Download Lateralization of Cerebral Blood Flow Velocity Changes

Lateralization of Cerebral Blood Flow Velocity Changes
During Cognitive Tasks
A Simultaneous Bilateral Transcranial Doppler Study
Guy Vingerhoets, PhD; Nathalie Stroobant, DPsych
Downloaded from http://stroke.ahajournals.org/ by guest on June 18, 2017
Background and Purpose—Transcranial Doppler ultrasonography (TCD) permits the assessment of cognitively induced
cerebral blood flow velocity (BFV) changes. We sought to investigate the lateralization of BFV acceleration induced
by a variety of cognitive tasks and to determine the influence of age, gender, IQ, and quality of the performance on the
relative BFV changes.
Methods—Simultaneous bilateral TCD monitoring of BFV in the middle cerebral arteries (MCAs) was performed in 90
normal right-handed volunteers during 13 verbal and visuospatial tasks and their preceding rest periods.
Results—All tasks induced a significant bilateral BFV increase in the MCAs compared with the preceding rest periods.
Five verbal tasks showed a significant left-hemispheric BFV acceleration. Linguistic tasks that required active or
creative processing of the verbal stimuli, such as sentence construction or word fluency, elicited the most asymmetric
response. Five visuospatial tasks revealed a significant right-hemispheric BFV shift. Paradigms that combined
visuospatial attention and visuomotor manipulation showed the most lateralized acceleration. Older volunteers (aged
.50 years) showed higher relative BFV changes, but lateralization was not influenced by age. Gender, IQ, and
performance quality did not reveal significant effects on BFV change.
Conclusions—Bilateral TCD is a noninvasive technique that has the potential to connect the particular change in flow
pattern of the MCA distribution with selective cognitive activity and thus offers specific functional information of
scientific and clinical value. (Stroke. 1999;30:2152-2158.)
Key Words: blood flow velocity n cognition n neuropsychological tests n ultrasonography, Doppler, transcranial
T
ranscranial Doppler ultrasonography (TCD) is a noninvasive diagnostic tool with high temporal resolution that
allows a continuous and bilateral monitoring of blood flow
velocity (BFV) of the basal cerebral arteries. Functional TCD
(fTCD) research examines BFV changes during the performance of mental tasks. There is growing evidence to support
the hypothesis of a relationship between mental activity and
BFV measured by TCD and that BFV is more rapid when
subjects engage in cognitive activities compared with rest
periods.1–17 Evidence has accumulated that the diameter of
the large cerebral arteries does not change significantly under
a variety of physiological stimuli.18 –22 Assuming that the
diameter of the basal cerebral arteries remains unchanged
with time, BFV changes under successive mental conditions
are necessarily related to volume flow changes. Hence,
changes in cerebral BFV reflect changes in cerebral metabolism due to cerebral activation.
The aim of the present study is to investigate the change in
the flow pattern of the MCA distribution during 13 mental
tasks selected to induce lateralized cognitive activity and
metabolic demand. Tasks with high lateralizing power are of
interest to fundamental and clinical research and may even be
useful for the individual patient.10 Because the MCA carries
approximately 80% of the flow volume received by the
cerebral hemisphere23 and is very easy to monitor by TCD in
most patients, we have focused on this artery. In addition, we
will evaluate the influence of demographic variables and
quality of performance on BFV changes.
Subjects and Methods
Subjects
Ninety normal volunteers (38 men and 52 women; mean6SD age
36613.3 years, range 18 to 62 years) participated in the study. All
subjects were right-handed, as measured by the Edinburgh Handedness Inventory (Laterality Index, mean6SD 90.2615.9%).24 A
Dutch version of the National Adult Reading Test25 measured a
mean6SD IQ of 10267.6). The mean6SD years of education was
13.862.3). State anxiety was measured by the Dutch version of the
Spielberger State Anxiety Questionnaire, which showed low-state
anxiety scores in all subjects (mean6SD 30.365.4).26 None of the
subjects took psychoactive medication, had an active medical disease, or had a history of cardiovascular, neurological, or psychiatric
disorders. They all refrained from drinking caffeine-containing
beverages or smoking for at least 12 hours before the study. All
Received June 10, 1999; final revision received July 12, 1999; accepted July 12, 1999.
From the Department of Psychiatry and Neuropsychology (G.V., N.S.) and the Center for Cardiac Surgery (N.S.), University Ghent, Ghent, Belgium.
Correspondence and reprint requests to Guy Vingerhoets, Department of Psychiatry and Neuropsychology, University Hospital Ghent, De Pintelaan
185-4K3, B-9000 Ghent, Belgium. E-mail [email protected]
© 1999 American Heart Association, Inc.
Stroke is available at http://www.strokeaha.org
2152
Vingerhoets and Stroobant
Flemish-Dutch speaking subjects had normal or corrected-to-normal
vision and were experimentally naive about TCD procedures. No
reading disorders were reported. In 11 additional subjects, TCD
measurement was not possible because of an insufficient signal
through the temporal bone window.
TCD Apparatus
Downloaded from http://stroke.ahajournals.org/ by guest on June 18, 2017
A commercially available 2-Mhz pulsed-wave TCD unit (Multidop
X2 hardware, DWL version 2.53j of TCD 7 software, DWL
Elektronische systeme GmbH) continuously and simultaneously
monitored BFV of the MCA. Two dual 2-Mhz transducers, fitted on
an elastic headband (DWL 4038) and placed on the left and right
temporal skull window, transmitted the ultrasonic signal and received the echoes. Details of the insonation technique, and the
correct insonation of the MCA have been described elsewhere.27
Starting from an insonation depth of 50 mm, depth and angles of
insonation were adjusted to obtain the highest signal intensity of the
M1 segment of the MCA (insonation depth ranged from 42 to
56 mm). The outline or envelope of the velocity spectrum and mean
maximal BFV were calculated by the standard algorithm implemented on the instrument with use of a fast Fourier transform. The
TCD unit allowed continuous-wave Doppler recording of the intracranial artery with online calculation of mean flow velocity in
centimeters per second.
Procedure
All tests were performed in a quiet room without any visual or
auditory stimulation and with illumination held constant. The subjects were seated in a comfortable chair in front of a computer
screen. The basic principles of the equipment and the general design
of the study were explained to promote a relaxed atmosphere and
reduce possible anxiety. After written informed consent was obtained, demographic data were noted, and the Edinburgh Handedness
Inventory and the Spielberger State Anxiety Inventory were assessed. The 2 TCD probes were fixed over the left and right temporal
regions of the subject’s head and adjusted to obtain optimal signals.
Blood pressure, respiratory rate, hematocrit, or end-tidal CO2 were
not monitored. There is ample evidence that these variables do not
change in a significant way during the course of the experimental
procedure.2,7,14 –16 Following an initial 6-minute rest phase, subjects
were confronted with 6 verbal and 7 visuospatial tasks, most of
which were presented on a computer screen. All tasks were performed in 1 session of approximately 1.5 hours. The order of the
tasks was rotated from subject to subject, thus beginning with a
different task each time without changing the remainder of the
sequence. The nature of each task was explained and the subjects
were familiarized with the task requirements by means of 2 practice
items. Each activation condition lasted 120 seconds. The subjects
were instructed to work as accurately as possible. The speed of the
stimulus presentation was individualized to reduce frustration with
stimulus pacing (either too slow or too fast) and to maximize the
individual’s mental activity. As soon as the subjects gave a response,
the next item was shown. To obtain a stable measurement during
activation, only the middle 60 seconds of each 120-second activation
condition were used to determine the mean BFV for that task. Each
activation phase was preceded by a 120-second rest period. During
the 120-second rest periods, subjects were asked to look at an
illuminated blank computer screen, to relax and breathe regularly
without falling asleep, and to “think of nothing.” They were not
allowed to move or speak, nor were they spoken to. The first 60
seconds of each rest period served as a recovery period in which
posttask activation could subside.5 Only the last 60 seconds of the
rest period served as the baseline measurement for the subsequent
activation phase.
Cognitive Tasks
We selected cognitive tasks that had demonstrated potential for
lateralized cognitive activity (and lateralized hemodynamics) in
previous functional imaging or TCD research. In addition, we also
added some tasks that have never been used in this research before.
Functional Transcranial Doppler Velocimetry
2153
The order in which the tasks are described represents the sequence
presented to the first volunteer.
(1) Reading. Subjects were instructed to read a list of 50 words
aloud. The list was a Dutch version of the National Adult Reading
Test.25 Because the entire list had to be read (and scored), this task
was of variable duration.
(2) Verbal Similarities (List). Subjects were requested to select those
2 words from a list of 6 that belong to a close superordinate semantic
category (eg, reckless, crucial, obliging, dynamic, profitable, energetic). Subjects had to indicate their choice on the computer screen
by pointing out the words with both index fingers simultaneously to
avoid unilateral activation of the motor cortex.
(3) Visuospatial Design Comparison. This task involved the comparison of very similar complex molecule-like designs (Figure 1a).
Subjects had to detect subtle differences between 2 designs and had
to indicate these with both index fingers simultaneously.
(4) Syntactic Sentence Construction. The words of a sentence were
shown in a mixed-up order. Subjects were asked to whisper a
grammatically correct sentence using as many words as possible (eg,
radio-exploded-this-in-I-the-station-morning-the-heard-had-a-onthat-bomb). Whispering minimizes the acoustic interference on the
TCD signal by preventing voice artifacts caused by the conduction of
the normal voice spectrum via the cranial bones to the temporally
placed probes.
(5) Visuospatial Cube Construction. Simple to complex diagrams of
unfolded cubes were presented (Figure 1b). One of the ribs was
marked with an asterisk; letters marked 5 other ribs. Subjects were
requested to refold the cube in their imagination and decide on which
rib (letter) the asterisk would touch by indicating the answer with
both index fingers simultaneously.
(6) Verbal Similarities (Pairs). Subjects were asked to decide
whether 2 simultaneously presented nouns were semantically similar
(eg, tarry-linger) or different (eg, reputation-concentration). They
responded by pressing a button held in the left hand (different) or
right hand (similar) that activated a red or green light, respectively.
Left- and right-handed responses were balanced over the 2-minute
period to avoid disproportionate activation of 1 motor cortex.
(7) Mental Rotation (Alphanumeric). This task was based on previous positron emission tomography research.28 Alphanumeric stimuli
were presented in either “normal” or “backward” (ie, mirror image)
form. The stimuli were also presented in 1 of 3 orientations: 120°,
180°, and 240°. Subjects had to decide whether the stimulus was
shown in its normal or backward (mirror) form (Figure 1c). The
subjects responded by pressing hand-held buttons (cf verbal similarities [pairs], above).
(8) Syntactic Sentence Comparison. Pairs of sentences differing only
in syntactic complexity (eg, active versus passive voice) were
presented. Subjects had to indicate whether the sentences were either
semantically identical (eg, He entered the room when almost
everybody was gone/Almost everybody was gone when he entered
the room) or semantically different (eg, She writes him a letter/The
letter to her has been written by him). The subjects responded by
pressing hand-held buttons (cf verbal similarities [pairs], above).
(9) Mental Rotation (Figures). Two identical typographic symbols or
simple line drawings of hand positions were presented on the screen
(Figure 1 d). The stimulus on the left was always presented in a
“normal,” upright position. The stimulus on the right side was
presented in 1 of 3 orientations (120°, 180°, or 240°) and in either its
“normal” orientation (ie, identical to the left stimulus) or as a mirror
image of the left stimulus. Subjects had to decide whether the right
figure was shown in its normal or backward form. The subjects
responded by pressing hand-held buttons (cf verbal similarities
[pairs], above).
2154
Stroke
October 1999
Figure 1. Examples of stimuli of visuospatial tasks: a, visuospatial design comparison; b, visuospatial cube construction; c, mental rotation (alphanumeric);
and d, mental rotation (figures).
Downloaded from http://stroke.ahajournals.org/ by guest on June 18, 2017
(10) Word Fluency. The subjects were required to produce as many
words as possible (excluding proper names) beginning with a
designated letter that was presented in the center of the screen. The
letters N, A, K, and P were shown for 30 seconds each. The subjects
were instructed to whisper the words to minimize acoustic interference with the TCD signal.
(11) Visual Searching. The task consisted of finding a grid pattern
(out of 24 similar designs) that matched the one in the center of the
screen and is part of the Fepsy computer program for neurocognitive
assessment.29 Subjects had to point to the identical grid with both
index fingers simultaneously.
(12) Computer Game. The task consisted of a commercially available computer game (Monster Truck Madness, version 1.00 TV 4,
Microsoft). Subjects used a steering wheel and pedals to drive a car
in a race circuit. Subjects were allowed a 2-minute drive regardless
of speed or accuracy of the performance.
(13) Three-Dimensional Puzzle. A commercially available 3D puzzle, illustrated in Figure 2, was used (Eureka bvba, 3D Puzzle).
Subjects were allowed 2 minutes to try to free the ring from the
game.
Tasks 1, 2, 4, 6, 8, and 10 are generally assumed to be processed
predominantly by the left hemisphere and tasks 3, 5, 7, 9, 11, 12, and
13 by the right hemisphere.
Results
All tasks showed a bilateral increase in absolute BFV
compared with their preceding rest phase (Table 1). Comparison of the relative changes indicated that the most marked
increase occurred in the computer game task. The smallest
BFV increase was observed in the syntactic sentence comparison task.
To evaluate the effect of lateralization, a repeatedmeasures MANOVA with side as within-subjects factor and
gender (male/female), age (,30 years, ,50 years, ,65
years) and IQ (.1 SD below mean/mean 61 SD/.1 SD
above mean) as between-subjects factors was calculated.
Relative changes were used as dependent variables. The
MANOVA revealed a significant effect for side (Hotelling
T213,61515.09, P,0. 001). Post hoc analyses with univariate F
tests showed a significant lateralization for all tasks except
visuospatial cube construction, verbal similarities (pairs), and
mental rotation (alphanumeric) (Table 1). In decreasing
Statistical Analysis
We calculated the average of all mean maximal BFVs over the last
60 seconds of the rest periods and the middle 60 seconds of the
activation periods. We always used the immediately preceding rest
period to determine the BFV change of the cognitive task under
study. Because TCD cannot detect the difference between real
asymmetries in BFV and differences caused by slightly different
insonation angles, we calculated the relative increase from baseline
to activation: (BFV activation2BFV baseline/BFV baseline)3100).12 Data were analyzed by means of repeated-measures
MANOVA. The quality of the task performance was expressed as
the percentage of correct answers except for word fluency and
syntactic sentence construction, in which the absolute number of
words was taken into account.
Figure 2. 3D puzzle used in one cognitive task in the study.
Vingerhoets and Stroobant
TABLE 1.
Functional Transcranial Doppler Velocimetry
BFV in the MCA During Baseline and Cognitive Tasks
Task/Side
Baseline*
Activation*
% Change†
Left
60.9 (11.8)
70.0 (13.7)
15.2 (9.3)
Right
60.0 (11.5)
67.5 (13.3)
12.6 (8.7)
Left
59.9 (11.8)
66.0 (12.8)
10.5 (7.8)
Right
58.5 (10.9)
62.9 (11.8)
7.7 (6.7)
Left
59.4 (12.2)
64.5 (13.1)
9.0 (9.4)
Right
58.3 (11.4)
64.7 (12.5)
11.4 (8.9)
Left
59.8 (12.1)
67.3 (13.5)
13.0 (7.9)
Right
58.5 (11.3)
63.8 (12.2)
9.4 (7.1)
Left
59.5 (12.0)
65.9 (13.2)
11.2 (7.4)
Right
58.3 (11.2)
65.2 (12.6)
12.2 (6.9)
Left
59.5 (12.2)
66.5 (13.2)
12.3 (8.0)
Right
58.5 (11.4)
64.2 (12.5)
10.1 (7.9)
Left
59.4 (12.1)
65.9 (12.6)
11.8 (9.1)
Right
58.3 (11.5)
65.5 (12.2)
12.9 (8.4)
Left
59.2 (11.9)
64.9 (12.5)
10.0 (6.7)
Right
58.1 (11.0)
62.2 (11.6)
7.4 (7.1)
Left
59.5 (11.5)
64.7 (11.9)
9.2 (6.7)
Right
58.3 (10.8)
64.6 (11.8)
11.1 (6.9)
Left
59.0 (11.9)
66.5 (13.2)
13.2 (10.7)
Right
58.1 (11.0)
63.6 (12.3)
10.0 (10.7)
Left
59.7 (11.4)
65.0 (12.3)
9.2 (7.3)
Right
58.4 (10.5)
65.0 (11.8)
11.5 (7.3)
Left
59.0 (11.3)
69.6 (13.4)
18.3 (8.4)
Right
58.1 (10.8)
70.4 (12.8)
21.6 (9.2)
Left
59.7 (11.9)
67.7 (12.9)
13.8 (7.1)
Right
58.5 (11.3)
68.4 (12.4)
17.4 (8.1)
F‡
P§
Reading
26.67
0.000
15.18
0.000
12.21
0.001
28.73
0.000
Verbal similarities (list)
Visuospatial design
comparison
Syntactic sentence
construction
Downloaded from http://stroke.ahajournals.org/ by guest on June 18, 2017
Visuospatial cube
construction
0.878
0.352
3.64
0.060
2.18
0.144
10.72
0.002
7.14
0.009
18.58
0.000
14.75
0.000
18.87
0.000
29.73
0.000
Verbal similarities (pairs)
Mental rotation
(alphanumeric)
Syntactic sentence
comparison
Mental rotation (figures)
Word fluency
Visual searching
Computer game
3D puzzle
*Mean velocity values are given in cm/s (SD).
†Mean % change above baseline value (SD).
‡F value (df always 1, 77).
§Difference between left and right sides in % change.
2155
2156
Stroke
October 1999
Downloaded from http://stroke.ahajournals.org/ by guest on June 18, 2017
order, syntactic sentence construction, word fluency, verbal
similarities (list), reading, and syntactic sentence comparison
showed a significant lateralization in favor of the left side.
Again in decreasing order, the 3D puzzle, computer game,
visuospatial design comparison, visual searching, and mental
rotation (figures) showed a significant difference in favor of
the right side.
We found no between-subjects effects for IQ or gender,
although the effect of gender came close of reaching statistical
significance, Hotelling T213,6151.82, P50.06. Age appeared to
be a significant between-subjects factor, Hotelling T226,12052.27,
P50.002). Post hoc univariate analyses of variance revealed that
the differences between the 3 age groups were significant for
syntactic sentence construction (F2,7753.77, P50.028), visuospatial cube construction (F2,7758.06, P50.001), verbal similarities (pairs) (F2,7753.30, P50.43), mental rotation (alphanumeric) (F2,7757.02, P50.002), syntactic sentence comparison
(F2,77511.58, P,001), mental rotation (figures) (F2,7753.71,
P50.029), visual searching (F2,7754.94, P50.01), and the computer game (F2,7755.21, P50.008). Closer inspection of the data
showed that the relative increase in BFV was always the highest
in the eldest age subgroup ($50 years). The age3side interaction effect was not significant. The mean BFV over the entire
experiment (average of 13 rest and 13 task conditions of both
sides) measured 67.3, 60.7, and 56.6 cm/s for the ,30, ,50, and
,65 age groups, respectively. This difference is significant, F2,87
6.83, P50.002.
The quality of the task performance was generally high,
with a mean of 78.4% (SD 21.8) correct answers for verbal
similarities (list), 57.7% (SD 16.5) for design comparison,
66.5% (SD 27) for cube construction, 92.3% (SD 6.9) for
verbal similarities (pairs), 92.4% (SD 8.2) for mental rotation
(alphanumeric), 91% (SD 12) for sentence comparison,
90.2% (SD 9.5) for mental rotation (figures), and 93.4% (SD
8.5) for visual searching. During the sentence construction
task an average of 38 words (SD 16) were correctly linked up,
and during word fluency an average of 33 words (SD 9) were
generated. We used Pearson correlations to evaluate the
association between BFV change, IQ, and quality of performance. We used a significance level of 0.01 to take the
multiple correlations into account. Because no objective score
could be obtained for the computer game task and the 3D
puzzle, these tasks were not included in the analysis of
performance quality. No significant relationship was found
between left and right BFV changes and quality of performance. IQ was significantly associated with quality of performance (except for visuospatial cube construction, mental
rotation figures, and visual searching). No significant association was obtained between BFV change and IQ.
Discussion
In right-handed subjects, the prediction is that the left
hemisphere is dominant for linguistic functions whereas the
right hemisphere would be more involved in nonlinguistic or
visuospatial functioning.30 In general, fTCD research has
confirmed a marked left-hemispheric lateralization for language functioning.11,12,31
The strongest left-hemispheric BFV lateralization was elicited
by a syntactic sentence construction task. A lesser, although still
significant, left-sided asymmetry was found in another grammatical task that required the comparison of sentences. This
finding is in agreement with the results on a similar syntactic
sentence comparison task used by Rihs et al.12
Significant left-hemispheric BFV lateralization of word
fluency tasks in right-handed subjects has been reported
repeatedly.4,9,15,32 Only Harders et al5 failed to find a significant lateralization for this task. The fact that 34% of Harders’
subjects were left-handed may have obfuscated the outcome.
The significant left-sided lateralization of our verbal similarities (list) task is in agreement with the results on a similar
task used by Hartje et al6 and Bulla-Hellwig et al1 who found
a significant and close to significant left-hemispheric lateralization respectively. Our verbal similarities (pairs) task,
however, failed to reach significance although a trend toward
left-hemispheric lateralization was observed (P50.06). This
finding is in agreement with previous results on a similar
(paired) synonym task,12 where a BFV shift to the left was
observed that just failed significance from the lateralization
observed during baseline.
The significant left-hemispheric lateralization of our reading aloud task is in line with the results of Droste et al4 and
Rihs et al.12 Both studies found a tendency toward left-sided
lateralization in relatively smaller samples of right-handed
subjects (n528 and n514, respectively). Again, Harders et
al5 failed to find any lateralization for this task in a larger
(N570), but mixed handedness group.
To summarize the research on verbal paradigms, it appeared that the magnitude of the left-sided lateralization was
the greatest for linguistic tasks that required more active or
creative processing of the verbal material, such as constructing a sentence with given words or retrieving words that
begin with a designated letter. Tasks that merely required
comparison of verbal stimuli (even if these stimuli were of a
syntactic nature) or depended on well-learned automatic
processing, such as reading, showed a lesser though still
significant lateralization. If the semantic task became too
simple, such as judging whether a pair of words were
synonyms, the lateralization effect failed to reach
significance.
The alleged right-hemispheric BFV lateralization for nonverbal visuospatial tasks is generally considered to be less
straightforward.1,6,15 In our study, however, only 2 of 7
visuospatial tasks failed to show a significant righthemispheric effect.
Lesion studies have provided conflicting evidence regarding hemispheric specialization for mental rotation.33–38
Positron emission tomography (PET) research with a task
requiring mental rotation of alphanumeric stimuli28 found a
regional cerebral blood flow increase in the right and left
temporoparietal regions. These authors suggested that activation of the right posterosuperior parietal cortex and the
bilateral posterior temporal cortex reflected the recognition of
(transformed) visual patterns, whereas activation of the left
inferior parietal lobule and the right head of the caudate
nucleus reflected the mental rotation of the stimuli. A similar
task in our study (mental rotation (alphanumeric)) showed a
significant increase in BFV but no significant lateralization.
These data suggest that both hemispheres are symmetrically
Vingerhoets and Stroobant
Downloaded from http://stroke.ahajournals.org/ by guest on June 18, 2017
involved in this task. In contrast, our second mental rotation
task, which used simple pictures or typographic symbols and
required actual comparison with the “upright” stimulus (instead of comparison against a remembered stimulus), showed
a significant right-hemispheric BFV asymmetry. Perhaps the
stronger visuoperceptual demand of this task was responsible
for the significant right-hemispheric BFV shift. In other
fTCD research, a similar task requiring the mental rotation
and comparison of visual figures failed to find an asymmetry
in MCA blood flow acceleration in a smaller right-handed
sample, although a trend toward a right-hemispheric asymmetry was observed.6 In view of the current disagreement
with regard to the hemispheric representation of the processes
of mental rotation and visualization39 – 41 and in view of the
low spatial resolution of fTCD data, mental rotation tasks
appear not to be the method of choice for eliciting a robust
right-hemispheric lateralization in BFV.
A second visuospatial task that failed to show the expected
right-hemispheric lateralization was our cube construction
task. Despite the fact that the task required the mental
manipulation of a complex visual image, a significant righthemispheric asymmetry was not obtained. Here, too, the fact
that no significant lateralization could be induced may be
interpreted in favor of a complex and bilateral hemispheric
activation in the mental manipulation of visual stimuli.
The significant right-hemispheric asymmetry elicited by
the visual searching task is in agreement with a similar task
used by Hartje et al6 and Bulla-Hellwig et al.1 Both studies
found a significant right-hemispheric MCA blood flow acceleration in what they defined as a typical example of a
perceptual speed test. We also found a significant righthemispheric effect in a design comparison task. Again, this is
a task that requires visual attention and perceptual speed. Its
significant right-hemispheric activation is in agreement with
the hypothesis of a dominant right-hemispheric role in (at
least visual) attention that has been illustrated in PET42 and
TCD research.9
The most asymmetric right-sided BFV shift in our study
was elicited by a computer game and a 3D puzzle. In contrast
to the other visuospatial tasks that required a simple (bilateral) motor response, the motor manipulation of steering wheel
and 3D puzzle were much less under experimental control
and could have resulted in a predominant left-hemispheric
motor cortex activation in right-handed subjects, thus masking an expected right-hemispheric acceleration for these
visuomotor tasks. This was not the case, and both tasks
showed a strong and highly lateralized right-hemispheric
activation that was probably due to the visuospatial, visuomotor, and attentional demands of these tasks. Kelley et al7
used a computer game that just failed to find a righthemispheric BFV shift (P,0.10). However, the study consisted of a smaller sample (n521), including 5 ambidextrous
subjects and 1 left-handed subject, and the game was played
with a joystick held in the left hand and manipulated by the
right hand. These methodological differences might explain
the nonsignificant finding in this study. To our knowledge,
3D puzzles have never before been used in TCD research.
We conclude from these data that paradigms which combined visuospatial attention and visuomotor manipulation
Functional Transcranial Doppler Velocimetry
2157
showed a strong bilateral BFV increase and elicited the most
asymmetric right-hemispheric blood flow acceleration. Tasks
that required the mental rotation of visual stimuli appeared to
activate both hemispheres more symmetrically and reduce the
lateralization effect that can be measured through TCD.
The decrease of CBF and absolute BFV with age has
frequently been reported.3,4,27,43– 46 This was also the case in
our study, in which overall mean absolute BFV significantly
decreased with increasing age. In contrast, all tasks elicited a
higher percentage in BFV change from rest to mental activation in older people compared with younger. This age effect
on relative BFV change was significant in 8 of the 13 tasks.
Similar findings in 2 of 6 tasks have been reported elsewhere.3 The nonsignificant side3age interaction effect indicated that despite higher relative BFV reactivity, the effects
of lateralization remained constant over the age groups.
Interpretation of these findings remains to be determined.
Most previous studies failed to obtain (or report) data on
the qualitative performance of their subjects, although a
possible relationship with BFV has been hypothesized.15 One
of the main reasons for not obtaining data on performance
quality was that subjects were often not allowed to communicate their answers during the activation phase. Verbal or
motor responses were believed to interfere with and mask
lateralization effects or to influence the Doppler signal.
Because we wanted to evaluate the relationship between
performance quality and BFV and because we believed that
communication of answers after the trial is of rather questionable reliability, we assessed our subjects’ responses
during activation. In most tasks, subjects were instructed to
give a bilateral motor response to avoid lateralized activation
of one motor cortex. During the reading task subjects were
instructed to read the words aloud, whereas during syntactic
sentence construction and word fluency, subjects were instructed to whisper their answers. Reading aloud did not
interfere with the visual Doppler spectrum and showed the
expected left-hemispheric lateralization. A similar observation was made for the tasks in which the responses had to be
whispered. This is in contrast with the belief that the
production of speech sound (whether whispered or spoken
aloud) might cloud potential lateralization effects15 because it
involves larger bilateral areas of the brain.47 Although we
managed to evaluate the actual performance quality for most
tasks, no significant relationship was found between quality
of performance and BFV change. In addition, no association
was found between BFV change and IQ.
Our results demonstrate that bilateral TCD of the MCA is
sufficiently sensitive to simultaneously compare the BFV
response of the 2 hemispheres during various cognitive tasks.
In general, our findings agree with present neuropsychological theories of hemispheric lateralization for cognitive functions and with the findings of fTCD research. Our data further
suggest that left-hemispheric lateralization can best be elicited by linguistic tasks that require active or creative processing of the verbal material. Right-hemispheric lateralization
appeared most readily in tasks that combined visual attention
and visuomotor manipulation. Finally, we found no relationship between performance quality and BFV change, which
implies that the sheer process of trying to solve a specific task
2158
Stroke
October 1999
activates specific brain regions regardless of whether the final
response is correct or not. Further evaluation and refinements
of tasks that show important hemispheric asymmetries in
BFV are warranted. This research can contribute to our
understanding of hemispheric specialization, it can serve as
an inexpensive testing ground for new and promising cognitive paradigms, and it can be used, after further refinement of
the experimental paradigms and validation against other
techniques,10 as a noninvasive clinical tool to determine
hemispheric dominance in the individual patient.
Acknowledgment
This research was supported by grant G.0011.98 from the Fund for
Scientific Research, Flanders, Belgium.
References
Downloaded from http://stroke.ahajournals.org/ by guest on June 18, 2017
1. Bulla-Hellwig M, Vollmer J, Götzen A, Skreczek W, Hartje W. Hemispheric asymmetry of arterial blood flow velocity changes during verbal
and visuospatial tasks. Neuropsychologia. 1996;34:987–991.
2. Cupini LM, Matteis M, Troisi E, Sabbadini M, Bernardi G, Caltagirone
C, Silvestrini M. Bilateral simultaneous transcranial Doppler monitoring
of flow velocity changes during visuospatial and verbal working memory
tasks. Brain. 1996;119:1249 –1253.
3. Droste DW, Harders AG, Rastogi E. A transcranial Doppler study of
blood flow velocity in the middle cerebral arteries performed at rest and
during mental activities. Stroke. 1989;20:1005–1011.
4. Droste DW, Harders AG, Rastogi E. Two transcranial Doppler studies on
blood flow velocity in both middle cerebral arteries during rest and the
performance of cognitive tasks. Neuropsychologia. 1989;27:1221–1230.
5. Harders AG, Laborde G, Droste DW, Rastogi E. Brain activity and blood
flow velocity changes: a transcranial Doppler study. Int J Neurosci.
1989;47:91–102.
6. Hartje W, Ringelstein EB, Kistinger B, Fabianek D, Willmes K. Transcranial Doppler ultrasonic assessment of middle cerebral artery blood
flow velocity changes during verbal and visuospatial cognitive tasks.
Neuropsychologia. 1994;32:1443–1452.
7. Kelley RE, Chang JY, Scheinman NJ, Levin BE, Duncan RC, Lee SC.
Transcranial Doppler assessment of cerebral flow velocity during cognitive tasks. Stroke. 1992;23:9 –14.
8. Kelley RE, Chang JY, Suzuki S, Levin BE, Reyes-Iglesias Y. Selective
increase in the right hemisphere transcranial Doppler velocity during a
spatial task. Cortex. 1993;29:45–52.
9. Knecht S, Henningsen H, Deppe M, Huber T, Ebner A, Ringelstein EB.
Successive activation of both cerebral hemispheres during cued word
generation. Neuroreport. 1996;7:820 – 824.
10. Knecht S, Deppe M, Ebner A, Henningsen H, Huber T, Jokeit H, Ringelstein
EB. Noninvasive determination of language lateralization by functional transcranial Doppler sonography: a comparison with the Wada test. Stroke. 1998;
29:82–86.
11. Markus HS, Boland M. “Cognitive activity” monitored by non-invasive
measurement of cerebral blood flow velocity and its application to the
investigation of cerebral dominance. Cortex. 1992;28:575–581.
12. Rihs F, Gutbrod K, Steiger HJ, Sturzenegger M, Mattle HP. Determination of cognitive hemispheric dominance by “stereo” transcranial
Doppler sonography. Stroke. 1995;26:70 –73.
13. Schnittger C, Johannes S, Münte TF. Transcranial Doppler assessment of
cerebral blood flow velocity during visual spatial selective attention in
humans. Neurosci Lett. 1996;214:41– 44.
14. Schnittger C, Johannes S, Arnavaz A, Münte TF. Blood flow velocity
changes in the middle cerebral artery induced by processing of hierarchical visual stimuli. Neuropsychologia. 1997;35:1181–1184.
15. Silvestrini M, Cupini LM, Matteis M, Troisi E, Caltagirone C. Bilateral
simultaneous assessment of cerebral flow velocity during mental activity.
J Cereb Blood Flow Metab. 1994;14:643– 648.
16. Sturzenegger M, Newell DW, Aaslid R. Visually evoked blood flow
response assessed by simultaneous two-channel transcranial Doppler
using flow velocity averaging. Stroke. 1996;27:2256 –2261.
17. Varnadore AE, Roberts AE, McKinney WM. Modulations in cerebral
hemodynamics under three response requirements while solving
language-based problems: a transcranial Doppler study. Neuropsychologia. 1997;35:1209 –1214.
18. Harder DR. Pressure-dependent membrane depolarization in cat middle
cerebral artery. Circ Res. 1984;55:197–202.
19. Heistad DD, Marcus AL, Abboud FM. Role of larger arteries in regulation of cerebral blood flow in dogs. J Clin Invest. 1978;234:371–383.
20. Huber P, Handa J. Effect of contrast material, hypercapnia, hyperventilation, hypertonic glucose and papaverine on the diameter of the cerebral
arteries: angiographic determination in man. Invest Radiol. 1967;2:17–32.
21. Kontos HA, Wei EP, Navari RM, Levasseur JE, Rosenblum WI,
Patterson JL. Responses of cerebral arteries and arterioles to acute hypotension and hypertension. Am J Physiol. 1978;234:H371–H383.
22. Radü EW, duBoulay GH. Paradoxal dilatation of large cerebral arteries in
hypocapnia in man. Stroke. 1976;7:569 –572.
23. Toole JF. Cerebrovascular Disorders. 3rd ed. New York, NY: Raven
Press Publishers; 1984.
24. Oldfield RC. The assessment and analysis of handedness: the Edinburgh
inventory. Neuropsychologia. 1971;9:97–113.
25. Schmand B, Lindeboom J, van Harskamp F. Nederlandse Leestest voor
Volwassenen (Dutch Adult Reading Test). Lisse, the Netherlands: Swets
and Zeitlinger BV; 1992.
26. van der Ploeg HM, Defares PB, Spielberger CD. Handleiding bij de
Zelfbeoordelingsvragenlijst (ZBV) (Manual of the Self-Report Questionnaire). Lisse, the Netherlands: Swets and Zeitlinger BV; 1980.
27. Ringelstein EB, Kahlscheuer B, Niggemeyer E, Otis SM. Transcranial
Doppler sonography: anatomical landmarks and normal velocity values.
Ultrasound Med Biol. 1990;16:745–761.
28. Alivisatos B, Petrides M. Functional activation of the human brain during
mental rotation. Neuropsychologia. 1997;35:111–118.
29. FEPSY. The Iron Psyche: Manual. Heemstede, the Netherlands; Nederlands Instituut voor Epilepsiebestrijding; 1995.
30. Kolb B, Whishaw IQ. Fundamentals of Human Neuropsychology. 3rd ed.
New York, NY: WH Freeman; 1990.
31. Njemanze PC. Cerebral lateralization in linguistic and nonlinguistic perception: analysis of cognitive styles in the auditory modality. Brain Lang.
1991;41:367–380.
32. Silvestrini M, Troisi E, Matteis M, Razzano C, Caltagirone C. Correlations of flow velocity changes during mental activity and recovery from
aphasia in ischemic stroke. Neurology. 1998;50:191–195.
33. Dee HL. Visuoconstructive and visuoperceptive deficit in patients with
unilateral cerebral lesions. Neuropsychologia. 1970;8:305–314.
34. De Renzi E, Faglioni P. The relationship between visuo-spatial
impairment and constructional apraxia. Cortex. 1967;3:327–342.
35. Ditunno P, Mann VA. Right hemisphere specialization for mental rotation
in normals and brain damaged subjects. Cortex. 1990;26:177–188.
36. Mehta Z, Newcombe F, Damasio H. Visuospatial processing. Cortex.
1987;23:447– 461.
37. Ratcliff G. Spatial thought, mental rotation and the right cerebral hemisphere. Neuropsychologia. 1979;17:49 –54.
38. Vingerhoets G, Lannoo E, Bauwens S. Analysis of the Money Road-Map
test performance in normal and brain-damaged subjects. Arch Clin Neuropsychol. 1996;11:1–9.
39. Burton LA, Wagner N, Lim C, Levy J. Visual field differences for
clockwise and counterclockwise mental rotation. Brain Cogn. 1992;18:
192–207.
40. Cohen MS, Kosslyn SM, Breiter HC, DiGirolamo GJ, Thompson WL,
Anderson AK, Bookheimer SY, Rosen BR, Belliveau JW. Changes in
cortical activity during mental rotation: a mapping study using functional
MRI. Brain. 1996;119:89 –100.
41. Van Strien JW, Bouma A. Mental rotation of laterally presented random
shapes in males and females. Brain Cogn. 1990;12:297–303.
42. Pardo JV, Fox PT, Raichle ME. Localization of a human system for sustained
attention by positron emission tomography. Nature. 1991;349:61–64.
43. Ackerstaff RGA, Keunen RWM, van Pelt W, van Swijndregt ADM,
Stijenen T. Influence of biological factors on changes in mean CBF
velocity in normal ageing: a TCD study. Neurol Res. 1990;12:187–191.
44. Melamed E, Lavy S, Bentin S, Cooper G, Finot Y. Reduction in regional
cerebral blood flow during normal aging in man. Stroke. 1980;11:31–35.
45. Orlandi G, Murri L. Transcranial Doppler assessment of cerebral flow
velocity at rest and during voluntary movements in young and elderly
healthy subjects. Int J Neurosci. 1996;84:45–53.
46. Warren LR, Butler RW, Katholi CR, Halsey JH. Age differences in
cerebral blood flow during rest and during mental activation with and
without monetary incentive. J Gerontol. 1985;40:53–59.
47. Damasio AR, Damasio H. Brain and language. Sci Am. 1991;267:62–71.
Lateralization of Cerebral Blood Flow Velocity Changes During Cognitive Tasks: A
Simultaneous Bilateral Transcranial Doppler Study
Guy Vingerhoets and Nathalie Stroobant
Downloaded from http://stroke.ahajournals.org/ by guest on June 18, 2017
Stroke. 1999;30:2152-2158
doi: 10.1161/01.STR.30.10.2152
Stroke is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231
Copyright © 1999 American Heart Association, Inc. All rights reserved.
Print ISSN: 0039-2499. Online ISSN: 1524-4628
The online version of this article, along with updated information and services, is located on the
World Wide Web at:
http://stroke.ahajournals.org/content/30/10/2152
Permissions: Requests for permissions to reproduce figures, tables, or portions of articles originally published
in Stroke can be obtained via RightsLink, a service of the Copyright Clearance Center, not the Editorial Office.
Once the online version of the published article for which permission is being requested is located, click
Request Permissions in the middle column of the Web page under Services. Further information about this
process is available in the Permissions and Rights Question and Answer document.
Reprints: Information about reprints can be found online at:
http://www.lww.com/reprints
Subscriptions: Information about subscribing to Stroke is online at:
http://stroke.ahajournals.org//subscriptions/