c o r t e x 4 9 ( 2 0 1 3 ) 6 1 1 e6 2 5

Available online at www.sciencedirect.com

Journal homepage: www.elsevier.com/locate/cortex

Review

The neural basis of semantic cognition: Converging evidence

from neuropsychology, neuroimaging and TMS

Elizabeth Jefferies*
Department of Psychology, University of York, York, UK

article info abstract

Article history: Recent studies suggest that a complex, distributed neural network underpins semantic
Received 27 June 2011 cognition. This article reviews our contribution to this emerging picture and traces the
Reviewed 05 September 2011 putative roles of each region within this network. Neuropsychological studies indicate that
Revised 24 October 2011 semantic cognition draws on at least two interacting components: semantic representa-
Accepted 9 January 2012 tions [degraded in semantic dementia (SD)] and control processes [deficient in patients
Action editor Stefano Cappa with multimodal semantic impairment following stroke aphasia (SA)]. To explore the first
Published online 13 November 2012 component, we employed distortion-corrected functional magnetic resonance imaging
(fMRI) and transcranial magnetic stimulation (TMS) in healthy volunteers: these studies
Keywords: convergently indicated that the anterior temporal lobes (ATLs; atrophied in SD) combine
Semantic cognition information from different modalities within an amodal semantic “hub”. Regions of cortex
Neuropsychology that code specific semantic features (“spokes”) also make a critical contribution to
fMRI knowledge within particular categories. This network of brain regions interacts with
Transcranial magnetic stimulation semantic control processes reliant on left inferior frontal gyrus (LIFG), posterior middle
Semantic dementia temporal gyrus (pMTG) and inferior parietal cortices. SA patients with damage to these
Aphasia regions have difficulty focussing on aspects of knowledge that are relevant to the current
goal or context, in both verbal and non-verbal tasks. SA patients with LIFG and tempor-
oparietal lesions show similar deficits of semantic control, suggesting that a large-scale
distributed cortical network underpins semantic control. Convergent evidence is again
provided by fMRI and TMS. We separately manipulated the representational and control
demands of a semantic task in fMRI, and found a dissociation within the temporal lobe:
ATL was sensitive to the number of meanings retrieved, while pMTG and LIFG showed
effects of semantic selection. Moreover, TMS to LIFG and pMTG produced equal disruption
of tasks tapping semantic control. The next challenges are to delineate the specific roles of
each region within the semantic control network and to specify the way in which control
processes interact with semantic representations to focus processing on relevant features
of concepts.
ª 2012 Elsevier Ltd. All rights reserved.

Semantic cognition is a fundamental component of mind and knowledge to drive context- and time-appropriate behaviour
behaviour: it brings meaning to our ongoing verbal and non- (Lambon Ralph and Patterson, 2008; Corbett et al., 2009a). As
verbal experiences and memories and allows us to use this such, it is at the core of language and communication as well

* Department of Psychology, University of York, York YO10 5DD, UK.

E-mail address: ej514@york.ac.uk.
0010-9452/$ e see front matter ª 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.cortex.2012.10.008
612 c o r t e x 4 9 ( 2 0 1 3 ) 6 1 1 e6 2 5

as non-verbal, everyday skilled behaviours (e.g., using objects

and sequencing actions to achieve a goal). Our semantic
knowledge is multimodal: it allows us to determine the
meanings of items encountered via any of our senses. We can
recognise and understand pictures, faces, smells, environ-
mental sounds, words and sentences and events, and estab-
lish the identity of objects through touch. However,
multimodal semantic representations are not sufficient for
successful semantic cognition because we store a wealth of
information about the meanings of words/objects and typi-
cally only a subset of this knowledge is required for a task e
other aspects of knowledge may actually be inappropriate and
unhelpful. For example, thinking about “coins” and “loans” is
probably not helpful when trying to understand the sentence
“The bank was slippery” (since in this context, the word
“bank” is likely to refer to a river). Similarly, playing the piano
requires information about fine movements of the fingers to
be retrieved, yet if your task is to move a piano across the
room, it is necessary to retrieve very different actions (Saffran,
2000). Control processes therefore play an essential role in
shaping the activation within the semantic system, such that
context- and task-relevant aspects of meaning are brought to
the fore. Although in some circumstances, it may be sufficient
to retrieve dominant aspects of meaning relatively automati-
cally, in many other situations, we need to retrieve distant
semantic associations or weakly activated features in a more
controlled way, and/or select pertinent aspects of knowledge
whilst inhibiting irrelevant semantic features. We may also
need to configure the components of the semantic network in
line with our current goals or expectations and to monitor our
semantic retrieval so that control processes can be adjusted if
necessary.
Semantic representation and control are not encapsulated
in single, modular brain areas but reflect the joint action of
a widely distributed set of cortical regions (in common with
other higher brain functions; see Fig. 1). To make progress in
understanding this network of brain regions, we have con-
ducted neuropsychological studies comparing the nature of
semantic deficits that arise from different aetiologies and
areas of brain injury. (1) Patients can show deficits in
comprehension that are specific to a particular modality: for
example, patients with ‘pure word deafness’ have difficulty
accessing semantic knowledge from spoken words, while
those with visual agnosia have difficulty assessing knowledge
from vision (e.g., Farah, 2004; Franklin et al., 1996). The fact
that comprehension from other modalities is intact in such
patients indicates that the central store of conceptual
knowledge is preserved. (2) Individuals with semantic
dementia (SD) show progressive degradation of central
conceptual representations, while other aspects of language
and cognition remain largely intact (e.g., Hodges et al., 1992;
Snowden et al., 1989; Warrington, 1975). This erosion of
semantic knowledge gives rise to poor comprehension across
all input and output modalities (Bozeat et al., 2000; Patterson
et al., 2007). (3) Multimodal semantic deficits can also occur
in patients with stroke aphasia (SA), although they are asso-
ciated with different areas of brain damage that do not overlap
with the regions in SD (see below; Jefferies and Lambon Ralph,
2006). These patients inconsistently access the meanings of
items: in particular, they have difficulty in semantic tasks
Fig. 1 e Convergent evidence for the distributed neural
network underpinning semantic cognition (adapted from
Whitney et al., 2011b, with permission).
Footnote: figure shows patient lesions (SD in blue and
semantic aphasia in pink, from Jefferies and Lambon Ralph,
2006); activation peak in ATL identified using distortion-
corrected fMRI (purple circle, from Binney et al., 2012); fMRI
peaks produced by manipulations of semantic control
( green circles, Thompson-Schill et al., 1997; Wagner et al.,
2001; Badre et al., 2005), and sites used in our TMS studies
( yellow circles, e.g., Whitney et al., 2011b; Pobric et al.,
2007).
with greater executive demands. This suggests that SA
patients have an intact store of conceptual knowledge but
damage to semantic control processes.
Following these case-series comparisons of patients with
SD and SA, which have highlighted the effects of impairment
to amodal semantic representations and control processes
respectively, we have used complementary neuroscientific
methods e functional neuroimaging and transcranial
magnetic stimulation (TMS) e to seek converging evidence for
our hypotheses about the neural basis of these two key
components of semantic cognition in healthy volunteers.
1. Neural basis of semantic representation
Where is semantic knowledge represented in the brain? Many
researchers propose an ‘embodied’ view in which semantic
information draws on a distributed network of sensory and
motor representations (e.g., Pulvermuller, 2005; Martin, 2007;
Barsalou, 1999). According to this view, the meaning of an
item like “scissors” is derived from links between neural
assemblies that represent this object’s distinctive shape, the
“snip” sound that it makes, information about how you hold
and use scissors, linguistic properties of the word “scissors”
and so on. These links allow all of the information you have
about an object to be activated from a single modality e so
that, on hearing the word “scissors”, you can easily imagine
 c o r t e x 4 9 ( 2 0 1 3 ) 6 1 1 e6 2 5
what they look, sound and feel like. Functional neuroimaging
studies provide support for this proposal: the retrieval of
semantic information, such as an object’s colour or action,
elicits activation in cortical areas that are adjacent to (or
overlapping with) perceptual/motor areas (Martin et al., 1995;
Chao et al., 1999; Goldberg et al., 2006; Hauk et al., 2004).
Patients who are unable to access semantic knowledge from
a specific input, such as an object’s visual form or spoken
name (as in visual agnosia or pure word deafness), are likely to
have damage to these modality-specific aspects of meaning.
Despite these findings, there is ongoing controversy about
the extent to which sensory and motor activation is necessary
and sufficient for semantic processing (e.g., Meteyard et al.,
2012; Bedny et al., 2008a). Functional neuroimaging studies
cannot conclusively show that sensory and motor activation
is essential for computing meaning, since this could reflect
spreading activation from amodal semantic regions and, in
any case, such activation is unlikely to be essential for pro-
cessing the meaning of abstract concepts, such as “truth”,
which do not have sensory or motor correlates. Some theo-
rists have suggested that there are “convergence zones”
where different types of information are combined into more
abstract, multimodal semantic representations (Damasio,
1989; Patterson et al., 2007); by this view, modality-specific
activation on its own is insufficient to explain conceptual
processing. Multiple regions distributed across the cerebral
hemispheres may underpin the convergence of different
types of information e for example, one convergence zone to
link vision to language, and another to link environmental
sounds to language (Damasio, 1989, 1990). However, distrib-
uted convergence zones and/or direct links between sensory,
motor and language-specific regions may not provide an
adequate account of central semantic disorders that affect all
modalities equally, at least when these occur in the absence
of widespread brain injury (Patterson et al., 2007). As
a consequence, Patterson, Lambon Ralph and colleagues
have proposed that all knowledge pertaining to a single
concept is combined within semantic representations in the
anterior temporal lobes (ATLs; Patterson et al., 2007; Lambon
Ralph et al., 2010; Rogers et al., 2004a; Pobric et al., 2010b).
According to this “hub and spokes” model, conceptual cate-
gorisation requires central amodal representations in addition
to sensory, motor and language areas. This is because objects
that are semantically similar can nevertheless be very
different in many of their features e for example, pineapples
and grapes are different in shape, colour, size and texture, yet
are highly related conceptually. By this view, the assignment
of meaning always involves the ATL semantic hub, irre-
spective of whether the items are pictures, sounds, smells,
objects, faces, actions or words denoting concrete or abstract
concepts.
1.1. Degradation of conceptual knowledge in semantic
dementia
Much of the evidence for a central, amodal semantic store in
the ATL comes from patients with SD, who have atrophy and
hypometabolism that is predominately focussed on the ante-
rior inferior temporal lobes bilaterally (Mummery et al., 2000;
Galton et al., 2001; Studholme et al., 2004; Rosen et al., 2002;
613
Desgranges et al., 2007; Diehl et al., 2004; Nestor et al., 2006;
Mion et al., 2010). These patients display progressively wors-
ening semantic deficits that affect all modalities, including
words (concrete nouns, verbs and abstract concepts e which
show equivalent deficits as long as frequency/familiarity are
matched), pictures, sounds, smells and actions (Bozeat et al.,
2000, 2002, 2003; Luzzi et al., 2007; Coccia et al., 2004; Garrard
and Carroll, 2006; Ikeda et al., 2006; Hoffman and Lambon
Ralph, 2011; Jefferies et al., 2009; Bird et al., 2000). Despite this
all-encompassing conceptual deficit, other aspects of cogni-
tion e for example, phonology and syntax, digit span, visuo-
spatial processing and executive control e are largely
preserved (Jefferies et al., 2004, 2005; Kramer et al., 2003;
Hodges et al., 1999).
Several features of SD support the view that these patients
have degradation of central amodal semantic representations
(see Patterson et al., 2007; Lambon Ralph et al., 2010; Lambon
Ralph and Patterson, 2008). Patients exhibit a systematic
decline in their knowledge, which affects less familiar, atypical,
and specific-level concepts more severely and at an earlier stage
of the disease (Hodges et al., 1995; Bozeat et al., 2003; Woollams
et al., 2008; Patterson et al., 2007; Rogers et al., 2004a). General
information that is shared across many semantically-related
concepts (e.g., animals have four legs) is better preserved than
specific information that is not shared (e.g., giraffes have long
necks). SD patients show this specific-to-general decline across
a wide variety of semantic tasks, involving verbal or non-verbal
input, differing output (production vs comprehension) and
a variety of task demands (e.g., matching, similarity and asso-
ciation judgements) e for example, this pattern is evident in
picture naming, wordepicture-matching, picture copying and
object decision (Bozeat et al., 2003; Woollams et al., 2008;
Patterson et al., 2006, 2007; Rogers et al., 2004a). In object deci-
sion tasks, patients are likely to accept pictures in which
a relatively unique feature has been replaced by an incorrect
shared feature (such as a giraffe with a short neck) but can
readily reject picture in which a shared feature has been
replaced by a unique one (such as an elephant with a long neck)
(Rogers et al., 2004b). In addition, when the same concepts are
probed using different input/output modalities or different
types of semantic task, SD patients are highly consistent in the
concepts they can demonstrate knowledge of and the concepts
that are impaired, even when frequency/familiarity is taken
into account (Bozeat et al., 2000; Jefferies and Lambon Ralph,
2006). This suggests that SD produces degradation of a central
store of amodal semantic representations: the degree of
damage to a particular concept in an individual patient there-
fore predicts their performance on any given semantic task.
1.2. Convergent support for an amodal semantic hub in
the ATLs
Despite the story emerging from studies of patients with SD,
the view that the ATL plays a central role in the representation
of semantic knowledge has proved controversial. This partly
reflects the fact that, until recently, there was relatively
little corroborating information from other neuroscience
methods, such as functional magnetic resonance imaging
(fMRI) and transcranial magnetic stimulation (TMS). Conver-
gent evidence from healthy participants using these methods
614 c o r t e x 4 9 ( 2 0 1 3 ) 6 1 1 e6 2 5
is essential because while SD patients have relatively focal
atrophy of bilateral ATL, many also have mild atrophy and
hypometabolism in mid-inferior temporal and/or orbito-
frontal areas. In addition, SD patients have bilateral ATL
damage and this makes it difficult to assess the roles of left
and right ATL separately. In contrast, functional neuro-
imaging and TMS studies can explore the roles of smaller
anatomical regions, and separately consider the roles of left
and right ATL. This work can therefore determine which
portions of ATL are critical for semantic processing, and if there is
any differentiation of function across this region.
1.2.1. Functional neuroimaging
While some functional neuroimaging studies, particularly
those employing positron emission tomography (PET), have
highlighted the role of ATL in semantic processing (e.g., Devlin
et al., 2000; Bright et al., 2004; Rogers et al., 2006; Scott et al.,
2000; Crinion et al., 2003; Noppeney and Price, 2002), many
fMRI studies have failed to observe activation in this area, and
instead have reported that key semantic regions fall within
inferior frontal, posterior temporal and inferior parietal cortex
(e.g., Wible et al., 2006; Gold et al., 2006; Demb et al., 1995;
Mechelli et al., 2006). Given the pre-eminence of fMRI within
cognitive neuroscience, this probably explains why some
influential models of the neural basis of semantic cognition do
not include a key role for the ATL (Martin, 2007; Thompson-
Schill, 2003; Catani and Ffytche, 2005).
With Maya Visser, we recently conducted a meta-analysis
of over 160 functional neuroimaging studies which explored
(1) the factors that influence the likelihood of observing ATL
activation during semantic tasks and (2) the location of reli-
able activation across studies (Visser et al., 2010b). ALE anal-
yses showed reliable activation within ATL for both words and
pictures, from mid-temporal lobe sites to the pole (e.g.,
y ¼ 2e22; although there was some variation in function
across this large region, detailed below). ATL activation was
found more often in studies (1) with a large field of view,
ensuring data acquisition from even the most inferior parts of
the ATL, (2) when a demanding baseline task was used to
prevent semantic processing during ‘non-semantic’ periods
(see also Binder et al., 1999) and (3) when the ATL was selected
as a region of interest (which is unlikely for researchers
adopting one of the models above that do not emphasise the
role of the ATL). (4) There was also a very strong influence of
imaging modality, with 53% of PET studies revealing ATL
activation compared with only 30% of fMRI studies. In line
with our meta-analysis, Devlin et al. (2000) directly compared
PET and fMRI using the same category judgement task:
substantial ATL activation was detected with PET, but none
with fMRI. This difference is likely to reflect susceptibility
artefacts caused by variations in magnetic field strength at the
interface between brain, bone and the air-filled sinuses: in
fMRI studies, these produce signal loss and distortion in ATL
and orbitofrontal cortex (Ojemann et al., 1997; Gorno-Tempini
et al., 2002; Weiskopf et al., 2006; Visser et al., 2010a). PET
investigations are not subject to these difficulties.
Karl Embleton, Geoff Parker, Matt Lambon Ralph and
colleagues at the University of Manchester have developed
a distortion-corrected spin echo fMRI method in order to try to
maximise signal acquisition from the ATL (Embleton et al.,
2010; Visser et al., 2010a). We used this method to address
questions about the role of the ATL in semantic processing
that emerge directly from studies of SD patients e for
example, (1) which area(s) within ATL are important in
semantic processing (since the patients’ atrophy encom-
passes several potentially functionally-independent regions),
and (2) do left and right ATL contribute to semantic processing
for both words and pictures (a question that is difficult to
address in studies of SD patients with bilateral atrophy). In our
first distortion-corrected fMRI study (Visser et al., 2010a), we
used the category decision task employed by Devlin et al.
(2000): this fMRI method revealed significant ATL activation
in line with Devlin et al.’s PET results. Distortion-corrected
fMRI has also revealed significant ATL activation in several
tasks adapted from investigations of patients with SD (see
Binney et al., 2010; Visser et al., 2012), including synonym
judgement (Jefferies et al., 2009) and verbal and picture tests of
semantic association (Bozeat et al., 2000; Jefferies and Lambon
Ralph, 2006). These studies point to a distributed semantic
network, involving left inferior frontal cortex (LIFG), posterior
middle temporal gyrus (pMTG) and ATL (Fig. 1). The ATL
activation extended to the lateral surface of MTG and ITG but
was centred on the anterior fusiform gyrus, which is the site of
maximal atrophy and hypometabolism in SD (Binney et al.,
2010; Mion et al., 2010). These findings suggest that the key
site for the semantic hub may not be the temporal pole (TP),
but instead inferior and medial parts of the ATL which are
more posterior (i.e., within the anterior portions of the mid-
temporal lobe).
We have used distortion-corrected fMRI to confirm that left
and right ATL show activation to both word and picture tasks
(along with LIFG and pMTG, which are also multimodal; Visser
et al., 2012). This study therefore confirmed the bilateral
amodal pattern seen previously in ATL with PET
(Vandenberghe et al., 1996; Bright et al., 2004). In contrast,
modality-specific patterns of activation were found in posterior
temporal areas: bilateral occipitaletemporal cortex was
specifically recruited during picture tasks, while left posterior/
mid STG/MTG showed greater activation in the verbal task
(Visser et al., 2012). These findings are highly consistent with
the hub and spoke model of Patterson et al. (2007), which
proposes that posterior temporal regions correspond to
modality-specific ‘spokes’, while the anterior temporal cortex
forms an amodal semantic ‘hub’.
These results do not rule out some differentiation of
function within ATL. For example, ATL has been associated
with social concepts (Olson et al., 2007; Skipper et al.,
2011) and combinatorial semantics/narrative comprehension
(Ferstl et al., 2008; Baron and Osherson, 2011), in addition to
amodal conceptual representations. It is likely that different
regions within ATL make a greater or lesser contribution to
these different aspects of conceptual processing. Moreover,
even within an amodal hub, there may be graded specialisa-
tion which reflects the strength of connection of different ATL
regions with posterior temporal modality-specific areas. One
possibility is that left and right ATL have somewhat different
functions, following stronger connections between (i) left ATL
and left-lateralised speech production and phonological
processes and (ii) right ATL and right-lateralised face recog-
nition areas. In line with this view, researchers have noted
 c o r t e x 4 9 ( 2 0 1 3 ) 6 1 1 e6 2 5
that while SD patients always show bilateral ATL atrophy, the
degree of tissue loss can be lateralised: patients with
left > right atrophy have disproportionate problems in picture
naming, while those with right > left atrophy have greater
difficulty recognising faces than names (Lambon Ralph et al.,
2001; Snowden et al., 2004). Similar associations between left
versus right-sided ATL atrophy and verbal semantic versus
object recognition deficits have also been reported across
a broader range of patient groups (e.g., Acres et al., 2009;
Vandenbulcke et al., 2006). A second (not mutually exclusive)
possibility is that superior ATL may show greater involvement
in word semantics, while inferior regions of ATL are more
strongly focussed on picture semantic tasks, reflecting the
differential connectivity of these areas with modality-specific
regions associated with processing verbal inputs (posterior
STG) and picture inputs (fusiform cortex).
Our own findings support the second but (so far) not the
first of these possibilities. In our meta-analysis (Visser et al.,
2010b), there were no differences between verbal and picture
tasks in the distribution of peaks across left and right ATL.
However, the ATL peaks for picture-based tasks were, on
average, more inferior than the peaks for word-based tasks.
This pattern was confirmed with distortion-corrected fMRI:
word and picture judgements both produced significant acti-
vation of left and right ATL, with no clear hemispheric
differences, but the anterior fusiform showed greater activa-
tion to pictures, while the anterior STG showed greater acti-
vation to words (Visser et al., 2012; see also Skipper et al.,
2011). It seems, therefore, that even within the ATL, there is
a graded pattern of modality-specificity; in regions just
posterior to the TP, responses in MTG are wholly amodal (i.e.,
equivalent for words and pictures), while STG and fusiform
cortex show a preference for words and pictures respectively
(although fusiform cortex in Visser et al.’s study showed
a significant response to both modalities). Computational
modelling work by Plaut (2002) reveals how functional
specialisation within the semantic system could be driven by
connection strengths with modality-specific inputs: this
proposal fits well with our data, since anterior STG is strongly
connected with posterior superior temporal regions associated
with phonology and auditory processing, while anterior fusi-
form receives input from posterior inferior temporal and fusiform
areas associated with object recognition. As a consequence of
this graded specificity, it is conceivable that a patient could
show an impairment of semantic representation which
disproportionately affected words, leaving pictures more
intact, or vice versa (although such a pattern is highly unlikely
in SD). Verbal > non-verbal impairment would be expected
following damage to STG in the mid-temporal lobe, while mid-
to-posterior fusiform lesions might elicit the reverse pattern e
i.e., semantic deficits for pictures > words. Since other neu-
ropsychological and functional neuroimaging research has
suggested that right fusiform gyrus is crucial for knowledge of
visual attributes (Vandenbulcke et al., 2006), it is also possible
that two gradients of functional specialisation co-exist within
anterior temporal cortex (i.e., graded differences between left vs
right ATL and fusiform vs lateral cortex in both hemispheres).
This would explain why lesions of right fusiform have
a particularly catastrophic impact on knowledge of visual (not
functional) attributes (Vandenbulcke et al., 2006).
615
1.2.2. TMS
We have also been employing TMS to establish whether the
ATL makes a critical contribution to semantic cognition in
healthy participants. TMS generates magnetic pulses over the
scalp that induce electrical activity in the underlying neurons:
when this is done repeatedly, TMS can be used to temporarily
disrupt cortical activity, making it possible to explore the
consequences of a ‘virtual lesion’ in an otherwise normal
brain (Cowey and Walsh, 1998). This corroborating evidence is
essential because, as noted above, the fMRI literature has
underemphasised the importance of ATL in semantic cogni-
tion. Moreover, while SD patients support the proposal of an
amodal semantic hub in ATL, their semantic deficits could
reflect subtle atrophy or hypometabolism in posterior
temporal cortex (Martin, 2007). TMS, in contrast, produces
relatively focal and reversible effects, making it possible to
(i) compare the contribution of several sites in the same
participants and (ii) differentiate between cortical regions
which are typically damaged together in patients e such as
left and right ATL in SD.
We used an offline inhibitory TMS procedure (low
frequency stimulation for 10 min) which disrupts tasks reliant
on the underlying cortex for approximately 10 min after
stimulation. Post-TMS performance was compared with
‘baseline’ testing either before TMS was applied or 30 min
after the end of stimulation, by which time the effects of TMS
have washed out. In a series of studies, we have demonstrated
that (i) ATLeTMS disrupts semantic tasks involving a range of
input and output modalities (e.g., picture naming; semantic
judgements about words and pictures; see Fig. 2); (ii) TMS over
this region produces more disruption of specific than basic-
level picture naming (e.g., “Dalmatian” vs “dog”); and (iii)
both left and right ATL are involved in verbal and non-verbal
Fig. 2 e Effects of TMS to left and right ATL on semantic
judgements to words and pictures (reproduced from Pobric
et al., 2010a, with permission).
Footnote: each bar represents the reaction time (RT) change
caused by TMS. For example, the white bar above the Left
TP site indicates that rTMS over left TP caused an RT delay
of 177 msec for picture association judgements, when
compared to the no-TMS condition. Negative figures
indicate RTs on TMS trials were faster than no-TMS trials.
Error bars indicate standard error of mean (SEM) adjusted
to reflect the between-condition variance used in repeated-
measure designs (Loftus and Masson, 1994). Occ
Pole [ Occipital Pole (control site not thought to be
involved in semantic cognition). TP [ temporal pole.
616 c o r t e x 4 9 ( 2 0 1 3 ) 6 1 1 e6 2 5
semantic processing (Pobric et al., 2007, 2009, 2010a,b; Lambon
Ralph et al., 2009). These effects were specific to semantic
tasks: response times on number judgement and number
naming tasks, which do not rely on ATL, were unchanged. Our
findings simulate (in milder form) the impairment seen in SD
patients and suggest that the ATL plays an essential role in
a wide range of semantic judgements in healthy volunteers.
We used the offline 1 Hz paradigm primarily because this
allowed us to undertake behavioural testing in the absence of
the jaw contractions and eye blinks that are elicited via facial
nerve stimulation when TMS is applied to ATL. However,
a caveat should be noted: the behavioural effects we observed
do not necessarily show highly focal involvement of ATL,
because this TMS method is thought to not only suppress
activation directly below the coil, but also produce distal
effects, influencing processing in other parts of the network.
These distal effects can be compensatory in nature (i.e.,
increased responsiveness following TMS) or alternatively can
reflect reduced activity in connected brain regions. Although
these considerations pose a potential problem for the inter-
pretation of our previous studies, they provide an opportunity
to study interactions between regions within the distributed
neural network underpinning semantic cognition. Binney
(2010) used a combined fMRIeTMS approach to chart the
effects of 1 Hz TMS to left ATL: this stimulation (1) suppressed
activation beneath the coil, (2) reduced activity in other con-
nected regions in the left-hemisphere (posterior temporal and
LIFG), yet (3) increased activation in right ATL, supporting our
hypothesis that ATL is bilateral system which supports
semantic processing along with posterior temporal and
frontal regions.
Finally, we have also directly compared the contribution of
the ATL ‘hub’ and feature-specific ‘spokes’ to semantic pro-
cessing using TMS. This approach overcomes the problem
that functional neuroimaging studies are correlational and
cannot be used to make causal inferences. If the application of
TMS to regions of cortex associated with visual processing or
praxis (i.e., the hand shapes and movements critical to tool
use) is shown to disrupt semantic tasks (and if this effect is
specific to relevant classes of stimuli), then it is possible to
make a stronger case for the ‘spokes’ being necessary for
semantic processing. In our experiment, 1 Hz TMS over the
ATL slowed picture naming for all categories equally, while
stimulation of an inferior parietal (IPL) site, involved in coding
praxis, induced a category-specific deficit only for manipu-
lable objects (Pobric et al., 2010b). These findings suggest that
the ATL semantic ‘hub’ and the modality-specific ‘spokes’
both make a critical contribution to the representation of
semantic knowledge. This was apparent even in a picture
naming task that did not explicitly require access to these
praxis features. In future work, it would be interesting to
extend this approach to primary sensory/motor cortex, since
the site we stimulated is likely to integrate somatosensory and
motor aspects of praxis.
1.3. Summary of brain regions involved in semantic
representation
This review, focussed on our own research, suggests that the
key regions involved in semantic representation include both
bilateral ATL (amodal ‘hub’) and ‘spokes’ representing specific
modalities or features of objects; for example, posterior infe-
rior temporal cortex (linked to visual object recognition) and
inferior parietal lobule (linked to praxis representations). This
account of the neural basis of semantic knowledge overlaps
substantially with several recent meta-analyses that also
implicate large swathes of temporal cortex in semantic pro-
cessing (Price, 2010; Binder et al., 2009). However, there are
detailed differences between these accounts: we suggest that
ATL is crucial for all aspects of knowledge e for example,
knowledge of semantic features, categories and associations,
and representations of both animals and artefacts (in line with
the absence of category-specific semantic impairment in SD;
Lambon Ralph et al., 2007, 2003). In contrast, other researchers
have assigned a more category-selective role to the ATL for
animals and/or faces and specific entities (e.g., Warrington
and Shallice, 1984; Damasio, 1990), while tool/action knowl-
edge is captured within posterior temporal lobe areas (in
particular, pMTG; e.g., Martin et al., 1995; Chao et al., 1999;
Perani et al., 1999). The ‘hub and spokes’ account is consistent
with the notion of category effects in posterior temporal and
parietal areas e for example, pMTG and IPL may be crucial for
the representation of actions/tools/verbs, given that these
regions are thought to represent visual motion and praxis
features that are particularly pertinent to these classes of
stimuli. In contrast, the role of ATL in animals and faces may
reflect general processing principles that apply to all domains
of knowledge e anterior fusiform regions may be critical for
semantic judgements with a high degree of specificity, or that
require discrimination between highly similar concepts that
share a lot of features (such as faces and animals) (Rogers
et al., 2005).
In addition, some researchers have suggested that there
might be two separate amodal semantic “hubs”, which
represent taxonomic and thematic relationships. Using
a voxel-lesion symptom mapping approach to examine
picture naming errors in patients with SA, Schwartz et al.
(2011) found that “taxonomic” errors (e.g., ‘pear’ for apple)
were associated with damage to ATL, while “thematic” errors
(e.g., ‘worm’ for apple) were associated with damage to tem-
poroparietal cortex. Schwartz et al. suggested that tempor-
oparietal regions (including pMTG and IPL) might be involved
in simulating events, capturing action, causal and spatial
relations, and that this function might be linked to the role of
these regions in action understanding. An alternative view
(although not mutually exclusive, and potentially connected
to this idea), is that pMTG and IPL form part of a distributed
semantic control network (see below).
2. Deregulated semantic cognition in
semantic aphasia
Studies of patients with SD have been enormously important
in advancing our understanding the role of the ATL in
semantic memory. However, deficits of semantic cognition
are seen more frequently following left-hemisphere stroke.
These patients typically implicate a different set of regions in
semantic processing, most notably left posterior temporal,
inferior parietal and inferior frontal regions (Chertkow et al.,
 c o r t e x 4 9 ( 2 0 1 3 ) 6 1 1 e6 2 5 617

1997; Berthier, 2001; Hart and Gordon, 1990; Hillis et al., 2001;
Dronkers et al., 2004). As a consequence, models of the neural
basis of semantic memory based on stroke data alone often
consider left temporoparietal and inferior frontal regions to be
the critical substrate for semantic memory. Stroke rarely
produces lesions in the inferior parts of ATL thought to be
critical for semantic processing for two reasons: First, middle
and inferior parts of the ATL typically receive blood from two
arteries: (i) the anterior temporal cortical artery, which
branches off the middle cerebral artery (Phan et al., 2005), and
(ii) the anterior temporal branch of the distal posterior cere-
bral artery (Phan et al., 2007). It is unusual for both of these
blood supplies to be affected by stroke simultaneously (Conn,
2003). Secondly, the anterior temporal cortical artery branches
off the middle cerebral artery below its major trifurcation: this
might make it less vulnerable to emboli, which can pass
beyond this point (Borden, 2006).
In a series of studies, we have contrasted the nature of the
semantic impairment in SD and SA. We selected stroke
patients who showed deficits across both verbal and non-
verbal semantic tests (as in SD), yet we found these
patients had qualitatively different patterns of impairment
(see also Ogar et al., 2011). In contrast to SD (which produces
gradual degradation of core amodal conceptual knowledge
following bilateral ATL atrophy), multimodal semantic
impairment in SA was associated with left prefrontal and
temporoparietal infarcts, and poor executive control over
conceptual processing (Corbett et al., 2009a; Jefferies et al.,
2007, 2008; Jefferies and Lambon Ralph, 2006; Noonan et al.,
2010). There were a number of qualitative differences
between these groups: (i) SD patients were strikingly
consistent across different semantic tasks that tapped the
same concepts, while SA patients were inconsistent. (ii) In
picture naming, SD patients made coordinate and superor-
dinate errors (e.g., producing “dog” or “animal” for squirrel).
The SA patients additionally made associative errors (e.g.,
“nuts” for squirrel), suggesting they had difficulty directing
activation towards the target and away from irrelevant pre-
potent associations. This is related to the distinction
between taxonomic and thematic errors noted by Schwartz
et al. (2011) but we have suggested an alternative interpre-
tation e patients with left prefrontal and temporoparietal
lesions have deficits of semantic control, and as a result, they
retrieve task-irrelevant but strong associations (i.e., thematic
errors). In contrast, patients with ATL lesions have degraded
semantic representations; consequently, they are unlikely to
make thematic errors (which require the retention of asso-
ciations). Instead, they largely make high frequency coordi-
nate errors (e.g., ‘dog’ for goat) and superordinate errors (e.g.,
‘animal’ for goat), reflecting their poor knowledge of less
familiar and specific-level concepts. (iii) SA patients showed
stronger benefits of cues (e.g., phonemic cues in picture
naming) that reduced the need for internally-generated
semantic control (see Fig. 3; Jefferies et al., 2008). The SA
patients were also highly sensitive to miscues designed to
activate semantic competitors (e.g., picture of a cat plus/d/;
Noonan et al., 2010). (iv) The SD patients showed strong
effects of frequency/familiarity, consistent with the view that
less frequent concepts are more vulnerable to damage. In
contrast, the SA patients showed negligible or even reverse
frequency effects. This fits with the prediction that high
frequency words have greater semantic selection demands
because they appear in more contexts and have more vari-
able meanings (Robinson et al., 2010; Almaghyuli et al., 2012;
Hoffman et al., 2011a,b). (v) In tasks designed to directly
manipulate the requirement for semantic control, the SA
patients were poor at (a) inhibiting strongly associated dis-
tracters and (b) focussing on less dominant aspects of
meaning (Noonan et al., 2010). (vi) Semantic impairment in
SA correlated with executive dysfunction (see also Baldo
et al., 2005; Wiener et al., 2004), while executive functions
were largely spared in SD.

Fig. 3 e Qualitative differences between SD and SA patients in the effect of progressive phonemic cueing on picture naming
(reproduced from Jefferies et al., 2008, with permission)
Footnote: patients with SD and multimodal semantic impairment following SA attempted to name black and white line
drawings. If they were unable to provide the correct name without a prompt, they were provided with progressive
phonemic cues. Phonemes were added to cue one at a time until the patient produced the correct response or the cue
consisted of the whole word minus the last phoneme (referred to as the ‘final cue’). Cueing produced small but significant
benefits for SD patients and more dramatic benefits in SA: even the most impaired SA patients were able to retrieve almost
all of the target names by the final cue, consistent with the proposal that their semantic knowledge remains intact.
618 c o r t e x 4 9 ( 2 0 1 3 ) 6 1 1 e6 2 5
These findings suggest that semantic cognition is under-
pinned by a large-scale neural network comprising at least
two interacting principle components e (i) semantic knowl-
edge, including amodal representations in the ATL (degraded
in SD) and (ii) semantic control processes that allow task- and
context-relevant aspects of knowledge to be brought to the
fore, while irrelevant information is suppressed (disrupted by
left prefrontal and temporoparietal lesions in SA) (Jefferies
and Lambon Ralph, 2006; Noonan et al., 2010). However,
further studies were needed to establish the underlying
nature of the semantic control deficit in SA e for example,
whether the impairment is specific to verbal semantics (since
the tasks above all involved words), or if it extends to non-
verbal conceptual tasks, even though the key presenting
symptom in this group is aphasia. Studies led by Faye Corbett
have demonstrated semantic control deficits across a wide
range of verbal and non-verbal tasks (Corbett et al., 2009a,b,
2011). In one study, we compared SD and SA patients on
a battery of object use tasks and found qualitative differences
that resembled the pattern in the verbal domain. While the SD
patients performed consistently across tasks that tapped
different aspects of knowledge and object use for the same
items, the SA participants’ performance reflected the control
requirements of the tasks. They were able to complete
straightforward item matching tasks, such as wordepicture-
matching, but performed more poorly on associative picture-
matching involving the same items, and on complex
mechanical puzzles (Corbett et al., 2009a). The SA group also
showed strong sensitivity to manipulations of semantic
control in the domain of object use: they had difficulty using
their knowledge of specific semantic features to flexibly
support the non-canonical uses of objects (e.g., using a news-
paper as a fly swat), they showed poor inhibition of semanti-
cally-related distracters, and their object use improved with
the provision of verbal and pictorial cues designed to
constrain the task (Corbett et al., 2011).
These findings have important consequences for how we
approach aphasia rehabilitation. If semantic knowledge is
largely intact in SA but these patients have difficulty retrieving
task- and context-relevant aspects of meaning following
executive deficits that are correlated with the degree of
semantic impairment, interventions that minimise the exec-
utive demands of semantic tasks are likely to be effective in
improving comprehension. Indeed, cues that are consistent
with the target response and inconsistent with distracters,
and which therefore minimise the requirement for internally-
generated semantic control, boost the performance of SA
patients in both verbal and non-verbal tasks (Corbett et al.,
2011; Jefferies et al., 2008). Longer-lasting gains in compre-
hension may follow from a combination of training on
executively-demanding semantic tasks, plus brain stimula-
tion techniques such as transcranial direct current stimula-
tion (tDCS) to augment neural plasticity.
2.1. Convergent support for a distributed network
underpinning semantic control
The prefrontal cortex has long been associated with cognitive
control and there is strong neuropsychological evidence
linking left inferior frontal gyrus (LIFG) to deficits in the
control of linguistic and semantic processing (Schnur et al.,
2009; Thompson-Schill et al., 1998; Novick et al., 2009;
Robinson et al., 2010). However, as noted above, our research
suggests that semantic control impairment in SA follows from
both left prefrontal and temporoparietal lesions. SA cases
with LIFG and temporoparietal lesions have almost indistin-
guishable deficits: both groups have difficulty rejecting
strongly related distracters, retrieving the less frequent
meanings of ambiguous words and overcoming the effects of
miscues (Noonan et al., 2010). This suggests that anterior and
posterior brain regions form a large-scale distributed cortical
network underpinning semantic control.
Nevertheless, patients with large and variable lesions are
not ideally suited to producing a detailed neural model of
semantic control: SA patients’ deficits could conceivably
follow damage to white matter tracts and/or their cortical
damage could span several functionally-separable regions e
for example, temporoparietal patients often have damage to
both posterior temporal and inferior parietal cortex, which
might make separate contributions to semantic control.
Similarly, frontal SA patients might have damage encom-
passing several functionally discrete regions, such as LIFG and
dorsomedial PFC (which is associated with executive control
beyond the semantic domain; Duncan, 2010). Although SA
patients show deficits on standard measures of executive
function which correlate with their degree of comprehension
impairment (Jefferies and Lambon Ralph, 2006; Baldo et al.,
2005; Wiener et al., 2004), the large lesions in this group may
mask functional specialisation, potentially within both the
frontal and posterior components of the semantic control
network. Some regions may be selectively involved in linguistic
control, some may underpin conceptual control for both verbal
and non-verbal stimuli, and others may particulate in execu-
tive control irrespective of task (semantic vs non-semantic) or
modality (verbal vs non-verbal). Once again, it is therefore
important to seek convergent evidence from neuroimaging
and TMS methods that have better spatial resolution. The key
questions are: (1) is there convergent evidence for a large-
scale distributed neural network underpinning semantic
control that encompasses areas beyond LIFG; (2) which
specific sites within the areas of brain-injured in SA are crucial
for semantic control and (3) what is the functional organisa-
tion of the semantic control network e i.e., how does semantic
control relate to linguistic control and domain-free executive
control?
2.1.1. Functional neuroimaging
fMRI studies of healthy participants partially converge with
the conclusions of our neuropsychological investigations,
although their primary focus has been on LIFG (BA44,45,47)
(Thompson-Schill et al., 1997; Wagner et al., 2001; Badre et al.,
2005). This region responds strongly to experimental manip-
ulations of semantic control demands: it shows more activa-
tion for (i) ambiguous words (with multiple meanings)
compared with unambiguous words (Bedny et al., 2008b; Rodd
et al., 2005; Whitney et al., 2009), (ii) associations based on
specific semantic features (i.e., colour, shape) as opposed to
associations based on global semantic relatedness, (iii) deci-
sions involving many versus few response options and (iv)
cue-target pairs when associative strength is low versus high
 c o r t e x 4 9 ( 2 0 1 3 ) 6 1 1 e6 2 5
(Badre et al., 2005; Thompson-Schill et al., 1997; Wagner et al.,
2001). However, while SA patients typically have widespread
damage in LIFG, fMRI suggests a possible functional subdivi-
sion, with anterior regions (BA47) acting to bias semantic
retrieval according to current goals, and posterior regions
(BA45/44) underpinning semantic selection when several
competing representations are active (Badre et al., 2005).
Unlike our patient studies, the fMRI literature does not
highlight a role for temporoparietal areas in semantic control.
This apparent discrepancy between methods is important
because some researchers propose that posterior temporal
cortex (as opposed to ATL) is the central site for semantic
representation (e.g., Martin, 2007). In reality, there are likely to
be dissociable regions within temporal cortex that support
semantic control and the storage of knowledge. Many neuro-
imaging studies have, in fact, observed sites in posterior
temporal and inferior parietal cortex that show activation
modulated by semantic control demands (e.g., Badre et al.,
2005; Nagel et al., 2008; Thompson-Schill et al., 1997; Wagner
et al., 2001). We recently conducted a meta-analysis of func-
tional neuroimaging studies that confirmed that, like LIFG,
pMTG, intraparietal sulcus (Noppeney et al., 2004) and
portions of the left inferior parietal lobule (particularly a site at
the boundary of dorsal angular gyrus (AG) and supramarginal
gyrus) are reliably influenced by manipulations of semantic
control (Noonan et al., submitted for publication). In this
study, we selected 53 neuroimaging studies which contrasted
semantic tasks with high versus low executive requirements.
Moreover, we were able to demonstrate a functional dissoci-
ation between ATL and pMTG within a single fMRI study utilis-
ing ambiguous words in a double-prime paradigm (Whitney
et al., 2011a): ATL was sensitive to the number of meanings
that were retrieved, consistent with a role for this region in
semantic representation, while pMTG and LIFG showed
greater activation when the dominant meanings of words had
to be inhibited, supporting our hypothesis that these regions
underpin semantic control.
2.1.2. TMS
Once again, we have used TMS to confirm a role for these sites
in semantic control. First, in a convergent neuropsychological
and TMS investigation, we focussed on the role of LIFG in
semantic judgements for abstract words (Hoffman et al.,
2010) e one of the brain regions most reliably activated by
tasks involving abstract as opposed to concrete words (Binder
et al., 2009). Abstract concepts are generally more difficult to
process than concrete concepts but there are at least two
alternative (although not mutually exclusive) explanations for
this. One view, referred to as the “dual-coding account”,
(Pavio, 1986) is that abstract concepts rely predominately on
language areas: therefore, they do not benefit from broader
‘embodied’ activation within sensory and motor areas. An
alternative approach suggests that abstract words are used in
a broader range of contexts and this makes it more difficult to
activate associations relevant to these words (Schwanenflugel
and Shoben, 1983). From these accounts, we might predict
that abstract concepts would require more semantic and
linguistic control compared with concrete concepts because (i)
they are used in a broader range of contexts and their mean-
ings are therefore ambiguous (Hoffman et al., 2011b) and (ii)
619
they have higher lexical retrieval or phonological working
memory demands (Binder et al., 2005). First, we established
that SA patients with LIFG damage had greater difficulty in
a synonym judgement task for abstract than concrete items.
Similar difficulties have been demonstrated before for
patients with left perisylvian lesions, consistent with the view
that linguistic processes are particularly critical for these
concepts (e.g., Goodglass et al., 1969); however, as noted
above, our SA patients showed comparable deficits in verbal
and non-verbal semantic tasks, suggesting they had impair-
ment of amodal control processes. Moreover, their problems
were ameliorated by providing a sentence cue that placed the
word in a specific context. Our interpretation of this finding is
that the sentence cues reduced the need for internally-
generated semantic and linguistic control by focussing acti-
vation on relevant aspects of meaning. When TMS was
applied to LIFG (BA45) in healthy participants, we replicated
this pattern: response times were slowed for abstract and not
concrete words, but only in the absence of a sentence cue.
We have also used TMS to investigate the wider neural
network underpinning semantic control for words, by con-
trasting the effects of stimulation of LIFG and pMTG (Whitney
et al., 2011b). We found that TMS to these sites produced an
identical pattern: there was no effect of TMS on semantic
judgements to strongly associated pairs of words (i.e., SALT-
PEPPER), which are thought to be underpinned by automatic
spreading activation potentially within the language system
itself (Simmons et al., 2008); in contrast, judgements about
distantly-associated words, which are thought to require
additional semantic control processes (e.g., SALT-GRAIN),
were equally slowed by TMS delivered to LIFG and pMTG.
These findings suggest that semantic control effects in pMTG
in fMRI studies cannot be ‘explained away’ in terms of, for
example, strong coupling with LIFG; instead both LIFG and
pMTG appear to play an essential role in a distributed neural
network underpinning semantic control (however, it remains
unclear from these results whether these control processes
are specific to language or extend to conceptual processing
more widely; see below).
Recently, in an as yet unpublished study, we explored the
same tasks in a combined fMRI–TMS investigation. We applied
1 Hz TMS to LIFG (BA45) and used fMRI to measure the effect
on neural activity in other putative components of the
semantic control network. Additional activation was seen in
pMTG, compared to a baseline scan with no stimulation, and
these changes were restricted to situations where the demand
on the semantic control network was high. These results
therefore strongly suggest that LIFG and pMTG are both
components of a distributed cortical system underpinning
semantic control: when the contribution of LIFG is disrupted
via TMS, pMTG shows compensatory increases in activation.
One important yet unresolved issue is whether the sites
within the semantic control network e i.e., LIFG, pMTG and
dorsal AG plus IPS e make different contributions to semantic
control. Although SA patients with LIFG and temporoparietal
lesions have highly similar deficits, cases with LIFG lesions
have greater difficulty inhibiting previously relevant semantic
information e they show (i) more perseverations of their
earlier responses in tasks like picture naming and (ii) declining
accuracy in ‘cyclical’ tasks that present a set of semantically-
620 c o r t e x 4 9 ( 2 0 1 3 ) 6 1 1 e6 2 5
related items repeatedly, leading to a build-up of competition
between previous and current targets (Jefferies et al., 2007;
Gardner et al., 2012). Similarly, pMTG and sites within parietal
cortex may play distinct roles in the regulation of semantic
processing although these regions do not easily dissociate in
studies of brain-injured patients. In fMRI, IPS is activated in
tasks requiring the topedown selection of specific semantic
features (Badre et al., 2005; Thompson-Schill et al., 1997),
while pMTG is sensitive to cue-target associative strength,
which influences the degree of stimulus-driven semantic
control that is required (Badre et al., 2005; Wagner et al., 2001).
To develop a detailed understanding of the distinct roles of
these regions, it is also imperative to examine the relationship
between control over (i) amodal conceptual processing, (ii)
semantic control specific to language and (iii) domain-general
executive processes. SA patients show correlations between
their scores on semantic and executive tests (Jefferies and
Lambon Ralph, 2006) but their large lesions may mask
potential dissociations between these functions. We have new
and as yet unpublished data showing that patients with dys-
executive syndrome (without aphasia) have semantic
impairment that resembles SA: this suggests that ‘multiple-
demand’ regions like inferior frontal sulcus, frontal oper-
culum, dorsomedial prefrontal cortex and IPS, which are
recruited during a wide variety of executively-demanding
tasks (Duncan, 2010), make an important contribution to
semantic control (see also Nagel et al., 2008). However, the
involvement of some regions e e.g., LIFG and pMTG e may be
more specific to semantic control (Nagel et al., 2008; Devlin
et al., 2003; Gough et al., 2005). Therefore, in a recent TMS
study (Whitney et al., 2012), we contrasted two different
manipulations of semantic control (based on associative
strength and feature selection respectively) with a non-
semantic task involving the selection of specific visual
features (based on Navon letters with opposing local and
global features). We found an intriguing dissociation between
LIFG/pMTG and IPS. While TMS to LIFG and pMTG disrupted
both tasks requiring semantic control, leaving the non-
semantic task unaffected, stimulation of IPS differed from
this pattern in two ways: (i) it only influenced the selection of
specific semantic features (e.g., matching ‘tomato’ with ‘stop
sign’, based on shared colour), not the ability to detect global
distant relationships (e.g., matching ‘salt’ with a relatively
distantly-associated word, such as ‘grain’) and (ii) it disrupted
both the semantic and non-semantic Navon trials, consistent
with the notion that IPS forms part of the multiple-demand
network. Our findings therefore provide support for
a complex, distributed semantic control network that shows
(i) some specialisation of function, such that different sites
contribute to different aspects of semantic control and (ii)
partial overlap with sites supporting domain-general execu-
tive control.
2.3. Summary of brain regions involved in semantic
control
This review, focussed on our own research, suggests that the
key regions involved in semantic control include LIFG, pMTG
and dorsal AG/IPS. Binder et al.’s (2009) meta-analysis of
neuroimaging studies of semantic cognition highlights similar
regions, but provides a differing account of their functions.
First, there is controversy about the role of the AG. Binder et al.
(2009) propose that this region integrates multimodal
semantic concepts into a single, coherent meaning, noting for
example that this site shows late activation in sentence
comprehension tasks, which is maximal at the point when
the constituent words are linked together conceptually
(Humphries et al., 2007). It is likely that AG contains several
distinct functional regions (Seghier et al., 2010): for example,
the dorsal AG bordering IPS might play a role in selection/
inhibition in semantic and non-semantic tasks. In contrast,
the more ventral AG might have a selective semantic inte-
gration role. Binder et al. (2009) note that “fluent conceptual
combination” is an essential component of many tasks that
require “problem solving and planning” and in this way, we
might anticipate AG regions to contribute to executive aspects
of semantic processing.
Our proposal that pMTG forms part of the semantic control
network is perhaps the most controversial aspect of our
account, since, as noted above, this area has been linked to the
representation of tool, action and verb knowledge (Martin,
2007; Martin et al., 1995; Chao et al., 1999; Perani et al., 1999).
A key issue for future research will be to determine whether
the precise cortical areas that respond to tool/action knowl-
edge and semantic control manipulations are overlapping or
distinct, and to provide an explanatory framework for the
overlap (should it exist). For example, it might be that both
pMTG and IPL are involved in mental simulation of mean-
ingful events/contexts (Schwartz et al., 2011), and that this
type of simulation is helpful in many control-demanding
semantic tasks.
Binder et al. (2009) additionally note that many fMRI
studies yield significant and extensive activation in dorso-
medial prefrontal cortex (BA8 and 9). This region has not been
the focus of substantial research effort within the field of
semantic cognition (including in our own studies), but
nevertheless this site is linked to planning, attention and
motivation and overlaps with the multiple-demand network
of brain regions linked to domain-free executive function and
fluid intelligence (Duncan, 2010).
3. Conclusion and future directions
Our research over the last 5 years has contributed to our
understanding of the distributed neural network underpin-
ning semantic cognition in several ways: (1) We have obtained
convergent evidence from distortion-corrected fMRI and TMS
studies of healthy volunteers that points to a role of both left
and right ATL in the representation of word and picture
meanings, in line with findings from investigations of patients
with SD. (2) The distortion-corrected fMRI studies indicate
graded specialisation of function within ATL, with more
superior areas playing a greater role in semantic judgements
about words, and inferior regions making a stronger contri-
bution to semantic judgements about pictures. (3) We have
shown that the degradation of semantic knowledge in SD is
qualitatively different from the difficulties in semantic control
shown by patients with multimodal semantic impairment
following SA. This suggests that semantic cognition draws on
 c o r t e x 4 9 ( 2 0 1 3 ) 6 1 1 e6 2 5
at least two interacting components e semantic representa-
tions (degraded in SD) and semantic control processes (defi-
cient in SA). (4) SA patients have damage to different cortical
regions beyond ATL e in particular, LIFG, posterior temporal
and/or inferior parietal cortices. This suggests that a large-
scale distributed cortical network underpins semantic
control. We have again obtained convergent evidence for this
view from fMRI and TMS. In our fMRI study, ATL was sensitive
to the number of meanings retrieved, while pMTG and LIFG
showed effects of semantic selection/inhibition. Moreover,
TMS to LIFG and pMTG produced equal disruption of tasks
tapping semantic control.
The next challenges are (i) to delineate the specific roles of
each region within the semantic control network and (ii) to
specify the way in which control processes interact with
semantic representations. We have started to make progress
on the first of these issues; however, many questions remain
unanswered e for example, studies have not yet fully char-
acterised the different functions of LIFG, pMTG and IPL and
how they contribute to bottomeup and topedown aspects of
semantic control, nor how these sites interact to give rise to
control over semantic activation in different contexts. A
related question is whether the semantic control network that
underpins verbal tasks is identical to the network supporting
control-demanding non-verbal semantic tasks; our theoretical
account predicts that semantic control mechanisms are
amodal but functional neuroimaging and TMS research has
almost exclusively relied on verbal tasks, so the existence of
separate linguistic control areas is currently hard to rule out.
We still know relatively little about how semantic control
processes interact with the store of knowledge such that
processing is focussed on task-relevant features, or how these
task-relevant elements are integrated: this is likely to be an
exciting avenue for research over the next few years. Progress
may follow the use of experimental paradigms that manipu-
late control and representational demands simultaneously,
and through the use of additional imaging methodologies,
such as magnetoencephalography (MEG), that allow us to
chart the interactions between brain regions with high
temporal resolution.
Finally, we are starting to explore the practical implica-
tions of our research for the patients who initiated it. Our
conclusion that multimodal semantic impairment in SA is
linked to poor semantic/executive control has clear implica-
tions for speech and language therapy e in particular, it
suggests that recovery may be facilitated by the use of
training tasks that focus on strengthening semantic control
processes, as opposed to attempts to retrain ‘lost’ semantic
knowledge. We are starting to explore these ideas in studies
that use tDCS to augment the effects of semantic and exec-
utive training.
Acknowledgements
The work reported in this article would not have been possible
without the efforts of my colleagues and collaborators: I have
benefited enormously from their ingenuity and kindness. I am
particularly indebted to Matt Lambon Ralph at the University
621
of Manchester, who has provided me with invaluable support
for many years. I would also like to extend special thanks to
the following people who played a key role in particular
projects: Azizah Almaghyuli, Richard Binney, Faye Corbett,
Sheeba Ehsan, Hannah Gardner, Paul Hoffman, Katya Krieger-
Redwood, Krist Noonan, Karalyn Patterson, Gorana Pobric,
Tim Rogers, Maya Visser and Carin Whitney. I am very
grateful to the British Neuropsychological Society for nomi-
nating me for the Cortex Prize, awarded by the Federation of
the European Societies of Neuropsychology (ESN), which led to
an invitation to write this review of my recent research. We
are indebted to the patients and their carers for their generous
assistance with our research. I would also like to thank Matt
Lambon Ralph, Carin Whitney and two anonymous reviewers
for their helpful comments on a draft of this manuscript.
Financial support was provided by MRC (G0501632), the
Wellcome Trust (078734/Z/05/Z) and Research into Ageing/Age
UK (Ref. 335).
references
Acres K, Taylor KI, Moss HE, Stamatakis EA, and Tyler LK.
Complementary hemispheric asymmetries in object naming
and recognition: A voxel-based correlational study.
Neuropsychologia, 47(8e9): 1836e1843, 2009.
Almaghyuli A, Lambon Ralph MA, and Jefferies E. Deficits of
semantic control produce reverse frequency effects: Evidence
from neuropsychology and dual task methodology.
Neuropsychologia, 50: 1968e1979, 2012.
Badre D, Poldrack RA, Pare-Blagoev EJ, Insler RZ, and Wagner AD.
Dissociable controlled retrieval and generalized selection
mechanisms in ventrolateral prefrontal cortex. Neuron, 47(6):
907e918, 2005.
Baldo J, Dronkers N, Wilkins D, Ludy C, Raskin P, and Kim J. Is
problem solving dependent on language? Brain and Language,
92: 240e250, 2005.
Baron SG and Osherson D. Evidence for conceptual combination
in the left anterior temporal lobe. NeuroImage, 55(4):
1847e1852, 2011.
Barsalou LW. Perceptual symbol systems. Behavioral and Brain
Sciences, 22: 577e660, 1999.
Bedny M, Caramazza A, Grossman E, Pascual-Leone A, and
Saxe R. Concepts are more than percepts: The case of action
verbs. The Journal of Neuroscience, 28(44): 11347e11353, 2008a.
Bedny M, McGill M, and Thompson-Schill SL. Semantic
adaptation and competition during word comprehension.
Cerebral Cortex, 18(11): 2574e2585, 2008b.
Berthier ML. Unexpected brainelanguage relationships in
aphasia: Evidence from transcortical sensory aphasia
associated with frontal lobe lesions. Aphasiology, 15(2): 99e130,
2001.
Binder JR, Desai RH, Graves WW, and Conant LL. Where is the
semantic system? A critical review and meta-analysis of 120
functional neuroimaging studies. Cerebral Cortex, 19:
2767e2796, 2009.
Binder JR, Frost JA, Hammeke TA, Bellgowan PSF, Rao SM, and
Cox RW. Conceptual processing during the conscious resting
state: A functional MRI study. Journal of Cognitive Neuroscience,
11: 80e93, 1999.
Binder JR, Westbury CF, McKiernan KA, Possing ET, and
Medler DA. Distinct brain systems for processing concrete and
abstract concepts. Journal of Cognitive Neuroscience, 17(6): 1e13,
2005.
622 c o r t e x 4 9 ( 2 0 1 3 ) 6 1 1 e6 2 5
Binney RJ, Embleton KV, Jefferies E, Parker GJM, and Lambon
Ralph MA. The ventral and inferolateral aspects of the anterior
temporal lobe are crucial in semantic memory: Evidence from
a novel direct comparison of distortion-corrected fMRI, rTMS
and semantic dementia. Cerebral Cortex, 20: 2728e2738, 2010.
Binney RJ, Parker GJ, and Lambon Ralph MA. Convergent
connectivity and graded specialization in the rostral human
temporal lobe as revealed by diffusion-weighted imaging
probabilistic tractography. Journal of Cognitive Neuroscience,
24(10): 1998e2014, 2012.
Binney RJ. Exploring the role of the anterior temporal lobe in semantic
cognition. Doctoral thesis, School of Psychological Sciences. UK:
University of Manchester, 2010.
Bird H, Lambon Ralph MA, Patterson K, and Hodges J. The rise and
fall of frequency and imageability: Noun and verb production
in semantic dementia. Brain and Language, 73: 17e49, 2000.
Borden NM. 3D Angiographic Atlas of Neurovascular Anatomy and
Pathology. Cambridge: Cambridge University Press, 2006.
Bozeat S, Lambon Ralph MA, Graham KS, Patterson K, Wilkin H,
Rowland J, et al. A duck with four legs: Investigating the structure
of conceptual knowledge using picture drawing in semantic
dementia. Cognitive Neuropsychology, 20(1): 27e47, 2003.
Bozeat S, Lambon Ralph MA, Patterson K, Garrard P, and
Hodges JR. Non-verbal semantic impairment in semantic
dementia. Neuropsychologia, 38(9): 1207e1215, 2000.
Bozeat S, Lambon Ralph MA, Patterson K, and Hodges JR. When
objects lose their meaning: What happens to their use?
Cognitive, Affective & Behavioural Neuroscience, 2: 236e251, 2002.
Bright P, Moss H, and Tyler LK. Unitary vs multiple semantics: PET
studies of word and picture processing. Brain and Language, 89:
417e432, 2004.
Catani M and Ffytche DH. The rises and falls of disconnection
syndromes. Brain, 128(10): 2224e2239, 2005.
Chao LL, Haxby JV, and Martin A. Attribute-based neural
substrates in temporal cortex for perceiving and knowing
about objects. Nature Neuroscience, 2: 913e919, 1999.
Chertkow H, Bub D, Deaudon C, and Whitehead V. On the status
of object concepts in aphasia. Brain and Language, 58(2):
203e232, 1997.
Coccia M, Bartolini M, Luzzi S, Provinciali L, and Lambon Ralph MA.
Semantic memory is an amodal, dynamic system: Evidence
from the interaction of naming and object use in semantic
dementia. Cognitive Neuropsychology, 21(5): 513e527, 2004.
Conn PM. Neuroscience in Medicine. Humana Press, 2003.
Corbett F, Jefferies E, Eshan S, and Lambon Ralph MA. Different
impairments of semantic cognition in semantic dementia and
semantic aphasia: Evidence from the non-verbal domain.
Brain, 132: 2593e2608, 2009a.
Corbett F, Jefferies E, and Lambon Ralph MA. Exploring
multimodal semantic control impairments in semantic
aphasia: Evidence from naturalistic object use.
Neuropsychologia, 47: 2721e2731, 2009b.
Corbett F, Jefferies E, and Lambon Ralph MA. Deregulated
semantic cognition follows prefrontal and temporoparietal
damage: Evidence from the impact of task constraint on non-
verbal object use. Journal of Cognitive Neuroscience, 23:
1125e1135, 2011.
Cowey A and Walsh V. Magnetic stimulation studies of visual
cognition. Trends in Cognitive Sciences, 2(3): 103e110, 1998.
Crinion JT, Lambon-Ralph MA, Warburton EA, Howard D, and
Wise RJS. Temporal lobe regions engaged during normal
speech comprehension. Brain, 126(5): 1193e1201, 2003.
Damasio AR. The brain binds entities and events by multiregional
activation from convergence zones. Neural Computation, 1:
123e132, 1989.
Damasio AR. Category-related recognition defects as a clue to the
neural substrates of knowledge. Trends in Neurosciences, 13:
95e98, 1990.
Demb JB, Desmond JE, Wagner AD, Vaidya CJ, Glover GH, and
Gabrieli JDE. Semantic encoding and retrieval in the left
inferior prefrontal cortex: A functional MRI study of task-
difficulty and process specificity. Journal of Neuroscience, 15(9):
5870e5878, 1995.
Desgranges B, Matuszewski V, Piolino P, Chetelat G, Mezenge F,
Landeau B, et al. Anatomical and functional alterations in
semantic dementia: A voxel-based MRI and PET study.
Neurobiology of Aging, 28(12): 1904e1913, 2007.
Devlin JT, Matthews PM, and Rushworth MF. Semantic processing
in the left inferior prefrontal cortex: A combined functional
magnetic resonance imaging and transcranial magnetic
stimulation study. Journal of Cognitive Neuroscience, 15(1):
71e84, 2003.
Devlin JT, Russell RP, Davis MH, Price CJ, Wilson J, Moss HE, et al.
Susceptibility-induced loss of signal: Comparing PET and fMRI
on a semantic task. NeuroImage, 11(6): 589e600, 2000.
Diehl J, Grimmer T, Drzezga A, Riemenschneider M, Forstl H, and
Kurz A. Cerebral metabolic patterns at early stages of
frontotemporal dementia and semantic dementia. A PET
study. Neurobiology of Aging, 25(8): 1051e1056, 2004.
Dronkers N, Wilkins D, Van Valin R, Redfern B, and Jaeger J.
Lesion analysis of the brain areas involved in language
comprehension. Cognition, 92: 145e177, 2004.
Duncan J. The multiple-demand (MD) system of the primate
brain: Mental programs for intelligent behaviour. Trends in
Cognitive Sciences, 14: 172e179, 2010.
Embleton KV, Haroon HA, Morris DM, Ralph MAL, and Parker GJM.
Distortion correction for diffusion-weighted MRI tractography
and fMRI in the temporal lobes. Human Brain Mapping, 31(10):
1570e1587, 2010.
Farah MJ. Visual Agnosia. Cambridge MA: US MIT Press, 2004.
Ferstl EC, Neumann J, Bogler C, and von Cramon DY. The extended
language network: A meta-analysis of neuroimaging studies on
text comprehension. Human Brain Mapping, 29(5): 581e593, 2008.
Franklin S, Turner J, Lambon Ralph MA, Morris J, and Bailey PJ.
A distinctive case of word meaning deafness? Cognitive
Neuropsychology, 13: 1139e1162, 1996.
Galton CJ, Patterson K, Graham K, Lambon Ralph MA, Williams G,
Antoun N, et al. Differing patterns of temporal atrophy in
Alzheimer’s disease and semantic dementia. Neurology, 57(2):
216e225, 2001.
Gardner HE, Lambon Ralph MA, Dodds N, Jones T, Eshan S, and
Jefferies E. The differential contributions of prefrontal and
temporoparietal cortices to multimodal semantic control:
Exploring refractory effects in semantic aphasia. Journal of
Cognitive Neuroscience, 22(7): 1597e1613, 2012.
Garrard P and Carroll E. Lost in semantic space: A multi-modal,
non-verbal assessment of feature knowledge in semantic
dementia. Brain, 129: 1152e1163, 2006.
Gold BT, Balota DA, Jones SJ, Powell DK, Smith CD, and
Andersen AH. Dissociation of automatic and strategic lexical-
semantics: Functional magnetic resonance imaging evidence
for differing roles of multiple frontotemporal regions. Journal
of Neuroscience, 26(24): 6523e6532, 2006.
Goldberg R, Perfetti Charles A, and Schneider Walter. Perceptual
knowledge retrieval activates sensory brain regions. Journal of
Neuroscience, 26: 4917e4921, 2006.
Goodglass H, Hyde MR, and Blumstein S. Frequency,
picturability and availability of nouns in aphasia. Cortex, 5:
104e119, 1969.
Gorno-Tempini ML, Hutton C, Josephs O, Deichmann R, Price C,
and Turner R. Echo time dependence of BOLD contrast and
susceptibility artifacts. NeuroImage, 15: 136e142, 2002.
Gough PM, Nobre AC, and Devlin JT. Dissociating linguistic
processes in the left inferior frontal cortex with transcranial
magnetic stimulation. Journal of Neuroscience, 25(35):
8010e8016, 2005.
 c o r t e x 4 9 ( 2 0 1 3 ) 6 1 1 e6 2 5
Hart J and Gordon B. Delineation of single-word semantic
comprehension deficits in aphasia with anatomical
correlation. Annals of Neurology, 27: 226e231, 1990.
Hauk O, Johnsrude I, and Pulvermuller F. Somatotopic
representation of action words in human motor and premotor
cortex. Neuron, 41: 301e307, 2004.
Hillis A, Wityk R, Tuffiash E, Beauchamp NJ, Jacobs MA, Barker PB,
and Selnes O. Hypoperfusion of Wernicke’s area predicts
severity of semantic deficit in acute stroke. Annals of Neurology,
50: 561e566, 2001.
Hodges JR, Graham N, and Patterson K. Charting the progression
in semantic dementia e Implications for the organization of
semantic memory. Memory, 3(3e4): 463e495, 1995.
Hodges JR, Patterson K, Oxbury S, and Funnell E. Semantic
Dementia: Progressive fluent aphasia with temporal-lobe
atrophy. Brain, 115: 1783e1806, 1992.
Hodges JR, Patterson K, Ward R, Garrard P, Bak T, Perry R, and
Gregory C. The differentiation of semantic dementia and
frontal lobe dementia (temporal and frontal variants of
frontotemporal dementia) from early Alzheimer’s disease: A
comparative neuropsychological study. Neuropsychology, 13:
31e40, 1999.
Hoffman P, Jefferies E, and Lambon Ralph MA. The role of
ventrolateral prefrontal cortex in abstract word
comprehension: Convergent neuropsychological and rTMS
evidence. Journal of Neuroscience, 30: 15450e15456, 2010.
Hoffman P, Jefferies E, and Lambon Ralph MA. Remembering
‘zeal’ but not ‘thing’: Reverse frequency effects as
a consequence of deregulated semantic processing.
Neuropsychologia, 49: 580e584, 2011a.
Hoffman P and Lambon Ralph MA. Reverse concreteness effects
are not a typical feature of semantic dementia: Evidence for
the hub-and-spoke model of conceptual representations.
Cerebral Cortex, 21(9): 2103e2112, 2011.
Hoffman P, Rogers TT, and Lambon Ralph MA. Semantic diversity
accounts for the “missing” word frequency effect in stroke
aphasia: Insights using a novel method to quantify contextual
variability in meaning. Journal of Cognitive Neuroscience, 23(9):
2432e2446, 2011b.
Humphries C, Binder JR, Medler DA, and Liebenthal E. Time
course of semantic processes during sentence
comprehension: An fMRI study. NeuroImage, 36: 924e932,
2007.
Ikeda M, Patterson K, Graham KS, Ralph MAL, and Hodges JR. A
horse of a different colour: Do patients with semantic
dementia recognise different versions of the same object as
the same? Neuropsychologia, 44(4): 566e575, 2006.
Jefferies E, Baker SS, Doran M, and Lambon Ralph MA. Refractory
effects in stroke aphasia: A consequence of poor semantic
control. Neuropsychologia, 45: 1065e1079, 2007.
Jefferies E, Jones R, Bateman D, and Lambon Ralph MA. A
semantic contribution to nonword recall? Evidence for intact
phonological processes in semantic dementia. Cognitive
Neuropsychology, 22: 183e212, 2005.
Jefferies E and Lambon Ralph MA. Semantic impairment in stroke
aphasia vs. semantic dementia: A case-series comparison.
Brain, 129: 2132e2147, 2006.
Jefferies E, Patterson K, Jones R, Bateman D, and Lambon
Ralph MA. A category-specific advantage for numbers in
verbal short-term memory: Evidence from semantic
dementia. Neuropsychologia, 42: 639e660, 2004.
Jefferies E, Patterson K, Jones RW, and Lambon Ralph MA.
Comprehension of concrete and abstract words in semantic
dementia. Neuropsychology, 23: 492e499, 2009.
Jefferies E, Patterson K, and Lambon Ralph MA. Deficits of
knowledge versus executive control in semantic cognition:
Insights from cued naming. Neuropsychologia, 46: 649e658,
2008.
623
Kramer JH, Jurik J, Sha SJ, Rankin KP, Rosen HJ, Johnson JK, and
Miller BL. Distinctive neuropsychological patterns in
frontotemporal dementia, semantic dementia, and Alzheimer
disease. Cognitive and Behavioral Neurology, 16(4): 211e218,
2003.
Lambon Ralph M, Sage K, Jones R, and Mayberry E. Coherent
concepts are computed in the anterior temporal lobes.
Proceedings of the National Academy of Sciences of the United States
of America, 107: 2717e2722, 2010.
Lambon Ralph MA, Lowe C, and Rogers T. Neural basis of
category-specific semantic deficits for living things: Evidence
from semantic dementia, HSVE and a neural network model.
Brain, 130: 1127e1137, 2007.
Lambon Ralph MA, McClelland JL, Patterson K, Galton CJ, and
Hodges JR. No right to speak? The relationship between object
naming and semantic impairment: Neuropsychological
abstract evidence and a computational model. Journal of
Cognitive Neuroscience, 13(3): 341e356, 2001.
Lambon Ralph MA and Patterson K. Generalization and
differentiation in semantic memory: Insights from semantic
dementia. Annals of the New York Academy of Sciences, 1124:
61e76, 2008.
Lambon Ralph MA, Patterson K, Garrard P, and Hodges JR.
Semantic dementia with category specificity: A comparative
case-series study. Cognitive Neuropsychology, 20(3e6): 307e326,
2003.
Lambon Ralph MA, Pobric G, and Jefferies E. Conceptual
knowledge is underpinned by the temporal pole bilaterally:
Convergent evidence from rTMS. Cerebral Cortex, 19(4):
832e838, 2009.
Loftus GR and Masson M. Using confidence intervals in within-
subject designs. Psychonomic Bulletin & Review, 1: 476e490,
1994.
Luzzi S, Snowden JS, Neary D, Coccia M, Provinciali L, and
Lambon Ralph MA. Distinct patterns of olfactory impairment
in Alzheimer’s disease, semantic dementia, frontotemporal
dementia, and corticobasal degeneration. Neuropsychologia, 45:
1823e1831, 2007.
Martin A. The representation of object concepts in the brain.
Annual Review of Psychology, 58: 25e45, 2007.
Martin A, Haxby JV, Lalonde FM, Wiggs CL, and
Ungerleider LG. Discrete cortical regions associated with
knowledge of color and knowledge of action. Science, 270
(5233): 102e105, 1995.
Mechelli A, Sartori G, Orlandi P, and Price CJ. Semantic relevance
explains category effects in medial fusiform gyri. NeuroImage,
30(3): 992e1002, 2006.
Meteyard L, Cuadrado SR, Bahrami B, and Vigliocco G. Coming of
age: A review of embodiment and the neuroscience of
semantics. Cortex, 48(7): 788e804, 2012.
Mion M, Patterson K, Acosta-Cabronero J, Pengas G, Izquierdo-
Garcia D, Hong YT, et al. What the left and right anterior
fusiform gyri tell us about semantic memory. Brain, 133:
3256e3268, 2010.
Mummery CJ, Patterson K, Price CJ, Ashburner J,
Frackowiak RSJ, and Hodges JR. A voxel-based morphometry
study of semantic dementia: Relationship between temporal
lobe atrophy and semantic memory. Annals of Neurology,
47(1): 36e45, 2000.
Nagel IE, Schumacher EH, Goebel R, and D’Esposito M. Functional
MRI investigation of verbal selection mechanisms in lateral
prefrontal cortex. NeuroImage, 43(4): 801e807, 2008.
Nestor PJ, Fryer TD, and Hodges JR. Declarative memory
impairments in Alzheimer’s disease and semantic dementia.
NeuroImage, 30(3): 1010e1020, 2006.
Noonan K, Jefferies E, Corbett F, Hopper S, and Lambon Ralph MA.
Elucidating the nature of deregulated semantic cognition in
semantic aphasia: Evidence for the roles of prefrontal and
624 c o r t e x 4 9 ( 2 0 1 3 ) 6 1 1 e6 2 5
temporoparietal cortices. Journal of Cognitive Neuroscience, 22:
1597e1613, 2010.
Noonan K, Jefferies E, Visser M, and Lambon Ralph MA. Aligning
evidence from functional neuroimaging and neuropsychology
for the neural network underpinning semantic control: A
meta-analytic investigation. submitted for publication.
Noppeney U, Phillips J, and Price C. The neural areas that control
the retrieval and selection of semantics. Neuropsychologia,
42(9): 1269e1280, 2004.
Noppeney U and Price C. A PET study of stimulus- and task-
induced semantic processing. NeuroImage, 15: 927e935, 2002.
Novick J, Kan I, Trueswell J, and Thompson-Schill S. A case for
conflict across multiple domains: Memory and language
impairments following damage to ventrolateral prefrontal
cortex. Cognitive Neuropsychology, 26: 527e567, 2009.
Ogar JM, Baldo JV, Wilson SM, Brambati SM, Miller BL,
Dronkers NF, and Gorno-Tempini ML. Semantic dementia and
persisting Wernicke’s aphasia: Linguistic and anatomical
profiles. Brain and Language, 117(1): 28e33, 2011.
Ojemann J, Akbudak E, Snyder A, McKinstry R, Raichle M, and
Conturo T. Anatomic localization and quantitative analysis of
gradient refocused echo-planar fMRI susceptibility artifacts.
NeuroImage, 6: 156e167, 1997.
Olson IR, Plotzker A, and Ezzyat Y. The Enigmatic temporal pole:
A review of findings on social and emotional processing. Brain,
130(7): 1718e1731, 2007.
Patterson K, Lambon Ralph MA, Jefferies E, Woollams A, Jones R,
Hodges J, and Rogers TT. ‘Pre-semantic’ cognition in semantic
dementia: Six deficits in search of an explanation. Journal of
Cognitive Neuroscience, 18: 169e183, 2006.
Patterson K, Nestor PJ, and Rogers TT. Where do you know what
you know? The representation of semantic knowledge in the
human brain. Nature Reviews Neuroscience, 8(12): 976e987, 2007.
Pavio A. Mental Representations: A Dual-coding Approach. Oxford:
Oxford University Press, 1986.
Perani D, Schnur T, Tettamanti C, Gorno-Tempini M, Cappa SF,
and Fazio F. Word and picture matching: A PET study of
semantic category effects. Neuropsychologia, 37: 293e306, 1999.
Phan TG, Donnan GA, Wright PM, and Reutens DC. A digital map of
middle cerebral artery infarcts associated with middle cerebral
artery trunk and branch occlusion. Stroke, 36: 986e991, 2005.
Phan TG, Fong AC, Donnan G, and Reutens DC. Digital map of
posterior cerebral artery infarcts associated with posterior
cerebral artery trunk and branch occlusion. Stroke, 38:
1805e1811, 2007.
Plaut DC. Graded modality-specific specialisation in semantics: A
computational account of optic aphasia. Cognitive
Neuropsychology, 19(7): 603e639, 2002.
Pobric G, Jefferies E, and Lambon Ralph MA. Anterior temporal
lobes mediate semantic representation: Mimicking semantic
dementia by using rTMS in normal participants. Proceedings of
the National Academy of Sciences of the United States of America,
104(50): 20137e20141, 2007.
Pobric G, Jefferies E, and Lambon Ralph MA. Amodal semantic
representations depend on both left and right anterior
temporal lobes: New rTMS evidence. Neuropsychologia, 48:
1336e1342, 2010a.
Pobric G, Jefferies E, and Lambon Ralph MA. Induction of
category-specific vs. general semantic impairments in normal
participants using rTMS. Current Biology, 20: 964e968, 2010b.
Pobric G, Lambon Ralph MA, and Jefferies E. The role of the
anterior temporal lobes in the comprehension of concrete and
abstract words: rTMS evidence. Cortex, 45: 1104e1110, 2009.
Price CJ. The anatomy of language: A review of 100 fMRI studies
published in 2009. Annals of the New York Academy of Sciences,
1191: 62e88, 2010.
Pulvermuller F. Brain mechanisms linking language and action.
Nature Reviews Neuroscience, 6: 576e582, 2005.
Robinson G, Shallice T, Bozzali M, and Cipolotti L. Conceptual
proposition selection and the LIFG: Neuropsychological
evidence from a focal frontal group. Neuropsychologia, 48:
1652e1663, 2010.
Rodd JM, Davis MH, and Johnsrude IS. The neural mechanisms of
speech comprehension: fMRI studies of semantic ambiguity.
Cerebral Cortex, 15(8): 1261e1269, 2005.
Rogers TT, Hocking J, Mechelli A, Patterson K, and Price C.
Fusiform activation to animals is driven by the process, not
the stimulus. Journal of Cognitive Neuroscience, 17(3): 434e445,
2005.
Rogers TT, Hocking J, Noppeney U, Mechelli A, Gorno-Tempini M,
Patterson K, and Price C. Anterior temporal cortex and
semantic memory: Reconciling findings from
neuropsychology and functional imaging. Cognitive, Affective &
Behavioral Neuroscience, 6: 201e213, 2006.
Rogers TT, Lambon Ralph MA, Garrard P, Bozeat S, McClelland JL,
Hodges JR, and Patterson K. Structure and deterioration of
semantic memory: A neuropsychological and computational
investigation. Psychological Review, 111(1): 205e235, 2004a.
Rogers TT, Lambon Ralph MA, Hodges JR, and Patterson K.
Natural selection: The impact of semantic impairment on
lexical and object decision. Cognitive Neuropsychology, 21:
331e352, 2004b.
Rosen HJ, GornoeTempini ML, Goldman WP, Perry RJ, Schuff N,
Weiner M, et al. Patterns of brain atrophy in frontotemporal
dementia and semantic dementia. Neurology, 58(2): 198e208,
2002.
Saffran EM. The organization of semantic memory: In support of
a distributed model. Brain and Language, 71(1): 204e212, 2000.
Schnur TT, Schwartz MF, Kimberg DY, Hirshorn EA, Coslett HB,
and Thompson-Schill S. Localizing interference during
naming: Convergent neuroimaging and neuropsychological
evidence for the function of Broca’s area. Proceedings of the
National Academy of Sciences of the United States of America, 106:
322e327, 2009.
Schwanenflugel P and Shoben E. Differential context effects in
the comprehension of abstract and concrete verbal materials.
Journal of Experimental Psychology: Learning, Memory and
Cognition, 9: 82e102, 1983.
Schwartz MF, Kimberg DY, Walker GM, Brecher A, Faseyitan OK,
Dell GS, et al. Neuroanatomical dissociation for taxonomic
and thematic knowledge in the human brain. Proceedings of the
National Academy of Sciences, 108: 8520e8524, 2011.
Scott SK, Blank CC, Rosen S, and Wise RJS. Identification of
a pathway for intelligible speech in the left temporal lobe.
Brain, 123(12): 2400e2406, 2000.
Seghier ML, Fagan E, and Price C. Functional subdivisions in the
left angular gyrus where the semantic system meets and
diverges from the default network. Journal of Neuroscience, 30:
16809e16817, 2010.
Simmons WK, Hamann SB, Harenski CL, Hu XP, and Barsalou LW.
fMRI evidence for word association and situated simulation in
conceptual processing. Journal of Physiology-Paris, 102(1e3):
106e119, 2008.
Skipper LM, Ross LA, and Olson IR. Sensory and semantic
category subdivisions within the anterior temporal lobes.
Neuropsychologia, 49(12): 3419e3429, 2011.
Snowden JS, Goulding PJ, and Neary D. Semantic dementia: A
form of circumscribed cerebral atrophy. Behavioural Neurology,
2: 167e182, 1989.
Snowden JS, Thompson JC, and Neary D. Knowledge of famous
faces and names in semantic dementia. Brain, 127(4): 860e872,
2004.
Studholme C, Cardenas V, Blumenfeld R, Schuff N, Rosen HJ,
Miller B, and Weiner M. Deformation tensor morphometry of
sematic dementia with quantitative validation. NeuroImage,
21(4): 1387e1398, 2004.
 c o r t e x 4 9 ( 2 0 1 3 ) 6 1 1 e6 2 5
Thompson-Schill SL. Neuroimaging studies of semantic memory:
Inferring “how” from “where”. Neuropsychologia, 41(3):
280e292, 2003.
Thompson-Schill SL, D’Esposito M, Aguirre GK, and Farah MJ. Role
of left inferior prefrontal cortex in retrieval of semantic
knowledge: A reevaluation. Proceedings of the National Academy
of Sciences of the United States of America, 94(26): 14792e14797,
1997.
Thompson-Schill SL, Swick D, Farah MJ, D’Esposito M, Kan IP, and
Knight RT. Verb generation in patients with focal frontal
lesions: A neuropsychological test of neuroimaging findings.
Proceedings of the National Academy of Sciences of the United States
of America, 95: 15855e15860, 1998.
Vandenberghe R, Price C, Wise R, Josephs O, and Frackowiak RSJ.
Functional anatomy of a common semantic system for words
and pictures. Nature, 383: 254e256, 1996.
Vandenbulcke M, Peeters R, Fannes K, and Vandenberghe R.
Knowledge of visual attributes in the right hemisphere. Nature
Neuroscience, 9: 964e970, 2006.
Visser M, Embleton KV, Jefferies E, Parker GJM, and Lambon
Ralph MA. The anterior temporal lobes and semantic memory
clarified: Novel evidence from distortion-corrected spin-echo
EPI fMRI. Neuropsychologia, 48: 1689e1696, 2010a.
Visser M, Jefferies E, Embleton KV, and Lambon Ralph MA. Both
the middle temporal gyrus and the ventral anterior temporal
area are crucial for multimodal semantic processing:
Distortion-corrected fMRI evidence for a double gradient of
information convergence in the temporal lobes. Journal of
Cognitive Neuroscience, 24: 1766e1778, 2012.
Visser M, Jefferies EA, and Lambon Ralph MA. Semantic
processing in the anterior temporal lobes: A meta-analysis of
the functional neuroimaging literature. Journal of Cognitive
Neuroscience, 22: 1083e1094, 2010b.
Wagner AD, Pare-Blagoev EJ, Clark J, and Poldrack RA. Recovering
meaning: Left prefrontal cortex guides controlled semantic
retrieval. Neuron, 31(2): 329e338, 2001.
625
Warrington EK. Selective impairment of semantic memory.
Quarterly Journal of Experimental Psychology, 27(Nov): 635e657,
1975.
Warrington EK and Shallice T. Category specific semantic
impairments. Brain, 107(Sep): 829e854, 1984.
Weiskopf N, Hutton C, Josephs O, and Deichmann R. Optimal EPI
parameters for reduction of susceptibility-induced BOLD
sensitivity losses: A whole-brain analysis at 3 T and 1.5 T.
NeuroImage, 33(2): 493e504, 2006.
Whitney C, Grossman M, and Kircher T. The influence of multiple
primes on bottomeup and topedown regulation during
meaning retrieval: Evidence for two distinct neural networks.
Cerebral Cortex, 19: 2548e2560, 2009.
Whitney C, Jefferies E, and Kircher TTJ. Heterogeneity of the left
temporal lobe in semantic representation and control: Priming
multiple vs. single meanings of ambiguous words. Cerebral
Cortex, 21: 831e844, 2011a.
Whitney C, Kirk K, O’Sullivan J, Lambon Ralph MA, and Jefferies E.
The neural organization of semantic control: TMS evidence for
a distributed network in left inferior frontal and posterior
middle temporal gyrus. Cerebral Cortex, 21(5): 1066e1075, 2011b.
Whitney C, Kirk K, O’Sullivan J, Lambon Ralph MA, and Jefferies E.
Executive-semantic processing is underpinned by a large-
scale neural network: Revealing the contribution of left
prefrontal, posterior temporal and parietal cortex to
controlled retrieval and selection using TMS. Journal of
Cognitive Neuroscience, 24(1): 133e147, 2012.
Wible CG, Han SD, Spencer MH, Kubicki M, Mh N, Jolesz FA, et al.
Connectivity among semantic associates: An fMRI study of
semantic priming. Brain and Language, 97(3): 294e305, 2006.
Wiener D, Connor L, and Obler L. Inhibition and auditory
comprehension in Wernicke’s aphasia. Aphasiology, 18:
599e609, 2004.
Woollams AM, Cooper-Pye E, Hodges JR, and Patterson K. Anomia:
A doubly typical signature of semantic dementia.
Neuropsychologia, 46(10): 2503e2514, 2008.