Neuron, Vol. 35, 589–597, August 1, 2002, Copyright 2002 by Cell Press

Specialization in the Left Prefrontal Cortex
for Sentence Comprehension
Ryuichiro Hashimoto1 and Kuniyoshi L. Sakai1,2,3
Department of Cognitive and Behavioral Science
Graduate School of Arts and Sciences
The University of Tokyo, Komaba
3-8-1 Komaba, Meguro-ku
Tokyo 153-8902
2
CREST
Japan Science and Technology Corporation
Kawaguchi-shi 332-0012
Japan

1

Summary
Using functional magnetic resonance imaging (fMRI),
we examined cortical activation under syntactic decision tasks and a short-term memory task for sentences, focusing on essential properties of syntactic processing. By comparing activation in these tasks witha short-term memory task for word lists, we foundthat two regions in the left prefrontal cortex showed
selective activation for syntactic processing: the dorsal prefrontal cortex (DPFC) and the inferior frontal
gyrus (IFG). Moreover, the left DPFC showed more
prominent activation under the short-term memorytask for sentences than that for word lists, which cannot be explained by general cognitive factors such as
task difficulty and verbal short-term memory. These
results support the proposal of specialized systems forsentence comprehension in the left prefrontal cortex.
Introduction
It is a central issue in cognitive neuroscience whether
language ability is subserved by a distinct module, separable from other cognitive modules (Shallice, 1988;
Smith and Tsimpli, 1995; Sakai et al., 2001). Modularists
have proposed such language modules, further claiming
the existence of specialized submodules for syntactic
processing and other linguistic faculties (Fodor, 1983;
Chomsky, 1984; Coltheart, 1999). Syntactic processing
in sentence comprehension refers to the mental processes that apply grammatical rules to analyzing sentence meaning. Consistent with the modular view, previous imaging studies have identified cortical regions,which are suggested to be selectively involved in syntactic processing, in the left inferior frontal gyrus (L. IFG;
Brodmann’s areas [BAs] 44 and 45) (Dapretto and Bookheimer, 1999; Embick et al., 2000), as well as in the left
dorsal prefrontal cortex (L. DPFC; BAs 6, 8, and 9) andthe left dorsolateral prefrontal cortex (L. DLPFC; BAs 46
and 9) (Kang et al., 1999; Indefrey et al., 2001; Newman
et al., 2001).
In contrast, there has been a proposal that does notassume any modularity in language processing, suchthat syntactic processing is fully carried out by a systemof verbal working memory (Just and Carpenter, 1992;
3

Correspondence: sakai@mind.c.u-tokyo.ac.jp

Dick et al., 2001). Verbal working memory refers to abrain system that provides temporal storage and manipulation of verbal information necessary for language
comprehension and other cognitive tasks (Baddeley,1992). Baddeley’s model of verbal working memory assumes the phonological store, in which verbal information is registered and maintained by the subvocal rehearsal system. Typical examples of verbal information
maintained are word/letter identity (what) and word/letter order (when). As to the “what” aspect, several imaging studies reported activations of the bilateral
DLPFC, DPFC, and IFG (Paulesu et al., 1993; Cohen etal., 1994; Fiez et al., 1996; Clark et al., 2000). As to the“when” aspect, neuropsychological studies have suggested that short-term memory for the temporal orderof words requires the involvement of L. DLPFC (Milner
et al., 1991). This proposal has been supported by recent
imaging studies (Cabeza et al., 1997; Marshuetz et al.,2000) in which DPFC was also activated.
In addition to the phonological store and the subvocal
rehearsal system, it has been proposed that the central
executive is engaged when a verbal task involves demanding mnemonic processes. Previous imaging studies have investigated the neural basis of the central
executive by increasing task difficulty stemming fromverbal memory load, that is, the number of verbal items
to be memorized (Braver et al., 1997; Cohen et al., 1997;
Rypma et al., 1999). These studies have consistently
reported enhanced activation of DLPFC, DPFC, and IFG.
By increasing task difficulty with a dual-task condition,it has been suggested that these prefrontal regions constitute the common neural basis for verbal executive
processes, such as sentence comprehension and verbal
memorization (Bunge et al., 2000). On the other hand,a previous imaging study reported task difficulty-related
modulation in IFG and DPFC (but not in DLPFC), withmemory load held constant while manipulating verbal
effects of difficulty, such as word length, phonologicalsimilarity, and lexicality (Chein and Fiez, 2001). However,
it is also possible that activations of IFG and DPFC are
modulated by other verbal-specific factors than taskdifficulty and executive processes.
Given the controversy between the two opposing
views on syntactic modularity, a crucial question iswhether syntactic processing is dissociable from theverbal working memory system. Indeed, some previous
behavioral studies have indicated such a dissociation(Martin, 1993). First, it has been shown that an English
sentence of up to 14 words can be understood and
immediately recalled with near perfect accuracy when
the rate of presentation is as high as 12 words per second, while only 2 or 3 unrelated words can be recalledat the same presentation rate (Potter, 1993). This observation led to the proposal that grammatically structuralized information is immediately transformed into stable
representation, while maintenance of memory for unrelated words requires continuous subvocal rehearsal.
Second, neuropsychological studies have reported patients with profound verbal short-term memory deficits,
whose ability for sentence comprehension is well pre-

Neuron590

served (Martin, 1987; Waters et al., 1991). Third, a double
dissociation has been shown, such that the spanimpaired aphasics were better at repeating sentences(up to five or seven words) than repeating three-wordlists, whereas the span-preserved aphasic showed the
opposite pattern of performance (McCarthy and Warrington, 1987). Fourth, a previous neuropsychologicalstudy investigated the syntactic ability of patients with
deficits in the central executive, showing that the effectof syntactic complexity was unaffected by a concurrent
verbal memory load (Waters et al., 1995). Based on thesefindings, it has been claimed that there is a specialized
system for assigning the syntactic structure of a sentence and using that structure in determining sentence
meaning (Caplan and Waters, 1999). However, its precise neural substrates have not been elucidated.
A possible separation between syntactic processing
and verbal working memory has been also examined byevent-related brain potential (ERP) studies. One ERP
component, the left anterior negativity (LAN), has been
associated with grammatical errors (Neville et al., 1991;
Münte et al., 1993; Friederici et al., 1993). However, its
syntactic specificity has been challenged by the observation that the LAN effect was independent of grammaticality and correlated with working memory required insentence processing (Kluender and Kutas, 1993; Rösler
et al., 1998). Moreover, it has been shown that the amplitude of the LAN was modulated by the combination ofsyntactic complexity and additional working memory
load (Vos et al., 2001). Recent imaging studies havemanipulated syntactic complexity (canonical/noncanonical word order) and a maintenance delay interval(the distance of a filler-gap linkage), and reported increased activation of the left BA 44 or BA 47, which was
induced by delay intervals but not by complexity alone(Fiebach et al., 2001; Cooke et al., 2002). Delay intervals,
however, are necessarily confounded with general taskdifficulty, because it is more difficult to process a sentence while keeping an item longer in memory. Besides,
the memory demands in these studies may not be syntax-specific but domain-independent verbal short-term
memory. Therefore, it still remains to be elucidated
whether or not syntactic processing is separable fromgeneral task difficulty and verbal short-term memory.
The present study addressed whether or not there are
specialized neural systems for sentence comprehension. Toward this objective, we focused on two essential
properties of syntactic processing that contrast withproperties of task difficulty and verbal working memory.
First, syntactic processing is based not only on word
identities and the linear order of words, but on the structure-dependent rules underlying a sentence as well. In
the example shown in Figure 1A, the structure dependency refers to the information that Taro is in the mainclause, whereas Saburo is in the subordinate clause.
On the other hand, the linear order of words only provides the information that Taro precedes Saburo, butoffers no structural information. The structure-dependency of rules is one of the unique properties of syntax,
universally observed in all known natural languages(Chomsky, 1980; Comrie, 1989; Baker, 2001). Second,in natural reading conditions, syntactic information isprocessed immediately and automatically as each newword is encountered (Neville et al., 1991; Gunter andFriederici, 1999). This automaticity clearly contrasts withtask difficulty, which involves conscious effort and strategies in control of conflicting or competitive responses.
To identify neural systems reflecting these essential
properties of syntactic processing, we contrasted two
syntactic decision (SYN) tasks (SYN-1 and SYN-2) with
two short-term memory (STM) tasks (STM-S andSTM-W) (Figure 1A). In SYN-1 and SYN-2, participants
read Japanese sentences, each of which consisted ofsequentially presented phrases. After one complete
sentence, we presented a pair of words to participants
who were instructed to make syntactic judgments onargument-predicate (noun-verb) relations in SYN-1, andon coreference (noun-noun) relations in SYN-2 (see Experimental Procedures). These two tasks explicitly required participants to utilize the structure-dependent
rules. In STM-S (an STM task for sentences), participants
were presented with the same set of sentences as thatused in the SYN tasks but were asked to memorize eachphrase. Participants were then presented with a pair ofphrases and judged their temporal order in the original
sequence (Figure 1A). While this judgment does not require explicit syntactic decisions, reading sentences
obligatorily accompanies syntactic processes. In STM-W(an STM task for words), phrases of one sentence wererearranged into separate groups of nouns and verbs, sothat they were syntactically unrelated (Figure 1A). Itstask requirements including memory encoding and retrieval were the same as those in STM-S, which arecommonly involved in standard verbal working memorytasks.
During these four tasks, we measured cortical activity
using functional magnetic resonance imaging (fMRI),and performed random effects analyses. Because behavioral studies have indicated that grammatical sentences can be more easily understood and recalled thanlists of unrelated words, SYN-1, SYN-2, and STM-S
would be easier tasks than STM-W that lacks syntactic
relationships among words. Thus, STM-W would activate regions reflecting verbal working memory, together
with additional regions due to task difficulty. If syntactic
processing is fully carried out by the verbal working
memory system, then the regions activated in STM-W
would completely include the regions recruited in theother three tasks. If this is not the case, however, it willturn out that syntactic processing cannot be explainedby nonmodular views. Our goal in this novel paradigm
was to separate syntactic processing from verbal working memory processes by directly comparing syntactic
decision tasks and verbal short-term memory tasks.
Results
Behavioral Data
The accuracy in SYN-1, SYN-2, STM-S, and STM-W was
87.7% ⫾ 5.4%, 84.8% ⫾ 7.0%, 90.1% ⫾ 4.0%, and79.5% ⫾ 7.5% (mean ⫾ SD, n ⫽ 16), respectively. Reaction times (RTs) for these tasks were 1071 ⫾ 145 ms,
1109 ⫾ 117 ms, 1298 ⫾ 142 ms, and 1354 ⫾ 155 ms,
respectively. An ANOVA showed significant main effectsof task, in both accuracy and RT (p ⬍ 0.0001). According
to a post hoc test, RTs in both STM-W and STM-S weresignificantly longer than those in the two SYN tasks (p ⬍Sentence Comprehension in Left Prefrontal Cortex
591

Figure 1. Four Tasks to Identify the Neural Substrates for Syntactic Processing(A) Examples of stimuli used in the four tasks: two syntactic decision (SYN) tasks (SYN-1 and SYN-2) and two short-term memory (STM) tasks(STM-S [an STM task for sentences] and STM-W [an STM task for words]). In each trial for 6 s, five phrases (0.5 s each) were sequentiallypresented, followed by paired phrases (2.2 s) for judgment. An example of a Japanese sentence is shown: “Taro-wa Saburo-ga kare-wo
homeru-to omou.” Its word by word translation is “Taro-topic Saburo-nominative him praise that think.” A red cross for fixation wasalways shown at the center of the screen, but it was omitted from the figure. Note that the task label was presented at the initiation of every
trial.
(B) The cognitive components involved in each task, the contributions of which are shown in a black and white scale: black (maximum),crosshatched, hatched, and white (none). Syntactic processing is explicitly required in both SYN tasks, whereas it is implicitly involved in
STM-S. Memory for temporal order is explicitly required in both STM tasks, whereas it is implicitly included for syntactic analyses in both
SYN tasks. Behavioral data indicated that STM-W was the most difficult among the four tasks, and that SYN-2 was more difficult than STM-S.
STM-S and SYN-1 were comparable in task difficulty. Word recognition was commonly involved in the four tasks.

0.0001), and RT in STM-W was marginally longer thanthat in STM-S (p ⫽ 0.06). STM-W showed significantly
lower accuracy than the other three tasks (p ⬍ 0.01),
and accuracy in SYN-2 was significantly lower than thatin STM-S (p ⬍ 0.01). These results showed that STM-W
was the most difficult task (Figure 1B).
Selective Activation for Sentence Processingin L. DPFC and L. IFG
First, we directly compared the STM-S and STM-W tasks(Figure 2A and Table 1). Although the task requirement
was the same in these two tasks, STM-S involved syntactic processing at the sentence level, while STM-W
required the most demanding mnemonic processes
without syntactic relationships among words (Figure
1B). We found that L. DPFC (BAs 6, 8, and 9) showedsignificantly larger responses to STM-S. In contrast, se-lective responses to STM-W were observed in the ventral portion of the left precentral gyrus, the left parietal
operculum, and the right anterior cingulate cortex. The
anterior border of L. DPFC activation was on the superior
frontal sulcus, whereas its posterior border was on theprecentral sulcus. This result demonstrates the existence of a specialized neural system for sentence comprehension, which is separable from task difficulty andverbal working memory.
In addition to the region activated for sentence processing in STM-S, we further examined whether there
are neural substrates that are specifically recruited whenemploying structure-dependent syntactic rules in sentence comprehension. For this purpose, we contrasted
the two SYN tasks (SYN-1 ⫹ SYN-2) with STM-W (Figure
2B and Table 1). Selective activation for the SYN tasks
was found in the same regions of L. DPFC as thoseNeuron592

Figure 2. Selective Activation for Syntactic Processing in the Left Prefrontal Cortex(A) Regions identified by STM-S ⫺ STM-W (red) and STM-W ⫺ STM-S (green). They were projected together onto a surface-rendered
representative brain in MNI space. For display purposes, the threshold is set at uncorrected p ⬍ 0.00005 with an extent threshold of 16 voxels,
but the local maxima of t values (yellow and black dots) reached a threshold of p ⬍ 0.05, corrected for multiple comparisons.
(B) Regions identified by (SYN-1 ⫹ SYN-2) ⫺ STM-W (red) and STM-W ⫺ (SYN-1 ⫹ SYN-2) (green). We found that L. DPFC and L. IFG showed
selective activation for the SYN tasks.
(C) Regions identified by (SYN-1 ⫹ SYN-2) ⫺ STM-S (red) and STM-S ⫺ (SYN-1 ⫹ SYN-2) (green). The posterior focus of L. DPFC in each of(A), (B), and (C) was located within the left inferior precentral sulcus.

observed by the contrast of STM-S ⫺ STM-W, as wellas in an additional region of L. IFG, which was mainly
localized in the pars triangularis (BA45). In contrast, selective activation for STM-W was found in the bilaterallingual gyrus and the right cuneus.
Finally, we performed the remaining comparison(SYN-1 ⫹ SYN-2) versus STM-S (Figure 2C and Table1). In this comparison, the regions with selective activation for the SYN tasks would include L. IFG for the application of structure-dependent syntactic rules. Moreover, the L. DPFC activation for syntactic processing in
STM-S would be enhanced in the SYN tasks because
the SYN tasks directed more attention to syntactic processing than STM-S. Indeed, we found that both L. IFG

Table 1. Cortical Regions Identified by Syntactic Decision versus Short-Term Memory Tasks
Brain Region

BA

x

y

z

Z Value

6/8/9

⫺27
⫺39

15
6

48
36

4.8
4.7

4/6
43
24/32

⫺63
⫺51
12

⫺3
⫺15
33

15
15
21

4.9
5.4
5.4

L. DPFC

6/8/9

L. IFG

45

⫺27
⫺39
⫺54

15
3
27

57
42
21

5.5
5.8
4.9

18/19
18/19
18/19

⫺6
15
9

⫺84
⫺78
⫺66

3
0
9

5.5
5.5
5.4

6/9
45

⫺36
⫺39

6
24

36
18

4.8
5.2

18/19
18/19
7/39/40

⫺9
18
30

⫺87
⫺78
⫺75

0
⫺12
42

4.8
5.4
5.3

STM-S ⬎ STM-W
L. DPFC
STM-W ⬎ STM-S
L. Precentral gyrus
L. Parietal operculum
R. Anterior cingulate cortex(SYN-1 ⫹ SYN-2) ⬎ STM-W

STM-W ⬎ (SYN-1 ⫹ SYN-2)
L. Lingual gyrus
R. Lingual gyrus
R. Cuneus(SYN-1 ⫹ SYN-2) ⬎ STM-S
L. DPFC
L. IFGSTM-S ⬎ (SYN-1 ⫹ SYN-2)
L. Lingual gyrus
R. Lingual gyrus
R. Posterior parietal cortex

Stereotactic coordinates (x, y, z) in Montreal Neurological Institute (MNI) space are shown for each voxel with a local maximum of Z values
in the contrasts indicated (p ⬍ 0.05, corrected for multiple comparisons). BA, Brodmann’s area; L, left; R, right; DPFC, the dorsal prefrontal
cortex; IFG, the inferior frontal gyrus.

Sentence Comprehension in Left Prefrontal Cortex
593

Figure 3. Task-Dependent Activation of L. DPFC and IFG
Taking STM-S as a reference, the percent signal changes (mean ⫾SEM of participants) under SYN-1, SYN-2, and STM-W are shownfor L. DPFC (A) and L. IFG (B) at the local maxima shown in Figure
2C.

and L. DPFC showed significantly larger activation in
the SYN tasks than STM-S. On the other hand, we foundselective activation for STM-S in the bilateral lingual
gyrus and the right posterior parietal cortex.
Because STM-S was identical with STM-W as to task
requirements, while being identical with the SYN tasks
as to sentence stimuli, STM-S would serve as an idealreference task for other tasks. Therefore, we calculated
the mean signal changes under SYN-1, SYN-2, andSTM-W from STM-S for each participant at the coordinates corresponding to local maxima of t values in thecontrast of (SYN-1 ⫹ SYN-2) ⫺ STM-S. We found that
L. DPFC (Figure 3A) and L. IFG (Figure 3B) showed anotable difference in signal changes for STM-W ⫺STM-S, whereas signal changes for the SYN tasks werecomparable between the two regions. Furthermore,
SYN-1 and SYN-2 showed similar activation (p ⬎ 0.1, Ftest) in each region. A two-way ANOVA (region ⫻ task)
indicated significant interaction effects of region andtask (p ⬍ 0.05), as well as significant main effects oftask (p ⬍ 0.0001). These results indicate selective contributions of L. DPFC and L. IFG to sentence comprehension.
Discussion
In the present study, we identified two regions in theleft prefrontal cortex that showed selective activations
for syntactic processing involved in sentence comprehension: L. DPFC and L. IFG. Previous imaging studies
have reported that L. IFG activation increased with syntactic complexity of a sentence (Stromswold et al., 1996;
Just et al., 1996). However, two contrasting positions
have been based on these similar findings. While
Stromswold et al. (1996) attributed their results to demands made on a specialized working memory system(i.e., a modular interpretation), Just et al. (1996) attributed their results to demands made on a general-purpose verbal working memory system (i.e., a nonmodular
interpretation). According to the nonmodular view, activations of L. DPFC and L. IFG have been attributed to the
executive processes for working memory or cognitive
demands in general (Smith and Jonides, 1999; Duncan
and Owen, 2000). In contrast, our previous imaging
study showed syntax-selective activation of L. IFG, evenwhen syntactic complexity (using identical sentences)
as well as cognitive demands was approximately
equated in each of contrasting tasks (Embick et al.,2000). The present study demonstrates specializationin the prefrontal cortex for sentence comprehension bydirectly comparing syntactic decision tasks and verbal
short-term memory tasks.
A number of previous imaging studies on verbal working memory have interpreted greater activation of theprefrontal regions as reflecting general task difficulty
stemming from memory load (Braver et al., 1997; Cohenet al., 1997; Rypma et al., 1999) or delay intervals (Barchet al., 1997). Chein and Fiez (2001) suggested that
DLPFC plays a more prominent role in nonverbal (domain-independent) mnemonic factors that affect taskdifficulty, which is consistent with the absence of its
activation in the present study. The prefrontal regions
have been also suggested to be involved in effortful
mnemonic retrieval of verbal information (Petrides et al.,
1995; Buckner et al., 1998). In the present study, L. DPFC
(rather than L. DLPFC) showed larger responses to
STM-S than STM-W. As to task difficulty as well as
employment of the subvocal rehearsal system, STM-S
was less demanding than STM-W, as demonstrated bybehavioral data. The following cognitive factors were
thoroughly equated between STM-S and STM-W: word
recognition, mnemonic encoding and retrieval of “what”
and “when” information, the verbal memory load (thenumber of verbal items held in the phonological store),delay intervals (immediate recall after the sequential presentation of five phrases), and recency judgments.
Therefore, only remaining factors for explaining selective activation of L. DPFC for STM-S are processes ofanalyzing syntactic structures as well as the selection
and integration of semantic information during sentencecomprehension. It is still possible that L. DPFC activation can be modulated by task difficulty in general, but
our results clearly established that sentence processing
is a much more prominent factor for the activation of L.
DPFC.
By the comparisons between the SYN tasks and the
STM tasks, we consistently observed that L. IFG was
selectively activated when the use of syntactic rules was
explicitly required by the SYN tasks. Although the SYNtasks and STM-S involved syntactic processing of thesame sentences, only the SYN tasks explicitly required
employment of syntactic rules in sentence comprehension. It is possible that structure-dependent computations performed in L. IFG was not fully evoked by STM-S,
because the task directed attention to the linear orderof words rather than structure-dependent relationships.
According to a previous imaging study, it has been proposed that verbal-specific difficulty modulates the activation of the left prefrontal cortex (BAs 44 and 6) (Chein
and Fiez, 2001). In the present study, however, the SYNtasks showed larger responses in L. IFG than the mostdemanding STM-W. Furthermore, SYN-1 and SYN-2
showed comparable responses (Figure 3B), although
SYN-2 was a more difficult task than SYN-1. Therefore,
we conclude that L. IFG activation in the present study
reflects explicit recruitment of syntactic rules rather thanverbal executive processes imposed by task difficulty.
Previous imaging studies have proposed that the subregions in the left prefrontal cortex are involved in differ-Neuron594

ent aspects of language processing. There has been a
proposal of anterior (BA 45/47) and posterior (BA 44/45)
prefrontal regions as reflecting semantic and phonological/lexical processing, respectively (Poldrack et al.,1999). On the other hand, L. IFG (BA 44/45) has beensuggested to be selectively involved in syntactic processing (Dapretto and Bookheimer, 1999; Embick et al.,2000), which is consistent with the L. IFG activation in
the present study. It should be noted that L. IFG and
L. DPFC (BA 9) are also activated in syntactic tasks
independent of lexico-semantics (Friederici et al., 2000;
Indefrey et al., 2001; Moro et al., 2001). Recently, we
found that the left BA 45/47 is involved in the selection
and integration of semantic information during sentencecomprehension that are separable from lexico-semantic
processing (Homae et al., 2002). Because this region
barely overlaps with the extent of activated regions inFigure 2B, we suggest that major roles of L. DPFC and
L. IFG in the present study may be also distinct fromsemantic aspects of sentence comprehension.
Although individual roles of L. DPFC and L. IFG in
sentence comprehension remain to be clarified by futurestudies, selective contributions of these regions to thepresent tasks are intriguing. Compared with STM-W, L.
DPFC was activated not only by the SYN tasks but also
by STM-S in which syntactic information is processed
without explicit instructions. In contrast, L. IFG was activated only when the explicit use of syntactic rules was
required by the SYN tasks. Specific task demands would
play a critical role for the present findings, as we haverecently demonstrated the impact of syntactic demands
on sentence processing (Embick et al., 2000). It may bethat L. DPFC is sensitive to the presence of sentence
processing in STM-S and that further syntactic demandsof the SYN tasks may recruit L. IFG in addition to L.
DPFC. As to the requirements of the two STM tasks,
one difference lies in the aspect of case marking; nounphrases in STM-S were always case marked correctly
in a sentence, whereas all three noun phrases in STM-W
were marked with the same case marker. Participants
had to encode and retrieve the case marking for eachnoun phrase in STM-S, while case marking in STM-W
can be encoded only once. Thus the activation of L.
DPFC in STM-S ⫺ STM-W could be due to the conscious
encoding and retrieval of either case or thematic information, which is more demanding in STM-S thanSTM-W. Compared with STM-S, this process may be
more demanding for sentence comprehension explicitly
required by the SYN tasks.
Linguistic computations based on structure-dependent syntactic rules involve organizing and maintaining
transient representations of combinations of words andphrases. Both L. DPFC and L. IFG showed larger activation for the SYN tasks than STM-S (Figure 2C), probably
because the SYN tasks required more of such syntactic
computations than STM-S. Interestingly, a previous imaging study suggested that the activation of L. DLPFC(BA 9/46, close to our L. DPFC) reflects the creation ofan organizational structure (Fletcher et al., 1998). This
result is consistent with our study, in that syntactic processing also involves processes for organization, suchas combining words into phrases and sentences. Our
results further suggest that these organization processes may proceed obligatorily in syntactic pro-cessing, as involved in STM-S, without intentional efforts
to create artificial organizational structures. Furthermore, syntax-selective activation of L. IFG (BA45), which
is close to our L. IFG, has been reported in a recent
imaging study (Caplan et al., 1999), suggesting that its
activation reflects syntactic complexity of sentences.
Our hypothesis is consistent with this suggestion, inthat the L. IFG activation is attributable to structuredependent computations of sentences.
We observed several other regions that were involvedin nonsyntactic processing. In the contrast of STM-W ⫺STM-S, the left precentral gyrus, the left parietal operculum, and the right anterior cingulate cortex showed selective responses to STM-W. A previous imaging study
has indicated that the region implicated in subvocal
rehearsal or phonological processing extends into theleft precentral gyrus and the left parietal operculum(Paulesu et al., 1993). According to another imaging
study, which segregated semantic components andphonological components involved in reading words,
phonological processing has been associated with theleft precentral gyrus (Price et al., 1997). Thus, activationof these Rolandic operculum regions may reflect
involvement of intense articulatory rehearsal in memorizing lists of syntactically unrelated phrases. On theother hand, it has been shown that the anterior cingulate
cortex is involved in performance monitoring that is engaged in control of conflicting or competitive responses(Botvinick et al., 1999; Barch et al., 2000). Selective activation of this region for STM-W may reflect such processes induced by task difficulty. In the contrast of
STM-W ⫺ (SYN-1 ⫹ SYN-2), we observed STM-W-selective activation in the bilateral lingual gyrus and the rightcuneus. Similarly, in the contrast of STM-S ⫺ (SYN-1 ⫹SYN-2), we observed STM-S selective activation in thebilateral lingual gyrus and the right posterior parietal
cortex. Some of these regions were shown to be selectively involved in verbal short-term memory tasks withrecency judgment (Cabeza et al., 1997; Marshuetz etal., 2000). Therefore, STM-selective activation of theseregions is likely to reflect mnemonic processes for temporal order of verbal items, especially required in the
STM tasks.
Conclusion
The present study demonstrated that there exist neuralsystems in the left prefrontal cortex specialized for sentence comprehension: L. DPFC and L. IFG. The activation of these regions is related to processes of analyzing
syntactic structures, and it cannot be explained either
by task difficulty or by verbal working memory components, such as the phonological store, the subvocal rehearsal system, and the central executive. Moreover,these cortical regions are affected differently by the conditions that are required when one recalls the serial orderof words either in a sentence or in a scrambled series
of words, and when one makes syntactic judgments
on a sentence. We also clarified that there is a further
distinction between unconscious, obligatory sentence
processing and conscious, controlled sentence processing. Linguists have provided a clear conceptualization of what distinctions need to be made between syntactic processing and other cognitive processes in orderSentence Comprehension in Left Prefrontal Cortex
595

to account for linguistic competence (Chomsky, 1980).
We believe that identification of cortical regions responsible for the essential properties of syntactic processing
eventually leads to understanding how language is specialized and instantiated in the human brain.
Experimental Procedures
Participants
Sixteen male native Japanese speakers (ages 18–37) participated in
the present study. All but one participant showed right handedness.
During the study, participants wore prism glasses and earplugs,
and were in a supine position in the magnet, while the participant’shead was immobilized with padding inside the radio-frequency coil.
Informed consent was obtained from each participant after the nature and possible consequences of the studies had been explained.
Approval for these experiments was obtained from the institutional
review board of the University of Tokyo, Komaba.
Stimuli and Tasks
As shown in Figure 1, we presented each word in yellow letters inhiragana and kanji against a dark background (maximum visual
angle, 1.5⬚ ⫻ 12⬚ for a pair of phrases). The visual stimuli were always
presented at the center of the screen. Participants read the stimuli
covertly through prism glasses. Each sentence was a center-embedded sentence that included two proper nouns (names), two verbs,
and one pronoun. The sentence set consisted of six types of grammatical collocations as follows; [N1-wa N2-ga P-wo V1-to V2], [N1-ga
N2-ni P-ga V1-to V2], [N1-ni N2-ga P-wo V1-to V2], [N1-ga P-wo V1-to
N2-ni V2], [N1-ga P-wa N2-to V1-to V2], and [N1-ga P-ni V1-to N2-ni V2](N, proper noun; V, verb; P, pronoun; -ga, nominative or accusative
marker; -wa, topic marker; -ni, dative marker; -wo, accusative
marker; N2-to, postposition “with N2”; and V1-to, complementizer“that V1”) (Tsujimura, 1996). For each type, we prepared twelve sentences that contained different lexical items. Because -ga can markeither nominative or accusative case, participants had to analyze
syntactic structures for assigning a thematic role to each nounphrase.
In SYN-1, participants were asked to judge whether the subjectof an underlined verb corresponded to the person in paired words.
The underlined verb was presented again in the paired words. In
SYN-2, participants judged whether an underlined pronoun was able
to refer to the person in paired words. The underlined pronoun waspresented again in the paired words, and it had only one possible
sentence-internal antecedent. Participants responded by pressing
yes/no buttons. These tasks were further controlled by the following
conditions. With the presence of an embedded clause, the subject
and verb were not always adjacent in a sentence as a result of theJapanese word order of subject-object (an embedded clause)-verb.
An underlined pronoun was either the pronominal kare/kanojo (he/she, him/her in English) or the reflexive zibunzishin (himself/herself
in English), with the pronominal and reflexive referring to different
people when occurring in the same position. In the example shownin Figure 1A, when him is replaced with himself, the reflexive himself
refers to Saburo, whom the pronominal him cannot refer to (Haegeman, 1994; Tsujimura, 1996).
In STM-S, participants were presented with the same set of sentences used in the SYN tasks and were asked to memorize eachsentence. Paired phrases including an underlined phrase were presented, and participants judged whether the left phrase preceded
the right one in the original sequence or not. The paired phrases werealways adjacent in the original sequence. Participants responded bypressing yes/no buttons. In STM-W, participants were presented
with nouns and verbs separately that were used in a sentence andwere asked to memorize individual phrases within either noun orverb group. We added the Japanese case marker of -wo (accusative)
or -ni (dative) to all of the three nouns, so that one noun had no
syntactic relationship with the other nouns and verbs, while thenumber of phonological units was equated between STM-W andthe other three tasks. Paired phrases (no underlined phrase in
STM-W) were presented, and participants judged whether the left
phrase preceded the right one in the original sequence or not. The

paired phrases were always adjacent in the noun or verb group. To
control the serial position effect on memory recall, the randomized
positions of paired phrases within the original sequence were
equated between STM-S and STM-W. In one out of six trials of the
STM tasks, we presented paired phrases with a different casemarker for nouns or a different tense for verbs, to which participants
were to respond “No.” As a result of this procedure, participants
had to memorize whole phrases as well as phrase orders.
Participants underwent practice sessions before scanning so thatthey were fully familiarized with each task. Furthermore, the tasklabel was presented at the initiation of each trial (see Figure 1A) to
exclude the possible ambiguity or conflict caused by task transitions. The four tasks were conducted in a conventional block designof fMRI. One trial with a fixed duration of 6 s was repeated six times
in each task block. STM-W served as a baseline task of a single
scanning session, in which STM-W and each of SYN-1, SYN-2, andSTM-S were alternatively presented (seven blocks per session). All
sentences were different within each session. We prepared three
types of sessions, each using a different order of tasks: SYN-1,
SYN-2, STM-S; SYN-2, STM-S, SYN-1; and STM-S, SYN-1, SYN-2.
We tested 12 sessions (four sessions for each type) for each participant, and the order of tasks was counterbalanced within and acrossparticipants.
Imaging and Data Analyses
The fMRI scans were conducted using a 1.5 T scanner (Stratis II,
Premium, Hitachi Medical Corporation, Tokyo, Japan). We scannedover 15 horizontal slices, each 6 mm thick, covering from z ⫽ ⫺24
to 66 mm, with a gradient echo echo-planar imaging sequence(repetition time, 3 s; echo time, 50 ms; flip angle, 90⬚; field of view,
192 ⫻ 192 mm2; resolution, 3 ⫻ 3 mm2 ). High-resolution structural
T1-wighted images were also acquired from all participants in orderto permit anatomical localization of activation foci. For analyses offunctional data, we used statistical parametric mapping software(SPM99, Wellcome Department of Cognitive Neurology, London,
UK). The data were realigned, spatially normalized to the standard
brain space, resampled every 3 mm using sinc interpolation, andsmoothed with an isotropic Gaussian kernel of 8 mm full width at
half maximum. Low-frequency noise and global changes in activity
were further removed. Task-specific effects were estimated using
a general linear model with a delayed (6 s) boxcar waveform. For
random effects analyses, a contrast image between tasks was generated for each participant and used for intersubject comparisons.
A statistical threshold was set to p ⬍ 0.05, corrected for multiple
comparisons.
Acknowledgments
This work was supported by a Core Research for Evolutional Scienceand Technology (CREST) grant from Japan Science and Technology
Corporation and by a Young Investigators’ Grant from Human Frontier Science Program (HFSP) to K.L.S. We would like to thank Yasushi Miyashita for encouragement; Colin Phillips, Christopher Tancredi, and Noriaki Yahata for critical comments; Alec Marantz, David
Poeppel, and David Embick for comments on the earlier draft; David
Caplan and Michael W.L. Chee for helpful discussion; Fumitaka
Homae, Kei Suzuki, Yasuki Hashimoto, and Yasuki Noguchi for technical assistance; and Hiromi Matsuda for administrative assistance.
Received: December 13, 2001
Revised: May 13, 2002
References
Baddeley, A. (1992). Working memory. Science 255, 556–559.
Baker, M.C. (2001). The Atoms of Language (New York: Basic
Books).
Barch, D.M., Braver, T.S., Nystrom, L.E., Forman, S.D., Noll, D.C.,
and Cohen, J.D. (1997). Dissociating working memory from taskdifficulty in human prefrontal cortex. Neuropsychologia 35, 1373–
1380.
Barch, D.M., Braver, T.S., Sabb, F.W., and Noll, D.C. (2000). AnteriorNeuron596

cingulate and the monitoring of response conflict: evidence from an
fMRI study of overt verb generation. J. Cogn. Neurosci. 12, 298–309.

the short-term maintenance of verbal information. J. Neurosci. 16,
808–822.

Botvinick, M., Nystrom, L.E., Fissell, K., Carter, C.S., and Cohen, J.D.
(1999). Conflict monitoring versus selection-for-action in anterior
cingulate cortex. Nature 402, 179–181.

Fletcher, P.C., Shallice, T., and Dolan, R.J. (1998). The functionalroles of prefrontal cortex in episodic memory. I. Encoding Brain 121,
1239–1248.

Braver, T.S., Cohen, J.D., Nystrom, L.E., Jonides, J., Smith, E.E.,
and Noll, D.C. (1997). A parametric study of prefrontal cortex involvement in human working memory. Neuroimage 5, 49–62.

Fodor, J.A. (1983). The Modularity of Mind (Cambridge, MA: The
MIT Press).

Buckner, R.L., Koutstaal, W., Schacter, D.L., Wagner, A.D., and Rosen, B.R. (1998). Functional-anatomic study of episodic retrieval
using fMRI. I. Retrieval effort versus retrieval success. Neuroimage
7, 151–162.
Bunge, S.A., Klingberg, T., Jacobsen, R.B., and Gabrieli, J.D.E.
(2000). A resource model of the neural basis of executive working
memory. Proc. Natl. Acad. Sci. USA 97, 3573–3578.
Cabeza, R., Mangels, J., Nyberg, L., Habib, R., Houle, S., McIntosh,
A.R., and Tulving, E. (1997). Brain regions differentially involved inremembering what and when: a PET study. Neuron 19, 863–870.
Caplan, D., and Waters, G.S. (1999). Verbal working memory andsentence comprehension. Behav. Brain Sci. 22, 77–126.
Caplan, D., Alpert, N., and Waters, G. (1999). PET studies of syntactic
processing with auditory sentence presentation. Neuroimage 9,343–351.
Chein, J.M., and Fiez, J.A. (2001). Dissociation of verbal working
memory system components using a delayed serial recall task.
Cereb. Cortex 11, 1003–1014.
Chomsky, N. (1980). Rules and Representations (New York: Columbia University Press).
Chomsky, N. (1984). Modular Approaches to the Study of the Mind
(San Diego, CA: San Diego State University Press).
Clark, C.R., Egan, G.F., McFarlane, A.C., Morris, P., Weber, D., Sonkkilla, C., Marcina, J., and Tochon-Danguy, H.J. (2000). Updating
working memory for words: a PET activation study. Hum. Brain
Mapp. 9, 42–54.
Cohen, J.D., Forman, S.D., Braver, T.S., Casey, B.J., ServanSchreiber, D., and Noll, D.C. (1994). Activation of the prefrontal cortex in a nonspatial working memory task with functional MRI. Hum.
Brain Mapp. 1, 293–304.
Cohen, J.D., Perlstein, W.M., Braver, T.S., Nystrom, L.E., Noll, D.C.,
Jonides, J., and Smith, E.E. (1997). Temporal dynamics of brain
activation during a working memory task. Nature 386, 604–608.
Coltheart, M. (1999). Modularity and cognition. Trends Cogn. Sci.
3, 115–120.
Comrie, B. (1989). Language Universals and Linguistic Typology(Chicago: The University of Chicago Press).
Cooke, A., Zurif, E.B., De Vita, C., Alsop, D., Koenig, P., Detre, J.,
Gee, J., Pinãngo, M., Balogh, J., and Grossman, M. (2002). Neuralbasis for sentence comprehension: grammatical and short-term
memory components. Hum. Brain Mapp. 15, 80–94.

Friederici, A.D., Pfeifer, E., and Hahne, A. (1993). Event-related brain
potentials during natural speech processing: effects of semantic,
morphological and syntactic violations. Cogn. Brain Res. 1, 183–192.
Friederici, A.D., Meyer, M., and von Cramon, D.Y. (2000). Auditory
language comprehension: an event-related fMRI study on the processing of syntactic and lexical information. Brain Lang. 74, 289–300.
Gunter, T.C., and Friederici, A.D. (1999). Concerning the automaticity
of syntactic processing. Psychophysiology 36, 126–137.
Haegeman, L. (1994). Introduction to Government and Binding Theory (Oxford: Blackwell Publishers Ltd).
Homae, F., Hashimoto, R., Nakajima, K., Miyashita, Y., and Sakai,
K.L. (2002). From perception to sentence comprehension: the convergence of auditory and visual information of language in the left
inferior frontal cortex. Neuroimage, 16, 883–900.
Indefrey, P., Hagoort, P., Herzog, H., Seitz, R.J., and Brown, C.M.
(2001). Syntactic processing in left prefrontal cortex is independentof lexical meaning. Neuroimage 14, 546–555.
Just, M.A., and Carpenter, P.A. (1992). A capacity theory of comprehension: individual differences in working memory. Psychol. Rev.
99, 122–149.
Just, M.A., Carpenter, P.A., Keller, T.A., Eddy, W.F., and Thulborn,
K.R. (1996). Brain activation modulated by sentence comprehension.
Science 274, 114–116.
Kang, A.M., Constable, R.T., Gore, J.C., and Avrutin, S. (1999). An
event-related fMRI study of implicit phrase-level syntactic and semantic processing. Neuroimage 10, 555–561.
Kluender, R., and Kutas, M. (1993). Bridging the gap: evidence from
ERPs on the processing of unbounded dependencies. J. Cogn. Neurosci. 5, 196–214.
Marshuetz, C., Smith, E.E., Jonides, J., DeGutis, J., and Chenevert,
T.L. (2000). Order information in working memory: fMRI evidence forparietal and prefrontal mechanisms. J. Cogn. Neurosci. 12, 130–144.
Martin, R.C. (1987). Articulatory and phonological deficits in shortterm memory and their relation to syntactic processing. Brain Lang.
32, 159–192.
Martin, R.C. (1993). Short-term memory and sentence processing:
Evidence from neuropsychology. Mem. Cognit. 21, 176–183.
McCarthy, R.A., and Warrington, E.K. (1987). The double dissociation of short-term memory for lists and sentences: evidence fromaphasia. Brain 110, 1545–1563.
Milner, B., Corsi, P., and Leonard, G. (1991). Frontal-lobe contribution to recency judgements. Neuropsychologia 29, 601–618.

Dapretto, M., and Bookheimer, S.Y. (1999). Form and content: dissociating syntax and semantics in sentence comprehension. Neuron
24, 427–432.

Moro, A., Tettamanti, M., Perani, D., Donati, C., Cappa, S.F., andFazio, F. (2001). Syntax and the brain: disentangling grammar byselective anomalies. Neuroimage 13, 110–118.

Dick, F., Bates, E., Wulfeck, B., Utman, J.A., Dronkers, N., and Gernsbacher, M.A. (2001). Language deficits, localization, and grammar:
evidence for a distributive model of language breakdown in aphasic
patients and neurologically intact individuals. Psychol. Rev. 108,759–788.

Münte, T.F., Heinze, H.-J., and Mangun, G.R. (1993). Dissociationof brain activity related to syntactic and semantic aspects of language. J. Cogn. Neurosci. 5, 335–344.

Duncan, J., and Owen, A.M. (2000). Common regions of the humanfrontal lobe recruited by diverse cognitive demands. Trends Neurosci. 23, 475–483.
Embick, D., Marantz, A., Miyashita, Y., O’Neil, W., and Sakai, K.L.
(2000). A syntactic specialization for Broca’s area. Proc. Natl. Acad.
Sci. USA 97, 6150–6154.
Fiebach, C.J., Schlesewsky, M., and Friederici, A.D. (2001). Syntactic
working memory and the establishment of filler-gap dependencies:
insights from ERPs and fMRI. J. Psycholinguist. Res. 30, 321–338.
Fiez, J.A., Raife, E.A., Balota, D.A., Schwarz, J.P., Raichle, M.E., andPetersen, S.E. (1996). A positron emission tomography study ofNeville, H., Nicol, J.L., Barss, A., Forster, K.I., and Garrett, M.F.
(1991). Syntactically based sentence processing classes: evidence
from event-related brain potentials. J. Cogn. Neurosci. 3, 151–165.
Newman, A.J., Pancheva, R., Ozawa, K., Neville, H.J., and Ullman,
M.T. (2001). An event-related fMRI study of syntactic and semantic
violations. J. Psycholinguist. Res. 30, 339–364.
Paulesu, E., Frith, C.D., and Frackowiak, R.S.J. (1993). The neuralcorrelates of the verbal component of working memory. Nature 362,
342–345.
Petrides, M., Alivisatos, B., and Evans, A.C. (1995). Functional activation of the human ventrolateral frontal cortex during mnemonic retrieval of verbal information. Proc. Natl. Acad. Sci. USA 92, 5803–
5807.

Sentence Comprehension in Left Prefrontal Cortex
597

Poldrack, R.A., Wagner, A.D., Prull, M.W., Desmond, J.E., Glover,
G.H., and Gabrieli, J.D.E. (1999). Functional specialization for semantic and phonological processing in the left inferior prefrontal
cortex. Neuroimage 10, 15–35.
Potter, M.C. (1993). Very short-term conceptual memory. Mem. Cognit. 21, 156–161.
Price, C.J., Moore, C.J., Humphreys, G.W., and Wise, R.J.S. (1997).
Segregating semantic from phonological processes during reading.
J. Cogn. Neurosci. 9, 727–733.
Rösler, F., Pechmann, T., Streb, J., Röder, B., and Hennighausen,
E. (1998). Parsing of sentences in a language with varying word
order: word-by-word variations of processing demands are revealedby event-related brain potentials. J. Mem. Lang. 38, 150–176.
Rypma, B., Prabhakaran, V., Desmond, J.E., Glover, G.H., and Gabrieli, J.D.E. (1999). Load-dependent roles of frontal brain regions in
the maintenance of working memory. Neuroimage 9, 216–226.
Sakai, K.L., Hashimoto, R., and Homae, F. (2001). Sentence processing in the cerebral cortex. Neurosci. Res. 39, 1–10.
Shallice, T. (1988). From Neuropsychology to Mental Structure(Cambridge, UK: Cambridge University Press).
Smith, E.E., and Jonides, J. (1999). Storage and executive processes
in the frontal lobes. Science 283, 1657–1661.
Smith, N., and Tsimpli, I.-M. (1995). The Mind of a Savant: Language
Learning and Modularity (Oxford: Blackwell Publishers).
Stromswold, K., Caplan, D., Alpert, N., and Rauch, S. (1996). Localization of syntactic comprehension by positron emission tomography. Brain Lang. 52, 452–473.
Tsujimura, N. (1996). An Introduction to Japanese Linguistics (Cambridge, MA: Blackwell Publishers).
Vos, S.H., Gunter, T.C., Kolk, H.H.J., and Mulder, G. (2001). Working
memory constraints on syntactic processing: an electrophysiological investigation. Psychophysiology 38, 41–63.
Waters, G.S., Caplan, D., and Hildebrandt, N. (1991). On the structureof verbal short-term memory and its functional role in sentencecomprehension: evidence from neuropsychology. Cogn. Neuropsychol. 8, 81–126.
Waters, G.S., Caplan, D., and Rochon, E. (1995). Processing capacity
and sentence comprehension in patients with Alzheimer’s disease.
Cogn. Neuropsychol. 12, 1–30.