameresponse
as healthy volunteers suggesting that carotid stenosis have no
or only little impact on PCA flow velocities during various

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Table 5: Correlation between mean blood flow velocities in physiological conditions and mean blood flow velocities during the white light
stimulation and in the dark in healthy subjects.
Healthy (n = 30)
LightDark
Mean blood flow velocities in posterior cerebral artery (cm/s)
Right
0.8812,
P = 0.001∗
0.7556,
P = 0.001∗
Left
0.7035,
P = 0.001∗
0.9235,
P = 0.001∗
Right
0.8459,
P = 0.001∗
0.7553,
P = 0.001∗
Left
0.6690,
P = 0.001∗
0.9450,
P = 0.001∗
Baseline(eyes
opened)
Right
Left
n: number of healthy subjects.
cm/s: centimeters in second.
∗statistically significant.
Table 6: Correlation between mean blood flow velocities in physiological conditions and mean blood flow velocities during the white light
stimulation and in the dark in severe carotid disease patients.
Pateints with severe carotid disease (n = 49)
LightDark
Mean blood flow velocities in posterior cerebral artery (cm/s)
Right
0.7953,
P = 0.001∗
0.4463,
P = 0.001∗
Left
0.2421,
P = 0.094
0.6851,
P = 0.001∗
Right
0.7589,
P = 0.001∗
0.3384,
p = 0.017∗
Left
0.2125,
P = 0.143
0.6944,
P =
0.001∗
Baseline(eyes
opened)
Right
Left
n: number of patients.
cm/s: centimeters in second.
∗statistically significant.
stimulation conditions suggesting an independent cerebral
vascular reserve capacity of the posterior part of Willis circle.
Since the primary and associative visual areas located in
the occipital lobes receive blood supply almost exclusively
from the PCAs [14], every change in arterial blood flow due
to differences in the metabolism of the visual cortex neurons
is expected to have reflection on arterial blood flow in PCAs.
Therefore, changes in blood flow in PCAs could indirectly
reflect changes in metabolism of the visual cortex [15].
Although different authors used different methods and dif-
ferent kind of visual stimulation, making direct comparison
quitedifficult,previousfTCDstudieshaveprovidedconverg-
ing support for the view that visual stimulation might cause
a greater activation of the visual cortex in right occipital
lobe [16–22]. These studies on hemispheric asymmetry of
the visual cortex were done on healthy subjects, raising ques-
tionsaboutthepotentialimpactofpathologyontheresearch
findings. In the present study, we, therefore, used fTCD
to investigate hemispheric asymmetries of the visual cortex
in patients with severe carotid stenosis and compromised
anterior cerebral circulation, considering the importance
of posterior collateral pathway via PCA. In the group of
healthy subjects, we recorded statistically significant differ-
ence between MBFV in left and right PCA at baseline and
MBFV in both PCAs during the white light stimulation
and in the dark, regardless of the side of the measurement
(P = 0.001). In the group of severe carotid disease patients,
statistically significant correlation between MBFV in right
PCA at baseline and MBFV in right PCA during the
white light stimulation and in the dark was also found.
On the contrary, correlation between MBVF in right PCA
at baseline conditions and contralateral left PCA either
during the white light stimulation or in the dark was not
statistically significant. Moreover, analyzing the correlation
betweenMBFVinleftPCAatbaseline,statisticallysignificant
correlation between MBFV in ipsilateral left PCA, as well as
contralateral right PCA was found, both during the white
lightstimulationandinthedark,butthecorrelationbetween
ipsilateral left side was significantly higher than the one with
contralateralright side.Followingourresults,thecorrelation
of MBFV with functional reserve capacity is more evident
in the healthy subjects while the right-sided lateralization
of the evoked responses more pronounced in the patients.
Furthermore, the lateralization is less evident in the healthy
subjects. The lower correlation coefficients in the group of
patients with severe carotid stenosis could imply that carotid
stenosis affects functional reserve capacity in the patients.
5.Conclusions
Considering the presented results obtained in our study,
we can conclude that there is a clear trend towards the
lateralization of the visual evoked response in the right PCA,
being highly consistent with results of the previous studies
and showing a general dominance of the right occipital
lobe in the visual process. The right occipital lobe is more
responsive to visual stimuli in terms of functional activation
than the left one, indicated by a consistently higher blood

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Stroke Research and Treatment5
flow velocity response on the right. fTCD was able to assess
hemispheric visual dominance not only in healthy individu-
als, but also in patients with severe carotid disease and thus
compromised anterior cerebral circulation. Furthermore,
velocity changes between sides as a measure of hemispheric
perfusion lateralization could be an indicator of posterior
collateralpathway.Thedemonstratedright-sidedasymmetry
in posterior cerebral circulation in patients with severe
carotid disease could possibly be taken into consideration in
further trials according to stroke risk or outcome.
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