A multilevel investigation of sensory sensitivity and responsivity in autistic adults.

Atypical sensory processing is a core symptom of autism spectrum disorders (ASD). We aimed at better characterizing visual sensitivity and responsivity in ASD at the self-reported, behavioral and neural levels, and at describing the relationships between these levels. We refer to sensory sensitivity as the ability to detect sensory stimuli and to sensory responsivity as an affective response to sensory stimuli. Participants were 25 neurotypical and 24 autistic adults. At the self-reported level, autistic participants had higher scores of sensory sensitivity and responsivity than neurotypicals. The behavioral and neural tasks involved contrast-reversing gratings which became progressively (in)visible as their contrast or spatial frequency evolved. At the behavioral level, autistic participants had higher detection and responsivity thresholds when gratings varied in spatial frequency, but their thresholds did not differ from neurotypicals when gratings varied in contrast. At the neural level, we used fast periodic visual stimulations and electroencephalography to implicitly assess detection thresholds for contrast and spatial frequency, and did not reveal any group difference. Higher self-reported responsivity was associated with higher behavioral responsivity, more intolerance of uncertainty and anxiety, in particular in ASD. At the self-reported level, higher sensitivity was associated with more responsivity in both groups, contrary to the behavioral level where these relationships were not found. These heterogeneous results suggest that sensitivity and responsivity per se are not simply increased in ASD, but may be modulated by other factors such as environmental predictability. Multi-level approaches can shed light on the mechanisms underlying sensory issues in ASD.

Frequency-Tagging EEG of Superimposed Social and Non-Social Visual Stimulation Streams Provides No Support for Social Salience Enhancement after Intranasal Oxytocin Administration.

The social salience hypothesis proposes that the neuropeptide oxytocin (OT) can impact human social behavior by modulating the salience of social cues. Here, frequency-tagging EEG was used to quantify the neural responses to social versus non-social stimuli while administering a single dose of OT (24 IU) versus placebo treatment. Specifically, two streams of faces and houses were superimposed on one another, with each stream of stimuli tagged with a particular presentation rate (i.e., 6 and 7.5 Hz or vice versa). These distinctive frequency tags allowed unambiguously disentangling and objectively quantifying the respective neural responses elicited by the different streams of stimuli. This study involved a double-blind, placebo-controlled, cross-over trial with 31 healthy adult men. Based on four trials of 60 s, we detected robust frequency-tagged neural responses in each individual, with entrainment to faces being more pronounced in lateral occipito-temporal regions and entrainment to houses being focused in medial occipital regions. However, contrary to our expectation, a single dose of OT did not modulate these stimulus-driven neural responses, not in terms of enhanced social processing nor in terms of generally enhanced information salience. Bayesian analyses formally confirmed these null findings. Possibly, the baseline ceiling level performance of these neurotypical adult participants as well as the personal irrelevance of the applied stimulation streams might have hindered the observation of any OT effect.

Monitoring the effect of oxytocin on the neural sensitivity to emotional faces via frequency-tagging EEG: A double-blind, cross-over study.

The neuropeptide oxytocin (OXT) is suggested to exert an important role in human social behaviors by modulating the salience of social cues. To date, however, there is mixed evidence whether a single dose of OXT can improve the behavioral and neural sensitivity for emotional face processing. To overcome difficulties encountered with classic event-related potential studies assessing stimulus-saliency, we applied frequency-tagging EEG to implicitly assess the effect of a single dose of OXT (24 IU) on the neural sensitivity for positive and negative facial emotions. Neutral faces with different identities were presented at 6 Hz, periodically interleaved with an expressive face (angry, fearful, and happy, in separate sequences) every fifth image (i.e., 1.2 Hz oddball frequency). These distinctive frequency tags for neutral and expressive stimuli allowed direct and objective quantification of the neural expression-categorization responses. The study involved a double-blind, placebo-controlled, cross-over trial with 31 healthy adult men. Contrary to our expectations, we did not find an effect of OXT on facial emotion processing, neither at the neural, nor at the behavioral level. A single dose of OXT did not evoke social enhancement in general, nor did it affect social approach-avoidance tendencies. Possibly ceiling performances in facial emotion processing might have hampered further improvement.

Investigating automatic emotion processing in boys with autism via eye tracking and facial mimicry recordings.

Difficulties in automatic emotion processing in individuals with autism spectrum disorder (ASD) might remain concealed in behavioral studies due to compensatory strategies. To gain more insight in the mechanisms underlying facial emotion recognition, we recorded eye tracking and facial mimicry data of 20 school-aged boys with ASD and 20 matched typically developing controls while performing an explicit emotion recognition task. Proportional looking times to specific face regions (eyes, nose, and mouth) and face exploration dynamics were analyzed. In addition, facial mimicry was assessed. Boys with ASD and controls were equally capable to recognize expressions and did not differ in proportional looking times, and number and duration of fixations. Yet, specific facial expressions elicited particular gaze patterns, especially within the control group. Both groups showed similar face scanning dynamics, although boys with ASD demonstrated smaller saccadic amplitudes. Regarding the facial mimicry, we found no emotion specific facial responses and no group differences in the responses to the displayed facial expressions. Our results indicate that boys with and without ASD employ similar eye gaze strategies to recognize facial expressions. Smaller saccadic amplitudes in boys with ASD might indicate a less exploratory face processing strategy. Yet, this slightly more persistent visual scanning behavior in boys with ASD does not imply less efficient emotion information processing, given the similar behavioral performance. Results on the facial mimicry data indicate similar facial responses to emotional faces in boys with and without ASD. LAY SUMMARY: We investigated (i) whether boys with and without autism apply different face exploration strategies when recognizing facial expressions and (ii) whether they mimic the displayed facial expression to a similar extent. We found that boys with and without ASD recognize facial expressions equally well, and that both groups show similar facial reactions to the displayed facial emotions. Yet, boys with ASD visually explored the faces slightly less than the boys without ASD.

Neural processing of facial identity and expression in adults with and without autism: A multi-method approach.

The ability to recognize faces and facial expressions is a common human talent. It has, however, been suggested to be impaired in individuals with autism spectrum disorder (ASD). The goal of this study was to compare the processing of facial identity and emotion between individuals with ASD and neurotypicals (NTs). Behavioural and functional magnetic resonance imaging (fMRI) data from 46 young adults (aged 17-23 years, NASD = 22, NNT = 24) was analysed. During fMRI data acquisition, participants discriminated between short clips of a face transitioning from a neutral to an emotional expression. Stimuli included four identities and six emotions. We performed behavioural, univariate, multi-voxel, adaptation and functional connectivity analyses to investigate potential group differences. The ASD-group did not differ from the NT-group on behavioural identity and expression processing tasks. At the neural level, we found no differences in average neural activation, neural activation patterns and neural adaptation to faces in face-related brain regions. In terms of functional connectivity, we found that amygdala seems to be more strongly connected to inferior occipital cortex and V1 in individuals with ASD. Overall, the findings indicate that neural representations of facial identity and expression have a similar quality in individuals with and without ASD, but some regions containing these representations are connected differently in the extended face processing network.

Combined frequency-tagging EEG and eye-tracking measures provide no support for the "excess mouth/diminished eye attention" hypothesis in autism.

BACKGROUND: Scanning faces is important for social interactions. Difficulty with the social use of eye contact constitutes one of the clinical symptoms of autism spectrum disorder (ASD). It has been suggested that individuals with ASD look less at the eyes and more at the mouth than typically developing (TD) individuals, possibly due to gaze aversion or gaze indifference. However, eye-tracking evidence for this hypothesis is mixed. While gaze patterns convey information about overt orienting processes, it is unclear how this is manifested at the neural level and how relative covert attention to the eyes and mouth of faces might be affected in ASD. METHODS: We used frequency-tagging EEG in combination with eye tracking, while participants watched fast flickering faces for 1-min stimulation sequences. The upper and lower halves of the faces were presented at 6 Hz and 7.5 Hz or vice versa in different stimulation sequences, allowing to objectively disentangle the neural saliency of the eyes versus mouth region of a perceived face. We tested 21 boys with ASD (8-12 years old) and 21 TD control boys, matched for age and IQ. RESULTS: Both groups looked longer at the eyes than the mouth, without any group difference in relative fixation duration to these features. TD boys looked significantly more to the nose, while the ASD boys looked more outside the face. EEG neural saliency data partly followed this pattern: neural responses to the upper or lower face half were not different between groups, but in the TD group, neural responses to the lower face halves were larger than responses to the upper part. Face exploration dynamics showed that TD individuals mostly maintained fixations within the same facial region, whereas individuals with ASD switched more often between the face parts. LIMITATIONS: Replication in large and independent samples may be needed to validate exploratory results. CONCLUSIONS: Combined eye-tracking and frequency-tagged neural responses show no support for the excess mouth/diminished eye gaze hypothesis in ASD. The more exploratory face scanning style observed in ASD might be related to their increased feature-based face processing style.

Frequency-Tagging Electroencephalography of Superimposed Social and Non-Social Visual Stimulation Streams Reveals Reduced Saliency of Faces in Autism Spectrum Disorder.

Individuals with autism spectrum disorder (ASD) have difficulties with social communication and interaction. The social motivation hypothesis states that a reduced interest in social stimuli may partly underlie these difficulties. Thus far, however, it has been challenging to quantify individual differences in social orientation and interest, and to pinpoint the neural underpinnings of it. In this study, we tested the neural sensitivity for social versus non-social information in 21 boys with ASD (8-12 years old) and 21 typically developing (TD) control boys, matched for age and IQ, while children were engaged in an orthogonal task. We recorded electroencephalography (EEG) during fast periodic visual stimulation (FPVS) of social versus non-social stimuli to obtain an objective implicit neural measure of relative social bias. Streams of variable images of faces and houses were superimposed, and each stream of stimuli was tagged with a particular presentation rate (i.e., 6 and 7.5 Hz or vice versa). This frequency-tagging method allows disentangling the respective neural responses evoked by the different streams of stimuli. Moreover, by using superimposed stimuli, we controlled for possible effects of preferential looking, spatial attention, and disengagement. Based on four trials of 60 s, we observed a significant three-way interaction. In the control group, the frequency-tagged neural responses to faces were larger than those to houses, especially in lateral occipito-temporal channels, while the responses to houses were larger over medial occipital channels. In the ASD group, however, faces and houses did not elicit significantly different neural responses in any of the regions. Given the short recording time of the frequency-tagging paradigm with multiple simultaneous inputs and the robustness of the individual responses, the method could be used as a sensitive marker of social preference in a wide range of populations, including younger and challenging populations.

Rapid neural categorization of angry and fearful faces is specifically impaired in boys with autism spectrum disorder.

BACKGROUND: Difficulties with facial expression processing may be associated with the characteristic social impairments in individuals with autism spectrum disorder (ASD). Emotional face processing in ASD has been investigated in an abundance of behavioral and EEG studies, yielding, however, mixed and inconsistent results. METHODS: We combined fast periodic visual stimulation (FPVS) with EEG to assess the neural sensitivity to implicitly detect briefly presented facial expressions among a stream of neutral faces, in 23 boys with ASD and 23 matched typically developing (TD) boys. Neutral faces with different identities were presented at 6 Hz, periodically interleaved with an expressive face (angry, fearful, happy, sad in separate sequences) every fifth image (i.e., 1.2 Hz oddball frequency). These distinguishable frequency tags for neutral and expressive stimuli allowed direct and objective quantification of the expression-categorization responses, needing only four sequences of 60 s of recording per condition. RESULTS: Both groups show equal neural synchronization to the general face stimulation and similar neural responses to happy and sad faces. However, the ASD group displays significantly reduced responses to angry and fearful faces, compared to TD boys. At the individual subject level, these neural responses allow to predict membership of the ASD group with an accuracy of 87%. Whereas TD participants show a significantly lower sensitivity to sad faces than to the other expressions, ASD participants show an equally low sensitivity to all the expressions. CONCLUSIONS: Our results indicate an emotion-specific processing deficit, instead of a general emotion-processing problem: Boys with ASD are less sensitive than TD boys to rapidly and implicitly detect angry and fearful faces. The implicit, fast, and straightforward nature of FPVS-EEG opens new perspectives for clinical diagnosis.

Combined frequency-tagging EEG and eye tracking reveal reduced social bias in boys with autism spectrum disorder.

Developmental accounts of autism spectrum disorder (ASD) state that infants and children with ASD are spontaneously less attracted by and less proficient in processing social stimuli such as faces. This is hypothesized to partly underlie social communication difficulties in ASD. While in some studies a reduced preference for social stimuli has been shown in individuals with ASD, effect sizes are moderate and vary across studies, stimuli, and designs. Eye tracking, often the methodology of choice to study social preference, conveys information about overt orienting processes but conceals covert attention, possibly resulting in an underestimation of the effects. In this study, we recorded eye tracking and electroencephalography (EEG) during fast periodic visual stimulation to address this issue. We tested 21 boys with ASD (8-12 years old) and 21 typically developing (TD) control boys, matched for age and IQ. Streams of variable images of faces were presented at 6 Hz alongside images of houses presented at 7.5 Hz or vice versa, while children were engaged in an orthogonal task. While frequency-tagged neural responses were larger in response to faces than simultaneously presented houses in both groups, this effect was much larger in TD boys than in boys with ASD. This group difference in saliency of social versus non-social processing is significant after 5 sec of stimulus presentation and holds throughout the entire trial. Although there was no interaction between group and stimulus category for simultaneously recorded eye-tracking data, eye tracking and EEG measures were strongly correlated. We conclude that frequency-tagging EEG, allowing monitoring of both overt and covert processes, provides a fast, objective and reliable measure of decreased preference for social information in ASD.

Fast Periodic Visual Stimulation EEG Reveals Reduced Neural Sensitivity to Fearful Faces in Children with Autism.

We objectively quantified the neural sensitivity of school-aged boys with and without autism spectrum disorder (ASD) to detect briefly presented fearful expressions by combining fast periodic visual stimulation with frequency-tagging electroencephalography. Images of neutral faces were presented at 6 Hz, periodically interleaved with fearful expressions at 1.2 Hz oddball rate. While both groups equally display the face inversion effect and mainly rely on information from the mouth to detect fearful expressions, boys with ASD generally show reduced neural responses to rapid changes in expression. At an individual level, fear discrimination responses predict clinical status with an 83% accuracy. This implicit and straightforward approach identifies subtle deficits that remain concealed in behavioral tasks, thereby opening new perspectives for clinical diagnosis.

Reduced neural sensitivity to rapid individual face discrimination in autism spectrum disorder.

BACKGROUND: Individuals with autism spectrum disorder (ASD) are characterized by impairments in social communication and interaction. Although difficulties at processing social signals from the face in ASD have been observed and emphasized for many years, there is a lot of inconsistency across both behavioral and neural studies. METHODS: We recorded scalp electroencephalography (EEG) in 23 8-to-12 year old boys with ASD and 23 matched typically developing boys using a fast periodic visual stimulation (FPVS) paradigm, providing objective (i.e., frequency-tagged), fast (i.e., few minutes) and highly sensitive measures of rapid face categorization, without requiring any explicit face processing task. We tested both the sensitivity to rapidly (i.e., at a glance) categorize faces among other objects and to individuate unfamiliar faces. OUTCOMES: While general neural synchronization to the visual stimulation and neural responses indexing generic face categorization were undistinguishable between children with ASD and typically developing controls, neural responses indexing individual face discrimination over the occipito-temporal cortex were substantially reduced in the individuals with ASD. This difference vanished when faces were presented upside-down, due to the lack of significant face inversion effect in ASD. INTERPRETATION: These data provide original evidence for a selective high-level impairment in individual face discrimination in ASD in an implicit task. The objective and rapid assessment of this function opens new perspectives for ASD diagnosis in clinical settings.

Three shades of grey: detecting brain abnormalities in children with autism using source-, voxel- and surface-based morphometry.

Autistic spectrum disorder (ASD) is a neurodevelopmental disorder characterized by deficits in social interactions, communication and stereotyped behaviour. Recent evidence from neuroimaging supports the hypothesis that ASD deficits in adults may be related to abnormalities in a specific frontal-temporal network [Autism-specific Structural Network (ASN)]. To see whether these results extend to younger children and to better characterize these abnormalities, we applied three morphometric methods on brain grey matter (GM) of children with and without ASD. We selected 39 sMRI images of male children with ASD and 42 typically developing (TD) from the Autism Brain Imaging Data Exchange database. We used source-based morphometry (SoBM), a whole-brain multivariate approach to identify GM networks, voxel-based morphometry (VBM), a voxel-wise comparison of the local GM concentration and surface-based morphometry (SuBM) for the estimation of the cortical parameters. SoBM showed a bilateral frontal-parietal-temporal network different between groups, including the inferior-middle temporal gyrus, the inferior parietal lobule and the postcentral gyrus; VBM returned differences only in the right temporal lobe; SuBM returned a thinning in the right inferior temporal lobe thinner in ASD, a higher gyrification in the right superior parietal lobule in TD and in the middle frontal gyrus in ASD. For the first time, we investigated the brain abnormalities in children with ASD using three morphometric techniques. The results were relatively consistent between methods, stressing the role of an Autism-specific Structural Network in ASD individuals. We also make methodological speculations on the relevance of using multivariate and whole-brain neuroimaging analysis to capture ASD complexity.