Neural correlates of semantic priming for ambiguous words: An event-related fMRI study

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a v a i l a b l e a t w w w. s c i e n c e d i r e c t . c o m

w w w. e l s e v i e r. c o m / l o c a t e / b r a i n r e s

Research Report

Neural correlates of semantic priming for ambiguous words: An event-related fMRI study David A. Copland a,⁎, Greig I. de Zubicaray b , Katie McMahon b , Matt Eastburn b a

Centre for Research in Language Processing and Linguistics, Division of Speech Pathology, The University of Queensland, St Lucia, QLD, 4072, Australia b Centre for Magnetic Resonance, The University of Queensland, QLD, Australia

A R T I C LE I N FO

AB S T R A C T

Article history:

We investigated the neural correlates of semantic priming by using event-related fMRI to

Accepted 2 November 2006

record blood oxygen level dependent (BOLD) responses while participants performed

Available online 14 December 2006

speeded lexical decisions (word/nonword) on visually presented related versus unrelated prime–target pairs. A long stimulus onset asynchrony of 1000 ms was employed, which

Keywords:

allowed for increased controlled processing and selective frequency-based ambiguity

Semantic priming

priming. Conditions included an ambiguous word prime (e.g. bank) and a target related to its

Lexical decision

dominant (e.g. money) or subordinate meaning (e.g. river). Compared to an unrelated

fMRI

condition, primed dominant targets were associated with increased activity in the LIFG, the

Lexical ambiguity

right anterior cingulate and superior temporal gyrus, suggesting postlexical semantic

Suppression

integrative mechanisms, while increased right supramarginal activity for the unrelated condition was consistent with expectancy based priming. Subordinate targets were not primed and were associated with reduced activity primarily in occipitotemporal regions associated with word recognition, which may be consistent with frequency-based meaning suppression. These findings provide new insights into the neural substrates of semantic priming and the functional–anatomic correlates of lexical ambiguity suppression mechanisms. © 2006 Elsevier B.V. All rights reserved.

1.

Introduction

The present study sought to further elucidate the brain regions involved in semantic priming of lexical ambiguities, as elicited during a lexical decision task. The semantic priming paradigm provides a useful means of examining operations within the mental lexicon including the access of semantic representations via automatic versus controlled mechanisms. The semantic priming effect refers to the increased speed and accuracy for pronunciation or lexical decisions made on target words when preceded by a semantically/associatively related

prime word (e.g. doctor–nurse), compared to an unrelated word (e.g. bread–nurse). While automatic semantic priming mechanisms have been traditionally conceptualised in terms of rapid automatic spreading activation, controlled or attentional semantic priming mechanisms are slower to develop, may be under conscious control, and can inhibit lexical representations (Neely, 1991). One of the proposed controlled or attentional semantic priming mechanisms is expectancyinduced priming. This process occurs when the participant develops expectancies of potential candidate targets on presentation of the prime, such that targets within the

⁎ Corresponding author. Fax: +61 7 3365 1877. E-mail address: [email protected] (D.A. Copland). 0006-8993/$ – see front matter © 2006 Elsevier B.V. All rights reserved. doi:10.1016/j.brainres.2006.11.016

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expectancy set are facilitated, and those targets not included in the expectancy set are inhibited. Expectancy-based priming can be influenced by manipulation of the relatedness proportion (the proportion of related word prime–target trials in a list), and is more prominent at longer prime–target stimulus onset asynchronies (SOAs), given the time required to generate an expectancy set from the prime (Neely, 1991). It has also been argued that priming effects in lexical decision tasks may be influenced at the post-lexical decision stage, that is, after lexical access has occurred and prior to the overt lexical decision. This semantic matching or post-lexical meaning integration involves the participant checking whether the prime and target are related, with evidence of a semantic relationship providing information regarding the word/nonword status of the target (De Groot, 1984; Neely, 1991). The timecourse of this semantic matching mechanism is a matter of contention, with Neely (1991) arguing that semantic matching is only effective at longer SOAs given the time-consuming nature of the process, and De Groot (1984) suggesting that postlexical meaning integration can occur at short SOAs also. Few neuroimaging studies have investigated the regions involved in controlled or strategic forms of semantic priming with a lexical decision paradigm. In a block-design PET study, Mummery et al. (1999) manipulated the relatedness proportion for prime–target pairs. The left anterior temporal lobe showed decreased activity with increasing relatedness proportion, except for the highest proportion, where activity increased. This nonlinear response was interpreted as possibly reflecting two processes; namely, automatic priming which results in reduced activity and strategic priming which results in increased activity and is invoked with a higher relatedness proportion. Activity also decreased in the anterior cingulate with increasing relatedness proportion, particularly from 50% to 100% relatedness proportions. This finding was explained in terms of the anterior cingulate becoming less active as the task becomes more routine through increased expectancies. It is still difficult to draw conclusions regarding the regions involved in controlled semantic priming from this study, given the short SOA which usually precludes expectancy generation, and the block design which prevents direct comparison of related and unrelated trials (see also Rossell et al., 2001). The confounds associated with block-design priming studies were overcome in a recent event-related fMRI study by Rossell and Nobre (2003) who employed a short and long SOA to investigate automatic versus controlled semantic priming. A main effect for SOA was observed in the anterior cingulate, indicating increased activity in this region for long SOAs regardless of whether targets were related or unrelated, implicating a role in task demands rather than semantic priming per se. The only priming by SOA interaction was observed in the right posterior superior temporal gyrus at the junction with the supramarginal gyrus, which showed a greater reduction in activity for primed targets during the long SOA compared to the short SOA, suggesting the detection of a mismatch between expectancies and target words (Rossell and Nobre, 2003). Increased left supramarginal activity was observed for the related condition compared to the unrelated condition, however, this was not modulated by SOA. More

recently, Gold et al. (2006) investigated the neural correlates of semantic priming at short versus long SOAs, observing a greater priming effect at the long SOA in the bilateral anterior cingulate and posterior and anterior LIFG. A further experiment employing a neutral condition demonstrated a dissociation between strategic facilitation in the anterior LIFG and strategic inhibition in the posterior LIFG. Rossell and Nobre (2003) also investigated the effect of semantic priming on the N400 event-related potential (ERP) component, observing that the N400 effect started earlier with a long SOA which may reflect involvement of the anterior medial temporal cortex (e.g. McCarthy et al., 1995) in semantic expectancies and/or integration. In an ERP study of semantic priming with a short and long SOA, Hill et al. (2002) also concluded that the N400 component represented controlled semantic integration and suggested that a more prominent late positive complex at the short SOA reflected the delayed effects of spreading activation, which might also be reflected in early fronto-central effects. In a priming study with a 600 ms SOA, Matsumoto et al. (2005) observed that the magnitude of the repetition suppression effect in the left superior temporal gyrus activity correlated with the size of the N400 priming effect. The present investigation represents a companion to a previous fMRI study of automatic semantic priming (Copland et al., 2003). This study used a lexical ambiguity priming paradigm whereby lexical ambiguity primes were paired with targets related to dominant (e.g. bank–money) or subordinate (e.g. bank–river) meanings of the prime using a short SOA. Behavioral priming of both meanings was associated with decreased activity for dominant related condition in the left middle temporal region and decreased activity for the subordinate related condition in the left inferior prefrontal region (see also Kotz et al., 2002). The specific regions implicated support the well established role of the left temporal region in semantic processing and lend some credence to the proposal that the left inferior frontal region is involved in accessing weakly instantiated semantic information (e.g. Wagner et al., 2001). The present study employed an identical event-related fMRI paradigm but increased the SOA to allow for increased controlled semantic priming mechanisms and associated brain activity. One of the principle aims of the study was to examine what functional anatomy is engaged during increased controlled priming. In terms of candidate neural mechanisms for controlled priming processes, expectancybased priming has been associated with the anterior cingulate (but see Rossell and Nobre, 2003), anterior temporal regions (Mummery et al., 1999), the right supramarginal region (Rossell and Nobre, 2003) and posterior LIFG (Cardillo et al., 2004). Postlexical semantic matching operations may involve the LIFG, the dorsolateral prefrontal cortex and left superior/ middle temporal gyrus, given that these regions have been associated with semantic relatedness judgments in a priming paradigm (Giesbrecht et al., 2004) and attending to semantic relations (e.g. McDermott et al., 2003). The findings of Gold et al. (2006) also suggest a possible dissociation within the LIFG for strategic facilitation versus strategic inhibition during priming. When lexical ambiguity primes are presented without preceding context and a long SOA, typically only the dominant

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meaning is primed, signifying the end of the automatic stage of exhaustive access, where both dominant and subordinate meanings are activated to approximately the same level, and the completion of the second stage of lexical ambiguity processing whereby attention is presumably focused on the dominant meaning while the subordinate meaning is inhibited (Simpson and Burgess, 1985). The inclusion of the subordinate meaning condition will provide information regarding the neurocognitive mechanisms underlying this frequency based meaning suppression. Specifically, it has been proposed that the lack of priming for subordinate meanings at longer SOAs reflects the action of lateral inhibitory connections between word senses at the semantic level (Balota et al., 1999; Simpson and Burgess, 1985). This study sought to determine whether the neural mechanisms engaged are consistent with suppression effects at the semantic level. One possible neural candidate for meaning suppression is the LIFG, given that this region has been implicated in selection from among competing semantic representations which may reflect inhibitory processes engaged during controlled semantic processing (Johnson and Anderson, 2004; Thompson-Schill et al., 2005).

2.

Results

Behavioral data analyses were conducted on correct responses for real word targets. 16 errors were made on real word targets (1.27%) and 3.4% or nonword targets. Prior to analyses, outliers (RTs greater than 2 S.D.s from the participant's mean per condition) were replaced with Tukey's bi-weight mean estimators (4.04% of RTs were replaced). The resulting mean RTs are illustrated in Fig. 1. A repeated measures ANOVA showed a significant main effect for priming condition (F (2, 26) = 5.870, p = 0.008). The 39 ms priming effect for the dominant condition (unrelated minus dominant) was significant (F (1, 13) = 13.954, p = 0.002), however, there was no significant difference between the subordinate and unrelated conditions (F (1, 13) = 1.479, p = 0.246). ROI analyses revealed a significant increase in the left inferior frontal gyrus (pars opercularis) (39, 9, 12, z = 4.09, p = 0.000) for the dominant versus unrelated contrast, and a decrease for the dominant versus unrelated comparison in the

Table 1 – Experimental stimuli characteristics

Dominant primes Subordinate primes Unrelated primes Dominant targets Subordinate targets Unrelated targets a

Frequency a

Concreteness score (100–700)

4.2 (0.8)

57.4 (52.3)

519.8 (91.1)

4.5 (0.8)

39.4 (33.7)

530.7 (75.2)

4.8 (1.1)

54.1 (67.3)

470.5 (103.1)

4.2 (0.8)

85.7 (52.8)

534.7 (98.9)

4.3 (0.8)

79.6 (79.2)

499.9 (99.5)

4.4 (0.7)

85.6 (103.2)

449.1 (105.8)

In words per million (Kucera and Francis, 1967).

right supramarginal gyrus (54, 33, 45, z = 4.08, p = 0.000). The contrast between subordinate and unrelated conditions in the left inferior frontal gyrus (pars opercularis) ROI failed to reach significance using an alpha threshold of 0.05 small volume corrected (SVC) for multiple comparisons using the false discovery rate (FDR) method (Genovese et al., 2002). However, a trend was apparent at a more lenient uncorrected alpha threshold of 0.05 (peak − 42, 12, 12; z = 2.05). Significant BOLD signal changes between the dominant, subordinate, and unrelated conditions from the whole-brain analyses are presented in Table 1 and Fig. 2. The dominant versus unrelated contrast revealed increased activity for the dominant condition compared to the unrelated condition in the left inferior frontal gyrus (LIFG: pars operculum), right superior temporal gyrus (BA21), and the right anterior cingulate. Direct comparisons of the dominant and subordinate conditions showed decreased subordinate-related activity in the lingual gyrus bilaterally, the left fusiform and insula and the middle occipital gyrus bilaterally. Increased activity was observed for the subordinate condition in the left middle occipital gyrus and the left superior frontal gyrus. Relative to the unrelated condition, there was increased activity for the subordinate condition in the left middle occipital gyrus and decreased activity in the pre SMA and the middle occipital gyrus bilaterally, and the right precuneus and fusiform cortex. Fig. 3 shows timecourse plots of BOLD signal responses from ROIs showing significant differences.

3.

Fig. 1 – Mean reaction times (in ms) as function of priming condition.

Word length (letters)

Discussion

The present study investigated the neural correlates of lexical ambiguity priming in a lexical decision task combined with event-related fMRI. Consistent with previous behavioral studies employing a long SOA (Simpson and Burgess, 1985; Copland et al., 2003), we observed priming of the dominant but not the subordinate meaning which indicates predominantly controlled ambiguity processing (Simpson and Burgess, 1985), although it is acknowledged that some automatic processing was also possible with this paradigm. The lack of subordinate meaning priming at this stage has been previously shown to

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Fig. 2 – Regions showing significant BOLD responses for the comparisons of dominant, subordinate, and unrelated conditions (p < 0.001, uncorrected with a spatial extent minimum of 5 contiguous voxels per cluster). (a–c) dominant > unrelated (red circled), dominant < unrelated (green circles); (d–g) subordinate > unrelated (red circled), subordinate < unrelated (green circled); (h–k) dominant > subordinate (red circled) and dominant < subordinate (green circled). Images a, b, d, e, h, i are superimposed on a rendered canonical T1 image with cerebellum artificially removed. Images c, f, g shown on sagittal slices from SPM T1 high resolution image. Images j, k shown on axial slices from SPM T1 high resolution images.

reflect inhibition of less frequent meanings as limitedcapacity attention is focused on the dominant meaning, subsequent to automatic exhaustive lexical access where

both dominant and subordinate meanings achieve an equivalent level of activation (Simpson and Burgess, 1985). The primed dominant versus unrelated contrast showed increased

Fig. 3 – The time course of average hemodynamic response functions. The percent signal change represents the average signal across 14 participants. Error bars indicate standard error.

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LIFG, right anterior cingulate, and right superior temporal gyrus activity, consistent with postlexical semantic integrative mechanisms. The subordinate condition was associated with reduced activity, compared to the dominant and unrelated conditions, primarily in occipitotemporal regions associated with word recognition, suggesting frequency-based suppression of word forms. In the following discussion, we consider evidence for controlled priming mechanisms, and then discuss the neurocognitive mechanisms underlying subordinate meaning processing and suppression. First, we consider evidence consistent with postlexical semantic matching or integration, wherein the participant looks for a relationship between the prime and target. As outlined in the introduction, such processing may be expected to engage regions including the LIFG, DLPFC, and middle temporal gyrus (Booth et al., 2002; Giesbrecht et al., 2004; McDermott et al., 2003). We expected to find the most straightforward indication of semantic integration in the dominant condition compared to the unrelated condition, given that the dominant target should be most easily integrated in the context of the related prime and that the unrelated target is not activated and not able to be integrated with the prime. We observed increased activity for the dominant condition relative to the unrelated condition in a network which may be consistent with postlexical semantic integration, however, the direction of this BOLD signal change deserves consideration first. The finding of increased BOLD signal for the behaviorally primed dominant condition compared to the unrelated condition in several regions is striking, considering our recent finding of only decreased activity for the dominant and subordinate related conditions when a short prime–target interval was employed with identical stimuli and conditions to the present study (Copland et al., 2003). These signal increases lend credence to earlier predictions that automatic semantic priming mechanisms should invoke reduced cerebral activity for primed targets, whereas controlled semantic priming may elicit increased activity for related versus unrelated conditions (Mummery et al., 1999). It should also be noted that some priming studies have only investigated decreases in BOLD signal (e.g. Giesbrecht et al., 2004). While decreased BOLD signal for primed targets is consistent with evidence of response suppression, suggesting reduced neuronal computation requirements due to lowered recognition thresholds (Copland et al., 2003), its remains to be seen what an increased BOLD signal or response enhancement for the dominant condition reflects in the present priming paradigm which allowed for greater controlled processing. As there was a behavioral advantage for the dominant related condition, it appears that increased activity for this condition does not reflect increased computational effort in word recognition in this instance, but may indicate some form of attentional focus on dominant targets on the basis of prime-related meaning frequency, as has been proposed to occur in processing biased lexical ambiguities at longer SOAs (Simpson and Burgess, 1985). Increased brain activity or response enhancement for primed related targets has been observed previously in imaging studies allowing for postlexical semantic integration (Kotz et al., 2002; Rossell et al., 2001;

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Rossell and Nobre, 2003), and has in some instances been interpreted as reflecting the detection of semantic relationships between words (Rossell and Nobre, 2003) which would account for the present data. The increased proportion of word to nonword targets in the present study may have also encouraged semantic matching processes (see Neely et al., 1989). Based on instances of increased signal for primed targets in repetition priming paradigms, Henson (2003) proposed that repetition enhancement arises when the target is processed in a different way to the prime. While this argument is based on paradigms where there is generally a much larger time period between primes and targets, it is consistent with our proposal that these dominant related increases reflect successful postlexical semantic integration carried out on the dominant target in the context of the prime. The interpretation of increased activity in the LIFG for the dominant versus unrelated contrast as reflecting postlexical semantic integration processes is consistent with findings of increased LIFG activity during judgments of semantic relatedness (e.g. Muller et al., 2003) and the general view that the LIFG supports controlled semantic processing and semantic monitoring (Schacter and Buckner, 1998). However, the greater LIFG activity observed for the dominant versus unrelated condition and the lack of any LIFG involvement in the subordinate contrasts suggests that within this priming paradigm, the role of the LIFG is not consistent with semantic inhibition or increased involvement when more demanding selection from competing semantic representations (Thompson-Schill et al., 1997) or retrieval of weaker representations (Wagner et al., 2001) is required. It should be kept in mind, however, that the present task only requires lexical decision and not conscious selection of a competing meaning. Involvement of the left frontal region in lexical ambiguity priming is in keeping with evidence of impaired controlled lexical ambiguity priming following left frontal lesions (Hagoort, 1993; Metzler, 2001; Milberg et al., 1987) and increased LIFG involvement in comprehending ambiguous versus unambiguous sentences (Rodd et al., 2005). It should be noted that activation was observed in the posterior portion of the LIFG which has previously shown greater activation during phonological versus semantic decisions (see Badre and Wagner, 2002; Devlin et al., 2003), however, it has also shown activation during semantic processing (see Devlin et al., 2003). Given that studies have also implicated portions of the posterior LIFG in sentencebased controlled semantic priming (Cardillo et al., 2004) and strategic semantic inhibition during word pair priming (Gold et al., 2006), the present findings add further evidence that the posterior LIFG is involved in various forms of strategic or controlled linguistic processing during semantic priming. While we have interpreted the results for the LIFG in terms of increased activity for the dominant condition, the dominant-unrelated difference may also be interpreted as indicating decreased activity for the unrelated condition, which may suggest inhibition for unrelated information but is not consistent with the notion of increased LIFG involvement with increased semantic selection demands or the inhibition of competing information (Thompson-Schill et al., 2005).

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The remaining regions showing increased activity for the dominant primed condition relative to the unrelated condition were right lateralised. The involvement of the right hemisphere in more controlled forms of semantic priming, and more specifically, in postlexical mechanisms, is consistent with evidence from a number of divided visual field studies in healthy individuals that the right hemisphere contributes primarily to postlexical or retrospective semantic matching processes (Koivisto, 1998, 1999 but see Chiarello, 2000). If participants are engaging in retrospective semantic matching and are influenced primarily by meaning frequency, increased activity for the dominant condition in the right anterior cingulate and right superior temporal regions may reflect successful detection of a prime–target relationship. The finding of right hemisphere engagement during controlled lexical ambiguity processing is also consistent with evidence that right hemisphere lesions disrupt lexical ambiguity resolution (Tompkins et al., 2000). The anterior cingulate has been implicated in allocating attention to one of several competing meanings of lexical ambiguities (Posner and DiGirolamo, 1998) and has shown increased activity when generating words from lexical ambiguities, relative to non-ambiguities (Chan et al., 2004). Further, the anterior cingulate has been associated with controlled aspects of semantic priming (Mummery et al., 1999). The proposal that the right superior temporal gyrus is involved in semantic integration (Beeman et al., 2004) is also consistent with our interpretation of the present data. We now consider the possibility that the observed primingrelated brain activity reflected expectancy based priming. In the current study, the use of a long SOA allowed sufficient time for participants to generate expectancy sets of possible targets based on the presentation of the prime. However, it is assumed that such expectancies would be identical for dominant related, subordinate related, and unrelated conditions up until the presentation of the target, given that primes were matched for all conditions. It follows that any differential haemodynamic responses between conditions most likely reflects processing of the prime and target in a combined fashion, as has been recently suggested for functional imaging studies of priming in general (Henson, 2003). Activity may therefore reflect postlexical expectancy violations (identified on processing of the target) rather than pure expectancy generation processes per se. Clearest evidence of such expectancy violations was predicted in the dominant versus unrelated contrast, given that expectancy sets typically consist of dominant items which are most influenced by expectancy-based priming (Neely, 1991), and that unrelated targets would most clearly not be represented in any expectancy set (the status of subordinate targets in terms of expectancy generation is complicated by additional processes including possible decay or suppression). Cardillo et al. (2004) recently argued that such expectancy based priming effects result in increased brain activity for unrelated targets (see also Rossell and Nobre, 2003). We did not find evidence of increased activity for expectancy violations (as indicated by increased signal for unrelated versus dominant targets) in regions previously implicated in expectancy-based priming including the left anterior temporal lobe, anterior cingulate (Mummery et al., 1999; but see Rossell

and Nobre, 2003) and the LIFG (Cardillo et al., 2004). This lack of strong evidence for this form of controlled priming is not unexpected, given that it was not explicitly manipulated or invoked (there was a low relatedness proportion in terms of dominant targets compared to other real word conditions and there were no instructions regarding target expectancies), and that previous manipulation of relatedness proportion and expectancy-based instructions has not altered the long SOA pattern of dominant facilitation and subordinate suppression (Simpson and Burgess, 1985), suggesting that expectancy based strategies are not a major driver of controlled ambiguity priming. Yet one finding that may be consistent with expectancy based priming is increased right supramarginal activity for the unrelated versus dominant condition. Intriguingly, Rossell and Nobre (2003) recently found that the right supramarginal region was the only area showing a priming by SOA interaction, indicating a greater decrease in activity for the related condition at the long SOA than the short SOA. Rossell and Nobre (2003) speculated that increased activity for unrelated targets in this area may arise from a mismatch between expectancies and unrelated targets, based on analogous evidence of increased right supramarginal activity upon presentation of spatial targets in unexpected locations (Corbetta et al., 2000), and such a proposal may also account for the present data. Right supramarginal/inferior parietal activity has previously been observed during word generation for semantic ambiguities relative to non-ambiguous words (Chan et al., 2004) and when identifying the lexical ambiguity associated with two independent meanings (Weiss et al., 2001), further suggesting involvement of this region in lexical ambiguity processing. We finally consider the neural mechanisms underpinning processing of the subordinate condition which may be consistent with suppression mechanisms. It has been argued that the presentation of an ambiguity causes an obligatory activation of all word senses via bottom-up excitatory connections, while lateral inhibitory connections between word senses at the semantic level provide the mechanism for selective meaning facilitation on the basis of the meaning frequency (Balota et al., 1999; Nievas and Mari-Beffa, 2002; Tanenhaus et al., 1987, but see Balota and Paul, 1996). We argue that the lack of significant subordinate target priming and associated decreased brain activity in the present study may be consistent with frequency-based deactivation or suppression, given that subordinate meanings are active at earlier SOAs (Copland et al., 2003; Simpson and Burgess, 1985) and that this absence of priming has been demonstrated to reflect inhibition previously (Simpson and Burgess, 1985). The direct comparison of dominant and subordinate conditions revealed decreased activity for the subordinate condition in the left lingual and fusiform gyri. These areas are strongly associated with visual word recognition, with evidence that activity is enhanced in these regions when participants are required to respond or attend to stimuli (Nobre et al., 1998; Price, 2000). Decreased activity for the subordinate condition in these occipitotemporal regions is consistent with reduced attending to or processing of subordinate associated word representations during semantic matching due to frequency based meaning suppression. This interpretation of decreased

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activity is supported in principle by Carter et al. (1995) who reported greatly decreased extrastriate activity in the incongruent condition of a Stroop study, suggesting a neural correlate of gating or inhibiting task-irrelevant information in regions supporting lexical processing (see also Harrison et al., 2004; Milham et al., 2002). Our interpretation of the present data suggests that if suppression of lexical ambiguities occurs through inhibitory links at the semantic level (e.g. Balota et al., 1999; Nievas and Mari-Beffa, 2002; Tanenhaus et al., 1987), this process in turn modulates the neural processing of lexical level representations related to the inhibited meaning. Future inclusion of a neutral condition would provide a means of further testing this proposal and determining the nature of subordinate-unrelated activation differences in the absence of behavioral subordinate condition priming. In conclusion, this study demonstrates that priming of ambiguous words under conditions which allow increased controlled processing engages a different functional anatomy to that previously observed during an automatic ambiguity priming study (Copland et al., 2003). Priming of dominant meanings was primarily associated with increased activity in the LIFG and right anterior cingulate and superior temporal gyrus, suggesting a network supporting controlled semantic integration mechanisms, while increased right supramarginal activity for the unrelated condition suggested an expectancy based mechanism. Decreased activity for the weaker non-primed meaning in occipitotemporal regions may be consistent with suppression of lexical level representations. These findings further elucidate the neural substrates of semantic priming and the functional–anatomic correlates of frequency-based lexical ambiguity processing mechanisms.

(a) two distinct independent meanings, (b) associates provided with a high frequency, and (c) a dominant meaning which was provided as the first meaning at least 70% of the time and a secondary meaning provided second at least 70% of the time by respondents. 150 homographs were used as primes and paired with targets to make up 4 conditions (with different lexical ambiguity primes used in each condition); 30 dominant related word pairs (e.g. pen–write), 30 subordinate related word pairs (e.g. fence–sword), 30 unrelated word pairs (e.g. relish–born) and 60 word–nonword pairs using orthographically legal nonword targets (e.g. match–dobler). There were no significant differences (all p > 0.05) between prime words for each condition in terms of word length, word frequency (Kucera and Francis, 1967), or concreteness ratings from the MRC Psycholinguistic Database (see Table 2 for details on critical stimuli). Real word targets from each condition were matched such that there were no significant differences between targets (all p > 0.05) in length, frequency (Kucera and Francis, 1967), concreteness or lexical decision latency for the targets presented in isolation (Balota et al., 1999). Following a warning, primes were presented for 500 ms. After another 500 ms (blank screen), targets were presented for 2000 ms or until a response was made (see Fig. 4). Participants were instructed to make speeded lexical decisions on targets as quickly and accurately as possible by pressing a left or right response button indicating word or nonword respectively. Approximately 120 fixation (null) trials were also included. Presentation of the five trial types was randomised. Intertrial intervals were randomised to ensure optimal statistical efficiency for the fMRI experiment (Dale, 1999; range 2.1 to 18.9 s, mean 4.6 s). All participants completed a

4.

Experimental procedures

Table 2 – Regions showing significant BOLD signal changes as a function of priming condition

4.1.

Participants

Region

Fourteen right handed individuals (6 female) participated in the study (mean age was 26 years). Exclusion criteria included any history of psychiatric or neurological disorder, head trauma, substance abuse, or English as a second language. A subset of these individuals (8) had previously participated in the equivalent short SOA study (Copland et al., 2003) at least 12 months prior. The study was conducted in accordance with ethical clearance from the Medical Research Ethics Committee of the University of Queensland for MRI experiments on humans at the Centre for Magnetic Resonance. Participants received a small gratuity for their involvement.

4.2.

Priming paradigm

The stimuli used were identical to our previous fMRI study (Copland et al., 2003). 150 lexical ambiguities or homonyms (words with one orthographic and phonological code and two independent meanings) were selected from homograph norms (Nelson et al., 1980; Twilley et al., 1994). All ambiguities were further pretested on local University students to address any regional differences and to ensure that all ambiguities had

Dominant > unrelated Left inferior frontal gyrus, operculum Right superior temporal gyrus Right anterior cingulate cortex Dominant < unrelated Right supramarginal gyrus Subordinate > unrelated Left middle occipital gyrus Subordinate < unrelated Right pre-SMA Left middle occipital gyrus Right middle occipital gyrus Right fusiform gyrus Right fusiform gyrus Right precuneus Dominant > subordinate Left lingual gyrus Right lingual gyrus Left insula Right middle occipital gyrus Left middle occipital gyrus Dominant < subordinate Left middle occipital gyrus Left superior frontal gyrus

Z score

Coordinates x

y

z

4.09 3.87 3.61

−39 66 21

9 −18 42

12 −3 15

4.08

54

−33

45

3.53

−27

−81

39

4.65 3.84 3.77 3.59 3.55 3.44

9 −30 45 24 39 12

21 −96 −81 −81 −12 −72

48 −9 12 − 12 − 21 60

4.76 4.08 3.88 3.62 3.41

−21 30 −42 39 −30

−87 −84 3 −87 −99

− 15 − 18 0 6 9

3.98 3.61

−27 −21

−78 15

42 42

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Fig. 4 – Experimental priming paradigm.

practice block prior to scanning. During scanning, stimuli for the experiment were enlarged and back-projected onto the centre of a screen at the foot of the bore of the magnet.

4.3.

Image acquisition

Images were acquired on a 2T Bruker Medspec S200 system. A quadrature Helmholtz head coil was used for RF reception. A total of 690 T2⁎-weighted gradient echo echoplanar images (EPI) depicting blood oxygen level dependent (BOLD) contrast (Ogawa et al., 1999) were acquired over two consecutive imaging runs in each of 21 planes parallel to the anterior– posterior commissure with TE = 38 ms, TR = 2100 ms, and flip angle = 60°. In-plane resolution was 3.4 mm and slice thickness 5 mm (zero gap). The first five image volumes from each imaging session were discarded to ensure that steady state tissue magnetisation was reached. A high-resolution 3D T1 image was acquired in the same session, using an MP-RAGE sequence with TI = 850 ms, TR = 1300 ms, TE = 5.2 ms, and slice resolution of 0.9 mm3.

4.4.

Image analysis

Image processing and statistical analyses were performed using statistical parametric mapping software (SPM2; Wellcome Department of Cognitive Neurology, London, UK). Statistical analysis was performed in two stages of a mixed effects general linear model (GLM) using classical inference (Friston et al., 2002). All of the imaging results (including ROIs) are reported from second level (group) analyses. The time-series data were slice-timing corrected for the interleaved fMRI acquisition sequence (Aguirre et al., 1998), then realigned to the first image of the series using a rigid-body transformation procedure that included a correction for interpolation errors, and a mean image created from the realigned data (Friston et al., 1995a; Grootoonk et al., 2000). The high-resolution T1 and mean T2⁎-weighted images were then spatially normalised via non-linear basis functions to the T1 and EPI template images, respectively (Ashburner and Friston, 1999). The non-linear transformations for the mean T2⁎-weighted images were applied to the realigned timeseries data and the resulting normalised datasets were

convolved with an isotropic Gaussian smoothing kernel (full width half maximum [FWHM] = 8 mm) to increase signal to noise and to accommodate residual variability in gyral anatomy across participants. A general linear model was applied to the signal intensity time-course of each voxel (Friston et al., 1995b; Worsley and Friston, 1995). The fixedeffects model included separate covariates consisting of a synthetic haemodynamic response function (HRF) and its temporal derivative for transient BOLD responses to five different trial types: These included correctly-performed trials from the four experimental conditions, and trials in which participants were incorrect or omitted responses or made lexical decisions considered outliers (> 2 S.D.s from their own mean response time) (Josephs et al., 1997; Josephs and Henson, 1999). Covariates consisting of the six realignment parameters were included in the model to remove any residual movement-related variance. Planned contrasts were employed to compare the HRF parameter estimates only for the experimental conditions from each participant. The resulting contrast images from the single subject fixed effects analyses were entered into one-tailed t-tests (df = 13) in group random effects analyses to permit inferences about condition effects across participants (Friston et al., 1999), with the tvalues then transformed into corresponding Z-scores. ROIs were selected a priori within MNI atlas space using automated anatomical labeling software for analyses of data (Maldjian et al., 2003; Tzourio-Mazoyer et al., 2002). As per the introduction, ROIs were the left inferior frontal gyrus (pars triangularis, pars opercularis, pars orbitalis), right supramarginal gyrus, anterior cingulate, left dorsolateral prefrontal cortex, anterior temporal pole and the left middle temporal gyrus. ROI results are reported using alpha thresholds of 0.05 small volume corrected (SVC) for multiple comparisons using the false discovery rate (FDR) method (Genovese, Lazar, and Nichols, 2002). In addition to the ROI analyses, we conducted exploratory whole brain analyses (p < 0.001, uncorrected for multiple comparisons, with a spatial extent minimum of 5 contiguous voxels per cluster). All of the imaging results (including ROIs) are reported from a second level mixed effects model.

Acknowledgments This study was funded by a University of Queensland Early Career Researcher grant and an Australian Research Council grant (DP0452264). David Copland is supported by the Australian Research Council research fellowship.

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