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Revealing humans’ sensorimotor functions
with electrical cortical stimulation
rstb.royalsocietypublishing.org
Michel Desmurget1,2 and Angela Sirigu1,2
1
2
Review
Cite this article: Desmurget M, Sirigu A.
2015 Revealing humans’ sensorimotor
functions with electrical cortical stimulation.
Phil. Trans. R. Soc. B 370: 20140207.
http://dx.doi.org/10.1098/rstb.2014.0207
Accepted: 13 March 2015
One contribution of 15 to a theme issue
‘Controlling brain activity to alter perception,
behaviour and society’.
Centre de Neuroscience Cognitive, CNRS, UMR 5229, 67 boulevard Pinel, Bron 69500, France
Université Claude Bernard, Lyon 1, 43 boulevard du 11 novembre 1918, Villeurbanne 69100, France
Direct electrical stimulation (DES) of the human brain has been used by
neurosurgeons for almost a century. Although this procedure serves only clinical purposes, it generates data that have a great scientific interest. Had DES not
been employed, our comprehension of the organization of the sensorimotor
systems involved in movement execution, language production, the emergence of action intentionality or the subjective feeling of movement
awareness would have been greatly undermined. This does not mean, of
course, that DES is a gold standard devoid of limitations and that other
approaches are not of primary importance, including electrophysiology,
modelling, neuroimaging or psychophysics in patients and healthy subjects.
Rather, this indicates that the contribution of DES cannot be restricted, in
humans, to the ubiquitous concepts of homunculus and somatotopy. DES is
a fundamental tool in our attempt to understand the human brain because it
represents a unique method for mapping sensorimotor pathways and interfering with the functioning of localized neural populations during the
performance of well-defined behavioural tasks.
Subject Areas:
neuroscience
Keywords:
electrical stimulation, sensorimotor maps,
somatotopy, homunculus, language, human
Author for correspondence:
Angela Sirigu
e-mail: [email protected]
1. Electrical stimulation: a unique approach for probing brain
functions
One of the most important discoveries in modern neuroscience can indisputably be attributed to Luigi Galvani, who showed that electrical stimulation of
the sciatic nerve in a severed frog leg caused the attached muscle to contract
[1]. This finding sparked a flurry of research activity that has persisted up to
the present. In animals, the first systematic use of direct electrical stimulation
(DES) was conducted by Gustav Fritsch and Eduard Hitzig in Germany [2]
and David Ferrier in England [3]. These authors showed that stimulating the
cerebral cortex of dogs and monkeys evoked topographically organized
muscle contractions in the contralateral hemibody [4]. They also established
that lesions of the regions from which a movement was evoked caused a deficit
in the realization of this movement and even, sometimes, a total paralysis. In
the following years, DES was progressively generalized to human patients
with various levels of success and ethical concerns [5]. However, this technique
only reached its apogee in the 1930s with the well-known work of Wilder
Penfield [6]. Since then, the approach has remained roughly unchanged,
beyond minor technical and procedural adaptations [7,8].
Of course, in humans, the unique raison d’être of DES is (and has to be) clinical.
If neurosurgeons now use this mapping procedure almost universally, it is with
the purpose of identifying cerebral areas, resection of which could cause major
functional deficits [9,10]. Consistent with this goal, it has been shown that the surgical use of DES dramatically reduces the occurrence of permanent post-operative
sequelae in patients with brain tumours, while significantly improving long-term
survival [11–15]. However, the pre-eminence of clinical goals is not inconsistent
with the existence of fundamental inquiries. Obviously, the behavioural and
neurophysiological observations collected in per-operative contexts can also be
of major interest for fundamental research and, in particular, for understanding
the organization of the human brain.
& 2015 The Author(s) Published by the Royal Society. All rights reserved.
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2
At a time when the theory of brain localization was still
strongly questioned [30,31], Penfield’s work proved ground
breaking. As is the rule (see above), this neurosurgeon used
DES for clinical reasons ‘to define the motor area of the hemisphere so that an infiltrating tumour could be removed as
widely as possible without producing paralysis [and. . .] as a
preliminary to radical extirpation of an epileptogenic focus’
[6, p. 396]. However, using this approach he also reported
results of great fundamental interest. In particular, he was
the first to show, in humans, that functional specialization
existed not only across brain areas, but also within them.
In his main pioneering work, Penfield used DES in 163
patients, among whom 126 provided useful results [6]. He
observed that movements could be triggered from only a limited number of cortical regions, including the primary motor
cortex (M1), the primary somatosensory cortex (S1), the premotor cortex (PM) and the supplementary motor area (SMA).
Sensations were mostly evoked from the same regions. It is
unclear, however, whether stimulations (and how many)
were performed in non-central regions including the prefrontal
or posterior parietal cortices. Penfield found that more movements were triggered from the precentral gyrus, while more
body sensations were evoked from the post-central gyrus,
although sensory and motor responses were identified in
both of these two regions. He also reported that different cortical loci triggered movements and sensations in different body
parts. These observations led to the key idea that sensorimotor
regions are somatotopically organized in such a way that each
part of the body is represented within a different cortical space
in the pre- and post-central gyri. To formalize this finding, Penfield introduced the now famous concept of the homunculus.
According to him, within the central area, ‘toes begin at the
top and the members follow in order as though representing
a man hung upside down, but that thumb is followed by the
head as though the head and neck were erect and not inverted
(. . .) The homunculus may be said to be both motor and sensory as the sequence pattern is roughly the same, although
there are differences’ [6, pp. 431–432]. Most major biology textbooks still mention Penfield’s idea and display a version of his
drawing of the human homunculus (e.g. [32,33]).
The idea that M1 and S1 are somatotopically organized is
probably one of the very few proposals that have withstood
the test of time in modern neuroscience. The concept of
the homunculus has seen its general validity supported by
numerous neuroimaging and electrophysiological studies in
humans [34–41]. However, recent evidence has started to
suggest that this consensus may rely, when carefully considered, on a rather weak ground [42 –45]. According to this
view, the concept of the homunculus would mainly be an
emerging artefact of inter-individual averaging. It would
have no validity at the intra-individual level, where major
organizational differences are observed. In other words, the
homunculus as we know it would not represent a biological reality but rather a statistical construct that ‘does not appear to
exist’ [44, p. 292]. The same kind of criticism has been raised
with respect to neuroimaging data which ‘can produce the illusion of a localized process by emphasizing fortuitous regions of
overlap to the exclusion of the more widely distributed active
regions in the individual subjects’ [46, p. 197].
Clearly, these claims are consistent with the observation that the synoptic, regularly ordered sequence of body
Phil. Trans. R. Soc. B 370: 20140207
2. Mapping the sensorimotor system
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Certainly, this does not mean that DES is devoid of
limitations. In particular, the range of questions it allows us
to address is strongly restricted by clinical demands and peroperative constraints. This is why the results obtained with
this technique have to be interpreted in light of a more general
knowledge, generated by other approaches [16]. Consider, for
instance, neuroimaging (functional magnetic resonnance imaging—fMRI, positron emission tomography—PET) and
electrophysiology (electro and magneto encephalography—
EEG, MEG). During the past three decades these methods
have obviously played a major role in improving our understanding of the sensorimotor organization of the human
brain. However, it should not be forgotten that they too bear
important limitations [17–19]. In particular, they do not
allow us to neatly determine whether a responsive area is
truly critical for the expression of an investigated function
and whether an activated region receives afferent information,
sends efferent signals to the muscles or subserves computational processing. DES opens a window to this type of
knowledge. Of course, nobody would seriously argue that
this technique recruits neural populations as autogenous processes do. It should be evident that DES produces unnatural
patterns of cellular activation. However, such a limitation
does not, by any means, call into question the usefulness of
the method. Indeed, even if it relies on unnatural patterns of
neural activation, DES remains unparalleled in its ability to:
(i) drive descending pathways for identifying cortical regions
with outputs to motoneurons (e.g. [6,20]); (ii) elicit positive sensorimotor effects through the recruitment of neural populations
associated with the expression of high- (e.g. motor intention;
e.g. [21,22]) or low-level (e.g. sensory feelings; e.g. [6,20]) functions; (iii), elicit negative sensorimotor effects through
disruption of an endogenous neural activity involved in the
realization of an ongoing task (whether motor or cognitive;
e.g. [23,24]). It is true that interpretative biases related to a possible spread of the electrical current have always been a subject
of concern for researchers [25,26]. However, during the past
two decades solid evidence has been gathered, at least for the
high-intensity/high-frequency stimulation parameters typically
used in surgical protocols, that DES effects are typically
mediated by the cell population being stimulated [27–29]. In
other words, DES does not spread in a meaningless jumble.
It operates primarily at a local level and, doing so, offers an
invaluable way to investigate the anatomo-functional organization of the human brain. Among the multiple elements
supporting this conclusion (see [27,28] for detailed reviews),
the most convincing evidence comes probably from the successful use of DES for mapping brain functions in peroperative contexts. If, as is sometimes claimed [26], DES effects
were reflective of an artificial spread of current at distant sites,
then this method should be ineffective at preventing post-operative deficits in neurosurgical contexts. As reported above, this
is clearly not what the clinical literature demonstrates [11–15].
This being said, in the present review, we will focus on the
specificity and fundamental importance of DES. At a first
level, we intend to show that if this technique had not been
exploited in the past decades, several of our pillar concepts
and much of our knowledge on the anatomo-functional
organization of the sensorimotor system would be dramatically undermined. At a second level, we plan to emphasize
recent studies and technical developments to demonstrate
that DES remains a major approach for understanding
brain functions.
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3. Mapping complex sensorimotor synergies
From the data above, it appears that DES typically evokes
simple meaningless movements in humans. Nevertheless,
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Phil. Trans. R. Soc. B 370: 20140207
instance, are observed along the whole extent of the central
sulcus; they are not clustered in the medio-lateral region
and do not appear to be consistently medial with respect to
the responses recorded for other fingers, including the little
one (coloured in red). In fact, rather than observing independent contractions for each finger, Penfield reported, in most
cases, motor responses that involved all fingers together
without individual segregation (black dots). Recently, this
combined activation has been reproduced in monkeys,
where microstimulation was found to trigger organized patterns of finger synergies [60]. Also, data gathered in these
animals have clearly challenged the idea of a sequential representation of each individual finger along a medio-lateral
axis going from the little finger to the thumb [49,61].
Figure 1b displays, on the same plot, upper limb (shoulder,
elbow, wrist, hand, undissociated by Penfield, coloured in red)
and finger responses (coloured in blue). Eloquent sites for these
two segments exhibit a major level of overlap and redundancy.
It is hard to figure out how Penfield went from these intermingled responses to the nice sequential ordering presented
on the right panel, where upper limb representations are
located more medially than finger representations.
Data from the third panel (figure 1c) are even more disconcerting. They show face and neck representations.
Placing the neck above the face from these recordings really
seems questionable considering that all neck responses
except one are represented more laterally than face responses.
From a scientific point of view, the logic that led Penfield
to identify a precisely ordered homunculus on the basis of
his scattered data is hard to infer. However, a plausible
hypothesis might be that he got, at some point, the idea
of an inverted body map lined up over the cortical surface.
This map, drawn by Penfield himself in his pioneering work
[6], is shown on figure 1d. It implies, for instance, that the
neck should be represented more medially than the face.
Based on these remarks, it is tempting to speculate that
Penfield did not go from the data to the model, but was
rather biased toward forcing his clinical observations into
a predetermined map of representations.
In summary, DES has been a key approach for understanding the organization of the primary sensorimotor regions. The
early work of Wilder Penfield, in particular, proved fundamental for establishing the central idea that brain functions are
localized and that the sensorimotor system is organized
somatotopically in such a way that specific cortical sites control
specific muscles. Nevertheless, Penfield also went too far in his
attempt to describe a nicely ordered map of sensorimotor
representations within the central regions. Both recent results
[42–44,50] and a re-evaluation of his original observations
show that sensorimotor representations are not organized in
a sequential rigidly ordered way, but rather in a mosaic of intermingled representations where body parts overlap in multiple
non-contiguous areas. Such a fractured arrangement (a term
coined by Welker and his co-workers for describing the
somatosensory organization of the cerebellum [62]) has been
claimed to favour the production of complex motor responses
by making it easier to combine elemental body movements
within coordinated muscle synergies [59,61,63–65].
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movements and sensations described by Penfield on the basis
of the responses he recorded [6] is almost never observed at
the individual level. Although initial evidence came from
electrophysiological studies in monkeys [47– 49], recent data
have confirmed that this is also true in humans, where
sensory and motor maps are typically organized as an intermingled mosaic of neural populations related to different
body parts [43,44,50,51]. Major violations of Penfield’s
regular ordering are commonly found. It happens, for
instance, that mouth and face responses are represented
above finger or leg responses [43]. Moreover, both monkeys
[52] and humans [44] exhibit large variations of the sensorimotor cortical organization from individual to individual
and between hemispheres. More generally, recent data have
also suggested that the functional segregation between M1
and S1 might not be as strict as initially postulated by
Penfield [53]. In humans, in particular, it was found that
the hand ‘hot spot’, defined as the cortical area that evokes
hand or finger responses at the lowest electrical intensity,
was located in the post-central gyrus in a significant fraction
of subjects [54,55]. At a first level, this puzzling result highlights the necessity of considering Penfield’s anatomical
maps with caution. Indeed, 100 years ago, neuronavigation
tools were not available and localizing stimulation sites
was not easy. For instance, as acknowledged by Penfield &
Boldrey, there was a strong bias toward associating motor
response with M1 stimulation because ‘the Rolandic fissure
can hardly be recognized until after stimulation has identified
it’ [6, p. 398]. However, the idea that the hand hot spot
is commonly localized in S1 was recently contradicted by
clinical observations showing, in a large population of 165
patients, that motor responses were scarcely evoked from
the post-central gyrus [20]. This conclusion is consistent
with monkey data showing that the level of current required
to trigger overt movements is almost systematically lower in
M1 than S1 [56,57]. In fact, as shown by a study aiming at
comparing the output properties of these two regions, the
motor responses evoked from S1 are rare, weak and often
inhibitory [58]. Strikingly, in monkey experiments, the lowest
motor threshold is consistently identified in regions located
within the bank of the central sulcus for both M1 (Brodmann
area 4) and S1 (Brodmann area 3a). In humans, however,
these intrasulcal areas are not accessible and DES is only performed over the convexity of the pre- and post-central gyri.
Together with the limited number of sites that can be stimulated in each subject, this may explain why the hand hotspot
has sometimes been reported in S1 in humans.
The recent questioning of Penfield’s homunculus does not
seem surprising. In truth, what appears to be really puzzling
is the ubiquity of this schematic representation and how it
became so universally accepted. Indeed, looking at Penfield’s
own data, it seems quite clear that the nice arrangement of
body parts he described along the pre- and post-central gyri
is functionally deceitful, although, of course, graphically convenient. This can be seen in figure 1 for a few representative
examples. The left side of the three first panels (figure 1a–c)
shows the individual stimulation sites identified as eloquent
by Penfield [6]. The right side displays the classical homunculus
he constructed from these data.
Figure 1a investigates the claim that an ordered somatotopy exist for the fingers. Really, considering the actual
stimulation data, it seems hard to see any justification for
this hypothesis. Thumb contractions (coloured in blue), for
thumb
index
middle
ring
little
all
neck
face
(d)
(b)
Penfield’s homunculus
digits versus arm
arm
digits
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Phil. Trans. R. Soc. B 370: 20140207
Figure 1. The nicely ordered homunculus constructed by Penfield is not consistent with the individual data actually collected by this neurosurgeon. (a) (Left part.) Evoked responses identified by Penfield for the different digits; (right part)
corresponding homunculus. (b) (Left part.) Evoked responses identified by Penfield were reported on the same graph for the arm (including shoulder, elbow, wrist, hand; red colour) and the digits (blue colour); (right side) corresponding
homunculus. (c) (Left part.) Evoked responses identified by Penfield were reported on the same graph for the face (green colour) and the neck (red colour); (right side) corresponding homunculus. (d ) (Left part.) Penfield’s idea of an inverted
homunculus; (right side) corresponding formalization of this idea. Adapted from [6,59], with permission.
neck versus face
(c)
different digits
(a)
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(a)
(b)
complex motor synergies in monkeys
hand/mouth synergies in humans
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climbing/leaping
hand in
lower space
reach-to-grasp
manipulate in central space
defense
chewing/
licking
perioral exploration
Figure 2. (a) Action zones in the precentral gyrus of the monkey where complex movements are evoked in response to long-train electrical stimulations (adapted
from [65], with permission). (b) Sites where complex hand/mouth synergies are evoked by electrical stimulation in the human precentral gyrus. The top panel of the
figure displays motor sites (black squares) evoking hand-to-mouth synergies resembling self-feeding, in which DES causes the closing hand to progressively approach
the opening mouth. The bottom panel of the figure displays multimodal sites (black squares) that evoke hand/arm actions when stimulated while receiving mouth
sensory inputs. Adapted from [69], with permission.
following cortical stimulation some studies have reported the
development of relatively complex, apparently purposeful
actions, including joint hand –mouth responses, coordinated
arm–eye–head aversive synergies and organized reach-tograsp gestures [6,22,43,66,67]. Unfortunately, when observed,
these movements were generally not described in detail.
Also, they were often said to be artefactual and reflective of
the unspecific recruitment, through current spread, of body
parts having contiguous cortical representations [43].
Technically, a reason why complex movements have not
been more commonly observed in response to DES could be
related to the tendency of clinicians (in humans) and experimenters (in animals) to use short trains of stimulations.
As noted by Penfield & Welch [67, p. 310], for instance, it is
plausible that some of the simple motor responses they
found in their patients ‘would, with more prolonged stimulations, have gone on to become more elaborate and to have
approached the full synergic employment of all extremities
and the trunk. The stimulating electrode has frequently been
removed at the first evidence of response, and thus the opportunity of producing more of the elaborate synergic responses
may have been missed’. Michael Graziano et al. were the first
to investigate this possibility in awake macaque monkeys
[68]. These authors stimulated the precentral gyrus using
stimulation trains of long duration. They found that some
motor responses that would have had the form of simple
muscle twitches in the context of short train stimulations,
unfolded into complex coordinated actions when the duration
of the stimulation lasted long enough. These actions included,
for instance, self-feeding movements in which the hand closed
into a grip while moving toward the opening mouth; reach-tograsp synergies in which the arm extended while the fingers
opened progressively; defensive gestures in which the facial
muscles squinted while the head turned sharply to one
side and the arm flung up; etc. Interestingly, as shown in
figure 2a, each of these categories of action was evoked from
different, well-localized, zones of the precentral gyrus.
Recently, Graziano’s pioneering observations were reproduced in New World monkeys and prosimian galagos by
John Kaas and his co-workers [70,71]. Also, they were generalized to human subjects in a study aiming to investigate
whether hand –mouth synergies, a prominent example of
human behaviour with high ethological value, were represented as motor primitives in the precentral gyrus [69]. In
this study, electromyographic activity evoked by cortical
stimulation was recorded from the face and upper-limb
muscles in patients undergoing brain surgery. As shown in
figure 2b (top panel), this allowed identification of an integrated motor primitive resembling self-feeding, in which
DES caused the closing hand to progressively approach the
opening mouth. Of course, not all responses evoked by
long train stimulations evolved into complex movements
and coordinated hand –mouth synergies intermingled with
simpler isolated movements over the whole surface of the
precentral gyrus. This anatomical dispersion contrasted
with the more clustered pattern found in monkeys (figure
2b). Two main hypotheses may account for this difference.
First, it is possible that this cortical region is differently organized in humans and monkeys [72,73]. Second, the
pioneering data reported by Graziano et al. in monkeys [68]
could be biased toward intra-individual variability (multiple
replications in few animals), while the data gathered in
humans could be rather slanted toward inter-individual
variability (few replications in multiple subjects).
Phil. Trans. R. Soc. B 370: 20140207
hand-to-mouth movements
hand to mouth
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sensorimotor organization has been shaped by primate evolution to optimize the production of ethologically relevant
behaviours while preserving the ability to learn new complex
synergies [64,65,70].
4. Mapping high-level functions
Phil. Trans. R. Soc. B 370: 20140207
Per-operative mapping is not only useful for identifying brain
areas that evoke movements or sensations when stimulated.
This approach can also be used for probing the functional contribution of a given cortical region. In this case, DES is applied
while the subject is performing a sensorimotor task such as
opening–closing the hand, reading or counting. The effect of
the stimulation on the ongoing behaviour is then evaluated.
In an alternative approach, the neurosurgeon can also interfere
with brain activity at rest and ask the patients to report the
thoughts or feelings they have experienced in response to
the stimulation.
To date, per-operative evaluations of high-level functions
have been mainly conducted for language mapping in awake
patients [80–83]. Based on this approach, large amounts of
data have been collected and used for producing probabilistic
maps of anatomo-functional correlations [13,20]. In other
words, using DES in large populations of patients, neurosurgical teams were able to associate specific cortical regions
with particular language disorders such as speech arrest
(cessation of speech output in the absence of evoked motor
response); dysarthria (improper articulation of speech);
anomia (inability to name objects while still being able to
speak or repeat sentences); alexia (inability to read while
still being able to spell words or write); receptive aphasia
(fluent but meaningless speech and inability to understand
simple sentences); expressive aphasia (impaired speech
production); etc.
Together with neuroimaging and lesion observations, these
per-operative results proved of major interest for improving
our understanding of the neural bases of language comprehension and production [84–88]. A striking example
concerns Broca’s area, the long-postulated role of which as a
speech output region remains debated in neuroimaging and
lesion studies [89–92]. A recent per-operative investigation
involving 165 patients provides an important, potentially decisive, contribution to this issue [20]. As reported by the authors,
stimulation of Broca’s area only produces speech arrest in 4% of
the subjects, compared with 83% when the dorsal premotor
cortex (dPM) is targeted. The latter proportion is independent
of the localization of the tumour, i.e. of whether Broca’s area is
lesioned or not. Based on these results, it is tempting to suggest
that Broca’s area should no longer be considered a motor
region coordinating speech articulation but should rather be
viewed as a cognitive structure involved in high-level functions
such as verbal working memory, language comprehension or
lexical retrieval [20,93].
However, in the linguistic domain, the identification of
well-defined anatomo-functional correlations in response to
DES does not seem to be the norm. Indeed, a very striking
feature of per-operative evaluations of language abilities lies
in the wide distribution of functional sites across brain structures (figure 3). In contrast to the relatively circumscribed
networks that sometimes emerge from careful syntheses of
the lesion and neuroimaging literature (e.g. [90,94 –96]), it
appears that highly specific aspects of language production
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Notably, the true ethological nature of the complex synergies evoked through DES was recently questioned by Cheney
and colleagues. In monkeys, these authors provided evidence
that postural synergies evoked through cortical stimulation
were not produced by natural patterns of EMG activity but
instead resulted from an unnatural co-contraction of numerous
‘hijacked’ muscles that forced the limb to an equilibrium point
[74,75]. However, the generality of these observations remains
debatable for at least three reasons. First, muscle hijacking was
not observed in several studies where evoked-EMG and kinematic responses were found to be strikingly similar to the
responses seen in natural behaviours [60,68,76]. Second, the
non-teleonomic nature of the ‘hijacking’ hypothesis seems
hardly compatible with the repeated failure of DES to evoke
non-functional synergies where, for instance, the opening
hand would approach the closing mouth or the closing hand
would move away from the opening mouth [68,69]. Third,
beyond its ability to explain the emergence of postural equilibria, the ‘hijacking’ model cannot easily account for the
finesse and high functional specificity of some very complex
multi-segmental synergies. This includes, for instance, multijoint defensive postures specifically triggered from bimodal
neurons with tactile/visual receptive fields and made of the
following complementary elements (in Graziano’s terms): ‘a
facial grimmace, a squinting of the eye, a turning of the head
away from the side of the sensory receptive fields, a hunching
of the shoulders, a fast thrusting of the hand into the space
beside the head, and a turning of the hand such that the
palm faced outward, away from the head’ (fig. 4 in [77]).
Beyond these observations, it may be worth noting that
motor responses involving the coordinated recruitment of
distinct body segments were not the only type of complex
representation identified in the human precentral gyrus. Combined recording of motor and somatosensory evoked potentials
revealed that this region also harbours motor-sensory representations where cross-signal integration is realized at specific
cortical sites that generate hand/arm actions while receiving
mouth sensory inputs. It is tempting to speculate that these
multimodal sites underlie the behavioural process of perioral
exploration. Indeed, they are shaped as a hardwired feedback
loop capable of binding oral sensory inputs with upper limb
motor commands or, in other words, capable of guiding hand
movements according to mouth sensations. This view is consistent with a recent study on upper-limb reaching movements
showing, in humans and monkeys, that M1 contains fast feedback control loops integrating sensory and motor signals [78].
As shown in figure 2b (lower panel), complex hand–mouth sensorimotor sites are not evenly distributed over the precentral
surface of the patients. They are clustered in the dorsal sector of
the precentral gyrus, where hand/arm movements are most
commonly represented.
In summary, using long trains of stimulation, researchers
and clinicians have provided convincing (although still
disputed) evidence that specific sensorimotor synergies with
a high ethological value are represented as integrated motor
primitives in the precentral gyrus. This cortical region cannot
be seen any more as a sort of keyboard, where segregated
populations of neurons can be recruited in a specific spatiotemporal order to form complex symphonies of movements.
Overall, the use of DES reveals the complexity of primary
sensorimotor structures that can probably accommodate different types of representations with various levels of complexity
[79]. This hypothesis fits well with the suggestion that
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(a)
(b)
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cortical sites for anomia [13]
(d)
cortical sites for alexia [13]
cortical sites for speech arrest and anomia [20]
Figure 3. Language maps indicating, for the (left) dominant hemisphere, the cortical locations where DES induced speech dysfunctions in two large studies involving, respectively, 250 [13] and 165 [20] consecutive patients with gliomas. (a) Brain sites inducing speech arrest per square centimetre of the cortical surface
(reconstructed from [13]). (b) Brain sites inducing anomia per square centimetre of the cortical surface (reconstructed from [13]). (c) Brain sites inducing
alexia per square centimetre of the cortical surface (reconstructed from [13]). (d ) Brain sites inducing speech arrest (red circles) and anomia (blue circles).
Each individual circle represents a positive observation. Adapted from [20], with permission.
can be impaired through stimulations delivered over very
different cortical zones. Anomia or alexia, for instance, is
consistently found after stimulation of wide (sometimes overlapping) regions in the frontal, temporal and parietal cortices
(figure 3). This high level of scattering is not totally surprising. It can have two main origins. On the one hand, it may
mirror the multiplicity of the neural processing required for
naming an object or reading a word [90]. On the other
hand, it may also reflect the existence of a tremendous level
of inter-individual variability in the localization of language
functional sites [13]. Obviously, part of this variability is
owing to the plastic changes that occur in brain organization
in response to slow-growing tumoural invasion [97].
Together with the existence of substantial differences in the
tasks being evaluated [98], these changes could explain
some of the above-mentioned discrepancies between DES,
acute lesion and neuroimaging studies.
This being said, language is far from being the only
high-level function open to per-operative evaluation [99].
Recently, this approach has been used to study, for instance,
visuo-spatial processing [100], action inhibition [23], movement awareness [101,102] and sensorimotor intentionality
[103,104]. While reviewing the contribution made by DES
to all these fields would be beyond the scope of the present
paper, a brief focus on sensorimotor awareness and intentionality should help us provide another example of the unique
fruitfulness of this method.
Technically, sensorimotor intentionality has been very
difficult to address with classical electrophysiological, clinical
and neuroimaging tools given, in particular, the difficulty of
separating intentional and attentional processing [105,106].
Fortunately, DES does not have to deal with this ambiguity.
This was first shown by Penfield, who reported that some
frontal sites evoked a desire to move when stimulated [6].
Subsequent studies were able to confirm this observation,
but located the neural source of this desire on the frontal
medial wall, in a region encompassing the supplementary
and cingulate motor areas [22,107,108]. During stimulation,
the subjective experiences of the patients were characterized
by an uncontrollable urge to act. For instance, an epileptic
woman stimulated in the anterior cingulate sulcus at low
intensity through implanted intracerebral electrodes exhibited ‘an irresistible urge to grasp something, resulting in
exploratory eye movements scanning both sides of the
visual field, and accompanied by a wandering arm movement contralateral to the stimulation side. Then, after the
patient had visually localised a potential target, her left
hand moved towards the object to grasp it, as if mimicking
a spontaneous movement. This irrepressible need started
and ended with stimulation, and the patient was unable to
control it. Yet, the patient was aware of both her inability
to resist and of the movement she thus performed and
could describe very precisely’ [107, p. 265]. The same type
of urge was observed in another study, still in epileptic
Phil. Trans. R. Soc. B 370: 20140207
cortical sites for speech arrest [13]
(c)
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5. Concluding remarks
To summarize, the data above show that DES has provided
a unique body of knowledge since its pioneering use by
Wilder Penfield, in humans, almost a century ago [6]. Had
this technique not been employed, our comprehension of
the organization of the sensorimotor systems involved in
movement execution, language production, the emergence
of action intentionality or the subjective feeling of movement
awareness would have been greatly undermined. This is not
to say, of course, that DES is a gold standard devoid
of limitations, nor to deny the major importance of other
clinical, eletrophysiological, modelling or neuroimaging
approaches [27]. This just means that DES represents a
unique way to map sensorimotor pathways and interfere
with the functioning of localized neural populations during
the performance of well-defined behavioural tasks. Recent
advances suggest that there is still a lot to learn from this
technique. In particular, many structures remain to be carefully investigated including, for instance, the cerebellum
[113]. Also, cortico-cortical connectivity continues to be a difficult challenge that DES could help to address in humans
[114,115]. Finally, the use of probabilistic maps taking into
account inter-individual variability to link structures and
functions will allow a better targeting, during per-operative
evaluations, of the functions that are at risk for a given
lesion. Such a ‘tailored’ approach will favour the development of finer evaluation protocols and lead, potentially, to
a much better comprehension of the functional fine-grained
organization of the brain.
Authors’ contributions. Both authors contributed equally to the redaction
of this review paper.
Competing interests. We declare we have no competing interests.
Funding. This work was funded by CNRS, the ‘Cortex’ Labex Program
and the Agence Nationale de la Recherche (ANR-11BSV40271; ANR12-BSV4001801) to A.S. and M.D.
8
Phil. Trans. R. Soc. B 370: 20140207
Putting these observations together, a general model of
linking conscious motor intention and movement awareness
could be proposed that takes into account the functional
specificity of the parietal and frontal intentional regions
[103,104]. In brief, it was suggested that a general, unspecific
intention to act first emerges into consciousness within the
inferior parietal lobule. This intention is the neural signal
that triggers actual motor preparation. While the movement
is being planned, the cingulate and supplementary motor
regions exert inhibitory control over the motor output
regions. This is done to prevent an early, unwanted, release
of the motor command. Once the movement is ready, this
proactive inhibition is waived, which amounts to the emission of a ‘go’ signal that gives rise to a compulsive urge to
act. After movement onset, parietal control mechanisms
monitor action progression independently of sensory
inputs, through forward modelling. When an error is
detected that cannot be corrected through online control processes (e.g. the arm does not move when it should), dPM
emits a warning signal that reaches consciousness. Of
course, this model is not only based on the outcomes of
DES studies but also on a large array of clinical, neuroimaging and electrophysiological data. However, DES was a
key method through which the material generated by each
of these approaches could be interpreted and aggregated [16].
rstb.royalsocietypublishing.org
patients. In this case, however, the stimulation was located in
the supplementary motor area. This caused the participants
to experience an ‘urge to move the right leg inward’, an
‘urge to move the right thumb and finger’ or an ‘urge to
move the right arm away’ [22, p. 3661]. Although no movement
was evoked in response to these subjective feelings, overt
motor responses were observed when the intensity of the
stimulation was raised. For instance, a patient who reported
a ‘strong urge to raise the right elbow’ at 5 mA, experienced
a right-arm abduction at 6 mA [22, p. 3661].
Interestingly, the frontal medial wall is not the only cortical
area where intentional responses can be evoked. The emergence of a subjective desire to move was also reported
following stimulation of the inferior parietal lobule [21]. In
this case, however, the subjective feelings reported by the subjects were quite different from the ones observed after
stimulation of the supplementary and cingulate motor areas.
There was no dimension of urge or irrepressibility. Also, the
patients were unable to precisely describe the movements
they wanted to perform. When prompted to try, they either
said that they did not know or provided a very general description of their intentions in terms of action class. Representative
exchanges were as follows ([21]; electronic supplementary
material): (1) (Experimenter) Did you feel something? ; (Patient)
Yes. . . It felt like I wanted to move my foot. Not sure how to explain;
(E) Which foot? (P; showing the left leg): This one. (E) How did you
want to move it? ; (P): I don’t know, I just wanted to move it ; (2) (E)
Did you feel something? ; (P) I had a desire to do something ; (showing her chest) Here I have a desire to do. . . (E) In the chest? (P) Yes ;
(E) And what did you feel? ; (P) Like a, like a will to move.
Another striking specificity of the parietal intentional sites
lies in the absence of motor response when the intensity of
the stimulation was increased. When a higher current was
used, the patients experienced illusory movements; they felt
that the movements they wanted to make at low intensity
had actually occurred in the absence of any overt or electromyographic motor response. A representative exchange was
as follows ([21]; electronic supplementary material). (5 mA)
(Experimenter) Did you move?; (Patient) No. I had a desire to
roll my tongue. . . ; (E) To roll what? ; (P) To roll my tongue in
my mouth. (8 mA, same site) (E) Did you move? ; (P) Yes, yes,
a corner of the mouth ; (E) Did you move the mouth? ; (P) Yes.
To account for this phenomenon, it was hypothesized that
higher currents did not simply prime a motor representation
to consciousness (giving rise to motor intention), but also
recruited the executive network responsible for movement
monitoring through forward modelling, a process that is
known to rely on posterior parietal computations [109,110].
In sharp contrast to the illusory movements evoked
through parietal stimulation, it was also found that actual
motor responses evoked by stimulating the dPM were not
consciously perceived by the patients. In other words,
although overt mouth and contralateral limb movements
were observed following stimulation of this region, the patients
firmly denied that they had moved [21]. This result highlights
clinical data showing that dPM is the most commonly lesioned
region in hemiplegic patients with anosognosia [111]. It also
echoes neuroimaging observations showing that the dPM is
important for comparing the actual and expected sensory signals [112]. It is tempting to speculate that when dPM is
prevented from performing its function, no error signal is generated in response to an unexpected muscle contraction, which
causes the ongoing movement to remain undetected [101].
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