Published in 1994, this groundbreaking paper featured the research of Professor Per Roland, Professor Ryuta Kawashima (of “Brain Training” fame) and Professor Brendan O’ Sullivan. This landmark research was the first to prove in human brain imaging studies that visual attention is impaired when we do other attention-competing tasks such as manual tasks such as using mobile phones while driving.

1. Proc. Natl. Acad. Sci. USA
Vol. 92, pp. 5969-5972, June 1995
Neurobiology
Positron-emission tomography studies of cross-modality inhibition
in selective attentional tasks: Closing the "mind's eye"
(human brain activity/regional cerebral blood flow/attention/deactivation)
RYUTA KAWASHIMA, BRENDAN T. O'SULLIVAN, AND PER E. ROLAND
Division of Human Brain Research, Department of Neuroscience, Karolinska Institute, S-171 77, Stockholm, Sweden
Communicated by Seymour S. Kety, National Institutes of Health, Bethesda, MD, March 14, 1995 (received for review April 20, 1994)
matching (11)]. The two tasks were matched in terms of their
performance difficulty and regional changes in CBF were
identified by standard image subtraction techniques in which
the task state is compared to a similar control state. One of the
studies (tactile shape matching) was performed with the
subjects' eyes open in both the task and control states so that
the "eyes open" condition was matched before subtracting the
images. The other somatosensory study (roughness discrimination) was performed with the eyes closed in both the task
and control states, so that this condition also was matched
before image subtraction. The two somatosensory tasks were
chosen to specifically examine whether hypothesized decreases
in rCBF in nonattended areas such as the visual cortical areas
during somatosensory tasks would still occur irrespective of the
general level of visual input (and blood flow values).
It is a familiar experience that we tend to
ABSTRACT
close our eyes or divert our gaze when concentrating attention
on cognitively demanding tasks. We report on the brain
activity correlates of directing attention away from potentially
competing visual processing and toward processing in another
sensory modality. Results are reported from a series of
positron-emission tomography studies of the human brain
engaged in somatosensory tasks, in both "eyes open" and
"eyes closed" conditions. During these tasks, there was a
significant decrease in the regional cerebral blood flow in the
visual cortex, which occurred irrespective of whether subjects
had to close their eyes or were instructed to keep their eyes
open. These task-related deactivations of the association areas
belonging to the nonrelevant sensory modality were interpreted as being due to decreased metabolic activity. Previous
research has clearly demonstrated selective activation of cortical regions involved in attention-demanding modalityspecific tasks; however, the other side of this story appears to
be one of selective deactivation of unattended areas.
MATERIALS AND METHODS
Several points of methodology were critical to the performance of these studies. First, it was necessary to obtain
quantitative data on absolute rCBF changes (in ml per 100 g
of brain tissue per min) since normalization procedures routinely used in many other PET studies could artefactually lead
to increases and reciprocal decreases in rCBF values. Absolute
measures of rCBF required brachial arterial cannulation and
continuous arterial sampling to define input curves after each
bolus injection of the radioisotope. High-resolution functional
images (full width at half maximum, 4.5 mm) were obtained by
using an 8-ring (15 slice) PET camera (PC2048-15B), which has
an interslice interval of 6.7 mm (12). The freely diffusible tracer [15O]butanol (13) was used in preference to H2150. Anatomical standardization and accurate functional localization
was obtained by coregistration with magnetic resonance imaging (MRI)-defined anatomy by using a computerized brain
atlas program (14, 15), which corrects interindividual differences in brain shape and size by both linear and nonlinear
parameters in order to reformat all individual images into
standard atlas anatomy.
The roughness discrimination task reported here was performed with the eyes closed, while the tactile matching task
was performed with the eyes open. Both tasks were performed
with the right hand. In roughness discrimination, nine subjects
performed a series of two alternative forced-choice discriminations of quantified roughness stimuli of known wavelength,
amplitude, and stimulus energy (16) and indicated with a
thumbs-up response only if the stimulus presented second was
perceived as "rougher" than the first. The control state was rest
with eyes closed. The tactile matching task required other
subjects to match a spherical ellipsoid presented to their right
hand, with one member of a linear array of similar ellipsoids
hidden from view behind a white curtain in front of them. The
right hand was used for all palpations, and they indicated their
choice of a matching stimulus by pointing with their right index
Regional cerebral blood flow (rCBF) changes in the human
brain have now been extensively studied by positron-emission
tomography (PET) methods (1). Regional changes in rCBF are
monotonically related to regional changes in cerebral metabolic rate, in particular the metabolic demands of maintaining
the transmembrane ionic gradients of active neurons (1-4).
Brain structures that actively participate in the performance of
specific cognitive tasks can be identified as discrete regions of
increase in rCBF. During specific cognitive tasks, our attention
is selectively focused on the relevant sensory modality or
submodality from which information is necessary to successfully perform the task. In behavioral terms, stimuli within the
focus of attention are generally discriminated more quickly and
accurately, are registered more vividly in awareness and memory, and exert greater control over behavior than do unattended stimuli (5, 6). In physiological terms, selective attention
is described as changes in the excitability of cortical neurons
that are limited to, or focused on, a specific sensory modality
or submodality (1, 7). Increases in rCBF associated with these
changes in synaptic metabolic activity can then be identified in
modality-specific tasks (8, 9). Behavioral models of selective
attention generally accept the notion that attention has a
limited capacity, which must be flexibly distributed among
competing processes (5). The question arises, therefore, what
is happening neurobiologically to cortical areas of another
sensory modality which is not being attended during the
performance of a task? In particular, is there evidence of
inhibition or deactivation in these regions which are not being
attended during the performance of a cognitive task?
To answer this question, we performed two PET studies in
nine normal volunteers while they were engaged in somatosensory tasks [roughness discrimination (10) and tactile shape
The publication costs of this article were defrayed in part by page charge
payment. This article must therefore be hereby marked "advertisement" in
accordance with 18 U.S.C. §1734 solely to indicate this fact.
Abbreviations: rCBF, regional cerebral blood flow; PET, positronemission tomography; MRI, magnetic resonance imaging.
5969

2. 5970
Neurobiology: Kawashima et al.
finger. The subjects' eyes were open throughout this study and
fixated on a cross drawn on the curtain in front of them. In the
control state the subjects lay quietly without moving or speaking and fixated the cross with no specific task to perform.
Throughout the PET measurements, the electroencephalogram and the electrooculogram were monitored continuously.
The subjects' behavior was also monitored continuously with
video cameras. The tests started at the start of the injection of
isotope and continued for 180 sec.
Subjects had their PET studies as well as MRI tomographs
performed with the same bite-fixation stereotaxic helmets in
order to correlate functional and anatomical data. Anatomical
structures of each subject's MRI were fitted interactively using
the computerized brain atlas (14, 15). All PET and MRI
images were then transformed into the standard atlas brain
anatomy using these parameters. The precision of the reformation process has a SD of 2-3 mm in the localization of the
inner and outer brain surfaces (15). Subjects received 70 mCi
("1 mCi/kg; 1 Ci = 37 GBq) of [150]butanol as a bolus
intravenous injection at the commencement of each PET run,
which lasted for 80 sec. Images were reconstructed with a
Hanning filter of 4 mm and were displayed with a pixel size of
2.01 x 2.01 mm. There was no further filtering of images. The
arterial radiotracer concentration was measured continuously
and the arterial partial pressures of 02 and CO2 (Po2 and
Pco2) were measured repetitively. The rCBF was calculated by
the dynamic approach on the data sampled between 0 and 80
sec after the start of the injection in frames of 5 sec each (17,
18). The rCBF images were corrected according to the arterial
Pco2 measured during each PET procedure. The correction
was done before test minus control subtractions to the arterial
Pco2 level of the control (18). Increases in rCBF were calculated by voxel-by-voxel subtractions of the control state images
from the corresponding images of each task state. Decreases
in rCBF were calculated by voxel-by-voxel subtractions of the
task state images from the corresponding images of each
control state. All images of the brain were anatomically
standardized as described above, and mean change images,
variance images, and descriptive Student's t images were
calculated voxel by voxel. The procedures and statistical analysis were described extensively in a recent report (18). The
criterion used for accepting rCBF changes in adjacent clustered voxels as activations gives an average probability of 0.9
of finding one false-positive cluster (and <0.08 of finding
more) in the three-dimensional space representing the brain.
The descriptive t image was limited by accepting only voxels
having t > 1.83 and occurring in clusters of size 12 and above;
all other voxels were set to 0. This image is called a cluster
image. In this image only clusters of size 12 and above having
1.83 are shown and considered regions of changed rCBF.
In Table 1, the cluster sizes of the activated fields are shown
in cm3. One voxel had a volume of 44.03 mm3. Clusters of 12
or more contiguous voxels in the t images were considered
areas of significant physiological change in rCBF on the basis
of previous analysis of noise images (18). Areas of significant
rCBF change were identified from the final cluster images and
anatomical localization made by calling structures from the
CBA program. The values of rCBF change (ml per min per g
of tissue) and the volume of brain in which this occurred (cm3)
were calculated by voxel-by-voxel analysis of regions in mean
subtraction CBF images, which had been identified from
corresponding regions of significant change in cluster images.
Further details of the image analysis procedure have been
t>
described
(18).
RESULTS
Fig. 1 illustrates that activation (shown in red) of the contralateral sensorimotor strip is associated with diffuse decreases (shown in blue) in visual cortical and other cortical
Proc. Natl. Acad. Sci. USA 92
(1995)
FIG. 1. Increases (red) and decreases (blue) in the rCBF are shown
for roughness discrimination (Left) and for tactile matching (Right).
Corresponding sections are shown to illustrate somatosensory activation associated with decreases in activity in visual areas. The atlas
positions of the central, postcentral, and parietooccipital sulci are
shown. Right in the image is left in the brain. Roughness discrimination
was performed with the eyes closed while tactile matching was
performed with the eyes open. Both tasks were performed with the
right hand. The two somatosensory tasks were of comparable difficulty
with a percentage correct rate of 74% and 82%, respectively. There
was no significant difference in global blood flow in test and control
conditions in either experiment.
areas in both somatosensory tasks (roughness discrimination,
Left; tactile shape matching, Right). For the purposes of
discussion, we regarded visual areas as the whole of the
occipital lobe. The decreases in rCBF were most marked in
nonprimary visual regions, in particular in areas of the occipital lobe near the border of the occipital lobe and the parietal
lobe. In addition, there were decreases in rCBF in the precuneus, the posterior part of the superior parietal lobule, and the
posterior part of the angular gyrus, which are putative remote
visual areas (1). Some areas in the frontal lobe also showed
decreases in activity. The function of much of the frontal
cortex remains uncertain, but it is possible in this case that
these decreases in activity may have been related to the highly
significant decreases in activity identified in visual cortical
regions. There were no visual regions at all that showed any
increase in activity while performing the somatosensory tasks.
Similar decreases occurred both when the subjects' eyes were
closed (i.e., roughness discrimination) and when the subjects'
eyes were open during the task performance (i.e., tactile shape
matching).
The subjects fixated the cross hair in the open eyes conditions (tactile shape matching and control condition, fixation)
and had their eyes closed in the closed eyes condition (roughness and its control). The number of eye movements present
for the measurement period for control and shape matching,
respectively, and the number of eye blinks did not differ
(frequency of blinks and small eye movements 0.79 ± 3.3 and
0.87 ± 3.7 Hz; mean ± SD). There were no systematic changes
in arterial Pco2 between the test conditions and their respective control conditions (P > 0.1, P > 0.5; paired comparison,
t test for tactile matching versus control and roughness versus
control) and the global blood flow did not change (P > 0.9, P

3. Proc. Natl. Acad. Sci. USA 92 (1995)
Neurobiology: Kawashima et al.
> 0.5; paired comparison t test) for tactile matching versus
control 54.5 ± 2.7 and 57.1 ± 3.0 and roughness versus control
60.8 ± 4.0 and 60.9 ± 3.3.
Fig. 2 shows the mean values of decreased rCBF in primary
versus nonprimary visual areas in the occipital cortex of each
hemisphere, as well as the value of increased rCBF in the left
primary and nonprimary somatosensory cortex. Table 1 provides details of the specific anatomical location of significant
rCBF decreases including Talairach coordinates of the center
of each field, field volume, and the actual value of the rCBF
change. No specific fields of significant change were identified
in the primary visual cortex in either study. This is in contrast
with the number ofbroad cortical fields that showed significant
decreases in activity that were distributed across the nonprimary visual regions.
DISCUSSION AND CONCLUSIONS
The results of this study prompt a further examination of the
meaning of rCBF changes in PET studies. The underlying
mechanisms for the tight coupling of rCBF changes with
changing synaptic metabolic demands in active neuronal populations are still poorly understood (1, 20, 21). The highest
energy requirements in the brain are thought to be for active
transport of Na+ through ATP-dependent ion channels to
restore membrane potentials after depolarization (3, 7, 22, 23).
Depolarization may take the form of action potentials or
excitatory postsynaptic potentials (EPSPs). There is already
good evidence that EPSPs, without action potential formation,
make a sizeable contribution to this metabolic load of the brain
as reflected in rCBF studies (1, 7, 22, 23). It has been shown
that inhibition of the Na+ pump leads to a marked decrease in
rCBF (23). The best explanation of decreased rCBF would
appear to be that it reflects a net decrease in regional synaptic
metabolic demand (20, 23-25). Increase of GABAAergic local
inhibition in the neocortex decreases rCBF and most likely also
the local metabolism (24, 26). We call the decrease in rCBF
seen in the visual areas deactivation. This deactivation, for the
reasons described above, most likely was due to a decreased
excitation of these areas or a local net increase in synaptic
inhibition. The present results do not give any clues concerning
how the deactivation of visual areas is controlled by other
Eyes open
Eyes closed
cn
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-6.
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uz co
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FIG. 2. Histograms of increases and decreases in mean rCBF in ml
per 100 g per min by region: primary and nonprimaryvisual cortex (PV
and NV) and primary and nonprimary somatosensory cortex (PS and
NS). Lt, left; Rt, right. Primary visual cortex was defined as the area
of cortex lining the calcarine fissure visualized directly from MRI;
nonprimary visual cortex was defined as the remainder of cortex in the
occipital lobe. Primary somatosensory cortex was defined as the
anterior half of the postcentral gyrus as visualized on MRI; nonprimary somatosensory cortex was defined as the posterior half of the
postcentral gyrus. Changes in mean rCBF are shown in ml per min per
100 g of brain tissue ISE. Level of significance is indicated (*,
significant at P = 0.05). Note that these regions are larger than those
listed in Table 1.
structures in the brainstem or thalamus, since we were unable
to find any concomitant change in rCBF in these structures.
In studying both eyes open and eyes closed tasks with
matched control states, we found that decreases were independent of the level of rCBF in the visual cortical regions in
the control states-that is, independent of whether visual
information reached the visual cortices or not during the
somatosensory tests. The functional significance of this observed decrease in cortical activity in regions not directly
involved in performing a specific task may be understood as a
means of reducing the probability of interference of information from other sensory modalities. Deactivation of cortical
regions not associated with the task at hand may therefore be
an essential component of selective attentional processes
playing a complementary role to activation of those areas of
Table 1. Anatomic location of significant rCBF decreases
Talairach coordinate
Region
X
Superior occipital gyrus (left)
Middle occipital gyrus (left)
Middle occipital gyrus (left)
Inferior occipital gyrus (left)
Inferior occipital gyrus (left)
Middle occipital gyrus (right)
Inferior occipital gyrus (right)
31
33
46
27
41
-27
-26
Vol,
Y
Z
cm3
Tactile shape matching (eyes open)
-68
-74
-77
-79
-83
-78
-89
rCBF, ml
per 100 g
per mm
Decrease,
ml per
100 g per
mi
t value
32
1.63
61.6 (3.1)
14.1 (0.8)
2.62 (0.12)
19
1.01
67.9 (2.5)
14.0 (0.7)
3.03 (0.18)
4
0.84
47.5 (2.5)
12.9 (1.0)
2.25 (0.06)
-11
0.97
54.6 (3.6)
11.1 (0.5)
2.59 (0.14)
-8
0.62
51.6 (2.3)
13.8 (0.9)
2.42 (0.13)
11
0.84
53.8 (2.3)
12.3 (0.6)
2.19 (0.08)
-10
1.58
57.1 (2.2)
11.6 (0.7)
2.70 (0.21)
Roughness discrimination (eyes closed)
Middle occipital gyrus (left)
35
-61
22
1.58
62.2 (2.2)
7.1 (0.3)
1.86 (0.05)
Middle occipital gyrus (left)
48
-63
7
1.12
43.0 (1.8)
7.3 (0.5)
1.94 (0.08)
Middle occipital gyrus (right)
-43
-52
9
0.88
61.0 (2.4)
9.3 (0.8)
2.07 (0.11)
Inferior occipital gyrus (right)
-40
-65
-2
1.76
47.6 (1.8)
7.1 (0.4)
2.19 (0.09)
Talairach coordinates (19) of these identified structures were calculated as follows. First, the center of gravity of each cluster was identified.
Second, the stereotaxic coordinates of the center of gravity of each cluster were measured relative to the midpoint between the anterior and posterior
commissures. Third, these coordinates were transformed into Talairach coordinates by using linear parameters in order to correct differences in
size and baseline angle between the standard brain of the computerized brain atlas system and the original Talairach standard brain. The Talairach
coordinates (X,Y,Z) of each cluster were calculated in millimeters measured from the midpoint between the anterior and posterior commissures.
Coordinates are given in the order X (width), Y (anterior-posterior), and Z (height). rCBF decrease values are actual mean decreases in ml per
100 g per min (SE). t values are calculated by Student's t test.

4. 5972
Neurobiology: Kawashima et al.
Proc. Natl. Acad. Sci. USA 92
(1995)
cortex that are required to be active during a given task. This
finding may be related to the observations of unaltered global
blood flow and metabolism in the brains of subjects doing tests
that are associated with increases of the rCBF and regional
cerebral metabolism (25, 27). Earlier Seitz and Roland (25)
reported decreases of rCBF in parietal, superior temporal, and
prefrontal regions in a somatosensory task, and Haxby et al
(28) very recently reported significant decreases of normalized
rCBF (most likely concurrent with true rCBF decreases) in
auditory and prefrontal regions during a visual task. These
studies and the present study thus strongly suggest that associated cross-modal decreases in cortical activity in areas not
directly required in performing a given task may be a frequent
consequence of the regulation of attention. Decreases in visual
areas occurred in a somatosensory task in which the eyes were
open but also in a similar task in which the eyes were closed.
Put simply, in performing cognitive demanding somatosensory
tasks, even if you do not tend to close your eyes, the "mind's
eye" will close.
11. Kawashima, R., Roland, P. E. & O'Sullivan, B. (1992) Soc.
Neurosci. Abstr. 8, 1420.
12. Litton, J., Holte, S. & Eriksson, L. (1990) IEEE Trans. Nucl. Sci.
37, 743-748.
13. Berridge, M., Adler, L., Nelson, D., Cassidy, E., Muzic, R.,
Bednarczyk, E. & Miraldi, F. (1991) J. Cereb. Blood Flow Metab.
11, 707-715.
14. Bohm, C., Greitz, T., Blomqvist, G., Farde, L., Forsgren, P.,
Kingsley, D., Sjogren, I., Wiesel, F. & Wik, G. (1986)Acta Radiol.
369, 449-452.
15. Seitz, R., Bohm, C., Greitz, T., Roland, P., Eriksson, L.,
Blomqvist, G., Rosenqvist, G. & Nordell, B. (1990) J. Cereb.
Blood Flow Metab. 10, 443-457.
16. Roland, P. E. & Mortensen, E. (1987) Brain Res. Rev. 12, 1-42.
17. Koeppe, R., Holden, J. & Ip, W. (1985) J. Cereb. Blood Flow
Metab. 5, 224-234.
18. Roland, P. E., Levin, B., Kawashima, R. & Akerman, S. (1993)
Hum. Brain Mapp. 1, 3-19.
19. Talairach, J., Szikla, G., Tournoux, P., Prossalentis, A., BordasFerrer, M., Covello, L., Jacob, M. & Mempel, E. (1967) Atlas
1. Roland, P. E. (1993) Brain Activation (Wiley, New York), pp.
195-236.
2. Greenberg, F., Hand, P., Sylvestro, A. & Reivich, M. (1979)Acta
Neurol. Scand. Suppl. 72, 12-14.
3. Mata, M., Fink, D. & Gainer, H. (1980) J. Neurochem. 34,
213-215.
4. Juliano, S., Hand, P. & Whitsel, B. (1981) J. Neurophysiol. 46,
1260-1282.
5. Kahneman, D. & Treisman, A. (1984) in Varieties of Attention,
eds. Parasuraman, R. & Davies, D. (Academic, New York), pp.
929-961.
6. Posner, M. & Petersen, S. (1990)Annu. Rev. Neurosci. 13,25-42.
7. Roland, P. E. (1981) J. Neurophysiol. 46, 744-754.
8. Roland, P. E. (1982) J. Neurophysiol. 48, 1059-1078.
9. Corbetta, M., Miezen, F. & Dobmeyer, S. (1991) J. Neurosci. 11,
2383-2402.
10. O'Sullivan, B., Roland, P. E. & Kawashima, R. (1994) Eur. J.
Neurosci. 6, 137-148.
20. Sokoloff, L. & Kety, S. S. (1960) Physiol. Rev. 40, 38-44.
21. Lassen, N. A. (1991) in Brain Work and Mental Activity, eds.
Lassen, N. A., Ingvar, D. H., Raidke, M. L. & Friberg, L.
(Munksgaard, Copenhagen), pp. 68-77.
22. Creutzfeldt, 0. (1975) in Brain Work, eds. Lassen, N. A. & Ingvar,
D. H. (Munksgaard, Copenhagen), pp. 21-46.
23. Astrup, J., Blennow, G. & Nilsson, B. (1977) Brain Res. 177,
115-126.
24. Roland, P. E. & Friberg, L. (1988) J. Cereb. Blood Flow Metab. 8,
314-323.
25. Seitz, R. J. & Roland, P. E. (1992)Acta Neurol. Scand. 86,60-67.
26. Gjedde, A. (1993) in Functional Organization of the Human Visual
Cortex, eds. Gulyas, B., Ottoson, D. & Roland, P. E. (Pergamon,
Oxford), pp. 291-306.
27. Sokoloff, L., Mangold, R., Wechsler, R. L., Kennedy, C. & Kety,
d'Anatomie Stereo-taxique du Telencephale (Masson, Paris).
S. S. (1955) J. Clin. Invest. 34, 1101-1108.
28. Haxby, J. V., Horwitz, B., Ungerleider, L. G., Masiog, J. M.,
Pietrini, P., Grady, C. L. (1994) J. Neurosci. 14, 6336-6353.