First, we investigated whether the sensory attenuation for expected object stimuli was equally present when participants attended the objects or not, focusing on our a priori defined ROIs (see Figure 1A): primary visual cortex (V1), object-selective lateral occipital complex (LOC), and temporal occipital fusiform cortex (TOFC). In all three regions, expectation suppression was robustly present when participants attended the objects (V1: t₍₃₃₎ = 3.573, p=0.001, d_z = 0.613; LOC: t₍₃₃₎ = 3.860, p=5.0e-4, d_z = 0.662; TOFC: t₍₃₃₎ = 5.133, p=1.2e-5, d_z = 0.880), but absent when participants attended the characters at fixation; that is, when the predictable objects were unattended (V1: t₍₃₃₎ = −0.216, p=0.830, d_z = −0.037; LOC: t₍₃₃₎ = −0.831, p=0.412, d_z = −0.143; TOFC: t₍₃₃₎ = 0.072, p=0.943, d_z = 0.012). Indeed, Bayesian analyses showed moderate support for the null hypothesis (BF₁₀ <1/3) of no expectation suppression in all three regions during the character categorization task (V1: BF₁₀ = 0.188; LOC: BF₁₀ = 0.253; TOFC: BF₁₀ = 0.184). The robustness of this distinct pattern of expectation suppression for the two conditions was statistically confirmed by an interaction analysis (expectation by attention interaction, V1:, F_(1,33) = 7.706, p=0.009, η²=0.189; LOC: F_(1,33) = 12.580, p=0.001, η²=0.276; TOFC: F_(1,33) = 16.955, p=2.4e-4, η²=0.339).

Figure 1

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Figure 1—source data 1

Expectation suppression within the ventral visual stream depends on attention.

The source data file contains a separate JASP file per ROI, containing BOLD data for expected and unexpected stimuli for both attention conditions (objects attended and unattended tasks; Figure 1A). Also contained is a JASP file showing expectation suppression per ROI split into stimulus driven and not stimulus driven voxel (Figure 1B).

https://doi.org/10.7554/eLife.47869.003

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Thus, in V1, LOC, and TOFC, there was a significant suppression of BOLD responses for expected compared to unexpected object stimuli exclusively during the object categorization task. No such modulation of BOLD responses by expectation was observed in the objects unattended condition in any of the three a priori ROIs, and in fact, there was moderate evidence for the absence of such a modulation when objects were unattended. We repeated all ROI analyses within the same ROIs but with different ROI sizes in order to ensure that our results were not dependent on the a priori but arbitrarily defined ROI mask size. Results were highly similar (i.e., the same effects showing statistically significant results) to those mentioned above within all three ROIs (V1, LOC, TOFC) for all tested ROI sizes, ranging from 100 to 400 voxels (800 mm³ - 3200 mm³) in steps of 100 voxels. Thus, our results do not depend on the exact ROI size but represent responses within the respective areas well.

We also examined how expectation modulated neural activity outside our predefined ROIs by performing a whole-brain analysis. Results of this whole brain analysis are illustrated in Figure 2A. The upper row in Figure 2A shows extensive clusters of expectation suppression throughout the ventral visual stream when objects were attended, but no difference when the objects were unattended (middle row), leading to a significant interaction (bottom row). These results complement our ROI-based analysis by showing that the observed expectation suppression effect is not unique to the a priori defined ROIs but evident throughout the ventral visual stream.

Figure 2

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Figure 2—source data 1

Expectation suppression across cortex for attended object stimuli only.

The source data file contains nifti images for the whole brain contrast unexpected >expected (expectation suppression). Separate files are included for each attention condition, as well as their interaction (attended >unattended), both in terms of unthresholded parameter estimate, z and thresholded z-maps (Figure 2A). The thresholded z map of the conjunction analysis (Figure 2B) is also included.

https://doi.org/10.7554/eLife.47869.005

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Outside the ventral visual stream, additional clusters of expectation suppression are evident in anterior insula and the frontal operculum, the precentral and inferior frontal gyrus, superior frontal gyrus and supplementary motor cortex, superior parietal lobule, as well as parts of the cerebellum. All significant clusters are summarized in a table in Supplementary file 1. Again, all these non-sensory clusters showed reduced activity for expected objects only when the object stimuli were attended and categorized. There was no significant modulation of activity by expectation anywhere in the whole brain analysis when the objects were unattended.

During the object categorization task, the ability to form expectations about the trailing object stimulus was helpful for the participants, and indeed expected object stimuli were categorized more quickly and accurately (see Figure 5A and Expectations facilitate object classification). This begs the question whether the expectation suppression effect that we observed throughout multiple brain areas during the object categorization task reflects differences in task engagement. Participants had an incentive to (implicitly or explicitly) use their knowledge of the predictable relationship between the leading and trailing image to prepare their object categorization response. In order to examine which brain regions exhibited expectation suppression irrespective of the relevance of the predictable relationship between stimuli, we performed a conjunction analysis that highlighted regions that showed significant expectation suppression both in the current study (during the object categorization task) and in a similar study that we published previously (Richter et al., 2018). During this latter study, participants also attended the object stimuli, but were asked to press a button whenever an object appeared that was flipped upside-down. Upside-down images occurred rarely, and importantly, were not related to the (implicitly learned) statistical regularities. Figure 2B shows the whole-brain results of this conjunction analysis. Significant, bilateral clusters of expectation suppression were evident throughout most of the ventral visual stream. However, none of the non-sensory clusters showed significant expectation suppression during both experiments. Thus, only in the ventral visual stream we found strong and robust evidence for expectation suppression, regardless of whether the predictable relationship was task-relevant or task-irrelevant, as long as the predictable object pairs were attended.

Next, we investigated the stimulus specificity of expectation suppression. Stimulus specificity concerns the question whether only stimulus-driven voxels or also voxels that were not (strongly) driven by the object stimuli displayed expectation suppression. The rationale was that an unspecific suppression effect (i.e., expectation suppression that is also evident in not stimulus-driven voxels) may result from global non-sensory effects, such as changes in general arousal or global surprise signals. On the other hand, stimulus-specific suppression effects, being limited to stimulus-driven voxels, are rather suggestive of a more specific suppression mechanism that selectively operates on the neural populations that represent the expected stimulus; for example, the dampening of stimulus-specific prediction errors as a result of a match between prediction and input.

All three ROIs were split into two populations of gray matter voxels, according to their stimulus responsiveness (stimulus-driven: responding to the object images; not stimulus-driven: not significantly responding to the object images), using independent data from the localizer run. There were strong differences between the ROIs in terms of the stimulus specificity of expectation suppression (Figure 1B; ROI x drive interaction: F_{(1.245,41.080)} = 7.651, p=0.005, η²=0.188). Whereas there was clear evidence for a larger expectation suppression effect in stimulus-driven than not stimulus-driven voxels in higher visual areas (LOC: t₍₃₃₎ = 3.991, p=3.4e-4, d_z = 0.684; TOFC: t₍₃₃₎ = 4.654, p=5.1e-5, d_z = 0.798), suppression was not significantly different between stimulus-driven and not stimulus-driven voxels in V1 (t₍₃₃₎ = −1.057, p=0.298, d_z = −0.181). Indeed, a Bayesian analysis indicated moderate support for the absence of a difference between stimulus-driven and not stimulus-driven voxels in V1 (BF₁₀ = 0.307). Of note, all sub-populations in all three ROIs showed significant expectation suppression (all p<0.05), suggesting that there is a general suppression of activity for expected stimuli in visual cortex, irrespective of whether the visual cortical area is driven by the stimuli. However, in later visual cortical areas (LOC and TOFC) there was significantly more expectation suppression in neuronal subpopulations that were driven by the stimulus, implying a more selective suppression mechanism in these areas.

In view of the suggestion that a global, stimulus unspecific response modulation may partially account for expectation suppression, we performed an exploratory analysis to examine whether surprising stimuli were associated with a stronger pupil dilation in our task. Pupil responses have been with linked with changes in arousal (Reimer et al., 2014; Vinck et al., 2015), which in turn may account for the stimulus unspecific suppression component. Moreover, pupil dilation scales with surprise (Damsma and van Rijn, 2017; Kloosterman et al., 2015; Preuschoff et al., 2011). Thus, this account would predict enhanced pupil dilation to unexpected compared to expected stimuli when objects were attended.

There was indeed a larger pupil diameter for unexpected compared to expected trailing images during the objects attended task (Figure 3, left). This difference emerged gradually starting ~600 ms after the onset of the trailing object image, and was significant between 1.5–2.8 s, as assessed with a cluster permutation test (p_cluster = 0.017). When objects were unattended, no significant difference in pupil diameter was found between the expectation conditions, and in fact, no timepoint surpassed the cluster formation threshold (i.e., all timepoints p>0.05 uncorrected; Figure 3, right). However, the expectation induced difference in pupil diameter was not reliably different between attended and unattended stimuli (p_cluster = 0.393). Thus, the data showed that the pupil was significantly more dilated for unexpected than expected objects when the images were attended, mirroring the results of the neural data – albeit, without a reliable difference between attended and unattended stimuli. This tentatively suggests that the enhanced BOLD responses to unexpected stimuli might be partially accounted for by a global mechanism, such as increased arousal in response to surprising stimuli.

Figure 3 with 3 supplements see all

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Larger pupil dilations in response to unexpected compared to expected stimuli during the objects attended task.

The source data file contains the preprocessed pupil diameter traces (participants by timepoints) for each of the four experimental conditions separately (two attention by two expectation conditions).

https://doi.org/10.7554/eLife.47869.010

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We explored whether expectation suppression and pupil dilation differences between unexpected and expected objects were associated. In other words, we sought for evidence of an association between the effect of expectations on pupil dilation and the expectation induced neural response attenuation. For this analysis we rank correlated expectation suppression magnitudes with pupil dilation differences for each participant. Results, displayed in Figure 4A, suggest that, when objects were attended, expectation suppression in V1 was more pronounced for trailing images that also resulted in larger pupil dilation differences (t₍₃₁₎ = 2.464, p=0.019, d_z = 0.436). This association was not reliable in LOC (t₍₃₁₎ = 1.413, p=0.167, d_z = 0.250; BF₁₀ = 0.466) or TOFC (t₍₃₁₎ = 1.401, p=0.171, d_z = 0.248; BF₁₀ = 0.458). There was no correlation of pupil dilation differences and expectation suppression when stimuli were unattended in any of the ROIs (V1: t₍₃₁₎ = −0.159, p=0.875, d_z = −0.028; BF₁₀ = 0.191; LOC: t₍₃₁₎ = −0.125, p=0.901, d_z = −0.022; BF₁₀ = 0.190; TOFC: t₍₃₁₎ = 0.177, p=0.861, d_z = 0.031; BF₁₀ = 0.192). There was no significant overall difference in the correlation strength between attended and unattended stimuli (F_(1,31) = 1.892, p=0.179, η²=0.058), nor between ROIs (F_{(1.558,48.293)} = 0.134, p=0.823, η²=0.004), nor their interaction (F_(2,62) = 0.482, p=0.603, η²=0.015). Thus, when stimuli were attended there was evidence for an association of pupil dilation and expectation suppression in V1.

Figure 4

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Figure 4—source data 1

Neural effects of expectations are associated with pupil dilation differences and reaction time benefits.

The source data file contains two JASP files of the analyses conducted on the correlation coefficients (Fisher z-transformed Rho), correlating expectation suppression (neural metric) with (A) pupil dilation differences due to expectations and (B) RT benefits due to expectations (behavioral measure). Correlation coefficients for data from the three ROIs (V1, LOC, TOFC) and both attention tasks are provided.

https://doi.org/10.7554/eLife.47869.012

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In order to assess whether, concurrent with the neural effects of expectations, behavioral benefits of expectations were evident, we analyzed behavioral responses during MRI scanning in terms of reaction times (RTs) and response accuracy. Overall, the objects attended (classify electronic items) and objects unattended task (classify characters at fixation) showed very similar response accuracies (attended: 94.3 ± 5.4% vs. unattended: 94.0 ± 6.6%, mean ± SD) and only minor differences in RTs (attended: 574 ± 150 ms vs. unattended: 602 ± 131 ms, mean ± SD). This supports the notion that both tasks were of approximately equal difficulty.

During the object categorization task, participants could benefit from the foreknowledge of the identity of the trailing object image, as they were asked to categorize the trailing image. Such a benefit would however not be expected during the character categorization task, as the participants could fully ignore the object stimuli during this task. This is precisely what we observed, both in terms of accuracy and RTs (Figure 5A). During the object categorization task, participants were more accurate (W = 457, p=3.2e-4, r_B = 0.536) and faster (W = 9, p=3.8e-9, r_B = −0.970) for expected compared to unexpected trailing object stimuli. Conversely, during the character categorization task, no such benefit was observed in terms of accuracy (t₍₃₃₎ = 1.600, p=0.119, d_z = 0.274; BF₁₀ = 0.582) or RT (W = 252, p=0.447, r_B = −0.153; BF₁₀ = 0.273). The robustness of this distinct pattern of behavioral advantage for expected stimuli for the two conditions was statistically confirmed by an interaction analysis (accuracy: F_(1,33) = 5.203, p=0.029, η²=0.136; RT: F_(1,33) = 37.543, p=6.6e-7, η²=0.532).

Figure 5

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Behavioral results demonstrate statistical learning.

The source data file contains separate JASP files containing the behavioral performance data and conducted analyses for the object and letter classification tasks (both in terms of RTs and response accuracy; Figure 4A), as well as data from the post-scanning object recognition task (Figure 4B).

https://doi.org/10.7554/eLife.47869.014

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In order to explore whether the observed expectation suppression is associated with the behavioral benefits due to expectations, we correlated the magnitude of expectation suppression and the expectation induced RT benefits. Results, illustrated in Figure 4B, show that when the predictable objects were attended, behaviorally observed expectation RT benefits and neurally observed expectation suppression were associated in both, V1 (t₍₃₃₎ = 2.442, p=0.020, d_z = 0.419) and TOFC (t₍₃₃₎ = 2.236, p=0.032, d_z = 0.384), but no reliable correlation was found in LOC (t₍₃₃₎ = 1.384, p=0.176, d_z = 0.237, BF₁₀ = 0.439). There was no association in any ROI when objects were unattended (V1: t₍₃₃₎ = −0.418, p=0.679, d_z = −0.072, BF₁₀ = 0.199; LOC: t₍₃₃₎ = −0.374, p=0.711, d_z = −0.064, BF₁₀ = 0.196; TOFC: t₍₃₃₎ = 0.179, p=0.859, d_z = 0.031, BF₁₀ = 0.186). On average correlations were not reliably larger when objects were attended than when they were unattended (attention: F_(1,33) = 2.920, p=0.097, η²=0.081). The pattern of results was similar in all ROIs (F_{(1.636,53.988)} = 0.615, p=0.513, η²=0.018; interaction: F_{(1.461,48.203)} = 0.381, p=0.619, η²=0.011). Thus, there is some evidence that when the objects were attended, participants showed larger benefits (faster RTs) for expected trailing images for which they also showed larger magnitudes of expectation suppression in V1 and TOFC. These results suggest that the neural and behavioral effects of expectations are associated.

An alternative explanation for the absence of sensory attenuation for expected object stimuli during the character categorization task is that statistical regularities for the objects that are presented during this condition have simply not been learned. This explanation may be unlikely, because the vast majority of exposure to the expected pairs takes places in the learning session, during which the same task (upside-down image detection) was used for all image pairs. However, it is nonetheless important to ensure that statistical regularities were learned for the image pair sets of the object and the character categorization task. To empirically address this, we tested whether participants had explicit knowledge of the statistical regularities for all object pairs. During this post-scanning pair recognition task, participants were asked to indicate which one of two trailing images was more likely given the leading image. Participants indicated the correct trailing image with above chance accuracy for both, the set of object pairs that was previously attended (Figure 5B; performance = 62.1 ± 1.8%, mean ± SE; t₍₃₃₎ = 6.803, p=4.6e-8, d_z = 1.167) and the set that was previously unattended (performance = 58.7 ± 2.2%; t₍₃₃₎ = 3.905, p=2.2e-4, d_z = 0.670). There was no statistically significant difference in accuracy on the pair recognition task between these sets of objects (W = 365, p=0.256, r_B = 0.227; BF₁₀ = 0.737). Reaction times were also similar for both sets of objects (objects previously attended: RT = 458.8 ± 25.4 ms; objects previously unattended: RT = 466.5 ± 25.9 ms; t₍₃₃₎ = −1.208, p=0.236, d_z = −0.207; BF₁₀ = 0.358). Thus, the image pairs belonging to both task conditions (objects attended and unattended tasks) were reliably learned, most likely during the extensive behavioral training session, and there was no evidence for a significant difference in the learning of associations for the two sets of object pairs. This strongly suggests that the differences in sensory attenuation between the two attention conditions are unlikely to be explained by differences in the strength of the association between the object pairs.

Finally, one may wonder whether the lack of expectation suppression when objects were unattended is due to the fact that object stimuli simply did not elicit strong activity in the ventral visual stream, as they were not in the focus of attention. Although all three ROIs showed reliable above-baseline activity also when objects were unattended (Figure 1A), and activity in LOC and TOFC was of similar amplitude during both conditions, the overall activity level may partly represent stimulus-unrelated activity. Therefore, in an explorative analysis, we assessed the strength of stimulus-specific activity in our three ROIs, by means of a decoding analysis of the trailing images. In brief, a multi-class decoder was trained to differentiate between the six trailing images per attention condition. The classifier was trained on data obtained in an independent localizer run, during which participants performed a separate task (detection of dimming of fixation dot). Performance of this decoder was tested on the mean parameter estimates per trailing image for each of the two attention conditions of the main MRI task data. Because each task was comprised of six trailing images, chance performance was 16.7%. One-sample t-tests or Wilcoxon signed rank test (as applicable) showed that in each of the three ROIs (V1, LOC, TOFC) and tasks (objects attended, objects unattended) object identity could be decoded above chance (V1 attended: 81.1%; W = 595, p=3.3e-7, r_B = 1; V1 unattended: 84.8%; W = 595, p=3.2e-7, r_B = 1; LOC attended: 37.3%; t₍₃₃₎ = 6.303, p=4.0e-7, d_z = 1.08; LOC unattended: 38.0%; W = 583, p=9.7e-7, r_B = 0.96; TOFC unattended: 25.0%; W = 476, p=0.002, r_B = 0.60), except in TOFC in the attended condition (TOFC attended: 19.6%; W = 383, p=0.143, r_B = 0.287; BF₁₀ = 0.388).

Moreover, decoding accuracy was not different between the objects attended and unattended conditions in any of the ROIs (V1: t₍₃₃₎ = −1.197, p=0.240, d_z = −0.205, BF₁₀ = 0.354; LOC: t₍₃₃₎ = −0.214, p=0.832, d_z = −0.037, BF₁₀ = 0.188; TOFC: t₍₃₃₎ = −1.726, p=0.094, d_z = −0.296, BF₁₀ = 0.697). This suggests that the object stimuli evoked a reliable stimulus-specific activity pattern in all three sensory regions, which was not significantly different in strength between the two tasks (object categorization and character categorization). Note, the participants’ task during the localizer run, which we used to train the classifier, was to detect a dimming of the fixation dot. As such, object stimuli were unattended during the localizer run, which may render the training data more similar in terms of attention allocation to the objects unattended task than the objects attended task. This may explain why decoding accuracy is similar, or even higher, for unattended compared to attended objects. More importantly, overall visual processing of the object stimuli was clearly present even when the objects stimuli were not attended, as the identity of the objects could be reliably decoded from neural activity patterns throughout the ventral visual stream when objects were unattended.

Our results show that a core neural signature of perceptual expectations, expectation suppression (Alink et al., 2010; den Ouden et al., 2010; Kok et al., 2012a; Richter et al., 2018), is only evident when attention is directed to the predictable object stimuli. Specifically, when participants engaged in an object categorization task, we found a wide-spread reduction of neural activity for expected compared to unexpected stimuli throughout the ventral visual stream (V1, LOC, TOFC), as well as several non-sensory areas (anterior insula, inferior frontal gyrus, precentral gyrus, and superior parietal lobule). Strikingly, no modulation of neural activity by expectation was found when attention was drawn away from the object stimuli.

Interestingly, by directly comparing our present data with a previous dataset, in which we used a similar design (reported in Richter et al., 2018), we established that expectation suppression is present throughout the ventral visual stream irrespective of whether predictions are task-irrelevant, as long as the object stimuli are attended. In contrast, the larger activity for surprising stimuli in non-sensory areas (insular, frontal and parietal cortex) was only observed in the context of task-relevant expectations. This suggests that neural activity in the ventral visual stream is modulated by conditional probabilities, as long as the stimuli are attended, while the modulations in non-sensory regions are probably reflecting differences in task demands, given that unexpected stimuli were more difficult to categorize (reflected by a cost in speed and accuracy). During the object classification task, unexpected objects may require response inhibition, reevaluation of the category, and thus a new response decision. Given that the anterior insula has been associated with task control, action evaluation (Brass and Haggard, 2010), as well as general attentional processes (Nelson et al., 2010), and inferior frontal gyrus with response inhibition (Aron et al., 2003; Aron et al., 2004), the interpretation that the expectation modulation in non-sensory clusters may reflect task related aspects, but not conditional probabilities per se, appears well-supported by previous research.

Finally, our results also demonstrate that larger expectation suppression effects in V1 and TOFC are associated with increased reaction time benefits afforded by expectations when people are judging the predictable objects. This suggests that the observed expectation suppression effect may not merely constitute an epiphenomenon of more resource efficient neural processing. Instead, given the present data, it is plausible that the behavioral advantage of predicting stimuli may partially be rooted in improved and more effective sensory processing already at the early stages of visual processing. Predictions may thus help in converging more rapidly on an interpretation of the current sensory input, thereby contributing to faster reactions to expected than unexpected stimuli.

Our results corroborate and extend earlier work by Larsson and Smith (2012), who observed that stimulus expectation only affected repetition suppression when the stimuli were attended. However, they appear at odds with several previous studies that have reported expectation suppression in the visual system for stimuli that were not task-relevant and thus appeared unattended (den Ouden et al., 2009; Kok et al., 2012a; Kok et al., 2012b). However, in all these studies, while the predictable stimuli were task-irrelevant, attention was not effectively drawn away by a competing stimulus that required attention. While our attention manipulation is also based on task-relevance, we do engage attention elsewhere using a competing task. This is a crucial difference between the present and previous studies, because it is likely that any supraliminal stimulus, in the absence of competition, will be attended to some degree, even if it is not task-relevant, especially if the stimulus is surprising (Horstmann and Herwig, 2015). Indeed, synthesizing earlier and current findings, we can conclude that expectation suppression in the visual system occurs irrespective of exact task goals and relevance of the predictable objects and their predictable relationship, but it is abolished by drawing attention away from the stimuli. This suggests that the integration of prior knowledge and sensory input is gated by attention – that is, prior knowledge only exerts an influence on stimuli that are in the current focus of attention, instead of automatically and pre-attentively modulating sensory input as an obligatory component of perceptual processing.

It is however possible that other, more ‘stubborn’ prior expectations (Yon et al., 2019) that are derived over longer (ontogenetic or phylogenetic) time scales may persist even when attention is drawn away, such as perceptual fill-in during the Kanizsa illusion (Kok et al., 2016). Therefore, it is crucial to discriminate between different types of predictions, as expectations of different sources may rely on different neural mechanisms and therefore have distinct properties. Similarly, for simple stimuli, such as oriented gratings (Kok et al., 2012a; Kok et al., 2012b) or simple sequences (Ekman et al., 2017), the resolution of expectations may depend less on recurrent processing throughout the visual hierarchy than for complex objects. Thus, it is conceivable that the automaticity of predictive processing partially depends on the complexity of the predictable stimuli and their association, with increasing complexity requiring increasing processing across the hierarchy, and in turn a focus of attention on the predictable stimuli.

In LOC and TOFC expectation suppression was largest in neural populations that were driven by the stimuli. Surprisingly, this was not the case in V1, where the suppression was uniformly present in the population that was driven by the stimuli and the population that was not. This replicates the results of our previous study (Richter et al., 2018) and suggests that the expectation suppression we observe in V1 is not the result of a stimulus-specific reduction in prediction error responses of neurons processing the stimulus. Rather, they suggest that the observed expectation suppression effect in V1 may be accounted for by a more general response modulation. Widespread nonperceptual modulations of visual cortical activity have been documented in response to unexpected events (Jack et al., 2006; Donner et al., 2008) and have been suggested to be linked to the cholinergic or noradrenergic system (Aston-Jones and Cohen, 2005; Yu and Dayan, 2005a). Interestingly, both the cholinergic and noradrenergic systems have also been associated with fluctuations in pupil dilation (Reimer et al., 2016). In line with this, we found a significantly enhanced pupil dilation in response to unexpected stimuli when the objects were attended. This suggests two possible global mechanisms which may partially account for the observed unspecific expectation suppression effect. Given that both pupil dilation (Reimer et al., 2014; Vinck et al., 2015) and the noradrenergic system (Berridge et al., 2012) are associated with arousal changes, it is possible that expectation suppression is partially accounted for by an increased arousal in response to surprising stimuli. A related explanation is that enhanced pupil dilation to surprising stimuli (Damsma and van Rijn, 2017; Kloosterman et al., 2015; Preuschoff et al., 2011) results in enhanced retinal illumination, which in turn leads to stronger responses in early visual areas (Haynes et al., 2004), which could potentially also contribute to stimulus unspecific expectation suppression in V1. These interpretations are further supported by the fact that expectation suppression and pupil dilation differences between unexpected and expected attended stimuli were associated, with trailing images that elicit larger pupil dilation differences also showing more pronounced expectation suppression in V1.

It is unlikely however that these explanations can fully account for the observed expectation suppression effect across the visual hierarchy, given the stimulus-specificity of suppression in LOC and TOFC. Also, it is important to bear in mind that earlier studies, using different stimuli and paradigms, did observe stimulus-specific expectation effects in V1 (Kok et al., 2012a; Gavornik and Bear, 2014). Combined, the evidence suggests that the resolution of prediction errors crucially depends on the visual areas that are specifically coding the feature that is diagnostic of an expectation confirmation or violation, while areas below this level may only witness an unspecific, global modulation in their response, signifying the binary expectation confirmation or violation.

Within the predictive coding framework, it has been suggested that attention modulates the gain of prediction error units (Feldman and Friston, 2010). On first glance, our results may not appear compatible with the suggestion that attention modulates the gain of prediction errors, because we observe a stimulus-specific bottom-up signal (prediction error) when stimuli are unattended, but no difference in the size of this prediction error between expected and unexpected stimuli. However, it is conceivable that the gain modulation of activity in prediction error units only occurs after the initial feedforward activity sweep, once the object predictions are strongly activated and start exerting an effect on the resolution of the prediction error. In particular, the response to unexpected attended stimuli may be upregulated by attention, while prediction errors for expected attended stimuli are rapidly resolved, thus resulting in the difference in activity for attended objects. On the other hand, when attention is drawn away from the object stimuli, a reduced gain on prediction error units results in the observed attenuation of overall BOLD responses, and an absence of a reliable difference between expected and unexpected stimuli. A closely related, but conceptually distinct, interpretation is that attention constitutes a (modulation of the) prior itself (Rao, 2005; Yu and Dayan, 2005b). On this account, attention boosts relevant predictions, as during the object classification task, thus leading to wide-spread expectation suppression, due to larger prediction errors for unexpected compared to expected stimuli. However, when attention is disengaged from the object stimuli, object predictions are not generated, and thus do not exert an effect on sensory processing.

One may wonder whether the character categorization task at fixation may have drawn attention away from the objects so forcefully that the object stimuli were no longer processed by sensory cortex. It is important to note here that, although attention was engaged at fixation by the character categorization task, this task was of trivial difficulty. Thus, it seems unlikely that attentional resources were exhaustively engaged by the task, preventing any processing of the surrounding object stimuli, thereby causing the absence of predictive processing. Indeed, behavioral performance was at ceiling during both tasks. Furthermore, even when objects were unattended reliable visual processing took place, as evident by strong responses and object-specific neural patterns in the visual ventral stream. This suggests that in-depth visual processing of object stimuli did occur in the absence of attention, but predictive processes in particular ceased.

Another alternative explanation of the present results could be that predictive relationships were not learned for the set of objects that were used during the character categorization task, thereby accounting for the absence of a prediction effect. The pair recognition task at the end of the experiment however showed that associations were learned for both image pair sets. Thus, a lack of visual processing or absence of learning cannot account for the observed results. Also, it is worth noting that initially the used probabilistic associations (P(expected|cue)=0.5) may appear less strong than in some previous studies; for example, Egner et al. (2010), Kok et al. (2012a), and Summerfield et al. (2008) used P(expected|cue)=0.75. However, the likelihood ratio of expected/unexpected stimuli (0.5/0.1 = 5) used here is actually larger (i.e., each unexpected image is more surprising) than in the cited studies (0.75/0.25 = 3). Moreover, similar probabilistic associations have been successfully employed in studies investigating neural effects of statistical learning in both non-human primates (Meyer and Olson, 2011) and humans (Richter et al., 2018). In short, the utilized conditional probabilities are comparable to previous studies investigating statistical learning. Finally, it is worth emphasizing that neither adaptation nor familiarity effects can account for the observed results, because all trailing objects served both as expected and unexpected images, depending only on temporal context (i.e., the leading image).

In sum, our results suggest that visual statistical learning results in attenuated sensory processing for predicted input, but only when this input is attentively processed. Thus, attention seems to gate the integration of prior knowledge and sensory input. This places important constraints on neurocomputational theories that cast perceptual inference as a process of automatic integration of prior and sensory information.

The present study was preregistered at Open Science Framework (OSF) before any data were acquired. The preregistration document is available at DOI: 10.17605/OSF.IO/36TE7. All procedures and criteria outlined in the preregistration document were followed, unless explicitly specified in the Materials and method section below. In this manuscript, only research question 1 of the preregistration document is addressed. All data analyzed in the present paper are available here: http://hdl.handle.net/11633/aacg3rkw.

Our target sample size was n = 34. This sample size was chosen to ensure 80% power for detecting at least a medium effect size (Cohen’s d ≥ 0.5) with a two-sided paired t-test at an alpha level of 0.05. In total, 38 healthy, right-handed participants were recruited from the Radboud University research participation system. The study followed institutional guidelines of the local ethics committee (CMO region Arnhem-Nijmegen, The Netherlands). We excluded four participants, following our exclusion criteria (see preregistration document and Data Exclusion) resulting in the desired sample size of n = 34 participants (25 females, age 24.9 ± 4.8 years, mean ± SD) for data analysis. Of these four exclusions, three exhibited excessive motion during scanning, and one was caused by the participant falling asleep, thus resulting in an incomplete data set.

The following preregistered criteria were utilized for the rejection of data. If any of the following criteria applied, data from that participant were excluded from all analyses. (1) Subpar fixation behavior during scanning, indicative by a total duration of closed eyes exceeding 3 SD above the group mean – only trials with stimuli were considered in this analysis; that is, null events and instruction or performance screens were not included. (2) Excessive relative motion larger than ½ voxel size (i.e., 1 mm) during MRI scanning, as indexed by the total number of these motion events exceeding 2 SD above the group mean. (3) Task performance during MRI scanning indicating frequent attentional lapses, as indicated by a mean error rate 3 SD above the group mean.

A fourth rejection criterion, outlined in the preregistration document, based on chance level performance during the post-scan pair recognition task (see: Pair recognition task and 2AFC task in the preregistration document), was not enforced. This decision was based on feedback by participants, indicating that the short ITI during this task made it very challenging, even for participants who reported to have learned most of the associations. Thus, the preregistered pair recognition task based exclusion criterion would not fulfill the desired function of reliably indicating which participants did not explicitly learn the associations, as participants struggled with the task due to its fast pace. Indeed, the enforcement of the criterion would have resulted in the rejection of an additional nine participants (~26% of participants) from data analysis, which was deemed too stringent.

Sixty-four full color object stimuli were used during the experiment. The object images were a selection of stimuli from Brady et al. (2008) comprising typical object stimuli which were clearly electronic or non-electronic in nature (stimuli can be found here, DOI: 10.17605/OSF.IO/36TE7). Of these 64 object stimuli, 24 were randomly selected per participant, of which 12 were randomly assigned as leading images, while the other 12 served as trailing images. Thus, each specific image could occur as leading image for one participant, as trailing image for another participant, and not at all for a third participant, thereby minimizing the impact of any particular image’s features. Images spanned approximately 5° x 5° visual angle on a mid-gray background, both during the learning session and MRI scanning. During the learning session stimuli were presented on an LCD screen (BenQ XL2420T, 1920 × 1080 pixel resolution, 60 Hz refresh rate). During MRI scanning, stimuli were back-projected (EIKI LC-XL100 projector, 1024 × 768 pixel resolution, 60 Hz refresh rate) on an MRI-compatible screen, visible using an adjustable mirror mounted on the head coil.

We calculated the average relative luminance of the object stimuli by converting the stimulus images from sRGB to linear RGB, then calculated the relative luminance for all pixels (where relative luminance Y = 0.2126*R + 0.7152*G + 0.0722*B; Stokes et al., 1996), and finally averaged the obtained luminance values, thereby obtaining the mean relative luminance per image. On this relative luminance scale, 0 would be a completely black image, while one would be a white image. The average relative luminance of the stimulus set was 0.225, while the relative luminance of the mid gray background, presented during the ITI, was 0.216.

Anatomical and functional images were acquired on a 3T Prisma scanner (Siemens, Erlangen, Germany), using a 32-channel head coil. Anatomical images were acquired using a T1-weighted magnetization prepared rapid gradient echo sequence (MP-RAGE; GRAPPA acceleration factor = 2, TR/TE = 2300/3.03 ms, voxel size 1 mm isotropic, 8° flip angle). Functional images were acquired using a whole-brain T2*-weighted multiband-6 sequence (time repetition [TR]/time echo [TE]=1000/34.0 ms, 66 slices, voxel size 2 mm isotropic, 75° flip angle, A/P phase encoding direction, FOV = 210 mm, BW = 2090 Hz/Px). To allow for signal stabilization, the first five volumes of each run were discarded.

In an exploratory analysis we sought to provide additional evidence for an association between pupil dilation and expectation suppression. To this end, we correlated expectation suppression with pupil dilation differences between expected and unexpected objects per trailing image. First, we obtained per trailing image parameter estimates by fitting a voxel-wise GLM to the fMRI data for each run, following the same procedure as for the main fMRI data analysis, outlined in fMRI data analysis and Region of interest (ROI) analysis. The only difference was that a separate regressor per trailing image and expectation condition was fit, thus resulting in a model with 12 regressors of interest (six trailing images * two expectation conditions). As before, data were combined across runs using FSL’s fixed effect analysis. The resulting parameter estimate maps were extracted for each ROI (V1, LOC, TOFC) and converted to percent signal change. Finally, for each participant we calculated expectation suppression for each trailing image (expectation suppression = BOLD_unexpected – BOLD_expected). Similarly, we calculated the difference in pupil dilation between unexpected and expected occurrences of each trailing image. For this we extracted the preprocessed (see: Pupillometry) pupil size estimates for each trial and calculated the mean pupil size within the time window that showed a significant difference in pupil dilation between unexpected compared to expected attended stimuli on the group level (Figure 3, left panel); that is, 1.52 to 2.88 s after trailing image onset. Next, we calculated the average difference in pupil size for each trailing image for unexpected compared to expected occurrences, thus yielding six pupil size difference scores (unexpected – expected) for both attention tasks per participant. Spearman’s rank correlation was then used to estimate the correlation between the pupil dilation differences and expectation suppression magnitudes for each participant. Therefore, this correlation expresses the correlation in ranks of pupil dilation differences and expectation suppression magnitude for the trailing images, with positive correlations indicating that trailing images with large expectation suppression effects are also associated with larger pupil dilation differences. The obtained correlation coefficients were Fisher z-transformed and compared against zero (no correlation) using one-sample t-tests for each ROI and attention condition. We also submitted the coefficients to a repeated measures ANOVA with ROI and attention as factors.

In another exploratory analysis we investigated the relationship between behavioral and neural benefits of expectations by correlating expectation suppression with the behavioral RT benefit for expected stimuli observed during MRI scanning. First, we calculated the RT benefit for each trailing image during the main fMRI task (RT_benefit = RT_unexpected – RT_expected, per trailing image). Within each ROI we then correlated expectation suppression per trailing image (see: Linking pupil and neural measures) with RT benefit per trailing image using Spearman's rank correlation. Thus, this correlation coefficient indicates the rank correlation of expectation induced RT benefits and expectation suppression magnitude for the different trailing images. For statistical inference across participants, we Fisher z-transformed the correlation coefficients, and tested whether the observed correlation coefficients differ from zero (no correlation) in each condition by performing one-sample t-tests for each ROI and attention task separately. Finally, we also compared the magnitude of the correlations between ROIs and attention tasks using a 3 × 2 repeated measures ANOVA with ROI and attention condition (task) as factors.

In order to further evaluate any non-significant tests, in particular simple main effects, we performed the Bayesian equivalents of the above outlined analyses. JASP 0.9.0.1 (JASP Team, 2018; RRID:SCR_015823) was used to perform all Bayesian analyses, using default settings. Thus, for Bayesian t-tests a Cauchy prior width of 0.707 was chosen. Qualitative interpretations of Bayes Factors are based on criteria by Lee and Wagenmakers (2013).

MRI data preprocessing and analysis was performed using FSL 5.0.11 (FMRIB Software Library; Oxford, UK; www.fmrib.ox.ac.uk/fsl; Smith et al., 2004; RRID:SCR_002823). Custom Python 2.7.13 (Python Software Foundation, RRID:SCR_008394) scripts were used for additional analyses, data handling, statistical tests and data visualization. The following Python libraries and toolboxes were used: NumPy 1.12.1 (van der Walt et al., 2011; RRID:SCR_008633), SciPy 0.19.0 (Jones et al., 2001; RRID:SCR_008058), Matplotlib 1.5.1 (Hunter, 2007; RRID:SCR_008624), Statsmodels 0.8.0 (www.statsmodels.org) and Scikit-learn 0.18.1 (Pedregosa et al., 2011; RRID:SCR_002577). Additionally, Slice Display (Zandbelt, 2017), a MATLAB 2017a (The MathWorks, Inc, Natick, Massachusetts, United States, RRID:SCR_001622) data visualization toolbox, was used for displaying whole-brain results. JASP 0.9.0.1 (JASP Team, 2018; RRID:SCR_015823) was used for Bayesian analyses and RM ANOVAs. Stimuli were presented using Presentation software (version 18.3, Neurobehavioral Systems, Inc, Berkeley, CA, RRID:SCR_002521).

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

We thank Matthias Ekman, Mariya Manahova, Peter Kok and Karl Friston for helpful comments and discussions of the manuscript and results. We thank José Marques for assistance with MR sequence questions.

Human subjects: The study followed institutional guidelines of the local ethics committee (CMO region Arnhem-Nijmegen, The Netherlands; Protocol CMO2014/288), including informed consent of all participants.

© 2019, Richter and de Lange

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