Download Listening to Narrative Speech after Aphasic

Cerebral Cortex August 2006;16:1116--1125
doi:10.1093/cercor/bhj053
Advance Access publication October 26, 2005
Listening to Narrative Speech after
Aphasic Stroke: the Role of the Left
Anterior Temporal Lobe
The dorsal bank of the primate superior temporal sulcus (STS) is a
polysensory area with rich connections to unimodal sensory
association cortices. These include auditory projections that process
complex acoustic information, including conspecific vocalizations.
We investigated whether an extensive left posterior temporal
(Wernicke’s area) lesion, which included destruction of early
auditory cortex, may contribute to impaired spoken narrative
comprehension as a consequence of reduced function in the anterior
STS, a region not included within the boundary of infarction.
Listening to narratives in normal subjects activated the posterior-anterior extent of the left STS, as far forward as the temporal pole.
The presence of a Wernicke’s area lesion was associated with both
impaired sentence comprehension and a reduced physiological
response to heard narratives in the intact anterior left STS when
compared to aphasic patients without temporal lobe damage and
normal controls. Thus, in addition to the loss of language function in
left posterior temporal cortex as the direct result of infarction,
posterior ablation that includes primary and early association
auditory cortex impairs language function in the intact anterior left
temporal lobe. The implication is that clinical studies of language on
stroke patients have underestimated the role of left anterior temporal
cortex in comprehension of narrative speech.
Keywords: fusiform gyrus, narrative speech comprehension,
superior temporal sulcus
Introduction
Infarction of Wernicke’s area, the posterior left superior
temporal cortex, impairs speech comprehension. If the lesion
is large, the prognosis for recovery is poor (Selnes et al., 1983;
Naeser et al., 1987; Hart and Gordon, 1990). The inference is
that the unimodal processing of speech proceeds in a ventral
and posterior direction prior to processing for meaning (Hickok
and Poeppel, 2000, 2004). A similar conclusion comes from
studies of transcortical sensory aphasia (TCSA) after stroke.
Although these patients can still process the speech signal to
allow accurate repetition, the route to word comprehension is
impaired. Typically, but not always, the condition is associated
with lesions to, or disconnection of, inferolateral temporal and
inferior parietal cortex (Berthier, 1999). Recovery of speech
comprehension has been equated with restitution of function
within or around the lesion following Wernicke’s area reversible
ischemia (Hillis et al., 2001) or infarction (Heiss et al., 1999).
However, the literature on lesion location and aphasia is
selective. Infarction confined to anterior temporal cortex is
rare, as the artery supplying this region often arises proximally,
protecting it from emboli lodging at the more distal trifurcation
of the middle cerebral artery. Anterior left temporal lobectomy
The Author 2005. Published by Oxford University Press. All rights reserved.
For permissions, please e-mail: [email protected]
Jennifer T. Crinion1, Elizabeth A. Warburton2, Matthew A.
Lambon-Ralph3, David Howard4 and Richard J.S. Wise1
1
Division of Neurosciences and Mental Health and MRC
Clinical Sciences Centre, Imperial, Hammersmith Hospital,
London W12 0NN, UK, 2Department of Stroke Medicine,
Addenbrooke’s Hospital, Cambridge CB2 2QQ, UK,
3
Department of Psychology, University of Manchester, Oxford
Road, Manchester M13 9PL, UK and 4School of Education,
Communication and Language, Newcastle University,
Newcastle-upon-Tyne NE1 7RU, UK
to treat temporal lobe epilepsy is usually reported to impair
language comprehension only mildly, but the effects of recurrent left temporal lobe seizures on normal language organization limits the inferences that can be made (Janzsky et al.,
2003). In contrast, patients with the temporal variant of frontotemporal dementia commonly known as semantic dementia
(Snowden et al., 1989, 1992; Hodges et al., 1992; Edwards-Lee
et al., 1997; Gorno-Tempini et al., 2004), have an anterior-posterior gradient of temporal lobe atrophy. These patients
gradually lose single word comprehension although syntactic
comprehension, within the limits imposed by the loss of
knowledge about single word meaning, is usually well preserved
(see e.g. Gorno-Tempini et al., 2004). Their atrophy is most
marked at the temporal pole and within both inferotemporal
cortex and medial temporal lobe (limbic) structures (Chan
et al., 2001; Galton et al., 2001).
In the non-human primate, it has been proposed that anterior
and posterior projections from early auditory association cortex
have different functions (Rauschecker and Tian, 2000; Kaas and
Hackett, 2000) — an hypothesis supported by evidence that
posterior and anterior auditory processing ‘streams’ project to
different prefrontal targets (Romanski et al., 1999). Further,
neurons tuned to conspecific vocalizations are encountered
more often in primate anterior auditory association cortex (Tian
et al., 2001), sounds that also result in a lateralized difference in
the rate of glucose metabolism in temporal polar cortex
(Poremba et al., 2004). In neuroimaging studies of human
auditory perception, acoustic features that contribute to
discriminating speech sounds activate auditory association
cortex in both anterior and posterior directions (Scott and
Johnsrude, 2003). Sounds made by the human vocal tract,
whether intelligible or unintelligible, increase activity as far as
the dorsal bank of both left and right superior temporal sulci
(STS) (Belin et al., 2000). Listening to intelligible sentences after
subtraction of activity attributable to acoustic complexity and
paralinguistic features has been specifically related to activity in
the left STS, including its anterior extent (Scott et al., 2000;
Narain et al., 2003).
In non-human primates, auditory projections from the subcortical medial geniculate nuclear complex are distributed
widely throughout the ipsilateral superior temporal gyrus.
There are major parallel projections to primary auditory cortex
and adjacent periauditory cortex, known as belt and parabelt
cortex (Kaas and Hackett, 2000). Onward projections pass
in series from primary auditory cortex to belt and from belt
to parabelt. Parallel projections from belt and parabelt pass to
other regions in unimodal auditory association cortex, to
polysensory (heteromodal) cortex and to prefrontal cortex.
This hierarchical cortical organization applies to other sensory
systems (Pandya and Kuypers, 1969; Jones and Powell, 1970).
The manner whereby encoded sensory information passes
progressively through a number of synaptic levels in unimodal
association cortex to polysensory cortex, to paralimbic and
limbic structures, and to prefrontal cortex has been proposed as
an anatomical account of how language, spoken or written, is
processed (Mesulam, 1998).
We reasoned that infarction of primary and adjacent association auditory cortex as part of Wernicke’s area infarction, by
disrupting many of the subcortical--cortical auditory projections, impairs the onward polysynaptic transmission of encoded
speech information to structurally intact regions in auditory
association and polysensory temporal lobe neocortex. Further,
if the infarct destroys the posterior part of auditory unimodal
association and polysensory cortex, the additional loss of
posterior--anterior connections along the lateral temporal neocortex as, for example, have been demonstrated in the STS of
the non-human primate (see e.g. Seltzer and Pandya, 1989;
Padberg et al., 2003) may contribute to the behavioral consequences of a Wernicke’s area infarct. This would accord with
the many functional imaging studies on normal subjects that
have shown anterior temporal responses to spoken or written
single words, sentences and narratives (e.g. Mazoyer et al., 1993;
Bavelier et al., 1998; Perani et al., 1998; Schlosser et al., 1998;
Stowe et al., 1998; Mummery et al., 1999; Binder et al., 2000;
Scott et al., 2000; Ferstl and von Cramon, 2001; Wise et al.,
2001; Vandenberghe et al., 2002; Davis and Johnsrude, 2003;
Friederici et al., 2003; Narain et al., 2003; Scott and Wise, 2004).
Particularly compelling is a recent magnetoencephalographic
(MEG) study on normal subjects, which combined excellent
temporal resolution with good spatial resolution (Marinkovic
et al., 2003). An explicit task based on knowledge about object
size in response to hearing or reading object nouns resulted in
activity spreading forwards from early auditory cortex (to heard
words) and early visual cortex (for seen words). A strong
response to both modalities of word perception was observed
several hundreds of milliseconds later in the anterior STS and
temporal pole, left greater than right. Thus, the ability in this
study to follow cortical responses over time gave clear evidence
of a posterior--anterior response along the temporal lobe during
the processing of words for meaning. There was additional
activity in the left inferior frontal gyrus and medial prefrontal
cortex, which we have previously related to an explicit semantic task demand (Scott et al., 2003; Sharp et al., 2004). In response to ‘passive’ (i.e. automatic) processing of speech, after
‘subtraction’ of the signal related to early prelexical acoustic
processing by using a baseline of spectrally rotated or reversed
speech, we have also observed activity at anterior extent of the
left lateral temporal neocortex, centered on the STS (Scott et al.,
2000; Crinion et al., 2003).
To further confirm that one route for the processing of heard
speech involves projections to polysensory cortex in the anterior STS, we recruited aphasic stroke patients and grouped them
according to specific sites of pathological ablation. We used
positron emission tomography (PET) to investigate whether
Wernicke’s area infarction reduced normal anterior left temporal activation, even though the lesion had not directly involved
this area of cortex. We further investigated whether relative
activity within this area correlated with a measure of the patients’ residual spoken language comprehension, using the data
both from the patients with Wernicke’s area infarction and from
patients with aphasic stroke that spared the left temporal lobe.
The motivation was to reconcile those anatomical models of
language processing, based predominantly on lesion-deficit
analyses of aphasic stroke patients, that depict speech mapping
on to meaning via projections to the left posterior temporal and
inferior parietal cortex and those, based on neuropsychological
and anatomical imaging studies of patients with semantic dementia, that emphasize the role of anterior temporal cortex.
Materials and Methods
Subjects
Eleven normal subjects (nine males, aged 37--76 years) and 24 patients
(18 males, aged 32--85 years) were studied. All were right-handed and
had English as their first language. Each gave informed consent to
participate in the study. The local ethics committee approved the
project. Permission to administer radioisotopes was given by the
Department of Health, UK. The results from the normal subjects have
been previously reported (Crinion et al., 2003). The patients became
aphasic following a single left hemisphere stroke. The time from the
onset of stroke was very variable, between 2 and 204 months (mean
32 months). Each had a volumetric MRI to co-register with the PET scan
and to identify the site of their lesion. A neurologist (RJSW) classified
each patient according to whether the infarct involved the left temporal
lobe and, if it did, the posterior--anterior distribution of the temporal
lobe damage. At the time of classification, he was not aware of the
behavioral and PET data that corresponded to the individual MR images.
There were six patients with a left hemisphere lesion sparing the
left temporal lobe (T-- group), as judged from the T1-weighted volumetric images. The remaining 18 patients had temporal lobe damage
(T+ group). Of these, the anterior lateral temporal cortex was preserved
in nine patients but the volume of their infarcts was judged to include
part or all of primary and adjacent association auditory cortex in the
supratemporal plane (Wernicke’s group), based on the probabalistic
atlas of Rademacher et al. (2001) as reference. In this atlas, the anterior-posterior extent of primary auditory cortex in the supratemporal plane
is from y = --4 mm at its lateral border to y = --35 mm at its medial border,
using the stereotactic coordinate system of Talaraich and Tournoux
(1998). All nine patients had the left STS intact anterior to y coordinate
--20 mm: the STS extends from y = --60 mm at its posterior end to y = 15
mm, approximately. The distribution of infarction in the sub-groups of
patients is shown in Figure 1.
Behavioral Assessment
Twenty-two aphasic patients underwent neuropsychological testing
using a range of tests. For the analysis of the PET imaging results,
the results from the Comprehensive Aphasia Test (CAT) were used
(Swinburn et al., 2004). This includes a range of language comprehension and production tests. One patient in the T+ group died and another
in the T-- group had a second left hemisphere stroke before behavioral
testing was completed.
Scanning Stimuli
All patients had at least some preservation of spoken single word
comprehension, and most had at least some preservation of spoken
sentence comprehension. To maximize comprehension by the patients,
we chose simple children’s stories designed for a normal reading age
of 4--6 years, obtained from the Oxford Reading Tree Scheme (www.
oup.co.uk/oxed/primary/ort/): nouns of high frequency and imageability are incorporated within simple sentence structures. Using
SoundEdit16 computer software the waveform for each story was
also reversed (RSt), which destroys intelligibility while retaining the
overall spectrotemporal complexity of the original speech signal. The
reversed versions of the narratives were expected to control for much
of the prelexical acoustic processing of the speech signal in both left
and right superior temporal cortex. Each version of St and RSt were used
only once during each subject’s study, across 12--16 scans. The order
of presentation was randomized, both within and between subjects.
The subjects were asked to simply listen and try to understand the St.
Cerebral Cortex August 2006, V 16 N 8 1117
Figure 1. Overlap intensity maps, on representative coronal, sagittal and transaxial slices, with more detail in multiple coronal slices, showing the degree of involvement of each
voxel in the lesions of the T-- and T+ groups and the Wernicke’s sub-group, normalized to the smoothed MNI template. The extent and location of lesions were visualized using the
MRIcro software package (www.mricro.com). The range of the color scale derives from the relative involvement (bins of 12.5%) of each voxel in the lesions of the patients in each
group: from involvement in very few patients (dark blue = 12.5%) to involvement in all patients (dark red = 100%).
They were aware that the RSt were unintelligible but were asked to pay
attention to the sound.
PET Scanning
All normal subjects and 16 aphasic patients were studied at the MRC
Clinical Sciences Centre, Hammersmith Hospital using a CTI-Siemens
ECAT EXACT HR++/966 PET scanner operated in high-sensitivity 3D
mode. The remaining eight aphasic patients were studied at the Wolfson
Brain Imaging Centre, Addenbrooke’s Hospital using the General
Electric Medical Systems (Milwaukee, WI) Advance PET Scanner in 3D
mode. H15
2 O; administered i.v., was used to estimate regional cerebral
blood flow (rCBF) while the subjects either heard St or RSt. The stories,
and thus the reversed stories, were delivered at a normal rate of
speaking (~120--150 words/min), with 5--16 words per sentence. The
most sensitive period of each scan is during the rapid uptake of tracer
into cerebral tissue, which begins ~10--15 s after the head counts begin
to rise and continues for about 20 s. The stimuli were begun ~10 s before
the head counts began to rise and continued throughout the period of
data acquisition during each scan. Measured attenuation correction was
applied to all emission scans.
1118 Narrative Speech Comprehension and Left STS
d
Crinion et al.
Analyses of PET data
The Statistical Parametric Mapping (SPM99) software package (Wellcome Department of Cognitive Neurology, Institute of Neurology,
London, UK; www.fil.ion.ucl.ac.uk/spm/) was used for the analysis of
the PET data in this study. The SPM approach is voxel based: images are
realigned, spatially normalized into a standard Montreal Neurological
Institute (MNI) stereotactic space, and smoothed using an isotropic
10 mm full-width, half-maximum Gaussian kernel to account for variation in gyral anatomy and to improve the signal-to-noise ratio.
With stroke patients, distortions of normal anatomy ipsilateral to the
volume loss accompanying mature infarcts may reduce the certainty
that identical brain regions are being sampled across all subjects, despite
image smoothing. To further minimize the error the spatial normalization of the patients’ scans used the cost function masking method, in
which a hand-drawn mask of the infarct (derived from the MRI scan)
was used, preventing the normalization algorithm from defining the
edge of the infarct as part of the brain surface (Brett et al., 2001).
Within SPM, parametric statistical models are assumed at each voxel,
using the General Linear Model GLM to describe the data in terms of
experimental and confounding effects, and residual variability. Classical
statistical inference is used to test hypotheses that are expressed
in terms of GLM parameters. This uses an image whose voxel values
are statistics, a Statistic Image, or Statistical Parametric Map (SPMftg,
SPMfZg, SPMfFg). For such classical inferences, the multiple comparisons problem is addressed using continuous random field theory RFT,
assuming the statistic image to be a good lattice representation of an
underlying continuous stationary random field. This results in inference
based on corrected P-values.
In all SPM analyses, unless otherwise stated, a blocked AnCova with
global counts as confound was used to remove the effect of global
changes in perfusion across scans in each subject. The type of scanner
on which the subject was studied was also entered as confound. The
statistical threshold for the imaging analyses was set at P < 0.05,
corrected for whole brain volume, using the correction for familywise
error rate (FWE), which, although conservative, is reliable when both
detecting an experimentally induced signal and locating this effect in
the brain (Peterrson et al., 1999).
Normal Subjects
The normal subjects were entered into a single-group, multi-subject design matrix to investigate the contrast of St with RSt, using a fixed effects
statistical model to initially investigate the results in this group alone.
Comparing Patients and Normal Subjects
Random-effect analyses in SPM99 which emulate full mixed-effects
analyses were used to investigate any differences between the normal
and patient groups, T-- and T+ groups. This involved taking the contrasts
of parameters estimated from the first-level (fixed-effect) analysis ST-RSt and entering them into a second-level (random-effect) analysis. This
ensured that there is only one observation (i.e. contrast) per subject in
the second-level analysis and that the error variance was computed
using the subject to subject variability of estimates from the first level.
The second-level design matrix simply tests the null hypothesis that the
contrasts are zero (implementing a single-sample t-test). Random-effects
analyses are usually more conservative but allow the inference to be
generalized to the T-- and T+ populations from which the patients were
selected.
ROI Analysis
As we had an a priori hypothesis about the role of the left anterolateral
temporal lobe in speech comprehension, a region of interest (ROI)
analysis, using the MARSBAR toolbox within SPM99, was performed on
all subjects who did not have infarction there, i.e. the normal, T-- and
Wernicke’s groups. The ROI was defined using the binary activation
image obtained from the contrast of St with RSt in the normal group
alone. To ensure that that any changes observed in this region were not
just part of a general reorganization of the language system, two
additional ROI were defined, using the same technique, for the left
ventral and right anterolateral temporal regions. The mean voxel values
for individual patient’s ROIs, from the contrast of St with RSt were
extracted. First, these ROI values from the T-- and Wernicke’s groups
were correlated with the sentence comprehension data from the CAT
using a Pearson correlation. Second, the ROI values from the
T--, Wernicke’s and normal control groups were contrasted using independent samples t-test, equal variances not assumed.
Thus, the ROI was an irregularly shaped region extracted from the
functional data on normal subjects and not based on anatomical
landmarks. It transpired that its anatomical distribution was centered
on the most anterior extent of the STS (the peak voxel lay at Talaraich
and Tournoux stereotactic coordinates --52, 8, --20 mm), and encompassed a volume of ~12 cc within its boundary.
Figure 2. Scatter plots for scores (y-axis) on subtests of the Comprehensive Aphasia
Test (for details, see text). The maximum score for each subtest is shown as
a horizontal solid line, with 2 SD below the mean score in 50 normal subjects (age
range 30--60 years) shown as a horizontal dashed line. Chance score on spoken and
written single word and sentence comprehension = 7--8. The symbols are: T-- group,
black squares; Wernicke’s group, red triangles; T+ group, excluding the Wernicke’s
group, blue circles. SW = single words.
remained well above chance; by contrast, heard sentence-picture matching was more variable, being at chance in one
patient (7/30) and close to chance in a further three (10--12/30).
As can be inferred from Figure 2, the T-- group was significantly
better than the T+ group on the CAT tests of both auditory
and written sentence comprehension (unpaired Student’s t-test,
P < 0.01). Across all patients, heard single word comprehension correlated with heard sentence comprehension. Otherwise, measures of picture naming, single word repetition and
semantic fluency (free retrieval of animal names in one
minute) was very variable, both within groups and across all
patients (Fig. 2).
Results
Behavioral Data
Overall, spoken and written single word-picture matching were
better than spoken and written sentence--picture matching in
the patients (Fig. 2). Although heard single word--picture
matching was below normal in many patients, their scores all
PET Data -- Normal Subjects
In the normal group, St contrasted with RSt (Fig. 3) demonstrated activation of the left temporal cortex, with three voxel
clusters: in the anterior STS, extending into the temporal pole;
in the posterior STS as far as the temporo-parietal junction; and
in the anterior left fusiform gyrus. In the right temporal cortex
Cerebral Cortex August 2006, V 16 N 8 1119
Figure 3. The St--RSt contrast for the normal subjects and T-- and T+ patient groups. The activated voxels (P < 0.05, corrected) are displayed in black on statistical parametric
views in sagittal, coronal and transaxial views. For the two patient groups, the activations are also shown projected onto representative mean T1-weighted MR coronal images for
that group, with the extent of the group lesion shown as a red mask and the activated voxels in intact cortex in yellow. 1, activation in the anterior left STS, spreading into the
temporal pole; 2, activation in the posterior left STS; 3, activation in the anterior left fusiform gyrus; 4, activation in the anterior right STS, spreading into the temporal pole. L = left.
there was one cluster, in the anterior STS and extending into
the temporal pole.
PET Data -- Comparison of Patients and Normal Subjects
There were no significant differences between the patients, as
one group, and the normal subjects within the voxels that were
preserved in all patients. Thus, activations common to the two
groups were observed in the anterior left fusiform gyrus and the
anterior right STS. When the patients were analysed separately
as T-- and T+ groups, again there were no significant differences
between either of them and the normal group. The pattern of
activation in the T-- group was identical to that in the normal
group, and there were no differences between the T+ and
normal groups within the voxels that were preserved in all
patients (Fig. 3).
PET Data -- ROI Analysis
The brain tissue within the anterior left temporal ROI, encompassing the anterior third of the STS and extending into the
lateral temporal pole, was intact in the T-- and Wernicke’s
groups. Within this ROI, activity was identified as the percentage increase in activity in response to hearing speech relative to
the unintelligible baseline auditory condition. Behavioral data
was available for only 5/6 patients in the T-- group. In one of
these five patients whose performance on tests of single word
1120 Narrative Speech Comprehension and Left STS
d
Crinion et al.
and sentence comprehension were within the normal range,
activity within the ROI was identified as an outlier within SPSS
( > 3 SD above the mean for the group). His data were therefore
excluded from the analysis. Across the 13 patients included in
the analysis, ROI activity correlated significantly with the scores
on heard sentence comprehension (r = 0.57, P < 0.05; Pearson’s
correlation). Including the outlying data point from the fourteenth subject improved the correlation coefficient a little
(r = 0.62), and so excluding the data from this one subject in the
final analysis did not bias the result. Importantly, there was no
correlation between activity with the ROI and time since the
onset of stroke (r = 0.06, P > 0.8), and so the correlation cannot
simply be attributed to recovery over time after acute focal
brain injury. Inspection of Figure 4 demonstrates that the four
patients from the T-- group had both high ROI activity and good
sentence comprehension relative to the nine patients from
the Wernicke’s group. This was confirmed with independent
t-tests (mean ROI activity ± SEM: 6.7 ± 1.1 and 2.7 ± 0.8, P < 0.05;
mean auditory sentence comprehension ± SEM: 25.5 ± 2.2 and
14.9 ± 1.8, P < 0.01), although with data from only four patients
in one group these results can only be considered reliable
for this study group. ROI activity within the normal group was
6.3 ± 1.4, significantly greater than the activity in the Wernicke’s
group (P < 0.05). By contrast, ROI activity did not correlate significantly with the scores on heard single word comprehension
Figure 4. Individual percentage differences in activity in region 1 from Figure 3, in the
St--RSt contrast, plotted against individual auditory single word comprehension scores.
Data from the Broca’s group are indicated as black squares, and from the Wernicke’s
group as gray triangles. The results of the statistical analyses are given in the text.
Chance score on spoken single word and sentence comprehension = 7--8.
(r = 0.39, P > 0.1; Pearson’s correlation), reflecting no difference in the behavioral performance of the T-- and Wernicke’s
groups (mean auditory single word comprehension ± SEM:
27.3 ± 1.2 and 24.2 ± 1.4, P > 0.1).
Discussion
The study demonstrated that activity in the intact anterior left
STS in a contrast of listening to narratives with listening to
reversed narratives was reduced in patients with Wernicke’s
area infarction. Expanding the group of aphasic patients to
include a number without left temporal lobe infarction demonstrated that left anterior STS activity correlated with a
measure of sentence comprehension.
The activity we observed was dependent on a simple ‘subtractive’ contrast, using auditory stimuli that were processed
automatically by the subjects. The contrast ‘subtracted’ early
processing of the speech signal, evidenced by the absence of
signal in primary auditory cortex and the supratemporal plane;
these regions are also activated by sounds that are acoustically
less complex than speech (Scott and Johnsrude, 2003). The
observed signal reliably reflected ‘bottom-up’ implicit processing of intelligible sentences, connected by a narrative plot. In
reality, the observed signal will have reflected less than this. One
pervasive problem in functional imaging is that there is no
universal baseline state of cognitive ‘neutrality’ with which to
compare the activation conditions under investigation. This has
been highlighted by studies that have shown the regional
activity associated with the ‘rest’ or ‘passive’ state (Binder
et al., 1999; Gusnard and Raichle, 2001), a period when the
subject in the scanner is likely to be engaged in stimulus
independent thoughts. Such thoughts may draw on declarative
memories, episodic and semantic, and, possibly, imagery.
Therefore, stimulus independent thoughts during ‘passive’
listening to reversed narratives will have reduced or abolished
signal in systems also engaged during language comprehension.
PET and functional magnetic resonance imaging (fMRI)
studies in normal subjects that have demonstrated activity in
anterior temporal cortex in response to single words, sentences
and narratives (e.g. Mazoyer et al., 1993; Bavelier et al., 1998;
Perani et al., 1998; Schlosser et al., 1998; Stowe et al., 1998;
Mummery et al., 1999; Binder et al., 2000; Scott et al., 2000;
Ferstl and von Cramon, 2001; Wise et al., 2001; Vandenberghe
et al., 2002; Davis and Johnsrude, 2003; Friederici et al., 2003;
Narain et al., 2003; Scott and Wise, 2004). A few study designs
demonstrated that these anterior regions are activated more
strongly when processing language at the sentence rather than
the single content word level (e.g. Mazoyer et al., 1993; Stowe
et al., 1998; Vandenberghe et al., 2002). Vandenberghe et al.
(2002) specifically propose that left anterior temporal cortex is
involved in binding together the components of a sentence into
one message, and differentiate this from the controlled performance of specific syntactic operations. On this account, activity
will be greater for sentences and narratives than word lists.
This interpretation appears to be equivalent to that taken by
electrophysiologists studying the N400, an event-related potential sensitive to content word meaning within the context of
a sentence. This view envisages that meaning builds gradually
and continuously throughout the processing of sentences (for
review, see Kutas and Federmeier, 2000).
An alternative view considers that the rule-based grammar
system and the acquired lexical system are anatomically as
well as functionally distinct. In the functional neuroimaging
studies that have attempted to distinguish these processes (e.g.
Kuperberg et al., 2000; Ni et al., 2000; Friederici et al., 2003),
there is little consistency between them in terms of results. For
example, Friederici et al. (2003) demonstrate both common
and distinct activations in the supratemporal planes of both
hemispheres for syntactic and semantic processes. By contrast,
Kuperberg et al. (2000) could not distinguish between semantic and syntactic processes, other than activations specific to
semantics in the right temporal lobe alone, but they did relate
a common activation in left inferotemporal cortex to pragmatic,
syntactic and semantic processes. Both clinical neuropsychological and some fMRI studies provide evidence that activity
in the superior temporal gyrus is associated with syntactic
operations during speech processing, including the supratemporal plane (Humphries et al., 2001; Friederici and Kotz, 2003;
Dronkers et al., 2004). However, in the present study on normal
subjects there was no detectable difference in activity (P > 0.1,
uncorrected) between listening to stories and reversed stories
within either supratemporal plane. This lack of consistency
raises a number of issues. Localizing function in clinical neuropsychological studies using the ‘lesion overlap’ technique, in
which a common behavioral deficit is related to a common
lesioned site across patients with very differently distributed
Cerebral Cortex August 2006, V 16 N 8 1121
lesions, has its limitations (Hillis et al., 2004). Further, the deficit
may be attributable as much to white matter damage disconnecting intact regions of cortex as to the local cortical damage.
In functional imaging studies, if neural networks for the
acoustic, lexical and syntactic processing of connected speech
are intermingled in the supratemporal plane, it is entirely possible that the signal from acoustic processing of both speech
and speech-like stimuli may predominate and mask additional
co-localized signal from the automatic linguistic processing of
sentences. Nevertheless, the use of explicit tasks to isolate
syntactic operations must engage, as well as language systems,
prefrontal executive processes not used in normal language
comprehension. Altered fronto-temporal functional interactions and differences in attentional processes may modulate
the signal in language-related temporal cortex in an unpredictable manner. Any of these factors may confound a simple
‘subtraction’ experimental design (Friston et al., 1996) and
potentially alter the relationship between an observable hemodynamic response and the localization of a specific psychological operation. This encapsulates some of the arguments
contained in a review by Kaan and Swaab (2002). They conclude
that syntactic processing is distributed between the posterior-anterior extent of superior and lateral temporal neocortex and
the left inferior frontal gyrus (Broca’s area), the latter region
having been observed in a number of other studies of controlled
processing of syntax (reviewed in Kaan and Swaab, 2002). They
argue that variations in processing load required of the subjects
may alter the balance between observed frontal and temporal
lobe activations, with or without the appearance of additional
activations associated with the recruitment of parallel processes
for the execution of a study-specific task. They take the view
that process-specific language networks may be very broadly
distributed, and it may be the dynamic interactions between
language-related brain regions, rather than loci of activations,
that are specific to the processes of extracting lexical and
syntactic information from the speech stream; to the extent that
right hemisphere regions may be recruited in the comprehension of complex sentences (e.g. Caplan et al., 1996; Just
et al., 1996).
However, an anatomical separation of lexical semantics and
the comprehension of syntactical structure may be evident
from clinical studies. A recent example comes from a behavioural and anatomical study of patients with primary progressive
aphasia. The anterior temporal lobe atrophy in patients classified as semantic dementia resulted in a ‘striking dissociation’
between their impaired performance on single word comprehension and their intact performance on a test of sentence
comprehension comprising different levels of syntactic complexity: the reverse dissociation was observed in patients with
what was termed logopenic progressive atrophy, in whom the
left posterior temporal and inferior parietal lobes were most
atrophied (Gorno-Tempini et al., 2004). Although the combined
evidence from the clinical and functional imaging studies
suggests that the comprehension of grammatical structure can
exist in the presence of anterior temporal cortical atrophy, the
correlation of left anterior temporal activity in response to
listening to narratives with the patients’ performance on
a sentence comprehension task in the present study has to be
viewed in the context of infarction elsewhere in the left
hemisphere language system. The posterior left STS was
activated by the narratives in the normal subjects, but in the
patients from the Wernicke’s group this region was either
1122 Narrative Speech Comprehension and Left STS
d
Crinion et al.
destroyed or disconnected from primary auditory and periauditory cortex. Therefore, the implicit comprehension of sentences is normally dependent on activity along the length of the
left STS, but we have only observed a relationship between
sentence comprehension and left anterior STS activity in the
context of destruction or disconnection of the posterior STS.
The complementary study would be to investigate patients with
isolated left anterior temporal lobe infarction and correlate
activity within the posterior left STS with measures of language
recovery, but such lesions are rare for reasons outlined in the
introduction.
The normal activation of the anterior left fusiform gyrus of the
patients, within the region identified by electrophysiological
studies at the time of temporal lobe epilepsy as the basal
language area (Burnstine et al., 1990), reflected their relative
preservation of single object word comprehension. It has been
demonstrated with direct electrical recordings that the anterior
fusiform gyrus responds to lists of object words but not function
words (Nobre et al., 1994). This region consists of high-order
visual association cortex (Insausti et al., 1998). When contrasting the perception of lists of imageable (concrete) nouns with
lists of less imageable (abstract nouns), increased activity has
been observed in polysensory perirhinal cortex (Wise et al.,
2000); part of memory-related temporal lobe lying medial to the
fusiform gyrus in the collateral sulcus (Insausti et al., 1998). The
equivalent regions in the non-human primate, visual area TE
and perirhinal area 36, form a functional unit that operates to
learn and remember long-term arbitrary visual--visual associations (Naya et al., 2003). In the human, long-term crossmodal associations between arbitrary sounds (words) and visual
objects may be formed in the same way. Once these associations
are ‘consolidated’, their automatic recall during implicit narrative comprehension may become less dependent on memoryrelated (limbic) cortex (for reviews, see Zola-Morgan and
Squire, 1993; Murre et al., 2001), which would explain the
absence of left perirhinal cortical activation in this study.
However, the absence of observable medial temporal lobe
activation is not proof of an absence of involvement, especially
as the choice of baseline task can be critical when attempting to
visualize activity within limbic cortex (Stark and Squire, 2001).
This study demonstrated an apparent left-lateralization for
speech comprehension in inferotemporal cortex, whereas previous electrophysiological and functional imaging studies of
automatic single object word processing have shown bilateral
involvement (Nobre et al., 1994; Wise et al., 2000). However,
the asymmetry we have reported needs to be qualified (Jernigan
et al., 2003). We did not investigate contrast 3 region 3
hemisphere interactions with multiple ROI analyses, and in
fact mean activity in the anterior right fusiform gyrus was
greater in the speech than reversed speech condition in the
normal subjects, although the Z-score in this region (= 3.9) was
below the threshold we selected for the analyses. Further,
automatic speech perception was associated with activity in the
anterior right STS, in both the normal subjects and the patients.
As reversed speech lacks the normal segmental stress patterns,
suprasegmental prosody and voice identity of normal speech,
the conservative assumption is that the anterior stream of
auditory processing on the right predominantly reflects processing of one or more aspects of non-linguistic speech
information (for review, see Wong, 2002). However, activation
of the anterior right superior temporal sulcus was observed in,
for example, the study by Ferstl and von Cramon (2001) on
written text comprehension, in which paralinguistic speech
information is absent. There is also a study on patients with
semantic dementia, which provided evidence that both temporal lobes have a role in lexical semantics (Lambon Ralph et al.,
2001). Thus, we cannot assume that the right temporal lobe did
not contribute to linguistic processing in both the normal
subjects and patients. Further, although we did not demonstrate
significant differences between the activation patterns in the
right hemisphere between normal subjects and patients, reorganization may have occurred in the right temporal lobe of
patients without this change necessarily being captured by any
difference in hemodynamic response. In other words, lack of
evidence of post-stroke neural plasticity in this study is not
evidence for its absence.
As a final footnote, this study does not imply that the language
functions of the STS are confined to spoken language. Written
text comprehension activates both the anterior and posterior
left STS (e.g. Ferstl and von Cramon, 2001). This accords with
the abundant anatomical evidence from non-human primates
that the length of the STS is an important zone of convergence
for sensory information from different modalities. Thus, if this
study had investigated written rather than spoken narrative
comprehension, the result and conclusions might have been
very similar.
In summary, the results from this study are best interpreted
as evidence that automatic speech comprehension engages
the length of the left STS in normal subjects and that language functions in the intact anterior STS are disrupted by a
Wernicke’s area lesion. Polysensory cortex in the dorsal bank of
the anterior STS in non-human primates, the anterior superior
temporal polysensory area, receives reciprocal projections from
the highest-order auditory, visual and somatosensory association cortices. Onward reciprocal connections connect the
anterior superior temporal polysensory area to limbic, parietal
and prefrontal cortex (e.g. Seltzer et al., 1996; Saleem et al.,
2000; Padberg et al., 2003). These afferent and efferent
connections lend plausibility to the hypothesis that the anterior
STS is one of perhaps several ‘convergence zones’ or ‘transmodal
areas’ in a hierarchy that ultimately maps the encoded speech
signal on to long-term memories of attributes, associations and
concepts (Damasio, 1989; Mesulam, 1998). Although the
primate anterior STS has become equated with visual processing (e.g. Bruce et al., 1981; Oram and Perrett, 1996; Anderson
and Siegel, 1999), comparative studies of auditory neurophysiology between primates and humans may indicate a functional
homology between the non-human primate and human anterior
STS in auditory processing, This may provide insights into the
evolution of speech perception and comprehension that
parallel inferences being made about mirror neurons in the
inferior frontal gyrus and the evolution of speech production
(Rizzolatti and Arbib, 1998).
Notes
Address correspondence to Richard Wise, Division of Neurosciences
and Mental Health and MRC Clinical Sciences Centre, Imperial,
Hammersmith Hospital, London W12 0NN, Uk. Email: richard.wise@
csc.mrc.ac.uk.
References
Anderson KC, Siegel RM (1999) Optic flow selectivity in the anterior
superior temporal polysensory area, STPa, of the behaving monkey.
J Neurosci 19:2681--2692.
Bavelier D, Corina DP, Neville HJ (1998) Brain and language:a perspective from sign language. Neuron 21:275--278.
Belin P, Zatorre RJ, Lafaille P, Ahad P, Pike B (2000) Voice-selective areas
in human auditory cortex. Nature 403:309--312.
Berthier ML (1999) Transcortical aphasias. Hove: Psychology Press.
Binder JR, Frost JA, Hammeke TA, Bellgowan PSF, Springer JA,
Kaufman JN, Possing ET (2000) Human temporal lobe activation
by speech and nonspeech sounds. Cereb Cortex 10:512--528.
Brett M, Leff AP, Rorden C, Ashburner J (2001) Spatial normalization of
brain images with focal lesions using cost function masking. Neuroimage 14:486--500.
Bruce C, Desimone R, Gross CG (1981) Visual properties of neurons in
a polysensory area in superior temporal sulcus of the macaque.
J Neurophysiol 46:369--384.
Burnstine TH, Lesser RP, Hart J Jr, Uematsu S, Zinreich SJ, Krauss GL,
Fisher RS, Vining EP, Gordon B (1990) Characterization of the basal
temporal language area in patients with left temporal lobe epilepsy.
Neurology 40:966--970.
Caplan D, Hildebrandt N, Makris N (1996) Location of lesions in stroke
patients with deficits in syntactic processing in sentence comprehension. Brain 119:933--949.
Chan D, Fox NC, Scahill RI, Crum WR, Whitwell JL, Leschziner G, et al.
(2001) Patterns of temporal lobe atrophy in semantic dementia and
Alzheimer’s disease. Ann Neurol 49:433--442.
Crinion JT, Lambon-Ralph MA, Warburton EA, Howard D, Wise RJS
(2003) Temporal lobe regions engaged in normal speech comprehension. Brain 126:1193--1201.
Damasio AR (1989) Time-locked multiregional retroactivation: a systemslevel proposal for the neural substrates of recall and recognition.
Cognition 33:25--62.
Davis MH, Johnsrude IS (2003) Hierarchical processing in spoken
language comprehension. J Neurosci 23:3423--3431.
Dronkers NF, Wilkins DP, Van Valin RD Jr, Redfern BB, Jaeger JJ (2004)
Lesion analysis of the brain areas involved in language comprehension. Cognition 92:145--177.
Edwards-Lee T, Miller BL, Benson DF, Cummings JL, Russell GL, Boone K,
Mena I (1997) The temporal variant of fronto-temporal dementia.
Brain 120:1027--1040.
Ferstl EC, von Cramon DY (2001) The role of coherence and cohesion in
text comprehension:an event-related fMRI study. Cogn Brain Res
11:325--340.
Friederici AD, Rüschemeyer S-A, Hahne A, Fiebach CJ (2003) The role of
left inferior frontal and superior temporal cortex in sentence
comprehension: localizing syntactic and semantic processes. Cereb
Cortex 13:170--177.
Friederici AD, Kotz SA (2003) The brain basis of syntactic processes:
functional imaging and lesion studies. NeuroImage 20 (Suppl
1):S8--S17.
Friston KJ, Price CJ, Fletcher P, Moore C, Frackowiak RS, Dolan RJ
(1996) The trouble with cognitive subtraction. NeuroImage
4:97--104.
Galton CJ, Patterson K, Graham K, Lambon-Ralph MA, Williams G,
Antoun N et al. (2001) Differing patterns of temporal atrophy in
Alzheimer’s disease and semantic dementia. Neurology 57:216--225.
Gorno-Tempini ML, Dronkers NF, Rankin KP, Ogar JM, La
Phengrasamy BA, Rosen HJ, et al. (2004) Cognition and anatomy in
three variants of primary progressive aphasia. Ann Neurol 55:
335--346.
Gusnard DA, Raichle ME (2001) Searching for a baseline: functional
imaging and the resting human brain. Nat Rev Neurosci 2:685--694.
Hart J, Gordon B (1990) Delineation of single-word semantic comprehension deficits in aphasia, with anatomical correlation. Ann Neurol
27:226--231.
Heiss WD, Kessler J, Thiel A, Ghaemi M, Karbe H (1999) Differential
capacity of left and right hemispheric areas for compensation of
poststroke aphasia. Ann Neurol 45:430--438.
Hickok G, Poeppel D (2000) Towards a functional neuroanatomy of
speech perception. Trends Cogn Sci 4:131--138.
Hickok G, Poeppel D (2004) Dorsal and ventral streams: a framework for
understanding aspects of the functional anatomy of language.
Cognition 92:67--99.
Cerebral Cortex August 2006, V 16 N 8 1123
Hillis AE, Kane A, Tuffiash E, Ulatowski JA, Barker PB, Beauchamp NJ,
Wityk RJ (2001) Reperfusion of specific brain regions by raising
blood pressure restores selective language functions in subacute
stroke. Brain Lang 79:495--510.
Hillis AE, Work M, Barker PB, Jacobs MA, Breese EL, Maurer K (2004) Reexamining the brain regions crucial for orchestrating speech
articulation. Brain 127:1479--1487.
Hodges JR, Patterson K, Oxbury S, Funnell E (1992) Semantic dementia:
progressive fluent aphasia with temporal lobe atrophy. Brain
115:1783--1806.
Humphries C, Willard K, Buchsbaum B, Hickok G (2001) Role of anterior
temporal cortex in auditory sentence comprehension: an fMRI study.
Neuroreport 12:1749--1752.
Insausti R, Juottonen K, Soininen H, Insausti AM, Partanen K, Vainio P.
et al. (1998) MR volumetric analysis of the human entorhinal,
perirhinal, and temporopolar cortices. Am J Neuroradiol 19:
659--671.
Janszky J, Jokeit H, Heinemann D, Schulz R, Woermann FG, Ebner A
(2003) Epileptic activity influences the speech organization in
medial temporal lobe epilepsy. Brain 126:2043--2051.
Jernigan TL, Gamst AC, Fennema-Notestine C, Ostergaard AL (2003)
More ‘mapping’ in brain mapping: statistical comparison of effects.
Hum Brain Mapp 19:90--95.
Jones EG, Powell TPS (1970) An anatomical study of converging sensory
pathways within the cerebral cortex of the monkey. Brain
93:793--820.
Just MA, Carpenter PA, Keller TA, Eddy WF, Thulborn KR (1996) Brain
activation modulated by sentence comprehension. Science
274:114--116.
Kaan E, Swaab, TY (2002) The brain circuitry of syntactic comprehension. Trends Cogn Sci 5:350--356.
Kaas JH, Hackett TA (2000) Subdivisions of auditory cortex and
processing streams in primates. Proc Natl Acad Sci USA
97:11793--11799.
Kuperberg GR, McGuire PK, Bullmore ET, Brammer MJ, Rabe-Hesketh S,
Wright IC, et al. (2000) Common and distinct neural substrates for
pragmatic, semantic, and syntactic processing of spoken sentences:
an fMRI study. J Cogn Neurosci 12:321--341.
Kutas M, Federmeier KD (2000) Electrophysiology reveals semantic
memory use in language comprehension. Trends Cogn Sci
4:463--470.
Lambon Ralph MA, McClelland JL, Patterson K, Galton CJ, Hodges JR
(2001) No right to speak? The relationship between object naming
and semantic impairment:neuropsychological evidence and a computational model. J Cogn Neurosci 13:341--356.
Marinkovic K, Dhond RP, Dale AM, Glessner M, Carr V, Halgren E (2003)
Spatiotemporal dynamics of modality-specific and supramodal word
processing. Neuron 38:487--497.
Mazoyer B, Dehaene S, Tzourio N, Frak V, Cohen L, Murayama N, Levrier
O, Salamon G, Mehler J (1993) The cortical representation of speech.
J Cogn Neurosci 5:467--479.
Mesulam MM (1998) From sensation to cognition. Brain 121:
1013--1052.
Mummery CJ, Ashburner J, Scott SK, Wise RJS (1999) Functional
neuroimaging of speech perception in six normal and two aphasic
subjects. J Acoust Soc Amer 106:449--457.
Murre JM, Graham KS, Hodges JR (2001) Semantic dementia: relevance to connectionist models of long-term memory. Brain 124:
647--675.
Naeser MA, Helm-Estabrooks N, Haas G, Auerbach S, Srinivasan M (1987)
Relationship between lesion extent in ‘Wernicke’s area’ on computed tomographic scan and predicting recovery of comprehension
in Wernicke’s aphasia. Arch Neurol 44:73--82.
Narain C, Scott SK, Wise RJ, Rosen S, Leff A, Iversen SD, Matthews PM
(2003) Defining a left-lateralized response specific to intelligible
speech using fMRI. Cereb Cortex 13:1362--1368.
Naya Y, Yoshida M, Miyashita Y (2003) Forward processing of long-term
associative memory in monkey inferotemporal cortex. J Neurosci
23:2861--2871.
Ni W, Constable RT, Mencl WE, Pugh KR, Fulbright RK, Shaywitz SE,
Shaywitz BA, Gore JC, Shankweiler D (2000) An event-related
1124 Narrative Speech Comprehension and Left STS
d
Crinion et al.
neuroimaging study distinguishing form and content in sentence
processing. J Cogn Neurosci 12:120--133.
Nobre AC, Allison T, McCarthy G (1994) Word recognition in the human
inferior temporal lobe. Nature 372:260--263.
Oram MW, Perrett DI (1996) Integration of form and motion in the
anterior superior temporal polysensory area (STPa) of the macaque
monkey. J Neurophysiol 76:109--129.
Padberg J, Seltzer B, Cusick CG (2003) Architectonics and cortical
connections of the upper bank of the superior temporal sulcus in the
rhesus monkey:an analysis in the tangential plane. J Comp Neurol
467:418--434.
Pandya DN, Kuypers HG (1969) Cortico-cortical connections in the
rhesus monkey. Brain Res 13:30--36.
Perani D, Paulesu E, Galles NS, Dupoux E, Dehaene S, Bettinardi V,
Cappa SF, Fazio F, Mehler J (1998) The bilingual brain. Proficiency
and age of acquisition of the second language. Brain 121:1841--1852.
Petersson KM, Nichols TE, Poline JB, Holmes AP (1999) Statistical
limitations in functional neuroimaging. II. Signal detection and
statistical inference. Philos Trans R Soc Lond B Biol Sci 1999
354:1261--1281.
Poremba A, Malloy M, Saunders RC, Carson RE, Herscovitch P, Mishkin M
(2004) Species-specific calls evoke asymmetric activity in the
monkey’s temporal poles. Nature 427:448--451.
Rademacher J, Morosan P, Schormann T, Cshleicher A, Werner C, Freund
H-J, Zilles K (2001) Probabilistic mapping and volume measurement
of human primary auditory cortex. NeuroImage 13:669--683.
Rauschecker JP, Tian B (2000) Mechanisms and streams for processing
of ‘what’ and ‘where’ in auditory cortex. Proc Natl Acad Sci USA
97:11800--11806.
Rizzolatti G, Arbib MA (1998) Language within our grasp. Trends
Neurosci 21:188--194.
Romanski LM, Tian B, Fritz J, Mishkin M, Goldman-Rakic PS,
Rauschecker JP (1999) Dual streams of auditory afferents target
multiple domains in the primate prefrontal cortex. Nat Neurosci
2:1131--1136.
Saleem KS, Suzuki W, Tanaka K, Hashikawa T (2000) Connections
between anterior inferotemporal cortex and superior temporal
sulcus regions in the macaque monkey. J Neurosci 20:5083--5101.
Schlosser MJ, Aoyagi N, Fulbright RK, Gore JC, McCarthy G (1998)
Functional MRI studies of auditory comprehension. Hum Brain Mapp
6:1--13.
Scott SK, Johnsrude IS (2003) The neuroanatomical and functional
organization of speech perception. Trends Neurosci 26:100--107.
Scott SK, Wise RJ (2004) The functional neuroanatomy of prelexical
processing in speech perception. Cognition 92:13--45.
Scott SK, Blank CC, Rosen S, Wise RJS (2000) Identification of a pathway
for intelligible speech in the left temporal lobe. Brain
123:2400--2406.
Selnes OA, Knopman DS, Niccum N, Rubens AB, Larson D (1983)
Computed tomographic scan correlates of auditory comprehension
deficits in aphasia: a prospective recovery study. Ann Neurol
13:558--566.
Seltzer B, Pandya DN (1989) Intrinsic connections and architectonics of
the superior temporal sulcus in the rhesus monkey. J Comp Neurol
290:451--471.
Seltzer B, Cola MG, Gutierrez C, Massee M, Weldon C, Cusick CG
(1996) Overlapping and nonoverlapping cortical projections to
cortex of the superior temporal sulcus in the rhesus monkey:
double anterograde tracer studies. J Comp Neurol 370:
173--190.
Sharp DJ, Scott SK, Wise RJ (2004) Monitoring and the controlled
processing of meaning: distinct prefrontal systems. Cereb Cortex
14:1--10.
Snowden JS, Goulding PJ, Neary D (1989) Semantic dementia:a form of
circumscribed cerebral atrophy. Behav Neurol 2:167--182.
Snowden JS, Neary D, Mann DM, Goulding PJ, Testa HJ (1992) Progressive language disorder due to lobar atrophy. Ann Neurol
31:174--183.
Stark CE, Squire LR (2001) When zero is not zero: the problem of
ambiguous baseline conditions in fMRI. Proc Natl Acad Sci USA
98:12760--12766.
Stowe LA, Broere CA, Paans AM, Wijers AA, Mulder G, Vaalburg W,
Zwarts F (1998) Localizing components of a complex task:
sentence processing and working memory. Neuroreport 9:
2995--2999.
Swinburn K, Porter G, Howard D (2004) The Comprehensive Aphasia
Test. Hove: Psychology Press.
Talaraich J, Tournoux P (1998) Co-planar stereotaxic atlas of the human
brain: a 3-dimensional proportional system, an approach to cerebral
imaging. New York: Thieme.
Tian B, Reser D, Durham A, Kustov A, Rauschecker JP (2001) Functional
specialization in rhesus monkey auditory cortex. Science
292:290--293.
Vandenberghe R, Nobre AC, Price CJ (2002) The response of left
temporal cortex to sentences. J Cogn Neurosci 14:550--560.
Wise RJ, Howard D, Mummery CJ, Fletcher P, Leff A, Buchel C, Scott SK
(2000) Noun imageability and the temporal lobes. Neuropsychologia
38:985--994.
Wise RJ, Scott SK, Blank SC, Mummery CJ, Murphy K, Warburton EA
(2001) Separate neural subsystems within ‘Wernicke’s area’. Brain
124:83--95.
Wong PC (2002) Hemispheric specialization of linguistic pitch patterns.
Brain Res Bull 59:83--95.
Zola-Morgan S, Squire LR (1993) Neuroanatomy of memory. Annu Rev
Neurosci 16:547--563.
Cerebral Cortex August 2006, V 16 N 8 1125