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Human Brain Mapping 17:89 –99(2002) 䉬

Lateralized Activation in the Inferior Frontal
Cortex during Syntactic Processing: EventRelated Optical Topography Study
Yasuki Noguchi,1 Tatsuya Takeuchi,1 and Kuniyoshi L. Sakai1,2*
1

Department of Cognitive and Behavioral Science, Graduate School of Arts and Sciences,
The University of Tokyo, Komaba, Tokyo, Japan
2
CREST, Japan Science and Technology Corporation, Kawaguchi-shi, Japan䉬䉬

Abstract: Functional imaging with near-infrared light has the potential to provide novel information thatcannot be obtained with other imaging techniques. An event-related paradigm has not been fully
established for studying human cognitive functions with near-infrared optical imaging. We conductedlanguage experiments to develop an event-related paradigm with optical topography (OT). We directlycompared cortical activation during syntactic and semantic decision tasks, both of which involved error
detection in a sentence stimulus that consisted of a noun phrase and a verb. In the syntactic decision task,
subjects judged whether the presented sentence is syntactically correct, where the syntactic knowledge
about the distinction between transitive and intransitive verbs was required. In the semantic decision task,
subjects judged whether the presented sentence is semantically correct, where the lexico-semantic knowledge about selectional restrictions was indispensable. We found local increases in oxyhemoglobin concentration, which were selectively associated with the syntactic decision task. Activation in the left inferior
frontal gyrus was detected when syntactically anomalous sentences were presented, whereas there was no
significant activation in this region when semantically anomalous sentences were presented. Moreover,identical stimuli of normal sentences elicited activation in the left inferior frontal gyrus, only when theemployment of syntactic knowledge was required. This task-selective activation was not observed in any
other measured regions, including the right homologous region. These results demonstrate that OT
techniques, when coupled with the event-related paradigm, are useful for studying the higher cognitive
functions of the human cerebral cortex. Hum. Brain Mapping 17:89 –99, 2002. © 2002 Wiley-Liss, Inc.
Key words: near-infrared spectroscopy; optical topography; functional imaging; hemodynamics; language; syntax; semantics䉬䉬

INTRODUCTION

Contract grant sponsor: Japan Science and Technology Corporation(JST); Contract grant sponsor: Human Frontier Science Program(HFSP).
*Correspondence to: Dr. Kuniyoshi L. Sakai, 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, Japan. E-mail: sakai@mind.c.u-tokyo.ac.jp
Received for publication 12 October 2001; accepted 19 April 2002
DOI 10.1002/hbm.10050
Published online 00 Month 2002 in Wiley InterScience (www.
interscience.wiley.com).
© 2002 Wiley-Liss, Inc.

The light absorption spectra of oxyhemoglobin anddeoxyhemoglobin differ in a near-infrared range. The
near-infrared spectroscopy (NIRS) techniques haveenabled the assessment of hemoglobin concentration
changes in brain tissues [Chance et al., 1988; Frostig etal., 1990; Jöbsis, 1977; Villringer et al., 1993]. Based on
the same principle, optical topography (OT) was recently developed as a non-invasive technique for functionally mapping the human cerebral cortex [Koizumi
et al., 1999; Maki et al., 1995; Yamashita et al., 1996]. A
major difference between OT and NIRS is that OT

䉬 Noguchi et al. 䉬measures spectroscopic reflection and scattering simultaneously from multiple measurement points,
whereas NIRS measures these effects with one or afew pairs of a light emitter and a detector. Using OT,
we have previously reported focal activation in the left
superior temporal cortex, by comparing speech recognition of stories and repeated sentences [Sakai et al.,
2001; Sato et al., 1999].
NIRS and OT techniques provide several advantages over other imaging methods. First, these techniques provide independent measurement of the concentration changes in oxy- and deoxyhemoglobin.
Second, they produce no instrument noise interferingwith the auditory stimuli. Third, they do not require ahead constraint; thus their application may enable
developmental mapping studies of infants. Previous
NIRS and OT studies have investigated the hemodynamic changes associated with various functions suchas visual processing [Kato et al., 1993; Villringer et al.,1993] and language processing [Fallgatter et al., 1998;
Hock et al., 1997; Sakatani et al., 1998; Watanabe et al.,1998].
All of these studies, however, have used a blockedtask paradigm that measures accumulated activation
over many trials presented in close succession. Such a
procedure does not distinguish individual trials
within one block, and thus, an analysis according toindividual trial types (e.g., stimulus types or subjects’
responses) is not possible. Several recent studies havereported an event-related paradigm using NIRS in the
motor and visual areas [Obrig et al., 2000; Wobst et al.,2001]. We combined an event-related experimental
design with the OT techniques, and applied it to thestudy of cortical responses during language processing. The advantages of our OT techniques over previous NIRS studies of language functions are two-fold.
By employing an event-related design, stimulus types
in each language task, such as normal and anomalous
sentences, can be intermixed, making selective averaging according to stimulus types possible. By using
OT, we can simultaneously measure cortical responses
in a large area, including the frontal and temporal
association areas. This is important because higherlevel cognitive events like language processing may
elicit activity in various cortical regions.
MATERIALS AND METHODS
Subjects
Eight male native Japanese speakers (ages 22–36
years) participated in the present study. They showed
right-handedness (laterality quotients: 81–100) by the䉬

Edinburgh inventory [Oldfield, 1971]. Informed consent from each subject was obtained according to thedeclaration of Helsinki. Approval for the human experiments was obtained from the institutional review
board of the University of Tokyo, Graduate School ofArts and Sciences.
Tasks
In the present experiment, subjects were asked tolisten to spoken language stimuli and to make linguistic decisions with their eyes closed. Speech sounds
presented in the tasks were digitized (16 bit; the normal audio cut-off, 11,025 Hz) using speech synthesis
software (Oshaberi-mate, Fujitsu, Tokyo, Japan) thatconverted Japanese written text into sound waveforms. They were presented with a stereophonic headphone at maximum sound pressure levels of 80 dB.
We compared cortical activation mainly between
two explicit linguistic tasks: syntactic decision (Syn)and semantic decision (Sem) tasks (Fig. 1). These tasks
were basically error detection in a sentence stimulus:
one stimulus of a noun phrase (a noun and a caseparticle), followed by a verb stimulus for each trial.
Each noun phrase and each verb was always threesyllable long and presented for 350 msec to ensure a
constant listening time. The same set of words wereused to make normal (N) and anomalous (A) sentences for each task. We prepared an original set of 60
pairs of a noun phrase and a verb. One half of theoriginal pairs were used as N stimuli for each task. An
additional 30 pairs were made from the original set as
A stimuli for each task, by varying noun phrase-verb
combinations (Fig. 1A). Thus, each A stimulus of one
task was matched for where a single anomaly occurred. These stimuli formed minimal pairs for both
intratask pairs (N and A sentences) and intertask pairs(e.g., A sentences for Syn and Sem). We named thisnovel task design as a minimal-pair paradigm.
In the Syn task, subjects judged whether sentenceswere either syntactically normal or anomalous, while
word combinations in each sentence were semantically related. We focused on a universal aspect ofsyntactic operations that are common to both English
and Japanese: a distinction between transitive verbs(vt) and intransitive verbs (vi). This distinction is critical in sentence comprehension because the choice of atransitive or intransitive verb determines the syntactic
structure of a sentence [Smith and Wilson, 1979]. Subjects were explicitly instructed to detect a syntactic
anomaly, but they were not instructed to pay attention
to the distinction between vt and vi. In the Sem task,
subjects judged whether sentences were either seman-90 䉬䉬 Event-Related OT Study of Syntactic Processes 䉬

Figure 1.
A: Sentence comprehension tasks that contrast syntactic and particle were not used in the Syn task, because they produced only
semantic processing. In the syntactic decision (Syn) task, partici- syntactically N sentences. In the Sem task, Acc and Nom produced
pants were asked to distinguish whether a given sentence was either N or A sentences, depending on the denotative meaning ofsyntactically normal (N) or anomalous (A). In a semantic decision the verb used. B: The distinction between the Syn and Sem tasks.
(Sem) task, participants were asked to decide whether a given Distinct types of linguistic processing were required to performsentence was semantically N or A. In the Syn task, the accusative the two tasks correctly. The syntactic knowledge about vt/vi dis(Acc) case particle could produce either N or A sentences, de- tinction was required for judging Syn N or Syn A, while thepending on whether a transitive verb (vt) or intransitive verb (vi) lexico-semantic knowledge about selectional restrictions was inwas used. Stimuli (gray shaded) with the nominative (Nom) case dispensable for judging Sem N or Sem A.

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䉬 Noguchi et al. 䉬

TABLE I. Behavioral data*

Accuracy (%)
Reaction time
(msec)

Syn N

Syn A

Sem N

Sem A

Pitch-match

Pitch-nonmatch

88.9 ⫾ 2.7

93.1 ⫾ 2.8

85.7 ⫾ 2.5

92.4 ⫾ 3.7

97.5 ⫾ 1.9

97.1 ⫾ 1.5

546 ⫾ 65593 ⫾ 58558 ⫾ 79585 ⫾ 59390 ⫾ 85403 ⫾ 68

* Values are expressed as mean ⫾ SE (n ⫽ 8 subjects).

tically normal or anomalous, while presented sentences were syntactically correct as to the usage of vt
and vi. We focused on the lexico–semantic relationship(selectional restrictions) between a verb and a noun.
For example, ‘snow’ and ‘lie’ (Sem N) are lexico-semantically associated, whereas ‘snow’ and ‘scold’ or‘snow’ and ‘escape’ (Sem A) have little association(Fig. 1). This distinction was confirmed by high accuracy in the Sem task (Sem N, 85.7%; Sem A, 92.4%;
Table I).
The Syn task cannot be solved on the basis of thelexico–semantic relationship between a verb and anoun, because it is always correct for both Syn N and
Syn A. In Syn A, there was an anomaly in the syntactic
relationship between a verb and a noun phrase
marked for object. Moreover, transitive and intransitive verbs in Japanese are clearly segregated into different words, and there are a number of morphologically related verb pairs (e.g., tomeru (vt) and tomaru(vi); gloss: ‘stop’), which are similar to raise–rise distinction in English [Tsujimura, 1996]. Although the
ambiguity of English verbs (vt/vi) like ‘stop’ is resolved by both syntactic (presence/absence of object)and semantic information of a sentence, transitivity ofJapanese verbs is primarily determined by morphosyntax or words per se. Therefore, the Syn task explicitly requires syntactic knowledge for distinguishingtransitive and intransitive verbs.
Before the experiments, we explicitly explained thenature of two tasks to the subjects, providing examples for each of Syn A, Sem A, Syn N, and Sem N withthe following instruction: “The sentence ‘yuki-wo
tsumoru’ (snow-Acc lie; Acc, the accusative case particle) is anomalous because of the syntactic violation
between a verb and a noun phrase. Because ‘yuki’(snow) and ‘tsumoru’ (lie) are lexico-semantically associated, as ‘yuki-ga tsumoru’ (snow-Nom lies; Nom,the nominative case particle) is acceptable, it is not asemantic but a syntactic error. In contrast, the sentence‘yuki-wo shikaru’ (snow-Acc scold) is anomalous because of the lexico-semantic mismatch between ‘yuki’(snow) and ‘shikaru’ (scold). Because this sentence issyntactically correct as to the relationship between averb and a noun phrase, this is not a syntactic but a䉬semantic error. Finally, the sentence ‘yuki-wo sawaru’(snow-Acc touch) is normal because it is both syntactically and semantically correct.”
Taking the distinctions between the Syn and Sem
tasks into account, our task design can be summarized
as the scheme shown in Figure 1B. The two tasks
explicitly required these distinct task demands. Therefore, the task demands correspond to the different
components of sentence processing. Similar task designs have been used in previous fMRI studies [Kanget al., 1999; Ni et al., 2000] for contrasting implicit
syntactic and semantic processes. In these studies withEnglish sentences, syntactic anomalies, such as ‘Trees
can grew’, and semantic anomalies, such as ‘Trees caneat’ were introduced.
To control for non-linguistic components such as
auditory perception of sounds, decision of two
choices, and motor responses, we employed a pitch
judgment (Pitch) task. In this task, a pair of pure tones(300 Hz or 400 Hz) superimposed in white noises (thelow-pass cut-off, 5,512 Hz) was presented for 350 msec
for each tone, and subjects judged whether the pair
was at the same pitch (Match) or different pitches(Nonmatch).
During the experiments, the three tasks were conducted in separate runs. Before each run, the subjects
were explicitly informed about which task they shouldhave performed. In the Syn task, we instructed: “Press
the green button if the presented sentence is syntactically correct; press the red button if it is syntacticallyincorrect.” In the Sem task, we instructed: “Press thegreen button if the presented sentence is semanticallycorrect; press the red button if it is semantically incorrect.” In the Pitch task, we instructed: “Press the green
button if the pair is at the same pitch; press the red
button if it is at different pitches.” A single run contained ten trial events, with variable inter-trial intervals (20, 22, 24, 26, and 28 sec, pseudo-randomized
within a run). Our event-related design corresponds toa single-event study, in which single, well-separated
events were analyzed. The order of N/A or Match/Nonmatch stimuli was pseudo-randomized in eachrun, and the number of presentations of N/A or
Match/Nonmatch stimuli was equated in each task.

92 䉬䉬 Event-Related OT Study of Syntactic Processes 䉬

Figure 2.
The measurement points in the present OT experiment. Images of images of a representative subject, and measurement points werethe left lateral surface (L) and the right lateral surface (R) are superimposed onto the cortical surface image. The numbers deshown. The cortical surface image was reconstructed from 3D MR note channel numbers of the measurement points.

During the scanning, both accuracy and RT were measured on line [Hashimoto et al., 2000]. As a baseline,
subjects were asked to attend to a continuous tone (400Hz) until the next stimulus was presented. There were
12 runs in one imaging session (four runs for eachtask) and the orders of tasks were counterbalanced.
Each subject was tested in two sessions.
Optical topography measurements
We used two OT systems (ETG-100 and ETG-A1;
Hitachi Medical Corporation, Tokyo, Japan), one foreach hemisphere. Near-infrared laser diodes with two
wavelengths (ranges: 782–793 and 823– 833 nm) wereused as the light sources (maximum intensity: 2 mW/
mm2, intensity modulation: 1–10 kHz). The reflected
lights were detected with avalanche photodiodes located 30 mm from an emitter. In each hemisphere,
eight emitters and seven detectors were alternately
placed on a head shell at square intersection points ofa 3 ⫻ 5 grid. This configuration formed 22 pairs of
optic probes, or 22 channels, each of which consistedof a detector and one of adjacent emitters. Opticalsignals from multiple emitters with independently
modulated laser intensities were separated by rock-in
amplifiers without cross talk between the signals [Yamashita et al., 1999]. Forty-four channels in both hemispheres were simultaneously recorded every 500 msec
to obtain the transmittance data lnT(␭,t) as a functionof wavelength (␭) and a measurement time (t). The
measured region centered on the Sylvian fissures and䉬covered an area of 6 ⫻ 12 cm2 in each hemisphere(Fig. 2).
Data analyses
We extracted 10 event periods from time-series dataof lnT(␭,t) in a single run, allowing for overlaps during
the baseline. Each event period ranged from 6 sec
before the stimulus onset to 20 sec after the onset.
Excluding the activation period during 12 sec after the
stimulus onset [Ni et al., 2000], time points were baseline-corrected with a curve of the third degree [Sato etal., 1999]. For each session, the event data of six conditions (Syn N, Syn A, Sem N, Sem A, Pitch-Match,and Pitch-Nonmatch) were averaged separately ateach wavelength. Only the trials in which subjects had
responded correctly were incorporated to the averaging. After averaging, the relative changes in oxyhemoglobin concentration (Coxy) and deoxyhemoglobin
concentration (Cdeoxy) were calculated [Maki et al.,
1995].
For a group analysis, we averaged the data in eachcorresponding channel across subjects. The hemoglobin time points of Coxy in Pitch-Match and PitchNonmatch were averaged together for control responses. Then we subtracted the averaged control
responses from Coxy changes in one of four language
conditions. We calculated correlation coefficients (rvalues) between these subtracted data and a basis
function of the peri-stimulus time for hemodynamics[Friston et al., 1998a]. This subtraction method was

93 䉬䉬 Noguchi et al. 䉬

Figure 3.
Oxyhemoglobin r-maps under four language conditions compared were used for linear interpolation, and then r-values at intermeto a pitch judgment task: Syn N (A), Syn A (B), Sem N (C), and diate voxels were bilinearly interpolated and color-coded, as
Sem A (D). In each r-map, r-values at the measurement points shown by a color bar at the right.

based on the assumption that hemodynamic responses in each task condition are proportional to thebasis function [Boynton et al., 1996; Cohen, 1997].
Therefore, the subtracted time-series is considered to
be also proportional to the basis function. A thresholdof r-values for statistical significance was set to 0.45
(time points, N ⫽ 52; P ⫽ 0.05), based on an equation
in a previous study [Bandettini et al., 1993], thereby
taking into account the multiple comparisons (44channels in both hemispheres).

Image reconstruction
After each session, a 3D magnetic resonance (MR)image was obtained to precisely determine anatomical
positions of the channels. Alfacalcidol beads (0.25 ␮g)buried in the head shells were used as MR markers,
which can be identified on the MR image as spheres(diameter: 3 mm). Each MR marker was located at the
midpoint between an emitter and a detector. The MR
marker points were projected onto the cortical surface

Figure 4.
Localized activation in the left inferior frontal gyrus, selectively same comparison using deoxyhemoglobin data; this region did notassociated with the Syn task. Oxyhemoglobin r-maps of Syn–Sem show significant correlations at these left channels (r-values: 0.34,
are shown on the lateral surface images. Note the prominent ⫺0.11, and 0.30, respectively). The corresponding right channels
activation in the left inferior frontal gyrus at left channels 14, 15, 17, 18, and 22 showed little activation for oxyhemoglobin data
and 19 (r-values: 0.73, 0.68, and 0.69, respectively). We made the (r-values: 0.25, 0.35, and 0.10, respectively).

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䉬 Event-Related OT Study of Syntactic Processes 䉬

image as follows, using custom-made software forimage reconstruction (K.G.T., Tokyo, Japan). First, acurved surface was obtained for each hemisphere by aspline interpolation of the 3D positions of 22 MR
markers. Next, the curved surface was projected to theextracted cortical surface image of the same subject,perpendicularly to the curved surface. A measurement point was defined as an intersection of the cortical surface image and the perpendicular line from amarker point, which corresponds to the anatomical
position of each channel. These procedures conformed
to the assumption that optical signal changes are maximum at the measurement points, as shown by thespatial distribution of regionally averaged photonpath length calculated from stored photon paths[Maki et al., 1996]. Using these procedures for eachsession, we confirmed that the three measurement
points of left channels 14, 15, and 19 were within theleft inferior frontal gyrus (see Fig. 2).
In Figures 3 and 4, r-maps for averaged data acrosssubjects were superimposed on cortical surface imagesof a representative subject. For this image reconstruction with the same software mentioned above, r-values at the measurement points were used for linear
interpolation to make a 5 ⫻ 9 grid at spatial intervalsof 15 mm, and then r-values at voxels within eachsquare area were bilinearly interpolated and colorcoded to obtain an entire r-map on the cortical surface
image.
RESULTS
Behavioral accuracy and reaction time measured
from the onset of a latter stimulus are shown in Table
I. An ANOVA indicated a significant main effect oftask as regards both accuracy and reaction time (accuracy: F(2,45) ⫽ 5.3, P ⬍ 0.01, reaction time: F(2, 45)⫽ 33.6, P ⬍ 0.0001). Post-hoc tests (Fisher’s PLSD)
showed a difference between Syn and Pitch (accuracy:
P ⬍ 0.05, reaction time: P ⬍ 0.0001), and between Sem
and Pitch (accuracy: P ⬍ 0.01, reaction time: P⬍ 0.0001). The difference between Syn and Sem, however, was not significant (accuracy: P ⬎ 0.1, reaction
time: P ⬎ 0.5). These results suggest that Syn and Sem
tasks were equally balanced for task difficulty in termsof behavioral control. To examine the effect of stimuli(N or A), another two-way ANOVA was performed:
task (Syn, Sem) ⫻ stimulus (N, A). Main effects andthe interaction were not significant both in accuracy
and reaction time (P ⬎ 0.05 for all).
Figure 3 shows the r-maps for Coxy changes in thefour language conditions. In Syn N, there was signif-䉬

icant activation in the left inferior frontal gyrus (L.
IFG), the bilateral middle frontal gyrus, and the rightsuperior temporal cortex. The left supramarginal gyrus was also activated, although its activity was relatively weak. In Syn A, L. IFG as well as the right
middle frontal gyrus and the right superior temporalgyrus showed similar activation, whereas additional
activation was observed in the left superior temporal
cortex. In Sem N and Sem A, activation was much
weaker than in Syn N and Syn A. The left supramarginal gyrus and the right middle temporal gyrus wereweakly activated only in Sem N.
To show regions reflecting a difference between the
Syn and Sem tasks, we directly compared Syn responses (averaged data for Syn N and Syn A) and Sem
responses (averaged data for Sem N and Sem A), as
shown in oxyhemoglobin r-maps of Syn–Sem (Fig. 4).
The most significant difference was observed in L.
IFG, spreading among the three measurement pointsof left channels 14, 15, and 19. We averaged the data ofthese three points and calculated the time-series of
Coxy in each of four language conditions (Fig. 5A, B).
Event-related increases of Coxy were clearly observedin Syn N and Syn A (Fig. 5A; r ⫽ 0.83 and 0.66,
respectively), while they were observed neither in Sem
N nor in Sem A (Fig. 5B; r ⫽ 0.02 and ⫺0.35, respectively). We further calculated the mean Coxy changes
in this region, using temporal points from 3–9 sec after
the stimulus onset (Fig. 5C). A two-way ANOVA (task⫻ stimulus) indicated the significant main effect oftask (F(1, 28) ⫽ 5.3, P ⬍ 0.05), but without the main
effect of stimulus and the interaction (P ⬎ 0.5). Finally,
we confirmed that the subtracted data indeed followed the basis function. The subtracted time-series in
Figure 5D (blue line) showed a high coefficient ofdetermination (r2 ⫽ 0.63) for fitting the data with thebasis function (orange line).
In contrast, the right hemisphere did not show thisSyn-selective activation. Figure 5E and F showed thetime-series of Coxy in the right homologous region (R.
IFG) at right channels 17, 18, and 22. There was no
significant Coxy change in any of the four conditions(r-values; Syn N: 0.24, Syn A: 0.05, Sem N: 0.05, Sem A:⫺0.33), and an ANOVA indicated no significant main
effects or the interaction among the mean Coxychanges (Fig. 5G; P ⬎ 0.5). The coefficient of determination for fitting with a hemodynamic response function in the right IFG was much lower (r2 ⫽ 0.11) thanthat in L. IFG (Fig. 5H). We performed two-way
ANOVA at other channels, but neither significant
main effects nor interactions were observed (P ⬎ 0.05
for all). These results confirmed the left-lateralized95 䉬䉬 Noguchi et al. 䉬

Figure 5.
Event-related hemodynamic changes in the left and the right infe- errors of the mean (SE) across eight subjects. C: Mean Coxyrior frontal gyrus. A,B: Coxy time-series in Syn (A) and Sem (B) changes of the four language conditions in (A) and (B). Error bars
tasks, averaged across three measurement points in the left infe- indicate SE across the subjects (N ⫽ 8). D: A differential hemorior frontal gyrus. Hemodynamics for normal (green) and anom- dynamic response between Syn and Sem in the left inferior frontal
alous (red) sentences were plotted in each panel. Sentence stimuli gyrus. The averaged time-series of Sem N and Sem A was subwere presented at time zero, and responses were completed in 2 tracted from the averaged time-series of Syn N and Syn A. The
sec (events chart). The vertical axis represents relative hemoglo- subtracted time-series (blue line) were fitted to the basis function
bin changes (mMmm), which are the values of hemoglobin con- (orange line) with a least square method. Error bars indicate SE
centration (mM) multiplied by the effective path length in brain across the subjects. E–H: Coxy time-series, mean Coxy changes,
tissues (mm). For display purposes, data points were smoothed and subtracted time-series in the right inferior frontal gyrus, using
using a five-point moving average. Error bars indicate standard the same format as that in (A–D).

and localized activation of the inferior frontal gyrus
when the Syn task was performed.
DISCUSSION
In the present study, we demonstrated that an
event-related paradigm with OT techniques was sufficiently sensitive to investigate linguistic processes in
the human brain. We directly compared cortical activation during syntactic and semantic tasks and demonstrated task-selective Coxy changes in L. IFG, whichwere highly lateralized to the left hemisphere. Furthermore, this region was activated in Syn N and Syn䉬A, both of which required syntactic processing. Because stimuli in Syn N and Sem N were physically
identical, differential activation patterns between Syn
N and Sem N may reflect distinct linguistic factors
required in the Syn and Sem tasks. Therefore, ournovel language paradigm with strict linguistic controls, used together with event-related OT techniques,unequivocally showed specific cortical activation insentence processing.
We found differential activity during the Syn task
between L. IFG and R. IFG; significant Coxy increases
associated with the Syn task were observed only in L.
IFG. These results are consistent with previous func-

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䉬 Event-Related OT Study of Syntactic Processes 䉬

tional imaging studies [Dapretto and Bookheimer,
1999; Kang et al., 1999], which reported selective activation in a part of L. IFG during implicit syntactic vs.
semantic processing of sentences or phrases. Our previous fMRI study also showed that L. IFG is criticallyinvolved in explicit syntactic processing [Embick et al.,2000]. In the present study, increased Coxy changes in
L. IFG may reflect not just syntactic processing but thedifference between it and semantic processing. It
should be noted that the comparisons of both Sem N
vs. Pitch and Sem A vs. Pitch showed no significant
difference in L. IFG (Fig. 3C,D), suggesting that thesemantic processing have no effect on the activation in
L. IFG. Therefore, as to L. IFG activation, the effect ofthe difference between syntactic and semantic processing becomes equivalent to that of the syntactic
processing alone.
The sentences in Syn A had intransitive verbs thatwere accompanied by nouns case-marked for object(intransitivity violations). Because meaning of a sentence is derived from syntactic analyses of the sentence structure, the sentences in Syn A become semantically impossible. This type of semantic anomalies
stems from intransitivity violations imposed in the
Syn task, and thus it is indirect or secondary anomaly,
which should be conceptually distinguished from theprimary anomaly in the Syn task. It was not known
whether the subjects explicitly made their decisions on
the basis of the characteristics of the stimuli. The subjects could have based their decisions on the secondary anomaly in sentences. Nevertheless, the semantic
anomalies created by intransitivity violations in the
Syn task are qualitatively different from the semantic
anomalies created by selectional restriction violationsin the Sem task. Moreover, the semantic anomalies in
the Syn task are all-or-none type, because intransitivity violations can be present or not in sentences. In
contrast, the range of anomalies in the Sem task is
continuous, as it corresponds to the acceptability ofword-to-word associations. Therefore, semantic
anomalies in the two tasks are quantitatively different
as well. We cannot rule out entirely the possibility thatthe oxygenation effects in L. IFG reflected the semantic
anomalies in the Syn task. On the other hand, previous
imaging studies have accumulated evidence that L.
IFG is involved in syntactic processing [Friederici etal., 2000; Indefrey et al., 2001; Moro et al., 2001]. In
these studies, Jabberwocky sentences were used, inwhich all content words were replaced withpseudowords while inflections and function words
were maintained to preserve syntactic structures.
Without any contribution of semantic factors, activation in the left pars opercularis [Friederici et al., 2000]

䉬

and in the left pars triangularis [Moro et al., 2001] wasobserved during syntactic judgments. Indefrey et al.
[2001] also reported activations around the left inferior
frontal sulcus, which may correspond to the activationof the left middle frontal gyrus in Syn N. These results
indicate that activations in L. IFG and its adjacent area
are closely related to syntactic processing, suggestingthat L. IFG activation in the present study may be due
to syntactic processing of sentence structures.
The validity of the subtraction method we employed was confirmed by the high coefficient of determination for fitting the Coxy data in L. IFG with thebasis function, indicating that the time-series difference between Syn and Sem was proportional to thebasis function. Moreover, given the low frequency ofword presentation in the present study (mean in asingle run: 5 words/min), the nonlinear second-ordercomponent of the hemodynamic response function
can be regarded as negligible [Friston et al., 1998b].
We also confirmed that our results were robust anddid not depend on the shape of a hemodynamic function. Calculating a correlation between the subtracted
time-series and a box-car waveform (duration: 3– 8 sec
after the onset of a former stimulus, full-width halfmaximum of standard hemodynamics), the resultant
r-map was almost identical with Figure 4.
Previous event-related fMRI studies have identified
activation in L. IFG when syntactically anomalous as
opposed to normal sentences were presented [Kang etal., 1999; Ni et al., 2000]. In the present study, however, L. IFG was activated both in Syn N and Syn A,
and Coxy changes in these two conditions did notshow a significant difference (Fig. 5A,C). Previous
studies have used implicit or passive tasks for bothsyntactic and semantic conditions, and these task designs lack a control for the apparent attention to syntactic/semantic processing and difference involved.
The present task differed from previous ones in controlling for deployment of attention to the nature of
the anomaly, as ensured by the following three procedures. First, we explicitly explained the nature of thetwo tasks to the subjects before the experiments (seeMaterials and Methods). Second, there were two distinct task demands for linguistic knowledge: the syntactic knowledge about vt/vi distinction in the Syntask, and the lexico-semantic knowledge about selectional restrictions in the Sem task (Fig. 1B). Third, thetwo tasks were conducted in separate runs, and before
each run, we explicitly informed the subjects about
which task they should perform. Because of thesethree procedures, the explicit task demands directedattention either to syntactic processing or to semantic
processing, even if the sentences used for Syn N and97 䉬䉬 Noguchi et al. 䉬

Sem N are physically identical. Our results of L. IFG
activation are consistent with this differentiation. In
contrast to previous studies reporting L. IFG activation induced by syntactic anomalies, the present results suggest that the activation is not due to thepresence or absence of a syntactic anomaly, but due tosyntactic processing per se required in both Syn N and
Syn A.
CONCLUSIONSThe present study demonstrates that an event-related paradigm with OT techniques is useful in studying human cognitive functions. We found the taskselective activation that was localized in L. IFG. To
obtain such a spatial information is one advantage ofour techniques, which cannot be achieved by the previous NIRS studies. Furthermore, by using the eventrelated paradigm, we were able to analyze two kindsof stimuli (N and A) separately in each task. Consequently, this paradigm provided the novel finding,such that the physically identical stimuli used for Syn
N and Sem N induced the differential activation in L.
IFG. Although we were not able to separate primarysyntactic factors and secondary semantic factors
within the Syn task from the oxygenation effects in L.
IFG, it is noteworthy that the present study successfully dissociated different linguistic processes in the
Syn and Sem tasks, whereas previous NIRS or OT
studies have compared linguistic and non-linguistic
processes. A strict comparison among cognitive factors, such as that of subcomponents of sentence processing, was possible in our minimal-pair paradigm.
From the several advantages of OT techniques (seeIntroduction), it is clear that optical imaging has thepotential to provide novel information not obtained
previously with other imaging methods. Because
event-related fMRI paradigms have been successfully
applied for neuroimaging of various cognitive functions, the event-related OT techniques developed here
would introduce new possibilities for understanding
functional aspects of the human cerebral cortex.
ACKNOWLEDGMENTS
We thank Dr. H. Koizumi and Dr. A. Maki fortechnical advice on OT; Dr. N. Yahata for commentson the manuscript; Mr. R. Hashimoto, Mr. F. Homae,
Mr. K. Suzuki, and Mr. Y. Hashimoto for their technical assistance; and Ms. H. Matsuda for her administrative assistance. This work was supported in part by
a CREST grant from JST (K.L.S.) and by Young Investigators’ Grants from HFSP (K.L.S.).

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