The Journal of Neuroscience, February 16, 2005 • 25(7):1637–1644 • 1637

Behavioral/Systems/Cognitive

Language-Related Activations in the Left Prefrontal Regions
Are Differentially Modulated by Age, Proficiency, andTask Demands
Yoshinori Tatsuno1,2 and Kuniyoshi L. Sakai1,2
1Department of Basic Science, Graduate School of Arts and Sciences, The University of Tokyo, Komaba, Tokyo 153-8902, Japan, and 2Core Research for
Evolutional Science and Technology, Japan Science and Technology Agency, Kawaguchi-shi 332-0012, JapanIt remains to be elucidated how cortical activations are modulated by factors of age, proficiency, and language task demands whenmastering first language (L1) and a second language (L2). Using functional magnetic resonance imaging, we tested subjects aged 13 (theage 13 group) and 19 (the age 19 group), thereby comparing the cortical activations involved in past-tense verb identification with those
involved in verb matching. We found that the activation in the dorsal triangular part of the left inferior frontal gyrus (IFG) was lower,
corresponding to a higher proficiency in English (L2) in the older subjects, suggesting that the proficiency level plays a major role in theactivation of this region during L2 acquisition. Moreover, the lower activation in the triangular and orbital parts of the left IFG (F3t/F3O)
for the irregular past tense corresponding to a higher proficiency in L2, together with the nonsignificant activation for the regular pasttense when its performance almost reached perfection for age 19, suggests that the modulation of the left F3t/F3O activation reflects
language task demands for identifying correct past-tense forms. On the other hand, the left F3t/F3O activation in Japanese (L1) for age 13
was significantly greater than that for age 19, despite the matched performances in L1. These results suggest that the left IFG subserves
language-specific functions that are critically required when mastering any language.
Key words: language acquisition; grammar; prefrontal cortex; fMRI; cortical plasticity; critical period

Introduction
The developmental processes in the brain for mastering first language (L1) and a second language (L2) are essentially unknown,
and the question of whether they share the same neural mechanisms remains controversial. Given the fact that the proficiency
level (PL) of L2 rarely becomes comparable with that of L1 if L2 isacquired beyond the hypothesized sensitive period around puberty (Lenneberg, 1967; Johnson and Newport, 1989), the age ofacquisition (AOA) is regarded as one critical factor. It has beenreported that L1 (AOA, before ⬃6 years) and L2 (AOA, after ⬃7years) are represented differentially in cortical areas during discourse production or passive listening tasks (Dehaene et al., 1997;
Kim et al., 1997), whereas other studies have reported that they
have common neural substrates during passive listening or word
generation tasks (Perani et al., 1998; Chee et al., 1999). A recent
functional magnetic resonance imaging (fMRI) study supports
the AOA effect on cortical activations, such that the left inferior
frontal gyrus (IFG) activation for grammatical processing in L2 is
Received May 13, 2004; revised Nov. 19, 2004; accepted Nov. 27, 2004.
This work was supported by a Core Research for Evolutional Science and Technology grant from the Japan Scienceand Technology Agency and by a Young Investigators’ Grant from the Human Frontier Science Program (K.L.S.). We
thank Y. Muraishi, K. Miura, N. Narafu, T. Mitsuhashi, K. Hirano, M. Fukushima, Y. Tanabe, A. Katsumata, and Y.
Sugiura for their help in studying school students and N. Saeki for technical assistance.
Correspondence should be addressed to Dr. Kuniyoshi L. Sakai, Department of Basic Science, Graduate School ofArts 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.
DOI:10.1523/JNEUROSCI.3978-04.2005
Copyright © 2005 Society for Neuroscience 0270-6474/05/251637-08$15.00/0

greater than that in L1 (Wartenburger et al., 2003). However,another fMRI study claims that the degree of exposure to language affects the left IFG activation, even if the AOA is matched(Perani et al., 2003). Indeed, the PL effect is known to modulate
the left IFG activation in adults during semantic or grammaticaldecision tasks (Chee et al., 2001; Musso et al., 2003), as well as thebilateral temporal lobe activation while listening to stories (Perani et al., 1998). It has also been pointed out that the left frontal
and extrastriate regions were differentially modulated by either
age or task performance among children (aged 7–10) and adults(Schlaggar et al., 2002). However, the age and PL effects on cortical activations are often confounded with the demands requiredin each language task and the resultant task performance, and it
remains unknown whether these factors are actually separablefrom each other.
Given these uncertainties, the purpose of the present study
was to clarify the relative contributions of age, PL, language task
demands, and task performance to modulating activations in theleft prefrontal cortex as the subjects performed language tasks. In
our previous study, we examined whether training in the conjugation of English (L2) verbs from the present to past tense alteredbrain activation in 13-year-old native Japanese (L1) speakers (Sakai et al., 2004). A past-tense verb identification task in English
was contrasted with a verb-matching task; the former required
linguistic knowledge, and the latter did not. We found that theleft IFG exhibited significant activation increases for the pasttense task and that these were positively correlated with individ-

Tatsuno and Sakai • Prefrontal Activation Modulated by L2 Acquisition

1638 • J. Neurosci., February 16, 2005 • 25(7):1637–1644

ual improvements in PL. In the present study, by using the same
paradigm, we tested native Japanese speakers aged 13 and 19 toclarify how the language task-selective activations in the left IFG
are modulated by the above-mentioned factors. Here, we predictthat L2 acquisition involves not only general learning skills but
specific language mechanisms that are represented in distinct
prefrontal regions.

Materials and Methods
Subjects. The subjects in the present study were 29 right-handed native
Japanese speakers in two age groups: age 13 (13 years, 0 – 8 months) andage 19 (18 years, 8 months to 19 years, 8 months). All of the subjects hadstudied English only in Japan, and the age at which they had begun
acquiring English was 12 (12 years, 3 months to 13 years, 0 month).
Fourteen first-year students (eight females and six males) from a secondary education school were in the age 13 group. These subjects had studied
English for 8 months at school. Before the experiment, the students inthis group had participated in 2 months of classroom training in the
English past tense, as described in our previous study (Sakai et al., 2004).
Fifteen undergraduate students (seven females and eight males) fromThe University of Tokyo were in the age 19 group. These subjects hadstudied English for 6 years only at school, through which they hadlearned the English past tense. Informed consent was obtained from all
subjects, as well as from the parents of the 13-year-old subjects. The study
was approved by the Secondary Education School Attached to the Facultyof Education of The University of Tokyo and by the institutional review
board of The University of Tokyo, Komaba.
Four tasks were tested in the fMRI sessions: an English verb-matching(EM) task, an English past-tense (EP) task, a Japanese verb-matching(JM) task, and a Japanese past-tense (JP) task, as described previously(Sakai et al., 2004). In the analyses for EP and EM, each of the age 13 andage 19 groups was divided into two subgroups. The age 13 group was
divided into 13EH (the higher score subgroup in English; n ⫽ 6) and
13EL (the lower score subgroup in English; n ⫽ 8) at 40% accuracy of theirregular verbs presented in the EP tasks, which was the median of accuracy for age 13. The accuracy of irregular verbs was appropriate for thisgroup division, because we reported previously that 13-year-old students
showed significant improvements in accuracy at conjugating irregularverbs by the end of 2 months of training (from 22 ⫾ 3.9 to 43 ⫾ 6.9%) but
not for regular verbs (from 79 ⫾ 3.9 to 77 ⫾ 3.7%) (Sakai et al., 2004).
The age 19 group was divided into 19EH (n ⫽ 7) and 19EL (n ⫽ 8) at 96%
accuracy of irregular verbs presented in the EP tasks, which was themedian of accuracy for age 19. To compare the age 13 and age 19 groups
under the matched performance of JP, we chose subjects who committed
four errors or less out of 80 JP trials (⬎95%) from age 13 as the 13JH
subgroup (the higher score subgroup in Japanese for age 13; n ⫽ 6) andthose who committed one to three errors (96 –99%) from age 19 as the
19JL subgroup (the lower score subgroup in Japanese for age 19; n ⫽ 8).
Stimuli and tasks. For the fMRI sessions, we used 48 English verbs (24regular and 24 irregular), as well as 48 Japanese verbs that were presented
in both the “hiragana” and “kanji” writing systems, and were matchedwith English verbs of the same meaning. The stimulus presentation andbehavioral data collection were controlled using the LabVIEW softwareand interface (National Instruments, Austin, TX). The subjects wore
earplugs and an eyeglass-like MRI-compatible display (resolution, 800 ⫻
600) (VisuaStim XGA; Resonance Technology, Northridge, CA).
In each 3 s trial of the fMRI experiments, word or pseudoword stimuli
in yellow letters against a dark background were visually presented. For
fixation, a red cross was always shown at the center of the screen. First, theletter “E” (EM), an “E” with a circle around it (EP), a “J” (JM), or a “J”
with a circle around it (JP) was presented for 400 ms at the initiation of
every trial, indicating the task to be performed. Next, a present-tense verb
was shown for 1300 ms. The subjects covertly read the presented verb for
EM and JM or covertly read its past-tense form for EP and JP if they knew
the past-tense form (if not, they read the presented verb). Finally, twochoice stimuli were shown for 1000 ms, and the subjects attempted
to choose the same present-tense verb for EM and JM or attempted tochoose the correct past-tense form for EP and JP, even if the verb was

unfamiliar to them, by pushing one of two buttons. The time limit given
for responses was as short as 1000 ms, so that responses with preplanningduring the preceding period became necessary. No feedback on performance was given to any subject. General cognitive factors such as word
recognition and response selection were controlled by the EM and JM
tasks, which were directly compared with the EP and JP tasks,
respectively.
The four tasks were conducted in a block design; six trials were tested
in each EM block, and eight trials were tested in each block for the othertasks. There were two EP task blocks in a single fMRI run: one block (EPi)with seven irregular verbs and one regular verb (at a randomized position), the other (EPr) with seven regular verbs and one irregular verb.
One EM block and one block each of JM, EPi, EPr, and JP were alternately
presented (a total of nine blocks) for each run. Because the main goal of
the present study was to clarify the cortical activations for the English pasttense, i.e., EPi–EM and EPr–EM, the alternating EM blocks served as thesteady referential baseline. Ten fMRI runs were performed in a single day,and the order of tasks was counterbalanced across subjects.
fMRI data acquisition and analyses. The fMRI scans were conductedusing a 1.5 T MRI system (STRATIS II, Premium; Hitachi Medical Corporation, Tokyo, Japan). Using a gradient-echo echo-planar imaging
sequence (repetition time, 3 s; echo time, 50.5 ms; flip angle, 90°; field ofview, 192 ⫻ 192 mm 2; resolution, 3 ⫻ 3 mm 2), we scanned 16 horizontal
slices, each 6 mm thick and having a 1 mm gap, covering from z ⫽ ⫺49
to 62 mm. We performed group analyses using SPM99 statistical parametric mapping software (Wellcome Department of Imaging Neuroscience, London, UK). We realigned the functional volume data in multiple runs and removed runs that included data with a translation of ⬎2
mm in one of the three directions and a rotation of ⬎1.4°. The data werenormalized to the standard brain, resampled every 3 mm using bilinear
interpolation, and smoothed with an isotropic Gaussian kernel of 9 mm
full-width at half-maximum. Low-frequency noise and global changes in
activity were further removed. Task-specific effects were estimated with ageneral linear model (fixed-effects analyses) using a boxcar waveform
convolved with the canonical hemodynamic response function. In group
analyses, statistical parametric maps in each comparison were thresholded at the corrected p ⬍ 0.05 for the voxel level. Statistical significanceof negative correlation between the accuracy of irregular verbs in the EP
tasks and the signal change in either EPi–EM or EPr–EM was tested using
Spearman rank correlation (one-sided), which is resistant to outliers, i.e.,high leverage points.

Results
Behavioral results
We first examined the in-scanner accuracy and reaction times of
the EPi and EPr tasks for the individual subject groups. The accuracy of EPi was higher for the older subjects, and the differencesamong the 13EL, 13EH, 19EL, and 19EH subgroups were all significant (t test; p ⬍ 0.01) (Fig. 1 A). The mean reaction times ofEPi for 19EH were also significantly faster than those for 19EL
( p ⬍ 0.05), indicating that there were true performance differences of EPi between 19EL and 19EH, even with an accuracy of⬎90%. On the other hand, the accuracy of EPr for 19EL wassignificantly higher than that for 13EH ( p ⬍ 0.0001) (Fig. 1 B),
whereas the difference in accuracy and reaction times between
19EL and 19EH was not significant ( p ⬎ 0.1), suggesting that theperformance of EPr almost reached perfection for the age 19
groups. In addition, the accuracy of EPr for 13EL was significantly higher than that for 13EH ( p ⬍ 0.001), which indicatedthe higher probability of choosing verbs ending in “-ed.” Nevertheless, the accuracy and reaction times of all irregular verbs ofthe EP tasks, i.e., seven verbs in a single EPi block and one verb ina single EPr block for each run, showed the same pattern as EPi(Fig. 1C). Taking both the accuracy and reaction times into account, the accuracy of irregular verbs in the EP tasks is a reliablemeasure of language attainment in the four subgroups ofsubjects.

Tatsuno and Sakai • Prefrontal Activation Modulated by L2 Acquisition

J. Neurosci., February 16, 2005 • 25(7):1637–1644 • 1639

( p ⬎ 0.05). These subgroups also showedsimilar matched performances for JM( p ⬎ 0.1) (Fig. 1 F).
Activation of the dorsal triangular partof the left IFG in L2 selectively
modulated by PL
The contrasts of EPi–EM and EPr–EM
were first examined to establish the taskselective activations for the past-tense
processing in L2 (Fig. 2 A–D). The overall
activation patterns were similar between
EPi–EM and EPr–EM, as well as between
age 13 and age 19 groups; consistent activations were observed in the left IFG,
spanning from the precentral gyrus(PrCG) to the opercular part and triangular part of the IFG (F3op/F3t), the right
F3op/F3t, the supplementary motor area,
the bilateral parieto-occipital cortex, andthe bilateral cerebellum (Table 1). For age
13, additional activation was observed in
the right orbital part of the IFG and the
middle frontal gyrus (F3O/F2O) in EPi–
EM. For age 19, the caudate nucleus andthe calcarine cortex showed additional activations in both the contrasts, as well as
the right insula and the left middle frontal
gyrus (F2) in EPi–EM and the bilateralinsula and the left middle temporal gyrus
in EPr–EM (Table 1). Regarding the difference between EPi–EM and EPr–EM,
the left F3t/F3O activation was found in
EPi–EM for both ages (Fig. 2 A, C, whitecircles), but not in EPr –EM (Fig. 2 B, D).
The similar region is shown to be active in
Figure 2 D, but the activation projected
onto the lateral surface was actually located in the left insula and did not extend
to the lateral F3t/F3O.
Figure 1. Accuracy and reaction times of past-tense and verb-matching tasks in English (L2) and Japanese (L1). Four tasks wereWe reported previously that the lefttested in the fMRI sessions: an English verb-matching (EM) task, an English past-tense (EP) task, a Japanese verb-matching (JM) dorsal F3t (dF3t) [Montreal Neurologicaltask, and a Japanese past-tense (JP) task. There were two EP task blocks: one block (EPi) with seven irregular verbs and one regular Institute (MNI) coordinates (⫺51, 24,verb, and the other (EPr) with seven regular verbs and one irregular verb. A–D, The accuracy and reaction times (mean ⫾ SEM of 24)] showed activation increases for age
the subjects) of EPi ( A), EPr ( B), irregular verbs of the EP tasks ( C), and EM ( D) are shown for each of the four subgroups: 13EL (the13, positively correlated with individual
lower score subgroup in English for age 13), 13EH (the higher score subgroup in English for age 13), 19EL (the lower score subgroup
PL improvements for English past-tense
in English for age 19), and 19EH (the higher score subgroup in English for age 19). Open and filled circles denote the accuracy andreaction times, respectively. E, F, The accuracy and reaction times of JP ( E) and JM ( F) are shown for each age group and for verbs (Sakai et al., 2004). For the subject
performance-matched 13JH (the higher score subgroup in Japanese for age 13) and 19JL (the lower score subgroup in Japanese for groups in the present study, the mean sigage 19). Note that the ordinate scale is different between A–C and D–F. Asterisks indicate the significant difference in accuracy or nal changes in EPi–EM and EPr–EM werereaction times between a pair of two groups (t test; p ⬍ 0.05). n.s., A nonsignificant difference. The accuracy of each English task, calculated at the same locus (Fig. 2 A–D,
i.e., EPi, EPr, EP (irregular), and EM, was significantly higher for 19EL than for 13EH ( p ⬍ 0.05).
yellow dots). We found that the mean signal change for 19EH was significantly
In contrast to the EPi and EPr tasks, the EM, JP, and JM tasks
lower compared with that for 19EL, in both EPi–EM and EPr–EM
were less demanding on the subjects. In fact, the accuracy differ( p ⬍ 0.05) (Fig. 2 E, F ). It is striking to note that the activation inence of EM between the subgroups within age 13 or age 19 was
EPi–EM and in EPr–EM at the left dF3t was lower, corresponding
not significant ( p ⬎ 0.05), and the difference in reaction times
to a higher proficiency in English (L2) in the older subjects. The
was not significant between any pairs of subgroups ( p ⬎ 0.1)
direct comparison between EPi and EPr (Fig. 2G) exhibited no(Fig. 1 D). Although the accuracy of JP was significantly different
significant difference for any subgroups ( p ⬎ 0.1), and none of
between the age 13 and age 19 groups ( p ⬍ 0.0001) (Fig. 1 E), thethe pairs of groups showed significant differences ( p ⬎ 0.1).
reaction times of JP were not significantly different between age
When we considered PL (i.e., the accuracy of irregular verbs in
13 and age 19 ( p ⬎ 0.1). When the subgroups of 13JH and 19JL
the EP tasks) as a continuous variable treating subjects as a ranwere selected to equate the accuracy of JP ( p ⬎ 0.1) (Fig. 1 E), thedom effect, we found a significant negative correlation between
reaction times of JP were also matched between these subgroups
PL and the left dF3t activation in EPi–EM (r ⫽ ⫺0.55; Spearman1640 • J. Neurosci., February 16, 2005 • 25(7):1637–1644

Tatsuno and Sakai • Prefrontal Activation Modulated by L2 Acquisition

rank correlation coefficient, rs ⫽ ⫺0.53;
p ⬍ 0.05) (Fig. 2 H), as well as in EPr–EM(r ⫽ ⫺0.61; rs ⫽ ⫺0.44; p ⬍ 0.05) (Fig.
2 I). Because EPi–EM and EPr–EM resulted in the same pattern of activations
among the individuals despite the differential performances of EPi and EPr (Fig.
1 A, B), the modulation of the left dF3t activation cannot be explained by the task
performance. Moreover, the EM task
served as the control condition for the individual groups, and thus the effects ofgeneral cognitive factors on cortical activations would have been canceled out in
EP–EM. Therefore, either the PL effectalone or the interaction of PL by age explains our previous observation that theleft dF3t activation increases at the earlystage of L2 acquisition, and our present
results that it is lower when a higher proficiency in L2 is attained.
Left F3t/F3O activation in L2 selectively
modulated by language task demands
Given the differential activation in the left
F3t/F3O between EPi–EM and EPr–EM(Fig. 2 A–D), we next conducted a voxelwise ANOVA for task (EPi and EPr) andage (13 and 19) for the fMRI data sets to
examine any task-related or age-relateddifferences. The main effects of task resulted in a single activated region in theleft F3t/F3O for EPi–EPr (Table 2),
whereas EPr–EPi resulted in no significant
activation. The main effects of age wereobserved in the left PrCG for age 13–age
19. For age 19 –age 13, the main effects ofage were observed in the left F3t, the left
inferior parietal gyrus, the right middle
occipital gyrus, and the calcarine cortex Figure 2. Past-tense task-selective activations in L2 and the left dF3t activation modulated by PL. A–D, Significant activationsin the contrasts of EPi–EM and EPr–EM ( p ⬍ 0.05, corrected for multiple comparisons) for age 13 (A and B, respectively) and those(Table 2). The interaction of task by age for age 19 (C and D, respectively). The activated regions are projected onto a surface-rendered standard brain (L, left). Note theshowed no significant activation.
significant left F3t/F3O activation in EPi–EM for both age 13 and age 19 (white circles in A and C). E–G, At the left dF3t [(⫺51, 24,
The comparison of EPi–EPr was fur- 24), yellow dots in A–D], percentage signal changes (mean ⫾ SEM of the subjects) in EPi–EM ( E), EPr–EM ( F), and EPi–EPr ( G) arether performed separately for the age 13 shown for each subgroup. Asterisks indicate the significant difference in signal changes between the 19EL and 19EH subgroups (tand age 19 groups. For age 13, the direct test; p ⬍ 0.05). H, I, Significant negative correlations between PL (i.e., the accuracy of irregular verbs in the EP tasks) andcomparison EPi–EPr did not reach the sig- percentage signal changes in the left dF3t (⫺51, 24, 24) in EPi–EM ( H ) and EPr–EM ( I ) are shown for age 19. Circles and triangles
nificance level, although the left F3t/F3O correspond to the 19EL and 19EH subgroups, respectively. A regression line is shown for each panel.
activation was observed in EPi–EM but
comparable signal changes between 13EH and 19EL in EPi–EM
not in EPr–EM (Fig. 2 A, B). For age 19, the significant activation( p ⬎ 0.5), despite their significant difference in the performance
was localized in the left F3t/F3O in EPi–EPr [Fig. 3A, yellow circleof EPi (Fig. 1 A), indicate that the modulation does not primarily(⫺48, 21, ⫺3)]. In EPi–EM (Fig. 3B), the mean signal changes atreflect the task performance or difficulty in general. The greater
this locus were significant for all subgroups ( p ⬍ 0.05) except
left F3t/F3O activation in EPi–EM for 19EL than for 19EH, to19EH, and the signal change for 19EH was significantly lower
gether with the nonsignificant activation in EPr–EM for 19EL
compared with that for 19EL ( p ⬍ 0.05), which was similar to theand 19EH when the performance of EPr almost reached perfecmodulation of the left dF3t activation (Fig. 2 E). However, intion, suggests that the modulation of the left F3t/F3O activation
EPr–EM (Fig. 3C), no subject group showed significant activareflects language task demands for identifying correct past-tensetion ( p ⬎ 0.05), and none of the pairs of subgroups showed aforms.
significant difference ( p ⬎ 0.05). We also found a significant
negative correlation between PL and the left F3t/F3O activation
Left F3t/F3O activation in L1 selectively modulated by age
in EPi–EM (r ⫽ ⫺0.34; rs ⫽ ⫺0.49; p ⬍ 0.05) (Fig. 3D). In
contrast, the absence of a significant correlation in EPr–EM (r ⫽Given the activation modulations of the left IFG (the dF3t and the0.07; rs ⫽ ⫺0.007; p ⬎ 0.5) (Fig. 3E) indicated that the left F3t/
F3t/F3O) in L2, we next examined whether the cortical activation
could also be modulated in L1, i.e., JP–JM. For the age 13 group,
F3O activation was not modulated by PL itself. Moreover, theTatsuno and Sakai • Prefrontal Activation Modulated by L2 Acquisition

J. Neurosci., February 16, 2005 • 25(7):1637–1644 • 1641

Table 1. Activated regions for L2 past-tense verb identification
Brain regions
BA
Side
x
EPi–EMyz

Zx

Age 13

PrCG/F3op/F3t

6/44/45

F3op/F3t
F3t/F3O
F3O/F2O
InsulaF2
SMA
CaudateParieto-occipital

44/45
45/47
47

Calcarine
Cerebellum

17/18

46/9
6
40/39/19/18

⫺48
⫺45
⫺48
54
⫺33
48

L
L
L
R
L
R
R
L
M
M
L
R
M
L
R

EPr–EM

30
9
45
24
24
42

30
30
3
30
⫺3
⫺9

⬎8.0
⬎8.0
⬎8.0
6.9
⬎8.0
5.6

0

27

45

⬎8.0

⫺36
30

⫺48
⫺66

42
39

⬎8.0
5.9

⫺27
30

⫺87
⫺69

⫺15
⫺24

6.0
7.1

⫺48
⫺45
51

30
9
12

24
30
30

⬎8.0
⬎8.0
6.8

3

24

45

⬎8.0

⫺42
30

⫺51
⫺81

54
24

7.6
6.1

⫺45
33

⫺66
⫺72

⫺18
⫺21

7.1
⬎8.0

Age 13

PrCG/F3op/F3t

6/44/45

F3op/F3t
Insula44/45

SMA
CaudateMiddle temporal g.
Parieto-occipital

6

Calcarine
Cerebellum

17/18

21
40/39/19/18

L
L
R
L
R
M
M
L
L
R
M
L
R

y

z

Z

Age 19
⫺45
⫺48
⫺45
54
⫺33

30
15
45
18
24

21
30
⫺3
30
⫺6

⬎8.0
⬎8.0
⬎8.0
7.5
⬎8.0

36
⫺36
0
⫺12
⫺27
36
12
⫺12
12

24
3
24
3
⫺66
⫺63
⫺87
⫺81
⫺81

⫺6
57
48
9
39
60
⫺3
⫺33
⫺27

6.7
6.8
⬎8.0
7.2
⬎8.0
7.6
⬎8.0
5.3
6.2

36
6
15
27
27
24
0
⫺57
⫺66
⫺60
⫺87
⫺81
⫺81

18
33
30
0
⫺3
48
9
0
39
45
⫺3
⫺33
⫺27

⬎8.0
7.2
⬎8.0
⬎8.0
5.7
6.8
5.0
6.6
⬎8.0
7.2
⬎8.0
6.4
6.7

Age 19
⫺48
⫺42
54
⫺30
33
0
⫺12
⫺57
⫺27
33
12
⫺9
9

Stereotactic coordinates (x, y, z) in the MNI space are shown for each activation peak of Z values. The threshold is set at corrected p ⬍ 0.05 for voxel level, and clusters smaller than six voxels were removed from the table for brevity. BA,
Brodmann’s area; L, left hemisphere; R, right hemisphere; M, medial; g, gyrus; F2, middle frontal gyrus; SMA, supplementary motor area.

Table 2. Main effects of task and age for L2 past-tense processing
Brain regions
BA
Side
x
y
z

Z

EPi ⫺ EPr: age 13 ⫹ age 19
F3t/F3O

45/47

L

⫺51

24

⫺3

5.3

L

⫺48

⫺9

48

5.3

L
L
R
M

⫺39
⫺60
45
9

21
⫺33
⫺75
⫺78

12
39
18
⫺3

4.7
⬎8.0
⬎8.0
5.0

(EPi ⫹ EPr)–EM: age 13–age 19
PrCG

6(EPi ⫹ EPr)–EM: age 19 –age 13
F3t
Inferior parietal gyrus
Middle occipital gyrus
Calcarine

45
40
39/19
17/18

Stereotactic coordinates (x, y, z) in the MNI space are shown for each activation peak of Z values. The threshold is set
at corrected p ⬍ 0.05 for voxel level, and clusters smaller than six voxels were removed from the table for brevity.

the most prominent activation was localized in the left IFG (cluster size, 624), spanning from the PrCG to the F3op/F3t, including
the dF3t and the F3t/F3O (Fig. 4 A, Table 3). It should be notedthat the activated regions in the left IFG were similar to thoseobserved in EPi–EM and EPr–EM (Fig. 2 A, B). Additional activations were observed in the right F3O and in the left inferiorparietal gyrus. In contrast to the age 13 group, no significant
activation was observed for the age 19 group, although the left
IFG activation (cluster size, 189) became evident when thethreshold was lowered to uncorrected p ⬍ 0.001. In fact, the left
dF3t [Fig. 4 A, yellow dot (⫺51, 24, 24)], which exhibited significant activation for the EP tasks (Fig. 2 A–D), showed comparable
activations in JP–JM between the age 13 and age 19 groups ( p ⬎0.05) (Fig. 4C). The interaction of task by age, JP–JM: age 13–age
19, revealed a significant activation in the left F3t/F3O [Fig. 4 B,
yellow circle (⫺45, 21, ⫺3)], the left F3t/F2, and the right F3O.
The signal changes in JP –JM at the left F3t/F3O locus were significantly different between the age 13 and age 19 groups ( p ⬍0.005) (Fig. 4 D), as well as at the other two loci. It is intriguingthat this left F3t/F3O locus matched that found in EPi–EPr: age
19 (Fig. 3A). To confirm that the activation difference in Figure
4 D truly reflected the effects of age, we further compared theactivation for 13JH and 19JL, whose performances of JP and JM
were matched (Fig. 1 E, F ). The signal changes in JP–JM at the left
F3t/F3O locus were also significantly different between these subgroups ( p ⬍ 0.05) (Fig. 4 E). Because both the age 13 and age 19
groups were old enough compared with the ideal ages at which toacquire L1 (before 6 years old), their PLs of L1 should be equivalent, and thus the performance-matched 13JH and 19JL subgroups would have comparable task demands for the JP task.
Moreover, the JM task served as the control condition for theindividual groups, and thus the general developmental changes
in cortical activations would have been canceled out in JP–JM.
These results suggest that the activation in the left F3t/F3O ismore sensitive to the comparable language task demands for age
13 than age 19.

Discussion
In the present study, we demonstrated that the distinct dorsal andventral regions in the left IFG exhibited language task-selective
activations that are indeed modulated by separable factors. The
results were striking in three ways. First, the left dF3t activation in
EPi–EM and EPr–EM was lower, corresponding to a higher PL

Tatsuno and Sakai • Prefrontal Activation Modulated by L2 Acquisition

1642 • J. Neurosci., February 16, 2005 • 25(7):1637–1644

Figure 4. Past-tense task-selective activations in L1 and the left F3t/F3O activation modulated by age. A, Significant activations in the contrast of JP–JM for age 13. B, Significant activations in the interaction of task by age, JP–JM: age 13–age 19. C, At the left dF3t [(⫺51, 24,24), a yellow dot in A], the percentage signal changes in JP–JM are shown for age 13 and age 19.
D, E, At the left F3t/F3O [(⫺45, 21, ⫺3), a yellow circle in B], the percentage signal changes in
JP–JM are shown for age 13 and age 19 ( D) and for the performance-matched 13JH and 19JL
subgroups ( E). Asterisks indicate the significant difference in signal changes between the age
13 and age 19 groups (p ⬍ 0.05). n.s., A nonsignificant difference.
Table 3. Activated regions for L1 past-tense verb identification
Brain regions
BA
Side
x
y

z

Z

45
27
15
⫺6
⫺6
54

6.3
6.3
5.5
6.6
5.8
5.6

JP–JM: age 13
Figure 3. Left F3t/F3O activation in L2 selectively modulated by language task demands. A,
A region identified by the contrast EPi–EPr for age 19 was projected in three orthogonal planes(sagittal, coronal, and horizontal from the top left panel) and onto a left surface-rendered
standard brain. B, C, At the left F3t/F3O [(⫺48, 21, ⫺3), a yellow circle in A], the percentage
signal changes in EPi–EM ( B) and EPr–EM ( C) are shown for each subgroup. Dots indicate
the significant signal changes (t test; p ⬍ 0.05). An asterisk indicates the significant differencein signal changes between the 19EL and 19EH subgroups (p ⬍ 0.05). D, E, The relationships
between PL and percentage signal changes in the left F3t/F3O (⫺48, 21, ⫺3) in EPi–EM ( D)and EPr–EM ( E) are shown for age 19. Circles and triangles correspond to the 19EL and 19EH
subgroups, respectively. A regression line is shown for each panel.

for age 19, suggesting that PL plays a major role in the left dF3t
activation during L2 acquisition. Second, the greater left F3t/F3O
activation in EPi–EM for 19EL than for 19EH, together with thenonsignificant activation in EPr–EM for 19EL and 19EH when
the performance of EPr almost reached perfection, suggests thatthe modulation of the left F3t/F3O activation reflects language
task demands for identifying correct past-tense forms. Third, in

PrCG/F3op/F3t/F3O

6/44/45/47

F3O
Inferior parietal gyrus

47
40

L
L
L
L
R
L

⫺48
⫺57
⫺51
⫺48
42
⫺48

0
9
33
21
39
⫺42

Stereotactic coordinates (x, y, z) in the MNI space are shown for each activation peak of Z values. The threshold is set
at corrected p ⬍ 0.05 for voxel level, and clusters smaller than six voxels were removed from the table for brevity.

JP–JM, the left F3t/F3O activation for age 13 was significantly
greater than that for age 19, even if the performances of JP and JM
were matched between the 13JH and 19JL subgroups. Together,
the present results provide converging evidence that the left dF3t
and the left F3t/F3O activations are differentially modulated byage, PL, and language task demands. These results further suggestthat the cortical plasticity for L2 acquisition specifically involves
the left IFG, observable even in adolescents.
We reported previously that the left F3t/F3O [(⫺54, 33, ⫺3)
and (⫺54, 27, ⫺6) according to Homae et al., 2002], as well as theTatsuno and Sakai • Prefrontal Activation Modulated by L2 Acquisition

left F3op/F3t [(⫺57, 18, 0) and (⫺57, 9, 6) according to Embick
et al., 2000; Suzuki and Sakai, 2003], was selectively activatedwhen adult subjects performed sentence tasks in L1, which located closely to the left F3t/F3O (⫺48, 21, ⫺3) in the present
study. Here we reported the age-related modulation of the activation of this region even after fully acquiring L1 (Fig. 4 D, E). We
suspect that the weaker activation in JP–JM for age 19 was attributable to the higher stringency of this task contrast comparedwith that of the previous studies and that the higher task-selective
sensitivity for age 13 than age 19 resulted in enhanced activation
for the same contrast. Schlaggar et al. (2002) reported age-related
activation differences independent of language tasks, which may
reflect general cognitive factors. Indeed, previous neuroimaging
studies have reported a repetition priming effect in which therepeated presentation of visual objects resulted in an activation
decrease in broad regions, including the frontal and occipital
cortices (Schacter and Buckner, 1998; Van Turennout et al., 2000;
Dehaene et al., 2001; Soon et al., 2003). Because the order of tasks
was counterbalanced across subjects in the present study, therepetition or familiarization effects on activation, if any, cannot
explain the results of JP–JM (Fig. 4). Recent fMRI studies also
indicated that the left orbitofrontal cortex [e.g., BA 45/47 (⫺45,
23, ⫺4) according to Kesler-West et al., 2001] is related to emotional and social experience (Sprengelmeyer et al., 1998; KeslerWest et al., 2001; Berthoz et al., 2002). However, these factors, ifany, would have been canceled out in JP–JM, as well as in EP–EM,
for the individual groups in the present study. On the other hand,
it has been established recently that the left IFG is selectively
involved in grammatical processing (Stromswold et al., 1996; Dapretto and Bookheimer, 1999; Kang et al., 1999; Embick et al.,
2000; Friederici et al., 2000; Sakai et al., 2002; Suzuki and Sakai,2003), independent of general cognitive factors such as task difficulty and short-term memory (Hashimoto and Sakai, 2002),
and of unreal language rule usage (Musso et al., 2003). The
present results suggest that the modulation of the left F3t/F3O
activation is related to the sensitivity to specific language task
demands rather than associated with cognitive development ingeneral (Piattelli-Palmarini, 1980; Karmiloff and KarmiloffSmith, 2001).
The developmental changes in regional cerebral blood flow
and cerebral metabolic rates are known to manifest initially as anincrease, and later, after age of ⬃9, as a decrease, reaching adultlevels between the ages of 15 and 19 (Chugani et al., 1987; Chiron
et al., 1992). Therefore, physiological differences between children and adults might affect the acquisition, analysis, and interpretation of fMRI data in group analyses. However, recent neuroimaging studies have clarified that both anatomical andfunctional differences between children (aged 7– 8) and adults
have no significant effects on the fMRI data (Burgund et al., 2002;
Kang et al., 2003). In the present study, the EM and JM tasks
served as the control condition for the individual groups and thus
the general developmental changes in cortical activations would
have been canceled out in EP–EM and JP–JM. Therefore, thepresent results indicate that language-specific factors have stronger modulation effects on the left prefrontal regions, which can befurther differentiated within the left IFG.
Combining the findings of our previous study (Sakai et al.,2004) and those of the present one, we clarified that the left dF3t
activation increases with PL improvements at the earlier stage ofL2 acquisition and that it is lower when a higher proficiency in L2
is attained (Fig. 2 E, F ). This latter result is consistent with a previous fMRI study reporting weaker left IFG activation for bilingual subjects with higher PLs during a semantic decision task

J. Neurosci., February 16, 2005 • 25(7):1637–1644 • 1643

(Chee et al., 2001). Regarding the initial increase in activation,
consistent results have been reported recently showing that activation in the left F3t increases when subjects first learn the grammatical rules of L2 (Musso et al., 2003). On the other hand, another fMRI study reported that the left IFG is more activated bymaking grammatical judgments in L2 than in L1, but that it occurred independent of PLs in L2 (Wartenburger et al., 2003).
However, the present results indicate that the left dF3t may show
higher, lower, or comparable activation, depending on which
stages of L2 acquisition are compared. Wartenburger et al. (2003)
also reported that the left IFG activation is greater for subjects at
a later AOA than for those at an earlier AOA, even when theirhigh PLs were matched. Here, it should be noted that the subject
groups’ mean intervals of exposure to two languages in theirstudy differed by 16 years, and thus the differences between thosegroups might have disappeared if the degree of exposure had
been equated. Additional research is necessary to determine
whether the left IFG activation depends on exposure to the language at a particular stage of the developing brain.
Finally, we posed one remaining question about the nature oflanguage task demands that elicited more enhanced activation in
the left F3t/F3O for age 13 than for age 19 (Fig. 4), which may also
modulate the activation of the same region before completely
mastering past-tense regularity in L2 (Fig. 3). A recent fMRI
study with lexico-semantic tasks proposed that the left F3t/F3O isrelated to controlled semantic retrieval (Wagner et al., 2001). The
local maximum of the activated region in the study by Wagner etal. (2001) was actually in F3O. Another fMRI study suggested thatthe left F3t/F3O is related to controlled retrieval of nonsemantic
information as well as semantic attributes at the lexical level(Gold and Buckner, 2002). It remains possible that the activation
can be modulated by such retrieval of nonsemantic information,
but the present study suggests that it may specifically reflect thedemands of retrieving past-tense forms that the EP tasks required. This possibility is consistent with the greater signal
change in EPi–EM for 19EL than for 19EH (Fig. 3B), as well as thenonsignificant signal change in EPr–EM for 19EL and 19EH (Fig.
3C) when the performance of EPr almost reached perfection (Fig.
1 B). Another possibility for language task demands would be
syntactic demands for past tense processing. If we assume that thesyntactic process is involved in making not only regular but irregular past-tense forms, the greater signal change in EPi– EM for
19EL than for 19EH (Fig. 3B), as well as the nonsignificant signal
change in EPr–EM for 19EL and 19EH (Fig. 3C), can also be
explained by the difference in syntactic demands. We prefer thispossibility, because it is supported by accumulating evidence ofthe syntactic specialization in the left IFG, as discussed above.
Taking these results together, we reached the conclusion that theleft IFG subserves language-specific functions that are criticallyrequired when mastering any language.

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