Task-Specific Change of Unconscious Neural Priming in the Cerebral Language Network

Task-specific change of unconscious neural priming in the cerebral language network

Kimihiro Nakamura*†‡, Stanislas Dehaene§, Antoinette Jobert§, Denis Le Bihan¶, and Sid Kouider*§

*Laboratoire des Sciences Cognitives et Psycholinguistique, L’E´ cole des Hautes E´ tudes en Sciences Sociales/Centre National de la Recherche Scientiﬁque/E´ cole Normale Supe´rieure, 75005 Paris, France; §Institut National de la Sante´et de la Recherche Me´dicale U562 and ¶Unite´de Neuroimagerie Anatomique et Fonctionelle, Service Hospitalier Fre´de´ ric Joliot, Commissariat a`l’E´ nergie Atomique/Direction des Sciences du Vivant, 91401 Orsay, France; and †Department of Speech Physiology, Graduate School of Medicine, University of Tokyo, 3-7-1, Hongo, Tokyo 113-0033, Japan

Edited by Edward E. Smith, Columbia University, New York, NY, and approved October 15, 2007 (received for review May 15, 2007) We explored the impact of task context on subliminal neural method with fMRI. Our behavioral paradigm consisted of a priming using functional magnetic resonance imaging. The repe- timed sequence of a subliminal prime and a visible target, each tition of words during semantic categorization produced activation written in either logographic Kanji or syllabic Kana (Fig. 1A). reduction in the left middle temporal gyrus previously associated For Japanese readers, unconscious priming occurs even when with semantic-level representation and dorsal premotor cortex. By the same word is repeated across Kanji and Kana formats, such contrast, reading aloud produced repetition enhancement in the as “煙草” and ‘‘たばこ’’ (6). Because these logographic and left inferior parietal lobe associated with print-to-sound conver- syllabic scripts have no mutual correspondence at the subword sion and ventral premotor cortex. Analyses of effective connectiv- level, this ‘‘cross-script priming’’ paradigm targets the cognitive ity revealed that the task set for reading generated reciprocal locus of across-script convergence between the two writing excitatory connections between the left inferior parietal and su- systems, allowing us to isolate the neural codes associated with perior temporal regions, reflecting the audiovisual integration higher-order, abstract-level representation beyond orthography. required for vocalization, whereas categorization did not produce Crucially, the pattern of the neural priming may change with the such backward projection to posterior regions. Thus, masked task set engaged by participants, because the behavioral re- repetition priming involves two distinct components in the task- sponse facilitation involves different cognitive components ac- specific neural streams, one in the parietotemporal cortex for cording to the task requirements. That is, masked repetition task-specific word processing and the other in the premotor cortex priming during reading aloud has been attributed to either the for behavioral response preparation. The top-down influence of orthography-to-phonology computation (11) or further down- task sets further changes the directions of the unconscious priming stream to the motor-articulatory codes (12). By contrast, repe- in the entire cerebral circuitry for reading. tition priming during categorization reflects the unconscious activation of lexicosemantic knowledge (6), and may also involve effective connectivity ͉ masked priming ͉ reading ͉ repetition suppression a motor representations of the manual response (4). We further and enhancement ͉ task set examined the influence of cognitive sets on the cerebral language network by computing the effective connectivity between PSYCHOLOGY nconscious exposure to written words facilitates the subse- the brain structures showing task-specific priming effects. Uquent conscious processing of the same stimuli, a behavioral phenomenon known as subliminal priming (1). At the neural Results level, such response facilitation is mediated in part by the visual Behavioral results. Mean accuracy was 96.9% for reading aloud word recognition system in the left occipitotemporal cortex. By and 94.8% for semantic categorization. The prime visibility did the use of functional magnetic resonance imaging (fMRI), the not depart from the chance level [51.2% correct, t (15) ϭ 0.56, hierarchical architecture of this region has been demonstrated as P Ͼ 0.5 for reading; 52.3% correct, t (15) ϭ 0.60, P Ͼ 0.5 for a serial, posterior-to-anterior processing stream for increasingly categorization], suggesting that participants were unable to see abstract representations (2–4). For instance, a shape-invariant the prime words consciously under both tasks. neural code for letter strings has been found at the left middle The behavioral priming effect for each experiment is illus- fusiform gyrus (FG) showing response attenuation to the re- trated in Fig. 1B. For reading aloud, the global effect of priming peated presentation of words and word roots, whereas a more (i.e., collapsed across the four types of script change) was highly anterolateral sector of the posterior temporal cortex exhibits significant [F (1, 15) ϭ 44.12, P Ͻ 0.001]. Participants responded sensitivity to semantic-level representations (5). For nonalpha- 25 ms faster to Kana-targets than to Kanji-targets [F (1, 15) ϭ betic languages, the repetition of logographic Kanji elicits a 409.51, P Ͻ 0.001]. These effects interacted with each other [F similar neural adaptation at the left middle temporal gyrus (1, 15) ϭ 18.34, P Ͻ 0.001]. There was a significant interaction (MTG) associated with semantic knowledge (6). between prime script and target script [F (1, 15) ϭ 12.25, P Ͻ Importantly, most previous work measured the unconscious 0.005]. No other main effects and interactions were significant. neural priming under a single word-recognition task tapping For categorization, the main effect of priming was also signifi- lexicosemantic representation (5–7). Thus, it remains open cant [F (1, 15) ϭ 44.83, P Ͻ 0.001]. Neither prime script nor whether, and to what extent, the adoption of a voluntary task set target script affected the participants’ performance [F (1, 15) ϭ modulates subliminal priming in the cerebral reading network. In fact, such an influence of intentional behavior on nonconscious cognitive processing has been proposed by neurocognitive mod- Author contributions: K.N., S.D., D.L.B., and S.K. designed research; K.N., S.D., A.J., and S.K. els of consciousness (8, 9). Our transcranial magnetic stimulation performed research; K.N., S.D., A.J., and S.K. analyzed data; and K.N., S.D., and S.K. wrote study has further demonstrated a differential effect of task on the paper. subliminal priming (10). However, no previous work has exam- The authors declare no conflict of interest. ined the entire extent of the cerebral structures involved in This article is a PNAS Direct Submission. unconscious word processing as a function of task context. ‡To whom correspondence should be addressed. E-mail: [email protected]. In the present work, we explored how subliminal neural This article contains supporting information online at www.pnas.org/cgi/content/full/ priming changed under two different task instructions, reading 0704487104/DC1. aloud and semantic categorization, by using a masked priming © 2007 by The National Academy of Sciences of the USA

www.pnas.org͞cgi͞doi͞10.1073͞pnas.0704487104 PNAS ͉ December 4, 2007 ͉ vol. 104 ͉ no. 49 ͉ 19643–19648 Downloaded by guest on October 1, 2021 A Reading Categorization 500 ms 煙草 .03 .02 L-IPL 29 ms x=-36, y=-57, z=32 .02 29 ms たばこ x=-36 .01 .01 29 ms % signal change 0 0 271 ms Kanji Kanji Kana Kana -Kanji -Kana -Kanji -Kana .04 .08 B Reading Categorization .03 580 660 .06 L- post. FG .02 560 640 .04 x=-37, y=-67, z=-12 .01 540 620 .02 520 600 L- post. MTG 0 0 .015 500 580 .03 x=-50, y=-54, z=6 480 560 x=-48 Reaction time (ms) .02 .01 460 540 ji a a n ji an an K Kan .005 ji-Ka -K - Repeated .01 nji na an a K ana- Non-repeated Ka K K 0 0 Fig. 1. Experimental paradigm and behavioral results. (A) Sequence of .03 .01 events used for the behavioral tasks. Participants either read aloud visible L- ant. MTG targets or categorized them as representing natural or artiﬁcial objects. (B) .02 x=-46, y=-35, z=-7 Mean reaction times (ϮSEM) during reading and categorization. .005 .01 Repeated Non-repeated 3.37, P Ͼ 0.05; F (1, 15) ϭ 1.45, P Ͼ 0.2]. No other interactions 0 0 reached significance. Planned comparisons confirmed that the repetition of words Fig. 2. Neural priming in the left parietotemporal cortex. Global priming effects (green blobs) were signiﬁcant in the left IPL and posterior FG for accelerated the participants’ response systematically in each of ϭ reading and in the left MTG for categorization (shadowed in dark gray). The the four priming conditions, both for reading [F (1, 15) 38.36, left posterior MTG (blue blob) exhibited cross-script repetition enhancement P Ͻ 0.001; F (1, 15) ϭ 6.58, P Ͻ 0.05; F (1, 15) ϭ 26.67, P Ͻ 0.001; during reading (in light gray). Bars represent the mean percent signal change F (1, 15) ϭ 5.74, P Ͻ 0.05, for the Kanji–Kanji, Kanji–Kana, (ϮSEM) for each condition relative to the baseline. Kana–Kanji, Kana–Kana trials, respectively] and for categorization [F (1, 15) ϭ 24.54, P Ͻ 0.001; F (1, 15) ϭ 37.33, P Ͻ 0.001; F (1, 15) ϭ 7.78, P Ͻ 0.05; F (1, 15) ϭ 14.54, P Ͻ 0.005, each cortex (PMv), inferior parietal lobe (IPL), and posterior FG respectively]. (Figs. 2 and 3). Note that the script-dependent, asymmetric Between-task comparison revealed that participants re- pattern of priming at this fusiform cluster came mainly from sponded 85 ms faster in reading than in categorization [F (1, primes in Kana. Only the left lateral prefrontal cortex and ϭ Ͻ 30) 15.05, P 0.001]. The magnitude of priming was 11 ms posterior MTG exhibited response enhancement in cross-script greater for categorization relative to reading [F (1, 30) ϭ 8.67, Ͻ trials (i.e., when primes and targets were presented in different P 0.01], suggesting that the task context affects the subliminal scripts). However, no significant repetition suppression was priming during word recognition. This task-by-priming interac- found throughout the entire brain volume. tion changed with target script [triple-interaction; F (1, 30) ϭ For semantic categorization, the main effect of repetition 9.71, P Ͻ 0.01] but not with prime script [F (1, 30) ϭ 2.63, P Ͼ 0.1], suggesting greater saving effects for Kana targets during suppression was significant only in the left anterior MTG (see categorization and for Kanji targets during reading. No other Fig. 2). This region exhibited reduced response in cross-script interactions with task were significant.

Imaging Results Reading Categorization Repetition Priming Effects. Both reading aloud and semantic .015 L-PMd x=-22, y=-13, z=43 .02 categorization produced widespread activation of the bilateral .01 .015 frontoparietotemporal regions. We searched for the brain re- y = -6 gions showing script-specific activation irrespective of the task .01 .005 requirements. In the cerebral network for reading, Kanji targets ϭϪ ϭϪ % signal change .005 activated a medial part of the bilateral FG (x 30, y 51, 0 z ϭϪ18, Z ϭ 3.68, and x ϭ 42, y ϭϪ67, z ϭϪ12, Z ϭ 3.80) 0 Kanji Kanji Kana Kana -Kanji -Kanji relative to Kana targets [supporting information (SI) Fig. 6]. .05 -Kana -Kana .03 Conversely, Kana targets activated the bilateral occipital pole .04 ϭϪ ϭϪ ϭϪ ϭ ϭ ϭϪ L-PMv .02 (x 14, y 97, z 10, Z 5.12, and x 20, y 97, .03 z ϭϪ4, Z ϭ 3.71) relative to Kanji targets. No other region x=-36, y=0, z=30 .02 exhibited significant script-specific activation across the two .01 .01 Repeated tasks. Non-repeated We then examined two forms of neural priming, i.e., repetition 0 0 suppression and enhancement (13), by searching for the cerebral Fig. 3. Neural priming in the premotor cortex. The left PMv (green) exhibited regions showing the repetition-induced decrease and increase of repetition enhancement during reading, whereas the PMd (blue) showed activation. For reading aloud, the global priming effect was repetition suppression during categorization across the four priming detected as repetition enhancement in the left ventral premotor conditions.

19644 ͉ www.pnas.org͞cgi͞doi͞10.1073͞pnas.0704487104 Nakamura et al. Downloaded by guest on October 1, 2021 trials but not in within-script trials. When the search was A Reading Categorization extended to the brain regions involved in hand response (masked at P Ͻ 0.05 for categorization vs. baseline), the main effect of IPL IPL PMv PMv repetition suppression was detected in the bilateral dorsal premotor cortex (PMd; x ϭϪ22, y ϭϪ13, z ϭ 43, ϭ 3.03, and x ϭ 16, y ϭ 5, z ϭ 53, Z ϭ 2.88). Note that the left PMv, which showed STG STG repetition enhancement during reading aloud, now exhibited FG FG repetition suppression under categorization for both the within- script (8 voxels, x ϭϪ24, y ϭϪ12, z ϭ 41, Z ϭ 2.96) and PMv IPL cross-script conditions. For each task, other regions showing Reading vs. Reciprocal Categorization priming effects are presented in SI Table 1. FG Unidirectional The task-dependent change of priming directions was also STG found in the left IFG, which showed repetition enhancement during reading but exhibited a nonsignificant trend of repetition B Reading Categorization suppression during categorization (Z ϭ 2.70). The categorization PMd PMd task produced no significant repetition enhancement in the entire search volume, neither at the global nor at the within- script levels. Only the cross-script repetition produced response STG STG ϭϪ ϭϪ ϭ FG FG enhancement in the left precentral area (x 61, y 14, z MTG MTG 34, Z ϭ 3.90), bilateral basal ganglia (x ϭ 24, y ϭ 15, z ϭ 10, Z ϭ 3.89), and cerebellum (x ϭϪ8, y ϭϪ67, z ϭϪ13, Z ϭ 3.36). In the joint analysis of reading and categorization, the global Fig. 4. Contextual effects on the task-specific neural pathways. (A) The repetition enhancement across the two tasks was significant at influence of task set over the neural circuitry involved in reading aloud. the left frontoparietal junction and bilateral posterior parietal Spoken word production relies on distributed forward and backward area and cerebellum. In this neural circuit, the repetition effect connections in the left hemisphere, whereas categorization partially re- cruits the same network (Upper). The task-context exerts a differential interacted with task at the left IPL (x ϭϪ38, y ϭϪ57, z ϭ 32, ϭ ϭϪ ϭϪ ϭ ϭ impact at the reciprocal STG-IPL connections and the PMv-STG projection Z 3.48) and precuneus (x 8, y 78, z 43, Z 3.47). (Lower). (B) The influence of task set over the neural circuitry involved in A weaker trend of between-task difference was found for the left categorization. The left FG was involved in reciprocal couplings with PMd PMv (x ϭϪ34, y ϭϪ2, z ϭ 31, Z ϭ 2.94). In contrast, the global and MTG during categorization. These two structures received excitatory repetition suppression across the two tasks was detected only as input from STG during both reading and categorization. However, none of a nonsignificant trend in the bilateral medial frontal and pos- these connections differed in coupling strength between the two tasks. terior temporal cortices and deep nuclei. However, the priming- by-task interaction (corrected at P Ͻ 0.05 across the search volume) was significant in the left medial superior temporal (Fig. 4B). However, these connections were also significant gyrus (STG; x ϭϪ36, y ϭϪ30, z ϭ 25), caudate (x ϭϪ26, y ϭ during reading aloud and did not differ between the two tasks Ͻ PSYCHOLOGY 27, z ϭ 8), MTG (x ϭϪ46, y ϭϪ35, z ϭϪ7), and PMd (x ϭ (both ts 1). The categorization task produced reciprocal Ϫ20, y ϭϪ13, z ϭ 43). excitatory inputs from FG to MTG and PMd, but neither of these connections differed from those under reading aloud (all ts Ͻ Effective Connectivity Analysis. We examined the interregional 1.2). The intrinsic coupling from PMd to MTG was marginally connectivity between the left premotor and parietotemporal significant during categorization, but did not survive the be- regions showing global priming effects during each task. We tween-task comparison (t Ͻ 0.1). No other intrinsic connections focused on the influence of cognitive set over the two task- differed between the two tasks (all ts Ͻ 1). dependent cerebral networks for reading, each of which was For each task, we further estimated the modulatory effects of assumed to receive the visual input commonly at the FG during repetition (across the four priming conditions) on the task- the execution of tasks. Specifically, we constructed a dynamic relevant regions. The repetition of words induced an increase of causal model (DCM), which comprises the IPL and PMv for the connectivity from PMv to IPL for reading aloud [mean connec- ‘‘dorsal’’ stream involved in reading aloud (Fig. 4). For the tion strength: ϩ0.021/Ϫ0.007 for repeated/unrepeated trials, ‘‘ventral’’ stream involved in categorization, we created another respectively; F (1, 15) ϭ 4.45, P ϭ 0.05] but not for categorization DCM comprising the MTG and PMv. Based on the known role [ϩ0.0006/ϩ0.0007; F (1, 15) Ͻ 0.1]. In between-task compari- of the left temporal lobe in word comprehension, we additionally sons, this modulatory influence interacted with task set at a included the left STG in both DCMs (see Methods). The trend level [F (1, 30) ϭ 2.80, P ϭ 0.10]. For categorization, the stimulus-free contextual effects were then estimated as the latent repetition of words produced a marginally significant change of or intrinsic interregional coupling under a given task (14). connectivity in two forward projections, i.e., increase at the Mean intrinsic connection parameters for each task are pre- FG-PMd [ϩ0.0040/Ϫ0.0015; F (1, 15) ϭ 3.73, P ϭ 0.07] and sented in SI Table 2. For the dorsal network, there were decrease at the FG-STG [Ϫ0.0004/ϩ0.0002; F (1, 15) ϭ 3.71, P ϭ significant excitatory inputs from STG to PMv and IPL during 0.07] connections, but it was not the case for reading aloud, reading aloud, whereas these connections were not significant neither for FG-PMd [ϩ0.0038/Ϫ0.0018; F (1, 15) ϭ 3.08, P ϭ 0.1] under categorization (Fig. 4A). No other within-task connec- nor for FG-STG [ϩ0.0002/Ϫ0.0007; F (1, 15) ϭ 0.36]. The tions exceeded zero, neither for reading nor for categorization modulatory effect at the FG-PMd projection was significant (all ts Ͻ 2.1). Between-task comparisons confirmed that the task across two tasks [F (1, 30) ϭ 6.73, P Ͻ 0.02] but did not differ set for reading increased the reciprocal intrinsic coupling be- between the two tasks [F (1, 30) Ͻ1]. No other projections tween STG and IPL relative to the task set for categorization (t ϭ exhibited significant modulatory effects, neither for within-task 2.98, P ϭ 0.006 for STG-IPL; t ϭ 3.02, P ϭ 0.005 for IPL-STG). nor for across-task analyses. The between-task difference was marginally significant for the PMv-STG projection (t ϭ 1.95, P ϭ 0.06). No other intrinsic Discussion connections differed between the two tasks (all ts Ͻ 1.3). We performed the two subliminal priming experiments to For the ventral stream, there were significant excitatory investigate the influence of task instructions over the neural projections from STG to PMd and MTG during categorization network involved in unconscious word processing. Behavior-

Nakamura et al. PNAS ͉ December 4, 2007 ͉ vol. 104 ͉ no. 49 ͉ 19645 Downloaded by guest on October 1, 2021 articulatory planning (25), supporting the proposal that the PMd masked priming in word naming occurs in the speech production manual response IPL process (12). However, another neural locus of this behavioral preparation print-to-sound conversion priming was found at the left IPL, a region known to play a role in translating written words into spoken forms (26). Indeed, our PMv transcranial magnetic stimulation study (10) has shown that this articulatory planning FG dorsal pathway from FG to IPL is involved in masked priming MTG abstract during reading aloud, for both words and nonwords. These semantic orthographic results thus point to the existence of two separate neurocognitive knowledge codes components of the dorsal processing stream for reading, one in the IPL associated with print-to-sound conversion and the other Fig. 5. Neurocognitive components of unconscious repetition priming. The in the PMv associated with speech planning. left FG receiving the visual input is associated with abstract, shape-invariant representations of pronounceable letter-strings (3). The ventral stream from Shifting of Neural Priming Directions. Repetition priming is thought the FG, comprising the IPL for print-to-sound translation and PMv for speech to reflect a neural adaptation mechanism operating for visual planning (dark gray), operates in the generation of subliminal priming during reading aloud. In contrast, the dorsal stream from the left FG, comprising the object recognition and mediating more efficient processing of MTG for semantic representations and PMd for manual response preparation stimuli (13). Combined with psychological priming, the repetition- (light gray), is involved in repetition priming during categorization. suppression phenomenon gives access to the neural coding mechanisms associated with a specific cognitive function beyond the limits of conventional brain-imaging paradigms (27). How- ally, significant priming effect was obtained across the four ever, the opposite pattern of neural priming, i.e., repetition script conditions, both for reading aloud and semantic cate- enhancement, may occur depending on the psychophysiological gorization. These two types of behavioral priming each should features of stimuli, such as familiarity (28), perceptual difficulty have at least two distinct components, one from linguistic and (29), and prime-target semantic relationship (24). It is an the other from motoric levels (4). For semantic categorization, unresolved question as to how the directions of neural priming motor-response priming could occur because the unrepeated changes with other experimental factors. trials consisted of primes and targets that belonged to opposite We found that unconscious word perception elicits response categories (e.g., prime natural/target artifact). Thus, the un- enhancement in the task-relevant processing stream only under conscious processing of primes would lead to covert prepara- the reading task. Our results also revealed that reading, but not tion of an appropriate motor response, which needs to be categorization, relies on excitatory connections within the STG- overcome by the overt response on targets. Indeed, we previ- IPL-PMv stream in the left hemisphere. Moreover, the repeti- ously showed that such response bias contributes to the tion of written words and their spoken output during reading generation of behavioral priming under the same design (6). produced a modulatory backward projection between these The difference in motoric congruity between repeated and structures, whereas unconsciously perceived words during cate- unrepeated trials would yield a similar response bias in the gorization primed only the bottom-up projections from FG to reading-aloud task involving an articulatory output. At the the downstream regions. These findings suggest that the direc- neural level, such motor priming has been associated with tion of priming changes with additional inputs from other downstream regions beyond the classical language regions, components of the neural circuitry involved in the same task. including the primary motor cortex (15), premotor area (16) In fact, spoken word production may require such reciprocal and basal ganglia (17). interactions in the task-relevant network, because the auditory perception of speech sounds is known to activate the PMv Task-Specific Neural Connections in Unconscious Priming. We found automatically (30). Another recent study has further shown a two task-specific neural connections operating for unconscious functional coupling between auditory and motor areas during word processing. Namely, the main effect of priming was found vocalization (31). The premotor and inferior parietal cortices, as repetition suppression at the MTG-PMd during categoriza- also involved in speech production, exhibit increased connectiv- tion but was detected as repetition enhancement at the IPL-PMv ity during speech perception (32). These observations have been and posterior FG during reading aloud (Fig. 5). These findings taken as reflecting the self-monitoring and feedback regulation overall suggest that the task instructions engaged by participants whereby speech perception engages the motor system to access induce a biasing influence over the task-relevant regions even for a phonetic code with motoric properties. Thus, the STG-IPL- unconsciously perceived stimuli. PMv circuitry might be recruited twice, i.e., first by the visual For categorization, the observed activation reduction in the prime-target pairs and then by the auditory monitoring of one’s PMd is in accord with a recent fMRI study showing that own voice. The observed shift in neural priming would then stimulus–response congruency induces response attenuation in occur because these additional cognitive processes operate on the same area (18). This region is involved in the learning of the target stimuli, resulting in repetition enhancement, rather arbitrary associations between visual cues and hand response, in than suppression (13). both primates (19) and humans (20). Hence, the observed Alternatively, the backward projections during reading may be priming in PMd can be attributed to the accumulated response attributed to an attentional modification of the task-relevant bias for generating the manual response required for the cate- network, because repetition enhancement has been observed gorization task. under conditions that may increase attentional demands (e.g., Consistent with our previous work (6), the left MTG exhibited visually unfamiliar or degraded stimuli). Indeed, a recent be- global repetition suppression during categorization. Neuropsy- havioral study has proposed that reading aloud is not fully chological (21, 22) and functional brain imaging (23, 24) studies automatic but may require central attention to maintain the converge to suggest that this region is associated with amodal, functional architecture of the reading system (33). This account conceptual-level representations. Our finding thus suggests the is supported by neurophysiological evidence showing that the existence of another distinct component of cross-script priming repetition of visual stimuli produces enhanced response in the that is mediated by the activation of semantic knowledge. inferotemporal cortex under a top-down attentional modulation The motor priming during reading aloud was mirrored by by the prefrontal cortex (34). Raposo et al. (24) reported that the response enhancement in the PMv previously associated with semantic overlap between prime and target produced enhanced

19646 ͉ www.pnas.org͞cgi͞doi͞10.1073͞pnas.0704487104 Nakamura et al. Downloaded by guest on October 1, 2021 response during concrete-abstract judgment about consciously optimized for a gradient echo-echo planar imaging sequence (26 perceived words. This observation may also reflect the strategic contiguous axial slices, thickness 4.5 mm with 0.5 mm gap, echo allocation of attention, because the task demand could interact time ϭ 40 ms, flip angle ϭ 90°, field-of-view ϭ 192 ϫ 256 mm2,64ϫ with the semantic relatedness of stimuli [see Neely (35) for a 64 pixels). The repetition time was 2,400 ms for both tasks but review]. included a 1,000-ms silence period for reading aloud (thus acqui- It is interesting to note that such temporal shifting of fMRI sition time was 2,400 ms for categorization and 1,400 ms for priming after the backward or top-down modification may reading). Participants received four scanning sessions each of which correspond to the reversal of priming directions observed in lasted Ϸ8 min, giving 207 volumes for reading and 205 volumes for magnetoencephalography studies (36, 37). Namely, the left categorization. occipitotemporal cortex exhibits increased response to the repeated presentation of words at Ϸ230 ms after the stimulus Data Analysis. After image reconstruction, the functional images onset. By contrast, a distributed left hemisphere network, ex- were processed by using the SPM2 software (Wellcome Depart- tending from the parietotemporal to lateral prefrontal regions, ment of Cognitive Neurology, London, U.K.). Five initial images exhibits attenuated response in a later period (Ϸ400 ms), were discarded to eliminate nonequilibrium effects of magnetiza- whereas this late neural priming is more pronounced in the tion. Images were corrected for head motion, resampled every 2 frontal and anterior temporal regions. mm by using trilinear interpolation and normalized to the standard brain space, and spatially smoothed with an isotropic Gaussian filter Conclusion (5 mm full-width at half-maximum). These images were high-pass Our results suggest that unconscious word perception primes the filtered at 120 s and smoothed with a 4-s Gaussian kernel. entire task-relevant neural circuit for processing visible targets, For each participant, a weighted-mean image for each contrast setting up more efficient functional coupling between the left was computed by fitting each voxel time series with the known parietotemporal regions associated with word processing and time series of the nine event types convolved with a canonical premotor regions associated with behavioral response. The hemodynamic response function with time and dispersion de- voluntary task control guides even invisible words to the task- rivatives. Group-based statistical inference was made by using relevant processing streams in the left hemisphere, whereas the random-effect analysis. We first identified the brain regions top-down influence of task sets affects the neural priming active during reading aloud by pooling the eight word-present direction within the task-relevant language network. conditions relative to the baseline (voxel-level P Ͻ 0.05). The resulting SPM served as a masking image for searching the Methods priming effects in the cerebral network involved in reading. For Participants. Two groups of sixteen right-handed, native Japanese each task, mean percent signal change was calculated for the speakers (age range 25–38 years) were recruited separately for eight word-present conditions by using the most significant voxel the reading aloud and semantic categorization experiments. The for each participant. behavioral and brain imaging results for categorization were The effects of repetition suppression and enhancement each reported previously (6). All participants gave written informed were calculated as the decrease and increase of activation in consent before the imaging experiment. The protocol of this repeated trials relative to nonrepeated trials (13). We examined study was approved by the regional ethical committee. the neural priming effects associated with the ‘‘within-script PSYCHOLOGY priming’’ (including prime–Kanji/target–Kanji and prime–Kana/ Materials and Procedures. The visual stimuli consisted of 40 target–Kana trials) and those associated with ‘‘cross-script prim- Japanese nouns written commonly both in Kanji and Kana. ing’’ (including Kanji–Kana and Kana–Kanji trials) correspond- These words were composed of 1–2 characters when written in ing to more abstract, script-independent representations beyond Kanji and 2–3 characters when written in Kana. Half of them orthographic processing. For each task, global priming effects represented natural objects and the other half artifacts. Each were computed by collapsing the four priming conditions. trial consisted of a precisely timed sequence of a masked prime The neural priming effects were compared between reading and and a visible target (Fig. 1A). In the reading-aloud task, partic- categorization by entering the two sets of 16 individual contrast ipants named the visible targets as quickly as possible, whereas images into one-way ANOVA, treating the task as a between-group in the categorization task, they responded by key-press to classify factor. We examined the priming-by-task interaction by selecting the targets as natural or artificial as quickly and as accurately as the voxels showing either global repetition suppression or enhance- possible. ment across the two tasks (inclusive masking at P Ͻ 0.05). Unless Each fMRI experiment was arranged in a 2 ϫ 2 ϫ 2 factorial stated otherwise, all effects were tested at voxel-level P Ͻ 0.005 design in which the main effects of interest were repetition (spatial extent Ͼ 15 contiguous voxels). (identity or control), prime script (Kanji or Kana) and target We used dynamic causal modeling to estimate the effective script (Kanji or Kana). A ninth type of trials comprising the same connectivity between the brain regions involved in task-specific sequence of masks without prime and target words served as a priming effects. In brief, DCM treats the brain as a nonlinear baseline to measure the event-related activation by words. In dynamic system that is subject to inputs and produces outputs. By each experiment, participants received four scanning sessions, using a bilinear approximation to the dynamics of interactions each comprising five initial training trials followed by 200 trials among states, the parameters of the implicit causal model reduces (20 trials for each event type except for the ‘‘word-absent’’ to three sets, i.e., (i) parameters of the extrinsic input to the system, baseline with 40 trials, all in random order). (ii) parameters representing the intrinsic or latent connections that Immediately after the imaging sessions, participants per- couple responses in one area to the state of others, and (iii) the formed a forced-choice test for prime visibility (64 trials). Each bilinear parameters representing the changes in the intrinsic cou- trial comprised the same sequence of masks and words as in the pling induced by inputs (14). The connectivity parameters are activation task, followed by a pair of choices (a same word as the estimated in the Bayesian framework whereby inferences about prime and a distractor) presented left and right of the fixation. particular connections are made by using the posterior or condi- Participants determined which of the two items corresponded to tional density. Based on the group results from random-effect the prime word in the preceding event sequence. analyses, we constructed two different DCMs with four interconnected regions, each of which was seeded with the left FG receiving fMRI Procedures. Both experiments were conducted by using a the visual input. One is the cerebral network including the left PMv 3-Tesla whole-body system (Bruker) with a standard head coil and IPL that exhibited neural priming during reading aloud

Nakamura et al. PNAS ͉ December 4, 2007 ͉ vol. 104 ͉ no. 49 ͉ 19647 Downloaded by guest on October 1, 2021 (see SI Table 1 for their respective coordinates). The other was neural circuits for reading, the intrinsic-connection parameters involved in the repetition priming during categorization and com- from four sessions were collapsed per participant and submitted prised the left PMd and MTG. The two fully interconnected models to a second-level analysis by using the classical t-statistics. For were used based on the known anatomical connections in the each of the interregional coupling, we performed a one-sample frontoparietotemporal cortex (38) and previous functional brain t test to examine whether the across-participant mean differed imaging data (39). The left FG was identified as a common from zero for each task. A lenient statistical threshold (P Ͻ 0.05, activation site across reading and categorization by using conjunc- two-tailed) was used to determine the significant neural con- tion analysis (x ϭϪ42, y ϭϪ71, z ϭϪ12, Z ϭ 5.07, relative to the nections during each task. We selected the connections that baseline). Both models also included the left posterior STG that reached the significance in either of reading and categorization survived the voxel-level threshold at P Ͻ 10Ϫ6 during reading aloud and then compared the coupling strength between the two tasks relative to the baseline (x ϭϪ63, y ϭϪ19, z ϭ 5, Z ϭ 5.19). This using unpaired t test. All across-task comparisons of connection region, previously associated with spoken-word comprehension parameters were made for each DCM, and not between different (26), was active during categorization relative to the baseline (Z ϭ models. The modulatory effects of repetition were further 2.41) but responded more strongly during reading relative to examined within and across tasks by submitting the bilinear categorization (Z ϭ 4.21). coupling parameters to repeated-measures ANOVA treating the For each model, we computed the connectivity parameters main effect of repetition as a within-participant factor and the representing the intrinsic strength of interregional connections task set as an additional between-group factor (the latter only for during each task. Regional responses per session per participant between-task comparisons). were extracted by calculating the principal eigenvariate across all This work was supported by Institut National de la Sante´etdela voxels within a 6-mm sphere centered at the most significant ´ voxel in the group analyses for each task. For each model, we Recherche Me´dicale, Commissariat` a l’Energie Atomique, a centennial fellowship of the McDonnell foundation (to S.D.), a postdoctoral then computed the contextual effects on the interregional con- fellowship from the Fondation de la Recherche Me´dicale, and Grants- nectivity per session per participant. The design matrix included in-Aid from the Japan Ministry of Education, Culture, Sports, Science the eight word-present conditions as direct input to the FG. and Technology (15700252) and the Japan Society for the Promotion of Because our main interest was the impact of task set on the Science (19500264) (to K.N.).

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