Functional Magnetic Resonance Imaging of Language
Sara J. Swanson & David S. Sabsevitz &
Thomas A. Hammeke & Jeffrey R. Binder
Received: 24 September 2007 /Accepted: 5 October 2007 / Published online: 16 November 2007
# Springer Science + Business Media, LLC 2007
Abstract Functional magnetic resonance imaging (fMRI)
has revolutionized our understanding of functional networks
and cerebral organization in both normal and pathological
brains. In the present review, we describe the use offMRI for
mapping language in epilepsy patients prior to surgical
intervention including a discussion of methodological issues
and task design, comparisons between fMRI and the intra-
carotid sodium amobarbital test, fMRI studies of language
reorganization, and the use of fMRI laterality indexes to
predict outcome after anterior temporal lobectomy.
Clinical neuropsychology historically has studied brain
behavior relationships through the examination of the
behavioral correlates of focal lesions or neurological
diseases. With the advent of functional magnetic resonance
imaging (fMRI) in the early 1990s, neuropsychologists and
neuroscientists have examined cognitive processing in
intact brains, in individuals with neurological disease, and
prior to and following neurosurgical intervention. These
studies have challenged older notions of cerebral organiza-
tion and expanded our knowledge of the complexity of
functional localization. For example, investigations that aim
to activate cerebral language zones in healthy adults have
yielded data that partially conflicts with classical models of
anterior expressive (Broca’s area) and posterior receptive
(Wernicke’s area) language organization (Binder et al.
1997). These data reveal a more extensive language
network than previous focal lesion studies have suggested.
Thus, fMRI has advanced our knowledge of localization of
cognitive operations relevant to both healthy and patient
One of the most studied clinical applications of fMRI has
been the pre-operative evaluation of epilepsy patients.
Clinical applications for epilepsy surgery candidates include
determination of hemispheric lateralization of memory
functions, (Detre et al. 1998; Golby et al. 2002; Koylu
et al. 2006; Powell et al. 2004) and localization of language
networks or component language functions, which will be
described below. In addition, fMRI has been used for
predicting side of seizure focus (Bellgowan et al. 1998;
Jokeit et al. 2001b) and to predict outcome after temporal
lobectomy with regard to seizures (Killgore et al. 1999),
language (Sabsevitz et al. 2003), and memory (Rabin et al.
2004; Richardson et al. 2004). The present review will
include: (1) adiscussionofmethodologicalissuesrelevantto
language assessment during fMRI; (2) a review of studies
comparing fMRI and the intracarotid amobarbital test (IAT);
(3) comparisons between fMRI and IAT in patients with
atypical (bilateral or right hemisphere) language dominance
(5) the use of fMRI language activation for predicting
cognitive outcome after temporal lobectomy.
Neuropsychol Rev (2007) 17:491–504
S. J. Swanson (*):D. S. Sabsevitz:
T. A. Hammeke:J. R. Binder
Department of Neurology, Medical College of Wisconsin,
Milwaukee, WI, USA
Functional magnetic resonance imaging is a noninvasive
and widely available technique for detecting regional
changes in blood oxygenation resulting from neural activity
(Kwong et al. 1992; Moonen and Bandettini 1999; Ogawa
et al. 1992). To use fMRI effectively and responsibly as a
clinical tool requires a full understanding of methodological
issues affecting reliability and validity. The usefulness of
fMRI language maps depends on how well the activation
protocols, including both probe and control or contrast
tasks, are designed to identify specific cognitive domains as
well as the sensitivity and specificity of the cerebral
activation patterns with regard to the clinical predictions
being made. Activation maps and their reproducibility
change with alterations in a number of imaging parameters,
including the statistical threshold, voxel size, cluster size,
degree of spatial smoothing, number of images acquired,
and magnetic field strength (Binder 2003; Jansen et al.
2006). Intrasubject factors that affect the signal to noise
ratio include head motion, age, body habitus (head size,
neck length), motivational state, task strategy, and task
performance (Hammeke et al. 2000; Weber et al. 2006).
Improved control and detection of task-correlated movement
artifacts and the availability of new higher performance
gradient systems operating at 3 Tesla are leading to better
signal-to-noise ratios. The effects of antiepileptic medications
on imaging results should also be considered. While few
studies have examined the effects of AEDs on blood oxygen
level dependent (BOLD) response, bilateral medial temporal
lobe activation was negatively correlated with serum carba-
mazepine levels in one study (Jokeit et al. 2001a).
Behavioral Monitoring The importance of knowing how
well subjects perform tasks during fMRI studies is becoming
increasingly evident. Behavioral monitoring of performance
during language activation tasks helps ensure task compli-
ance and reduce unsolicited cognitive processing. Care
should be taken to match the control and probe task for task
difficulty and behavioral performance accuracy. Epilepsy
patients have varying levels of cognitive abilities and will
have different performance levels on the activation tasks. For
example, there are likely large differences across patients in
the number of words generated during covert fluency tasks.
Little is known about the relationship between number of
words generated and activation volumes or activation
laterality indexes (LIs). A recent study examined fMRI
language maps in patients with vastly different performance
levels on a semantic decision task (Weber et al. 2006).
Activation volumes and lateralization were examined
relative to performance levels in 195 epilepsy patients.
The task was to determine if visually presented words were
semantically related and the control task was to determine
whether visually presented consonants strings were the
same or different. There was no significant difference in the
LIs for the group with the best performance compared to
patients with the worst performance; however, task perfor-
mance was related to the intrahemispheric activation
profile. A larger area of activated volume in temporopar-
ietal areas and a smaller area in the inferior frontal region
was found in those with better task performance. The
authors concluded that since the fMRI language LIs seem
to be independent of task performance, at least for this task
contrast, language LIs can be used in patients with variable
levels of performance accuracy.
Task Design The field is far from developing standardized
tasks for mapping language. Similar to the IAT, investi-
gators tend to retain task paradigms known to them.
Currently, a wide variety of language activation protocols
are being used. With regard to the variety of language tasks,
the most common methodological limitation of previous
language functional imaging studies has been the failure to
incorporate a control or contrast task in the activation
protocol that serves to minimize the effects of unwanted
mental activity. Rigorously designed probe and control
tasks that include measures of behavioral performance are
critical. Most task designs use a subtraction or contrast
technique. The contrast between the component functions
subsumed by the tasks is theoretically selected to isolate the
substrate of interest. For example, a semantic decision task
used by Binder et al. (1995, 1997), based on a task
introduced by Demonet et al. (1992), requires subjects to
press a button in response to an animal name if the animal
is both found in the United States and used by humans.
This is contrasted with a tone monitoring task in which a
series of brief tones of varying pitch are presented. Subjects
are instructed to press a button in response to tone trains
containing two high tones. The semantic and tone tasks
were matched for stimulus intensity, stimulus duration, trial
duration, and frequency of positive targets. The contrast
task is nonlinguistic and controls for auditory, motor,
executive, and working memory functions that are not
specific to language (See Table 1, part A). Comparing a
language with a perceptual control task allowed areas equally
activated by both tasks, i.e., not specific to language, to be
subtracted from the language activation maps.
Rest, which can be characterized as unconstrained
conceptual processing, does not provide an optimal baseline
condition for language or memory studies (Stark and Squire
2001). Since most tasks will not activate only the specific
cognitive function of interest, rest, fixation on a crosshair,
or fixation on a dark screen are inadequate contrasts for
studying cognitive operations. Rest is known to be an
active state during which self-initiated linguistic and
semantic processes occur (Binder et al. 1999; McKiernan
492Neuropsychol Rev (2007) 17:491–504
et al. 2003, 2006). In fact, contrasts between a language
task, tone monitoring task, and a resting state demonstrated
that there is more activation in many regions during a
conscious resting state than during a tone monitoring task
(see Fig. 1). Thus fewer areas of activation were seen in the
contrast [semantic decision—rest] compared to the contrast
[semantic decision—tone monitoring]. Specifically, as
shown in Fig. 1, activation observed in the left angular
gyrus, posterior cingulate gyrus, left medial frontal lobe,
and left medial temporal lobe during semantic decision
contrasted with tone monitoring disappeared when semantic
decision was contrasted with rest. Since semantic retrieval
and information manipulation occur during resting states,
language activation protocols employing rest as a contrast
may lack sensitivity. More specifically, this potentially
could lead to a poor cognitive outcome from surgery since,
when language maps derived from task contrasts employing
rest are used, a portion of the language zones will be
inadvertently removed from the activation maps.
While rest is not an appropriate control condition for
activation paradigms designed to image higher cognitive
functions, results will be equally obfuscated when the
control task is not theoretically designed to subtract specific
unwanted cognitive components. For example, some
investigators have used a verb generation task where
participants covertly generate a verb in response to an
auditorily presented noun (Rutten et al. 2002). The control
task involved viewing symbols (/ or *) and pressing a
button in response to an asterisk. Table 1 shows the
hypothetical cognitive components engaged during the
semantic decision task and this covert fluency task as well
as their respective control tasks components. Specifically,
the control task for semantic decision subtracts attention,
auditory processing, and motor response components,
isolating semantic and phonetic processing. The control
task for covert fluency subtracts a motor response (though
none was made during the probe task), visual processing
(though there is no visual processing in the probe task) but
Fig. 1 Activation patterns obtained for contrasts between a Tone
discrimination versus rest, b Semantic decision versus rest, and c Semantic
decision versus tone monitoring. Three fMRI activation maps were
obtained from the same 30 healthy adult participants. The maps show
group activations thresholded at whole-brain corrected p<0.05. The left
side of the brain is on the reader’s left. a Tone monitoring contrasted with
“rest.” Note regions in blue that are more active during the resting state
(“default network”) than during this non-linguistic task, including angular
gyrus, posterior cingulate gyrus, medial and ventral frontal lobe, and
ventral temporal lobe. b Semantic decision contrasted with “rest.” Note that
the default network regions in (a) show relatively little activation,
indicating equivalent BOLD signals during the semantic decision task
and the resting state. c Semantic decision contrasted with tone monitoring.
Strong left-lateralized activation is observed throughout the default
network, inferior frontal lobe, and temporal lobe. BOLD = blood oxygen
level dependent; fMRI = functional magnetic resonance imaging
Table 1 Functional components of two language activation tasks
A. Semantic monitoring
B. Covert fluency task
Auditory processing +
Neuropsychol Rev (2007) 17:491–504 493
does not subtract auditory processing involved with the
presentation of the nouns. With this covert fluency
paradigm, one has not isolated language components and
has subtracted functions not activated in the probe task.
Thus, more activation might be seen in the control than the
The sensitivity and specificity of language activation
maps depend largely on how well the activation and control
tasks are designed. In addition, sensitivity may vary when
event-related designs are compared to traditional block
designs, with block designs yielding greater sensitivity
(Narayan et al. 2005) Event-related single trial designs
provide a means for segregating activation trials based on
response accuracy or later recall of the stimulus. This has
particular relevance in identifying the integrity of functional
circuits, e.g., memory encoding circuits. New clustered
acquisition techniques allow patients to speak in the
scanner, enhancing our ability to image language produc-
tion systems. In addition, some investigators have advocat-
ed use of multiple language tasks or a task panel to improve
concordance with the IAT (Gaillard et al. 2004). Sensitivity
is also affected by susceptibility artifacts, with brain regions
near the sinuses and borders of the brain such as the
temporal lobes suffering loss of BOLD signal (Jezzard and
Reproducibility Despite the fact that fMRI studies are
noninvasive and repeatable, limited data exist describing
test–retest reliability of language lateralization indexes. In
one such investigation, Binder and colleagues found a high
correlation between lateralization indexes derived from two
separate activation runs of a semantic decision task
conducted within the same imaging session (r=0.89),
demonstrating that such language asymmetry measures
can be highly reliable (Binder et al. 2001). Moreover, these
authors found that language activation patterns were similar
in matched samples of controls—voxel-by-voxel correla-
tion between the activation maps from two subgroups of 15
subjects each was 0.86, with a Spearman–Brown estimated
reliability coefficient for the 30 subjects of 0.92 (Binder et al.
Several studies have examined reliability of activation
profiles across imaging sessions. One study examined the
test–retest reliability of language LIs as well as language
activation maps from epilepsy patients within and across
sessions (Fernandez et al. 2003). The reliability of the
language LIs derived from different regions of interest
(ROIs) was compared using a split-half comparison
(comparing the first and second half of a session). In
addition, test–retest reliability was examined in a small set
of patients who had fMRI across two separate sessions. In
this study a synonym judgment task was contrasted with a
letter string matching task, both of which were visually
presented. Higher reliability was found in frontal regions
(range r=0.837 to 0.982) than in parieto-temporal regions
(r=0.695). The percentage of spatial overlap in the
activation clusters for first and second sessions ranged
from 42 to 49% depending on the threshold used. These
authors concluded that the activation maps were sufficiently
reproducible in individual patients for these maps to be
clinically useful. Similar results were found in small groups
of patients tested twice using a variety of language tasks.
Laterality indexes were found to be reproducible, with the
highest test–retest reliability found in frontal ROIs for verb
or word generation tasks (Harrington et al. 2006). Maldjian
and colleagues found higher reproducibility but more
extraneousactivationusing awordgenerationtask (Maldjian
et al. 2002) compared to a text listening task.
Subject Factors Not all epilepsy surgery candidates will be
able to undergo fMRI. Patients with vagal nerve stimulators
can be scanned on a 1.5 Tesla but not a 3 Tesla scanner. Just
as a few patients will not be able to undergo amobarbital
testing because of vascular anomalies, patients with
claustrophobia, obesity, slow processing speed, severe
inattention, cranial anomalies resulting in macrocephaly,
or mental retardation are not suitable for fMRI language
mapping with most paradigms in current use.
Comparisons between fMRI and the Intracarotid
Numerous studies have compared fMRI and IAT, as this
provided one of the first opportunities to examine the validity
dominance. These studies are listed in Table 2 with a
description of the task employed, region of interest, subject
sample size, number of participants with atypical language,
concordance or correlation, and activation patterns (Baciu
et al. 2001; Bahn et al. 1997; Benke et al. 2006; Benson et
al. 1999; Binder et al. 1996; Carpentier et al. 2001; Deblaere
et al. 2004; Desmond et al. 1995; Gaillard et al. 2002, 2004;
Hertz-Pannier et al. 1997; Lehericy et al. 2000; Liegeois
et al. 2002; Rutten et al. 2002; Sabbah et al. 2003; Spreer
et al. 2002; Woermann et al. 2003; Worthington et al. 1997;
Yetkin et al. 1998). The IAT (Wada 1949) is used routinely
and considered the “gold standard” for language lateraliza-
tion prior to epilepsy surgery, though the procedure provides
no information about localization within a hemisphere.
Comparisons can be made between fMRI and IAT by
examining the concordance between the methods in a
qualitative fashion (left, right or bilateral) or by examining
correlations between quantitative laterality indexes. Later-
alization indexes often are computed for fMRI using the
494Neuropsychol Rev (2007) 17:491–504
Table 2 Concordance rates and correlations between IAT and fMRI
IFG, Brodman’s areas
45, 46, 47
Lateral frontal, temporo-
Frontal and temporal
Inferior, middle and
superior frontal gyrus
IFG, precentral gyrus,
SMA, anterior cingulate
−0.62 to 0.88b
IFG, superior temporal gyrus,
supramarginal gyrus, angular
gyrus, middle frontal gyrus,
cingulate gyrus, insula, middle
occipital gyrus, superior parietal lobule
(visual and auditory)
and BA45and BA22
Temporal, fusiform, and frontal
Inferior and middle frontal gyrus,
Frontal, temporal, parietal
Neuropsychol Rev (2007) 17:491–504495
Table 2 (continued)
Inferior frontal gyrus
Inferior frontal gyrus
Different regions activated
for Left and right TLE patients
Inferior frontal gyrus, middle
and superior frontal gyri, preand post central gyri,
supplementary area, inferior
middle and superior temporal gyri
IFG, MFG, middle and superior
Covert word chain
The n includes only those with valid fMRI and IAT
IAT Intracarotid sodium amobarbital test, IFG Inferior frontal gyrus, MFG medial inferior frontal gyrus, ROI regions of interest, SMA supplementary motor area, TLE temporal lobe epilepsy.
aLanguage dominance was assessed using IAT in 12 patients and electrocortical stimulation in 11 patients.
bCorrelations between IAT and fMRI varied by ROI and task (18 correlations were reported).
cLanguage dominance was assessed using IAT in four patients and electrocortical stimulation in four patients
dTwenty-nine patients had atypical language, but it was not specified if dominance was right or bilateral. Also, all 100 had IAT, but six had an artifactual fMRI.
eFourteen patients had atypical language, but it was not specified if dominance was right or bilateral.
496 Neuropsychol Rev (2007) 17:491–504
formula VL? VR
are activation volumes for the left and right hemispheres.
Functional magnetic resonance imaging studies using
quantitative indexes of activated language voxels in
neurologically normal individuals and epilepsy patients
have demonstrated a continuum of language distribution
with a higher incidence of atypical (bilateral or right)
hemisphere language representation in both adult (Berl
et al. 2005; Springer et al. 1999) and pediatric (Yuan et al.
2006) epilepsy patients relative to neurologically normal
controls. Springer and colleagues’ study of 50 right-handed
epilepsy patients and 100 neurologically normal individuals
found that 78% of the epilepsy patients were left hemi-
sphere dominant, 16% had bilateral language and 6% were
right hemisphere dominant for language. When the epilepsy
group was separated into those with onset of epilepsy or
brain injury prior to age five versus those whose epilepsy or
brain injury occurred after age five, the language domi-
nance patterns from fMRI were fairly similar to those
reported in previous studies examining dominance patterns
based on IAT (Rasmussen and Milner 1977), though
bilateral language is reported at a higher rate with fMRI
(See Table 3). Studies have shown that atypical language
dominance is associated with left-handedness or weaker
right hand dominance, having first degree biological
relatives who are left-handed, left extra-temporal epilepsy,
left lesion or left-sided seizure focus, and earlier age at
onset of seizures or brain injury (Berl et al. 2005; Springer
et al. 1999; Szaflarski et al. 2002; Weber et al. 2006;
Woermann et al. 2003).
The first published study comparing fMRI and IAT was
conducted using a frontal lobe ROI in seven patients, six of
whom had undergone anterior temporal lobectomy (Desmond
½?= VLþ VR
½ ? ? 100, where VL and VR
et al. 1995). Epilepsy patients performed a semantic
judgment task contrasted with a perceptual judgment task
using visually presented abstract and concrete nouns pre-
sented in either lower or upper case. The task was to press a
button for abstract or concrete nouns in one condition and to
press for upper or lower case in the control condition. The
stimulus characteristics of the tasks are perfectly matched,
and the task includes behavioral monitoring. The control task
may inadvertently result in some language activation since
the patients likely automatically read the text while making
the perceptual judgment, though more semantic activity
would be expected in the semantic judgment task. Activation
was seen in the inferior frontal gyrus and orbital cortex
corresponding to Brodmann’s areas 45, 46, and 47. The sum
of the functional activation values was used to compute a
lateralization index for each patient. Four patients had left
and three had right hemisphere dominance based on IAT, and
100% concordance was found between IAT and fMRI. In a
study of pre-surgical epilepsy patients who underwent whole
brain imaging, a high correlation (r=0.96) and 100%
concordance was found between fMRI LIs and IAT LIs
(Binder et al. 1996). Most studies have not computed
laterality indexes for IAT, and some have only conducted
visual analyses of the activation on fMRI. However, in this
study the IAT LIs were computed from scores on measures
of language comprehension, naming, repetition, reading and
a rating of paraphasic errors during each injection. The IAT
LI was the difference [PL−PR] where PLand PRare the
percentage scores based on correct responses during the IAT
language tasks. Activation on fMRI was observed primarily
in lateral frontal lobe, temporal lobe, and temporal–parietal–
occipital junction. More specifically, activation was observed
in inferior and middle frontal gyri, superior precentral sulcus,
superior frontal gyrus and sulcus, angular gyrus, posterior
inferior temporal gyrus, fusiform gyrus, posterior superior
temporal sulcus, and middle temporal gyrus. Frontal areas of
activation are similar to those reported by Desmond et al.
The largest study to date comparing IAT and fMRI,
conducted by Woermann et al. (2003), included 100
epilepsy patients (71 left language dominant, 29 atypical
dominance) who performed a covert fluency task alternat-
ing with rest in a block design. Images were visually
inspected for asymmetries; no voxel counts or lateralization
indexes were calculated. The concordance between IAT and
fMRI was 91%. Five patients found to have left hemisphere
dominance on IAT had bilateral language on fMRI, and
three patients with bilateral or right hemisphere language on
IAT had left language dominance on fMRI. In addition,
25% of the patients with left-sided extratemporal epilepsy
were falsely categorized with fMRI.
A number of studies have compared IAT and fMRI using
covert fluency tasks alternating with rest (Hertz-Pannier et al.
Table 3 Rates of language dominance in right-handed subjects based
on fMRI and IAT
et al. 1999
Early brain injury
No early brain injury
Early brain Injury
No early brain injury
1977 817 12
fMRI Functional magnetic resonance imaging, IAT intracarotid sodium
Reprinted from (Springer et al. 1999)
Neuropsychol Rev (2007) 17:491–504497
1997; Woermann et al. 2003; Worthington et al. 1997; Yetkin
et al. 1998) with generally good concordance or correlation
(Yetkin et al. 1998). Concordance was low in one study
(55%), and the authors acknowledged that this may have
been related to their language paradigm (Worthington et al.
1997). Yet other studies reported good concordance with a
similar task (Hertz-Pannier et al. 1997). In general the
fluency or word generation tasks have shown reasonable
concordance with IAT but activation is predominantly
frontal. In an effort to obtain more temporal lobe activation,
Gaillard et al. (2002) designed a reading responsive naming
task (name an object described by a written phrase) that
alternated with a visual perceptual control task. They found
left lateralized activation in the inferior and middle frontal
gyri and in the posterior temporal lobe, with a concordance
rate between fMRI and IAT of 83% and somewhat greater
discordance in those with atypical language on IAT or fMRI.
Concordance Rates Differ by ROI Concordance rates
between fMRI and IAT may differ depending on the task
used as well as the region of interest. Several studies have
reported higher concordance rates using frontal rather than
temporoparietal ROIs (Benke et al. 2006; Deblaere et al.
2004; Spreer et al. 2002). Deblaere et al. (2004) examined
the concordance between IAT and fMRI LIs from various
ROIs including whole hemisphere, frontal and temporal–
parietal using a 1.0 Tesla magnet. They used a covert word
chain task where subjects were instructed to generate a list
of words starting with the last letter of the previous word.
This language task alternated with covert counting. Con-
cordance was 100% for fMRI and IAT using a frontal ROI.
This included 15 patients found to have left hemisphere
dominance for language on IAT and two who were bilateral
on IAT. The concordance was lower using a whole
hemisphere or temporal–parietal ROI, with patients who
were bilateral on IAT more likely to be classified as right
dominant with fMRI. Using a semantic decision task
alternating with a color discrimination task, higher concor-
dance between IAT and fMRI was found in frontal (100%)
compared to temporoparietal regions (91%) (Spreer et al.
2002). The discordant cases were both patients with
atypical language on IAT (one right and one bilateral)
who appeared to have left language based on the tempor-
oparietal ROI. Another study found that fMRI and IAT
scores were more highly correlated in frontal than temporal
ROIs using both covert semantic fluency and story listening
tasks (Lehericy et al. 2000). Carpentier et al. (2001) found
modality specific activation patterns when comparing
visual and auditory semantic decision tasks. The visual
semantic decision task resulted in more lateralized frontal
activation compared to the auditory task.
As noted above, a number of studies report better
concordance between IAT and fMRI in frontal regions of
interest but this may be function of the language task
selected. Most language tasks do not produce robust
anterior temporal lobe activation, the region typically
resected in epilepsy surgery. A series of studies by
Hamberger and colleagues demonstrated that auditory
responsive naming sites are located anterior to visual
picture naming sites in the temporal lobe using electro-
cortical stimulation mapping (see Hamberger article from
this issue) (Hamberger et al. 2001, 2007). Furthermore,
these authors noted that sparing of visual naming sites did
not prevent post-operative naming decline while resection
or sparing of auditory naming sites was associated with
post-operative naming outcome (Hamberger et al. 2005). In
an effort to obtain better anterior temporal lobe activation
and based on the findings of topographically distinct
modality specific naming sites, an fMRI responsive naming
task was developed at our center (Hammeke et al. 2003). A
clustered acquisition scanning protocol was used that
allows patients to orally name nouns in response to brief
auditory definitions (e.g., “What a king wears on his
head”). This task is contrasted with an auditory discrimina-
tion task that also requires a verbal response. Preliminary
findings indicate that the language LIs derived from this
responsive naming task are highly correlated with LIs
naming task produced more extensive activation of the
anterior temporal lobes than the semantic decision task.
Gaillard et al. (2004) noted that previous studies have
found discordance between IAT and fMRI in approximately
10% of epilepsy patients. Several authors have suggested
that the discordance rate between IAT and fMRI can be
reduced by using a panel of language tasks (Gaillard et al.
2004; Rutten et al. 2002). Agreement between IAT and
fMRI using a visual clinical rating of the activation images
was improved using a panel of language tasks designed to
activate different language functions. Some studies employ-
ing multiple language tasks with rest or non-perceptually
matched control tasks or a limited number of runs may be
more likely to note improved concordance when the results
of multiple tasks are combined as this increases their
One issue with determining the concordance between
IAT and fMRI is that most investigators typically assume
that fMRI is inaccurate when discordance occurs. There is
room for error in the IAT, for example in association with
abnormal vasculature (Hietala et al. 1990), obtundation or
reduced level of arousal (Malmgren et al. 1992), persever-
ation, dysarthria, abulia, and other behavioral disturbances
that can interfere with language assessment and result in
false positive language errors. Conversely, early motor
return or short drug effect may result in over-interpreting
the presence of language. Thus, the discordance or error
rate between the two methods can be related to measure-
498 Neuropsychol Rev (2007) 17:491–504
ment error with either method. This issue can be addressed
by examining the degree to which IAT or fMRI is better
able to predict language outcome, as discussed below.
Hemispheric language representation as determined by
fMRI has been compared to the results of extra- and intra-
operative cortical stimulation mapping (Carpentier et al.
2001) with concordance reported in seven of seven cases.
However, this comparison is limited because the region of
electrode coverage is typically limited to only a portion of
Concordance and Atypical Language Another issue affect-
ing concordance rates between IAT and fMRI involves
dichotomizing (left versus atypical language) or trichoto-
mizing (left, right, bilateral language) a continuous variable.
Bilateral language is on a continuum that is not easy to
demarcate. Further, some patients with atypical or bilateral
language will have dissociations between the hemispheres
in what are traditionally considered anterior and posterior
language functions (Kurthen et al. 1992; Risse et al. 1997).
The utility of fMRI for mapping language in individuals
with atypical language or right hemisphere dominance has
been questioned (Bookheimer 1996). Some authors have
suggested that a panel of language tasks results in improved
concordance between IAT and fMRI in patients with
atypical language representation (Gaillard et al. 2004;
Rutten et al. 2002). These authors have noted that while
fMRI and IAT may be highly correlated, fMRI as a
predictor of language dominance in individual patients has
not been demonstrated. One could argue that this has been
demonstrated based on the studies of concordance rates
between fMRI and IAT as well as by the fact that fMRI
language LIs have been shown to predict language outcome
(Sabsevitz et al. 2003).
Nevertheless, because most studies have included only a
limited number of patients with atypical language domi-
nance,investigators have questioned theaccuracy offMRI in
patients with right or bilateral language. Using a multi-task
language protocol in patients with temporal lobe epilepsy,
Rutten et al. (2002) found concordance rates of 91, 75 and
67% respectively in patients who had left (n=11), bilateral
(n=4), or right (n=3) language dominance. Concordance
rates thus appear to be lower in those with atypical
language, though sample sizes were very small in this
study. When the patients with atypical language in the
Gaillard study are examined, 13 were left on IATand fMRI,
2 were bilateral on IAT and left on fMRI, and one was left
on IAT and bilateral on fMRI (Gaillard et al. 2002).
Therefore all of the patients with atypical language on
IAT had results that were discordant with fMRI. Adcock et
al. (2003) found that two of 19 patients were discordant
between IAT and fMRI. Of these two, one had bilateral
language on IAT but was left dominant on fMRI, and one
was left dominant by IAT but bilateral on fMRI. The
concordance rates were 89% for the whole group, 93% for
patients who are left dominant on IAT, and 75% for the
three patients with atypical language. Some findings of
discordance could be spurious depending on the LI cutting
score used. For example, if a cutting score of +30 to −30 is
used for bilateral language and a patient has a score of 30
on fMRI and 33 on IAT, they technically could be
Those with atypical language in other studies had the
same concordance rates as those with left language
dominance (Binder et al. 1996; Desmond et al. 1995;
Hertz-Pannier et al. 1997; Liegeois et al. 2002). Further, in
the largest IAT fMRI comparison to date, the discordance
rates were 10% for the patients with atypical language and
7% for the patients with left dominance (Woermann et al.
2003) suggesting that fMRI has utility for assessing
language localization in patients with bilateral or right
hemisphere language dominance.
Several areas that need further investigation include (1)
scrutiny of cases where IAT and fMRI are discordant; (2)
comparisons between maps obtained from fMRI and
cortical stimulation (either intra-operatively or with extra-
operative grid mapping) as has been conducted with tumor
patients (Lurito et al. 2000); (3) examination of the
concordance and correlation differences between different
ROIs relative to task selection; and (4) examination of the
concordance rates or correlations between fMRI and IAT in
a large series of patients who show atypical language
dominance on either IAT or fMRI. Despite the instances of
discordance, fMRI is a reasonable alternative for determin-
ing lateralization of language in individual patients prior to
Language Plasticity and Reorganization
Language plasticity may be studied by examining organi-
zation of language following lesions of different types and
locations, and lesions occurring at different ages (Ewing-
Cobbs et al. 2003). Functional magnetic resonance imaging
language maps in patients with seizure onset or injury to the
left hemisphere at different ages provides information about
plasticity and the manner of reorganization of function.
Second, conducting serial fMRI scanning prior to and
following a known lesion (e.g., temporal lobectomy)
provides the opportunity to watch recovery and potentially
learn about neural plasticity. For example, patients with
post-stroke aphasia have been followed with serial fMRI
during their recovery, with imaging revealing dynamic
changes in brain activation over time that was not present in
control subjects (Fernandez et al. 2004).
Neuropsychol Rev (2007) 17:491–504499
Patients with early onset epilepsy may experience intra-
or interhemispheric reorganization of language, particularly
when the epilepsy or initial precipitating event encom-
passed a large region in the language dominant hemisphere.
As previously noted, earlier age of insult is associated with
more bilateral or rightward shift of language, supporting the
notion of an early critical window period for reorganization.
Swanson and colleagues (Swanson et al. 2002), using a
semantic decision fMRI paradigm, showed that age at onset
of seizures was correlated with the degree of language
lateralization only in patients with left hemisphere seizures.
Early onset seizures in the left hemisphere were associated
with more atypical or right hemisphere representation of
language. Examination of the group fMRI maps revealed
that language reorganized to contralateral homologous
regions in the frontal and posterior temporal parietal
heteromodal regions in those with early left hemisphere
seizures. Functional magnetic resonance imaging studies
using other language activation paradigms, such as covert
verbal fluency (Adcock et al. 2003; Brazdil et al. 2005;
Janszky et al. 2006; Sabbah et al. 2003) or object naming in
response to a sentence description of the object (Berl et al.
2005), have also shown higher rates of atypical or
rightward lateralization of language in patients with left
FMRI has also been shown to be useful in examining
intra hemispheric language reorganization. Liegeois et al.
(2004) reported on a small group of children with
intractable epilepsy who sustained early left hemisphere
lesions either adjacent to or remote from classic language
regions. They found that language functions, as identified
by a verb generation fMRI task, did not always shift to the
contralateral hemisphere. In this study, four of five patients
with lesions in or near Broca’s area showed peri-lesional
activation within the damaged left hemisphere rather than
interhemispheric shift. One advantage of fMRI over IAT is
the ability to provide data on intrahemispheric reorganiza-
FMRI can also be used to examine mechanisms of
neuroplasticity in post-surgical epilepsy patients. Hertz-
Pannier et al. (2002) scanned a child with intractable
seizures secondary to Rasmussen’s syndrome both before
and 1.5 years after left hemispherectomy at age nine. The
child acquired normal language prior to his surgery, and
preoperative fMRI using a covert semantic fluency task
relative to rest revealed strong left lateralization of language
functions. The child developed a profound aphasia and
alexia following the surgery but regained a substantial
degree of language (comprehension more so than speech
production) over time. Postoperative fMRI using covert
semantic fluency, sentence generation, and passive sentence
listening relative to rest showed a shift of language
functions to the right hemisphere in regions not previously
detected on his preoperative scan. Activation was found in
homologous right hemisphere regions, including inferior
frontal, temporal, and parietal cortex.
The ability to use fMRI data to predict language and memory
morbidity is a powerful new pre-surgical use for fMRI.
Several studies have shown that the degree of preoperative
activation asymmetry in the hippocampus or in medial
temporal lobe predicted decline in scene recognition (Rabin
et al. 2004) and verbal memory (Richardson et al. 2004)
following surgery. Only one study to date has examined the
validity of fMRI language LIs for predicting language
morbidity after epilepsy surgery (Sabsevitz et al. 2003).
Dysnomia, or impaired naming, is a common cognitive
complication of dominant temporal lobectomy (Bell et al.
2000; Davies et al. 1998; Hermann et al. 1999; Langfitt and
Rausch 1996; Ruff et al. 2007; Stafiniak et al. 1990). The
ability to identify epilepsy patients at greatest risk for post-
operative naming decline has important clinical implica-
tions to not only the patient but also to the treatment team
during the pre-surgical planning stage. Historically, clinical
variables, such as age at onset of epilepsy or age at first
neurologic insult, have been used to predict naming
outcome following dominant temporal resection (Hermann
et al. 1999; Ruff et al. 2007; Saykin et al. 1995; Stafiniak
et al. 1990). Left temporal lobe epilepsy patients with
earlier age at onset have been shown to be at lower risk for
language decline following surgery than patients with later
age at onset, presumably because they have a greater
opportunity to “shift” language to the non-surgical hemi-
sphere. Better pre-surgical naming performance has also
been shown to predict poorer language outcome following
dominant temporal resection (Hermann et al. 1994). One
possible explanation for this relationship is that preopera-
tive naming performance serves as an indirect measure of
the functional integrity of the to-be-resected temporal lobe,
with better pre-operative performance indicating the pres-
ence of more functional or intact tissue. The presence of
more viable language tissue pre-operatively increases the
likelihood that it will be removed during surgery, resulting
in greater post-operative language decline. In addition to
these clinical variables, clinicians often rely on IAT
language testing to identify those patients at risk for
developing postoperative language complications. Intra-
carotid amobarbital language testing is based on the
assumption that lateralization of language toward the
surgical hemisphere places a patient at greater risk for
language decline following dominant temporal resection
than if language is lateralized to the non-surgical hemi-
sphere. While there are anecdotal reports that patients with
500 Neuropsychol Rev (2007) 17:491–504
right hemisphere language dominance do not decline
following left temporal lobectomy, there has been only
one study to date that has formally examined the predictive
power of IAT laterality scores and language outcome in this
patient group (Sabsevitz et al. 2003). This study found that
IAT language laterality scores were in fact predictive of
naming outcome following left temporal lobectomy (r=
One advantage that fMRI has over IAT in predicting
intrahemispheric localization of language. The ability to
localize language within a given hemisphere or more ideally
within the to-be-resected temporal lobe can provide valuable
information to the neurosurgeon when planning the surgical
boundaries. Sabsevitz et al. (2003) examined the clinical
utility of preoperative fMRI in predicting postoperative
naming outcome following left anterior temporal lobectomy.
In this study, 24 patients with left temporal lobe epilepsy
underwent preoperative fMRI language mapping and both
pre- and six-month-postoperative neuropsychological testing
were examined. Preoperative fMRI language mapping used a
semantic decision paradigm alternating with a tone decision
task as depicted in Table 1 and described above. The degree
of fMRI language lateralization in the temporal lobe
significantly predicted naming outcome. That is, stronger
lateralization toward the surgical temporal lobe was associ-
ated with greater postoperative decline on the Boston
Naming Test (r=−0.64, p<0.001; see Figs. 2, and 3).
Preoperative fMRI accounted for 41% of the variance in
predicting naming outcome. Language lateralization in
frontal and parietal ROIs was also predictive of naming
outcome, but the temporal lobe ROI was more predictive.
Using the temporal lobe ROI, fMRI showed 100% sensitiv-
ity and 73% specificity in predicting significant naming
decline (i.e., >2 SD decline as compared to a right temporal
lobectomy control group). IAT also predicted naming
outcome in these patients (92% sensitivity and 45%
specificity) but not as well as fMRI. Using multiple
regression analysis, both fMRI and IAT were found to be
more predictive of naming outcome than age at seizure onset
and preoperative naming status. The findings from this study
suggest that fMRI can be used to stratify patients in terms of
risk, potentially allowing patients and physicians to more
accurately weigh the risks and benefits of surgery.
The ultimate test of fMRI is the usefulness of the activation
maps for guiding the surgical boundaries. While language
lateralization toward the surgical temporal lobe has been
found to be predictive of naming outcome (Sabsevitz et al.
Fig. 2 TherelationshipbetweenanfMRItemporal lobelateralityindex
and Boston Naming Test outcome. Reprinted from (Sabsevitz et al.
2003). fMRI = functional magnetic resonance imaging
Fig. 3 Activation maps and corresponding naming decline in raw
score points for three different patients who underwent left anterior
temporal lobectomy. BNT = Boston Naming test, LI = lateral index
Neuropsychol Rev (2007) 17:491–504 501
2003), no studies to date have specifically examined
whether surgical removal of activated voxels in and/or near
the surgical cavity predicts outcome. Several scenarios are
possible with regard to resection of brain tissue in the
context of fMRI. First, if resection of activated voxels
correlates with cognitive decline, then it can be assumed
that these voxels are critical for the cognitive function in
question and should be avoided, if possible, during surgical
planning. If resection of activated voxels does not correlate
with cognitive outcome, then it can be assumed that these
voxels are either involved but not critical for a given
cognitive function or perhaps represent false positive
activation due to inadequate control of non-essential
cognitive functions. The other question is whether tissue
that shows no activation can be safely removed. Distinction
between activated voxels that are critical versus expendable
can be determined by examining language and memory
decline relative to the number of activated voxels resected
and by comparing cognitive morbidity across randomly
assigned groups for whom the neurosurgeon operates with
or without the guidance of fMRI language maps. The use of
fMRI language maps to tailor resections still requires
Integration systems that co-register three-dimensional
fMRI images and extra-operative stimulation maps are being
developed to aid in surgical planning (O’Shea et al. 2006).
New research combining data from different imaging
methods, such as fMRI and event-related potential data
(Calhoun et al. 2006) or fMRI and diffusion weighted
imaging tractography (Aron et al. 2007), or, in the future,
perhaps fMRI and magnetic source imaging may provide
more powerful combinations of mapping data. Such combi-
nations integrating the best features of each imaging method
may be useful for further delineating functional networks.
cal Diseases and Stroke grant R01 NS35929, National Institutes of
Health General Clinical Research Center grant M01 RR00058,
National Research Service Award Fellowship F32 MH11921, and
the Charles A. Dana Foundation.
Supported by National Institute of Neurologi-
Adcock, J. E., Wise, R. G., Oxbury, J. M., Oxbury, S. M., & Matthews,
P. M. (2003). Quantitative fMRI assessment of the differences in
lateralization of language-related brain activation in patients with
temporal lobe epilepsy. NeuroImage, 18(2), 423–438.
Aron, A. R., Behrens, T. E., Smith, S., Frank, M. J., & Poldrack, R. A.
(2007). Triangulating a cognitive control network using diffu-
sion-weighted magnetic resonance imaging (MRI) and functional
MRI. Journal of Neuroscience, 27(14), 3743–3752.
Baciu, M., Kahane, P., Minotti, L., Charnallet, A., David, D., Le Bas,
J. F., et al. (2001). Functional MRI assessment of the hemispheric
predominance for language in epileptic patients using a simple
rhyme detection task. Epileptic Disorders, 3(3), 117–124.
Bahn, M. M., Lin, W., Silbergeld, D. L., Miller, J. W., Kuppusamy,
K., Cook, R. J., et al. (1997). Localization of language cortices
by functional MR imaging compared with intracarotid amobar-
bital hemispheric sedation. American Journal of Roentgenology,
Bell, B. D., Davies, K. G., Hermann, B. P., & Walters, G. (2000).
Confrontation naming after anterior temporal lobectomy is
related to age of acquisition of the object names. Neuro-
psychologia, 38(1), 83–92.
Bellgowan, P. S., Binder, J. R., Swanson, S. J., Hammeke, T. A.,
Springer, J. A., Frost, J. A., et al. (1998). Side of seizure focus
predicts left medial temporal lobe activation during verbal
encoding. Neurology, 51(2), 479–484.
Benke, T., Koylu, B., Visani, P., Karner, E., Brenneis, C., Bartha, L.,
et al. (2006). Language lateralization in temporal lobe epilepsy:
A comparison between fMRI and the Wada Test. Epilepsia, 47
Benson, R. R., FitzGerald, D. B., LeSueur, L. L., Kennedy, D. N.,
Kwong, K. K., Buchbinder, B. R., et al. (1999). Language
dominance determined by whole brain functional MRI in patients
with brain lesions. Neurology, 52(4), 798–809.
Berl, M. M., Balsamo, L. M., Xu, B., Moore, E. N., Weinstein, S. L.,
Conry, J. A., et al. (2005). Seizure focus affects regional language
networks assessed by fMRI. Neurology, 65(10), 1604–1611.
Binder, J. R. (2003). Now you see it now you don’t. Epilepsy &
Behavior, 4(1), 91–92.
Binder, J. R., Frost, J. A., Hammeke, T. A., Bellgowan, P. S., Rao, S.
M., & Cox, R. W. (1999). Conceptual processing during the
conscious resting state. A functional MRI study. Journal of
Cognitive Neuroscience, 11(1), 80–95.
Binder, J. R., Frost, J. A., Hammeke, T. A., Cox, R. W., Rao, S. M., &
Prieto, T. (1997). Human brain language areas identified by
functional magnetic resonance imaging. Journal of Neuroscience,
Binder, J. R., Hammeke, T. A., & Possing, E. T. (2001). Reliability
and validity of language dominance assessment with functional
MRI. Neurology, 56(Suppl. A), 158.
Binder, J. R., Rao, S. M., Hammeke, T. A., Frost, J. A., Bandettini, P. A.,
Jesmanowicz, A., et al. (1995). Lateralized human brain language
systems demonstrated by task subtraction functional magnetic
resonance imaging. Archives of Neurology, 52(6), 593–601.
Binder, J. R., Swanson, S. J., Hammeke, T. A., Morris, G. L., Mueller,
W. M., Fischer, M., et al. (1996). Determination of language
dominance using functional MRI: A comparison with the Wada
test. Neurology, 46(4), 978–984.
Bookheimer, S. Y. (1996). Functional MRI applications in clinical
epilepsy. NeuroImage, 4(3 Pt 3), S139–S146.
Brazdil, M., Chlebus, P., Mikl, M., Pazourkova, M., Krupa, P., &
Rektor, I. (2005). Reorganization of language-related neuronal
networks in patients with left temporal lobe epilepsy—An fMRI
study. European Journal of Neurology, 12(4), 268–275.
Calhoun, V. D., Adali, T., Pearlson, G. D., & Kiehl, K. A. (2006).
Neuronal chronometry of target detection: Fusion of hemodynamic
and event-related potential data. NeuroImage, 30(2), 544–553.
Carpentier, A., Pugh, K. R., Westerveld, M., Studholme, C., Skrinjar,
O., Thompson, J. L., et al. (2001). Functional MRI of language
processing: Dependence on input modality and temporal lobe
epilepsy. Epilepsia, 42(10), 1241–1254.
Davies, K. G., Bell, B. D., Bush, A. J., & Wyler, A. R. (1998).
Prediction of verbal memory loss in individuals after anterior
temporal lobectomy. Epilepsia, 39(8), 820–828.
Deblaere, K., Boon, P. A., Vandemaele, P., Tieleman, A., Vonck, K.,
Vingerhoets, G., et al. (2004). MRI language dominance
assessment in epilepsy patients at 1.0 T: Region of interest
502Neuropsychol Rev (2007) 17:491–504
analysis and comparison with intracarotid amytal testing.
Neuroradiology, 46(6), 413–420.
Demonet, J. F., Chollet, F., Ramsay, S., Cardebat, D., Nespoulous, J. L.,
Wise, R., et al. (1992). The anatomy of phonological and semantic
processing in normal subjects. Brain, 115(Pt 6), 1753–1768.
Desmond, J. E., Sum, J. M., Wagner, A. D., Demb, J. B., Shear, P. K.,
Glover, G. H., et al. (1995). Functional MRI measurement of
language lateralization in Wada-tested patients. Brain, 118(Pt 6),
Detre, J. A., Maccotta, L., King, D., Alsop, D. C., Glosser, G.,
D’Esposito, M., et al. (1998). Functional MRI lateralization of
memory in temporal lobe epilepsy. Neurology, 50(4), 926–932.
Ewing-Cobbs, L., Barnes, M. A., & Fletcher, J. M. (2003). Early brain
injury in children: Development and reorganization of cognitive
function. Developmental Neuropsychology, 24(2–3), 669–704.
Fernandez, B., Cardebat, D., Demonet, J.-F., Joseph, P. A., Mazaux,
J.-M., Barat, M., et al. (2004). Functional MRI follow-up study
of language processes in healthy subjects and during recovery in
a case of aphasia. Stroke, 35(9), 2171–2176.
(2003). Intrasubject reproducibility of presurgical language lateraliza-
tion and mapping using fMRI. Neurology, 60(6), 969–975.
Gaillard, W. D., Balsamo, L., Xu, B., Grandin, C. B., Braniecki, S. H.,
Papero, P. H., et al. (2002). Language dominance in partial
epilepsy patients identified with an fMRI reading task. Neurology,
Gaillard, W. D., Balsamo, L., Xu, B., McKinney, C., Papero, P. H.,
Weinstein, S., et al. (2004). fMRI language task panel improves
determination of language dominance.Neurology, 63(8), 1403–1408.
Golby, A. J., Poldrack, R. A., Illes, J., Chen, D., Desmond, J. E., &
Gabrieli, J. D. E. (2002). Memory lateralization in medial
temporal lobe epilepsy assessed by functional MRI. Epilepsia,
Hamberger, M. J., Goodman, R. R., Perrine, K., & Tamny, T. (2001).
Anatomic dissociation of auditory and visual naming in the
lateral temporal cortex. Neurology, 56(1), 56–61.
Hamberger, M. J., McClelland, S. 3rd, McKhann, G. M. 2nd,
Williams, A. C., & Goodman, R. R. (2007). Distribution of
auditory and visual naming sites in nonlesional temporal lobe
epilepsy patients and patients with space-occupying temporal
lobe lesions. Epilepsia, 48(3), 531–538.
Hamberger, M. J., Seidel, W. T., McKhann, G. M. 2nd, Perrine, K., &
Goodman, R. R. (2005). Brain stimulation reveals critical
auditory naming cortex. Brain, 128(Pt 11), 2742–2749.
Hammeke, T. A., Bellgowan, P. S., & Binder, J. R. (2000). fMRI:
Methodology—Cognitive function mapping. In T. R. Henry, J. S.
Duncan&S.F.Berkovic(Eds.),Functional imaging in the epilepsies
(pp 221–233). Philadelphia: Lippincott Williams & Wilkins.
Hammeke, T. A., Swanson, S. J., Possing, E., Kortenkamp, S.,
Kilderman, J., & Binder, J. R. (2003). Functional MRI activation
of the anterior temporal lobe using a definition naming task.
Journal of the International Neuropsychological Society, 9, 322.
Harrington, G. S., Buonocore, M. H., & Farias, S. T. (2006).
Intrasubject reproducibility of functional MR imaging activation
in language tasks. American Journal of Neuroradiology, 27(4),
Hermann, B. P., Perrine, K., Chelune, G. J., Barr, W., Loring, D. W.,
Strauss, E., et al. (1999). Visual confrontation naming following
left anterior temporal lobectomy: A comparison of surgical
approaches. Neuropsychology, 13(1), 3–9.
Hermann, B. P., Wyler, A. R., Somes, G., & Clement, L. (1994).
Dysnomia after left anterior temporal lobectomy without func-
tional mapping: Frequency and correlates. Neurosurgery, 35(1),
52–56 (discussion 56–57).
Hertz-Pannier, L., Chiron, C., Jambaque, I., Renaux-Kieffer, V., Van
de Moortele, P.-F., Delalande, O., et al. (2002). Late plasticity for
language in a child’s non-dominant hemisphere: A pre- and post-
surgery fMRI study. Brain, 125(Pt 2), 361–372.
Hertz-Pannier, L., Gaillard, W. D., Mott, S. H., Cuenod, C. A.,
Bookheimer, S. Y., Weinstein, S., et al. (1997). Noninvasive
assessment of language dominance in children and adolescents
with functional MRI: A preliminary study. Neurology, 48(4),
Hietala, S. O., Silfvenius, H., Aasly, J., Olivecrona, M., & Jonsson, L.
(1990). Brain perfusion with intracarotid injection of 99mTc-
HM-PAO in partial epilepsy during amobarbital testing. Europe-
an Journal of Nuclear Medicine, 16(8–10), 683–687.
Jansen, A., Menke, R., Sommer, J., Forster, A. F., Bruchmann, S.,
Hempleman, J., et al. (2006). The assessment of hemispheric
lateralization in functional MRI—Robustness and reproducibility.
NeuroImage, 33(1), 204–217.
Janszky, J., Mertens, M., Janszky, I., Ebner, A., & Woermann, F. G.
(2006). Left-sided interictal epileptic activity induces shift of
language lateralization in temporal lobe epilepsy: An fMRI study.
Epilepsia, 47(5), 921–927.
Jezzard, P., & Clare, S. (1999). Sources of distortion in functional
MRI data. Human Brain Mapping, 8(2–3), 80–85.
Jokeit, H., Okujava, M., & Woermann, F. G. (2001a). Carbamazepine
reduces memory induced activation of mesial temporal lobe
structures: A pharmacological fMRI-study. BMC Neurology, 1, 6.
Jokeit, H., Okujava, M., & Woermann, F. G. (2001b). Memory fMRI
lateralizes temporal lobe epilepsy. Neurology, 57(10), 1786–1793.
Killgore, W. D., Glosser, G., Casasanto, D. J., French, J. A., Alsop,
D. C., & Detre, J. A. (1999). Functional MRI and the Wada test
provide complementary information for predicting post-operative
seizure control. Seizure, 8(8), 450–455.
Koylu, B., Trinka, E., Ischebeck, A., Visani, P., Trieb, T., Kremser, C.,
et al. (2006). Neural correlates of verbal semantic memory in
patients with temporal lobe epilepsy. Epilepsy Research, 72(2–3),
Kurthen, M., Helmstaedter, C., Linke, D. B., Solymosi, L., Elger,
C. E., & Schramm, J. (1992). Interhemispheric dissociation of
expressive and receptive language functions in patients with
complex-partial seizures: An amobarbital study. Brain and
Language, 43(4), 694–712.
Kwong, K., Belliveau, J., & Chesler, D. (1992). Dynamic magnetic
resonance imaging of human brain activity during primary
sensory stimulation. Proceedings of the National Academy of
Sciences of the United States of America, 89, 5675–5679.
anterotemporal lobectomy. Archives of Neurology, 53(1), 72–76.
Lehericy, S., Cohen, L., Bazin, B., Samson, S., Giacomini, E.,
Rougetet, R., et al. (2000). Functional MR evaluation of temporal
and frontal language dominance compared with the Wada test.
Neurology, 54(8), 1625–1633.
Liegeois, F., Connelly, A., Cross, J. H., Boyd, S. G., Gadian, D. G.,
Vargha-Khadem, F., et al. (2004). Language reorganization in
children with early-onset lesions of the left hemisphere: An fMRI
study Brain, 127(Pt 6), 1229–1236.
Liegeois, F., Connelly, A., Salmond, C. H., Gadian, D. G., Vargha-
Khadem, F., & Baldeweg, T. (2002). A direct test for lateraliza-
tion of language activation using fMRI: Comparison with
invasive assessments in children with epilepsy. NeuroImage, 17
Lurito, J. T., Lowe, M. J., Sartorius, C., & Mathews, V. P. (2000).
Comparison of fMRI and intraoperative direct cortical stimula-
tion in localization of receptive language areas. Journal of
Computer Assisted Tomography, 24(1), 99–105.
Maldjian, J. A., Laurienti, P. J., Driskill, L., & Burdette, J. H. (2002).
Multiple reproducibility indices for evaluation of cognitive
functional MR imaging paradigms. American Journal of Neuro-
radiology, 23(6), 1030–1037.
Neuropsychol Rev (2007) 17:491–504 503
Malmgren, K., Bilting, M., Hagberg, I., Hedstrom, A., Silfvenius, H.,
& Starmark, J. E. (1992). A compound score for estimating the
influence of inattention and somnolence during the intracarotid
amobarbital test. Epilepsy Research, 12(3), 253–259.
McKiernan, K. A., D’Angelo, B. R., Kaufman, J. N., & Binder, J. R.
(2006). Interrupting the “stream of consciousness”: An fMRI
investigation. NeuroImage, 29(4), 1185–1191.
McKiernan, K. A., Kaufman, J. N., Kucera-Thompson, J., & Binder,
J. R. (2003). A parametric manipulation of factors affecting task-
induced deactivation in functional neuroimaging. Journal of
Cognitive Neuroscience, 15(3), 394–408.
Moonen, C., & Bandettini, P. (1999). Functional MRI. New York:
Narayan, V. M., Kimberg, D. Y., Tang, K. Z., & Detre, J. A. (2005).
Experimental design for functional MRI of scene memory
encoding. Epilepsy & Behavior, 6(2), 242–249.
Ogawa, S., Tank, D. W., Menon, R., Ellermann, J. M., Kim, S. G.,
Merkle, H., et al. (1992). Intrinsic signal changes accompa-
nying sensory stimulation: Functional brain mapping with
magnetic resonance imaging. Proceedings of the National
Academy of Sciences of the United States of America, 89(13),
O’Shea, J. P., Whalen, S., Branco, D. M., Petrovich, N. M., Knierim,
K. E., & Golby, A. J. (2006). Integrated image- and function-
guided surgery in eloquent cortex: A technique report. The
International Journal Of Medical Robotics and Computer
Assisted Surgery, 2(1), 75–83.
Powell, H. W. R., Koepp, M. J., Richardson, M. P., Symms, M. R.,
Thompson, P. J., & Duncan, J. S. (2004). The application of
functional MRI of memory in temporal lobe epilepsy: A clinical
review. Epilepsia, 45(7), 855–863.
Rabin, M. L., Narayan, V. M., Kimberg, D. Y., Casasanto, D. J.,
Glosser, G., Tracy, J. I., et al. (2004). Functional MRI predicts
post-surgical memory following temporal lobectomy. Brain, 127
(Pt 10), 2286–2298.
Rasmussen, T., & Milner, B. (1977). The role of early left-brain injury
in determining lateralization of cerebral speech functions. Annals
of the New York Academy of Sciences, 299, 355–369.
Richardson, M. P., Strange, B. A., Thompson, P. J., Baxendale, S. A.,
Duncan, J. S., & Dolan, R. J. (2004). Pre-operative verbal
memory fMRI predicts post-operative memory decline after left
temporal lobe resection. Brain, 127(Pt 11), 2419–2426.
bilateral language representation based on the intracarotid amobar-
bital procedure. Brain and Cognition, 33(1), 118–132.
Ruff, I. M., Swanson, S. J., Hammeke, T. A., Sabsevitz, D., Mueller,
W. M., & Morris, G. L. (2007). Predictors of naming decline
after dominant temporal lobectomy: Age at onset of epilepsy and
age of word acquisition. Epilepsy & Behavior, 10(2), 272–277.
Rutten, G. J. M., Ramsey, N. F., van Rijen, P. C., Alpherts, W. C.,& van
Veelen, C. W. M. (2002). FMRI-determined language lateraliza-
tion in patients with unilateral or mixed language dominance
according to the Wada test. NeuroImage, 17(1), 447–460.
Sabbah, P., Chassoux, F., Leveque, C., Landre, E., Baudoin-Chial, S.,
Devaux, B., et al. (2003). Functional MR imaging in assessment
of language dominance in epileptic patients. NeuroImage, 18(2),
Sabsevitz, D. S., Swanson, S. J., Hammeke, T. A., Spanaki, M. V.,
Possing, E. T., Morris, G. L. 3rd, et al. (2003). Use of
preoperative functional neuroimaging to predict language deficits
from epilepsy surgery. Neurology, 60(11), 1788–1792.
Saykin, A. J., Stafiniak, P., Robinson, L. J., Flannery, K. A., Gur,
R. C., O’Connor, M. J., et al. (1995). Language before and after
temporal lobectomy: Specificity of acute changes and relation to
early risk factors. Epilepsia, 36(11), 1071–1077.
Spreer, J., Arnold, S., Quiske, A., Wohlfarth, R., Ziyeh, S.,
Altenmuller, D., et al. (2002). Determination of hemisphere
dominance for language: Comparison of frontal and temporal
fMRI activation with intracarotid amytal testing. Neuroradiology,
Springer, J. A., Binder, J. R., Hammeke, T. A., Swanson, S. J., Frost,
J. A., Bellgowan, P. S., et al. (1999). Language dominance in
neurologically normal and epilepsy subjects: A functional MRI
study. Brain, 122(Pt 11), 2033–2046.
Stafiniak, P., Saykin, A. J., Sperling, M. R., Kester, D. B., Robinson,
L. J., O’Connor, M. J., et al. (1990). Acute naming deficits
following dominant temporal lobectomy: Prediction by age at 1st
risk for seizures. Neurology, 40(10), 1509–1512.
Stark, C. E., & Squire, L. R. (2001). When zero is not zero: The
problem of ambiguous baseline conditions in fMRI. Proceedings
of the National Academy of Sciences of the United States of
America, 98(22), 12760–12766.
Swanson, S. J., Binder, J. R., Possing, E. T., Hammeke, T. A.,
Sabsevitz, D. S., Spanaki, M., et al. (2002). FMRI language
laterality during a semantic decision task: Age of onset and side
of seizure focus effects. Journal of the International Neuropsy-
chological Society, 8, 222.
Szaflarski, J. P., Binder, J. R., Possing, E. T., McKiernan, K. A., Ward, B.
and ambidextrous people: fMRI data. Neurology, 59(2), 238–244.
Wada, J. (1949). A new method for determination of the side of cerebral
of sodium amytal in man. Igaku Seibutsugaku, 4, 221–222.
Weber, B., Wellmer, J., Schur, S., Dinkelacker, V., Ruhlmann, J.,
Mormann, F., et al. (2006). Presurgical language fMRI in patients
with drug-resistant epilepsy: Effects of task performance.
Epilepsia, 47(5), 880–886.
Woermann, F. G., Jokeit, H., Luerding, R., Freitag, H., Schulz, R.,
Guertler, S., et al. (2003). Language lateralization by Wada test and
fMRI in 100 patients with epilepsy. Neurology, 61(5), 699–701.
Worthington, C., Vincent, D. J., Bryant, A. E., Roberts, D. R., Vera,
C. L., Ross, D. A., et al. (1997). Comparison of functional
magnetic resonance imaging for language localization and intra-
carotid speech amytal testing in presurgical evaluation for
intractable epilepsy. Preliminary results. Stereotactic and Func-
tional Neurosurgery, 69(1–4 Pt 2), 197–201.
Yetkin, F. Z., Swanson, S., Fischer, M., Akansel, G., Morris, G.,
Mueller, W., et al. (1998). Functional MR of frontal lobe
activation: Comparison with Wada language results. American
Journal of Neuroradiology, 19(6), 1095–1098.
Yuan, W., Szaflarski, J. P., Schmithorst, V. J., Schapiro, M., Byars, A.
W., Strawsburg, R. H., et al. (2006). fMRI shows atypical
language lateralization in pediatric epilepsy patients. Epilepsia,
504 Neuropsychol Rev (2007) 17:491–504