NeuroImage 95 (2014) 129–135

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Neural repetition suppression in ventral occipito-temporal cortex occursduring conscious and unconscious processing of frequent stimuli

Juan R. Vidal a,b,⁎, Marcela Perrone-Bertolotti a,b,c,d, Jonathan Levy e, Luca De Palma f, Lorella Minotti f,Philippe Kahane f, Olivier Bertrand a,b, Antoine Lutz a,b, Karim Jerbi a,b, Jean-Philippe Lachaux a,b

a INSERM U1028, CNRS UMR5292, Lyon Neuroscience Research Center, Brain Dynamics and Cognition Team, Lyon, Franceb Université Claude Bernard, Lyon 1, Lyon, Francec University Grenoble Alpes, LPNC, F-38040 Grenoble, Franced CNRS, LPNC, UMR 5105, F-38040 Grenoble, Francee The Gonda Multidisciplinary Brain Research Center, Bar Ilan University, Ramat Gan, Israelf CHU Grenoble and Department of Neurology, INSERM U704, F-38043 Grenoble, France

⁎ Corresponding author at: INSERM U1028, Centre deLyon, Equipe Dynamique Cérébrale et Cognition, Centre H452, 95 BD Pinel, Bron, F-69500, France. Fax: +33 4 72 13

E-mail address: juanrvidal@gmail.com (J.R. Vidal).

http://dx.doi.org/10.1016/j.neuroimage.2014.03.0491053-8119/© 2014 Elsevier Inc. All rights reserved.

a b s t r a c t

a r t i c l e i n f o

Article history:Accepted 17 March 2014Available online 22 March 2014

Keywords:Repetition suppressionConsciousnessHFAGamma-bandVentral occipito-temporal cortexIntracranial EEGVisual masking

Stimulus repetition can produce neural response attenuation in stimulus-category selective networks within theoccipito-temporal lobe. It is hypothesized that this neural suppression reflects the functional sharpening of localneuronal assemblies which boosts information processing efficiency. This neural suppression phenomenon hasbeen mainly reported during conditions of conscious stimulus perception. The question remains whether fre-quent stimuli processed in the absence of conscious perception also induce repetition suppression in those spe-cialized networks. Using rare intracranial EEG recordings in the ventral occipito-temporal cortex (VOTC) ofhuman epileptic patients we investigated neural repetition suppression in conditions of conscious and uncon-scious visual processing of words. To this end, we used an orthogonal design manipulating respectively stimulusrepetition (frequent vs. unique stimuli) and conscious perception (masked vs. unmasked stimuli). By measuringthe temporal dynamics of high-frequency broadband gamma activity in VOTC and testing for main and interac-tion effects, we report that early processing of words in word-form selective networks exhibits a temporal cas-cade of modulations by stimulus repetition and masking: neuronal attenuation initially is observed in responseto repeated words (irrespective of consciousness), that is followed by a second modulation contingent uponword reportability (irrespective of stimulus repetition). Later on (N300 ms post-stimulus), a significant effectof conscious perception on the extent of repetition suppression was observed. The temporal dynamics ofconsciousness, the recognitionmemory processes and their interaction revealed in this study advance our under-standing of their contributions to the neural mechanisms of word processing in VOTC.

© 2014 Elsevier Inc. All rights reserved.

Introduction

Compared to brain responses to novel stimuli, neuronal responses tothe repetition of identical stimuli are attenuatedwithin sensory cortices(Grill-Spector et al., 2006; Henson et al., 2000; Summerfield et al.,2008). Experimentally, neural suppression can be induced by the imme-diate repetition of stimuli (Summerfield et al., 2008) or by introducing alag, involving many inter-leaving stimuli between repetitions (Hensonet al., 2000; Vuilleumier et al., 2002). The later could rely on strongermemory processing probably associated to familiarity and priming pro-cesses (Henson et al., 2000).

Recherche en Neurosciences deospitalier le Vinatier, Bâtiment89 01.

Neural repetition suppression has been widely studied in sensorycortices using a variety of recording techniques (Grill-Spector et al.,2006), and is thought to reflect neural sharpening or adaptation(Gotts et al., 2012). Yet, despite the intense research, little is knownabout howneural repetition suppressionmight be associatedwith stim-ulus reportability, which some authors equate with conscious stimulusprocessing (Dehaene et al., 2006). Indeed, while some studies have ex-plored the effects of subliminal priming on consciously perceived stim-uli (Dehaene et al., 2001; Kouider et al., 2007; Naccache and Dehaene,2001), it remains unknown whether and how memory traces createdby frequently presented stimuli affect neural processing in the absenceof consciousness.

It has been proposed that access consciousness, classically definedby the ability of the participant to report the stimulus that was justshown to him if asked to do so, relies on global cortical activation re-sulting from top-down feedback signals onto sensory areas (Dehaeneet al., 2006). While reportability occurs spontaneously for unmasked

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stimuli, it is highly impaired when stimuli are masked after 30 ms(Dehaene et al., 2001; Kouider et al., 2007). Intracranial electrophysiolo-gy studies in humans have shown that conscious stimulus perception isassociated with the ignition of broadband high frequency activity (HFA)in cortical sensory regions (50 Hz–150 Hz) (Fisch et al., 2009; Gaillardet al., 2009). Though recent intracranial studies showed that consciousletter-string perception elicits a selective high frequency activation inventral occipito-temporal cortex (VOTC) (Hamame et al., 2013; Vidalet al., 2012), it remains unknownwhether these local signals directly re-flect either conscious or unconscious cortical processing and whetherthey are modulated by top-down predictions. Interestingly, a recentstudy probing this idea in other occipito-temporal regions failed to finda convincing link between local stimulus selective HFA responses andeither conscious perception or recognition-related processes (Aru et al.,2012), suggesting that local HFA increases in sensory corticesmaymost-ly reflect unconscious neural processing.

To address this gap in the literature, we analyzed in this study the ef-fect of conscious and unconscious processing on the neural suppressionelicited by frequent word repetition. Our analysis focused on a specificsensory region in VOTC which has been shown to contain networkswith high response selectivity to letter strings (Cohen et al., 2000;Glezer et al., 2009). Neural activity was recorded from intracranial elec-trodes located within word-selective VOTC sites of human epilepticpatients during the performance of a word detection task. We showedthat word-selective HFA responses in the VOTC were first modulatedby two distinct influences related respectively to stimulus repetitionmemory traces and conscious processing. Subsequently, consciousword perception and reportability, as induced by the absence of the vi-sual mask, enhanced the relative response suppression for frequent re-peated words.

Fig. 1. Experimental paradigms. A. Visual localizer paradigm. B. Themasking paradigmused a forMASKED condition.

Materials and methods

Stimulus and task

Experiment 1In an initial “visual localizer” task participants viewed pictures of 8

possible categories: houses, faces, animals, scenes, tools, pseudo-words,consonant strings, and scrambled images (Fig. 1A). Each stimulus waspresented for a duration of 200mswith an ISI of 1000–1200ms. Presen-tationswere grouped in series of 5 stimuli (i.e. 5 trials), each one belong-ing to a different category, interleaved by 3000 ms rest periods betweenseries (Vidal et al., 2010). Each category consisted of 50 trials.

Experiment 2In the second experiment we used a visual masking paradigm simi-

lar to the design by Gaillard and colleagues (Gaillard et al., 2009). Partic-ipants viewed words presented for 32 ms (2 video frames at a screenrefresh rate of 60 Hz). Each word could be a) masked or not (50% ofall trials), b) a target or a distractor (50% of all trials, participants wereinstructed to press a button if the word referred to a living entity andto do nothing otherwise), c) repeated within the experiment orshown just once (50% of total trials). Among the targets, the repeatedword was ‘casanova’ and among the distractors the repeated wordwas ‘corneille’ (French translation of crow). All other uniquewords, tar-gets and distractors, were shown just once. The combination of thosethree factors split the stimuli into 8 groups of equal size (N= 70 trials)and were presented in random temporal order. However, only targetswere analyzed in the rest of the manuscript. The percentage of behav-ioral responses elicited by targets per condition (i.e. masked andunmasked) corresponded to the ratio of the number of reports per

wardmask in all conditions. The targetwordwas followedby a backwardmask only in the

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condition divided by the total number of trials per condition, multipliedby 100. The contrast between repeated vs. unique words was used toexamine recognition memory effect and repetition suppression (notethat because frequently repeated words were always interleaved withan average of 7 non-repeating stimuli, we reduced the possibility of ob-serving neural repetition suppression effects that could be simply due topurely bottom-up sensory adaptation mechanisms (Grill-Spector et al.,2006)). Participants were explicitly informed about the words thatwould be repeated. The contrast between masked vs. non-maskedwords was used to test for conscious processing. The contrast betweenrepeated and unique words was used to test for recognition memoryprocessing. The words were either masked (forward and backwardmask, 50% of all trials) or unmasked (only forward mask, 50% of all tri-als). The forward and backward masks consisted of a string of symbolsand were shown respectively for 80 ms and 208 ms (Fig. 1B). We alsopresented masked and unmasked blank stimuli (70 trials each), ran-domly mixed among all other word presentations, to assess the effectsof unconscious processing.

In summary, we analyzed 4 different word presentation conditions:masked-repeated, masked-unique, unmasked-repeated and unmasked-unique. The experiment consisted of two blocks yielding a total of 70trials per condition. Participants 1 and 2 performed the two blocks, par-ticipant 3 only performed the first block (35 trials per condition).

Data recordings and analysis

iEEG was recorded in three patients (2 females, 1 male) with intrac-table epilepsy (Table 1). All participants gavewritten informed consent,and the experimental procedures were approved by the InstitutionalReview Board and by the National French Science Ethical Committee.Eleven to fifteen semi-rigid, multi-lead electrodes were stereotacticallyimplanted in each patient, with 10 to 15 recording sites on each elec-trode (2 mm wide, 3.5 mm center-to-center) (Jerbi et al., 2009b;Lachaux et al., 2012). Data were sampled at 512 Hz and each recordingsite was referenced to its adjacent neighbor, (bipolar montage). Toobtain high-frequency activity amplitudes between 50 Hz and 150 Hzwe applied the following processing steps. First we bandpass filterediEEG signals in multiple successive 10 Hz-wide frequency bands(e.g. 8–10 bands as [50–60 Hz], [60–70 Hz], etc.) using a zero phaseshift noncausal finite impulse filter with 0.5 Hz roll-off. Next, for eachbandpass filtered signal we computed the envelope using a standardHilbert Transform. For each frequency interval the time-varying ampli-tude was divided by its mean across the entire recording period of theexperiment andmultiplied by 100. This yields instantaneous amplitudeenvelope values as percentage-of-the-mean. Finally, the envelope sig-nals computed for each consecutive band were averaged to provideone single time series across the entire recording session. The obtainedenvelopes had a sampling rate of 64 Hz. This procedure has been previ-ously used in various studies in our group (Jerbi et al., 2010; Juphardet al., 2011; Ossandon et al., 2012; Vidal et al., 2012). Note that althoughiEEG signals provide access to neuronal population activity across awide range of frequencies, we focused here on broadband HFA becauseit has been closely related to population-level neuronal spiking activity(Manning et al., 2009; Ray and Maunsell, 2011) and it is increasinglyused as a proxy for active cortical processing (Buzsaki and Wang,

Table 1Demographic data of patients. Recording locations and demographic data of patients P1–P3. Sexwith WAIS-III); trial number per condition. Abbreviations: VOTC: ventral occipito-temporal cor

MNI coordinates

Patient Site Label x y z

P1 L'7 VOTC −39 −56 −9P2 L'10 VOTC −53 −60 −4P3 L'8 VOTC −46 −51 −15

2012; Lachaux et al., 2012). Compared to other frequencies, thehigh gamma band is also highly correlated with the BOLD signal mea-sured with fMRI (Lachaux et al., 2007b; Logothetis et al., 2001; Worrellet al., 2012) and has been shown to provide real-time mapping anddecoding of brain function and cognitive processes (Hamame et al.,2012; Jerbi et al., 2009a; Lachaux et al., 2007a).

The initial HFA responseswere estimated through a t-test comparingpost-stimulus amplitude with the average pre-stimulus amplitude (the‘baseline level’, averaged between −200 ms and −50 ms relative tostimulus onset). All further comparisons between conditions includeda baseline correction, i.e. a systematic subtraction of the mean baselineamplitude value from the post-stimulus data values at the single-triallevel. Moreover, to assess the modulation of the broadband gammaresponse by stimulus repetition and by masking we used a repeatedmeasures two-way ANOVA design with two factors (repetition andmasking) each with two levels (repeated/non repeated and unmasked/masked). All statistical p-values were FDR-corrected (False DiscoveryRate) (Genovese et al., 2002) for multiple comparisons across time. Themultiple interactions between levels were statistically evaluated with apost-hoc Scheffe's test when the corrected p-value of the main interac-tion between factors was significant. Subsequent specific post-hoc inde-pendent comparisons (t-tests) between conditions were done onaverage broadband gamma activity in the time-intervals of interestthat were identified in the above ANOVA analyses. All calculationswere performed using Matlab (The Mathworks, Inc, MA, USA).

Results

The visual localizer (Experiment 1) revealed that a total of threeVOTC sites, one in each patient, showed category-specific responses toconsonant string and pseudoword stimuli. These three recording siteswere localized directly onto the participants individual anatomicalMRI (Fig. 2 A–C) and their HFA responses in time revealed high selectiv-ity for letter-strings (as compared to other stimulus categories) in atime window of 200 to 400 ms after stimulus onset. For P1 and P3,pseudowords and consonant strings elicited an overall stronger HFAresponse than each one of the other categories (t-test, across allcomparisons, T(100) N 6.6, p b 0.001). For P2 only pseudowords showedthe strongest HFA response (t-test, across all comparisons, T(100) = 7.3,p b 0.001).

In the second experiment we used this information to investigatethe effect of conscious and unconscious processing on the neural sup-pression induced by the repeated presentation of written words. Back-ward masking abolished reportability (0%) while unmasked wordselicited 91% correct detection. Moreover, by repeating the same wordthroughout the trialswe expected to behaviorally accelerate the recogni-tion of this stimulus as compared to all other uniquely presented words.We indeed observed this effect: in the unmasked condition, reactiontimes were shorter for repeated words (mean RT 718 ms +/− 20sem) than for unique words (mean RT 884 ms +/− 34 sem, for allpatients, T(N50) N 2.4; p b 0.05), reflecting the behavioral facilitation ofword repetition on word recognition speed.

We measured in the VOTC the effect of top-down recognition pro-cessing on the modulation of HFA induced by words (frequent vs infre-quent, masked vs unmasked). At the neural level both masked and

; age; handedness (R; right-handed); verbal comprehension index in French (VCI, assessedtex; R: right handed; MNI: Montreal Neurological Institute.

Sex Age Handedness VCI No. trials/cond

F 22 R 94 70F 27 R 110 70M 53 R na 35

Fig. 2.High frequency activity responses to visual categories in VOTC. A. Patient 1. Left lower panel: single-trial HFA response to each of the 8 visual categories. Left upper panel: HFA re-sponse sem shades around the mean for three categories: pseudowords (bleu), consonant strings (red) and houses (green). The above bars indicate samples with significant changes inneural activity compared to baseline level (T-test, p b 0.05, FDR-corrected). Right panel: anatomical location of the recording site in P1. MNI coordinates [−39−56−9]. B. Patient 2. Sameas in (A). MNI coordinates [−53−60−4]. C. Patient 3 electrode 1. Same as in (A). MNI coordinates [−46 −51 −15].

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unmasked words elicited HFA responses starting between 100 and 250ms after the 80ms duration forwardmask onset (significant increase ofhigh-frequency activity relative to pre-stimulus baseline amplitudelevel, for all patients and time samples, T(N222) N 3.1, p b 0.001, FDRcorrected). The VOTC therefore reacts to words shown for merely32ms:masked (and unmasked)words elicited a stronger HFA responsethan masked blank stimuli (at latencies later than 200 ms, see Fig. 3middle and right panels).

The crucial analysis is the comparison of HFA responses followingthe two crossed experimental factors, word repetition and masking,which resulted in the comparison of 4 different conditions: masked re-peated words, masked unique words, unmasked repeated words andunmasked unique words. The repeated measures two-way ANOVAapplied to the HFA responses revealed a main effect of word repeti-tion. This effect driven by an early broadband gamma suppressionfor the repeated words relative to unique words for all three pa-tients (unique N repeated; for all time samples and all patients:F N 7.4, p b 0.05, FDR-corrected, Fig. 3, left column). The starting laten-cies of this effect were respectively 140 ms, 360 ms and 310 ms for P1,P2 and P3. The analysis also revealed amain effect ofmasking, producedby a stronger HFA gamma responses for unmasked words compared tomasked words (unmasked N masked; for all time samples and all pa-tients: F N 8.1, p b 0.05 FDR-corrected, Fig. 3, left column). These effectsstarted respectively for P1–P3 at 250ms, 390ms and 420ms after stim-ulus onset. Importantly, we also found a significant interaction betweenfactors in time for P1 and P2 (for all time samples and sites, F(1,70) N 8.2,p b 0.05 FDR-corrected). HFA response differentiated between repeatedvs uniquewords for unmasked words at starting latencies of 360ms forP1 and 420 ms for P2 (repeated unmasked b unique unmasked, posthoc comparisons Scheffe's test, p b 0.05, FDR-corrected). Masked andunmasked unique stimuli started differentiating at 360 ms for P1 and

at 420 ms for P2 (unique unmasked N unique masked, post hoc com-parisons Scheffe's test, p b 0.05 FDR-corrected). P1 was the only casefor which the difference between masked and unmasked repeatedstimuli showed a significant difference starting at 360 ms (repeatedunmasked b unique masked, post hoc comparisons Scheffe's test,p b 0.05 FDR-corrected).

To assess unconscious cortical processing we compared maskedwords versus masked blanks. The difference between these two condi-tions was significant for broadband gamma responses of P1 and P2 (forall time samples and patients, words N blank; T(N133) N 2.9, p b 0.05,FDR-corrected, Fig. 3, right panel). This effect shows that letter stringstimuli are actively processed in the local networks in the absenceof conscious perception. This effect was absent for P3 (T(86) b 2.3,p N 0.05).

The ANOVA analysis revealed amain effect of word repetition acrossconditions (masked and unmasked) within specific time intervals. Tofurther specifically investigate whether the repetition suppression ef-fect in these intervals was present conjointly formasked and unmaskedwords we performed additional statistical tests (t-test). We comparedthe mean HFA response amplitudes in the time-intervals of interestdefined by the ANOVA, for repeated and unique conditions for maskedand unmasked stimuli separately. For masked words we found a signif-icant effect (unique N repeated) for P1 (t-test, T(133) = 2.74, p b 0.01),for P2 (t-test, T(131) = 2.77, p b 0.01) but not for P3 (t-test, T(59) =1.59, p = 0.11). Interestingly, the absence of effect in patient 3 isconsistent with the absence of a statistically significant effect ofmemory-based predictions on masked words compared to blankstimuli in this patient (Fig. 3, right column). For unmasked wordswe found a significant effect (unique N repeated) for P1 (t-test,T(133) = 6.9, p b 0.0001), for P2 (t-test, T(131) = 4.99, p b 0.0001)and for P3 (t-test, T(49) = 4.59, p b 0.0001). This analysis indicates

Fig. 3. HFA response modulation by stimulus repetition and visual masking. Patients 1–3 (P1–3). Left panel: HFA response to masked and unmasked words (repeated and unique). Thestatistically significant time-samples (ANOVA analyses) are displayed below the curves: main effect of word repetition (black), main effect of masking (gray), repetition effect forunmasked words (interaction, yellow), masking effect for repeated words (interaction, green), masking effect for unique words (interaction, pink). Middle panel: HFA response tounmaskedwords (repeated and unique) and unmasked blank, including t-test statistical significant time samples of unmaskedwords versus unmasked blank. Right panel: HFA responsesto masked words (repeated and unique) and masked blank, including t-test statistical significant time samples of masked words versus masked blank.

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that repetition suppression occurred not only during conscious per-ception, but also during unconscious perception.

Discussion

In this study, we used the high temporal and spatial precision of in-tracranial EEG to measure the modulation of word selective neural ac-tivity in VOTC during processing of frequently presented versusunique stimuli. A key manipulation in our experimental design was toembed the repetition suppression task in a backward/forward maskingframework that allowed us to simultaneously address the contributionof conscious perception and the contribution of repetition-induced sup-pression. Beyond revealing that both conscious and unconscious neuralprocessing in VOTC elicits neural repetition suppression, we used thefine-scale temporal evolution of task-related HFA across all conditionsto disentangle across time the concurrent and distinct effects of recogni-tion and of conscious processing. While previous studies reported theeffects of conscious and unconscious stimulus priming on consciousprocessing, as in the case of subliminal priming (Dehaene et al., 2001;Henson et al., 2000; Kherif et al., 2011; Kouider et al., 2007), we hereshowed that frequent stimulus repetition can also affect unconscioussensory processing within word-form selective VOTC networks. Impor-tantly, this effect is weaker than for consciously perceived words whereneural suppression effect appears to undergo further amplification after300 ms following stimulus onset.

Frequent stimulus repetition may involve various cognitive pro-cesses, such as familiarity and recognition memory (Henson et al.,

2000; Vuilleumier et al., 2002), but possibly also prediction process-es (Summerfield et al., 2008) which have been associated to the pro-active use of memory-traces. Although our studywas not designed todistinguish between the putative contributions of each one of theseprocesses, we propose that the reported neural repetition suppres-sion is more related to a context-dependent recognition memoryprocess than by mere passive repeated bottom-up traces. Becausestimulus repetition occurs only after the presentation of variousother inter-leaving stimuli, we believe that the contribution of iconicand fleeting memory traces to be unlikely (or at least very weak)since they would be dramatically affected by subsequent sensorytraces. Importantly, this modulation involves for all patients mostlytime-samples beyond 300 ms post-stimulus, a latency at whichpure bottom-up influences are probably very rare. We therefore sug-gest the neural repetition suppression elicited by our paradigm after300 ms post-stimulus as being the result of a top-down modulatedmemory trace. This trace may originate in higher up temporal cortexnetworks like the parahippocampal cortex or the hippocampus(Eichenbaum et al., 2007; Rutishauser et al., 2006), though consider-ing our reported effects starting at ~300 ms this influence could re-sult from an interaction with closer-by networks within the VOTC.Moreover, a possible contribution of learned stimulus–response associ-ations to the reported neural suppression effects by stimulus repetitioncannot be fully discarded, though previous studies showed this affectsmainly neural responses in frontal cortex and not in occipito-temporalcortex (Horner andHenson, 2008, 2012; Race et al., 2010). Further stud-ies are needed to specifically address these issues.

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Non-invasive electrophysiological studies have shown that the braincan produce early distinct neural activity for frequent words as com-pared to novel or less frequent ones (Hauk et al., 2006; Proverbio et al.,2004). Specifically, scalp EEG gamma-band oscillatory power suppres-sion by stimulus repetition has been associated to neural sharpening(Fiebach et al., 2005; Gruber and Muller, 2005; Gruber et al., 2004).Moreover, recent intracranial studies showed that HFA could be modu-lated by word novelty and word repetition within sometimes distantcortical networks (McDonald et al., 2010; Rodriguez Merzagora et al.,2014). However, these studies did not show how these results relateto word-selectivity features of the explored sites in VOTC, which consti-tutes an important added value of our study to the understanding of cor-tical selectivity. Most importantly, the current study is the first toinvestigate the putative role of conscious processing in modulatingthe extent of neuronal repetition suppression as measured by HFA.Future studies with a broader sample group are needed in order toconfirm our observations.

HFA responses selective to letter strings andword form stimuli havebeen reported in the VOTC (Hamame et al., 2013; Vidal et al., 2012);here we showed that this selectivity exists for both conscious and un-conscious cortical processing, providing a putative electrophysiologicalcorrelation of previous results reported with fMRI (Dehaene et al.,2001; Kouider et al., 2007).Moreover, recent intracranial studies report-ed the amplification and temporal extension of local neural populationactivity through HFA responses in sensory cortices during conscious vi-sual stimulus perception (Asano et al., 2009; Fisch et al., 2009; Lachauxet al., 2005) and for conscious word reading specifically (Gaillard et al.,2009). By comparing the HFA responses of unmasked (visible) vs.masked (invisible) words, we were able to confirm this observationspecifically for VOTC neuronal populations that preferentially processletter strings. However, conscious task-relevant stimulus processingalso engages attentional resources in general, and reading-relatedprocesses that are both known to enhance HFA (Jung et al., 2008;Ossandon et al., 2012; Vidal et al., 2012). We therefore consider it likelythat the HFA response that we reported for unmasked words reflectscombined perceptual consciousness and reading related processing.

A previous study recorded HFA in the other sites of the occipito-temporal cortex that displayed a category selectivity for visual imagescontaining people, and showed that this local signal was not modulatedby prior stimulus exposure (Aru et al., 2012). The experimental manip-ulation used by the authors bares therefore some similaritywith our ex-perimental condition in which frequent word stimuli were presented.However, the authors also reported that both sensory evidence andprior stimulus exposure facilitated conscious stimulus perception andbehavioral report. Because only sensory evidence andnot prior informa-tion traces enhanced local broadband HFA the authors argued that thissignal probably does not reflect conscious cortical processing. In ourstudy we find a relative HFA response suppression by prior stimulus in-formation. Prior stimulus information appears to reduce not only thesensory processing load, but also the processing of perceptual evidenceof the stimulus. Our interpretation of this effect is that initial HFAdecreases are produced mainly by memory traces that later in timecan amplify suppression by interacting with conscious processing.Importantly, though all patients presented a neural selective responseto letter-strings at their respective VOTC recording site, only 2 out of 3patients showed an effect of word repetition. This functional differencesuggests a variability of word-selective VOTC networks regarding theirbottom-up and top-down influences, and has been recently acknowl-edged in the case of learning processes (Perrone-Bertolotti et al., 2014).

Previous studies have shown evidence supporting the fact that back-ward visual masking blocks stimulus visibility by interrupting feedbackprocessingwaves in visual cortices (Fahrenfort et al., 2007;Macknik andLivingstone, 1998). In our study unmasked words produced a strongerHFA response than masked words despite the weaker overall sensorystimulation (unmasked words don't require the extra sensory process-ing related to the 200 ms presentation of the backward mask as for

the masked word condition). We suggest that the HFA increase in theunmasked conditions reflects conscious-related cortical processing,probably related to top-down feedback processing, rather than uncon-scious sensory processing. As we show here, unconscious sensory evi-dence processing can occur within these local networks through amoderate enhancement of HFA yet significantly reduced as comparedto conscious processing.

Our results show the contribution of different, initially independent,influences in word-selective VOTC sites that may interact in the latterphase of word-processing (approximately 300–350 ms after wordpresentation). Whether these signals originate from different corti-cal regions is currently not known, though we speculate that memo-ry related signals sustaining familiarity could originate in medialtemporal lobe networks (Eichenbaum et al., 2007). Song and col-leagues nicely demonstrated the prominent role of the VOTC as aprocessor of bottom-up sensory processing, while at the same timeinteracting with higher areas for top-down phonology or meaning-related inputs (Song et al., 2012). It has also been shown with fMRIthat the inferior frontal cortex is active during conscious visualobject recognition (Bar et al., 2001). In addition, studies using MEGrecordings have suggested that this neural event occurs before thesignal enhancement in sensory cortices (Bar et al., 2006). Consistentwith this latter observation, we found that the modulation of HFA inall word-form selective VOTC recording sites occurred earlier forword repetition than for conscious perception.

Finally, previous electrophysiological studies nicely demonstratedthat the VOTC is activated at approximately 200 ms post word onsetas can be evidenced both by ERPs (Nobre et al., 1994) and BG response(Hamame et al., 2013). This early activation in the VOTC fits well withthe role of this region in processing pre-lexical and orthographic senso-ry input as demonstrated by fMRI (Levy et al., 2008). Amore recentMEGstudy also showed oscillatory alpha-band power suppression in this re-gion related to conscious word perception (Levy et al., 2013). The viewpresented here, namely of a first top-downmodulation of sensory infor-mation in the VOTC followed by a second top-down activation stage re-lated to consciousword processing is in agreementwith other views thatseparately emphasize on the one hand the early temporal selectivity ofVOTC in word form processing (Dehaene and Cohen, 2011), and on theother hand the role of top-down interactions related to acquired priorknowledge (Price and Devlin, 2011). Our data extend and complementthese parallel streams of research by providing evidence that consciousand unconscious word processing in VOTC both interact with memorytraces induced by frequent word repetitions. These findings are in linewith recent views on the role of top-down feedback influences in visualcortices during unconscious priming (Persuh and Ro, 2013).

Acknowledgments

We thank all patients for their participation; the staff of the GrenobleNeurological Hospital epilepsy unit; Dominique Hoffmann, PatriciaBoschetti, Carole Chatelard, Véronique Dorlin for their support. Thiswork was supported by ANR MLA, performed within the framework ofthe LABEX CORTEX (ANR-11-LABX-0042) of Université de Lyon, withinthe program "Investissements d'Avenir" (ANR-11-IDEX-0007) operatedby the French National Research Agency (ANR). International Re-integration Grants (IRG), FP7-PEOPLE-2009-RG for AL.

Conflict of interest statement

The authors declare no competing financial interests.

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