Motor areas beyond motor performance: deficits in serial prediction following ventrolateral premotor lesions.

Abstract

Previous functional MRI findings have indicated that a premotor-parietal network is involved in the perceptual processing of sequential information. Given that premotor functions have traditionally been restricted to behaviors requiring motor or sensorimotor computations, the goal of the present patient study was to further investigate whether the lateral premotor cortex is critical in purely perceptual sequencing. Patients with either ventral premotor or inferior parietal lesions, in addition to patients with prefrontal lesions and age- and gender-matched healthy controls, were tested during the processing of temporal, object-specific, and spatial sequences. Results revealed that premotor patients as well as parietal patients showed significantly higher error rates than did healthy controls on all sequence tasks. In contrast, prefrontal patients showed no behavioral deficits. These findings support the significance of the ventrolateral premotor cortex, in addition to parietal areas, in nonmotor (attentional) functions.

Full text

Page 1

Motor Areas Beyond Motor Performance: Deficits in Serial Prediction
Following Ventrolateral Premotor Lesions
Ricarda I. Schubotz, Katrin Sakreida, and
Marc Tittgemeyer
Max Planck Institute of Human Cognitive and Brain Sciences
D. Yves von Cramon
Max Planck Institute of Human Cognitive and Brain Sciences
and University of Leipzig
Previous functional MRI findings have indicated that a premotor–parietal network is involved in the
perceptual processing of sequential information. Given that premotor functions have traditionally been
restricted to behaviors requiring motor or sensorimotor computations, the goal of the present patient study
was to further investigate whether the lateral premotor cortex is critical in purely perceptual sequencing.
Patients with either ventral premotor or inferior parietal lesions, in addition to patients with prefrontal
lesions and age- and gender-matched healthy controls, were tested during the processing of temporal,
object-specific, and spatial sequences. Results revealed that premotor patients as well as parietal patients
showed significantly higher error rates than did healthy controls on all sequence tasks. In contrast,
prefrontal patients showed no behavioral deficits. These findings support the significance of the ventro-
lateral premotor cortex, in addition to parietal areas, in nonmotor (attentional) functions.
Recent functional MRI (fMRI) studies have shown that the
human ventrolateral premotor cortex (PMv) responds to sensory
events, particularly to-be-predicted events (Schubotz, Friederici, &
von Cramon, 2000; Schubotz & von Cramon, 2001a, 2001b,
2002a, 2002b, 2002c; Schubotz, von Cramon, & Lohmann, 2003).
In line with recent findings in humans (Aziz-Zadeh, Maeda,
Zaidel, Mazziotta, & Iacoboni, 2002; Chaminade, Meary, Orli-
aguet, & Decety, 2001; Hanakawa et al., 2002; Ramnani, Toni,
Josephs, Ashburner, & Passingham, 2000) and monkeys (Rizzo-
latti, Fogassi, & Gallese, 2002), these data suggest that the pre-
motor cortex subserves a variety of behavior that does not neces-
sarily result in motor output. We have proposed that the PMv
subserves prospective memory or, in other words, functions as a
forward model of sequential information. This allows such infor-
mation to be used in both motor planning and perceptual prediction
(i.e., in motor as well as nonmotor behavior).
However, in all of our studies the PMv has been coactivated
with parietal areas (i.e., those that have strong reciprocal connec-
tions to the PMv, as shown in monkeys; Murata et al., 1997;
Murata, Gallese, Kaseda, & Sakata, 1996; Rizzolatti, Fogassi, &
Gallese, 2000; Sakata & Taira, 1994; Sakata, Taira, Murata, &
Mine, 1995; Taira, Mine, Georgopoulus, Murata, & Sakata, 1990).
Thus, the question arises as to how the functional contributions of
lateral premotor areas and parietal areas differ in terms of percep-
tual prediction.
In the present study, we set out to investigate this question in
neurological patients. In a visual serial prediction task (SPT;
Schubotz, 1999), behavioral performance was tested among pa-
tients with lesions of either ventrolateral premotor or inferior
parietal areas. Functional MRI studies have shown that these two
regions are activated in temporal, object-specific, and spatial SPTs
(Schubotz & von Cramon, 2001a). Therefore, we based selection
of patients on our fMRI findings, including only those with lesions
inferior to the connection of the superior precentral sulcus and the
superior frontal sulcus (premotor patients) or within the inferior
parietal lobule (parietal patients). Both prefrontal control patients
and age- and gender-matched healthy controls were tested. Lesions
among the prefrontal patients were mainly restricted to the fron-
topolar region, excluding lesions among the premotor patients.
Patients and controls completed (a) an SPT involving temporal
rhythm sequences, object sequences, and spatial position se-
quences and (b) a nonprediction control task. We expected pre-
motor patients to be generally impaired in serial prediction, and we
expected patients with parietal lesions to show deficits in object
sequences and spatial sequences but not in rhythm sequences.
Prefrontal patients were expected to exhibit no impairment.
Method
Patients and Control Participants
Twenty-one patients of the Day Clinic of Cognitive Neurology at the
University of Leipzig participated in the study after providing informed
consent. The experimental standards were approved by the local ethics
committee of the University of Leipzig. Depending on lesion site, patients
were grouped as premotor (n ? 7; 3 female, 4 male; mean age ? 50.1
years), parietal (n ? 7; 2 female, 5 male; mean age ? 50.2 years), or
prefrontal (n ? 7; 3 female, 4 male; mean age ? 39.7 years). Healthy
controls, matched with each patient group for age and gender (premotor
control: n ? 7, mean age ? 49.4 years; parietal control: n ? 7, mean
age ? 49.7 years; prefrontal control: n ? 7, mean age ? 39.2 years), were
also tested.
Ricarda I. Schubotz, Katrin Sakreida, and Marc Tittgemeyer, Depart-
ment of Neurology, Max Planck Institute of Human Cognitive and Brain
Sciences, Leipzig, Germany; D. Yves von Cramon, Department of Neu-
rology, Max Planck Institute of Human Cognitive and Brain Sciences, and
Day Clinic of Cognitive Neurology, University of Leipzig, Leipzig,
Germany.
The Max Planck Institute of Human Cognitive and Brain Sciences was
formerly the Max Planck Institute of Cognitive Neuroscience.
Additional materials are on the Web at http://dx.doi.org/10.1037/0894-
4105.18.4.638.supp.
We thank Heike Ja ¨nicke, Corinna Koßack, Sonja Kotz, Anke Pitzmaus,
and Uta Wolfensteller for their contributions.
Correspondence concerning this article should be addressed to Ricarda I.
Schubotz, Department of Neurology, Max Planck Institute of Human Cogni-
tive and Brain Sciences, Leipzig, Germany. E-mail: schubotz@cbs.mpg.de
Neuropsychology
2004, Vol. 18, No. 4, 638–645
Copyright 2004 by the American Psychological Association
0894-4105/04/$12.00DOI: 10.1037/0894-4105.18.4.638
638

Page 2

Table 1 presents data on demographic and lesion characteristics for each
patient. All patients were classified as chronic, and average amounts of
time since lesion were 32.8 months among premotor patients, 51.7 months
among parietal patients, and 79.2 months among prefrontal patients. Lesion
sites were determined by T1-weighted MRI scans. Lesions among the
premotor patients mainly resulted from infarctions of the precentral sulci
artery or the posterior prefrontal artery; lesions among the parietal patients
were typically the result of infarctions of the parietal branches of the
middle cerebral artery.
On the basis of suggested functional homologies between nonhuman
primates and humans, researchers have proposed that the border be-
tween the ventral and dorsal premotor cortex is near the level of the
superior frontal sulcus (roughly referring to axial level z ? 50 of the
stereotactic frame of Talairach & Tournoux, 1988; see Rizzolatti et al.,
2002). Following this suggestion, we ensured that none of our premotor
patients’ lesions fell into the dorsal or medial premotor cortex. Regis-
tered to Talairach space, lesions extended axially to maximal z ? 46 in
the premotor group and to z ? 43 in the parietal group. Two premotor
patients (PMC1 and PMC4) suffered from mild speech apraxia. Two
premotor (PMC1 and PMC7) and 3 parietal (PAR3, PAR5, and PAR7)
patients had discrete or stronger hemiparesis. Two parietal patients
(PAR4 and PAR5) had hemianopia and lower quadranopia. Prefrontal
(FRO) patients had lesions of different etiology that were located in the
frontomedian, frontopolar, frontobasal, or frontolateral areas. Lesion
volumes were approximately 16.2 ml among premotor patients, 26.l ml
among parietal patients, and 42.4 ml among prefrontal patients. Note
Table 1
Patient Demographic and Clinical Data
Patients Gender
Age
(years)
TSL
(months)HEtiology Site of lesion Acute deficit(s) Persistent deficit(s)
Premotor patients
PMC1F 5871L MCAI Lateral frontal, anterior
insula, striatum
Lateral frontal, striatum
NoneSpeech apraxia
PMC2M 5351RMCAI Executive dysfunction, global
attentional deficit
None
Hemiparesis
PMC3M 41 48L AVMLateral frontal Nonaphasic
communication
disorder
Speech apraxia,
dysphasia
None
None
PMC4M 61 14L MCAILateral frontal None
PMC5
PMC6
F
F
71
49
13
22
L
R
MCAI
MCAI
Lateral frontal
Lateral frontal
Dysphasia
Executive dysfunction, global
attentional deficit
None PMC7M 1811L MCAILateral frontal, striatum Dysphasia, discrete
hemiparesis
Parietal patients
PAR1M 53 43L MCAIInferior parietal Dyslexia, dysgraphia,
dyscalculia
Dysphasia
None
PAR2F 70 44L MCAIInferior parietal,
posterior insula
Inferior parietal
Inferior parietal
None
PAR3
PAR4
F
M
50
55
57L
R
MCAI
MCAI
Dysphasia, dyscalculia
None
Hemiparesis
Hemineglect,
hemianopia
Quadranopia,
hemiparesis
None
144
PAR5M39 28RMCAI Inferior parietalGlobal attentional deficit,
visuospatial impairment
Dyslexia, dysgraphia,
dyscalculia
Dyslexia, dysgraphia,
dyscalculia
PAR6M 26 31L VI Temporoparietal,
posterior insula
Inferior parietal PAR7M 59 15L MCAI Discrete hemiparesis
Prefrontal patients (clinical control)
FRO1
FRO2
M
F
28
41
65
49
B
R
TBI
ACOA
Ventromedial prefrontal
Posterior orbital basal
forebrain
Ventromedial
Ventromedial
Executive dysfunction, anosmia
Apathy, memory dysfunction
None
None
FRO3
FRO4
F
M
51
41
104
249
B
B
TUM
TBI
Executive dysfunction, anosmia
Acquired sociopathy, executive
dysfunction, hyposmia
Apathy, executive dysfunction,
memory dysfunction
Apathy, executive dysfunction
Acquired sociopathy
None
None
FRO5F 4022L ACOA, ACAI,
MCAI
TBI
TBI
Frontobasal, striatumNone
FRO6
FRO7
M
M
30
47
20
46
R
B
Ventromedial prefrontal
Ventromedial
None
None
Note.
middle cerebral artery infarction; AVM ? arteriovenous malformation; PAR ? parietal patients; VI ? venous infarction; FRO ? prefrontal patients; TBI ?
traumatic brain injury; TUM ? tumor/meningioma; ACOA ? anterior communicating artery aneurysm; ACAI ? anterior cerebral artery infarction.
PMC ? premotor patients; F ? female; M ? male; TSL ? time since lesion; H ? hemisphere of lesion; L ? left; R ? right; B ? bilateral; MCAI ?
639
MOTOR AREAS BEYOND MOTOR PERFORMANCE

Page 3

that these considerable between-volumes differences favored the to-be-
rejected hypothesis (i.e., no impairment among premotor patients).
To enhance a comparison of respective lesion locations, we performed a
lesion registration. Lesion areas were segmented manually by a neurology
expert, and resulting segmented lesions were overlaid onto a template
brain. For this purpose, we applied the following mapping procedure.
Initially, we aligned the T1-weighted MRI scans for each patient with the
chosen template brain image using an affine transformation (i.e., including
translation, rotation, and scaling). We then used the respective transforma-
tion matrices to warp each segmented lesion onto the template. Routines
are described in more detail in Ja ¨nicke et al. (2002). Note that the resulting
overlaid images (see Figure 1) were not controlled for interindividual
variances in sulci and gyri. Thus, a certain amount of distortion within the
overlaid images has to be taken into consideration. The magnitudes of
distortion could also differ among the three patient groups, in that structural
differences increase from posterior to frontal brain sites. Therefore, indi-
vidual T1-weighted MRI scans for each patient are also depicted in
Figure 1.
Materials and Tasks
Stimulus examples are shown in Figure 2 (a color version of Figure 2 is
on the Web at http://dx.doi.org/10.1037/0894-4105.18.4.638.supp). Nine
stimuli were used in the experiment. Each stimulus consisted of a gray
circle 35 mm in diameter with a geometrical form (circle, triangle, or
square) placed in its center; these forms were of different colors (red, blue,
or yellow). On each screen, two identical objects were presented at oppo-
site locations on a virtual circle. An advantage of the rotating-twin stim-
ulation adapted from Schubotz and von Cramon (2001a) is that it can be
used for patients who have unilateral visual field defects (as did 2 patients
in our parietal group). Resulting spatial processing deficits (Vallar, 1993)
are compensated for by presenting the relevant information doubly on both
the right and left sides of fixation, with two identical objects at opposite
locations of a virtual circle on the screen center. Overall, there were six
possible positions at constant gaps of 60°. The screen center was marked
by a small fixation square to facilitate constant visual fixation. Thirty-six
trials were presented in each task in a block design. Each trial lasted 8.85 s,
and the intertrial interval was 5.7 s. Although tasks were presented in
separate blocks, each trial started with a visual cue that reminded patients
which task had to be performed next. Within each trial, 12 pictures were
presented successively for a mean duration of 600 ms each; the interstimu-
lus interval was 150 ms.
Three SPT conditions and a control task were used in the experiment. In
the SPT conditions, the first two pictures within each trial built a sequential
pattern that was repeated six times within the same trial. Patients and
controls were asked to attend only to a task-relevant stimulus property:
presentation duration, object, or spatial location. They were instructed to
memorize the task-relevant feature of the first two pictures (starting se-
quence) and to indicate whether this pattern reappeared five times within
the same trial. In the rhythm task, they were instructed to attend to the
temporal pattern associated with the presentation duration of the starting
sequence. This duration pattern could either be 300 ms/900 ms or 900
ms/300 ms. In the object task, the order of the two objects presented in the
starting sequence was the focus (e.g., blue square/red triangle or yellow
circle/red square). In the position task, participants were instructed to
attend to the order of the spatial locations of the objects in the starting
sequence (e.g., 120°/0° or 0°/60°). To minimize the influence of task-
irrelevant properties, pictures were presented for 600 ms each in an
isochronous rhythm in both the object and position conditions. Within all
SPT conditions, object and position properties varied in an ABAB manner,
as depicted in Figure 2. This made it easier for patients to orient themselves
within the ongoing sequence presentation.
In the SPT conditions (rhythm, object, and position), performance was
tested in a forced-choice response mode. In 50% of the trials, on the 10th
or 11th picture the task-relevant stimulus property was transferred to the
end of the trial, and thus sequential order was violated for the task-relevant
property. In these violation trials, the subsequent picture(s) moved up so
that no gap was perceived. Participants had to indicate, by pressing a
button, whether a deviant was (right button) or was not (left button) present
in the trial. Patients were allowed to respond with their preferred hand.
Responses could be made either immediately after detection of a deviant or
up to 3 s after the end of the stimulus sequence. Visual feedback was
provided indicating whether the answer was correct (indicated by a plus
sign) or incorrect (indicated by a minus sign). In addition, a nonsequential
task was used to control for perceptual requirements and motor responses.
In this control task, the same type of stimulus was used as in the SPT
conditions, with the starting sequence being repeated five times in an
isochronous rhythm. Patients and control participants attended to a gray
target stimulus presented on the 10th or 11th picture in 50% of the control
trials. After stimulus presentation, participants had to indicate whether a
target was present (right button) or absent (left button). Note that no serial
prediction was required for successful performance in the control task.
Figure 1.
premotor, parietal, and prefrontal patients. Numbers correspond to the
identification numbers shown in Table 1. Lesion sites are indicated by
triangles. The following sulci are highlighted in the intact hemisphere to
provide better orientation: central sulcus (white), inferior precentral sulcus
(red), and intraparietal sulcus (green). In addition, overlays are shown for
each patient group, with red indicating minimum overlap and blue indi-
cating maximum overlap.
Representative axial slices of T1-weighted MRI scans for
640
SCHUBOTZ, SAKREIDA, TITTGEMEYER, AND VON CRAMON

Page 4

Procedure
Participants received instructions and were briefly trained before the
experimental session. They were comfortably seated about 1 m in front of
the presentation screen, with the index and middle fingers of their response
hand positioned on the response buttons. They were told to pause if they
felt tired and to terminate the session at any time if necessary. The entire
experimental session lasted about 30 min and was continuously supervised.
Results
Behavioral performance was assessed by means of error rates
(see Figure 3). Reaction times were not analyzed so as to exclude
effects resulting from unspecific behavioral impairments (e.g.,
slowing). The small number of time-outs indicated that patients
were given enough time to answer. Time-outs were distributed as
follows: premotor patients, 0% (premotor controls, 1.4%); parietal
patients, 4.2% (parietal controls, 0.7%); and prefrontal pa-
tients, 2.1% (prefrontal controls, 2.1%). Averaged across all SPT
conditions, results (t tests for independent samples) showed that
patients with hemiparesis were not more affected than those with-
out motor deficits, t(12) ? ?0.59, p ? .565. Premotor patients
with hemiparesis made 2.8% fewer errors than those without
hemiparesis (11.6% vs. 14.4%, respectively), and parietal patients
with hemiparesis made 6.7% more errors than those without hemi-
paresis (18.5% vs. 11.8%, respectively). These findings indicate
that motor deficits have no significant impact on behavioral per-
formance on the SPT.
Owing to the small sample size, the performance levels of
patients with mild speech apraxia (average SPT error rate
of 16.2%, as compared with 12.6% for the other 5 premotor
patients) could not be compared statistically. However, a descrip-
tive analysis supported the finding that there were no outliers in the
premotor or parietal patients’ performance scores. We therefore
suggest that the higher error rate (3.6% more errors) observed
among the premotor patients with apraxia than among those with-
out apraxia cannot be interpreted as reflecting a specific interaction
between mild apraxia and SPT performance. Finally, the 2 parietal
patients with constricted visual fields showed no specific impair-
ment in the spatial SPT condition (both primarily made errors on
the rhythm task).
Error rates were normally distributed in each task and for each
group, as assessed with Kolmogorov–Smirnov tests (which could
not be performed for the baseline task in the case of either the
premotor or the prefrontal control group because there were no
errors in these groups). We conducted three repeated measures
analyses of variance (ANOVAs) with the two-level factor task
(SPT [collapsed across subconditions] vs. baseline task) and the
two-level between-subjects factor lesion (patients vs. controls).
For the premotor patients, analyses indicated a main effect of
Figure 2.
and in the baseline task. The presentation time (in milliseconds) of each picture is shown at the bottom of each
sequence. All SPT examples show deviant trials, with the deviant picture shown in the next to last frame. The
baseline task example shows a trial containing the predefined target, also shown in the next to last frame. For
task details, see the Method section. A color version of this figure is on the Web at http://dx.doi.org/10.1037/
0894-4105.18.4.638.supp.
Examples of stimulus presentation in the rhythm, object, and position serial prediction tasks (SPTs)
641
MOTOR AREAS BEYOND MOTOR PERFORMANCE

Page 5

task, F(1, 12) ? 29.51, p ? .0001; a main effect of lesion, F(1,
12) ? 32.55, p ? .0001; and a Task ? Lesion interaction, F(1,
12) ? 6.09, p ? .03. Because of our small sample size, we used a
nonparametric method to further analyze this interaction. A Wil-
coxon test (for dependent samples) revealed that premotor patients
(z ? ?2.36, p ? .018) as well as controls (z ? ?2.36, p ? .018)
made significantly more errors on the SPT than on the baseline
task. Furthermore, a Mann–Whitney U test (for independent sam-
ples) showed that the performance of premotor patients and that of
premotor controls differed significantly on the SPT (U ? 3.00, p ?
.004) but not on the baseline task (U ? 10.50, p ? .073). This
finding indicates that premotor patients are impaired in serial
prediction.
Among the parietal patients, the same analysis yielded a main
effect of task, F(1, 12) ? 20.29, p ? .001; a main effect of lesion,
F(1, 12) ? 8.48, p ? .013; and a Task ? Lesion interaction, F(1,
12) ? 7.68, p ? .017. A step-down analysis of the interaction
revealed the same pattern of results as in the premotor groups and,
hence, specific impairment in serial prediction. Both parietal pa-
tients and their controls made significantly more errors on the SPT
than on the baseline task (parietal patients: z ? ?2.36, p ? .018;
parietal controls: z ? ?1.94, p ? .051). Parietal patients and
controls differed significantly on the SPT (U ? 6.00, p ? .017) but
not on the baseline task (U ? 22.00, p ? .805).
Finally, among the prefrontal patients, the ANOVA yielded a
main effect of task, F(1, 12) ? 29.99, p ? .0001; no main effect
of lesion, F(1, 12) ? 2.63, p ? .131; and no Task ? Lesion
interaction, F(1, 12) ? 2.29, p ? .156.
In a final analysis, main effects of task were analyzed among
premotor and parietal patients and their respective controls. We
conducted a repeated measures ANOVA comprising the three-
level factor property (rhythm, object, or position) and the two-level
factor lesion (patients vs. controls). For both the premotor and
parietal groups, this analysis yielded a main effect of lesion, F(1,
12) ? 15.17, p ? .002, and F(1, 12) ? 8.62, p ? .012, respec-
tively; no main effect of property, F(2, 24) ? 2.82, p ? .110, and
F(2, 24) ? 2.40, p ? .112, respectively; and no Task ? Lesion
interaction, F(2, 24) ? 1.50, p ? .245, and F(2, 24) ? 0.26, p ?
.773, respectively.
Taken together, these results point to impaired serial prediction
performance on the part of both the premotor and parietal patients
but not the prefrontal patients. Although all of the groups (includ-
ing the healthy controls) had more difficulty with the SPT than
with the baseline task, the significant Lesion ? Task interactions
in the premotor and parietal groups (but not in the prefrontal
group) indicate that these two groups were specifically impaired in
serial prediction (see Figure 3, bottom right). Moreover, the final
analysis revealed that, among both the premotor and parietal
patients, the SPT performance deficit was not dependent on the
attended stimulus property.
Discussion
In the present study we investigated, by means of a visual SPT,
whether ventrolateral premotor lesions result in serial prediction
deficits. This task allowed us to test the functional significance of
premotor and parietal cortices that have been shown to be robustly
coactivated during serial prediction in previous fMRI studies
(Schubotz & von Cramon, 2001a, 2001b, 2002a, 2002b, 2002c;
Schubotz et al., 2003). In accord with our expectations, premotor
Figure 3.
right: Behavioral results. Open bars show performance of the premotor, parietal, and prefrontal patients in the three
types of serial prediction task (SPT; temporal rhythm, object, and spatial position sequences, respectively) and in the
baseline target detection task. Corresponding solid bars represent the performance of the respective healthy controls.
Bottom right: Lesion ? Task interactions, which were significant at p ? .01 (as indicated with asterisks) for the
premotor and parietal patients and their respective controls but were not significant for the prefrontal patients. Thus,
premotor and parietal patients showed a specific behavioral deficit in serial prediction, whereas performance in the
baseline task (BAS) was preserved. Error bars represent percentages of error.
Study results. Performance was assessed by means of error rate percentages. Top left, bottom left, and top
642
SCHUBOTZ, SAKREIDA, TITTGEMEYER, AND VON CRAMON

Page 6

patients showed significant deficits on the SPT. This impairment
did not depend on the stimulus property to which patients attended
but resulted from the temporal, object-related, and spatial predic-
tion to which they had to adhere. Parietal patients were likewise
impaired in serial prediction. The clinical control group with
prefrontal lesions, on the other hand, showed no deficits at all. This
outcome further confirms that both the ventrolateral premotor and
corresponding parietal areas are critical in serial prediction, as
previously reported in a series of fMRI studies.
The present study contributes to the view that processing of
perceptual events relies on premotor processes, even if no motor
output is required. In contrast to other premotor areas, the PMv
seems to involve the coding and transcoding of sensory features.
Generally, premotor lesion studies in humans and monkeys have
focused on the dorsal premotor cortex and the supplementary
motor area (SMA); lesions restricted to the PMv have rarely been
explored. Findings in monkeys indicate that the PMv and dorsal
premotor cortex contribute differently to sensorimotor transforma-
tion. The dorsal premotor cortex is relevant for the selection of a
particular movement on the basis of visual cues that provide an
abstract sensorimotor transformation instruction (i.e., conditional
tasks; Kurata & Hoffman, 1994; Passingham, 1985, 1988). In
contrast, the PMv is involved whenever tactile or visual informa-
tion is needed to guide the interaction of the body with an object
(i.e., reaching, grasping, and manipulating; Fogassi et al., 2001;
Gregoriou & Savaki, 2003; Schieber, 2000). This is in line with
results indicating that the PMv contains a high ratio of neurons
with sensory receptive fields. Because these are frequently regis-
tered by different body parts, the PMv is taken to code environ-
mental features as a reference frame for a particular set of effectors
(Fogassi et al., 1996).
A crucial characteristic of the SPT paradigm used in the present
study is its anticipatory requirements or, in other words, sequenc-
ing functions. Perceptually comparable tasks without this require-
ment, such as demanding serial match-to-sample tasks (Schubotz
& von Cramon, 2002b) and target detection in stimulus sequences
(as used as control conditions in other SPT studies), have not been
shown to activate the PMv in fMRI studies. Likewise, sequencing
functions are required in the “motor version” of the SPT, the serial
reaction task (Nissen & Bullemer, 1987). This task has also been
reported to engage the lateral premotor cortex (Gordon et al., 1995;
Grafton, Hazeltine, & Ivry, 1995; Hazeltine, Grafton, & Ivry,
1997; Hikosaka, Miyashita, Miyachi, Sakai, & Lu, 1998; Hikosaka
et al., 1996; Honda et al., 1998; Sadato, Campbell, Ibanez, Deiber,
& Hallett, 1996; Sakai et al., 1998; Toni, Krams, Turner, &
Passingham, 1998). Thus, premotor activation appears to be
caused by the processing of stimulus sequences rather than by the
transformation of those sequences into a corresponding motor
sequence.
In view of the present findings and earlier fMRI results, we
propose that motor sequencing impairments resulting from premo-
tor lesions reflect a sequence processing deficit rather than a motor
deficit (if primary motor cortices are functionally intact). The
disintegration of serially organized movements has been reported
as a result of premotor lesions (Derouesne, 1973; Lurija, 1966).
Forms of sequencing deficits differ slightly with respect to premo-
tor lesion sites. Premotor lesions that include parts of the SMA
appear to impair sequential movements that are internally (mem-
ory based) rather than sensory guided and often involve interlimb
coordination (Dick, Benecke, Rothwell, Day, & Marsden, 1986;
Lepage et al., 1999). Behavioral deficits caused by such lesions of
subacute status are typically characterized by paresis of the prox-
imal muscles (shoulder and hip) contralateral to the lesion side,
along with deficits in interlimb coordination (Freund, 1985, 1990;
Freund & Hummelsheim, 1984, 1985). In contrast, lesions con-
fined to the lateral premotor cortex impair sensory-guided sequen-
tial movement (Halsband & Freund, 1990; Halsband, Ito, Tanji, &
Freund, 1993; Halsband et al., 2001). These findings have been
taken as support for a suggested dichotomy between externally and
internally guided sequencing involving lateral and medial premo-
tor sites, respectively (Mushiake, Inase, & Tanji, 1991).
Finally, sequencing disorders are one of the main indicators of
apraxia, a deficit that often follows damage to either parietal or
premotor regions (Harrington & Haaland, 1992; Liepmann, 1920).
Several subtypes of such sequencing deficits in the planning and
programming of volitional acts have been described, including
limb-kinetic apraxia (Brown, 1972) and ideomotor apraxia
(Kimura, 1982; Motomura, Seo, Asaba, & Sakai, 1989; Rush-
worth, Nixon, Renowden, Wade, & Passingham, 1997). Most
prominent are sequencing deficits in apraxia of speech, which is a
loss of the capacity to program the positioning of the speech
musculature and the sequencing of muscle movements during
volitional production of phonemes (Darley, Aronson, & Brown,
1969). Disintegration of learned articulatory gestures in speech
apraxia has been specifically attributed to damage within the left
PMv region (Schiff, Alexander, Naeser, & Galaburda, 1983;
Ziegler, 2002).
In line with the literature on monkeys, the present findings
support the view that PMv functions provide a platform for both
motor and sensory representations as well as their linkage. We
have proposed that this linkage represents a short-term forward
model that can specify parameters of different anticipatory behav-
ior that may not result in overt motor output. Such a model may
underlie both planning (internally guided sequencing) and predic-
tion (externally guided sequencing) either with or without motor
output (Schubotz et al., 2003).
References
Aziz-Zadeh, L., Maeda, F., Zaidel, E., Mazziotta, J., & Iacoboni, M.
(2002). Lateralization in motor facilitation during action observation: A
TMS study. Experimental Brain Research, 44, 127–131.
Brown, A. W. (1972). Aphasia, apraxia and agnosia: Clinical and theo-
retical aspects. Springfield, IL: Charles C Thomas.
Chaminade, T., Meary, D., Orliaguet, J. P., & Decety, J. (2001). Is
perceptual anticipation a motor simulation? A PET study. NeuroRe-
port, 12, 3669–3674.
Darley, F. L., Aronson, A. E., & Brown, J. R. (1969). Clusters of deviant
speech dimensions in the dysathrias. Journal of Speech and Hearing
Research, 12, 246–269.
Derouesne, C. (1973). Le syndrome pre ´-motour: A propos de 5 observa-
tions de tumeurs rolando-pre ´rolandiques circonscrites [The premotor
syndrome: Apropos of 5 cases of circumscribed rolando-prerolandic
tumors]. Revue Neurologique Paris, 128, 353–363.
Dick, J. P., Benecke, R., Rothwell, J. C., Day, B. L., & Marsden, C. D.
(1986). Simple and complex movements in a patient with infarction of
the right supplementary motor area. Movement Disorders, 1, 255–266.
643
MOTOR AREAS BEYOND MOTOR PERFORMANCE

Page 7

Fogassi, L., Gallese, V., Buccino, G., Craighero, L., Fadiga, L., & Rizzo-
latti, G. (2001). Cortical mechanism for the visual guidance of hand
grasping movements in the monkey: A reversible inactivation study.
Brain, 124, 571–586.
Fogassi, L., Gallese, V., Fadiga, L., Luppino, G., Matelli, M., & Rizzolatti,
G. (1996). Coding of peripersonal space in inferior premotor cortex (area
F4). Journal of Neurophysiology, 76, 141–157.
Freund, H. J. (1985). Clinical aspects of premotor function. Behavioural
Brain Research, 18, 187–191.
Freund, H. J. (1990). Premotor area and preparation of movement. Revista
de Neurologia, 146, 543–547.
Freund, H. J., & Hummelsheim, H. (1984). Premotor cortex in man:
Evidence for innervation of proximal limb muscles. Experimental Brain
Research, 53, 479–482.
Freund, H. J., & Hummelsheim, H. (1985). Lesions of premotor cortex in
man. Brain, 108, 697–733.
Gordon, A. M., Flament, D., Lee, J. H., Ugurbil, K., Kim, S. G., & Ebner,
T. J. (1995). Functional MRI of cortical motor areas during sequential
typing movements. Proceedings of the Annual Conference of the Cog-
nitive Science Society, 1422.
Grafton, S. T., Hazeltine, E., & Ivry, R. (1995). Functional mapping of
sequence learning in normal humans. Journal of Cognitive Neuro-
science, 7, 497–510.
Gregoriou, G. G., & Savaki, H. E. (2003). When vision guides movement:
A functional imaging study of the monkey brain. NeuroImage, 19,
959–967.
Halsband, U., & Freund, H. J. (1990). Premotor cortex and conditional
motor learning in man. Brain, 113, 207–222.
Halsband, U., Ito, N., Tanji, J., & Freund, H. J. (1993). The role of
premotor cortex and the supplementary motor area in the temporal
control of movement in man. Brain, 116, 243–266.
Halsband, U., Schmitt, J., Weyers, M., Binkofski, F., Grutzner, G., &
Freund, H. J. (2001). Recognition and imitation of pantomimed motor
acts after unilateral parietal and premotor lesions: A perspective on
apraxia. Neuropsychologia, 39, 200–216.
Hanakawa, T., Honda, M., Sawamoto, N., Okada, T., Yonekura, Y.,
Fukuyama, H., & Shibasaki, H. (2002). The role of rostral Brodmann
area 6 in mental-operation tasks: An integrative neuroimaging approach.
Cerebral Cortex, 12, 1157–1170.
Harrington, D. L., & Haaland, K. Y. (1992). Motor sequencing with left
hemisphere damage: Are some cognitive deficits specific to limb
apraxia? Brain, 115, 857–874.
Hazeltine, E., Grafton, S. T., & Ivry, R. (1997). Attention and stimulus
characteristics determine the locus of motor-sequence encoding. Brain,
120, 123–140.
Hikosaka, O., Miyashita, K., Miyachi, S., Sakai, K., & Lu, X. (1998).
Differential roles of the frontal cortex, basal ganglia, and cerebellum in
visuomotor sequence learning. Neurobiology of Learning and Mem-
ory, 70, 137–149.
Hikosaka, O., Sakai, K., Miyauchi, S., Takino, R., Sasaki, Y., & Pu ¨tz, B.
(1996). Activation of human presupplementary motor area in learning of
sequential procedures: A functional MRI study. Journal of Neurophys-
iology, 76, 617–621.
Honda, M., Deiber, M. P., Ibanez, V., Pascual-Leone, A., Zhuang, P., &
Hallett, M. (1998). Dynamic cortical involvement in implicit and explicit
motor sequence learning: A PET study. Brain, 121, 2159–2173.
Ja ¨nicke, H., Khoromskaia, V., Tittgemeyer, M., & Kruggel, F. (2002). Fast
affine scaling of MR brain images with lesions. In Annual Report 2002
of the Max Planck Institute of Cognitive NeuroScience (p. 105). Re-
trieved fromhttp://www.cns.mpg.de/publikationen/annual/resources/
AnnualReport2002.pdf
Kimura, D. (1982). Left-hemisphere control of oral and brachial move-
ments and their relation to communication. Philosophical Transactions
of the Royal Society of London. Series B, 298, 135–149.
Kurata, K., & Hoffman, D. S. (1994). Differential effects of muscimol
microinjection into dorsal and ventral aspects of the premotor cortex of
monkeys. Journal of Neurophysiology, 71, 1151–1164.
Lepage, M., Beaudoin, G., Boulet, C., O’Brien, I., Marcantoni, W., Bour-
gouin, P., & Richer, F. (1999). Frontal cortex and the programming of
repetitive tapping movements in man: Lesion effects and functional
neuroimaging. Cognitive Brain Research, 8, 17–25.
Liepmann, H. (1920). Apraxie [Apraxia]. In T. Brugsch & A. Eulenberg
(Eds.), Real-encyclopedie der gesamten hheilkunde. Ergebnisse der ge-
samten medizin [Encyclopedia of medical science]. (Vol. 1, pp. 116–
143). Berlin, Germany: Urban & Schwarzenberg.
Lurija, A. R. (1966). Higher cortical functions in man. New York: Basic
Books.
Motomura, N., Seo, T., Asaba, H., & Sakai, T. (1989). Motor learning in
ideomotor apraxia. International Journal of Neuroscience, 47, 125–129.
Murata, A., Fadiga, L., Fogassi, L., Gallese, V., Raos, V., & Rizzolatti, G.
(1997). Object representation in the ventral premotor cortex. Journal of
Neurophysiology, 78, 2226–2230.
Murata, A., Gallese, V., Kaseda, M., & Sakata, H. (1996). Parietal neurons
related to memory-guided hand manipulation. Journal of Neurophysiol-
ogy, 75, 2180–2186.
Mushiake, H., Inase, M., & Tanji, J. (1991). Neuronal activity in the
primate premotor, supplementary, and precentral motor cortex during
visually guided and internally determined sequential movements. Jour-
nal of Neurophysiology, 66, 705–718.
Nissen, M. J., & Bullemer, P. (1987). Attentional requirements of learning:
Evidence from performance measures. Journal of Cognitive Psychol-
ogy, 19, 1–32.
Passingham, R. E. (1985). Premotor cortex: Sensory cues and movement.
Behavioural Brain Research, 18, 175–185.
Passingham, R. E. (1988). Premotor cortex and preparation for movement.
Experimental Brain Research, 70, 590–596.
Ramnani, N., Toni, I., Josephs, O., Ashburner, J., & Passingham, R. E.
(2000). Learning- and expectation-related changes in the human brain
during motor learning. Journal of Neurophysiology, 84, 3026–3035.
Rizzolatti, G., Fogassi, L., & Gallese, V. (2000). Cortical mechanisms
subserving object grasping and action recognition: A new view on the
cortical motor functions. In M. S. Gazzaniga (Ed.), The new cognitive
neurosciences (pp. 539–552). Cambridge, MA: MIT Press.
Rizzolatti, G., Fogassi, L., & Gallese, V. (2002). Motor and cognitive
functions of the ventral premotor cortex. Current Opinion in Neurobi-
ology, 12, 149–154.
Rushworth, M. F., Nixon, P. D., Renowden, S., Wade, D. T., & Passing-
ham, R. E. (1997). The left parietal cortex and motor attention. Neuro-
psychologia, 35, 1261–1273.
Sadato, N., Campbell, G., Ibanez, V., Deiber, M., & Hallett, M. (1996).
Complexity affects regional cerebral blood flow change during sequen-
tial finger movements. Journal of Neuroscience, 16, 2691–2700.
Sakai, K., Hikosaka, O., Miyauchi, S., Takino, R., Sakaki, Y., & Pu ¨tz, B.
(1998). Transition of brain activation from frontal to parietal areas in
visuomotor sequence learning. Journal of Neuroscience, 18, 1827–1840.
Sakata, H., & Taira, M. (1994). Parietal control of hand action. Current
Opinion in Neurobiology, 4, 847–856.
Sakata, H., Taira, M., Murata, A., & Mine, S. (1995). Neural mechanisms
of visual guidance of hand action in the parietal cortex of the monkey.
Cerebral Cortex, 5, 429–438.
Schieber, M. H. (2000). Inactivation of the ventral premotor cortex biases
the laterality of motoric choices. Experimental Brain Research, 130,
497–507.
Schiff, H. B., Alexander, M. P., Naeser, M., & Galaburda, A. M. (1983).
Aphemia: Clinical-anatomic correlations. Archives of Neurology, 40,
720–727.
Schubotz, R. I. (1999). Instruction differentiates the processing of temporal
and spatial sequential patterns: Evidence from slow wave activity in
humans. Neuroscience Letters, 265, 1–4.
644
SCHUBOTZ, SAKREIDA, TITTGEMEYER, AND VON CRAMON

Page 8

Schubotz, R. I., Friederici, A. D., & von Cramon, D. Y. (2000). Time
perception and motor timing: A common cortical and subcortical basis
revealed by fMRI. NeuroImage, 11, 1–12.
Schubotz, R. I., & von Cramon, D. Y. (2001a). Functional organization of
the lateral premotor cortex: fMRI reveals different regions activated by
anticipation of object properties, location and speed. Cognitive Brain
Research, 11, 97–112.
Schubotz, R. I., & von Cramon, D. Y. (2001b). Interval and ordinal
properties of sequences are associated with distinct premotor areas.
Cerebral Cortex, 11, 210–222.
Schubotz, R. I., & von Cramon, D. Y. (2002a). A blueprint for target
motion: fMRI reveals perceptual complexity to modulate a premotor-
parietal network. NeuroImage, 16, 920–935.
Schubotz, R. I., & von Cramon, D. Y. (2002b). Dynamic patterns make the
premotor cortex interested in objects: Influence of stimulus and task
revealed by fMRI. Cognitive Brain Research, 14, 357–369.
Schubotz, R. I., & von Cramon, D. Y. (2002c). Predicting perceptual
events activates corresponding motor schemes in lateral premotor cor-
tex: An fMRI study. NeuroImage, 15, 787–796.
Schubotz, R. I., von Cramon, D. Y., & Lohmann, G. (2003). Auditory
what, where, and when: A sensory somatotopy in lateral premotor
cortex. NeuroImage, 20, 173–185.
Taira, M., Mine, S., Georgopoulus, A. P., Murata, A., & Sakata, H. (1990).
Parietal cortex neurons related to the visual guidance of hand movement.
Experimental Brain Research, 83, 29–36.
Talairach, J., & Tournoux, P. (1988). Co-planar stereotaxis atlas of the
human brain. New York: Thieme.
Toni, I., Krams, M., Turner, R., & Passingham, R. E. (1998). The time
course of changes during motor sequence learning: A whole-brain fMRI
study. NeuroImage, 8, 50–61.
Vallar, G. (1993). The anatomical basis of spatial hemineglect in humans.
In I. H. Robertson & J. C. Marshall (Eds.), Unilateral neglect: Clinical
and experimental studies (pp. 211–231). Hove, England: Erlbaum.
Ziegler, W. (2002). Psycholinguistic and motor theories of apraxia of
speech. Seminars in Speech and Language, 23, 231–244.
Received April 11, 2003
Revision received October 14, 2003
Accepted October 20, 2003 ?
645
MOTOR AREAS BEYOND MOTOR PERFORMANCE