We compared conscious and nonconscious processing of briefly flashed words using a visual masking procedure while recording intracranial electroencephalogram (iEEG) in ten patients. Nonconscious processing of masked words was observed in multiple cortical areas, mostly within an early time window (<300 ms), accompanied by induced gamma-band activity, but without coherent long-distance neural activity, suggesting a quickly dissipating feedforward wave. In contrast, conscious processing of unmasked words was characterized by the convergence of four distinct neurophysiological markers: sustained voltage changes, particularly in prefrontal cortex, large increases in spectral power in the gamma band, increases in long-distance phase synchrony in the beta range, and increases in long-range Granger causality. We argue that all of those measures provide distinct windows into the same distributed state of conscious processing. These results have a direct impact on current theoretical discussions concerning the neural correlates of conscious access.
We adopted a theory-driven approach, trying to test experimentally a set of explicit predictions derived from the global workspace model of conscious access. This model, in part inspired from Bernard Baars' theory [30], proposes that at any given time, many modular cerebral networks are active in parallel and process information in an unconscious manner [22,23,31,32]. Incoming visual information becomes conscious, however, if and only if the three following conditions are met [23]: Condition 1: information must be explicitly represented by the neuronal firing of perceptual networks located in visual cortical areas coding for the specific features of the conscious percept. Condition 2: this neuronal representation must reach a minimal threshold of duration and intensity necessary for access to a second stage of processing, associated with a distributed cortical network involved in particular parietal and prefrontal cortices. Condition 3: through joint bottom-up propagation and top-down attentional amplification, the ensuing brain-scale neural assembly must “ignite” into a self-sustained reverberant state of coherent activity that involves many neurons distributed throughout the brain. Why would this ignited state correspond to a conscious state? The key idea behind the workspace model is that because of its massive interconnectivity, the active coherent assembly of workspace neurons can distribute its contents to a great variety of other brain processors, thus making this information globally available. The global workspace model postulates that this global availability of information is what we subjectively experience as a conscious state. Neurophysiological, anatomical, and brain-imaging data strongly argue for a major role of prefrontal cortex, anterior cingulate, and the associative areas that connect to them, in creating the postulated brain-scale workspace. In the present work, we measured the neural correlates of visually masked words and contrasted them with those of consciously visible unmasked words. On each trial, patients were randomly presented with a masked word, a visible word, or with corresponding control stimuli in which the words were replaced by blank screens. In the masked condition, words or blank screens were presented for 29 ms, preceded by a forward mask and followed by a backward mask. In the unmasked conditions, words or blank screens were made visible by simply removing the backward mask (see Materials and Methods and Figure 1 for details). In order to discard activations induced by the masks, we always subtracted from word-present conditions the corresponding blank condition. This subtraction allowed us to isolate the entire processing path evoked by the masked or unmasked word. In the light of our model, the masked–unmasked contrast corresponds to a comparison between a visual representation satisfying only condition 1 and a representation satisfying all three conditions for conscious access listed above. The global workspace model therefore leads to the following four predictions.
Unmasked words were consciously reportable, and were categorized better than chance level in a forced-choice categorization task on the emotional valence of words (mean discriminability index d′ = 2. 24 (+1. 14 to +3. 04), all individual χ2 p-values and group analysis Student t-test p-value < 0. 0001). In sharp contrast, masked words were not consciously visible, and forced-choice performance was at chance level for each of the implanted patients (mean d′ = 0. 02 (−0. 18 to +0. 27), all p-values >0. 2). Response times (RTs) were similar across the two masking conditions (p > 0. 38 in Student t-test performed on mean RTs; masked mean RT = 1,640 ms, unmasked mean RT = 1,300 ms). We defined masked effects by subtracting the voltages measured on masked blank trials from those associated with masked word trials. This subtraction allowed us to isolate, on a sample-by-sample basis, activations associated with masked word processing (see Figure 1 and Materials and Methods for our detailed three-step statistical procedure). Unmasked effects were defined similarly by subtraction of the unmasked word and unmasked blank conditions. Figure 1 shows the anatomical distribution of the 176 reconstructed bipolar montages (“electrodes”) from which we obtained valid data across the ten patients. The bipolar subtraction of nearby recording sites reduced distant influences, including those from the reference electrode, and resulted in a signal tightly localized to the implanted structure. Although measures were obtained for all four lobes, it should be kept in mind that major sectors of dorsolateral and polar prefrontal cortex as well as parietal cortex were not sampled. Among the 176 electrodes, 24. 4% (43 electrodes) showed a significant effect for masked words. These effects were observed across all implanted structures but with a predominance of effects on occipital electrodes: 22/55 (40%) within the occipital lobe, 11/78 (14. 1%) within the temporal lobe, 4/24 (16. 7%) within the parietal lobe and 6/19 (31. 6%) within the frontal lobe (χ2 p-value = 0. 004). Concerning unmasked words, 68. 8% of all electrodes (121 electrodes) showed a significant effect of word presence—a remarkably high percentage, given that electrodes had been placed at clinically relevant sites without consideration of their relevance to our visual stimuli. Unmasked effects were observed across all implanted structures but with a particular emphasis on the frontal lobe: 42/55 (76. 4%) within the occipital lobe, 49/78 (62. 8%) within the temporal lobe, 12/24 (50%) with the parietal lobe, and 18/19 (94. 7%) within the frontal lobe (χ2 p-value = 0. 005). The frontal lobe showed a major difference between trials containing masked and unmasked words: almost all contacts were systematically activated during conscious processing of unmasked words (∼95%), whereas this was not the case during unconscious processing of masked words (∼32%). In order to better assess the specificity of this last result, we ran an ANOVA to directly compare the impact of masking on the proportion of activated electrodes between occipital and frontal lobes. A main effect of masking was observed (86% versus 36%; p < 10−4), confirming the larger spatial extension of unmasked activations as compared to masked activations. No main effect was observed between frontal and occipital electrodes (58% versus 63%, p > 0. 5). Crucially, we observed a significant interaction between frontal and occipital cortices and masking condition (p = 0. 05), assessing the larger differential activation of frontal lobe between masked and unmasked conditions, as compared to the pattern observed in posterior visual cortex. Note that this spatial analysis is affected by the nonhomogenous sampling of brain regions, minimizing the contribution of cortical structures that were less frequently implanted. Nevertheless, masked effects were more frequent on posterior than on anterior electrodes, whereas unmasked effects were homogeneously distributed. To demonstrate this point, we examined the distribution of the anterior-posterior (y) coordinate, in Talairach space, of the electrodes showing a significant effect, and compared it to the spatial distribution of all 176 recorded electrodes (see Figure S1). For masked words, the spatial distribution of significant electrodes was strongly shifted towards posterior sites (p < 10−6, Kolmogorov-Smirnov test, relative to the distribution of either the whole set of 176 electrodes or to those showing an unmasked effect). The same analysis conducted on the cumulative distribution of unmasked effects showed a spatial distribution statistically indistinguishable from that of the whole set of electrodes. Masked and unmasked words were also distinguished by the temporal extension of their activation. A crude analysis, averaging across all electrodes, revealed that masked effects had a mean duration of 60 ms, much shorter than the mean of 378 ms for unmasked effects (p < 10−6). Masked effects also showed an earlier onset (mean = 366 ms; median = 301 ms) than unmasked effects (mean = 522 ms; median = 497 ms; t-test, p < 10−5). A more relevant analysis focusing on the first significant effect within the subset of electrodes with both masked and unmasked effects showed similar latencies between these two conditions (299 ms and 348 ms, respectively, for masked and unmasked conditions; t-test, p = 0. 30). Indeed, up to approximately 200 ms after word onset, glass brain visualization of the spatiotemporal dynamics of masked and unmasked effects showed a strikingly similar pattern of activations within posterior occipitotemporal cortical regions (see Figure 2). This dynamic pattern is very comparable to the “feedforward sweep” described by Lamme in the nonhuman primate visual cortex using multiunit recordings for latencies up to 100 ms after visual stimulus onset [5]. Clear differences between masked and unmasked effects appeared after 150 ms, with a progressive increase in the intensity and spatial extension of unmasked effects, while masked effects decayed and did not show a similar spatial extension (see Videos S1 and S2). This general pattern was observed on individual electrodes (see Figure 3). The initial response was often indistinguishable between masked and unmasked effects. This initial common response was usually followed by later effects specifically for the unmasked condition. Out of 14 electrodes showing this pattern with our statistical criteria, 11 of them also showed a polarity inversion of the late sustained effects relative to the polarity of the initial effect. A cortical lobe analysis focusing on the proportion of electrodes showing a significant effect over time (Figure 4) showed a similar proportion of electrodes activated by masked and unmasked words at short latencies, whereas at later latencies, the effects were increasingly specific to the unmasked condition. An analysis of the mean voltage power, averaged across electrodes within one lobe, showed a similar temporal dynamics, and additionally allowed us to detect a progressive time delay in the peak of the initial activation common to masked and unmasked words. The time point at which the first significant divergence between masked and unmasked effects occurred, as estimated by a t-test (p < 0. 05), progressively increased from 215 ms to 275 ms and 347 ms, respectively, for the occipital, temporal, and frontal lobes (see Figure 4). The divergence did not reach significance for the small set of 14 parietal lobe electrodes tested (those showing at least one significant effect, masked or unmasked). We then turned to frequency-domain analyses of the intracranial signals. Figure 5A shows a typical single-electrode example of the time-frequency transform applied to our data. The masks alone evoked a very strong sequence of event-related increase in the beta and gamma bands accompanied by alpha decrease, followed by a reversal of this pattern. Subtraction of each mask-only condition from the corresponding word-present condition, however, isolated the ERSP induced by the word alone, as a function of whether it was masked or unmasked. As can be seen in this example, masked words induced a slight increase in gamma power 100–200 ms after the stimulus, whereas unmasked words induced a much bigger effect that lasted throughout the epoch and was accompanied by alpha suppression. To evaluate the generality and significance of such effects, we averaged the time-frequency diagrams across all electrodes (Figure 5B). Statistical comparisons over time-frequency regions of interest, with Bonferroni correction (see Methods and Materials), identified several significant effects. In the 100–200-ms time window, masked words evoked highly significant power changes (beta suppression: p = 0. 0004; high-gamma increase: p = 0. 0005). In this time period, there was no significant difference with unmasked words, confirming that a volley of activation, reflected primarily in a gamma increase, can propagate nonconsciously while being largely unaffected by masking [7]. In the next time window (200–300 ms), whereas unmasked words created an even larger power increase in the high-gamma band (p < 10−11) and decreases in alpha (p < 10−8) and beta bands (p = 10−5), masked words induced only small effects of alpha suppression (p = 0. 0014) and high-gamma increase (p = 0. 038). Beta and high-gamma bands showed significantly stronger changes for unmasked compared to masked words (all p < 0. 0007). In the subsequent time window (300–500), alpha suppression, beta suppression, and high-gamma increase were very strong in the unmasked condition (all p < 0. 0003), but altogether absent in the masked condition, creating a significant difference (all p < 0. 0002). In summary, masked words induced significant changes in the power spectrum, particularly increases in the high-gamma band, but these induced oscillations quickly dissipated with time, whereas the ERSPs evoked by unmasked words exhibited a greater power and lasted significantly longer. Note that the above analysis was based on the pooling of ERSP results from all electrodes, regardless of their location. We also replicated this ERSP analysis while separating the electrodes as a function of their lobe of origin. Both the high-gamma increase and late alpha and beta suppression specific to the unmasked condition were replicated within each of the four lobes (see Figure S2). Interestingly, the high-gamma increase peaked earlier in occipital cortex than in temporal, parietal, or frontal, following an approximate posterior to anterior progression (see Videos S3 and S4). Furthermore, the lobar analysis showed that the early nonconscious effects were confined to the occipital and temporal lobes: the only significant effects were a high-gamma power increase in occipital cortex in the 100–200-ms and 200–300-ms windows (respectively, p = 0. 013 and p = 0. 016), and decreases in alpha (200–300 ms, p = 0. 007) and beta (100–200 ms, p < 10−3) in temporal cortex. In brief, the early ERPS evoked by nonconscious stimuli originated only from occipitotemporal regions, whereas conscious perception was associated with stronger and longer-lasting power changes spreading towards anterior cortical regions. In this respect, analyses of induced high-gamma power yielded conclusions very similar to those derived from iERP analyses. To better evaluate the relation between induced gamma activity and iERPs, we calculated for each segment for which a significant ERP difference was seen, the absolute value of the iERP effect as well as the mean power evoked in the high-gamma range, averaged over the same time period. A significant positive correlation between these two measures was found, for unmasked words (r2 = 14. 9%, 241 time segments, p < 10−8) and, crucially, for masked words (r2 = 9. 3%, 59 time segments, p = 0. 028). This means that periods in which a high-gamma–band activity is seen are also periods in which a high-voltage difference between word-present and word-absent conditions exists. In brief, high-gamma activity and iERP are correlated measures that both jointly reflect conscious as well as nonconscious processing stages. Indeed, videos of ERP and of high-gamma activity, provided as supplementary online material, present high similar profiles (see Videos S1, S2, S3, and S4). Spectral changes are complex phenomena that can be sensitive to local as well as global neuronal synchronization of thalamocortical networks [56]. To evaluate the global workspace model' s prediction that access to consciousness is associated with long-distance synchronization, we measured the phase synchrony between all electrode pairs. Phase synchrony can occur independently of changes in induced power: it solely evaluates whether oscillations are reproducibly synchronized across two distant sites in the sense that across trials, they exhibit a systematic phase relationship. Figure 6 shows a time-frequency diagram of the intertrial phase coherence (ITC) changes induced by the masked and unmasked words, both in an example electrode and in the mean overall electrodes. All statistics were Bonferroni corrected. Statistical analyses revealed no significant coherence changes induced by the masked words. For unmasked words, an increase in beta synchrony in the 300–500-ms time window was highly significant (t (1,282 df) = 7. 12, p < 10−10; difference with masked condition, t (1,282 df) = 5. 43, p < 10−6). It is particularly interesting to note that (1) this phase synchrony increase was concomitant with a decrease in induced spectral power (ERSP) within the same frequency band (see Figure 7A and 7B); (2) no phase synchrony increase was detected in the high-gamma band, although in this band, a highly significant increase in induced power had been detected by ERSP analysis. Thus, ERSP and phase synchrony appear to double dissociate, and beta synchrony appears as a highly selective marker of the late phase of conscious access. Figure 8 shows in graphic form the value of the beta coherence increase due to word presence in the critical time window 300–500 ms, separately for unmasked and masked words. Clearly, unmasked words create a more globally synchronous brain state than masked words. The figure makes apparent that this phase coherence analysis is importantly limited by the available electrodes: we can only analyze coherences between electrodes within a given patient, and these tend to be regrouped within a cortical area, thus preventing a thorough analysis of how coherence evolves across distant anatomical sites. For instance, it was not possible to evaluate the prediction that frontal electrodes should cohere more with posterior sites during conscious processing, because in our sample, these two regions were very rarely recorded simultaneously. Still, to probe long-distance connections, we could analyze a subset consisting of electrode pairs in which the two electrodes lie in different hemispheres, thus imposing a long-distance transfer across the corpus callosum. As predicted by global workspace theory, we observed an increase in long-distance interhemispheric beta coherence selective to unmasked words (t (71) = 2. 50, uncorrected p = 0. 015). In fact, interhemispheric beta coherence actually decreased when masked words were presented (t (71) = 3. 14, uncorrected p = 0. 003), thus creating a strong difference between visible and invisible conditions (t (71) = 3. 83, p = 0. 0003). Conversely, Figure 8 suggests that in the masked condition, there might have been a small local increase in beta coherence within posterior occipitotemporal cortices, which might have been missed in our analysis pooling across all electrode pairs. Indeed, when we restricted only to intrahemispheric electrodes lying within occipital cortex or within temporal cortex posterior to y = −20, we detected a significant increase in beta coherence for masked words during the 200–300-ms time window (t (734) = 2. 34, uncorrected p = 0. 02), which ceased to be significant in the 300–500-ms time window (t = 0. 41, not significant [n. s. ]). No such increase was seen in other frequency bands, or in other regions (e. g. , within frontal electrodes). Thus, nonconscious word processing resulted in only small and barely detectable transient increases in phase coherence within visual cortex, whereas conscious words yielded a massive increase in long-distance beta coherence A final measure of conscious processing that we evaluated is Granger causality [60,63–65], a mathematical tool that can estimate the causal influence that one electrode site exerts on another. Global neuronal workspace theory predicted that access to consciousness for unmasked words would be accompanied by a massive web of causal relations among distant cortical sites, not seen in the masked condition. Granger causality and phase coherence are similar in that both estimate the correlations among pairs of electrodes, but Granger causality looks for temporal contingencies inaccessible to coherence analyses. In a nutshell, the method estimates whether past samples of electrode j account for a significant amount of variance in electrode i, over and above a simpler “autoregressive” model using only past samples of electrode i (see [63] for details). It is possible for two time series to be strongly phase coherent, yet not causally related (for instance, two sine waves with constant phase lag and independent noise). Thus, Granger causality analysis is not redundant with phase coherence analysis: finding that Granger causality increases during conscious perception, perhaps simultaneously with the beta coherence increase, would provide additional evidence in favor of a large-scale reverberating neuronal assembly linking distant sites. Furthermore, unlike phase coherence, Granger causality is a directional measure: it is possible for electrode j to causally influence i without i causally influencing j (although it is also possible for two signals to exert mutual causal influences on each other). This analysis therefore provided an opportunity to examine the top-down versus bottom-up propagation of activation during conscious and nonconscious processing. As a concrete example, Figure 9 illustrates the causality analysis of a sample electrode pair consisting of one frontal and one occipital electrode. At the time of stimulus presentation, a massive increase in Granger causality is seen in the feedforward, occipitofrontal direction (Figure 9A, left panel) and, to a smaller extent in the top-down, fronto-occipital direction (Figure 9A, right panel). Importantly, the curves showing the evolution of the F-test for causality as a function of time exhibit two successive peaks: one early peak is evoked by the masks alone (146 ms after mask onset), whereas a second peak (325 ms after word onset) is seen only when a word is present and unmasked. As illustrated in Figure 9B, a strong “causal gain” is therefore observed, approximately 200–450 ms after word onset, when the word-present condition is contrasted to the word-absent condition. This effect is seen mostly in the feedforward direction, thus engendering a “causal imbalance” (higher causal gain in one direction than in the other). Similar increases in causal gain and causal imbalance in the unmasked condition were seen in a large set of electrode pairs. To evaluate their statistical significance, we first averaged the causal gains across all electrode pairs and both causal directions, separately for masked and unmasked conditions, and used t-tests to evaluate the significance of changes within three temporal windows (100–200,200–300, and 300–500 ms, similar to the ERSP and phase coherence analyses, with Bonferroni correction over the number of windows tested) (see Figure 9C). A massive increase in mean causal gain was observed during the 300–500-ms window in the unmasked condition (t (1805) = 7. 60, p < 10−13), but not in the masked condition (t = 1. 47, n. s.), resulting in a significantly larger causal gain during conscious than during nonconscious processing (t (1805) = 5. 46, p < 10−8). The effect was already perceptible in the 200–300-ms window, though it was much smaller (unmasked: t (1805) = 3. 03, p = 0. 0075; masked, t = −0. 86, n. s. ; difference: t (1805) = 2. 89, p = 0. 012). No effect reached significance in the 100–200-ms window. Figure 8B illustrates the anatomical distribution of the mean causal gains during the 300–500-ms window. In the unmasked condition, causal relations increased massively among many distant sites, both within the occipitotemporal cortex, between occipitotemporal cortex and distant frontal and insular sites, and across the corpus callosum. By contrast, increases were very scarce in the masked condition and never reached significance even when restricted to posterior electrodes only. With similar methods, we evaluated the statistical significance of changes in the variable of “causal imbalance, ” which is the subtraction of forward causal gain minus backward causal gain in the same electrode pair. This variable evaluated the dominant directionality of causality (posterior to anterior = feedforward, or anterior to posterior = feedback). During the 300–500-ms time window, in the unmasked condition, there was a small imbalance with a higher causality gain in the feedforward compared to the feedback direction (t (1,850) = 2. 07, p = 0. 039 before Bonferroni correction). Although marginally significant, this finding occurred in the predicted late time window and fits with our prior hypothesis that during this time period, and only in the unmasked condition, perceptual information gains access to consciousness and is therefore able to invade anterior areas in a feedforward manner. Indeed, in this time window, the imbalance was not significant for masked targets (t = −0. 90, n. s.), creating a difference for unmasked as opposed to masked targets (t (1,805) = 2. 09, p = 0. 037 before Bonferroni correction). Quite surprisingly, however, in the preceding time window (200–300 ms, see Figures 9D and S3), there was a significant imbalance in the converse direction (higher causality in the top-down or feedback). This was true only for the masked condition (t (1,805) = −2. 66, p = 0. 024, Bonferroni corrected), not the unmasked condition (t = 1. 11, n. s.), a significant difference (t (1,805) = 2. 70, p = 0. 021 Bonferroni corrected). This unexpected finding, further discussed below, may indicate that in the masked condition, there is a top-down component of attentional amplification, perhaps relating to an unsuccessful effort to identify the masked word.
It is important to keep in mind the limits of the present paradigm. First, when comparing the neural activity elicited respectively by a masked word and by an unmasked word, as was done here, one is actually comparing the correlates of a conscious representation with those of a degraded nonconscious representation. Early differences are therefore not guaranteed to isolate a neural signature of conscious processing per se [23]. Indeed, Del Cul et al. [1] demonstrated that early visual components such as the P1b, N1, or N2 are affected by masking, yet do not meet the criteria for a strong one-to-one correlation with subjective reports of conscious experience. It therefore seems likely that the early iERP differences that we observed at occipital sites only reflected the early and not-yet conscious effects of masking (see, for instance, the peak of activity observed on occipital lobe electrodes on Figure 4, bottom right panel). The three additional markers of conscious processing that occurred later on, around 300 ms, synchronous to the activation of frontal regions, appear to be more consistent with the existing literature on electrophysiological correlates of conscious access [1,2, 61]. Indeed, they concur nicely with ERP results obtained in the attentional blink [2,61], a paradigm that may be more appropriate for answering the early versus late debate because it involves an undegraded stimulus that is only made invisible by central competition. A second limitation relates to task confounds. In the present work, some of the observed differences might correspond to differences between a task being performed (in the conscious condition) and a task not being performed (in the nonconscious condition). Once a word was consciously perceived, subjects were able to complete the requested semantic emotional categorization task, a complex decision that presumably requires high-level coordination of multiple brain areas. In the masked condition, on the other hand, although subjects still responded to the task, objective performance was by chance. Some of the neurophysiological differences that we reported between masked and unmasked words might therefore be related to task performance rather than to conscious access itself. Mitigating this criticism, however, is the fact that our task appeared to be more difficult for masked words than for unmasked ones, as indicated by longer RTs and by informal subject reports. Indeed, the observed imbalance in the top-down direction for masked words not observed for unmasked words in the 200–300-ms window suggests that nonconscious processing was not free of attentional effects. Nevertheless, an important direction for future research will be to minimize task differences while still comparing neural activity associated with conscious and nonconscious perception. Passive viewing of stimuli could be a valuable instruction, but does not guarantee an absence of task differences (indeed, it seems obvious that subjects would continue to read and to memorize the conscious words, but not the nonconscious words). The task problem is notoriously difficult because performance levels are very rarely identical under nonconscious and conscious conditions. Nevertheless, using “blindsight” conditions with unseen but better than chance performance, matched with seen but degraded performance, Lau and Passingham [24] used fMRI to identify an activation of dorsolateral prefrontal cortex that was specifically associated with conscious experience. This type of paradigm may be usefully complemented with intracranial recordings. We close this issue with a general consideration, initially put forward by phenomenological philosophers [87]: whenever a subject is conscious, he is necessarily conscious of a given mental content. Consciousness is an transitive or “intentional” process (it is “about” a certain content), and therefore it may be illusory to look for a “pure” form of consciousness independent of its particular contents and of the tasks that it affords. Applied to neuroscientific experiments, this property of consciousness implies that when imaging a brain having some conscious experience, we will necessarily observe activations corresponding to a specific conscious content. Nevertheless, satisfactory solutions to overcome this major limitation may exist. For instance, it could be particularly relevant to replicate the present results while manipulating the subjects' task. This track of research may look for the common and invariant correlates of conscious access, irrespective of the task being performed and of the specific mental content being probed. Plausible candidates include late brain-scale activation and beta synchrony, since they were observed in the present results as well as other EEG and MEG studies of conscious perception [1,2, 61], with various tasks of letter perception, word reading, or digit comparison. The main motivation of our study was to probe the convergence of multiple neurophysiological measures of brain activity in order to define candidate neural signatures of conscious access. Conscious word processing was associated with the following four markers: (1) sustained iERPs within a late time window (>300 ms after stimulus presentation); (2) sustained and late spectral power changes, combining a high-gamma increase, beta suppression, and alpha blockage; (3) sustained and late increases in long-range phase coherence in the beta range; and (4) sustained and late increases in long-range causal relations. Our results suggest that in the search for neural correlates of consciousness, time-domain, frequency-domain, and causality-based electrophysiological measures should not be seen as competing possibilities. Rather, all of these measures may provide distinct glimpses into the same distributed state of long-distance reverberation. Indeed, it seems to be the convergence of these measures in a late time window, rather than the mere presence of any single one of them, that best characterizes conscious trials. For instance, masked words also elicited significant iERPs and significant increases in spectral power in the gamma band, contemporary with short-range synchronies in the beta range during the 200–300-ms window. Yet, those words were not consciously accessed, which implies that neither iERPs (even those recorded from frontal cortex), nor gamma-band activity or beta synchrony per se are unique markers of conscious experience. Our results suggest that only late sustained long-distance synchrony and late amplification (>300 ms) may be causally related to conscious-level processing. There are yet other mathematical measures derived from nonlinear dynamics that could have been applied to our dataset, such as dimensional activation [88] or neural complexity [21,89], although some of them remain to be made operational in a computationally tractable manner. We consider it likely that these measures would also show a pattern unique to conscious perception. The present work suggests that, rather than hoping for a putative unique marker (the neural correlate of consciousness), a more mature view of conscious processing should consider that it relates to a distributed pattern of brain activation that occurs at a specific level within a complex anatomical and functional architecture, and that it can therefore be reflected by many partially overlapping physiological measures.
Experiments were approved by the Ethical Committee for Biomedical Research of Pitié-Salpêtrière Hospital in Paris (agreement #99–04 issued on 15 December 2004), participants gave informed consent, and all clinical investigation have been conducted according to the principles expressed in the Declaration of Helsinki. Ten patients (five men) suffering from drug-refractory epilepsy were stereotactically implanted with depth electrodes as part of a presurgical evaluation. One patient was implanted twice. Patient ages ranged from 18 to 47 y. Eight patients were right-handed; one man was left-handed; one woman was ambidextrous. Neuropsychological assessment revealed normal or mild impairment in general cognitive functioning: verbal IQ ranged from 65 to 97 and performance IQ from 64 to 120. On each trial, patients were randomly presented either with a masked word (33%), a masked blank (17%), a visible word (33%), or a visible blank (17%). A total number of 548 trials were presented for each patient. Words or blanks were presented for 29 ms and were preceded by a visual forward mask (string of hash signs [#]) presented for 71 ms, and were followed by a backward mask (string of ampersands [&]) presented for 400 ms (see Figure 1). Words or blanks were made visible by simply removing the backward mask. Although mask removal in itself affected brain activity, in order to discard the activation induced by the masks, we systematically subtracted each word-present condition with its corresponding blank condition, thus isolating the processing path of the masked or unmasked word. In order to maximize attentional engagement and word processing, participants were engaged in a forced-choice task of categorizing each word as threatening or nonthreatening, even on the masked trials. Subjects responded by manually pressing one of two response buttons with the left and right index fingers, and hand response instructions were inverted halfway through the experiment. To prevent automatic stimulus–response learning, we used two distinct sets of 92 French words each for the masked trials and the visible trials, so that the masked words were never seen consciously. In each list, half of the words were threatening (e. g. , danger, kill), with variable frequencies, lengths (three to eight letters) and lexical categories (verbs and nouns). The other half included nonthreatening, emotionally neutral words (e. g. , cousin, see), matched for frequency, length, and category. RTs of less than 250 ms or more than 5,000 ms were discarded. Median RTs were calculated for each patient and for each condition. RTs were compared across conditions using analysis of variance (ANOVA) F-tests. For each patient, we also computed objective discriminability (d′) separately for each of the two masking conditions. We then assessed better-than-chance performance on d′ using both individual and group statistical criteria. First, individual χ2 statistics were calculated for each condition: proportions of correct and incorrect responses to emotional and neutral words were compared with those in the expected random distribution. Second, group analysis was performed using a Z-test testing distributions of d′ against a zero-centered Gaussian. Patients were implanted intracerebrally with depth electrodes, each bearing four to eight recording sites (Ad-Tech Medical Instruments). Recording sites were 2. 3-mm long, 1-mm diameter cylinders, separated by a distance of 10 mm. The structures to be explored were defined on the basis of ictal manifestations, electroencephalography (EEG), and neuroimaging studies. For each recording site, the Cartesian coordinates (x, y, z) were calculated after normalization of the anatomical three-dimensional spoiled gradient recalled (SPGR) anatomical cerebral MRI into Talairach space using SPM2 (Matlab). iERPs were digitized at 400 Hz, referenced to the vertex (Nicolet-BMSI). Epochs were then extracted (−500 ms plus 1,000 ms from word onset), submitted to automatic artifact rejection (±300-mV threshold), visually inspected, and notch filtered (50 Hz) using EEGLAB software (Matlab) [90]. Recording sites with more than 5% of rejected trials were discarded from analysis. To maximally prevent the measurement of the same electrical signals by multiple sites, for instance, through the common vertex reference, bipolar montages were calculated by subtracting the signals recorded from adjacent sites belonging to the same-depth electrode. This calculation resulted in a total of 176 bipolar recordings (here called “electrodes” for simplicity) across ten patients (corresponding to 11 distinct implantations). For each bipolar montage, the Cartesian coordinates (x, y, z) were calculated as the medium location of the two adjacent recording sites, resulting in the following anatomical repartition: 55 electrodes in the occipital lobe, 78 in the temporal lobe, 24 in the parietal lobe, and 19 within frontal lobes. For simplicity, in the remnant of this paper, we refer to these recomputed bipolar montages as “electrodes. ” Eighty-two electrodes were recorded within the left hemisphere and 94 in the right hemisphere. Baseline correction (from −500 to 0 ms before word onset) was applied, and potentials were averaged from −500 up to 800 ms in order to keep the same temporal windows for ERPs and time-frequency measures. We used a three-step strategy to assess the statistical significance of our results. First, the ERPs of masked words or of unmasked words were compared with those of masked or unmasked blanks by using sample-by-sample t-tests, with a criterion of significance being set at p < 0. 001 for a minimum of five consecutive samples. Second, we further checked the statistical significance of the observed effects (number of consecutive samples with p < 0. 001 on t-test) through Monte Carlo permutations. This method provides an estimation of type I error rate (false positives) by using resampling procedures. Precisely, for each patient and for each electrode showing a significant effect, we computed 20,000 random permutations of the observed trials in two surrogate conditions: trials were randomly assigned to one of the two groups, and then for each permutation, we counted the number of surrogate effects satisfying the observed effect anywhere within a time window of 0–1,000 ms after stimulus onset. Third, statistical values obtained in the Monte Carlo procedure were corrected for multiple comparisons across electrodes using the false discovery rate procedure [91]. The false discovery rate of a test is defined as the expected proportion of false positives among the declared significant results. Spectral analysis is exquisitely sensitive to small subcritical epileptic events of small amplitude, which are often hard to detect on conventional voltage time series yet can severely impact on time-frequency diagrams. For spectral analysis, our first stage was therefore a visual inspection of the individual time-frequency diagrams of all electrodes. Artifacts, in the form of large broad-band excursions on occasional trials, were detected in 19 additional electrodes that were therefore eliminated from further analysis. For the remaining 147 electrodes, we used the ‘newtimef' and ‘newcrossf' functions of EEGLAB software [90] to estimate and plot, respectively, the mean event-related (log) spectral perturbation (ERSP) and ITC around word onset. As illustrated in Figures 5 and 6, ERSP and ITC were first calculated separately within each of the four conditions, then the word-present and word-absent conditions within each masking condition were subtracted from each other to yield a time-frequency plot of masked and unmasked effects. We used a prestimulus baseline correction over −400 to 0 ms, and all results are expressed as increases or decreases relative to this baseline (in logarithmic decibel scale for ERSP, in coherence units ranging from 0 to 1 for ITC). Calculation was based on successive windows of 128 samples (= 320 ms) centered on time points −500 to 1,000 ms around stimulus onset. In order to avoid windowing artifacts, we only report results over a window of −400 to 800 ms. We used EEGLAB' s default algorithm (fast Fourier transform with Hanning window tapering), a frequency range of 0–100 Hz, and a padding ratio of 1. Prior to computation, individual trials were linearly detrended, and the mean ERP in each condition was removed. Thus, our analysis was aimed at detecting “induced” oscillatory activity, temporally associated with the stimuli but not phase-synchronized with them, while discarding any phase-synchronous “evoked” activity [92–96]. Because of the larger number of available electrodes, times, and frequencies, calculating a corrected-level statistic that evaluates the level of significance of a given time-frequency change in a given electrode poses a severe statistical problem. For simplicity, we therefore only tested significance of effects across groups of electrodes and time-frequency regions of interest. For statistical purposes, we distinguished three time periods (100–200,200–300, and 300–500 ms relative to word onset) and four frequency bands (alpha = 8–13 Hz; beta = 13–30 Hz; low gamma = 30–50 Hz; and high gamma = 50–100 Hz), thus defining 12 time-frequency regions of interest. For each region, we then computed the mean ERSP for each of the 147 electrodes, and then performed t-tests across electrodes to evaluate the significance of the activity induced by masked and unmasked words relative to zero (i. e. , relative to prestimulus baseline) and relative to each other. Unless otherwise stated, p-values are Bonferroni corrected for the 12 regions tested, and we only report Bonferroni-corrected effects at p < 0. 05. Identical analyses were performed on mean phase synchrony, except that there were now measures from 1,283 electrode pairs. We adapted a Matlab software package developed by Anil K. Seth [63]. Because our goal was to establish whether relations of causality between electrodes change in the course of the trial, we performed our analyses on successive time windows of 320-ms width, spaced every 25 ms, with Hanning window tapering. For each such window, for each of the four experimental conditions, and for each pair of distinct electrodes (i, j), the software computed two linear regressions. The first is an autoregressive model that predicts the signal observed on electrode i at time t based on the signal of the same electrode i at previous times t − δt, t − 2δt, … t − nδt. The second model is a causal model that adds as regressors to the above regression the signals of the other electrode j measured at previous times t − δt, t − 2δt, … t − nδt. Here the value of n was fixed at eight retrospective samples (= 20-ms retrospective time window) after piloting showed essentially similar results with n = 4 or n = 16. An associated F-value then probes whether the second causal regression accounted for significantly more variance than the first autoregressive model, indicating a putative causal influence of electrode j on electrode i (see Figure 9 for an example). Seth (2005) suggests using the logarithm of the F-test as an index of causality strength, but a problem with this index is that it varies with the number of trials, which differed in the word-present and word-absent conditions [63]. We therefore used a causal index independent of run length: the amount of residual variance that was gained by the second model compared to the first, expressed as a percentage of the residual variance in the second model. A general finding (see, e. g. , Figure 9) was that the presentation of the masks alone already created a considerable increase in Granger causality relative to the baseline. Because we were interested in the further increases due to the presence of the words, over and above the effect of the masks, we calculated a “causal gain” by subtracting the causal index in the word-absent condition from the causal index in the word-present condition. Finally, note that the causal gain is still a directional measure: there are distinct causal gains for the effects of electrode j onto electrode i and vice-versa. In the results section, we therefore perform the analysis in two steps: (1) analysis of the mean causal gain, averaged across the two directions of causality, thus probing the existence of causal relations independently of their direction; (2) analysis of the “causal imbalance, ” obtained by subtracting the causal gains in the feedforward and feedback directions, thus probing the existence of a preferred direction of causality. For the latter analysis, we defined the feedforward direction as a causal influence of the more posterior electrode onto the more anterior electrode (in case their y coordinates were identical, we used the z coordinate to define as feedforward an effect of the lowest onto the highest electrode). A positive causal imbalance, therefore, indicated stronger causality in the feedforward or bottom-up direction, and a negative causal imbalance indicated a stronger feedback or top-down causality. Statistical significance was evaluated by t-tests over the 1,806 electrode pairs, on causal gains averaged over time windows of 100–200,200–300, and 300–500 ms. Unless otherwise state, p-values are Bonferroni corrected for the three windows tested.
What is the neural signature of the conscious perception of a visual stimulus? To address this question, we recorded neural activity directly from the brains of human subjects (who were undergoing neural surgery for medical reasons). This rare opportunity afforded greater spatial and temporal resolution than noninvasive methods used previously to probe the neural basis of consciousness. We compared neural activity concomitant with conscious and nonconscious processing of words by using a visual masking procedure that allowed us to manipulate the conscious visibility of briefly masked words. Nonconscious processing of words elicited short-lasting activity across multiple cortical areas, including parietal and visual areas. In sharp contrast, only consciously perceived words were accompanied by long-lasting effects (>200 ms) across a great variety of cortical sites, with a special involvement of the prefrontal lobes. This sustained pattern of neural activity was characterized by a specific increase of coherence between distant areas, suggesting conscious perception is broadcasted widely across the cortex.
neuroscience
Converging Intracranial Markers of Conscious Access