J Neurophysiol 104: 902–910, 2010.
First published May 26, 2010; doi:10.1152/jn.01014.2009.
Deficits in Action Selection Based on Numerical Information After
Inactivation of the Posterior Parietal Cortex in Monkeys
Hiromasa Sawamura,1,2 Keisetsu Shima,1 and Jun Tanji1,3
1
Department of Physiology, Tohoku University School of Medicine, Sendai; 2Department of Ophthalmology, Tokyo University School
of Medicine; and 3Brain Science Research Institute, Tamagawa University, Tokyo, Japan
Submitted 19 November 2009; accepted in fianal form 21 May 2010
INTRODUCTION
Cortical area 5 in the superior parietal lobule has traditionally been thought to integrate somatosensory information
(Duffy and Burchfiel 1971; Hyvärinen 1982; Sakata et al.
1973) and to provide sensorimotor guidance for motor behaviors (Ashe and Georgopoulos 1994; Ferraina and Bianchi 1994;
Kalaska et al. 2003). Area 5 has also been implicated in motor
selection or goal-directed control of motor behavior, including
visuomotor guidance (Crammond and Kalaska 1989; Kalaska
1996). Furthermore, neuronal activity in area 5 represents
certain spatiotemporal information that is required to achieve
intended actions; this information includes kinematic attributes
of motor outputs (Hamel-Pâquet et al. 2006; Kalaska et al.
1990), haptic information that is retained for seconds before
motor selection is executed (Koch and Fuster 1989), centrally
generated representations of the goals or metrics of intended
movements (Kalaska 1996), and the location of potential motor
targets (Kalaska and Crammond 1995).
On the other hand, we examined neuronal activity in area 5
(Sawamura et al. 2002) while monkeys were required to
perform one of two movements (push or turn a handle). In that
Address for reprint requests and other correspondence: J. Tanji, Tamagawa
University, Brain Science Research Institute, 6-1-6, Tamagawa Gakuen,
Machida, Tokyo, 194-8610, Japan (E-mail: [email protected]).
902
study, the selection of the correct movement was based solely
on a numerically defined sequence of self-executed motions—
for instance, select movement A five times, followed by movement B five times, and then return to movement A in a cyclic
manner. We found that neuronal activity in area 5 reflected the
numerosity of the executed movement. The representation of
numerical information in the parietal cortex was first identified
in humans (Cohen Kadosh et al. 2007; Dehaene et al. 1999;
Eger et al. 2003; Naccache and Dehaene 2001; Piazza et al.
2004; Pinel et al. 2004). Numerosity representation of visual
objects has also been observed in the posterior parietal cortex
(the fundus of the intraparietal sulcus; Nieder and Miller 2004;
Nieder et al. 2006) and the lateral intraparietal area (Roitman et
al. 2007) in subhuman primates. In the study by Nieder and
Miller (2004), monkeys were required to enumerate a set of
visual objects presented on a screen and then perform a delayed
match task based on the numerosity. In contrast, in our previous study, the numerosity of movements performed by the
individuals themselves had to be determined and remembered.
Therefore cortical area 5 representation of the number of
self-movements may be crucial for selecting the correct movement. If this hypothesis is correct, inactivation of area 5 will
impair performance in motor tasks that require motor selection
based on numerical information describing a series of selfmovements. In the present study, we found that the monkeys
exhibited signs of difficulty in performing a numerosity-based
motor task after transient, chemical inactivation of area 5.
METHODS
Subjects
Two male Japanese monkeys (Macaca fuscata, 6 and 8 kg) served
as the subjects in this study. These monkeys were also used in a
previously reported study (Sawamura et al. 2002). All animal care and
experimental procedures were conducted in accordance with the
National Institutes of Health Guide for the Care and Use of Laboratory Animals, and the Guidance for Institutional Animal Care and Use
published by our institute.
Behavioral procedures
The behavioral task we used in this study is presented schematically
in Fig. 1A. The monkeys were trained to hold a handle using their
right arm in a fixed position. One second later, a low tone signaled the
beginning of the waiting period, after which a visual movement
trigger signal was presented with a light-emitting diode. The monkeys
had to choose to perform one of two movements: TURN or PUSH the
handle. After performing the correct movement, the monkey was rewarded with a drop of fruit juice after a 0.5-s delay. The correct
movement was unchanged for a block of five trials, such that the
0022-3077/10 Copyright © 2010 The American Physiological Society
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Sawamura H, Shima K, Tanji J. Deficits in action selection based
on numerical information after inactivation of the posterior parietal
cortex in monkeys. J Neurophysiol 104: 902–910, 2010. First published May 26, 2010; doi:10.1152/jn.01014.2009. A previous study
identified neuronal activity in area 5 of the monkey posterior parietal
cortex that reflects the numerosity of a series of self-performed
actions. It is not known, however, whether area 5 is crucially involved
in the selection of an action based on numerical information or,
instead, merely reflects numerosity-related signals that originate in
other brain regions. We transiently and focally inactivated area 5 to
test its functional contributions to numerosity-based action selection.
Two monkeys were trained to either push or turn a handle in response
to a visual trigger signal. The selection of the action was solely based
on numerical information from a series of actions performed by the
monkey: select A five times, select B five times, and then return to A
in a cyclical fashion. When muscimol was applied to a portion of area
5 in which the activity in the numerosity-selective cells was recorded,
the error rate in the selection task increased significantly. This transient neural inactivation also caused omission errors that were not
observed before the muscimol injection. A control task showed that
the errors were not caused by motor deficits or impaired ability to
select between two possible actions. Our results indicate that area 5 is
crucial for selecting actions on the basis of numerical information
about a series of actions performed by the tested individual.
NUMERICAL-PROCESSING DEFICITS AFTER AREA 5 INACTIVATION
903
A Time course of trials
Wait
75s
1.4
1
4 − 7.5
Start
E h ttrial
Each
i l
ITI
Go
Movement
Reward
L
Low
T
Tone
Time
Ti
B
3 4 5 1
1 2
Trial blocks
(20−46 s)
(20−
3
2
TURN
4
5
1 2 3 4 5
TURN
PUSH
Definition of correct & error trial blocks
m1
Correct
m2
w1
w2
w1
m4
w3
m1
Premature
Prematureshift
m3
m2
w2
m5
w4
w5
m3
m4
w3
w4
M
Movement
t shift
hift
w1
m5
Movement shift
w5
w5
w1
FIG. 1. Explanation of behavioral task and the sequence of
events in correct and error blocks. A: a diagram showing
behavioral events constituting each trial (top) and the sequence
of occurrences of trials requiring either TURN or PUSH in each
block of 5 trials (bottom). B: the definition of a correct trial
block and each of error blocks as depicted in the sequences of
successive trials. Monkeys were rewarded after the execution of
each correct movement (m1–m5) following each of the waiting
periods (w1–w5). If the monkeys made a premature movement
shift in response to the 5th wait signal (w5) or earlier, they were
not rewarded. In that case, an error signal was given. No reward
was given after the 6th movement (m6) in the late-shift block,
which prompted the animals to shift to an alternative movement.
Error signal
w1
1
m2
w2
2
m3
w3
3
m4
w4
4
m5
w5
5
m6
w1
1
w1
1
monkeys were required to serially execute the same movement. After
performing each block of five trials, the monkeys had to choose to
perform an alternative movement without external instructions and repeat
that movement during the next block of five trials. To prevent the
monkeys from selecting the movement based on the length of the waiting
period, the waiting period varied unpredictably from 1.4 to 7.5 s. As a result,
the total time for one block of trials varied in the range of 20–46 s.
Premature selection of the alternative movement before completing
a block of five trials was defined as a “premature-shift error” (Fig. 1B)
and resulted in an auditory error signal. Thus the monkeys had to
select and perform the correct movement until the block of five trials
A
Movement shift
was completed correctly. “Late-shift errors” occurred when the monkeys failed to switch to the alternative movement and repeated the
same movement six times. After these errors, the monkeys were not
rewarded following the last trial, which prompted the subjects to
perform the alternative movement in the next trial. “Limit-over errors”
occurred when the subject did not perform the required movement
within 4 s of the movement-trigger signal, at which point the trial
ended and the next trial started; the monkeys continued performing
the correct movement until a block of five trials was completed. The
success rate was calculated as the ratio of the number of correct blocks
divided by the number of total blocks.
B
C
D
E
40
imp/s
30
imp/s
20
imp/s
20
imp/s
1st
Neuronal response
2nd
3rd
4th
30
imp/s
5th
0.5 s
: Trial start
: Movement trigger
FIG. 2. Examples of numerosity-selective activity from cells recorded in area 5. The cells displayed in columns A to E exhibited selectivity to the 1st, 2nd,
3rd, 4th, and 5th trials, respectively, during a correct block of either the PUSH (A and D) or TURN (B, C, and E) movements. Cellular activity is displayed as
spike density histograms constructed from the data obtained in 10 trials, using 50-ms bins. The activity histograms are significantly tuned to a particular
numerosity of a trial (black). Activity was aligned with the onset (triangles at left) or with the end (arrows at right) of the waiting period, depicted along the
abscissa. Each unit along the ordinate represents 20, 30, or 40 spikes/s as indicated. Scale bar: 500 ms.
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m1
Late-shift
H. SAWAMURA, K. SHIMA, AND J. TANJI
At a stage when the monkeys were proficient in the trained
behavioral task, we examined the effect of the length of the cumulative waiting time during each trial block on the success rate of the
behavioral performance. For this purpose we examined the relationship between the time interval from the beginning of the first wait
signal to the end of the fifth waiting time and the correct performance
rate. We found that the two variables were not correlated (P ⬎ 0.1 by
linear regression analysis) in either of the two monkeys. This analysis
made it unlikely that the monkeys used time as a cue to trial position.
Data analysis
In a control experiment, we used an auditory stimulus to instruct
one of the subjects to select and execute one of two movements and
performed this experiment with the monkey subjected to the muscimol inactivation protocol. A high tone signal (1 kHz, 300 ms) was
presented at the beginning of the waiting period to signal the subject
to perform the alternative movement (the movement that was different
from a previously performed movement), irrespective of the numerosity of the trials in the block. The trial containing the auditory signal
was redefined as the first trial in a new block and the subject began a
new block of five trials.
RESULTS
After training, the daily success rate for task performance by
both monkeys was ⬎76%. Single-cell activity was recorded
from three hemispheres in two monkeys. There were 548
task-related cells in monkey A recorded bilaterally and 364
cells in monkey B recorded unilaterally (contralaterally to the
performing limb). They exhibited significantly different discharge rates (P ⬍ 0.05, Mann–Whitney U test) during the
waiting period compared with the control period (500 ms
before the onset of the waiting period). Among these cells, 181
cells from monkey A (33%) and 117 cells from monkey B
(32%) showed activities that reflected the numerosity of a
series of self-movements. That is, two-way ANOVA revealed
A
1.0
0.8
Muscimol administration
0.6
0.4
1 st
2 nd
3 rd
4 th
5 th
0.2
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0
1
B
50
Percentage of cells
After completing the behavioral training, single-cell activity was
recorded from the parietal cortex using standard electrophysiological
techniques (Sawamura et al. 2002; Shima and Tanji 1998a). Subsequently, a small area of the cortex was transiently inactivated using 5
␮g/␮L muscimol (Sigma), a ␥-aminobutyric acid receptor agonist,
dissolved in 0.1 M phosphate buffer (pH 7.4). The details for preparing muscimol and the injection technique have been described previously (Shima and Tanji 1998b). Muscimol was injected at a rate of 0.1
␮L/min through a pair of sharpened stainless steel tubes (ID, 150 ␮m;
OD, 300 ␮m). A millimeter scale was visible on the surface of the
injection tube at the time of insertion to determine the depth of
penetration into the dura. An Elgiloy microelectrode (50- to 80-␮m
shaft diameter) was attached to the side of the injection tube such that
its tip was within 0.5 mm of the tip of the injection tube. The
microelectrode allowed us to monitor the approximate depth at which
the injection tubes penetrated the cortex and to detect when the
muscimol silenced neuronal activity in the area. The injections were
made at a depth of 2.5 mm from the surface in the banks of
the intraparietal sulcus (IPS) and in the adjacent convexity, but not
in the white matter. In each daily session, the injection tube was
inserted into the desired hemisphere(s) and behavioral data were
collected for 30 min (preinjection period). Subsequently, 3 ␮L of
muscimol solution or 0.1 M phosphate buffer was injected through the
tube into the cerebral cortex for 30 min. After completing the
injection, behavioral data were collected for 90 min.
2
3
4
Ordinal number of trials
5
%
40
30
20
10
0
1
2
3
4
5
Preferred ordinal numbers
FIG. 3. A: response properties of cells with exclusive selectivity to one of
the 5 numerical positions. Mean values of normalized activity, calculated for
each category of cells judged to be selectively active during one of the 1st to
5th waiting periods, are plotted against the ordinal number of trials. Activity is
normalized relative to the maximal activity at most favorable number of trials.
Vertical bars denote SEs. B: distributions of preferred ordinal numbers for the
waiting periods, calculated for all cells that exhibited selective activity during
one or more of 5 waiting periods.
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We analyzed cellular activity during the waiting period and perimovement period (200 ms preceding and 250 ms following the onset
of either PUSH or TURN movement). We judged a cell as task-related
if its activity during either the waiting period or the perimovement
period showed significantly higher discharge rates (P ⬍ 0.05, Mann–
Whitney U test) from that during the control period (500 ms before the
onset of the waiting time). Subsequently, we performed a two-way
ANOVA for each of the task-related activities, looking at two factors:
ordinal number of trials in each block for a particular movement (first
through fifth) and the type of movement (PUSH or TURN). When the
cells showed the main effect of ordinal number of trials or interaction
between the ordinal number and type of movement, the activity was
classified as ordinal number selective. Where appropriate, individual
data classed as number-selective activity were compared directly
using Tukey’s test (for details, see Sawamura et al. 2002).
Throughout the pre- and postinjection periods, success and error
rates, reaction times (RTs), and movement times (MTs) were measured. The RT was defined as the interval between the appearance of
the movement trigger signal and the onset of movement (the time
when the handle moved out of the hold range) in the correct direction
for the required task. The MT was defined as the interval from the
onset of movement until the required motor target was attained. These
variables were statistically analyzed using appropriate statistical tests
as described in the following text (ANOVA).
Movement selection in an auditory cue task
Normalized activity
904
NUMERICAL-PROCESSING DEFICITS AFTER AREA 5 INACTIVATION
Ipsilateral
Contralateral
CS
CS
IPS
IPS
IPS
IPS
STS
STS
dorsal
dorsal
rostral
B
rostral
2 mm
2 mm
Contralateral
CS
IPS
IPS
STS
FIG. 4. Cortical maps indicating sites of recorded cells and
injections in both hemispheres of one monkey (A) and in one
hemisphere of the other (B). A lateral view of each hemisphere
is displayed in the top of each panel and the regions marked
with dotted circles in each hemisphere are enlarged in the
bottom of each panel. The sizes of the filled circles indicate the
number of numerosity-selective cells recorded at each site.
Numerosity-selective cells were not found at sites marked with
horizontal bars. Red circles and bars indicate sites affected and
not affected by muscimol injections, respectively. Blue circles
denote injection sites of vehicle only. Contralateral hemisphere
refers to the hemisphere located contralateral to the taskperforming limb. CS, central sulcus; IPS, intraparietal sulcus;
STS, superior temporal sulcus.
number of cells
0
1
2-3
>4
Muscimol : effect (+)
dorsal
rostral
Muscimol : effect (-)
Phosphate buffer
2 mm
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numerosity selectivity was distributed among all of the five
numerical positions, although most frequent for the first (27%).
The numerosity-selective cells were concentrated in the
anterior bank of the IPS and in its anteriorly adjacent convexity. On the other hand, we detected fewer numerosity-selective
cells in the bank or the convexity posterior to the IPS. The
distribution of the numerosity-selective cells (including both
cells showing selectivity during only one of the five numerical
positions and cells with selectivity during more than one
period) is displayed in Fig. 4. The sizes of the filled circles
indicate the number of cells exhibiting numerosity-selective
activity at each penetration position. The focal area was 5 mm
wide, spreading anteriorly from the IPS. Each penetration
reached ⬍4 mm from the surface when the selective cells were
observed. Deeper penetrations revealed an abrupt decrease in
the number of cells showing task-related activity. Numerosityselective cells were situated primarily in the convexity and not
in the banks of the IPS. We also examined somatosensory
responses of the cells in this region. Prominent responses were
obtained by touching or stroking the skin, pressing on muscles,
or manipulating limb joints, characteristic of responses in the
superior parietal lobule (Iwamura 2000; Sakata et al. 1973). At
that these 298 cells showed the main effect of ordinal number
of trials or interaction between the ordinal number and type of
movement. Subsequent analysis of the 298 cells revealed that
51% of the numerosity-selective cells showed activity during
more than one of the five waiting periods in a block of trials.
On the other hand, 49% of the cells displayed this selectivity
during only one of the five potential numerical positions in a
block. Examples of this exclusive relationship to a numerical
position are presented in Fig. 2. The increased activities of the
cells were observed at the onset of the waiting period (triangles
in Fig. 2, C and E) or at the end of the waiting period (i.e., at
the onset of the movement trigger signal; arrows in Fig. 2, A,
B, and D). Two-way ANOVA (movement and numerosity as
factors: P ⬍ 0.05) and pairwise Tukey’s tests (P ⬍ 0.05)
revealed that each cell depicted in the panels from A to E was
tuned to the first, second, third, fourth, and fifth trial in the task
block, respectively. The tuning function for cells with such
exclusive selectivity to one of the five numerical positions is
presented in Fig. 3A (n ⫽ 146). In the next analysis, we
examined the proportions of numerosity selectivity as a function of numerical position for all of the numerosity-selective
cells (n ⫽ 298). As displayed with the histogram in Fig. 3B, the
A
905
906
H. SAWAMURA, K. SHIMA, AND J. TANJI
100
Success rate (%)
80
60
40
Muscimol (Bilateral)
Muscimol (Unilateral)
Phosphate Buffer
0
0
30
60
90
120
Time after muscimol injection (min)
FIG. 5. The time course of the mean success rate every 30 min with
bilateral injections (solid line) and unilateral injections of muscimol (interrupted line). * indicates points at which the success rate was significantly lower
than that observed during the preinjection period (P ⬍ 0.01, Fisher’s exact
test). The dotted line denotes results obtained with vehicle injections. “0” on
the abscissa indicates the onset of injection. Error bars indicate SD. Numbers
in the abscissa indicate the center of the time period of 30 min during which
the success rate was calculated.
J Neurophysiol • VOL
injections (interrupted line). In contrast to the bilateral injections, however, the success rate with unilateral injections
tended to recover 60 min after the injection. To assess the
duration of effect of a unilateral injection of muscimol, we
calculated the success rate during each 10-min interval from
the onset of the injection. The success rate was significantly
lower (P ⬍ 0.05, Fisher’s exact test) in the period from 30 to
60 min after injection onset, whereas the decrease was not
significant during the period from 60 to 120 min after injection
onset (P ⬎ 0.1, Fisher’s exact test).
To examine the possibility of nonspecific effects of a topical
injection of fluid into the cortex during a behavioral task, we
injected the same volume of vehicle solution at three sites
bilaterally and two sites unilaterally near the sites of the
muscimol injections (blue circles in Fig. 4). The results are
shown with a dotted line in Fig. 5. The success rates remained
⬎75% throughout the sessions, indicating that the administration of vehicle did not affect task performance (P ⬎ 0.5,
Fisher’s exact test). This control study confirmed that the
effects on task performance were due to chemical inactivation
of area 5.
We then performed a more detailed assessment of the time
course of errors after muscimol injections. To visualize the
time courses across successive trial blocks after injections, we
calculated the cumulative number of error blocks (blocks in
which errors occurred) relative to the number of error blocks
that occurred during the corresponding blocks after vehicle
injection. In Fig. 6, we plotted the cumulative error blocks
against the number of blocks after the injection along the
abscissa. The data after the bilateral injection (Fig. 6A) revealed that 38 to 62 blocks postinjection of muscimol, the
number of error blocks exceeded the mean ⫹ 3SDs of the
number of error blocks observed following vehicle injections
(dotted line in Fig. 6), indicating that errors increased about 30
min after the onset of injection. Thereafter, the error blocks
continued to increase during the 120-min postinjection epoch
of data analysis. After the unilateral injection (Fig. 6B), the
error blocks increased at similar postinjection epochs, although
the increase reached a plateau at 100 –150 blocks after the
injection onset.
We also examined different types of errors. Both monkeys
committed premature-shift errors and late-shift errors. These
types of errors increased during the postinjection period such
that the ratio of premature-shift errors versus late-shift errors
did not differ from that observed during preinjection or vehicle-injection periods (Fig. 7; P ⬎ 0.5, Fisher’s exact test). This
finding made it unlikely that the monkeys adopted vastly
different strategies for selecting movements based on the
numerosity of the actions. On the other hand, we observed
some error types exclusively after the muscimol injections.
First, both monkeys committed “limit-over errors,” which
constituted 23% of the total postinjection errors (11% of the
entire trial blocks during the postinjection period). In the
limit-over error trials, the subjects failed to initiate either
movement within 4 s of the movement-trigger signal. In 42%
of these cases, the limit-over trial was the second or third trial
within a trial block, whereas 58% occurred during the fourth or
fifth trial. The subjects did not commit limit-over errors during
vehicle injections. Second, ⬎10% of the premature-shift errors
by both subjects were committed early in the trial block (at the
second or third trials in a block). This is noteworthy because
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recording sites corresponding to the muscimol-injection region, receptive fields were primarily found in the forearm,
upper arm, shoulder, and less frequently in the back. In addition to these response properties, subsequent histologic analysis indicated that the recorded task-related cells were in area 5
(Sawamura et al. 2002).
To transiently inactivate this area, muscimol was injected
into six sites bilaterally in monkey A (red circles or bars in Fig.
4) and into four sites contralaterally in monkey B. All of the
injection sites overlapped with the region in which the numerosity-selective cells were concentrated. We used the following
criteria to determine whether the muscimol was effective. First,
the success rate during the preinjection period had to be ⬎76%.
Second, the success rate during at least one of the 30-min
evaluation intervals during the postinjection period had to be
significantly lower than the rate observed during the preinjection period for that session (P ⬍ 0.01, Fisher’s exact test). If the
behavioral data from an injection session fulfilled these criteria,
the injection was determined to be effective. Muscimol was found
to be effective at five of six sites receiving bilateral injections and
at three of four sites receiving a unilateral injection (red circles in
Fig. 4). Subsequent analysis of the injection effects was performed
using data obtained at these sites. The effects of the injections at
the other sites on task performance were weak and were not
statistically significant (red horizontal bars). We also injected
muscimol into the inferior parietal cortex at four sites bilaterally
and three sites unilaterally. None of these injections significantly
affected task performance (red horizontal bars in Fig. 4; P ⬎ 0.5,
Fisher’s exact test).
We analyzed the time course of the injection effects by
plotting time-dependent changes in the success rates after the
injections. The mean success rates obtained during each 30min evaluation period after bilateral injections are displayed in
Fig. 5 (solid line). The success rate during the preinjection
period was ⬎75% and decreased to ⬍60% during the postinjection period (P ⬍ 0.01, Fisher’s exact test). This effect lasted
for ⬎90 min. A similar effect was observed with unilateral
NUMERICAL-PROCESSING DEFICITS AFTER AREA 5 INACTIVATION
907
Bilateral injection
40
Case 1
Case 2
Case 3
Case 4
Case 5
20
-10
-50
0
50
100
FIG. 6. The time course of the cumulative number of error
blocks relative to the number of error blocks that occurred
during the corresponding blocks with vehicle injections. Each
colored line represents an effective muscimol injection. The
black dotted lines indicate ⫾ 3 SDs for the cumulative sum of
error blocks with vehicle injections. The numbers displayed
below the abscissa indicate the number of blocks after injection
onset. A: data for each of 5 successive muscimol injections
(cases 1–5) into the bilateral area 5. B: data for each of 3
unilateral injections (cases 1–3) that was effective.
150
Onset of
injection
Task progress (number of blocks after injection)
Relative number of accumulated error blocks
(Muscimol - Vehicle)
B
Unilateral injection
40
Case 1
Case 2
Case 3
20
-10
-50
0
50
100
150
Onset of
injection
Task progress (number of blocks after injection)
during the preinjection periods, such early errors did not occur,
neither during trials after vehicle injections.
We performed a control experiment to examine whether the
subject was able to select and perform the proper movement
Pre-injection of muscimol
Postinjection of muscimol
Phosphate buffer
20%
10%
0%
premature
shift
late shift
limit over
FIG. 7. The distribution of error types observed during the preinjection
period (left), during the postinjection period (middle), and with vehicle (phosphate buffer) injections (right). The percentage of occurrence of errors belonging to each of the 3 categories is taken in the ordinate. The epoch of 30 –120
min after the injection onset was used to generate the data in this figure.
J Neurophysiol • VOL
based on any external signal, despite focal inactivation of area
5. Under the control conditions, the monkey was required to
respond to an auditory signal by always selecting a different
movement from the previously performed action. The success
rate after muscimol injections was 96.3% (n ⫽ 27), which was
similar to that observed with vehicle injection (93.3%, n ⫽ 30;
P ⬎ 0.5, Fisher’s exact test). This finding indicated that the
monkey was able to select and perform a movement based on
an external cue.
We then compared MTs for the behavioral task during the
preinjection and postinjection periods. The MTs during the two
periods did not differ significantly (P ⬎ 0.1, Mann–Whitney U
test; Table 1). We also analyzed RTs during the preinjection
and postinjection periods. For the monkey receiving bilateral
injections, the RTs during the postinjection period were significantly longer than those during the preinjection period (P ⬍
0.001, Mann–Whitney U test; Table 1). In a similar comparison, RTs after vehicle injection (282.9 ms for the PUSH task
and 265.2 ms for the TURN task) were not markedly altered
(P ⬎ 0.1, Mann–Whitney U test). We then performed a
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Relative number of accumulated error blocks
(Muscimol - Vehicle)
A
908
TABLE
H. SAWAMURA, K. SHIMA, AND J. TANJI
1. Comparison of movement times and reaction times
Movement Time for the TURN Task
Movement Time for the PUSH Task
Monkey
Preinjection
Postinjection
Preinjection
Postinjection
With bilateral injections
With unilateral injections
29.2 ⫾ 0.22
27.4 ⫾ 0.38
30.6 ⫾ 0.19
26.6 ⫾ 0.26
46.3 ⫾ 0.26
51.8 ⫾ 0.60
45.7 ⫾ 0.17
50.7 ⫾ 0.41
Reaction Time for the TURN Task
Reaction Time for the PUSH Task
Monkey
Preinjection
Postinjection
Preinjection
Postinjection
With bilateral injections
With unilateral injections
266.5 ⫾ 2.9
256.5 ⫾ 2.2
381.0 ⫾ 8.8*
251.8 ⫾ 1.2
281.3 ⫾ 1.8
278.1 ⫾ 2.5
401.3 ⫾ 7.5*
276.5 ⫾ 1.4
Values are means ⫾ SE, times are in milliseconds. *Indicates statistical significance (P ⬍ 0.01, Mann–Whitney U test).
These findings indicate that area 5 is necessary for the selection
of a movement based on numerical information about a series
of actions.
Although cortical area 5 of the posterior parietal cortex has
traditionally been viewed as an association cortex that is
involved in integrating somatosensory information (Hyvärinen
1982; Sakata et al. 1973), this area also plays an important role
in sensorial guidance of motor behavior (Kalaska 1996). Perception and introspective awareness of body form and posture
provide the basis for execution and monitoring of movements.
Moreover, a variety of sensory information that is useful for
guiding and/or adjusting movements is thought to be encoded
in cortical area 5. Neuronal activity in this area is strongly
coupled to the position of the arm and the direction of reaching
movements (Kalaska et al. 1983, 1990; Lacquaniti et al. 1995;
Scott et al. 1997). During the planning and execution of
reaching movements, area 5 cells have been shown to encode
movement kinematics, but not dynamics or kinetics (Crammond and Kalaska 1989; Hamel-Pâquet et al. 2006; Kalaska
et al. 1990). When a subject was required to remember a
sample object form to select the correct reach target, the
information for haptic recognition of the object form was
represented among area 5 cells (Koch and Fuster 1989). In
another study, when a correct reach target was defined using a
visual cue, area 5 cells reflected the appropriate direction of
reach, suggesting a role for this area in visuomotor analysis
during the guidance of arm movements (Kalaska and Crammond 1995). Thus the involvement of area 5 in somatomotor
and/or visuomotor guidance of movements has been well
established (Kalaska et al. 2003).
DISCUSSION
In this study, we found that focal inactivation of monkey
area 5 with muscimol increased the error rate in a task that
required the subjects to select and perform a movement based
on the numerosity of a series of movements performed by
individuals themselves. The lack of change in the monkeys’
MT during the postinjection period and the ability of the
monkey to select and perform a given movement in response to
an auditory cue despite muscimol injections suggested that the
observed impairment was not due to difficulties in executing
limb movements or in selecting between two movements.
Reaction time for PUSH
ms
ms
600
Reaction time for TURN
: pre-injection
FIG. 8. The reaction times (RTs) for each of 5 trials performed before (white bar) or after (gray bar) muscimol injections into the area 5 of monkey A performing the PUSH (left)
or TURN (right) movement. * indicates statistically significant
differences between trials (**P ⬍ 0.01 and *P ⬍ 0.05, post hoc
Tukey’s test). Error bars indicate SE.
: postinjection
400
200
0
1st 2nd 3rd 4th 5th
1st 2nd 3rd 4th 5th
1
st
2
nd
3
rd
4
th
5
th
1
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2
nd
3
rd
4
th
5
th
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detailed analysis of the RTs during the postinjection period to
identify systematic alterations as the monkey progressed
through the five trials in a block (Fig. 8). RTs became longer
as the number of trials increased (P ⬍ 0.001, ANOVA). In
particular, RTs for the fourth and fifth PUSH trials were
significantly longer than those observed in the first, second, and
third PUSH trials. Similarly, a progressive increase was also
observed in the RTs as the monkey progressed through the
TURN trials, particularly when the RTs from the third, fourth,
and fifth trials were compared with the RTs from the first and
second trials. During the preinjection period for both movements, RTs did not increase significantly as the trials progressed (P ⬎ 0.5, ANOVA). For the control experiment, we
analyzed RTs in trials performed with an auditory cue. The
postinjection RTs were 285 ms for the PUSH trials and 267 ms
for TURN trials, which were not significantly different from
the data obtained during the preinjection period (P ⬎ 0.2,
Mann–Whitney U test).
NUMERICAL-PROCESSING DEFICITS AFTER AREA 5 INACTIVATION
J Neurophysiol • VOL
et al. 1996; Wynn 1992), which may develop into a mature
understanding of numerical information in human adults with
highly organized cortical networks (Dehaene et al. 1999; Eger
et al. 2003; Piazza et al. 2004, 2007; Schuman and Kanwisher
2004). On the other hand, when numerical information in the
posterior parietal cortex is needed, the ample anatomical connections to frontal motor areas (Matelli et al. 1998) could
provide information that is required for selecting the appropriate action (Cisek and Kalaska 2005; Hoshi and Tanji 2006).
ACKNOWLEDGMENTS
We thank Dr. M. Takada and Dr. E. Hoshi for valuable comments on the
early version of this manuscript and M. Kurama and Y. Takahashi for technical
assistance.
GRANTS
This work was supported by Ministry of Education, Culture, Sports,
Science and Technology of Japan Grants 19790162 and 20019011 to H.
Sawamura and 16067101, 17021004, and 19300110 to J. Tanji.
DISCLOSURES
No conflicts of interest, financial or otherwise, are declared by the author(s).
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forthcoming movement, suggesting a role for area 5 in providing numerical information during limb movements performed
by the individuals themselves. This property may underlie
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