The Neurolinguistic Approach To Awake Surgery Reviewed

Clinical Neurology and Neurosurgery 115 (2013) 127145
Contents lists available at SciVerse ScienceDirect
Clinical Neurology and Neurosurgery

journal homepage: www.elsevier.com/locate/clineuro
Review
The neurolinguistic approach to awake surgery reviewed

Elke De Witte a , Peter Marin a,b,c,
a
Department of Clinical and Experimental Neurolinguistics, Vrije Universiteit Brussel, Pleinlaan 2, 1050 Brussels, Belgium
Department of Neurology, ZNA Middelheim, Antwerp, Belgium
c
VLAC (Vlaams Academisch Centrum), Advanced Studies Institute of the Royal Flemish Academy of Belgium for Sciences and the Arts, Brussels, Belgium
b
a r t i c l e
i n f o
Article history:
Received 6 May 2012
Received in revised form 6 August 2012
Accepted 7 September 2012
Available online 2 October 2012
Keywords:
Awake craniotomy
Direct electrical stimulation
Language mapping
Language testing
Review
a b s t r a c t
Objectives: Intraoperative direct electrical stimulation (DES) is increasingly used in patients operated
on for tumours in critical language areas. Although a positive impact of DES on postoperative linguistic
outcome is generally advocated, the literature is only scantily documented with information about the
linguistic methods applied in awake surgery. This article critically reviews the neurolinguistic procedures
currently used in awake studies.
Methods: Based on an extensive review of the literature, an overview is given of the language mapping techniques applied in brain tumour surgery. Studies investigating linguistic testing and outcome in
awake surgery were analysed. Information about the timing of the assessment(s), the linguistic tasks, the
linguistic stimuli and the indication for awake surgery was also discussed.
Results: Intraoperative DES remains the gold standard for language mapping, but pre- and postoperative
non-invasive mapping methods are important adjuncts. In the pre- and postoperative phase, standardised
linguistic test batteries are generally used to assess language function. In the intraoperative phase, only
naming and number counting are commonly applied. Most often no detailed information about the
linguistic stimuli is provided and no standardised protocols measuring different linguistic levels have
been described.
Conclusions: Awake surgery with DES is a useful tool for preserving linguistic functions in patients
undergoing surgery in critical brain regions. However, no studies exist that apply a well-balanced and
standardised linguistic protocol to reliably identify the critical language zones. The availability of a
standardised linguistic protocol might substantially increase intraoperative comfort and might improve
outcome and quality of life.
2012 Elsevier B.V. All rights reserved.
Contents
1.
2.
3.
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
History. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
State of the art . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
3.1.
Imaging techniques in awake surgery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
3.1.1.
Preoperative imaging techniques . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
3.1.2.
Intraoperative imaging techniques . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
3.1.3.
Postoperative imaging techniques . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
3.1.4.
Correlations between imaging techniques . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
3.1.5.
Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
3.2.
Language tasks in awake surgery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
3.2.1.
Preoperative language tasks . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
3.2.2.
Intraoperative language tasks . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
3.2.3.
Postoperative language tasks . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
3.2.4.
Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
128
128
129
129
129
129
131
132
132
132
132
136
136
142
Corresponding author at: Department of Neurology, ZNA Middelheim Hospital, Lindendreef 1, B-2020 Antwerp, Belgium. Tel.: +32 032803136; fax: +32 032813748.
E-mail addresses: peter.marien5@telenet.be, peter.marien@zna.be (P. Marin).
0303-8467/$ see front matter 2012 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.clineuro.2012.09.015
128
4.
5.
E. De Witte, P. Marin / Clinical Neurology and Neurosurgery 115 (2013) 127145
Future directions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Acknowledgement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1. Introduction
Surgical treatment of supratentorial tumours (particularly
gliomas) aims to maximise the quality of resection while minimising the risk of postoperative functional sequellae (including speech
and language impairments) [17]. Low-grade gliomas, classied as
WHO grade II tumours [8], are inltrative tumours characterised
by continuous and slow progression, migration, and anaplastic
transformation [912]. Since gliomas are often located in critical language areas, the preservation and restoration of language
function are of crucial importance [3,13]. Non-invasive language
mapping methods, such as functional magnetic resonance imaging
(fMRI), have been used to assess lateralisation and location of critical language areas for surgical preservation [14,15]. However, these
imaging techniques do not seem to be highly reliable measures
on which to base critical surgical decisions [16]. Direct electrical
stimulation (DES) is currently applied as the standard intraoperative approach to language mapping to identify critical language
areas and its pathways in the presence of a space-occupying lesion
[25,1315,17].
As DES requires conscious and cooperative patients, local anaesthesia (awake surgery) instead of general anaesthesia (classic
surgery) is used. During DES, patients perform language tasks,
such as picture naming tasks, verb-noun association tasks, comprehension tasks, repetition, reading, and writing tasks. Picture
naming is commonly used as basic language paradigm [6,18], and
the selection of additional language tasks differs widely across
centres. Transient disturbances of speech and language function
(speech arrest, anarthria, dysarthria, speech apraxia, phonological
and semantic decits, paraphasias, perseverations, anomia, comprehension disturbances, agraphia, alexia) occur if the cerebral
tissue is electrically stimulated at the level of a functional language
epicentre. Consequently, this stimulated area must be preserved
during tumour resection [3].
Awake surgery with intraoperative DES is generally considered to have a positive impact on postoperative linguistic outcome
[17,13,15,17,19,20]. Although transient language impairments are
common in the immediate postoperative phase, the majority of
patients seem to recover within three months, and permanent postoperative language decits seem to be rare [1,3,7,13,15,20]. As a
result, intraoperative DES is often regarded as the gold standard
to map linguistic functions in patients with tumoural lesions in the
language dominant hemisphere [25,1315,17].
However, no studies exist in which a standardised linguistic
protocol is applied to identify the critical language zones, and no
detailed, long-term linguistic data have been recorded. After ten
years of linguistic experimenting with language mapping in an
awake neurosurgical setting, a critical evaluation of the available
data is warranted. The aim of this article is to review whether
DES using language mapping is still the gold standard to identify
critical language areas in brain tumour surgery.
2. History
The traditional approach to brain tumour surgery is resection
of the mass lesion while preserving the main language centres
of the brain: Brocas and Wernickes area. In this approach, the
brain is considered to be static and to have a xed functional
neuroanatomical organisation that is similar in all patients [12].
142
143
143
143
This localisationists view, based on post-mortem studies on language representation in the brain, relies on the view that specic
language functions are invariably located in specic anatomical
areas of the brain [21].
Fritsch en Hitzig (1870) experimented with electrocortical
stimulation in animals and succeeded to elicit movements of
the extremities of the animals [22]. The rst evidence of brain
mapping with DES in humans dates back to 1874. Bartholow stimulated the cerebral cortex of a 30-year-old woman through a skull
defect resulting from osseous inltration of an epithelioma. The
electrical current caused movements in various parts of her body
depending on which brain area was stimulated [22]. In the early
1930s, Peneld and co-workers used brain surgery to treat patients
with intractable epilepsy. They hypothesised that if an aura could be
provoked with electrical stimulation, it would be possible to locate
the source of seizure activity and to resolve epilepsy by removing
or destroying that tissue [22]. Subsequently, Peneld and Boldry
(1937) introduced DES as a method to map the motor and sensory
cortex in order to resect supratentorial tumours located in critical areas [13,19,22]. Peneld and Rasmussen (1950) started to map
language and speech functions next to sensorimotor functions in
awake brain surgery [13,22,23]. But it was the pioneer Ojemann
(1979) who rened the technique. Ojemann showed that the areas
identied to be crucially implicated in linguistic processing were
not only located in the perisylvian language zone, but made up
a larger cerebral network also involving subcortical white matter
tracts. In addition, following renement of the technique, evidence
was found that language localisation is highly variable among individuals [13,2225].
During the last 20 years non-invasive structural neuroimaging
techniques (magnetic resonance imaging (MRI), computed tomography (CT)) and functional neuroimaging techniques (positron
emission tomography (PET), functional MRI) became popular
means to map the human brain and guide tumour surgery [23].
These techniques allowed researchers to study the whole brain,
both in healthy subjects and patients [4]. Functional mapping
methods also demonstrated that there is a large interindividual
variability in the neural organisation of linguistic functions. This
observation supported a more dynamic view on brain functions
and brain plasticity, which is crucial in the process of functional
recovery [12].
The rst studies of preoperative functional mapping in tumour
surgery used PET to map sensorimotor, language, and visual areas.
During the past decades, fMRI has largely replaced PET [12].
However, fMRI has some major limitations with regard to the
identication of functional language areas in patients with brain
tumours. It cannot map subcortical language pathways [3,4,14]
and cannot differentiate between essential and replaceable language areas [3,14]. The former limitation might be compensated
by the use of diffusion tensor imaging (DTI), a non-invasive technique that enables to identify white matter tracts (subcortical
language pathways). DTI however still needs to be validated and
only provides anatomical information [12] (see Section 3.1.1). By
contrast, on the basis of DES, essential language regions (which
should be preserved) and modulatory areas (which may be compensated and resected without permanent functional loss) can
be differentiated. Moreover, DES allows to map subcortical language areas as well. Although most studies [17,13,15,17,19,20]
postulate that DES is an accurate, reliable, and safe technique
to identify cortical and subcortical language areas, there are a

number of limitations to this approach. Indeed, the technique cannot map the entire brain and it is rather demanding for both
the awake patients and the staff. In addition, DES is time consuming because of its intensive character that requires in-depth
preparations in both the pre- and intraoperative phase [12,24]
(see Section 3.1.2).
The combination of intraoperative DES and preoperative fMRI is
currently often used in the work-up of surgical removal of gliomas
in critical areas [12]. As neuroimaging techniques are continuously
improving (e.g. diffusion tensor imaging, transcranial magnetic
stimulation) and new techniques are being developed (e.g. intraoperative MRI) [26], the question arises whether DES is still the gold
standard for intraoperative language mapping, and fMRI the gold
standard for preoperative language mapping in the content of brain
tumour surgery?
3. State of the art
3.1. Imaging techniques in awake surgery
3.1.1. Preoperative imaging techniques
3.1.1.1. Structural magnetic resonance imaging (MRI). Structural
MRI is used in the presurgical phase to evaluate the morphology,
size and topography (e.g. location) of a brain tumour [26]. In order
to plan the resection rate, the borders of the tumour are identied
by means of preoperative MRI [5,27,28].
3.1.1.2. Functional magnetic resonance imaging (fMRI). fMRI measures blood oxygen level-dependent (BOLD) changes in the magnetic
resonance signal, which is related to neuronal activity. The changes
in blood ow and oxygenation are detected by fMRI during cerebral activation when performing a cognitive, linguistic or motor
task [29,30]. In awake settings, fMRI helps to determine the limits of
resection, to predict risk factors, to reduce time of surgery/mapping
and to decrease craniotomy size [3,23,26,31]. Moreover, fMRI is a
non-invasive procedure and can be easily repeated in the postoperative period to follow-up patients over time [29].
However, fMRI has a number of shortcomings. First, fMRI cannot
visualise subcortical activity in critical language areas [3,4,14,32].
Second, it is impossible to reliably distinguish between essential areas and modulatory areas [3,14]. Third, despite constant
improvements the accuracy to identify language areas is still not
optimal. In contrast to its sensitivity for sensorimotor identication which ranges from 82 to 100% the sensitivity of fMRI to
identify linguistic functions is only 66% [3,13,18]. Since neurosurgical decision-making is conservative, 34% of false results is way
too high to solely rely on fMRI ndings [26]. Fourth, motion-related
artifacts induced by heartbeat, breathing and most importantly by
head motion constitute a problem of reliability [26,32]. Fifth, language maps may vary according to the language paradigm selected,
the neurological disease, the ability of the patient to perform a task
and the statistical analysis method chosen [29,32].
A nal drawback for fMRI is the signicance thresholds chosen
to generate language activation maps. Roux et al. [33] for instance
showed that variations in the threshold values disclose different
degrees in neural activity. Depending on the signicance thresholds
used to analyse raw fMRI data, changes in the spatial extent and
number of activated cortical areas are found.
3.1.1.3. Positron emission tomography (PET). Using PET imaging, a
wide range of functions (e.g. language) can be studied. The specicity depends on the behavioural and control task paradigm. In
comparison with fMRI the disadvantages of PET are a poor signalto-noise ratio, a mere moderate spatial resolution, and a poor
129
temporal resolution. In addition, PET is more invasive and timeconsuming than fMRI. As with fMRI and any other observational
technique, PET cannot separate functional essential from participating areas. PET imaging is therefore mainly used in neurosurgical
planning to localise seizure foci [29].
3.1.1.4. Diffusion tensor imaging (DTI). Magnetic resonance DTI is
a non-invasive MR imaging method to study white matter tracts
by measuring the direction of diffusion of water molecules (water
diffusion in the brain tends to track along bundles of white matter
bres). Because of the ability to map subcortical language pathways
(e.g. superior longitudinal fasciculus, inferior fronto-occipital fasciculus, uncinate fasciculus, and inferior longitudinal fasciculus), DTI
is increasingly becoming important in the preoperative planning
and guiding of awake surgery.
Furthermore, it can also be used to differentiate normal white
matter, oedematous brain tissue, and enhancing tumour margins.
DTI may also reveal whether bres are displaced, disrupted, or
inltrated by the tumour, which adds information to the selection
of surgical indications [9,12,23,26,29,30,34]. Until now DTI is not
routinely used in the neurosurgical setting as validation data are
still lacking. The technique has a poor signal-to-noise ratio, is vulnerable to artifacts from air spaces and has difculties visualising
crossing tracts. In addition, the tracking of bres in the vicinity of
or within a tumour is complicated due to associated phenomena
such as oedema, tissue compression, and degeneration [15,26,35].
Another restriction is that DTI provides little specic information
about the functional status of the white matter tracts. Young et al.
[26] indicated that fMRI may be more useful in the planning phase,
and DTI in the resection phase for guidance.
3.1.1.5. Transcranial magnetic stimulation (TMS). Single pulse TMS
can be used as an activation technique to map the motor cortex, and
repetitive TMS (rTMS) can be applied as an inhibition technique to
disrupt language processing and to assess language lateralisation
[29,36,37].
Disadvantages of TMS are its poor spatial resolution and a potential risk to cause seizures [29]. The use of TMS in presurgical
mapping procedures is growing. Duffau [12] and Picht et al. [38,39]
postulated that TMS could be highly informative during preoperative motor mapping for tumours near the rolandic cortex. Shamov
et al. [37] used rTMS combined with neuronavigation for preoperative mapping of the language area to treat opercular gliomas
of the dominant hemisphere. They found rTMS to be valuable for
preoperative localisation of the speech areas, for preoperative planning of the surgical approach and for intraoperative planning of the
direction of brain retraction and operative corridor.
3.1.1.6. Neuronavigation. Neuronavigation allows the coregistration and transfer of preoperative imaging data into the surgical
eld, the physical space of the head of the patient. Anatomical data
from MRI or CT image sets are loaded into the anatomical neuronavigation system. Currently, functional neuronavigation, integrating
functional data from PET, fMRI is increasingly used. Since a brain
shift occurs due to surgical retraction, mass effect, gravity, extent
of resection, or cerebrospinal uid leakage, signicant inaccuracies
in image-guided systems occur during surgery [12]. Because of this
risk, sole reliance on the neuronavigation system to decide which
area to resect is insufcient [12,30]. Intraoperative MRI, fMRI, DTI
(iMRI, ifMRI, iDTI) may provide an efcient solution to cope with
this drawback (see Section 3.1.2) [9,26,28].
3.1.2. Intraoperative imaging techniques
3.1.2.1. Direct electrical stimulation (DES). Procedure: DES has
become the gold standard for intraoperative mapping of motor
and language areas in the preparation phase of tumour resection.
130
Motor mapping with DES may be performed under general anaesthesia whereas for language (cognitive) mapping an
asleepawakeasleep procedure is generally used [28,40]. To eliminate potential risks such as respiratory complications when the
patient is woken-up from sedation, an awakeawake protocol is
sometimes used during which the patient is not sedated [4145]. As
there is no waken-up from anaesthesia in this approach, the patient
remains alert during the entire procedure [4145]. However, this
procedure is psychologically very demanding for the patient as
it can cause potential distress and discomfort (e.g. during craniotomy). For these reasons the awakeawake condition is rarely
applied [42].
Cortical mapping is used to identify the essential language sites
and to dene the boundaries of the resection [11,14,28]. DES is generally performed with a bipolar stimulator that produces biphasic
and rectangular pulses, each lasting 1 ms. Frequencies of 50 or 60 Hz
are used and the intensity is progressively increased from 1 to
10 mA with 0.5 mA each time. A stimulus duration of 1 or 2 s is usually applied to generate a motor response, but for language mapping
a more extensive duration of 34 s is required [5,11,27,46]. Patients
are asked to perform a variety of language tasks (naming, repetition, counting, verbal uency. . .) (see Section 3.2.2) during cortical
stimulation. The stimulation starts just before the presentation of
the test item. In a picture naming task, for example, the cortex is
stimulated and then the picture is presented. The patient produces
a short introductive phrase this is . . . before naming to ensure
that no seizures were generated that might explain distorted naming [6,10,27]. Linguistic disturbances are subsequently detailed
and categorised by a speech and language pathologist in speech
arrests, anomic disturbances, paraphasias (phonemic, semantic,
morphologic, visual), motor speech disturbances, perseverations,
etc.
To avoid seizures no site is stimulated twice in succession. It is
accepted that transient language decits occurring during 3 stimulations (with subsequent normalisation) is sufcient to ensure that
the stimulated site is essential for language processing [5,27,46].
The essential sites are marked on the cortex with sterile number
tags [5,27,46] or with a colour code on a mapping grid (computer
screen) which is a projection of the cortex divided into squares of
1 cm2 [18]. Language critical sites are spared and a resection margin
of 1 cm is generally agreed to [18,47].
Subcortical areas are mapped during tumour resection by means
of similar electrical parameters and language tasks used at the cortical level [5,27,46]. Functional subcortical pathways are identied
by repeated stimulations along the pathway [46].
Positive mapping, i.e. identication of at least one essential
region, is commonly accepted as the standard intraoperative technique to preserve essential functions [5,11]. On the other hand,
some studies suggest that craniotomies with negative mapping
(when no critical regions are found) in the setting of a limited cortical exposure allow aggressive resection of gliomas [4749]. Duffau
[50], however, postulated that decisions based on negative mapping are only acceptable for high-grade gliomas, since the aim of the
surgical intervention is to resect the enhanced part of the tumour.
As low-grade gliomas are poorly delineated, negative mapping is
not a reliable strategy on which to base decisions.
Advantages: One of the major advantages of DES is that no false
negative results occur if the method is rigorously applied. In other
words, DES has an optimal sensitivity and correctly identies essential regions that should be preserved to avoid permanent language
decits. This is in contrast with other functional mapping techniques (fMRI, PET) which cannot distinguish between essential
and modulatory language zones (see Section 3.1.1) [3,46]. Its high
sensitivity explains why DES is commonly considered the gold
standard in brain mapping and why DES is used to validate noninvasive functional methods such as fMRI, PET and DTI [14].
The ability to map subcortical pathways, and thus to detect

subcortical language pathways is another major advantage of
DES. The use of subcortical mapping is indeed increasingly
applied [3,9,11,35,51]. Studies [9,27,5154] showed that the use
of subcortical mapping next to cortical mapping optimises the
benet-to-risk ratio of surgery and offers the opportunity to study
language connectivity. In sum, DES allows to perform tumour
resection according to functional boundaries and minimises the
risk of permanent functional decits.
A benecial effect on postoperative outcome and quality of
life (QoL) is reported in several awake studies using DES (with
or without subcortical mapping). For example, Pereira et al. [7]
studied 79 patients with supratentorial brain tumours. They found
that DES with cortical and/or subcortical mapping is effective and
safe, showing clinical recovery in 40% of the cases (n = 32) and
neurological worsening in around 10% (n = 8). Duffau et al. [27]
described a series of 115 patients with grade II gliomas in the left
dominant hemisphere and reported persistent language impairments in only 2% of the patients. In a study by Bello et al. [51],
88 gliomas were mapped at the cortical and subcortical level. Three
days after surgery, 66,9% of the patients (n = 59) showed postoperative language decits. Three months after tumour removal, 79.5%
(n = 70) of the patients had normal language, 18.6% (n = 16) had mild
language decits and only 2.3% (n = 2) had a moderate or severe
language impairment. In conclusion, several awake studies have
shown that transient language decits frequently occur, but permanent linguistic impairments are indeed very rare (well below
5%) [7,13,27,51,55].
Some studies [1,2,19,20,5658] compared linguistic outcome of
awake surgery with the outcome of classic brain surgery. Though
reaching no statistical signicance at 3 months postsurgery, Gupta
et al. [56] reported a better outcome of the classic approach.
No cortical mapping however was used in the awake group.
In the other studies [1,2,19,20,57,58] signicantly better results
were reported in the awake group with DES. Peruzzi et al. [58]
found statistically signicant benecial effects in favour of the
awake group, that is a shorter hospital stay with reduced hospital expenses after postoperative intensive care unit. In a recent
meta-analysis of the literature De Witt Hamer et al. [59] conrmed a generally favourable outcome of the awake patient group.
The data of 8091 adult patients operated for supratentorial inltrative gliomas with or without DES were compared. The use of
DES resulted in fewer late severe neurological decits (3.4% versus
8.2%), more extensive resection (75% versus 58% gross total resections) and involved critical locations more frequently (99.9% versus
95.8%).
In addition, awake surgery with DES allows more extensive resection since only the critical/crucial language areas are
preserved. The classical surgical approach uses a larger safety margin since the identication of functional areas is based on the
activations found in preoperative functional mapping disclosing
involved language areas as well [1]. Though extensive resection
is still controversial in neuro-oncology, current surgical results
support the view that a total or at least subtotal resection has a
benecial effect on the natural history of the low-grade gliomas
and a positive impact on survival [3]. The 1 cm-safety rule (1 cm
between the resection margin and the nearest language site) was
generally recommended as it would prevent postoperative language decits and their persistence [18,47]. Nowadays a growing
number of studies have provided evidence that no safety margin
around critical structures is required in case of low-grade glioma
resection since a more extensive resection is associated with a more
favourable life expectancy [1,10,34]. Moreover, Yordanova et al.
[60] suggest a supratotal resection with a margin beyond MRI
abnormalities when low-grade gliomas involve non-critical areas,
even in the left hemisphere. The following results were reported in
a study by Duffau et al. [2]. A mortality rate of 20.6% was found

in cases of partial resection, whereas 8% mortality was found in
cases of subtotal resection and 0% in cases of total resection. Yordanova et al. [60] described transient neurological worsening in 60%
of cases, but three months after surgery no permanent decits were
found. Although an extensive resection after DES typically causes
transient language worsening, most patients recover and return to a
normal socio-professional life without permanent language decits
[1,3,7,13,15,20].
The phenomenon of temporary dysfunctions can be explained
by postoperative brain plasticity. The immediate postoperative
decits noticed in most patients conrm that some structures
remain functional within the tumour mass or peri-tumoural
brain tissues. Secondary recovery might be due to reshaping of the locoregional mechanism and/or the recruitment
of remote areas (e.g. homologous areas in the contralateral hemisphere) [3,12,61]. Recent studies suggest that a
second surgery should be performed when initially only partial resection was performed. Due to functional reshaping
total tumour removal is possible without permanent decits
[3,4,10,12,23,29,50,6264].
These ndings indicate that there exist multiple cortical representations or functional redundancy (short-term plasticity) which
facilitate postoperative recovery (long-term plasticity) [12,61]. As
such, this might conrm that language is not only subserved by
Brocas and Wernickes area (see Section 2), but processed within
multiple parallel networks.
DES studies have yielded new information about language
organisation in the (impaired) brain. Direct electrocortical and subcortical stimulation allow a better understanding of the critical
regions (and their functional role) and connectivity. As a result
the neural basis of language is considered an end product of the
well-synchronised functioning of parallel, distributed, and interactive cortico-subcortical networks rather than the sole product of
individual centres. This connectionist view, the so-called hodology, also underlines the dynamic character of the brain that allows
functional compensation within a large distributed network (brain
plasticity) [3,4,14,50,65,66].
Disadvantages: DES also has some disadvantages and limitations
that need to be taken into account. Firstly, while the sensitivity
of DES is 100%, its specicity remains a matter of debate. False
positive results may be linked to the patients tiredness, to partial seizures, to the spreading of DES along the axon (acute false
positives) and to brain plasticity (chronic false positives) [14]. Secondly, DES is time-consuming (lasts much longer than surgery
under general anaesthesia) and only allows locoregional mapping (cannot study reshaping in the contralateral brain) [3,12].
Thirdly, DES might also be demanding for the patients since
good compliance and cooperation from the patient are needed
when language mapping is executed. Feelings of anxiety, confusion and stress may appear because DES is an invasive method.
Nevertheless, recent studies have suggested that most patients
tolerate the awake procedure well [7,22,42,49,53,57,67,68]. Careful evaluation and selection of the patient, extensive planning, a
detailed supply of information about the procedures and intensive training in the preoperative phase seem to be fundamental
for good tolerance during awake surgery [11,25,42,68]. Fourthly,
DES requires highly qualied multidisciplinary teams. However,
since a good postoperative outcome and reduced duration of hospitalisation is consistently reported for awake surgery with DES,
postsurgery sequellae requiring long-lasting, intensive and expensive rehabilitation strategies are avoided or kept to a minimum
with a positive impact on Health Insurance costs (invalidity benet). Consequently, the high demands and requirements for staff
and logistical support have to be critically studied in a substantial
cost-benet analysis [11,13,24,58].
131
The nal important disadvantage of DES seems to be the lack

of standardised linguistic protocol to reliably identify the critical
language zones. This issue will be discussed in Section 3.2.2.
3.1.2.2. iMRI, intraoperative ultrasound, uorescence. MR imaging
has been recently introduced in the intraoperative phase to
identify residual tumour tissue during resection to overcome the
limitations of brain shift and to update preoperative information.
Thanks to the development of high-eld iMRI, high-quality images
are produced and iMRI appears to improve the extent of resection
for gliomas without increasing the risk of permanent postoperative
decits [26,30,69]. Parney et al. [70] combined DES with high-eld
iMRI to facilitate safe and extensive tumour resection, which
resulted in a total tumour resection of 90% and a benecial postoperative outcome with no new neurological decits. However, the
combination of DES with iMRI is a complicated and expensive
procedure and therefore not frequently used. The patient has to
be wrapped in sterile drapes to keep the sterile eld free from
contamination. This can cause claustrophobic reactions or may be
dangerous for sedated patients without denitive airway protection. In addition, the time of surgery is prolonged [69]. In the study
of Parney et al. [70] surgery time increased with approximately
40 min.
Although a high signal-to-noise quality and poor contrast resolution is frequently reported, intraoperative ultrasonography
may be an alternative for iMRI as it is inexpensive and easy
to use. The limitations of ultrasound are the image resolution
and the co-registration with preoperative MRI data. However, the
co-registration can nowadays be compensated with sonographic
integration into surgical navigation systems [30,71].
Fluorescent porphyrins can also be used to visualise intraoperative tumour tissue, but only in high-grade (malignant) gliomas. Fluorescent porphyrins reect tumour cell density and proliferation
and enable to distinguish cells of the brain parenchyma from those
of the tumour [71]. Preoperatively, the patients receive 5-ALA (5aminolevulinic acid) orally, dissolved in tap water. During the operation, when the tumour is reached, the degree of uorescence is
usually evaluated. Tumour tissue is coloured intensively red while
normal brain tissue is non-uorescent featuring a bluish colour
[71]. This method is easy to perform and less costly than iMRI [69].
3.1.2.3. ifMRI, iDTI. Intraoperative fMRI may be used to update
the neuronavigational system and to compensate for brain shift.
However, intraoperative fMRI is rarely performed since it is not
benecial to intraoperative DES [26]. By contrast, intraoperative
DTI may be a valuable tool as brain shift is a critical issue for deep
white matter pathways. A limitation of iDTI is the specic position
of the head, necessary for brain surgery and so nonstandard for
DTI, which requires manual recalculations and prolongs surgical
time [26].
3.1.3. Postoperative imaging techniques
3.1.3.1. MRI and DTI. Repeat structural MRI is usually performed
immediately after tumour removal, 3 months postsurgery, and then
every 6 months during follow-up. MR imaging evaluates the extent
of glioma removal, which is often categorised according to the classication method of Berger and colleagues [72] (total = no residue,
subtotal = residue < 10 cm3 , partial = residue 10 cm3 ). MRI and DTI
enable to repeatedly analyse the anatomical location of the language pathways (at the periphery of the cavity) in the postoperative
phase [5,27,28,52,53].
3.1.3.2. fMRI and TMS. Repeat fMRI may be performed after
surgery to evaluate linguistic outcome and to investigate neural
(re)organisation of linguistic functions. fMRI allows brain plasticity to be studied as it can show possible new redistribution
132
of functions following surgery that may be potentiated by specic rehabilitation procedures. Postoperative fMRI is not routinely
conducted, but it can be very useful since second surgery may
be considered after partial resection if reorganisation is found on
fMRI [3,4,10,12,23,29,50,6264]. Longitudinal functional imaging
studies after resection, linked to the results of intraoperative and
preoperative mapping enable a better understanding of brain connectivity and brain plasticity [50]. Next to fMRI, TMS can be applied
in the postoperative phase to map linguistic functions or facilitate
aphasia recovery [37]. As already mentioned (see Section 3.1.1.5.),
rTMS can localise speech areas [37]. In addition TMS can also be
used for recovery purposes since it may modulate both the function
of the stimulated area and the effective connectivity. Consequently,
it may improve e.g. picture naming [64].
3.1.4. Correlations between imaging techniques
In some studies [15,33,73,74] the correlation between the
neurolinguistic ndings of fMRI and DES is investigated. Poor
correlation was found for language mapping with fMRI (sensitivity
score of only 66% [15,33,73]). This result contrasts with higher
sensitivity scores (82100%) for the detection of the sensorimotor
areas [15,26,29,30,62,75]. DES precisely locates the cortical areas
critically involved in speech and language processes. By contrast,
fMRI identies many additional brain areas that are linked to
language processing, but not intrinsically involved [75,76]. Other
possible reasons for the poor correlation between fMRI and DES
may be the differences in pre- and intraoperative language tasks,
in correlation methods, and in study population characteristics
(tumour type, location, and craniotomy size) [15,23].
With regard to the linguistic paragdigms used, Petrovich et al.
[32] showed that the discordance between fMRI and DES could in
part be explained by the use of silent speech in fMRI (to avoid
motion artifacts) and vocalised speech in DES. It was found that
silent speech tasks under fMRI correctly predicted the sites of language decit with DES in the inferior and middle frontal gyrus but
failed to predict observed sites of speech arrest in the precentral
motor gyrus [26,32]. As a result, the use of at least one overt fMRI
speech task is recommended to support better concordance with
DES [26]. Similarly, in the study of Kim et al. [76], a much better
correlation was found when a battery of language tests with functional redundancy (e.g. both passive and active tasks that overlap
functional areas) was built into the task design. In other words, the
correlation between fMRI and DES needs to be further studied with
appropriate language tasks, but the use of fMRI as a sole language
mapping technique appears to be insufcient.
The correlation between PET or TMS, and DES has not been studied in much detail, as their use in the presurgical planning is still
limited. Sobottka et al. [77] showed a relatively poor correlation
between PET imaging and DES when language function was tested.
Correlations have been found for TMS and DES when motor function is examined [29,3739]. Correlations between TMS and DES
data for linguistic functions have not been extensively studied yet.
Because of the importance of subcortical language mapping
DTI has become an increasingly crucial tool in preoperative mapping and subcortical DES in intraoperative mapping. Correlations
between DTI and DES have been investigated and positive correlations were reported [3,9,15,35,78]. However, DTI cannot replace
subcortical DES since the estimated distance between DTI and the
location of electric stimulation is inuenced by the inaccuracies
of DTI, the invasiveness of the tumour, intraoperative brain shift
affecting navigation accuracy, and the various stimulation parameters and probe types used [35,62]. In the study by Bello et al. [78],
DTI ber tracking (DTI-FT) and subcortical DES were used to evaluate the reliability of tracking from a functional point of view. The
data yielded a good concordance between DTI-FT data and those
obtained during subcortical mapping.
In conclusion, recent advances in preoperative mapping with

fMRI and DTI are very promising, but intraoperative DES is still
crucial in awake procedures.
3.1.5. Conclusion
Several anatomic and functional imaging techniques for tumour
surgery in critical language areas have been briey discussed in
this overview. The strengths and weaknesses of each mapping
technique were set against those of the gold standard, that is intraoperative DES. Although the development and validation of preoperative mapping techniques are expanding, the reliability of these
techniques in neurosurgical practice remains limited because of the
lack of standardisation [26]. Intraoperative DES is the most accurate
technique to identify critical language areas and their pathways, yet
pre- and postoperative mapping are important adjuncts to intraoperative DES. Since fMRI and DTI identify essential and involved
cortical and subcortical language areas as well as their connecting pathways, both techniques are relevant to assist in settling
the kind of surgical approach and the limits of resection [9,12].
Preoperative mapping is an ideal component of surgical planning
and may reduce surgery time, which is valuable since DES is timeconsuming [13,24]. Utilisation of fMRI and DTI data (and even data
from PET, iMRI) during neuronavigation, may facilitate intraoperative guidance as well [9]. The integration of preoperative methods
and intraoperative DES in functional neuronavigation has extended
the indications for surgery of gliomas located in critical areas that
were previously considered inoperable [3]. Furthermore, longitudinal follow-up by repeat postoperative mapping with (f)MRI,
DTI or PET is important in studying the dynamic processes (brain
plasticity) involved in motor and cognitive rehabilitation [50]. Comparing the pre-, intra- and postoperative imaging data may predict
and show functional redistribution and reshaping [12,61].
3.2. Language tasks in awake surgery
3.2.1. Preoperative language tasks
In-depth linguistic assessments are performed preoperatively
to investigate speech and language functions. Due to a typically
slow growth of low-grade gliomas allowing neural reorganisation
(preoperative plasticity), no obvious linguistic decits may be
noted. However, formal neuropsychological assessments may
disclose clinically relevant impairments [55,7981]. Therefore,
extensive neuropsychological investigations in the preoperative
clinical work-up of brain tumours are advocated [55,79,80]. Type
and degree of aphasic, apraxic and dysarthric symptoms can be
identied and classied by a variety of standardised speech and
language test batteries. Most studies use the Boston Diagnostic
Aphasia Examination (BDAE) [85] or Aachener Aphasie Test (AAT)
[86] [6,15,17]. See sections tasks and stimuli in Table 1 for
more detailed information for each study. Naming tasks from the
AAT, BDAE, the Boston Naming Test (BNT) [87] or Dnomination
Orale 80 (DO80) [88] are usually included in the preoperative language protocol [2,6,47,51,53,55,60,63,78,79,81,8991].
and/or
semantic
verbal
uency
tasks
Phonological
[2,33,51,53,63,78,79,9093], verb generation tasks [15,33,74],
repetition tasks [2,6,33,47,51,53,55,63,78,90,92,93] and spontaneous speech tasks [2,51,53,78] are also often administered in the
preoperative phase. Assessments take place within 5 days before
surgery (see section timing of assessment(s) in Table 1).
If the preoperative cognitive and linguistic status (not too
severely impaired) allows awake surgery the patient is informed
in detail about the procedure. At the same time the patients psychological ability to undergo an awake intervention is critically
evaluated.
Functional language representation may be investigated by a
number of linguistic tasks. fMRI is generally used to measure brain
Table 1
Language (cognitive) tasks in the preoperative phase of awake surgery.
Study
Timing of
assessment(s)
Tasks
Stimuli
Ilmberger et al. [6]
13 days before
surgery
AAT-subtests:
Token Test
Repetition
Written language
Naming
Comprehension
Phonemes, words and sentences

Reading, writing
Objects, colours, scenes
NDI
fMRI language paradigm(s)

NI
Unknown
AAT
NDI
Listening to nouns produce verb (verb

generation) (active condition)
Counting from 1 to 10 (rest condition)
Picht et al. [17]
1 day before surgery
AAT
Test run of language testing
NDI
Patients with scores of at least 50% in all modules

of the test battery fMRI: word generation:
produce words beginning with that letter
presented (phonological uency)
Lubrano et al. [63]
10 days before
surgery
BDAE short version:

Oral and written
comprehension, naming, oral
uency, reading,
dictation, repetition, written
transcription, (calculation, and
object handling)
NDI
NI
Benzagmout et al. [10]
Unknown
BDAE adapted version
NDI
Repetition tasks, story listening, verbal uency
Duffau et al. [34]
Unknown
BDAE
NDI
NI
Yordanova et al. [60]
Unknown
BDAE
DO80
NDI
NI
Robles et al. [82]
Unknown
BDAE
NDI
NI
Lurito et al. [73]
Unknown
NI
Brennan et al. [83]
Unknown
BDAE
NDI
Object naming, number counting

Three paradigms
De Benedictis et al. [1]
Unknown
BDAE
NDI
NI
Duffau et al. [52]
Unknown
BDAE
NDI
Semantic uency, story listening and covert

sentence repetition tasks
Duffau et al. [27]
Unknown
BDAE
NDI
Semantic uency, story listening and covert

sentence repetition
Teixidor et al. [55]
Unknown
DO80
BDAE 8 subtests:
Comprehension
Written comprehension
Repetition
Written language
comprehension
Writing
Picture naming
Semantic uency task, covert sentence repetition

task, and story listening task
Sentence dictation
BDAE
NDI
Mandonnet et al. [46]
Unknown
Listening to reading of a narrative text from a

popular novel (patients were instructed to
carefully listen to the text and be prepared to
answer questions regarding its content)
Spena et al. [15]
Commands and logic

Reading
Words, concrete phrases, abstract phrases
Spelling test
Semantic verbal uency, covert sentence

repetition, and story listening
133
Table 1 (Continued)
Timing of
assessment(s)
Tasks
Stimuli
fMRI language paradigm(s)
Bizzi et al. [74]
Time between fMRI

and DES was within
3 weeks
NI
Verb generation (produce a verb silently in

response to a noun)
Santini et al. [93]
Unknown
BADA:
Phonemic discrimination
Repetition
Picture naming
Auditory and visual
word-to-picture matching
Auditory and visual
sentence-to-picture matching
Writing to dictation
Reading aloud
Word Fluency:
NI
Words
Nouns and verbs
Nouns and verbs
Unknown
Written, oral comprehension

Denomination
Language uency
Reading
(Computation)
Dictation
Repetition Copying
(Object handling)
NDI
NDI
Roux et al. [90]
Unknown

Naming
Language uency
Reading
(Computation)
Dictation
Repetition
Written transcription
(Object handling)
Scarone et al. [84]
Unknown
BDAE
Mechanics of writing
Recall of written symbols
Dictated words
Written confrontation naming
Written formulation
Sentences to dictation
Verb generation (nd verbs in relation to the

objects presented)
Naming (the patients were asked to name ve
objects shown by special MRI-design glasses)
Based on the patients written output

(name, address. . .)
Serial writing (automised), Primer-level
dictation
10 words with increasing length and
complexity
Pictures from oral naming tasks
Cookie theft scene, to dictation
10 sentences graded in length and
grammatical complexity
NI
Fluency in controlled word association, story

listening, and covert sentence repetition tasks
Wu et al. [81]
Unknown
BNT
MAE Visual Naming
MAE Token Test
NI
Sarubbo et al. [89]
Unknown
Laiacona-Capitani
Naming Test
Token Test
NI
Duffau et al. [53]

Duffau et al. [2]
Unknown
Verbal comprehension,
spontaneous speech, naming,
verbal uency, narrative tasks,
repetition
NDI
NI
Letters F, A, S
Roux et al. [33]
134
Study
Sanai et al. [47]
Unknown
Counting
Naming
Reading
Repeating
Writing
Counting 150
Object naming, slide show
Reading single words
Repeating complex sentences
Writing words and sentences
NI
Bello et al. [51]

Bello et al. [78]
Unknown
Spontaneous speech
Describe reason for admission to the

hospital
Letters F, P, L (1 min per letter)
Semantic uency, story listening, and covert

sentence repetition tasks
Phonological uency
Categories, such cars, fruit, and animals

(1 min)
Famous face naming
Famous and unknown faces, fame

judgment + naming
Nonliving, living categories, body parts,
musical instruments
Verb oral naming subtest
Match word (1) to pictures (5)
Match sentence (1) to pictures (2)
Non-words, words, sentence, syntagm
repetition
Object picture naming

Action picture naming
Word comprehension
Sentence comprehension
Transcoding tasks: repetition
Token Test
(Digit Span)
Counting
Talachi et al. [79]
Assessments were
performed in 2 or 3
sessions over a
period ranging from
1 to 5 days
Naming
Phonological uency
Visual objects
Letters F, A, S
NI
Leclerq et al. [94]
Unknown
Bedside examination
NDI
NI
Pereira et al. [7]
Unknown
(Neuropsychological testing:
WAIS III, Raven, MMPI)
NDI
NI
Vassal et al. [91]
Unknown
Phonological uency
Semantic uency
BDAE
Naming DO80
Montreal Evaluation of
Communication protocol
Letter P
Animals
Verb generation (produce a semantically

associated verb silently in response to an
auditorily presented noun) activation task
Countdown task control task
Phonological uency
Semantic uency
Naming
NDI
NDI
Famous faces, 50 items
Nouns, 82 items
Verbs, 50 items
Naming by description,38 items
48 items
Token Test
80 items
Syllables, words, nonwords, sentences
Papagno et al. [92]
In the week before

surgery
Pointing to picture
Picture-to-sentence matching
Repetition
Bertani et al. [11]
Quinones-Hinojosa et al.
[75]
Sacko et al. [57]
80 black and white pictures
Verb generation task (produce a semantically

associated verb in respond to an object picture)
Naming (objects)
Unknown
Unknown
NI
NI
NI
NI
Unknown
NI
NI
135
NI, no information (missing data); NDI, no detailed information; AAT, Aachener Aphasie Test; BDAE, Boston Diagnostic Aphasia Examination; DO80, Dnomination Orale (80 items); BNT, Boston Naming Test; BADA, Batteria per
lanalisi dei decit afasici; MAE, Multilingual Aphasia Examination; WAIS III, Wechsler Adult Intelligence Scale III; MMPI, Minnesota Multiphasic Personality Inventory.
Semantic uency
136
activity while the patient performs linguistic tests. In Table 1 the

language paradigms that have been used in fMRI settings are listed.
Benzagmout et al. [10], Duffau et al. [27,52], Bello et al. [51,78], Teixidor et al. [55], Scarone et al. [84] and Mandonnet et al. [46] used
uency tasks, repetition tasks, and story-listening tasks. A variety
of other fMRI language tasks have been used as well, including auditory narrative tasks [73], object naming tasks [33,83,92], number
counting tasks [15,83] and verb generation tasks [15,33,74,91,92].
In the study of Shamov et al. [37], counting (from 1 to 50)
and object naming were preoperatively performed during rTMS to
localise speech representation in the frontal lobe. Shamov et al.
[37] postulate that rTMS is a valuable method for preoperative
localisation and planning.
Finally, in the preoperative phase a set of tasks/stimuli is carefully selected. This selected set of stimuli is practised in the
preoperative phase so that the patient feels comfortable in the
awake setting. The tasks the patient is unable to perform correctly
are left out of the set for intraoperative testing to ensure that the
errors in the awake setting are due to cortical stimulation and not
to a pre-existing decit [46].
3.2.2. Intraoperative language tasks
The number and extent of language tasks that can be used during surgery is limited because of the constraints imposed by the
awake surgery procedures. First of all, to avoid seizures the time of
an electrical stimulation is maximally 4 s. Consequently, stimulus
presentation and response cannot last longer than 4 s [46,51,78].
The time pressure is challenging especially for semantic tasks that
often include sentence comprehension tasks taking longer than 4 s.
Second, the xed position of the patient on the operation table
makes it hard to perform certain language tasks, such as reading
a long text from a screen. Third, visual complexity has to be taken
into account, especially in cases of posteriorly localised tumours,
since the visual pathways may be under pressure during resection
[18]. Finally, patients get tired because the awake setting requires
intense and sustained attention during approximately 12 h [14].
Moreover, the wake-up phase from general anaesthesia can cause
disorientation and confusion [4144]. As a result, linguistic disturbances may be due to secondary problems, which may lead to false
positive results [14]. Therefore, there is a need to develop a set of
sensitive language tests by means of which maximum information
can be obtained in minimum exposure time.
In general, the descriptions of the linguistic tests used during
DES lack sufcient detail. In addition, little is known about the
construction of these tests, their validity, the availability of normative data, etc. Table 2 presents an overview of the linguistic
tasks, stimuli and indications for DES. Five studies [6,17,63,91,92]
only report the use of picture naming tasks (object naming) during cortical and subcortical stimulation in patients with lesions
near or within language-related brain areas. For naming tasks, both
experimental naming tasks and standardised naming tests such as
BNT [87], DO80 [88] and naming tasks from the BDAE [85] and
AAT [86] are used. Picture naming in combination with counting is
the most frequently used activation paradigm (n = 13) during intraoperative mapping [1,10,27,34,46,52,60,73,8284,89,94]. Brennan
et al. [83] compared object naming and counting during DES and
fMRI. They found that disruption of speech occurred in more brain
regions during object naming than during number counting. This
implies that more complex language tasks (involving phonology
and semantics) are more sensitive measures to localise language than overlearned speech. Reading tasks [2,47,53,55,57,90],
spontaneous speech [7,15], comprehension tasks [7,11,51,78]
and verb generation tasks [11,33,74] have also been used
sporadically.
In a few studies [2,51,53,78] a more tailored selection of tasks
is described taking into account the location of the tumour. In
addition to a counting, naming and reading task, Duffau et al. [2,53]

included a calculation task for lesions in the left angular and supramarginal gyri. Semantic or repetition tasks were used for tumours
in the left mid-posterior temporal lobe. In Bello et al. [51,78], counting and object naming tasks were used to investigate frontal lesions,
whereas object naming tasks and word and sentence comprehension tasks were used for temporal lesions. Mandonnet et al. [14]
postulated that repetition tasks should be added to study the functional impact of lesions involving the posterior superior temporal
gyrus. In the study of Polczynska [95], detailed information is given
about a set of language tasks for intraoperative mapping. Polczynska [95] postulates that the language protocol often restricted
to naming and counting tasks should be expanded in order to
improve postsurgical preservation of language function. Polczynska [95] developed three sets of home made tasks that were
used in patients with a multi-electrode subdural grid (extraoperative) and classied these tests as: (1) grammar-focused tests, (2)
non-dominant right-hemisphere tests, and (3) tests for subcortical stimulation. The syntax tests (1) include making questions
and negations of a presented stimulus sentence, producing inections (e.g. I go He. . .), production of regular and irregular plural
forms (e.g. carcars, sheepsheep), and spontaneous speech production. The language tests composed to examine non-dominant
right hemisphere function (2) contain tests investigating alternative meanings of words and broader semantic relationships (a),
and affective prosody (b). In a test of metaphorical expressions
(a) the patient, for example, needs to select one out of three
pictures that corresponds to the metaphorical meaning of the sentence. To assess emotional prosody (b) a picture of a face showing
some emotional state is presented to the patient together with
an orally produced sentence expressed in a happy, bored, or sad
way. The patient has to decide if the sentence has been said in
a way that matches the picture. The tests for subcortical stimulation (3) involve naming, articulation and language dynamics.
Though these tests have not yet been applied during intraoperative DES, it is suggested they may be implemented in intraoperative
DES testing once standardisation of the test protocol has been
completed.
A review of the linguistic tasks in these awake studies reveals that picture naming and/or counting are typically used as basic and sometimes sole language paradigms
[1,10,27,34,43,49,56,70,7981,86,89], and that the selection of
other language tasks varies greatly across different studies. However, the selection of the language paradigms to be used during
DES procedures is of crucial importance, because of its direct
effect on clinical outcome [96]. The sensitivity of various language tasks still has to be systematically examined to maximise
efciency during intraoperative language testing and to minimise
postoperative decits [55,79]. More specic and more sensitive
home-made tasks have been implemented in the language protocol [2,7,11,78,95], but there is still no consensus about the rationale
and no norms exist for these tasks.
3.2.3. Postoperative language tasks
Although formal linguistic testing is important to evaluate linguistic outcome, postoperative language investigations are not
routinely performed. In Table 3, the postoperative language tasks,
language stimuli and timing of the assessment(s) are described per
awake study. In most of these studies, immediately after surgery
or within 7 days, a short neurolinguistic evaluation is executed to
detect possible linguistic disturbances. After one week postsurgery,
speech and language functions are often examined by means of
standardised extensive test batteries such as the BDAE [85], AAT
[86] and naming tasks among which the BNT [87] and DO80 [88].
If necessary, speech and language rehabilitation is started. Repeat
assessments may be performed after 3 months, and then every 6
Table 2
Language (cognitive) tasks in the intraoperative phase of awake surgery.
Method
Tasks
Stimuli
Indication

Lubrano et al. [63]
Cortical, subcortical DES

Confrontation naming
Naming
Picht et al. [17]

Vassal et al. [91]

Naming
Naming: DO80
Pictures of objects
Pictures of objects line
drawing (black and white)
Pictures line drawings
Black and white pictures
Papagno et al. [92]
Naming
Quinones-Hinojosa
et al. [75]
Cortical DES
Counting
Living and non-living objects,

famous faces, verbs
Number counting
Counting
Naming: DO 80
110 over and over again

Duffau et al. [34]
Robles et al. [82]
Counting
Naming: DO 80
Counting
Naming: DO 80
Counting
Naming: DO 80

Lesions near or within language-related brain areas

Brain tumours and cavernomas located within or
invading the dominant inferior frontal cortex
Left hemisphere tumours
Right frontotemporal (close to the insula), right
temporal gliomas
Left temporal, frontal, parietal, right temporal and
parietal LGGs and HGGs
Lesions near precentral gyrus, central sulcus,
postcentral gyrus, frontal operculum, angular gyrus
LGGs in Brocas area (involving the pars opercularis
and pars triangularis of the left inferior frontal
gyrus, BA 44, 45)
LGGs located within the dominant hemisphere
Scarone et al. [84]
Counting
Naming DO80
Counting
Naming DO80
Brennan et al. [83]
Cortical DES
Lurito et al. [73]
Cortical DES
110, over and over again

110, over and over again
Slides with black and white
pictures
Number counting
Object naming paradigms
NDI
Object naming
Duffau et al. [52]
Duffau et al. [27]
Leclerq et al. [94]
Sarubbo et al. [89]
Santini et al. [93]
Duffau et al. [53]

Duffau et al. [2]
Sanai et al. [47]
Cortical DES
Counting
Naming (BDAE)
Counting
Naming
LGGs in noneloquent areas in left dominant

hemisphere
Patients with cortico-subcortical LGGs, selection of
patients with tumours involving dominant
striatum (putamen, caudate)
WHO grade II gliomas in left dominant hemisphere
(in eloquent regions)
LGGs located in language areas
Left frontal lesion, temporal lesion

Gliomas in left perisylvian region
Identication of Broca area
Identication of Wernicke area
LGGs in functional areas (already operated under
general anaesthesia)
Corticosubcortical LGGs in language regions in left
dominant hemisphere
Corticosubcortical WHO grade II gliomas located in
eloquent areas in left dominant hemisphere
LGGs or cortical dysplasia located in language areas
Counting
Naming
Counting
Naming
Counting
Naming
Counting
Naming
Counting
Naming
Counting
Naming
+ additional tasks
e.g. reading, comprehension
tasks
Counting, naming, reading
NDI
Pictures
NDI
Pictures
110 (over and over again)
Pictures
NDI
Pictures
010
Several naming tasks
If impairment was observed
in a specic BADA subtest,
additional tasks were
administered
Pictures
Corticosubcortical LGGs in eloquent brain areas
(+Calculation task)
+ Semantic, repetition task
NDI
ND
Counting
Naming
Reading
Counting 150
Object naming
Lesions in left angular and supramarginal gyri

Tumours in the left mid-posterior
temporal lobe
Dominant hemisphere gliomas in posterior inferior
frontal, anterior inferior parietal lobe, inferior to
midportion of the motor cortex, or any portion of
the temporal lobe
LGGs located in eloquent areas
Study
Gliomas in the left hemisphere
137
138
Table 2 (Continued)
Method
Tasks
Stimuli
Indication
NDI
LGGs located in language areas
Sacko et al. [57]

Pictures
Basic unrelated sentences
NDI
Lesions in eloquent areas
Pereira et al. [7]
Spena et al. [15]

Spontaneous speech
Reading from slides
NDI
Pictures of objects, actions,
famous people
Pictures of objects, actions,
famous people
Words and sentences
Eloquent area tumours
Bello et al. [51]

Bello et al. [78]
Counting
Picture naming
Reading
Naming
Reading
Naming objects
Recalling objects
Spontaneous naming
Counting per minute
Comprehension of complex
commands
Naming
Spontaneous speech
Reading
Counting
Oral naming
Oral naming
Bertani et al. [11]
Wu et al. [81]
Asleepawakeasleep
Bizzi et al. [74]
Cortical DES
Roux et al. [33]
Cortical DES
Roux et al. [90]
Cortical DES
Talachi et al. [79]
Awake mapping
Word and sentence

comprehension
Counting
Verbal naming
Verb generation
Word- and sentence
comprehension
Speech motor mapping
NI
Verb generation
Naming
Verb generation
Counting
Naming
Reading aloud
NI
NDI
Object naming and famous
faces naming
NDI
NDI
Lesions near eloquent cortex
Frontal lesion (Broca)

Frontal lesion (oral naming essential sites)
Temporal lesion
Temporal lesion
LGGs in eloquent regions
Insular gliomas
Produce a verb silently in
response to an auditorily
presented noun
Pictures of objects
In response to objects
NDI
30 pictures of various objects
30 different sentences
Focal mass in or adjacent to at least one eloquent

area of the language or motor systems
LGGs, HGGs, meningiomas in eloquent areas
Tumours or other lesions (such as cortical
dysplasia) in eloquent regions
Gliomas
NI, no information (missing data); NDI, no detailed information; DO 80, Dnomination Orale (80 items); LGGs, low-grade gliomas; HGGs, high-grade gliomas; BADA, Batteria per lanalisi dei decit afasici.
Study
Table 3
Language (cognitive) tasks in the postoperative phase of awake surgery.
Study
Timing of assessment(s)
Tasks
Stimuli
Within 21 days and 1-year after surgery
AAT-subtests:
Token Test
Repetition
Written language
Naming
Comprehension
AAT
Phonemes, words and sentences

Reading, writing
Objects, colours, scenes
NDI
NDI
Spena et al. [15]

Duffau et al. [34]
Immediately, 3 and 6 months after surgery

Immediately, 3 months after surgery
3, every 6 months thereafter
Robles et al. [82]

Lurito et al. [73]
Brennan et al. [83]

Unknown
Unknown
Immediately, 3 months, every 6 months after

surgery
Immediately, 3 and 6 months
Immediately (within 7 days) and 3 months
after surgery
Duffau et al. [52]

Duffau et al. [27]

Bizzi et al. [74]
Immediately, 3 months postsurgery

Within 7 days and at 3 months postsurgery
Santini et al. [93]
3, 6 months postsurgery
NI (probably same as preop phase)

BDAE short version:
Oral and written comprehension, naming, oral
uency, reading, dictation, repetition, written
transcription, (calculation, and object
handling)
BDAE (adapted version)
BDAE
BDAE
DO 80
BDAE
NI
BDAE:
Naming
BDAE
NI (probably same as preop phase)
BDAE
DO80
BDAE 8 subtests:
Auditory comprehension
Written comprehension
Repetition
Written language comprehension:
Writing
BDAE
Verbal uency
denomination
comprehension
BADA:
Phonemic discrimination
Repetition
Picture naming
Auditory and visual word-to-picture matching
Auditory and visual sentence-to-picture
matching
Writing to dictation
Reading aloud
Word uency
NDI
NDI
NDI
NDI
NDI
NDI
NDI
NDI
Picture naming
Commands, logic and reasoning
Reading
Words, concrete phrases, abstract phrases
Spelling test
NDI
NDI
NDI
Simple objects and categories
Words
Nouns and verbs
Nouns and verbs
Picht et al. [17]

Lubrano et al. [63]
1 Week, 3 months, 6 months after surgery and

then yearly
2 Weeks after surgery
Immediately, 2 and 3, months postsurgery
Patients with gliomas were systematically
tested again at 6 months postsurgery
Letters F, A, S
139
140
Table 3 (Continued)
Timing of assessment(s)
Tasks
Roux et al. [33]
Language and neuropsychological testing:

4 to 8 weeks postsurgery
fMRI in 7 patients (of 14 patients): 1 to 2
months after surgery

Denomination
Language uency
Reading
(Computation)
Dictation
Repetition
Copying
(Object handling)
Verb generation (during POSTOP fMRI)
Naming (during POSTOP fMRI)
Roux et al. [90]
NI
Scarone et al. [84]
Within 48 h, 3 months postsurgery, then every

6 months

Naming
Language uency
Reading
(Computation)
Dictation
Repetition
Written transcription
(Object handling)
Counting
Object naming
Spontaneous speech
BDAE:
Mechanics of writing examination
Recall of written symbols
Dictated words
Written confrontation naming
Written formulation
Wu et al. [81]
Immediately, 3 months postsurgery
Sarubbo et al. [89]
Unknown
Duffau et al. [53]

Duffau et al. [2]
Immediately, 3 months, every 6 months

postsurgery
Sanai et al. [47]
Unknown
Auditory comprehension
BNT
MAE Visual Naming
MAE Token Test
Laiacona-Capitani Naming Test
Token Test
Verbal comprehension, spontaneous speech,
naming, verbal uency, narrative tasks,
repetition
Counting
Naming
Reading
Repeating
Writing
Stimuli
Find verbs in relation to the objects presented

The patients were asked to name ve objects
shown by special MRI-design glasses
NDI
Based on the patients written output (name,

address . . .)
Serial writing (automised), Primer-level
dictation
10 words with increasing length and
complexity
Pictures from oral naming tasks
Cookie theft (free narrative, to dictation)
10 sentences graded in length and
grammatical complexity
NDI
Counting 150
Object naming (slide show)
Repeating complex sentences
Writing words and sentences
Study
Bello et al. [51]

Bello et al. [78]
3, 30 and 90 days after surgery
Spontaneous speech
Phonological uency
Semantic uency
Object picture naming

Action picture naming
Word comprehension
Transcoding tasks: Repetition
Talachi et al. [79]
2-3 months
Leclerq et al. [94]
Unknown
Pereira et al. [7]
Unknown
Vassal et al. [91]

Papagno et al. [92]
1 day, 4 and 5 days, 3 months postsurgery

3-7 days, 3 months postsurgery
Bertani et al. [11]

Quinones-Hinojosa
et al. [75]
Sacko et al. [57]
Token Test
(Digit Span)
Counting
Naming
Phonological uency
Counting
Naming
Writing ability
Speech questionnaire
DO80
Phonological uency
Semantic uency
Naming

Unknown
Pointing to picture
Picture-to-sentence matching
Repetition
NI
NI
3 months and 1 year after surgery
NI
Categories, such as cars, fruit, and animals

(1 min)
Famous and unknown faces, fame
judgment + naming
Nonliving, living categories, body parts,
musical instruments
Verb oral naming subtest
Match word (1) to pictures (5)
Match sentence (1) to pictures (2)
Non-words, words, sentence, syntagm
repetition
Visual objects
Letters F, A, S
NDI
Pictures
NDI
Grade system (from 0 to 5)
NDI
NDI
Famous faces (50 items),
nouns (82 items), verbs (50 items),
naming by description (38 items)
48 items
Token Test
80 items
Syllables, words, nonwords, sentences
Famous face naming
Describe reason for admission to the

hospital
Letters F, P, L (1 min per letter)
NI, no information (missing data); NDI, no detailed information; AAT, Aachener Aphasie Test; BDAE, Boston Diagnostic Aphasia Examination; DO80, Dnomination Orale (80 items); BNT, Boston Naming Test; BADA, Batteria per
lanalisi dei decit afasici; MAE, Multilingual Aphasia Examination.
141
142
months during follow-up. A longitudinal follow-up is relevant to

identify factors that may predict postoperative language outcome
[57,50,65,79,80,97]. Although postoperative fMRI may add to the
study of the dynamic processes subserving language reorganisation
only Roux et al. [33] performed fMRI studies in the postoperative
phase.
3.2.4. Conclusion
Although DES and the awake procedure are generally thoroughly described, the literature is only scantily documented with
information about the linguistic tasks applied in the pre-, intra-,
and postoperative phase of awake interventions. In addition, little
is known about the standardisation of the language paradigms used
in an awake setting.
In the pre- and postoperative phase, standardised linguistic
test batteries are usually applied to evaluate linguistic functions
[6,15,17,60]. However, extensive neuropsychological assessments
are often not performed [55,79,80]. No consensus exists with regard
to the linguistic tasks that may suit pre- and postoperative mapping
with fMRI, PET and TMS best.
In the intraoperative phase, extensive tests cannot be applied
to investigate language functions, and a tailored selection of tasks
is required [14,60]. The linguistic tasks currently used during DES
are restricted in number and often lack the sensitivity to examine
a variety of linguistic functions in sufcient detail (e.g. phonology, semantics, grammar) [2,51,61,95]. The variability of linguistic
tasks used during DES makes it difcult to compare the linguistic
outcome reported in the follow-up studies.
In conclusion, the linguistic tasks used for intraoperative language mapping with DES and pre- and postoperative fMRI, DTI
applications currently lack a solid scientic basis, and there are no
reliable guidelines for linguistic testing during awake interventions
[13].
4. Future directions
DES has high sensitivity and low specicity. According to Mandonnet et al. [14], improvement of the specicity of DES should
follow from: (1) studies recording the distant effects of axonal
stimulation to investigate brain effective connectivity; (2) biomathematical modelling to describe the neurophysiological mechanisms
involved at the level of single cells and long-range networks;
and (3) longitudinal studies with non-invasive imaging (e.g. fMRI)
to study neural reorganisation after surgical resection under
DES.
Advances in non-invasive mapping will improve surgical planning and functional follow-up. In this respect TMS, DTI and
tractography are promising techniques [12,26]. Further renement
of neuronavigational systems, and assisting devices such as the
mapping grid will enable to delineate more accurately functionally
critical brain regions and tumour location. As a result, the quality of
tumour removal and the duration of life expectancy will increase
[26]. The extent of resection and preservation of a margin around
the critical regions is currently a matter of debate. Further studies
are needed that investigate functional outcome after total or even
supratotal resection [1,10,65].
In addition, more evidence from studies comparing corticosubcortical DES with pre- and postoperative mapping techniques
is needed to increase insights in the (re)organisation of critical areas. Current connectionists models have to be critically
evaluated with regard to treatment (e.g. second surgery)
[3,4,10,12,23,29,47,58,60,61].
Considerable progress needs to be made with regard to the linguistic paradigms used in awake procedures. The linguistic test
battery should be expanded with more specic and sensitive tasks
taking into consideration the constraints of the awake procedures. A formal protocol is needed that includes different tasks
(phonological, semantic, grammar tasks) controlled for linguistic
variables (e.g. frequency, familiarity, word length, phonological
and morphological form, . . .). Consequently, further research is
necessary to develop and standardise a linguistic protocol for
awake surgery. A standardised approach will improve the scientic reliability of the neurosurgical procedure and will allow
a number of additional data analyses adding to current insights
in brain-behaviour relationships. Since intraoperative mapping
requires a personalised approach, a tailored selection per patient
based on the localisation of the tumour and the preoperative
level is of crucial importance. Therefore, a set of standardised
linguistic tests to choose from would be very useful for intraoperative linguistic mapping. In addition, cognitive tasks measuring
attention, memory, calculation, executive functioning, visual cognition, etc. should be included in the intraoperative protocol
depending on the localisation of the tumour and the specic
needs of the patient [79,98]. For instance, Roux et al. [99] used
a line bisection task to map visuo-spatial functioning during
cortico-subcortical stimulation of the right hemisphere in 50 brainlesioned patients. In the study of Gras-Combe et al. [100], the optic
radiations were subcortically mapped in 14 patients who underwent awake resection of a glioma involving visual pathways. A
modied picture-naming task with two pictures placed diagonally
on the screen (one in the quadrant to save, one in the opposite
quadrant) and a red cross at the centre of the screen was presented. While staring at the red cross, the patients had to name
both pictures. Examination of affective functions might be relevant as well. Giussani et al. [101] assessed emotional functions
with a facial emotion recognition task in 18 patients with right
hemisphere lesions. The patients were asked to name the facial
expression that was illustrated on a photo while the cortex was
stimulated.
The more functions are tested, the more critical areas are identied which may interfere with a total tumour resection. Therefore,
an optimal balance has to be found between the extent of resection
and the preservation of functions strongly related to outcome and
quality of life of the patient [98].
Comparisons have been made between the outcome of awake
surgery and classic surgery [1,2,19,20,56,57,59] indicating that
awake surgery with DES should be implemented as the standard
approach for glioma surgery. Randomised controlled studies to
determine the impact of DES on survival rate are difcult to conduct for ethical reasons [18,50]. Comparison studies in which
awake patients are matched with non-awake patients according
to tumour location, WHO tumour grade, tumour volume, patients
age, sex, handedness, intelligence, educational level, etc. would be
ideal [81]. Comparative studies using standardised methods may
lead to scientically reliable information about the most appropriate type of neurosurgical intervention and can show in which
conditions awake surgery with DES offers the most favourable
outcome.
Postoperative outcome of DES has been investigated in a number
of studies. Most of these studies [2,10,27,28,52,53,55,60,82,102]
had only a limited follow-up of 3 months to 1 year. However,
since tumours may recur, a more extended follow-up is needed.
Several studies [57,50,65,79,80,93,97,103] have emphasised the
importance of longitudinal neurolinguistic and quality of life
follow-up from the pre- to the postoperative phase until 2 years
postsurgery or even longer. It is expected that longitudinal studies
based on a large series of patients and detailed neurolinguistic
data will identify factors that may predict postoperative language
outcome and will enable objective evaluation of the qualitative
(linguistic outcome, quality of life) and quantitative outcome (real
life expectancy).
5. Conclusion
Awake surgery with DES is a reliable and safe technique for
the surgical treatment of tumours in critical language areas. The
criteria of operability have been modulated and it has become possible to maximise the resection while minimising the postoperative
linguistic decits. Yet, additional use of advanced non-invasive
imaging techniques such as fMRI, DTI, TMS is required to plan, guide
and evaluate surgical outcome.
Further research concerning the specicity of DES, integration of
multimodal imaging data, longitudinal follow-up and brain plasticity will improve the awake procedure. In addition, the development
and standardisation of a linguistic protocol for intraoperative mapping will offer unique opportunities to maximally reduce the risk
of permanent language impairments in the postoperative phase.
Acknowledgement
Elke De Witte is a PhD fellow of the Research FoundationFlanders (FWO).
References
[1] De Benedictis A, Moritz-Gasser S, Duffau H. Awake mapping optimizes the
extent of resection for low-grade gliomas in eloquent areas. Neurosurgery
2010;66(June (6)):107484.
[2] Duffau H, Lopes M, Arthuis F, Bitar A, Sichez J, Van Effenterre R, et al. Contribution of intraoperative electrical stimulations in surgery of low grade
gliomas: a comparative study between two series without (19851996) and
with (19962003) functional mapping in the same institution. Journal of Neurology, Neurosurgery and Psychiatry 2005;76(June (6)):84551.
[3] Duffau H. Contribution of cortical and subcortical electrostimulation in brain
glioma surgery: methodological and functional considerations. Neurophysiologie Clinique/Clinical Neurophysiology 2007;37:37382.
[4] Duffau H. The anatomo-functional connectivity of language revisited new
insights provided by electrostimulation and tractography. Neuropsychologia
2008;46(4):92734.
[5] Duffau H, Moritz-Gasser S, Gatignol P. Functional outcome after language
mapping for insular World Health Organization Grade II gliomas in the
dominant hemisphere: experience with 24 patients. Neurosurgical Focus
2009;27(2).
[6] Ilmberger J, Ruge M, Kreth F-W, Briegel J, Reulen H-J, Tonn J-C. Intraoperative mapping of language functions: a longitudinal neurolinguistic analysis.
Journal of Neurosurgery 2008;109(4):58392.
[7] Pereira LCM, Oliveira KM, L Abbate GL, Sugai R, Ferreira JA, Motta LA. Outcome
of fully awake craniotomy for lesions near the eloquent cortex: analysis of a
prospective surgical series of 79 supratentorial primary brain tumors with
long follow-up. Acta Neurochirurgica 2009;151(10):121530.
[8] Radner H, Blmcke I, Reifenberger G, Wiestler O. The new WHO classication
of tumours of the nervous system 2000. Pathology and Genetics Der Pathologe
2002;23(4):26083.
[9] Bello L, Castellano A, Fava E, Casaceli G, Riva M, Scotti G, et al. Intraoperative use of diffusion tensor imaging ber tractography and subcortical
mapping for resection of gliomas: technical considerations. Neurosurgical
Focus 2010;28(2):E6.
[10] Benzagmout M, Gatignol P, Duffau H. Resection of world health organization grade II gliomas involving Brocas area: methodological and functional
considerations. Neurosurgery 2007;61(4):74152.
[11] Bertani G, Fava E, Casaceli G, Carrabba G, Casarotti A, Papagno C,
et al. Intraoperative mapping and monitoring of brain functions for the
resection of low-grade gliomas: technical considerations. Neurosurgical
Focus 2009;27(4).
[12] Duffau H. Lessons from brain mapping in surgery for low-grade glioma:
insights into associations between tumour and brain plasticity. Lancet Neurology 2005;4(8):47686.
[13] Tonn JC. Awake craniotomy for monitoring of language function: benets and
limits. Acta Neurochirurgica 2007;149(12):11978.
[14] Mandonnet E, Winkler PA, Duffau H. Direct electrical stimulation as an input
gate into brain functional networks: principles, advantages and limitations.
Acta Neurochirurgica 2010;152(2):18593.
[15] Spena G, Nava A, Cassini F, Pepoli A, Bruno M, DAgata F, et al. Preoperative
and intraoperative brain mapping for the resection of eloquent-area tumors.
A prospective analysis of methodology, correlation, and usefulness based on
clinical outcomes. Acta Neurochirurgica 2010;152(11):183546.
[16] Giussani C, Roux F-E, Ojemann J, Sganzerla EP, Pirillo D, Papagno C. Is preoperative functional magnetic resonance imaging reliable for language areas
mapping in brain tumor surgery? Review of language functional magnetic
resonance imaging and direct cortical stimulation correlation studies. Neurosurgery 2010;66(1):11320.
143
[17] Picht T, Kombos T, Gramm H, Brock M, Suess O. Multimodal protocol for

awake craniotomy in language cortex tumour surgery. Acta Neurochirurgica
2006;148(2):12738.
[18] Colle H, Muller P, Robert E. Wakkere craniotomien met asleepawake-asleep anesthesia. Tijdschrift voor Neurologie en Neurochirurgie
2005;106(4):1706.
[19] Ali MZ, Fadel NA, Abouldahab HA. Awake craniotomy versus general anesthesia for managing eloquent cortex low-grade gliomas. Neurosciences
2009;14(3):26372.
[20] Reithmeier T, Krammer M, Gumprecht H, Gerstner W, Lumenta C. Neuronavigation combined with electrophysiological monitoring for surgery of lesions
in eloquent brain areas in 42 cases: a retrospective comparison of the neurological outcome and the quality of resection with a control group with similar
lesions. Minimally Invasive Neurosurgery 2003;46(2):6571.
[21] Giussani C, Roux F-E, Lubrano V, Gaini SM, Bello L. Review of language organisation in bilingual patients: what can we learn from direct brain mapping?
Acta Neurochirurgica 2007;149(11):110916.
[22] July J, Manninen P, Lai J, Yao Z, Bernstein M. The history of awake craniotomy
for brain tumor and its spread into Asia. Surgical Neurology 2009;71(May
(5)):6215.
[23] Bizzi A. Presurgical mapping of verbal language in brain tumors with functional. Neuroimaging Clinics of North America 2009;19(4):57396.
[24] McDermott KB, Watson JM, Ojemann JG. Presurgical language mapping. Current Directions in Psychological Science 2005;14(6):2915.
[25] Boatman D. Cortical bases of speech perception: evidence from functional
lesion studies. Cognition 2004;92(12):4765.
[26] Young RJ, Brennan N, Fraser JF, Brennan C. Advanced imaging in brain tumor
surgery. Neuroimaging Clinics of North America 2010;20(3):31135.
[27] Duffau H, Gatignol P, Mandonnet E, Capelle L, Taillandier L. Intraoperative
subcortical stimulation mapping of language pathways in a consecutive series
of 115 patients with Grade II glioma in the left dominant hemisphere. Journal
of Neurosurgery 2008;109(3):46171.
[28] Duffau H. A personal consecutive series of surgically treated 51 cases of insular
WHO Grade II glioma: advances and limitations clinical article. Journal of
Neurosurgery 2009;110(4):696708.
[29] Tharin S, Golby A. Functional brain mapping and its applications to neurosurgery. Neurosurgery 2007;60(4):185202.
[30] Ng WH, Mukhida K, Rutka JT. Image guidance and neuromonitoring in neurosurgery. Childs Nervous System 2010;26(4):491502.
[31] Petrella JR, Shah LM, Harris KM, Friedman AH, George TM, Sampson
JH, et al. Preoperative functional MR imaging localization of language
and motor areas: effect on therapeutic decision making in patients
with potentially resectable brain tumors. Radiology 2006;240(3):793
802.
[32] Petrovich N, Holodny A, Tabar V, Correa D, Hirsch J, Gutin P, et al. Discordance between functional magnetic resonance imaging during silent
speech tasks and intraoperative speech arrest. Journal of Neurosurgery
2005;103(2):26774.
[33] Roux F-E, Boulanouar K, Lotterie J-A, Mejdoubi M, LeSage JP, Berry I. Language functional magnetic resonance imaging in preoperative assessment
of language areas: correlation with direct cortical stimulation. Neurosurgery
2003;52(6):133547.
[34] Duffau H, Gatignol P, Mandonnet E, Peruzzi P, Tzourio-Mazoyer N, Capelle
L. New insights into the anatomo-functional connectivity of the semantic system: a study using cortico-subcortical electrostimulations. Brain
2005;128:797810.
[35] Szelenyi A, Bello L, Duffau H, Fava E, Feigl GC, Galanda M, et al. Intraoperative electrical stimulation in awake craniotomy: methodological aspects of
current practice. Neurosurgical Focus 2010;28(2):18.
[36] Epstein CM, Meador KJ, Loring DW, Wright RJ, Weissman JD, Sheppard S, et al. Localization and characterization of speech arrest during
transcranial magnetic stimulation. Clinical Neurophysiology 1999;110(6):
10739.
[37] Shamov T, Spiriev T, Tzvetanov P, Petkov A. The combination of neuronavigation with transcranial magnetic stimulation for treatment of opercular
gliomas of the dominant brain hemisphere. Clinical Neurology and Neurosurgery 2010;112(8):6727.
[38] Picht T, Mularski S, Kuehn B, Vajkoczy P, Kombos T, Suess O. Navigated transcranial magnetic stimulation for preoperative functional diagnostics in brain
tumor surgery. Neurosurgery 2009;65(6):938.
[39] Picht T, Schmidt S, Brandt S, Frey D, Hannula H, Neuvonen T, et al. Preoperative functional mapping for rolandic brain tumor surgery: comparison of
navigated transcranial magnetic stimulation to direct cortical stimulation.
Neurosurgery 2011;69(3):5818.
[40] Klimek M, Hol JW, Wens S, Heijmans-Antonissen C, Niehof S, Vincent
AJ, et al. Inammatory prole of awake function-controlled craniotomy
and craniotomy under general anesthesia. Mediators of Inammation
2009;46:38691.
[41] Tomasino B, Marin D. Foreign accent syndrome: a multimodal mapping study.
Cortex 2012:122.
[42] Wahab SS, Grundy PL, Weidmann C. Patient experience and satisfaction
with awake craniotomy for brain tumours. British Journal of Neurosurgery
2011;25(5):60613.
[43] Grundy PL, Weidmann C, Bernstein M. Day-case neurosurgery for brain
tumours: the early United Kingdom experience. British Journal of Neurosurgery 2008;22(3):3607.
144
[44] Goebel S, Nabavi A, Schubert S, Mehdorn HM. Patient perception of combined

awake brain tumor surgery and intraoperative 1.5-T magnetic resonance
imaging: the Kiel experience. Neurosurgery 2010;67(3):594600.
[45] Carrabba G, Venkatraghavan L, Bernstein M. Day surgery awake craniotomy
for removing brain tumours: technical note describing a simple protocol.
Minimally Invasive Neurosurgery 2008;51(4):20810.
[46] Mandonnet E, Nouet A, Gatignol P, Capelle L, Duffau H. Does the left inferior
longitudinal fasciculus play a role in language? A brain stimulation study.
Brain 2007;130(3):6239.
[47] Sanai N, Mirzadeh Z, Berger MS. Functional outcome after language mapping
for glioma resection. New England Journal of Medicine 2008;358(1):1827.
[48] Kim SS, McCutcheon IE, Suki D, Weinberg JS, Sawaya R, Lang FF, et al.
Awake craniotomy for brain tumors near eloquent cortex. Neurosurgery
2009;64(5):83646.
[49] Serletis D, Bernstein M. Prospective study of awake craniotomy used routinely and nonselectively for supratentorial tumors. Journal of Neurosurgery
2007;107(1):16.
[50] Duffau H. Surgery of low-grade gliomas: towards a functional neurooncology. Current Opinion in Oncology 2009;21(6):5439.
[51] Bello L, Gallucci M, Fava M, Carrabba G, Giussani C, Acerbi F, et al. Intraoperative subcortical language tract mapping guides surgical removal of gliomas
involving speech areas. Neurosurgery 2007;60(1):6782.
[52] Duffau H, Capelle L, Sichez N, Denvil D, Lopes M, Sichez J-P<EY-AL>.
Intraoperative mapping of the subcortical language pathways using direct
stimulations: an anatomo-functional study. Brain 2002;125(1):199214.
[53] Duffau H, Capelle L, Denvil D, Sichez N, Gatignol P, Taillandier L, et al.
Usefulness of intraoperative electrical subcortical mapping during surgery
for low-grade gliomas located within eloquent brain regions: functional
results in a consecutive series of 103 patients. Journal of Neurosurgery
2003;98(4):76478.
[54] Sakurada K, Sato S, Sonoda Y, Kokubo Y, Saito S, Kayama T. Surgical resection
of tumors located in subcortex of language area. Acta Neurochirurgica
2006;149(2):12330.
[55] Teixidor P, Gatignol P, Leroy M, Masuet-Aumatell C, Capelle L, Duffau H.
Assessment of verbal working memory before and after surgery for low-grade
glioma. Journal of Neuro-Oncology 2007;81(3):30513.
[56] Gupta DK, Chandra PS, Ojha BK, Sharma BS, Mahapatra AK, Mehta VS. Awake
craniotomy versus surgery under general anesthesia for resection of intrinsic
lesions of eloquent cortex a prospective randomised study. Clinical Neurology and Neurosurgery 2007;109(4):33543.
[57] Sacko O, Lauwers-Cances V, Brauge D, Sesay M, Brenner A, Roux F-E. Awake
craniotomy vs. surgery under general anesthesia for resection of supratentorial lesions. Neurosurgery 2011;68(5):11928.
[58] Peruzzi P, Bergese SD, Viloria A, Puente EG, Abdel-Rasoul M, Chiocca EA. A
retrospective cohort-matched comparison of conscious sedation versus general anesthesia for supratentorial glioma resection clinical article. Journal of
Neurosurgery 2011;114(3):6339.
[59] De Witt Hamer PC, Robles SG, Zwinderman AH, Duffau H, Berger MS.
Impact of intraoperative stimulation brain mapping on glioma surgery outcome: a meta-analysis. Journal of Clinical Oncology 2012;30(20):2265
559.
[60] Yordanova YN, Moritz-Gasser S, Duffau H. Awake surgery for WHO Grade
II gliomas within noneloquent areas in the left dominant hemisphere:
toward a supratotal resection Clinical article. Journal of Neurosurgery
2011;115(2):2329.
[61] Duffau H, Capelle L, Denvil D, Sichez N, Gatignol P, Lopes M, et al. Functional recovery after surgical resection of low grade gliomas in eloquent brain:
hypothesis of brain compensation. Journal of Neurology, Neurosurgery and
Psychiatry 2003;74(7):9017.
[62] Gil-Robles S, Duffau H. Surgical management of World Health Organization
Grade II gliomas in eloquent areas: the necessity of preserving a margin
around functional structures. Neurosurgical Focus 2010;28(2):E8.
[63] Lubrano V, Draper L, Roux F-E. What makes surgical tumor resection feasible
in Brocas area? Insights into intraoperative brain mapping. Neurosurgery
2010;66(5):86875.
[64] Duffau H. Brain plasticity: from pathophysiological mechanisms to therapeutic applications. Journal of Clinical Neuroscience 2006;13(9):88597.
[65] Duffau H. New insights into pre-intra- and post-operative brain mapping in
low-grade glioma surgery: towards a longitudinal study of cerebral plasticity.
Current Medical Imaging Reviews 2010;6(4):24653.
[66] De Benedictis A, Duffau H. Brain hodotopy: from esoteric concept to practical
surgical applications. Neurosurgery 2011;68(6):170923.
[67] Palese A, Skrap M, Fachin M, Visioli S, Zannini L. The experience of patients
undergoing awake craniotomy. Cancer Nursing 2008;31(2):16672.
[68] Manchella S, Khurana VG, Duke D, Brussel T, French J, Zuccherelli L. The experience of patients undergoing awake craniotomy for intracranial masses:
expectations, recall, satisfaction and functional outcome. British Journal of
Neurosurgery 2011;25(3):391400.
[69] Kubben PL, ter Meulen KJ, Schijns OE, ter Laak-Poort MP, van Overbeeke JJ,
van Santbrink H. Intraoperative MRI-guided resection of glioblastoma multiforme: a systematic review. The Lancet Oncology 2011;12(11):106270.
[70] Parney IF, Goerss SJ, McGee K, Huston III J, Perkins WJ, Meyer FB. Awake
craniotomy, electrophysiologic mapping, and tumor resection with high-eld
intraoperative MRI. World Neurosurgery 2010;73(5):54751.
[71] Berger MS, Hadjipanayis CG. Surgery of intrinsic cerebral tumors. Neurosurgery 2007;61(1):279304.
[72] Berger MS, Deliganis AV, Dobbins J, Keles GE. The effect of extent of resection
on recurrence in patients with low grade cerebral hemisphere gliomas. Cancer
1994;74(6):178491.
[73] Lurito J, Lowe M, Sartorius C, Mathews V. Comparison of fMRI and intraoperative direct cortical stimulation in localization of receptive language areas.
Journal of Computer Assisted Tomography 2000;24(1):99105.
[74] Bizzi A, Blasi V, Falini A, Ferroli P, Cadioli M, Danesi U, et al. Presurgical
functional MR imaging of language and motor functions: validation with
intraoperative electrocortical mapping. Radiology 2008;248(2):57989.
[75] Quinones-Hinojosa A, Ojemann S, Sanai N, Dillon W, Berger M. Preoperative correlation of intraoperative cortical mapping with magnetic resonance
imaging landmarks to predict localization of the Broca area. Journal of Neurosurgery 2003;99(2):3118.
[76] Kim PE, Singh M. Functional magnetic resonance imaging for brain mapping
in neurosurgery. Neurosurgical Focus 2003;15(1):17.
[77] Sobottka SB, Bredow J, Beuthien-Baumann B, Reiss G, Schackert G, Steinmeier R. Comparison of functional brain PET images and intraoperative
brain-mapping data using image-guided surgery. Computer Aided Surgery
2002;7(6):31725.
[78] Bello L, Gambini A, Castellano A, Carrabba G, Acerbi F, Fava E, et al. Motor
and language DTI Fiber Tracking combined with intraoperative subcortical
mapping for surgical removal of gliomas. NeuroImage 2008;39(1):36982.
[79] Talacchi A, Santini B, Savazzi S, Gerosa M. Cognitive effects of tumour
and surgical treatment in glioma patients. Journal of Neuro-Oncology
2011;103(3):5419.
[80] Tucha O, Smely C, Preier M, Becker G, Paul G, Lange K. Preoperative and postoperative cognitive functioning in patients with frontal meningiomas. Journal
of Neurosurgery 2003;98(1):2131.
[81] Wu AS, Witgert ME, Lang FF, Xiao L, Bekele BN, Meyers CA, et al. Neurocognitive function before and after surgery for insular gliomas clinical article.
Journal of Neurosurgery 2011;115(6):111525.
[82] Robles S, Gatignol P, Capelle L, Mitchell M, Duffau H. The role of dominant
striatum in language: a study using intraoperative electrical stimulations.
Journal of Neurology, Neurosurgery and Psychiatry 2005;76(7):9406.
[83] Brennan NMP, Whalen S, Branco D, de M, OShea JP, Norton IH, et al. Object
naming is a more sensitive measure of speech localization than number
counting: converging evidence from direct cortical stimulation and fMRI.
Neuroimage 2007;37:S1008.
[84] Scarone P, Gatignol P, Guillaume S, Denvil D, Capelle L, Duffau H.
Agraphia after awake surgery for brain tumor: new insights into the
anatomo-functional network of writing. Surgical Neurology 2009;72(3):
22341.
[85] Goodglass H, Kaplan E. The assessment of aphasia and related disorders.
Philadelphia: Lea and Fibiger; 1972.
[86] Huber W, Poeck K, Weniger D, WIllmes K. Aachener Aphasie Test. Gttingen:
Hogrefe; 1983.
[87] Kaplan EF, Goodglass H, Weintraub S. The Boston Naming Test. 2nd ed.
Philadelphia: Lea and Fibiger; 1983.
[88] Metz-Lutz MN, Kremin H, Deloche G, Hannequin D, Ferrand L, Perrier D. Standardisation dun test de dnomination orale: contrle des effets de lge, du
sexe et du niveau de scolarit chez les sujets adultes normaux. Neuropsychology Review 1991;1:7395.
[89] Sarubbo S, Latini F, Panajia A, Candela C, Quatrale R, Milani P, et al. Awake
surgery in low-grade gliomas harboring eloquent areas: 3-year mean followup. Neurological Sciences 2011;32(5):80110.
[90] Roux F, Lubrano V, Lauwers-Cances V, Tremoulet M, Mascott C, Demonet J.
Intra-operative mapping of cortical areas involved in reading in mono- and
bilingual patients. Brain 2004;127:1796810.
[91] Vassal M, Le Bars E, Moritz-Gasser S, Menjot N, Duffau H. Crossed aphasia elicited by intraoperative cortical and subcortical stimulation in awake
patients. Journal of Neurosurgery 2010;113(6):12518.
[92] Papagno C, Gallucci M, Casarotti A, Castellano A, Falini A, Fava E, et al. Connectivity constraints on cortical reorganization of neural circuits involved in
object naming. Neuroimage 2011;55(3):130613.
[93] Santini B, Talacchi A, Squintani G, Casagrande F, Capasso R, Miceli G. Cognitive
outcome after awake surgery for tumors in language areas. Journal of NeuroOncology 2012. Available from: http://www.ncbi.nlm.nih.gov/pubmed/
22350433
[94] Leclercq D, Duffau H, Delmaire C, Capelle L, Gatignol P, Ducros M,
et al. Comparison of diffusion tensor imaging tractography of language
tracts and intraoperative subcortical stimulations. Journal of Neurosurgery
2010;112(3):50311.
[95] Polczynska M. New tests for language mapping with intraoperative electrical
stimulation of the brain to preserve language in individuals with tumors and
epilepsy: a preliminary follow-up study. Poznan Studies in Contemporary
Linguistics 2009;45(2):26179.
[96] Hamberger MJ, Seidel WT, Mckhann GM, Perrine K, Goodman RR. Brain stimulation reveals critical auditory naming cortex. Brain 2005;128(11):27429.
[97] Correa DD, Shi W, Thaler HT, Cheung AM, DeAngelis LM, Abrey LE. Longitudinal cognitive follow-up in low grade gliomas. Journal of Neuro-Oncology
2007;86(3):3217.
[98] Duffau H. Awake surgery for nonlanguage mapping. Neurosurgery
2010;66(3):5238.
[99] Roux F-E, Dufor O, Lauwers-Cances V, Boukhatem L, Brauge D, Draper
L, et al. Electrostimulation mapping of spatial neglect. Neurosurgery
2011;69(6):121831.

[100] Gras-Combe G, Moritz-Gasser S, Herbet G, Duffau H. Intraoperative subcortical electrical mapping of optic radiations in awake surgery for glioma
involving visual pathways. Journal of Neurosurgery 2012:110.
[101] Giussani C, Pirillo D, Roux F-E. Mirror of the soul: a cortical stimulation study on recognition of facial emotions. Journal of Neurosurgery
2010;112(3):5207.
145
[102] Duffau H, Gatignol P, Moritz-Gasser S, Mandonnet E. Is the left uncinate fasciculus essential for language? Journal of Neurology 2009;256(3):3829.
[103] Waagemans ML, van Nieuwenhuizen D, Dijkstra M, Wumkes M, Dirven
CMF, Leenstra S, et al. Long-term impact of cognitive decits and epilepsy
on quality of life in patients with low-grade meningiomas. Neurosurgery
2011;69(1):728.

The Neurolinguistic Approach To Awake Surgery Reviewed

Diunggah oleh

Informasi Dokumen

Judul Asli

Hak Cipta

Format Tersedia

Bagikan dokumen Ini

Bagikan atau Tanam Dokumen

Opsi Berbagi

Apakah menurut Anda dokumen ini bermanfaat?

Apakah konten ini tidak pantas?

Hak Cipta:

Format Tersedia

The Neurolinguistic Approach To Awake Surgery Reviewed

Diunggah oleh

Hak Cipta:

Format Tersedia

Clinical Neurology and Neurosurgery 115 (2013) 127145

Contents lists available at SciVerse ScienceDirect

Clinical Neurology and Neurosurgery

The neurolinguistic approach to awake surgery reviewed

E. De Witte, P. Marin / Clinical Neurology and Neurosurgery 115 (2013) 127145

E. De Witte, P. Marin / Clinical Neurology and Neurosurgery 115 (2013) 127145

to identify cortical and subcortical language areas, there are a

E. De Witte, P. Marin / Clinical Neurology and Neurosurgery 115 (2013) 127145

The ability to map subcortical pathways, and thus to detect

E. De Witte, P. Marin / Clinical Neurology and Neurosurgery 115 (2013) 127145

a study by Duffau et al. [2]. A mortality rate of 20.6% was found

The nal important disadvantage of DES seems to be the lack

E. De Witte, P. Marin / Clinical Neurology and Neurosurgery 115 (2013) 127145

In conclusion, recent advances in preoperative mapping with

Ilmberger et al. [6]

Phonemes, words and sentences

fMRI language paradigm(s)

Listening to nouns produce verb (verb

Picht et al. [17]

1 day before surgery

Patients with scores of at least 50% in all modules

Lubrano et al. [63]

BDAE short version:

Benzagmout et al. [10]

BDAE adapted version

Repetition tasks, story listening, verbal uency

Duffau et al. [34]

Yordanova et al. [60]

Robles et al. [82]

Lurito et al. [73]

Brennan et al. [83]

Object naming, number counting

De Benedictis et al. [1]

Duffau et al. [52]

Semantic uency, story listening and covert

Duffau et al. [27]

Semantic uency, story listening and covert

Teixidor et al. [55]

Semantic uency task, covert sentence repetition

Mandonnet et al. [46]

Listening to reading of a narrative text from a

E. De Witte, P. Marin / Clinical Neurology and Neurosurgery 115 (2013) 127145

Spena et al. [15]

Commands and logic

Semantic verbal uency, covert sentence

fMRI language paradigm(s)

Bizzi et al. [74]

Time between fMRI

Verb generation (produce a verb silently in

Santini et al. [93]

Written, oral comprehension

Roux et al. [90]

Written, oral comprehension

Scarone et al. [84]

Verb generation (nd verbs in relation to the

Based on the patients written output

Fluency in controlled word association, story

Sarubbo et al. [89]

Duffau et al. [53]

E. De Witte, P. Marin / Clinical Neurology and Neurosurgery 115 (2013) 127145

Sanai et al. [47]

Bello et al. [51]

Describe reason for admission to the