Déjà vu and prescience in a case of severe episodic amnesia following bilateral hippocampal lesions.

Several studies pertaining to déjà vu have consistently made a connection with the perirhinal region, a region located below the hippocampus. This idea is strengthened by the fact that déjà vu is an erroneous sense of familiarity and that familiarity appears to largely depend on the perirhinal region in healthy subjects. In this context, the role of the hippocampus is particularly unclear as it is unknown whether or not it plays a role in the genesis of déjà vu. We report on the case of OHVR, an epileptic patient who suffers from severe episodic amnesia related to massive isolated bilateral damage to the hippocampus. In contrast, the perirhinal region is intact structurally and functionally. This patient reports frequent déjà vu but also another experiential phenomenon with a prominent feeling of prescience, which shows some of the characteristics of déjà vécu. She clearly distinguishes both. She also developed a form of synaesthesia by attributing affective valence to numbers. This study shows that déjà vu can occur in cases of amnesia with massively damaged hippocampi and confirms that the perirhinal region is a core region for déjà vu, using a different approach from previous reports. It also provides clues about a potential influence of hippocampal alterations in déjà vécu.

Synesthesia in children with difficulties in written language learning.

We tested whether the acquisition of grapheme-color synesthesia during childhood is related to difficulties in written language learning by measuring whether it is more frequent in 79 children receiving speech and language therapy for such difficulties than in the general population of children (1.3%). By using criteria as similar as possible to those used in the reference study (Simner et al., 2009), we did not identify any synesthete (Bayesian 95% credible interval [0, 4.5]% for a flat prior). The odds of the null model (no difference between 0/79 and 1.3%) over alternative models is 28 (Bayes Factor). A higher prevalence of grapheme-color synesthetes among children with learning difficulties is therefore very unlikely, questioning the hypothesis of a link between synesthesia and difficulties in language acquisition. We also describe the difficulty of diagnosing synesthesia in children and discuss the need for new approaches to do so.

Multivariate pattern analysis of fMRI data for imaginary and real colours in grapheme-colour synaesthesia.

Grapheme-colour synaesthesia is a subjective phenomenon related to perception and imagination, in which some people involuntarily but systematically associate specific, idiosyncratic colours to achromatic letters or digits. Its investigation is relevant to unravel the neural correlates of colour perception in isolation from low-level neural processing of spectral components, as well as the neural correlates of imagination by being able to reliably trigger imaginary colour experiences. However, functional MRI studies using univariate analyses failed to provide univocal evidence of the activation of the "colour network" by synaesthesia. Applying multivariate (multivoxel) pattern analysis (MVPA) on 20 synaesthetes and 20 control participants, we tested whether the neural processing of real colours (concentric rings) and synaesthetic colours (black graphemes) shared patterns of activations. Region of interest analyses in retinotopically and anatomically defined visual areas revealed neither evidence of shared circuits for real and synaesthetic colour processing, nor processing difference between synaesthetes and controls. We also found no correlation with individual experiences, characterised by measuring the strength of synaesthetic associations. The whole brain searchlight analysis led to similar results. We conclude that revealing the neural coding of the synaesthetic experience of colours is a hard task which requires the improvement of our current methodology: for example involving more individuals and achieving higher MR signal to noise ratio and spatial resolution. So far, we have not found any evidence of the involvement of the cortical colour network in the subjective experience of synaesthetic colours.

Shared premotor activity in spoken and written communication.

The aim of the present study was to uncover a possible common neural organizing principle in spoken and written communication, through the coupling of perceptual and motor representations. In order to identify possible shared neural substrates for processing the basic units of spoken and written language, a sparse sampling fMRI acquisition protocol was performed on the same subjects in two experimental sessions with similar sets of letters being read and written and of phonemes being heard and orally produced. We found evidence of common premotor regions activated in spoken and written language, both in perception and in production. The location of those brain regions was confined to the left lateral and medial frontal cortices, at locations corresponding to the premotor cortex, inferior frontal cortex and supplementary motor area. Interestingly, the speaking and writing tasks also appeared to be controlled by largely overlapping networks, possibly indicating some domain general cognitive processing. Finally, the spatial distribution of individual activation peaks further showed more dorsal and more left-lateralized premotor activations in written than in spoken language.

Two paradigms of bistable plaid motion reveal independent mutual inhibition processes.

Perception is sometimes bistable, switching between two possible interpretations. Levelt developed several propositions to explain bistable perception in binocular rivalry, based on a model of competing neural populations connected through reciprocal inhibition. Here we test Levelt's laws with bistable plaid motion. Plaids are typically tristable, either a coherent pattern, transparent with one component in front, or transparent with the opposite depth order. In Experiment 1, we use a large angle between component directions to prevent plaid coherence, limiting the ambiguity to alternations of grating depth order. Similar to increasing contrast in binocular rivalry, increasing component speed led to higher switch rates (analogous to Levelt's fourth proposition). In Experiment 2, we used occlusion cues to prevent one depth order and limit bistability to one transparent depth order alternating with coherence. Increasing grating speed shortened coherent motion periods but left transparent periods largely unchanged (analogous to Levelt's second proposition). Switch dynamics showed no correlation between the experiments. These data suggest that plaid component speed acts like contrast in binocular rivalry to vary switch dynamics through a mutual inhibition model. The lack of correlation between both experiments suggests reciprocal inhibition mediates bistability between a variety of neural populations across the visual system.

Magnetic resonance imaging does not reveal structural alterations in the brain of grapheme-color synesthetes.

Several publications have reported structural changes in the brain of synesthetes compared to controls, either local differences or differences in connectivity. In the present study, we pursued this quest for structural brain differences that might support the subjective experience of synesthesia. In particular, for the first time in this field, we investigated brain folding in comparing 45 sulcal shapes in each hemisphere of control and grapheme-color synesthete populations. To overcome flaws relative to data interpretation based only on p-values, common in the synesthesia literature, we report confidence intervals of effect sizes. Moreover, our statistical maps are displayed without introducing the classical, but misleading, p-value level threshold. We adopt such a methodological procedure to facilitate appropriate data interpretation and promote the "New Statistics" approach. Based on structural or diffusion magnetic resonance imaging data, we did not find any strong cerebral anomaly, in sulci, tissue volume, tissue density or fiber organization that could support synesthetic color experience. Finally, by sharing our complete datasets, we strongly support the multi-center construction of a sufficient large dataset repository for detecting, if any, subtle brain differences that may help understanding how a subjective experience, such as synesthesia, is mentally constructed.

Comment on "Ducklings imprint on the relational concept of 'same or different'".

Martinho and Kacelnik's (Reports, 15 July 2016, p. 286) finding that mallard ducklings can deal with abstract concepts is important for understanding the evolution of cognition. However, a statistically more robust analysis of the data calls their conclusions into question. This example brings to light the risk of drawing too strong an inference by relying solely on P values.

Are synesthetes exceptional beyond their synesthetic associations? A systematic comparison of creativity, personality, cognition, and mental imagery in synesthetes and controls.

Synesthesia has historically been linked with enhanced creativity, but this had never been demonstrated in a systematically recruited sample. The current study offers a broad examination of creativity, personality, cognition, and mental imagery in a small sample of systematically recruited synesthetes and controls (n = 65). Synesthetes scored higher on some measures of creativity, personality traits of absorption and openness, and cognitive abilities of verbal comprehension and mental imagery. The differences were smaller than those reported in the literature, indicating that previous studies may have overestimated group differences, perhaps due to biased recruitment procedures. Nonetheless, most of our results replicated literature findings, yielding two possibilities: (1) our study was influenced by similar biases, or (2) differences between synesthetes and controls, though modest, are robust across recruitment methods. The covariance among our measures warrants interpretation of these differences as a pattern of associations with synesthesia, leaving open the possibility that this pattern could be explained by differences on a single measured trait, or even a hidden, untested trait. More generally, this study highlights the difficulty of comparing groups of people in psychology, not to mention neuropsychology and neuroimaging studies. The requirements discussed here - systematic recruitment procedures, large battery of tests, and large cohorts - are best fulfilled through collaborative efforts and cumulative science.

Quantitative evaluation of fMRI retinotopic maps, from V1 to V4, for cognitive experiments.

FMRI retinotopic mapping is a non-invasive technique for the delineation of low-level visual areas in individual subjects. It generally relies upon the analysis of functional responses to periodic visual stimuli that encode eccentricity or polar angle in the visual field. This technique is used in vision research when the precise assignation of brain activation to retinotopic areas is an issue. It involves processing steps computed with different algorithms and embedded in various software suites. Manual intervention may be needed for some steps. Although the diversity of the available processing suites and manual interventions may potentially introduce some differences in the final delineation of visual areas, no documented comparison between maps obtained with different procedures has been reported in the literature. To explore the effect of the processing steps on the quality of the maps obtained, we used two tools, BALC, which relies on a fully automated procedure, and BrainVoyager, where areas are delineated "by hand" on the brain surface. To focus on the mapping procedures specifically, we used the same SPM pipeline for pretreatment and the same tissue segmentation tool. We document the consistency and differences of the fMRI retinotopic maps obtained from "routine retinotopy" experiments on 10 subjects. The maps obtained by skilled users are never fully identical. However, the agreement between the maps, around 80% for low-level areas, is probably sufficient for most applications. Our results also indicate that assigning cognitive activations, following a specific experiment (here, color perception), to individual retinotopic maps is not free of errors. We provide measurements of this error, that may help for the cautious interpretation of cognitive activation projection onto fMRI retinotopic maps. On average, the magnitude of the error is about 20%, with much larger differences in a few subjects. More variability may even be expected with less trained users or using different acquisition parameters and preprocessing chains.

A critical review of the neuroimaging literature on synesthesia.

Synesthesia refers to additional sensations experienced by some people for specific stimulations, such as the systematic arbitrary association of colors to letters for the most studied type. Here, we review all the studies (based mostly on functional and structural magnetic resonance imaging) that have searched for the neural correlates of this subjective experience, as well as structural differences related to synesthesia. Most differences claimed for synesthetes are unsupported, due mainly to low statistical power, statistical errors, and methodological limitations. Our critical review therefore casts some doubts on whether any neural correlate of the synesthetic experience has been established yet. Rather than being a neurological condition (i.e., a structural or functional brain anomaly), synesthesia could be reconsidered as a special kind of childhood memory, whose signature in the brain may be out of reach with present brain imaging techniques.

Assessment of the hemispheric lateralization of grapheme-color synesthesia with Stroop-type tests.

Grapheme-color synesthesia, the idiosyncratic, arbitrary association of colors to letters or numbers, develops in childhood once reading is mastered. Because language processing is strongly left-lateralized in most individuals, we hypothesized that grapheme-color synesthesia could be left-lateralized as well. We used synesthetic versions of the Stroop test with colored letters and numbers presented either in the right or the left visual field of thirty-four synesthetes. Interference by synesthetic colors was stronger for stimuli in the right hemifield (first experiment, color naming task). Synesthetes were also faster in the right hemifield when naming the synesthetic color of graphemes (second experiment). Overall, the lateralization effect was 7 ms (the 95% confidence interval was [1.5 12] ms), a delay compatible with an additional callosal transfer for stimuli presented in the left hemifield. Though weak, this effect suggests that the association of synesthetic colors to graphemes may be preferentially processed in the left hemisphere. We speculate that this left-lateralization could be a landmark of synesthetic grapheme-color associations, if not found for color associations learnt by non-synesthete adults.

Statistical inferences under the Null hypothesis: common mistakes and pitfalls in neuroimaging studies.

Published studies using functional and structural MRI include many errors in the way data are analyzed and conclusions reported. This was observed when working on a comprehensive review of the neural bases of synesthesia, but these errors are probably endemic to neuroimaging studies. All studies reviewed had based their conclusions using Null Hypothesis Significance Tests (NHST). NHST have yet been criticized since their inception because they are more appropriate for taking decisions related to a Null hypothesis (like in manufacturing) than for making inferences about behavioral and neuronal processes. Here I focus on a few key problems of NHST related to brain imaging techniques, and explain why or when we should not rely on "significance" tests. I also observed that, often, the ill-posed logic of NHST was even not correctly applied, and describe what I identified as common mistakes or at least problematic practices in published papers, in light of what could be considered as the very basics of statistical inference. MRI statistics also involve much more complex issues than standard statistical inference. Analysis pipelines vary a lot between studies, even for those using the same software, and there is no consensus which pipeline is the best. I propose a synthetic view of the logic behind the possible methodological choices, and warn against the usage and interpretation of two statistical methods popular in brain imaging studies, the false discovery rate (FDR) procedure and permutation tests. I suggest that current models for the analysis of brain imaging data suffer from serious limitations and call for a revision taking into account the "new statistics" (confidence intervals) logic.

Noise and adaptation in multistable perception: noise drives when to switch, adaptation determines percept choice.

We study the dynamics of perceptual switching in ambiguous visual scenes that admit more than two interpretations/percepts to gain insight into the dynamics of perceptual multistability and its underlying neural mechanisms. We focus on visual plaids that are tristable and we present both experimental and computational results. We develop a firing-rate model based on mutual inhibition and adaptation that involves stochastic dynamics of multiple-attractor systems. The model can account for the dynamic properties (transition probabilities, distributions of percept durations, etc.) observed in the experiments. Noise and adaptation have both been shown to play roles in the dynamics of bistable perception. Here, tristable perception allows us to specify the roles of noise and adaptation in our model. Noise is critical in considering the time of a switch. On the other hand, adaptation mechanisms are critical in considering perceptual choice (in tristable perception, each time a percept ends, there is a possible choice between two new percepts).

Mirror-touch and ticker tape experiences in synesthesia.

A fundamental question in the field of synesthesia is whether it is associated with other cognitive phenomena. The current study examined synesthesia's connections with phenomenal traits of mirror-touch and ticker tape experiences, as well as the representation of the three phenomena in the population, across gender and domain of work/study. Mirror-touch is the automatic, involuntary experience of tactile sensation on one's own body when others are being touched. For example, seeing another person's arm being stroked can evoke physical touch sensation on one's own arm. Ticker tape is the automatic visualization of spoken words or thoughts, such as a teleprompter. For example, when spoken to, a ticker taper might see mentally the spoken words displayed in front of his face or as coming out of the speaker's mouth. To explore synesthesia's associations with these phenomena, a diverse group (n = 3743) was systematically recruited from eight universities and one public museum in France to complete an online screening. Of the 1017 eligible respondents, synesthetes (across all subtypes) reported higher rates of mirror-touch and ticker tape than non-synesthetes, suggesting that synesthesia is associated with these phenomenal traits. However, effect sizes were small and we could not rule out that response bias influenced these associations. Mirror-touch and ticker tape were independent. No differences were found across gender or domain of work and study in prevalence of synesthesia, mirror-touch or ticker tape. The prevalence of ticker tape, unknown so far, was estimated at about 7%, an intermediate rate between estimates of grapheme-color (2-4%) and sequence-space synesthesia (9-14%). Within synesthesia, grapheme-personification, also called ordinal-linguistic personification (OLP) was the most common subtype and was estimated around 12%. Co-occurences of the different types of synesthesia were higher than chance, though at the level of small effect sizes.

[Synesthesia as a neuronal palimpsest]. / Synesthésie, expression subjective d'un palimpseste neuronal?

Synesthetes, a small fraction of the population, experience systematic, additional associations. For example, they may arbitrarily associate a specific color to each letter or number. Synesthesia has offered for the last ten years to cognitive science a unique opportunity to study the neural bases of subjective experience, drawing on individual differences just like in neuropsychology, but with healthy people. Here we review the current knowledge and propose a new theory, the "palimpsest hypothesis", a variant of the recycling hypothesis for reading. The neural development of written language expertise (a recent cultural invention acquired without any genetic modification) requires indeed the recycling of brain regions predisposed to expertise acquisition into reading regions. The palimpsest hypothesis supposes that for synesthetes recycling involves neuronal networks that were already specialized for color perception. Synesthetic colors would be the remains of this former expertise.

A BOLD signature of eyeblinks in the visual cortex.

We are usually unaware of the brief but large illumination changes caused by blinks, presumably because of blink suppression mechanisms. In fMRI however, increase of the BOLD signal was reported in the visual cortex, e.g. during blocks of voluntary blinks (Bristow, Frith and Rees, 2005) or after spontaneous blinks recorded during the prolonged fixation of a static stimulus (Tse, Baumgartner and Greenlee, 2010). We tested whether such activation, possibly related to illumination changes, was also present during standard fMRI retinotopic and visual experiments and was large enough to contaminate the BOLD signal we are interested in. We monitored in a 3T scanner the eyeblinks of 14 subjects who observed three different types of visual stimuli, including periodic rotating wedges and contracting/expanding rings, event-related Mondrians and graphemes, while fixating. We performed event-related analyses on the set of detected spontaneous blinks. We observed large and widespread BOLD responses related to blinks in the visual cortex of every subject and whatever the visual stimulus. The magnitude of the modulation was comparable to visual stimulation. However, blink-related activations lay mostly in the anterior parts of retinotopic visual areas, coding the periphery of the visual field well beyond the extent of our stimuli. Blinks therefore represent an important source of BOLD variations in the visual cortex and a troublesome source of noise since any correlation, even weak, between the distribution of blinks and a tested protocol could trigger artifactual activities. However, the typical signature of blinks along the anterior calcarine and the parieto-occipital sulcus allows identifying, even in the absence of eyetracking, fMRI protocols possibly contaminated by a heterogeneous distribution of blinks.

Multistability in perception: binding sensory modalities, an overview.

This special issue presents research concerning multistable perception in different sensory modalities. Multistability occurs when a single physical stimulus produces alternations between different subjective percepts. Multistability was first described for vision, where it occurs, for example, when different stimuli are presented to the two eyes or for certain ambiguous figures. It has since been described for other sensory modalities, including audition, touch and olfaction. The key features of multistability are: (i) stimuli have more than one plausible perceptual organization; (ii) these organizations are not compatible with each other. We argue here that most if not all cases of multistability are based on competition in selecting and binding stimulus information. Binding refers to the process whereby the different attributes of objects in the environment, as represented in the sensory array, are bound together within our perceptual systems, to provide a coherent interpretation of the world around us. We argue that multistability can be used as a method for studying binding processes within and across sensory modalities. We emphasize this theme while presenting an outline of the papers in this issue. We end with some thoughts about open directions and avenues for further research.

The initial phase of auditory and visual scene analysis.

Auditory streaming and visual plaids have been used extensively to study perceptual organization in each modality. Both stimuli can produce bistable alternations between grouped (one object) and split (two objects) interpretations. They also share two peculiar features: (i) at the onset of stimulus presentation, organization starts with a systematic bias towards the grouped interpretation; (ii) this first percept has 'inertia'; it lasts longer than the subsequent ones. As a result, the probability of forming different objects builds up over time, a landmark of both behavioural and neurophysiological data on auditory streaming. Here we show that first percept bias and inertia are independent. In plaid perception, inertia is due to a depth ordering ambiguity in the transparent (split) interpretation that makes plaid perception tristable rather than bistable: experimental manipulations removing the depth ambiguity suppressed inertia. However, the first percept bias persisted. We attempted a similar manipulation for auditory streaming by introducing level differences between streams, to bias which stream would appear in the perceptual foreground. Here both inertia and first percept bias persisted. We thus argue that the critical common feature of the onset of perceptual organization is the grouping bias, which may be related to the transition from temporally/spatially local to temporally/spatially global computation.

The neural bases of grapheme-color synesthesia are not localized in real color-sensitive areas.

The subjective experience of color by synesthetes when viewing achromatic letters and numbers supposedly relates to real color experience, as exemplified by the recruitment of the V4 color center observed in some brain imaging studies. Phenomenological reports and psychophysics tests indicate, however, that both experiences are different. Using functional magnetic resonance imaging, we tried to precise the degree of coactivation by real and synesthetic colors, by evaluating each color center individually, and applying adaptation protocols across real and synesthetic colors. We also looked for structural differences between synesthetes and nonsynesthetes. In 10 synesthetes, we found that color areas and retinotopic areas were not activated by synesthetic colors, whatever the strength of synesthetic associations measured objectively for each subject. Voxel-based morphometry revealed no white matter (WM) or gray matter difference in those regions when compared with 25 control subjects. But synesthetes had more WM in the retrosplenial cortex bilaterally. The joint coding of real and synesthetic colors, if it exists, must therefore be distributed rather than localized in the visual cortex. Alternatively, the key to synesthetic color experience might not lie in the color system.

Pupil dynamics during bistable motion perception.

Pupil size not only varies to changes in illumination but is also modulated by several cognitive factors, making it a potentially versatile physiological marker of cortical states. We recorded pupil dynamics while subjects continuously reported their bistable perception of ambiguous moving stimuli, plaids, and partially occluded rotating diamonds. We observed small (about 5% of surface change on average) but reliable pupil dilation around (-300 ms to 1.5 s) the button presses indicating the changes of percepts. We found that 70% of pupil dilation could be accounted for by the motor response. The remaining perceptual component was similar for spontaneously occurring transitions and transitions triggered by physical stimulus manipulations. Moreover, the amplitude of pupil modulation in the spontaneous condition was unrelated to the duration of each perceptual state. It is therefore unlikely that the mechanisms of endogenous perceptual bistability reflect in the pupil. In addition, we measured a clear constriction of the pupil after blinks (about 8% of surface change on average). As pupil changes have the potential to entail retino-cortical activity, their monitoring in studies of visual processing could prove worthwhile.