J Neurol (2007) 254:861– 865

DOI 10.1007/s00415-006-0452-0 ORIGINAL COMMUNICATION

Zlatko Trkanjec Hemispheric asymmetries in blood flow

Vida Demarin
during color stimulation

j Abstract Visual stimulation 38.9 ± 9.2 cm/s, for green

Received: 5 January 2004
Received in revised form: 20 July 2005
Accepted: 26 January 2006
Published online: 27 January 2007
Z. Trkanjec, MD, PhD (&)
V. Demarin, MD, PhD
University Dept. of Neurology
Sestre milosrdnice University Hospital
Vinogradska 29
HR-10 000 Zagreb, Croatia
Tel.: +385-1/3768282
Fax: +385-1/3768282
E-Mail: zlatko.trkanjec@zg.t-com.hr
influences mean blood flow
velocities (MBFV) in posterior
cerebral arteries (PCA). In 51
healthy, right-handed volunteers
MBFV were measured in PCA with
opened and closed eyes and while
watching colored light (red, yel-
low, green, blue) for 1 minute.
Volunteers had eyes closed
2 minutes between different
colors. MBFV in left PCA was
41.2 ± 8.6 cm/s (mean ± 2SD)
and 27.8 ± 8.5 cm/s with eyes
opened and closed, respectively.
For red light MBFV in left PCA
was 31.4 ± 7.1 cm/s, for yellow
31.4 ± 7.2 cm/s, for green
32.0 ± 8.3 cm/s, and for blue
33.0 ± 7.6 cm/s. MBFV in right
PCA 41.7 ± 8.9 cm/s and
28.2 ± 9.1 cm/s with eyes opened
and closed, respectively. For red
light MBFV in right PCA was
39.4 ± 8.4 cm/s, for yellow
37.8 ± 9.4 cm/s and for blue
38.0 ± 8.8 cm/s. There was no
significant difference in MBFV
between left and right PCA with
eyes opened and closed, but MBFV
were significantly higher in right
PCA for each color than corre-
sponding MBFV in left PCA. These
findings could indicate the greater
metabolism of visual cortex in
right occipital lobe while watching
colors. Visual cortex of right
occipital lobe could have greater
importance in color perception
than visual cortex of left occipital
lobe.
j Key words ultrasonography Æ
doppler Æ transcranial Æ
color perception Æ dominance Æ
cerebral Æ laterality

effect of any mechanical manipulation or functional

Introduction
In 1982, Rune Aaslid introduced transcranial Doppler
(TCD) that has several advantages over other methods
of cerebral blood flow visualization and measurement
[3]. TCD is a non-invasive, harmless, painless, and
relatively inexpensive method. It provides data in
stimulation on intracranial circulation [2]. In recent
years TCD has been used to measure blood velocities
in basal cerebral arteries during functional stimula-
tion of distinct brain regions (reading, writing, cog-
nitive tasks, visual stimuli, etc.). Also, different
functional tests and pharmaceutical substances have
been used during TCD monitoring to assess the
JON 2452

real time and has optimal time resolution of the cerebral circulatory reserve (hypercapnia, hypoxia,
measurement. TCD enables measurements of the acetazolamide, etc.) [15, 26].
862
Systolic, diastolic and mean blood flow velocities
are used to describe the flow in basal cerebral arteries.
However, mean blood flow velocity (MBFV) has a
greater physiological significance, since it least
depends on cardiovascular factors such as cardiac
frequency and contractility, peripheral resistance, and
aortic elasticity. Also, MBFV has a better time corre-
lation with perfusion than other values [23, 25].
Primary visual fields of cerebral cortex are located
in both occipital lobes around the calcarine sulcus in
Brodman’s area 17, and adjacent Brodman’s areas 18
and 19 are serving as associative visual areas. Visual
field is placed mainly on the medial aspect of the
occipital lobe, but at the apex of occipital lobe
primary visual area partially extends into the lateral
aspect of the occipital lobe [8].
The brain is receiving arterial blood through the
anterior (carotid) and posterior (vertebrobasilar)
system. The vertebrobasilar system consists of the left
and right vertebral arteries that fuse to form basilar
artery. Basilar artery, after a short course divides into
the right and left posterior cerebral arteries. Posterior
cerebral artery (PCA), emerging at the basilar artery
bifurcation, provides arterial blood supply for most
parts of the occipital lobe. Primary and associative
visual areas located in the occipital lobe also receive
arterial blood supply by way of posterior cerebral
arteries [9, 31, 43].
Since PCA supplies visual areas in occipital lobes
(visual cortex) with arterial blood it is easy to measure
changes in MBFV in PCA by TCD during various
visual stimuli that are processed in visual cortex.
Differences in MBFV in PCA detected by TCD could
indirectly indicate changes in metabolic needs of
neurons in visual cortex. We wanted to compare
MBFV in both PCA during visual stimulation with
different colors. This paper presents measurements
and comparison of MBFV in left and right PCA
during stimulation with colored light in healthy
volunteers.
Methods
Measurements were performed in a group of 51 right-handed
healthy volunteers with no eye abnormalities using 2 MHz probe
using Transscan 3D EME TCD device.
Probe was attached and fixed to volunteers’ head using ribbon
probe holder. PCA was identified and insonated through temporal
window using a standard technique [4, 35]. First MBFV were mea-
sured while volunteers had eyes wide open and afterwards with eyes
closed in order to confirm the decline of MBFV with closing of eyes
characteristic for PCA. Afterwards the subjects watched the center of
the rectangular source of light (35 cm wide and 25 cm high) con-
taining light bulb of 100 W and a color filter in the front. The source
of light was placed on the platform at the distance of 1 m from
volunteer and at the level of volunteer’s eyes. Volunteers watched
rectangular source of light with color filter for 1 minute while blood
flow velocity was measured in PCA using hand-held 2 MHz TCD
probe and averaged over that period to obtain MBFV. After a resting
phase of 2 minutes while volunteers relaxed with eyes closed, the
filter and the color of light was changed. All color filters were made
of same material. Four color filters were used: red, yellow, green and
blue, so each volunteer looked at red, yellow, green and blue light for
1 minute and had a 2 minute pause between different colors. In a
half of the subjects, the measurements were firstly performed on the
right-sided PCA, and afterwards on the left-sided PCA, while in the
other half the measurements were firstly performed on the left-sided
PCA, and then on the right-sided PCA. After measurements were
made on one PCA, the procedure was repeated on the opposite PCA.
So, each subject had MBFV measurements done in the right and left
PCA while looking at red, yellow, green and blue light. In subjects
with odd number (1, 3, 5 etc.) measurements began on right side
PCA, while in subjects with even number (2, 4, 6, etc.) measure-
ments began on left side PCA. All measurements were performed by
the same individual (first author) to avoid interobserver differences
that could interfere with results.
Statistical analysis was done using Wilcoxon’s matched-pair
signed-rank test. Statistically significant differences were consid-
ered at p value less than 0.01 (p < 0.01). All results are presented as
mean ± 2SD.
Results
The study group consisted of 51 healthy, right-handed
volunteers, 27 (52.9%) males and 24 (47.1%) females;
aged 20–59, mean age was 36.98 (SD 10.43) years,
median was 37 years, and mode was 20 years. Most of
volunteers were young and middle aged: 34 were
younger than 40 years, 10 were 40–49 years old, and
only seven of them were older than 50 years.
MBFV mean values in left PCA were 41.2 ± 8.6 cm/s
(mean ± 2SD) and 27.8 ± 8.5 cm/s with eyes wide
open and eyes closed, respectively. While volunteers
were watching red light MBFV mean values in left PCA
were 31.4 ± 7.1 cm/s, during watching yellow light
31.4 ± 7.2 cm/s, during watching green light
32.0 ± 8.3 cm/s, and during watching blue light
33.0 ± 7.6 cm/s. There was significant difference
between MBFV with eyes open and eyes closed
(z = )6.2146, p < 0.001), but there was no significant
difference between MBFV mean values in left PCA
while volunteers were watching different colors.
MBFV mean values in right PCA were
41.7 ± 8.9 cm/s and 28.2 ± 9.1 cm/s with eyes wide
open and eyes closed, respectively. During watching
red light MBFV mean values in right PCA were
39.4 ± 8.4 cm/s, during watching yellow light
38.9 ± 9.2 cm/s, during watching green light
37.8 ± 9.4 cm/s and during watching blue
light 38.0 ± 8.8 cm/s. There was significant differ-
ence between MBFV with eyes open and eyes closed
(z = )6.2146, p < 0.001), but there was no significant
difference between MBFV mean values in left PCA
while volunteers were watching different colors.
There were no statistical significant difference be-
tween MBFV with eyes wide open and eyes closed in
 863

Table 1 Mean blood flow velocities in both posterior cerebral arteries with 45
eyes open, eyes closed and while watching different colors 40 left PCA
right PCA
Left PCA Right PCA Statistical significance 35
(cm/s) (cm/s) 30
25

cm/s
Eyes wide open 41.2 ± 8.6 41.7 ± 8.9 z = )0.9940, p = 0.32 NS 20
Eyes closed 27.8 ± 8.6 28.2 ± 9.1 z = )1.0867, p = 0.28 NS
Red light 31.4 ± 7.1 39.4 ± 8.4 z = )6.1162, p < 0.0001 15
Yellow light 31.4 ± 7.2 38.9 ± 9.2 z = )6.0333, p < 0.0001 10
Green light 32.0 ± 8.3 37.8 ± 9.4 z = )5.6757, p < 0.0001 5
Blue light 33.0 ± 7.6 38.0 ± 8.8 z = )5.6302, p < 0.0001
0

eyes open

eyes closed

red light

green light

blue light
yellow
light
NS = not significant

both PCA. However, MBFV mean values were signif-

icantly higher in right PCA during watching each
color (red, yellow, green and blue) than correspond-
ing MBFV mean values in left PCA (Table 1, Fig. 1).
The difference was most prominent with colors of
longer wavelength (red), and it lessens with colors of
shorter wavelength (blue), but this difference did not
reach statistical significance.
MBFV values in both PCAs had a tendency to
become lower in older volunteers, but this difference
did not reach statistical significance.
Discussion
The vision is probably the most important sense in
humans [18]. On the other hand, light is a stimulus
that can be easily and precisely applied and con-
trolled. Therefore, the application of visual stimuli is
almost perfect method for different kinds of experi-
mental research of visual system.
There are many mechanisms presumed to play a
significant role in the autoregulation of the cerebral
blood flow, however, cerebral blood flow is definitely
increased by changes in the metabolic activity. Cere-
bral blood flow is directly or indirectly coupled with
the metabolic activity of the brain (vasoneural cou-
pling). In many instances, significant differences in
the regional cerebral blood flow may exist when dis-
tinct parts of the brain have an increased metabolism
[12, 14, 37]. Since the visual cortex in occipital lobes
receives blood supply almost exclusively from the
posterior cerebral arteries [9, 36, 43] every change in
arterial blood flow due to differences in the metabo-
lism of the visual cortex neurons is expected to have
reflection on arterial blood flow in posterior cerebral
arteries. Therefore changes in blood flow in posterior
cerebral arteries could indirectly reflect changes in
metabolism of the visual cortex neurons.
In the present study, we measured MBFV in both
posterior cerebral arteries while healthy volunteers
had eyes open, eyes closed and afterwards volunteers
were exposed to stimulation with colored light.
Fig. 1 Mean blood flow velocities in both posterior cerebral arteries N.S. = not
significant * = statistically significant (p < 0.0001)
Many authors recorded changes of blood flow
velocities with TCD in the posterior cerebral arteries
during visual stimulation. Most of these studies report
changes in blood flow velocities during simple visual
stimulation (opening and closing eyes, stimulation
with white light, either constant or flashing). In all
papers MBFV in PCA decreased with closing eyes, and
increased on opening the eyes and during visual
stimuli [1, 10, 17, 22, 35, 37, 38, 41].
In the present study we used TCD methodology
that has some limitations typical to all Transcranial
Doppler sonography studies. Our results in the group
of 51 right-handed relatively young volunteers
showed significant decrease of MBFV in both PCA
while volunteers closed their eyes compared with eyes
opened. We recorded no statistically significant
difference between MBFV in right and left PCA while
volunteers had eyes opened and eyes closed. Also,
there was no significant difference between MBFV in
each PCA while volunteers were looking at different
colors.
However, our results showed significantly higher
MBFV for every color in the right PCA than corre-
sponding value in the left PCA. Taking into consid-
eration the vasoneural coupling, results of this study
could indicate the greater metabolism of visual cortex
in right occipital lobe during receiving and processing
color information. Therefore, visual cortex of right
occipital lobe could have greater importance in color
perception than visual cortex of left occipital lobe.
The concept of cerebral dominance (i.e. special-
ization of one cerebral hemisphere for higher cerebral
functions) has been known for more than a century,
since Broca described that lesions in left cerebral
hemisphere in right-handed people causes aphasia
[7]. Left cerebral hemisphere is mainly dominant for
speech and understanding of speech, reading and
writing, manual skills, making concepts, compre-
864

hending of complex relationships and development of
behavior in solving problems, while right cerebral
hemisphere is mainly dominant for some orientation
in space and body schema, music ability and for
visual and audition analysis of non-verbal informa-
tion. Right hemisphere has greater importance in
spatial orientation than left hemisphere [16]. The
handedness is also in some extent connected with
dominance of one cerebral hemisphere [30].
Our understanding of color perception has greatly
increased in the last decades [11, 19, 20, 26, 27, 44, 45],
but color perception was not considered to have cere-
bral dominance.
Some other authors have recorded the differences
between cerebral hemispheres, e.g. Markus and
Boland [29], Hartje et al. [19], Rihs et al. [32],
Sturzenegger et al. [39], Klingelhofer et al. [24], Ow-
ega et al. [31], Tiecks et al. [40], Schmidt et al. [34],
Rihs et al. [33], Troisi et al. [42].
Some other authors found greater blood flow
velocity and/or greater activation of right hemisphere
during color visual tasks, e.g. Corbetta et al. [12],
Belliveau et al. [5], Kelley et al. [22]. However, Lueck
et al. found increase of activity greater in left visual
cortex [28] in three examinees (two of them being
left-handed). The possible explanation for this dis-
crepancy could be that left-handed persons have left
cerebral hemisphere dominant for color perception,
but this assumption requires further studies.
Although different authors used different methods
and different kinds of visual stimulation, and some
recordings were made in different arteries (posterior
and middle cerebral artery) making direct compari-
son quite difficult, in all these papers authors
described greater activation of left cerebral hemi-
sphere during different verbal tasks, while different
visual and visuospatial tasks caused greater activation
of right hemisphere and therefore greater blood flow
velocities in right-sided cerebral arteries. In our study
we found greater MBFV in right PCA during color
stimulation, so our results could corroborate findings
from previous studies, because color perception is
also a kind of visual task.
On the other hand, a loss of color perception
(dyschromaopsia or achromatopsia) has been
reported in patients most often after bilateral lesions
of occipital lobe [13, 44], and after lesions of right
occipital lobe [6]. However, deficits of color percep-
tion after cortical lesions with preservation of primary
visual functions are rare. Most of the lesions in right
occipital lobe are connected with visual neglect
making it is not easy to recognize color perception
defects [21].
The results of our study could imply that there is a
lateralization of color perception processing. We
could speculate that the right cerebral visual cortex
could have specific sensitivity for recognizing and
processing information about particular wavelength
of light, i.e. for colors. Since the right hemisphere has
greater importance in visuospatial orientation than
left hemisphere, the greater importance of right visual
cortex in another visual information, in this case
color, would not be unexpected. However, to prove
this speculative concept further research is needed,
preferably in combination of TCD and other tech-
niques (such as fMRI, SPECT, PET etc.).

References
1. Aaslid R (1987) Visually evoked
dynamic blood flow response of the
human cerebral cortex. Stroke 18:771–
775
2. Aaslid R, Lindegaard KF (1986) Cere-
bral hemodynamics. In: Aaslid R (eds)
Transcranial doppler sonography.
Springer-Verlag, Vienna, New York,
pp 60–85
3. Aaslid R, Markwalder TM, Nornes H
(1982) Non-invasive transcranial
Doppler ultrasound recordings of flow
velocity in basal cerebral arteries.
J Neurosurg 57:769–774
4. Alexandrov AV, Demarin V (1999)
Insonation techniques and diagnostic
criteria for transcranial Doppler
sonography. Acta Clin Croat 38:97–108
5. Belliveau JW, Kennedy DN, MacKinstry
RC, et al. (1991) Functional mapping of
the human visual cortex by magnetic
resonance imaging. Science 254:716–
719
6. Blanke O, Ortigue S, Landis T (2003)
Colour neglect in an artist. Lancet
361:264
7. Broca P (1861) Remarques sur le siege
de la faculte du langage articule, suivies
d’une observation d’aphemie. Bull Soc
Anat 6:398–407
8. Carpenter MB (1978) Core text of
neuroanatomy. 2nd ed. The Williams
and Wilkins Company, Baltimore,
pp 280–316
9. Carpenter MB (1978) Core Text of
Neuroanatomy. 2nd ed. The Williams
and Wilkins Company, Baltimore,
pp 317–339
10. Conrad B, Klingelhöfer J (1989)
Dynamic of regional cerebral blood
flow for various visual stimuli. Exp
Brain Res 77:437–441
11. Conway BR, Hubel DH, Livingstone MS
(2002) Color contrasts in macaque V1.
Cerebral Cortex 12:915–925
12. Corbetta M, Miezin FM, Dobmeyer S,
Shulman GL, Petersen SE (1990)
Attentional modulation of neural pro-
cessing of shape, color, and velocity in
humans. Science 248:1556–1559
13. Damasio A, Yamada MDT, Damasio H,
Corbett J, McKee J (1980) Central
achromatopsia: behavioral, anatomical,
and physiological aspects. Neurology
30:1064–1071

14. Daffertshofer M, Hennerici M (1995)
Cerebrovascular regulation and vaso-
neural coupling. J Clin Ultrasound
23:125–138
15. Demarin V, Rundek T (1992) Aceta-
zolamide test combined with Trans-
cranial Doppler (TCD): a simple non-
invasive test for the assessment of
cerebral vasoreactivity in humans.
Period Biol 94:193–200
16. Geschwind N, Galaburda AM (1985)
Cerebral lateralization. Biological
mechanisms, associations, and pathol-
ogy: I. A hypothesis and a program for
research. Arch Neurol 42:428–459
17. Gomez SM, Gomez CR, Hall IS (1990)
Transcranial Doppler ultrasonographic
assessment in intermittent light stimu-
lation at different frequencies. Stroke
21:1746–1748
18. Gregory RL (1996) Eye and brain. The
psychology of seeing. 4th ed. Princeton
University Press, Princeton
19. Hartje W, Ringelstein EB, Kistinger B,
Fabianek D, Willmes K (1994) Trans-
cranial Doppler ultrasonic assessment
of middle cerebral artery blood flow
velocity changes during verbal and
visuospatial cognitive task. Neuro-
psychologia 32:1443–1452
20. Hubel DH (1988) Eye, brain, and
vision. Scientific American Library,
New York
21. Jehkonen M, Ahoneh JP, Dastidar P,
Koivisto AM, Laippala P, Vilkki J
(1998) How to detect visual neglect in
acute stroke. Lancet 351:727–728
22. Kelley RE, Chang JY, Scheinman NJ,
Levin BE, Duncan RC, Lee SC (1992)
Transcranial Doppler assessment of
cerebral flow velocity during cognitive
tasks. Stroke 23:9–14
23. Kirkham FJ, Padayachee TS, Parsons S,
Seargeant LS, House FR, Gosling RG
(1986) Transcranial measurement of
blood velocities in the basal cerebral
arteries using pulsed Doppler ultra-
sound: velocity as index of flow.
Ultrasound Med Biol 12:15–21
24. Klingelhofer J, Matzander G, Sander D,
Schwarze J, Boecker H, Bischoff C
(1997) Assessment of functional hemi-
spheric asymmetry by bilateral simul-
taneous cerebral blood flow velocity
monitoring. J Cereb Blood Flow Metab
17:577–578
25. Kontos HA (1989) Validity of cerebral
arterial blood flow calculations from
velocity measurements. Stroke 20:1–3
26. Lampl Y, Kesler A, Lorberboyn M,
Gadot N, Sadeh M (2002) Cerebrovas-
cular reactivity in patients under long-
term acetazolamide treatment. Acta
Neurol Scand 105:59–62
27. Livingstone MS, Hubel DH (1984)
Anatomy and physiology of a color
system in the primate visual cortex.
J Neurosci 4:309–356
28. Lueck CJ, Zeki S, Friston KJ, et al.
(1989) The colour centre in the cerebral
cortex of man. Nature 340:386–389
29. Markus HS, Boland M (1992) ‘‘Cogni-
tive activity’’ monitored by non-inva-
sive measurement of cerebral blood
flow velocity and its application to the
investigation of cerebral dominance.
Cortex 28:575–581
30. Oldfield RC (1971) The assessment and
analysis of handedness: the Edinburgh
inventory. Neuropsychologia 9:97–113
31. Owega A, Klingelhofer J, Sabri O,
Kunert HJ, Albers M, Sass H. (1998)
Cerebral blood flow velocity in acute
schizophrenic patients. A Transcranial
Doppler ultrasonography study. Stroke
29:1149–1154
32. Rihs F, Gutbrod K, Gutbrod B, Steiger
HJ, Sturzenegger M, Mattle H (1995)
Determination of cognitive hemi-
spheric dominance by ‘‘stereo’’ trans-
cranial Doppler sonography. Stroke
26:70–73
33. Rihs F, Sturzeneger M, Gutbroth K,
Schrot G, Mattle H (1999). Determina-
tion of language dominance: Wada test
confirms functional transcranial
Doppler sonography. Neurology
52:1591–1596
865
34. Schmidt P, Krings T, Willmes K,
Roessler F, Reul J, Thorn A (1999)
Determination of cognitive hemi-
spheric lateralization by ‘‘functional’’
transcranial Doppler cross-validated by
functional MRI. Stroke 30:2491–2492
35. Sitzer M, Diehl RR, Hennerici M.
(1992) Visually evoked cerebral blood
flow responses - normal and patho-
logical conditions. J Neuroimaging
2:65–70
36. Smith CG, Richardson WFG (1966) The
course and distribution of the arteries
supplying the visual (striate) cortex.
Am J Ophthalmol 61:1391–1396
37. Sokoloff L (1981) Relationship among
local functional activity, energy
metabolism and blood flow in the
central nervous system. Federation
Proc 40:2311–2316
38. Spelsberg B, Bohning A, Kompf D,
Kessler C (1998) Visually induced
reactivity in posterior cerebral artery
blood flow. J Neuroophthalmol 18:263–
267
39. Sturzenegger M, Newell DW, Aaslid R.
(1996) Visually evoked blood flow
response assessed by simultaneous
two-channel transcranial Doppler
using flow velocity averaging. Stroke
27:2256–2261
40. Tiecks FP, Haberl RL, Newell DW
(1998) Temporal patterns of evoked
cerebral blood flow during reading.
J Cereb Blood Flow Metab 18:735–741
41. Trkanjec Z, Demarin V (1999) Trans-
cranial Doppler sonography during vi-
sual stimulation. Acta Clin Croat
38:285–288
42. Troisi E, Silverstrini M, Matteis M,
Monaldo BC, Vanieri F, Caltagirone C
(2000) Emotion-related cerebral asym-
metry: hemodynamics measured by
functional ultrasound. J Neurol
247:1172–1176
43. van der Zwan A, Hillen B (1991)
Review of the variability of the terri-
tories of the major cerebral arteries.
Stroke 22:1078–1084
44. Zeki S (1990) A century of cerebral
achromatopsia. Brain 113:1721–1777
45. Zeki S (1993) A vision of the brain.
Blackwell Scientitic, Oxford
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