Download Imaging the premotor areas Nathalie Picard* and Peter L Strick

663
Imaging the premotor areas
Nathalie Picard* and Peter L Strick†
Recent imaging studies of motor function provide new insights
into the organization of the premotor areas of the frontal lobe.
The pre-supplementary motor area and the rostral portion of
the dorsal premotor cortex, the ‘pre-PMd’, are, in many
respects, more like prefrontal areas than motor areas. Recent
data also suggest the existence of separate functional divisions
in the rostral cingulate zone.
Addresses
Department of Neurobiology, University of Pittsburgh School of
Medicine, W1640 Biomedical Science Tower, 200 Lothrop Street,
Pittsburgh, PA 15261, USA
*e-mail: [email protected]
† e-mail: [email protected]
Current Opinion in Neurobiology 2001, 11:663–672
0959-4388/01/$ — see front matter
© 2001 Elsevier Science Ltd. All rights reserved.
Abbreviations
CCZ
caudal cingulate zone
CMAd
dorsal cingulate motor area
CMAr
rostral cingulate motor area
CMAv
ventral cingulate motor area
FEF
frontal eye field
fMRI
functional magnetic resonance imaging
M1
primary motor cortex
PMd
dorsal premotor cortex
PMv
ventral premotor cortex
RCZ
rostral cingulate zone
RCZa
anterior rostral cingulate zone
RCZp
posterior rostral cingulate zone
SMA
supplementary motor area
VCA line
level of the anterior commissure
Introduction
Large regions of the brain located on the lateral surface and
on the medial wall of each hemisphere participate in the
generation and control of movement. The premotor areas
in the frontal lobe have the anatomical substrate to
influence motor output, both through connections with the
primary motor cortex (M1) and through direct projections
to the spinal cord (e.g. [1]). In monkeys, the frontal lobe
contains six well-defined premotor areas (Figure 1a). The
presence of analogous areas in humans has been inferred
from functional imaging studies (Figure 1b) [2,3].
However, the definition of premotor areas in humans is
still evolving. Some associations between anatomy and
function proposed in the past [2] have been validated by
recent imaging data, and other associations are emerging.
In this review, we present the results of salient imaging
studies that have helped to increase our understanding of
the underlying anatomical and functional organization of
the premotor areas. Much recent effort in the field of functional imaging has been to examine brain regions involved
in cognitive operations. The interpretation of activations
in premotor cortex during cognitive operations depends
critically on a clear definition of the location and boundaries
of these cortical areas. Thus, one focus of our review
synthesizes the new data that is relevant to this issue.
Medial wall
Pre-supplementary motor area and supplementary
motor area
In monkeys, it is now established that area 6 on the medial
wall of the brain contains two separate areas: the supplementary motor area proper (SMA) in the caudal portion of
area 6, and the pre-SMA in the rostral portion (Figure 1a;
reviewed in [2,4]). The SMA and pre-SMA are equivalent
to fields F3 and F6 described by Matelli et al. [5]. In
humans, the level of the anterior commissure (VCA line)
[6] marks the border between the two areas. The division
of medial area 6 into two distinct fields is based on a
collection of anatomical and functional data [2,4]. Because
the pre-SMA was born out of a premotor area — the traditional SMA of Woolsey et al. [7] — the common perception
is that the pre-SMA is also a motor area. However, the
connectivity and physiology of the pre-SMA suggest that it
is more like a prefrontal area than a motor area. Prefrontal
areas provide cognitive, sensory or motivational inputs for
motor behavior, whereas the motor areas are concerned
with more concrete aspects of movement (e.g. muscle
patterns). Two important differences in the anatomical
connections of the SMA and pre-SMA support this view.
First, only the SMA is directly connected to M1 and to the
spinal cord [1,8–11]. Second, only the pre-SMA is interconnected with the prefrontal cortex [12–14]. These
anatomical features, among others, are reflected by differential patterns of activity in the SMA and pre-SMA [4].
In neuroimaging studies, the pre-SMA/SMA distinction is
the clearest example of an anatomical and functional
dissociation that emerged from the primate model [2]. In
the following, we describe recent findings that provide
further support for this dissociation.
Initially, studies in monkeys suggested that the pre-SMA
has involved in learning sequential movements [15–17].
This motor view of pre-SMA function was supported by
the observation that, in humans, activation of the pre-SMA
increased in parallel to acquisition of a motor sequence
task [18]. In contrast, SMA activation during the same task
was related simply to aspects of motor execution. More
recent studies by the same group have resulted in a modified view of pre-SMA function. Sakai et al. [19] recently
compared pre-SMA activation in closely matched tasks
that all required visuo–motor associations, but varied in
motor and perceptual sequence components. Activation of
the pre-SMA occurred in all tasks related to visuo–motor
association demands rather than to sequential components.
In fact, pre-SMA activation was greatest in the conditional
task, in which non-sequential responses were arbitrarily
664
Motor systems
Figure 1
(a)
(b)
PreSMA SMA
Pre- SMA M1
SMA
CCZ
RCZp
RCZa
M1
CMAd
CMAr CMAv
PMd
PrePMd PMd
F4
PMv
PMv
F1
FEF
M1
FEF
M1
F7 F2
Motor areas of the frontal lobe in monkeys
(a) and homologous areas in the human (b).
In humans, the border between areas 6 and 4
on the lateral surface is located in the anterior
bank of the central sulcus [65]. For illustration,
the border is drawn on the surface of the
hemisphere along the central sulcus (bottom,
white dotted line). Except for the most medial
portion, M1 does not occupy the precentral
gyrus. Pictures of the monkey brain courtesy
of Richard P Dum; pictures of the human brain
reproduced with permission from [93].
45
44
F5
Current Opinion in Neurobiology
determined by the color of visual cues, and showed a
relative decrease in sequential paradigms. This important
study shows conclusively that activation of the pre-SMA in
these tasks has little to do with motor sequence learning
per se. Instead, pre-SMA activation occurs in association
with establishing or retrieving visuo–motor associations
(see also [20,21]). The activity in the pre-SMA in association with visually cued changes between motor sequences
[22,23] may also be due to the role of the pre-SMA in
retrieving visuo–motor associations.
motor preparation, during working memory delays of a
match to sample task [26] (Figure 2c). In addition, the
pre-SMA showed transient activation associated with shifts
of attention to visual object features (shape, color, location)
in a card sorting task [27]. Attending to various features of
visual stimuli was found to activate the pre-SMA equally in
another context [28]. These results suggest that pre-SMA
function is more closely related to processing or maintenance of relevant sensory information than response
selection or production.
Additional studies have extended the involvement of
the pre-SMA to associations based on auditory stimuli
[24••,25] (Figure 2a). Visual and auditory versions of a conditional choice reaction time paradigm generated pre-SMA
activations of equal magnitude [25]. Thus, the contribution of the pre-SMA to sensory–motor associations is
modality-independent. In addition, the contribution of
the pre-SMA appears to be effector-independent. Similar
regions are activated in conditional manual motor [24••,25]
and oculomotor tasks [21] (Figure 2b). This is consistent
with the poor somatotopic organization of the pre-SMA [2]
and supports the view that the pre-SMA operates at a more
abstract level. In contrast, SMA activation displayed only
movement-related activation in visual or auditory tasks.
Overall, neuroimaging studies leave no doubt that the
pre-SMA is fundamentally different from the SMA.
Activation of the SMA, caudal to the VCA line, is observed
primarily in relation to aspects of movement behavior. In
contrast, pre-SMA activation, rostral to the VCA line, is
associated with cognitive aspects of a variety of tasks (see
also [29–34]). These findings, together with anatomical
results, suggest that the pre-SMA might be functionally
considered a region of prefrontal cortex.
It must be emphasized that pre-SMA activation during
conditional motor behaviors was not due to response
selection or preparation [19,24••]. In fact, activation patterns
of the pre-SMA during non-conditional behavior suggest
that its contribution to sensory–motor association is
detached from motor aspects of the task. For example, the
pre-SMA displayed sustained activation, independent of
Cingulate motor areas
The cingulate sulcus contains three separate motor areas in
primates: the rostral cingulate motor area (CMAr), the caudal cingulate motor area in the ventral bank of the sulcus
(CMAv) and the caudal cingulate motor area in the dorsal
bank of the sulcus (CMAd; Figure 1a). We have proposed
[2] that corresponding areas are also present in humans: a
rostral cingulate zone (RCZ) with two subdivisions (anterior:
RCZa, and posterior: RCZp) and a caudal cingulate
zone (CCZ; Figure 1b). The anatomical variability of the
cingulate sulcus in humans complicates functional analysis
of this region [35–37]. As a consequence, a degree of
Imaging the premotor areas Picard and Strick
665
Figure 2
Anatomical and functional distinction of the
SMA and the pre-SMA in three different tasks.
(a) Top: activation in the SMA and pre-SMA
during an auditory conditional task; bottom:
selective activation in the pre-SMA during an
auditory–motor association task. Reproduced
with permission from [24••]. (b) Top: Activation
in the supplementary eye field (SEF) during
visually guided saccades; bottom: selective
activation of the pre-SMA for a mixed condition
of compatible and incompatible (Stroop-like)
conditional saccades. Reproduced with
permission from [21]. (c) Top: motor-related
activations in the SMA and CCZ; bottom:
sustained activation during working memory
delay in the pre-SMA and RCZ. Reproduced
with permission from [26].
(a) PreSMA
(b)
SMA
(c)
SMA
SEF
CCZ
PreSMA
uncertainty in the definition of the cingulate motor areas
remains. However, on the basis of results from recent
experiments, consistent patterns of activation are found in
the CCZ, and a new view of the RCZ is emerging.
The CCZ, which appears to be comparable to the CMAd
of monkeys, is activated primarily in relation to movement
execution ([2,3,26,38••], see also [39]). Painful stimuli
activate an area in or near the CCZ ventral to the area
associated with movement execution [38••]. Thus, different functional areas may exist for movement and for
painful stimuli. The site of movement-related activation in
the CCZ is remarkably similar across studies. For example,
in two different studies, finger movements activate virtually
identical sites in the CCZ [26,38••] (Figure 2c). In
addition, activation in the CCZ is consistently separable
from that in the SMA. These observations reinforce the
view that the CCZ is distinct from the SMA, despite the
proximity of the two areas and their tendency to be coactivated during manual tasks [40]. In the monkey, the
functional dissociation of the CMAd from the SMA occurs
under specific behavioral conditions [41]. Thus, future
studies are likely to find important functional differences
between the human CCZ and SMA.
Recent studies confirm that movement leads to activation
in the RCZ, rostral to the VCA line [26,38••]. Movementrelated activation in this region is best demonstrated in
analyses of single subjects [3,37,38 ••], presumably
because of anatomical variability. The activation in these
studies is clustered near the cingulate sulcus or its
ramifications. Similarly, the RCZ activation associated
with a word generation task is located in or near the
cingulate or paracingulate sulci and never extends onto
the cingulate gyrus [37]. Thus, some motor and cognitive
functions may share a common substrate within the RCZ.
In contrast, activations related to attention or arousal are
located at more rostral and ventral locations [38••,42],
which are probably outside the RCZ on the cingulate
gyrus proper.
PreSMA
PreSMA
RCZ
Current Opinion in Neurobiology
Two theories predominate about the overall function of
this region of cortex: ‘conflict monitoring’ [43] and ‘attention/selection for action’ [44]. The first theory emphasizes
the evaluative function of the RCZ, whereas the second
emphasizes its motor function ([45•], but see also [46]).
How do these two theories and functions relate to the
motor area(s) in the RCZ? We propose that they reflect the
properties of two different functional regions: conflict
monitoring within the RCZa and selection for action within the RCZp. For example, a series of imaging studies that
were carefully designed to control conflict monitoring,
found activation in the ‘anterior cingulate’ cortex
[43,45•,47,48•]. On average, the sites of these activations
were located 24 mm ± 7 mm (mean ± standard deviation)
anterior to the VCA line (Table 1). This location corresponds to the RCZa, which may correspond to the CMAr
of monkeys [2]. In contrast, when some of the same investigators used a similar paradigm that did not specifically
dissociate conflict monitoring from response selection,
they found response-related activation in the area of the
‘anterior cingulate’ cortex, located 1 mm anterior to the
VCA line [49]. This site corresponds to the RCZp, which
may correspond to the CMAv of monkeys [2].
The results of other imaging studies can be interpreted
within the same anatomical–functional framework. Two
groups of investigators, using single subject analysis, found
multiple foci of activation in the ‘anterior cingulate’ cortex
during word generation tasks that involved response selection [37,42] (Figure 3a). In both instances, the major site of
activation was located largely within the RCZp. Tasks that
can be interpreted as involving both conflict processing and
response selection (versions of Go/NoGo and STOP tasks)
evoked distinct sites of activation in the ‘anterior cingulate’
cortex [50•,51]. In a Go/NoGo task, different cues (e.g.
green or red stimuli) each determine a particular response
(Go or NoGo). Thus, this task is similar to a conditional
visuo–motor association task. Because only one cue is presented for each response to produce (no interference) and
because a cue is always associated with a single response,
666
Motor systems
Figure 3
Table 1
Talairach coordinates [6] of activation sites in the RCZ.
(a)
PreSMA
Ref Task
Type
x
[43] Flanker task: previous trial type effect
Conflict
–2 31
29
0
15
41
3
28
29
[48•] Flanker task: congruency x expectancy Conflict
–8 22
32
[92] Delayed recognition: high interference
vs no interference
Conflict
6
22
43
[50•] STOP task vs control
Conflict
6
25
37
Conflict & 3
selection 3
31
14
37
42
[45•]
RCZ
Stroop task: high conflict & low control Conflict
vs low conflict & high control
[47] Verb generation: high vs low response
competition
VCA
(b)
(STOP task vs control) & (Go/NoGo
vs control)
RCZa
Anatomical and functional division of the RCZ. (a) Activation during free
word generation. The dashed line separates activations located in the preSMA and in the RCZ. Reproduced with permission from [37].
(b) Activation related to conflict monitoring. Brain images from the two
studies were matched in size in the anterior–posterior axis. Dotted lines in
(b) represent the estimated locations of levels indicated in (a). Activations
related to conflict monitoring are located at the rostral edge of activations
found during word generation. This topography suggests that the RCZa is
involved in conflict monitoring (evaluative function) whereas the RCZp is
involved in response selection. Note that all cingulate activations are in
sulci, not on the cingulate gyrus, supporting the view that they overlap
with cingulate motor areas. Reproduced with permission from [43].
conflict is negligible in Go/NoGo tasks in which response
selection is required. Activation in the RCZ during the
Go/NoGo task was located, on average, 7.5 ± 9 mm in front
of the VCA line (Table 1). This site falls within the RCZp
[2]. In addition, activation in the RCZp was larger during
the Go/NoGo task than during the STOP task. In STOP
tasks, a cued Go response is prevented by the delayed
presentation of a second cue signaling NoGo. Thus, STOP
tasks present a high degree of response conflict because
contradictory instructions determine the subject’s response.
The RCZ activation in STOP tasks, like that in other high
conflict tasks, was located in a separate focus 25 mm rostral
to the VCA line (in the RCZa) [50•] (Table 1).
In sum, these data support the existence of at least three
functional areas in the anterior portion of the cingulate
z
[50•] Go/NoGo vs control
Selection –3 0
42
[50•]
Selection –6 0
42
Selection 4
46
Go/NoGo vs STOP task
[51] Go/NoGo vs Go
Current Opinion in Neurobiology
Conflict
y
16
sulcus: the CCZ and two subdivisions within the RCZ. The
CCZ appears to be activated during simple motor tasks,
whereas the RCZa and the RCZp appear to be differentially
involved in conflict monitoring and response selection.
Overall, proposals about the RCZ are founded on a relatively
small number of studies. Further research is necessary to
fully define the function(s) of these cortical regions.
Lateral surface
The dorsal part of the lateral premotor cortex
In monkeys, the dorsal part of the lateral premotor cortex
(PMd) has been divided into rostral (F7, PMdr) and caudal
(F2, PMdc) subdivisions [5,52], on the basis of anatomical
and physiological differences (Figure 1a). These differences
are analogous to those that generate the pre-SMA/SMA
split. In fact, in a number of important respects, the caudal
portion of the PMd has much in common with the SMA
proper. Both areas project to the primary motor cortex and
directly to the spinal cord [1,8,52,53]. Neither area has
substantial interconnections with prefrontal cortex [14].
Neurons in both regions are primarily involved in aspects of
motor control [4]. In contrast, the rostral portion of the PMd
has much in common with the pre-SMA. Neither of these
areas projects to the primary motor cortex or to the spinal
cord [1,8,52,53]. Instead, both regions are interconnected
with areas of prefrontal cortex and with the reticular formation [4,14,54]. Interestingly, neither the pre-SMA nor the
PMdr appears to have substantial interconnections with the
SMA proper or with the caudal portion of the PMd
[11,13,55]. Furthermore, the results of neuronal recording
and functional imaging studies suggest that the pre-SMA
and the rostral portion of the PMd are more involved in
cognitive than in motor processes (see below). On the basis
of these findings, we believe that there is heuristic value in
adopting a new terminology to refer to these cortical areas.
Imaging the premotor areas Picard and Strick
667
Figure 4
Anatomical and functional division of
dorsolateral area 6. (a) Top: activation of the
PMd proper during execution of finger
flexion/extension movements; bottom:
activation of the pre-PMd during imagined
movements of the fingers. Reproduced with
permission from [31]. (b) Activation of the
pre-PMd related to spatial attention/memory is
shown in red, activation of the PMd on the
precentral gyrus related to movement
preparation is shown in yellow, and the
overlap is shown in green. Reproduced with
permission from [59••].
(a)
PMd
(b)
PrePMd
PrePMd
PMd
Current Opinion in Neurobiology
We suggest that the rostral portion of the PMd (F7) be
termed the pre-PMd, and that the caudal portion of the
PMd (F2) be termed the PMd proper. This terminology
more clearly reflects the parallels between these areas and
the pre-SMA and SMA proper.
Recent studies in monkeys further support the distinction
between the pre-PMd and the PMd proper. Parietal cells
that project to the pre-PMd convey eye movement signals,
whereas those that project to the PMd convey hand movement signals [56,57]. The two subdivisions can be further
characterized on the basis of their differential involvement
in oculomotor control [58]. Eye movements are evoked by
stimulation of pre-PMd, whereas predominantly limb and
body movements are evoked from the PMd. Similarly,
neurons in the pre-PMd are more active during a saccade
task than during a limb movement task. In contrast, the
reverse is the case for neurons in the PMd. Thus, there is
ample evidence that the pre-PMd and the PMd are
anatomically and physiologically distinct [59••].
The functional distinction between the pre-PMd and the
PMd has not always been obvious in imaging studies of
human subjects. However, we have found that a consistent
pattern emerges when M1 activation related to hand movement is used as an ‘anchor point’ and activations in
premotor cortex, relating to other more cognitive types of
movement in the same subjects, are measured in relation to
this point. The data in Table 2 illustrates that, in a recent
group of studies, movement performance tasks produced
activations more caudally in the PMd than more cognitively
demanding tasks. Movement-related activations were
located on average 8.1 mm rostral to the center of M1
activation in the same subjects [31,32,60–64]. This value is
strikingly similar to the location of the hand representation
on the precentral gyrus. In humans, the precentral gyrus
corresponds to the premotor cortex (area 6) [65], which is
8.8 mm anterior to the hand representation in the central
sulcus [66]. Over a relatively large number of studies, the
average of the absolute coordinates for movement-related
activation in the PMd and the location of the hand representation on the precentral gyrus [66] are very similar
(Table 2). Conversely, activations related to higher-order
processing (e.g. conditional visuo–motor associations,
response selection or motor imagery) are located in the prePMd an average of 22.9 mm anterior to movement-related
activation in M1 [25,31,61,67].
The rostro-caudal gradient of activation across the
pre-PMd–PMd is most convincingly demonstrated within
subjects [24••,25,31,59••,61,67–69] (Figure 4). For example, activation that specifically relates to sensory–motor
association in an auditory conditional task is restricted to
the rostral edge of area 6 [24••]. The site of this activation
is likely to be in the pre-PMd, rather than in the PMd.
Similarly, activation in other conditional motor tasks is
located in the pre-PMd, 18–26 mm anterior to movementrelated activation in M1 [25,67] (Table 2). In addition,
rostral portions of area 6 in the pre-PMd are activated
during the presentation of visual cues or movement imagination, whereas caudal portions of area 6 in the PMd are
activated during movement preparation or execution
[59••,61,69]. This interpretation is compatible with the
response properties of neurons seen in recording studies of
668
Motor systems
Table 2
Talairach coordinates [6] of activation sites in the PMd relative to movement-related activations in M1*.
Refs Contrast
Type
[25] Choice RT (auditory mode): (control-rest)∩(response uncertainty-rest)∩
(time uncertainty-rest)∩(dual uncertainty-rest)
Movement-related
PMd
x, y, z
M1
x, y, z
∆y
∆z
–2
–42,–18,48
Choice RT (auditory mode): response uncertainty-control
Higher-order
–54,6,46
24
Choice RT (auditory mode): time uncertainty-control
Higher-order
–50,4,42
22
–6
Choice RT (auditory mode): dual uncertainty-control
Higher-order
–52,6,48
24
0
0
Choice RT (visual mode): (control-rest)∩(response uncertainty-rest)∩
(time uncertainty-rest)∩(dual uncertainty-rest)
Movement-related
Choice RT (visual mode): response uncertainty-control
Higher-order
–50,8,50
24
Choice RT (visual mode): time uncertainty-control
Higher-order
–44,2,50
18
0
Choice RT (visual mode): dual uncertainty-control
Higher-order
–52,10,46
26
–4
15
12
0
–3
21
21
–15
–6
12
6
0
12
21
24
–15
–15
[31] Finger movement-rest
–36,–16,50
Movement-related –36,–3,66
42,–3,60
Imagined finger movement-rest
Higher-order
(finger movement-rest)-(imagined movement-rest)
Movement-related –36,–6,69
24,–9,75
(imagined movement-rest)-(finger movement-rest)
Higher-order
–42,–18,66
39,–15,63
–42,3,51
42,6,57
–42,–18,69
39,–15,63
–42,3,51
48,9,48
[32] Self-paced finger movement-rest
Movement-related –12,–14,60
–34,–18,56
4
4
[60] Object manipulation-rest
Movement-related –40,–16,52
–46,–32,50
16
2
[61] Event-related: finger movement period
Movement-related –38,–4,60
–36,–8,54
36,–20,58
16
12
2
–4
26
12
[62] Conditional visual-perceptual control
Event-related: instruction & delay periods
Movement-related –34,–14,62
Higher-order
–18,6,70
–42,–28,52
14
10
[63] Hand movement-rest
Movement-related 32,–29,64
32,–29,54
0
10
–39,–29,63
–35,–27,53
6
–2
–1
–3
Movement-related –41,–23,62
–57,–21,48
–36,–23,53
0
2
9
–5
Higher-order
–33,–3,48
–33,–27,55
24
–7
Movement-related 37.3,–14.4,
60.3
38.2,–22.2,
56.9
8.1
2.4
4.0,5.9,6.5
6.5
5.8
[64] Hand reaching: (eye-arm-jump & eye-arm-stationary)-(eye-jump & eye-stationary) Movement-related –41,–23,62
–53,–29,50
Hand reaching: (eye-arm-stationary)-(eye-stationary)
[67] Conditional grip-mandatory grip
Average† (n=14)
Standard deviation†
Average† (n=13)
Standard deviation†
[66] High resolution fMRI & 3D reconstruction: finger movement-rest
Average (n=5)
Standard deviation
10.9,9.3,7.4
Higher-order
43.9,5.0,50.6
22.9 –4.8
10.1,3.5,7.1
2.4
7.9
Movement-related –35.5,–14.6, –36.6,–23.4, 8.8
8.5
65.3
6.0,4.5,5.6
56.8
7.6,4.1,9.4
*Only hand movement tasks were considered in this comparison. † Absolute values used for calculation of x averages and standard deviations.
∩, intersection.
awake trained monkeys [59••,70,71]. The PMd contains a
high proportion of neurons that display set- and movement-related activity. In contrast, neurons in the pre-PMd
are more responsive to sensory cues, and fewer are active
in relation to movement. Thus, neuroimaging studies and
neuron properties indicate that the PMd is primarily
involved in aspects of movement preparation or generation
(see also [72,73]), whereas the functions of the pre-PMd
are more closely related to cognitive processes than to
motor processes.
The ventral part of the lateral premotor cortex
In monkeys, the ventral part of the lateral premotor cortex
(PMv) lies in area 6 below the spur of the arcuate sulcus
(Figure 1a). The PMv, like the PMd proper, is densely interconnected with M1. In addition, the portion of the PMv in
and adjacent to the caudal bank of the arcuate sulcus contains
neurons that project directly to the spinal cord [1,53]. There
is general agreement that the PMv in humans lies ventral to
the frontal eye field (FEF). However, the precise location and
boundaries of the PMv in humans is uncertain [3,74•].
Imaging the premotor areas Picard and Strick
Matelli et al. [75] suggest that the PMv of monkeys consists
of two cytoarchitectonic fields, F4 and F5 (Figure 1a). The
connections of F4 with posterior parietal cortex and the
responses properties of F4 neurons have led Rizzolatti
et al. [76] to suggest that F4 is involved in ‘transforming
object locations into appropriate movements towards
them’ (see also [77]). This hypothesis has not been
explored by imaging studies in humans. Furthermore, the
location or even the existence of a human equivalent of
the monkey F4 remains to be established.
The F5 portion of the PMv has received more attention.
Rizzolatti et al. [76] have described two types of neurons in
monkey F5 that have unique responses to visual stimuli:
‘canonical’ and ‘mirror’ neurons [4,76,78,79]. Canonical neurons respond to the visual presentation of three-dimensional
objects of different size and shape. The motor responses of
these neurons are limited to specific goal-directed actions
towards these three-dimensional objects. Canonical neurons
are largely found in the portion of the PMv that is buried in
the bank of the arcuate sulcus. Mirror neurons are active
when a monkey watches someone else perform a specific
action, and when the monkey executes a similar action.
Mirror neurons are largely found in the portion of the PMv
that is on the cortical surface, caudal to the arcuate sulcus.
The unique properties of mirror neurons have prompted
the search for the equivalent of F5 in human subjects.
Neuroimaging studies have generated conflicting results
on this issue. In a recent meta-analysis, Grèzes and Decety
[74•] failed to find conclusive evidence for neuronal activity in inferior frontal areas, including ventral portions of
area 6, during action observation. In contrast, other studies
have reported activation of area 44 during imitation and
observation of finger movements [80,81], as well as when
objects are gripped and manipulated [60,82,83]. This has
led some investigators to suggest that area 44, which has
traditionally been considered part of Broca’s area, is the
human equivalent of the monkey F5 [76,84].
Other results raise doubts over this conclusion. Amunts
et al. [85] found considerable variation in the location of
the border between area 44 and rostro-ventral area 6, and
noted that this border cannot be determined solely on the
basis of gyral and sulcal landmarks. Area 44 is strongly
activated during tasks that involve silent or covert speech
(e.g. [86–88]). Thus, it is possible that activation of area 44
during action observation, in some cases, reflects internal
verbalization of the observed action (e.g. [74•]). This view
is compatible with the absence of activation in Broca’s area
during the observation of meaningless hand gestures that
cannot be named [89,90]. However, verbalization alone
cannot account for all activations related to action observation, which are also found in parts of premotor cortex
clearly outside of Broca’s area [74•,89–91].
A recent report by Buccino et al. [91] indicates that observation of recognizable face, hand or foot actions resulted in
669
a somatotopically organized pattern of activation that
involved all of the premotor cortex on the lateral surface
(i.e. both the PMd and the presumed PMv). These authors
also observed activation in or near Broca’s area in the action
observation tasks. Thus, the relationship between the
activation in area 44 and that observed in portions of area 6 is
unclear. Importantly, these results indicate that the human
PMv can’t be identified solely by the presence of activation
during movement observation tasks. In summary, on the
basis of previous data, it is not possible to establish a definite correspondence between the functional subdivisions of
the monkey PMv and the inferior frontal areas in humans.
Conclusions
The data presented in this review help to clarify the location
and boundaries of the premotor areas in the frontal lobe of
humans. For many of these areas, there is a clear correspondence with a specific premotor area in the monkey. For
other regions, such as the motor fields in inferior frontal
cortex, the correspondence with areas in the monkey brain
remains to be established. Two regions have generally been
considered to be motor fields: the rostral part of area 6 on the
medial wall of the hemisphere (pre-SMA), and the rostral
part of area 6 on the dorsal surface (pre-PMd). However,
both these areas display activation that is more closely
related to cognitive than to motor processes. Thus, it might
be more appropriate to consider the pre-SMA and the
pre-PMd as functional components of prefrontal cortex,
rather than as premotor areas. In other cases, cognitive and
motor functions appear to have a common anatomical
substrate. The RCZa, which may correspond to the CMAr
of monkeys, is involved in ‘conflict monitoring’. The RCZp,
which may correspond to the CMAv of monkeys, appears to
be involved in response selection. Other premotor areas,
including the SMA proper, the PMd proper and the CCZ
are involved in various aspects of movement generation and
control. Overall, we feel that it is important to continue to
seek correspondences between motor areas in the monkey
and human cortex, as this will result in important insights
into the functional organization of the frontal lobe.
Acknowledgements
Our work is supported by the Veterans Administration Medical Research
and Rehabilitation Research and Development Services (PL Strick), and
United States Public Health Service grant NS24328 (PL Strick).
References and recommended reading
Papers of particular interest, published within the annual period of review,
have been highlighted as:
• of special interest
•• of outstanding interest
1.
Dum RP, Strick PL: The origin of corticospinal projections from the
premotor areas in the frontal lobe. J Neurosci 1991, 11:667-689.
2.
Picard N, Strick PL: Medial wall motor areas: a review of their
location and functional activation. Cereb Cortex 1996, 6:342-353.
3.
Fink GR, Frackowiak RSJ, Pietrzyk U, Passingham RE: Multiple
nonprimary motor areas in the human cortex. J Neurophysiol 1997,
77:2164-2174.
4.
Geyer S, Matelli M, Luppino G, Zilles K: Functional neuroanatomy of
the primate isocortical motor system. Anat Embryol 2000,
202:443-474.
670
Motor systems
5.
Matelli M, Luppino G, Rizzolatti G: Architecture of superior and
medial area 6 and the adjacent cingulate cortex in the macaque
monkey. J Comp Neurol 1991, 311:445-462.
6.
Talairach J, Tournoux P: Coplanar Stereotaxic Atlas of the Human
Brain. Stuttgart: Thieme; 1988.
7.
Woolsey CN, Settlage PH, Meyer DR, Sencer W, Pinto Hamuy T,
Travis AM: Patterns of localization in precentral and
‘supplementary’ motor areas and their relation to the concept of a
premotor area. Assoc Res Nerv Ment Disord 1952, 30:238-264.
8.
Muakkassa KF, Strick PL: Frontal lobe inputs to primate motor
cortex: evidence for four somatotopically organized ‘premotor’
areas. Brain Res 1979, 177:176-182.
9.
Dum RP, Strick PL: Spinal cord terminations of the medial wall
motor areas in macaque monkeys. J Neurosci 1996,
16:6513-6525.
10. He SQ, Dum RP, Strick PL: Topographic organization of
corticospinal projections from the frontal lobe: motor areas on the
medial surface of the hemisphere. J Neurosci 1995,
15:3284-3306.
11. Wang Y, Shima K, Sawamura H, Tanji J: Spatial distribution of
cingulate cells projecting to the primary, supplementary, and presupplementary motor areas: a retrograde multiple labeling study
in the macaque monkey. Neurosci Res 2001, 39:39-49.
12. Bates JF, Goldman-Rakic PS: Prefrontal connections of medial
motor areas in the rhesus monkey. J Comp Neurol 1993,
336:211-228.
13. Luppino G, Matelli M, Camarda R, Rizzolatti G: Corticocortical
connections of area F3 (SMA-proper) and area F6 (Pre-SMA) in
the macaque monkey. J Comp Neurol 1993, 338:114-140.
14. Lu MT, Preston JB, Strick PL: Interconnections between the
prefrontal cortex and the premotor areas in the frontal lobe.
J Comp Neurol 1994, 341:375-392.
and a response selection control task. A similar dissociation is found in the
dorsal premotor cortex.
25. Sakai K, Hikosaka O, Takino R, Miyachi S, Nielsen M, Tamada T: What
and when: parallel and convergent processing in motor control.
J Neurosci 2000, 20:2691-2700.
26. Petit L, Courtney SM, Ungerleider LG, Haxby JV: Sustained activity in
the medial wall during working memory delays. J Neurosci 1998,
18:9429-9437.
27.
Nagahama Y, Okada T, Katsumi Y, Hayashi T, Yamauchi H,
Sawamoto N, Toma K, Nakamura K, Hanakawa T, Konishi J et al.:
Transient neural activity in the medial superior frontal gyrus and
precuneus time locked with attention shift between object
features. Neuroimage 1999, 10:193-199.
28. Schubotz RJ, von Cramon DY: Functional organization of the lateral
premotor cortex: fMRI reveals different regions activated by
anticipation of object properties, location and speed. Cogn Brain
Res 2001, 11:97-112.
29. Deiber MP, Honda M, Ibañez V, Sadato N, Hallett M: Medial motor
areas in self-initiated versus externally triggered movements
examined with fMRI: effect of movement type and rate.
J Neurophysiol 1999, 81:3065-3077.
30. Lee KM, Chang KH, Roh JK: Subregions within the supplementary
motor area activated at different stages of movement preparation
and execution. Neuroimage 1999, 9:117-123.
31. Gerardin E, Sirigu A, Lehéricy S, Poline JB, Gaymard B, Marsault C,
Agid Y, Le Bihan D: Partially overlapping neural networks for real
and imagined hand movements. Cereb Cortex 2000,
10:1093-1104.
32. Jenkins IH, Jahanshahi M, Jueptner M, Passingham RE, Brooks DJ:
Self-initiated versus externally triggered movements. II. The effect
of movement predictability on regional cerebral blood flow. Brain
2000, 123:1216-1228.
15. Nakamura K, Sakai K, Hikosaka O: Neuronal activity in medial
frontal cortex during learning of sequential procedures.
J Neurophysiol 1998, 80:2671-2687.
33. Crosson B, Sadek JR, Maron L, Gökçay D, Mohr CM, Auerbach EJ,
Freeman AJ, Leonard CM, Briggs RW: Relative shift of activity from
medial to lateral frontal cortex during internally versus externally
guided word generation. J Cogn Neurosci 2001, 13:272-283.
16. Nakamura K, Sakai K, Hikosaka O: Effects of local inactivation of
monkey medial frontal cortex in learning of sequential
procedures. J Neurophysiol 1999, 82:1063-1068.
34. Schubotz RI, von Cramon DY: Interval and ordinal properties of
sequences are associated with distinct premotor areas. Cereb
Cortex 2001, 11:210-222.
17.
35. Paus T, Otaky N, Caramanos Z, MacDonald D, Zijdenbos A,
D’Avirro D, Gutmans D, Holmes C, Tomaiuolo F, Evans AC: In vivo
morphometry of the intrasulcal gray matter in the human
cingulate, paracingulate, and superior-rostral sulci: hemispheric
asymmetries, gender differences and probability maps. J Comp
Neurol 1996, 376:664-673.
Shima K, Tanji J: Both supplementary and presupplementary motor
areas are crucial for the temporal organization of multiple
movements. J Neurophysiol 1998, 80:3247-3260.
18. Hikosaka O, Sakai K, Miyauchi S, Takino R, Sasaki Y, Pütz B:
Activation of human presupplementary motor area in learning of
sequential procedures: a functional MRI study. J Neurophysiol
1996, 76:617-621.
19. Sakai K, Hikosaka O, Miyauchi S, Sasaki Y, Fujimaki N, Pütz B:
Presupplementary motor area activation during sequence
learning reflects visuo-motor association. J Neurosci 1999,
19:RC1-6.
20. Dassonville P, Lewis SM, Zhu XH, Ugurbil K, Kim SG, Ashe J: The
effect of stimulus-response compatibility on cortical motor
activation. Neuroimage 2001, 13:1-14.
21. Merriam EP, Colby CL, Thulborn KR, Luna B, Olson CR, Sweeney JA:
Stimulus-response incompatibility activates cortex proximate to
three eye fields. Neuroimage 2001, 13:794-800.
22. Shima K, Mushiake H, Saito N, Tanji J: Role for cells in the
presupplementary motor area in updating motor plans. Proc Natl
Acad Sci USA 1996, 93:8694-8698.
23. Jäncke L, Himmelbach M, Shah NJ, Zilles K: The effect of switching
between sequential and repetitive movements on cortical
activation. Neuroimage 2000, 12:528-537.
24. Kurata K, Tsuji T, Naraki S, Seino M, Abe Y: Activation of the dorsal
•• premotor cortex and pre-supplementary motor area of humans
during an auditory conditional motor task. J Neurophysiol 2000,
84:1667-1672.
The anatomical and functional dissociation of the SMA and pre-SMA is
clearly shown in this study of conditional motor behavior. The results extend
the involvement of the pre-SMA to sensory–motor associations of auditory
stimuli. Only the pre-SMA showed activation specific to conditional associations. In contrast, the SMA was activated equally for the conditional task
36. Paus T, Tomaiuolo F, Otaky N, MacDonald D, Petrides M, Atlas J,
Morris R, Evans AC: Human cingulate and paracingulate sulci:
pattern, variability, asymmetry, and probabilistic map. Cereb
Cortex 1996, 6:207-214.
37.
Crosson B, Sadek JR, Bobholz JA, Gökçay D, Mohr CM, Leonard CM,
Maron L, Auerbach EJ, Browd SR, Freeman AJ, Briggs RW: Activity
in the paracingulate and cingulate sulci during word generation:
an fMRI study of functional anatomy. Cereb Cortex 1999,
9:307-316.
38. Kwan CL, Crawley AP, Mikulis DJ, Davis KD: An fMRI study of the
•• anterior cingulate cortex and surrounding medial wall activations
evoked by noxious cutaneous heat and cold stimuli. Pain 2000,
85:359-374.
Activations on the medial wall of the hemisphere related to the processing
of painful or innocuous thermal stimuli and during a motor task (finger to
thumb opposition) were evaluated with functional magnetic resonance imagine (fMRI). The single subject analyses of this study reveal a level of functional organization of the medial wall that is difficult to see in most group
analyses. The results confirm the motor role of the CCZ, as well as that of
the SMA. An important observation is that activations related to noxious stimuli in the caudal portion of the ‘anterior cingulate’ (behind the VCA line) were
located ventral to the area of CCZ activation related to hand movements
and, thus, may be located in a different functional area. Innocuous thermal
stimulations activated primarily a rostral and ventral cingulate region near the
genu of the corpus callosum. It is argued that these activations are nonspecifically related to arousal or attention.
39. Naito E, Ehrsson HH, Geyer S, Zilles K, Roland PE: Illusory arm
movements activate cortical motor areas: a positron emission
tomography study. J Neurosci 1999, 19:6134-6144.
Imaging the premotor areas Picard and Strick
671
40. Koski L, Paus T: Functional connectivity of the anterior cingulate
cortex within the human frontal lobe: a brain mapping metaanalysis. Exp Brain Res 2000, 133:55-65.
54. Keizer K, Kuypers HG: Distribution of corticospinal neurons with
collaterals to the lower brain stem reticular formation in monkey
(Macaca fascicularis). Exp Brain Res 1989, 74:311-318.
41. Picard N, Strick PL: Activation on the medial wall during
remembered sequences of reaching movements in monkeys.
J Neurophysiol 1997, 77:2197-2201.
55. Kurata K: Corticocortical inputs to the dorsal and ventral aspects
of the premotor cortex of macaque monkeys. Neurosci Res 1991,
12:263-280.
42. Davis KD, Taylor SJ, Crawley AP, Wood ML, Mikulis DJ: Functional
MRI of pain- and attention-related activations in the human
cingulate cortex. J Neurophysiol 1997, 77:3370-3380.
56. Marconi B, Genovesio A, Battaglia-Mayer A, Ferraina S, Squatrito S,
Molinari M, Lacquaniti F, Caminiti R: Eye–hand coordination during
reaching. I. Anatomical relationships between parietal and frontal
cortex. Cereb Cortex 2001, 11:513-527.
43. Botvinick M, Nystrom LE, Fissell K, Carter CS, Cohen JD: Conflict
monitoring versus selection-for-action in anterior cingulate
cortex. Nature 1999, 402:179-181.
57.
44. Petersen SE, Fox PT, Posner MI, Mintum M, Raichle ME: Positron
emission tomographic studies of the cortical anatomy of singleword processing. Nature 1988, 331:585-589.
45. Carter CS, Macdonald AM, Botvinick M, Ross LL, Stenger A, Noll D,
•
Cohen JD: Parsing executive processes: strategic vs. evaluative
functions of the anterior cingulate cortex. Proc Natl Acad Sci USA
2000, 97:1944-1948.
The evaluative function of the RCZa in conflict monitoring was demonstrated
using the Stroop task and event-related fMRI. Strategic and evaluative functions were dissociated by manipulating stimulus-response compatibility and
expectancy on a trial-by-trial basis. The RCZa showed patterns of activation
that reflected the degree of conflict present on individual trials. However,
the RCZa was less activated when strategic processes were engaged and
conflict reduced.
46. Paus T: Primate anterior cingulate cortex: where motor control,
drive and cognition interface. Nat Rev Neurosci 2001, 2:417-424.
47.
Barch DM, Braver TS, Sabb FW, Noll DC: Anterior cingulate and the
monitoring of response conflict: evidence from an fMRI study of
overt verb generation. J Cogn Neurosci 2000, 12:298-309.
48. Casey BJ, Thomas KM, Welsh TF, Badgaiyan RD, Eccard CH,
•
Jennings JR, Crone EA: Dissociation of response conflict,
attentional selection, and expectancy with functional magnetic
resonance imaging. Proc Natl Acad Sci USA 2000, 97:8728-8733.
The authors show that attentional conflict and selection are separate components, by examining the patterns of activation in distributed brain systems,
using fMRI and the Flanker task. Activation in the RCZa and in the dorsolateral prefrontal cortex was correlated with response conflict. Other regions of
the brain had activity patterns corresponding to simple violation of expectations (basal ganglia, insula) or selective visuo-spatial attention (area 8,
superior parietal lobule, cerebellum).
49. MacDonald AW III, Cohen JD, Stenger VA, Carter CS: Dissociating
the role of the dorsolateral prefrontal and anterior cingulate
cortex in cognitive control. Science 2000, 288:1835-1838.
50. Rubia K, Russell T, Overmeyer S, Brammer MJ, Bullmore ET,
•
Sharma T, Simmons A, Williams SCR, Giampietro V, Andrew CM,
Taylor E: Mapping motor inhibition: conjunctive brain activations
across different versions of go/no-go and stop tasks. Neuroimage
2001, 13:250-261.
An interesting finding of this study is the differential location of activation
within the RCZ for Go/NoGo and STOP tasks. The tasks differ in terms of
response conflict. Go/NoGo tasks are similar to conditional motor association tasks, in which motor responses are determined by arbitrary cues. Thus,
these tasks engage response selection processes and present relatively low
conflict. STOP tasks present a higher conflict situation because of the direct
competition between Go and NoGo cues for the production of a single
response. Activation in the RCZp was greater for the Go/NoGo task. This
observation supports the proposed role of the RCZp in response selection.
A separate focus of activation was found in the RCZa during both tasks. This
location corresponds to the region of the anterior cingulate cortex associated with conflict monitoring. Consistent with its role in establishing or
retrieving sensory–motor associations, the pre-SMA was activated in all
tasks. Areas of prefrontal and parietal cortex were also activated during
Go/NoGo or STOP tasks.
51. Menon V, Adleman NE, White CD, Glover GH, Reiss AL: Errorrelated brain activation during a Go/NoGo response inhibition
task. Hum Brain Mapp 2001, 12:131-143.
52. Barbas H, Pandya DN: Architecture and frontal cortical
connections of the premotor cortex (area 6) in the rhesus
monkey. J Comp Neurol 1987, 256:211-228.
53. He SQ, Dum RP, Strick PL: Topographic organization of
corticospinal projections from the fontal lobe: motor areas on the
lateral surface of the hemisphere. J Neurosci 1993, 13:952-980.
Battaglia-Mayer A, Ferraina S, Genovesio A, Marconi B, Squatrito S,
Molinari M, Lacquaniti F, Caminiti R: Eye–hand coordination during
reaching. II. An analysis of the relationships between visuomanual
signals in parietal cortex and parieto-frontal association
projections. Cereb Cortex 2001, 11:528-544.
58. Fuji N, Mushiake H, Tanji J: Rostrocaudal distinction of the dorsal
premotor area based on oculomotor involvement. J Neurophysiol
2000, 83:1764-1769.
59. Boussaoud D: Attention versus intention in the primate premotor
•• cortex. Neuroimage 2001, 14:S40-S45.
Here, the author presents anatomical and physiological evidence for the
presence of distinct functional subdivisions in dorsolateral area 6. In trained
monkeys, neurons in the caudal subdivision (PMd proper) are primarily active
in relation to movement preparation. Conversely, neurons in the rostral subdivision (pre-PMd) are primarily active in relation to spatial attention/memory
cues. Interestingly, the same dissociation was shown in a parallel fMRI study
in humans using a similar task.
60. Binkofski F, Buccino G, Posse S, Seitz RJ, Rizzolatti G, Freund HJ:
A fronto-parietal circuit for object manipulation in man: evidence
from an fMRI-study. Eur J Neurosci 1999, 11:3276-3286.
61. Toni I, Schluter ND, Josephs O, Friston K, Passingham RE: Signal-,
set- and movement-related activity in the human brain: an eventrelated fMRI study. Cereb Cortex 1999, 9:35-49.
62. Toni I, Passingham RE: Prefrontal-basal ganglia pathways are
involved in the learning of arbitrary visuomotor associations: a
PET study. Exp Brain Res 1999, 127:19-32.
63. Ehrsson HH, Naito E, Geyer S, Amunts K, Zilles K, Forssberg H,
Roland PE: Simultaneous movements of upper and lower limbs
are coordinated by motor representations that are shared by both
limbs: a PET study. Eur J Neurosci 2000, 12:3385-3398.
64. Desmurget M, Grea H, Grethe JS, Prablanc C, Alexander GE,
Grafton ST: Functional anatomy of nonvisual feedback loops
during reaching: a positron emission tomography study.
J Neurosci 2001, 21:2919-2928.
65. White LE, Andrews TJ, Hulette C, Richards A, Groelle M, Paydarfar J,
Purves D: Structure of the human sensorimotor system. I.
Morphology and cytoarchitecture of the central sulcus. Cereb
Cortex 1997, 7:18-30.
66. Moore CI, Stern CE, Corkin S, Fischl B, Gray AC, Rosen BR,
Dale AM: Segregation of somatosensory activation in the human
rolandic cortex using fMRI. J Neurophysiol 2000, 84:558-569.
67.
Grafton ST, Fagg AH, Arbib MA: Dorsal premotor cortex and
conditional movement selection: a PET functional mapping study.
J Neurophysiol 1998, 79:1092-1097.
68. Iacoboni M, Woods RP, Mazziotta JC: Bimodal (auditory and visual)
left frontoparietal circuitry for sensorimotor integration and
sensorimotor learning. Brain 1998, 121:2135-2143.
69. Pochon JB, Levy R, Poline JB, Crozier S, Lehéricy S, Pillon B,
Deweer B, Le Bihan D, Dubois B: The role of dorsolateral prefrontal
cortex in the preparation of forthcoming actions: an fMRI study.
Cereb Cortex 2001, 11:260-266.
70. Di Pellegrino G, Wise SP: A neurophysiological comparison of
three distinct regions of the primate frontal lobe. Brain 1991,
114:951-978.
71. Johnson PB, Ferraina S, Bianchi L, Caminiti R: Cortical networks for
visual reaching: physiological and anatomical organization of
frontal and parietal lobe arm regions. Cereb Cortex 1996,
6:102-119.
72. van Mier H, Tempel LW, Perlmutter JS, Raichle ME, Petersen SE:
Changes in brain activity during motor learning measured with
PET: effects of hand of performance and practice. J Neurophysiol
1998, 80:2177-2199.
672
Motor systems
73. Horwitz B, Deiber MP, Ibáñez V, Sadato N, Hallett M: Correlations
between reaction time and cerebral blood flow during motor
preparation. Neuroimage 2000, 12:434-441.
83. Ehrsson HH, Fagergren A, Forssberg H: Differential fronto-parietal
activation depending on force used in a precision grip task: an
fMRI study. J Neurophysiol 2001, 85:2613-2623.
74. Grèzes J, Decety J: Functional anatomy of execution, mental
•
simulation, observation, and verb generation of actions: a metaanalysis. Hum Brain Mapp 2001, 12:1-19.
This meta-analysis shows the involvement of the dorsal and ventral premotor
cortex in movement execution and imagination. However, the data reviewed
does not support the involvement of inferior frontal areas in movement observation. Three hypotheses regarding PMv location are examined [3]: area 6
on the precentral gyrus adjacent and inferior to the FEF; opercular area 6;
area 44. The review suggests that activation in Broca’s area is primarily related to overt or covert verbal processes. On the other hand, inferior area 6 was
frequently activated during motor execution or imagery.
84. Rizzolatti G, Arbib MA: Language within our grasp. Trends Neurosci
1998, 21:188-194.
75. Matelli M, Luppino G, Rizzolatti G: Pattern of cytochrome oxidase
activity in frontal agranular cortex of the macaque monkey. Behav
Brain Res 1985, 18:125-136.
76. Rizzolatti G, Luppino G, Matelli M: The organization of the cortical
motor system: new concepts. Electroencephalogr Clin Neurophysiol
1998, 106:283-296.
77.
Graziano MSA, Gross CG: Spatial maps for the control of
movement. Curr Opin Neurobiol 1998, 8:195-201.
78. Fadiga L, Fogassi L, Gallese V, Rizzolatti G: Visuomotor neurons:
ambiguity of the discharge or ‘motor’ perception? Int J
Psychophysiol 2000, 35:165-177.
79. Fogassi L, Gallese V, Buccino G, Craighero L, Fadiga L, Rizzolatti G:
Cortical mechanism for the visual guidance of hand grasping
movements in the monkey. A reversible inactivation study. Brain
2001, 124:571-586.
80. Iacoboni M, Woods RP, Brass M, Bekkering H, Mazziotta JC,
Rizzolatti G: Cortical mechanisms of human imitation. Science
1999, 286:2526-2528.
81. Binkofski F, Amunts K, Stephan KM, Posse S, Schormann T,
Freund HJ, Zilles K, Seitz RJ: Broca’s region subserves imagery of
motion: a combined cytoarchitectonic and fMRI study. Hum Brain
Mapp 2000, 11:273-285.
82. Ehrsson HH, Fagergren A, Jonsson T, Westling G, Johansson RS,
Forssberg H: Cortical activity in precision- versus power-grip
tasks: an fMRI study. J Neurophysiol 2000, 83:528-536.
85. Amunts K, Schleicher A, Bürgel U, Mohlberg H, Uylings HBM,
Zilles K: Broca’s region revisited: cytoarchitecture and intersubject
variability. J Comp Neurol 1999, 421:319-341.
86. Grafton ST, Fadiga L, Arbib MA, Rizzolatti G: Premotor cortex
activation during observation and naming of familiar tools.
Neuroimage 1997, 6:231-236.
87.
Friedman L, Kenny JT, Wise AL, Wu D, Stuve TA, Miller DA,
Jesberger JA, Lewin JS: Brain activation during silent word
generation evaluated with functional MRI. Brain Lang 1998,
64:231-256.
88. Papathanassiou D, Etard O, Mellet E, Zago L, Mazoyer B, TzourioMazoyer N: A common language network for comprehension and
production: a contribution to the definition of language epicenters
with PET. Neuroimage 2000, 11:347-357.
89. Grèzes J, Costes N, Decety J: The effects of learning and intention
on the neural network involved in the perception of meaningless
actions. Brain 1999, 122:1875-1887.
90. Hermsdörfer J, Goldenberg G, Wachsmuth C, Conrad B, CeballosBauman AO, Bartenstein P, Schwaiger M, Boecker H: Cortical
correlates of gesture processing: clues to the cerebral
mechanisms underlying apraxia during the imitation of
meaningless gestures. Neuroimage 2001, 14:149-161.
91. Buccino G, Binkofski F, Fink GR, Fadiga L, Fogassi L, Gallese R,
Seitz RJ, Rizzolatti G, Freund HJ: Action observation activates
premotor and parietal areas in a somatotopic manner: an fMRI
study. Eur J Neurosci 2001, 13:400-404.
92. Herrmann M, Rotte M, Grubich C, Ebert AD, Schiltz K, Münte TF,
Heinze HJ: Control of semantic interference in episodic memory
retrieval is associated with an anterior cingulate-prefrontal
activation pattern. Hum Brain Mapp 2001, 13:94-103.
93. Duvernoy HM: The Human Brain. Surface, Three-dimensional
Anatomy and MRI. New York: Springer-Verlag; 1991.