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Early identification of children on the autism spectrum is crucial for early intervention with long-term positive effects on symptoms and skills. The need for improved objective autism detection tools is emphasized by the poor diagnostic power in current tools. Here, we aim to evaluate the diagnostic power of genuine acoustic features of the voice in children with autism spectrum disorder (ASD) with respect to a heterogeneous control group (composed of neurotypical children and children with Developmental Language Disorder [DLD] and children with sensorineural hearing loss with Cochlear Implant [CI]). This retrospective diagnostic study was conducted at the University Child Psychiatry Center of Tours (France). A total of 108 children, including 38 diagnosed with ASD (8.5 ± 0.25 years), 24 typically developing (TD; 8.2 ± 0.32 years) children and 46 children with atypical development (DLD and CI; 7.9 ± 0.36 years) were enrolled in our studies. We applied a ROC (Receiving Operator Characteristic) supervised clustering algorithm combined with cross-validation to develop a diagnostic model that can differentially diagnose a child with unknown disorder. The acoustic properties of speech samples produced by children in the context of a nonword repetition task were examined. We showed that voice acoustics predicted the diagnosis of autism with an overall accuracy of 91% [CI95%, 90.40%-91.65%] against TD children, and of 85% [CI95%, 84.5%-86.6%] against an heterogenous group of non-autistic children. Accuracy reported here with multivariate analysis is higher than in previous studies. Our findings demonstrate that easy-to-measure voice acoustic parameters could be used as a diagnostic aid tool, specific of ASD.

Early intervention programs positively affect key behaviours for children with Autism Spectrum Disorder. Yet, most of these programs do not target children with severe autistic symptomatology associated with intellectual disability (ID).The aim of this study was to investigate psychological and clinical outcomes of children with severe autism and ID enrolled in the Tailored and Inclusive Program for Autism - Tours (TIPA-T). The first step of the TIPA-T is the Exchange and Development Therapy (EDT): an individual neurofunctional intervention, consisting of one-to-one exchanges between a child and a therapist taking place in a pared-down environment. It aims to rehabilitate psychophysiological abilities at the roots of social communication, through structured sequences of “social play”.Cognitive and socio-emotional skills and general development were evaluated with the Social Cognitive Evaluation Battery (SCEB) scale and the Brunet-Lézine scale-Revised, respectively, before and after 9 months of intervention in 32 children with ASD and ID. Autistic symptomatology was evaluated with the Behavior Summarized Evaluation-Revised (BSE-R) scale at 5 time-points in a subset of 14 children, both in individual and group settings. Statistically significant post-intervention improvements were found in cognitive and socio-emotional skills. All but one child showed improvements in at least one social domains, and 78% of children gained one-level in at least 4 social domains. 29 children improved in cognitive domains with 66% of children improving in at least 3 cognitive domains. Autistic symptomatology evaluated in one-to-one settings significantly decreased with therapy; this reduction was observed in more than 85% of children. In group settings, autistic symptomatology also decreased in more than 60% of children. Global developmental age significantly increased by 3.8 months.The TIPA-T, including EDT in particular, improves socio-emotional skills of most children with ASD and reduces autistic symptomatology; yet, with heterogeneous outcomes profiles, in line with the strong heterogeneity of profiles observed in ASD. At the group level, this study highlights the benefits of the TIPA-T for children with severe autism and associated ID. Assessment of autistic core symptoms showed an improvement of social interaction, both in one-to-one and group evaluations, demonstrating the generalizability of the skills learned during the EDT.

Atypical visual exploration of both social and nonsocial scenes is often reported in Autism Spectrum Disorder (ASD) with less precise and longer saccades, potentially reflecting difficulties in oculomotor control. To assess a subset of oculomotor functions in ASD, 20 children with ASD and 21 age-matched typically developing (TD) children (2.6-11.5 years) partook in three tasks of increasing complexity, while no explicit instruction was provided: a prosaccade gap task, a color and a "categorical" visual search tasks (a face among butterflies and vice-versa). In addition to classical saccade metrics, we measured Distance error, (the distance between the target and the closest gaze position) and Time-to-target (the time taken to reach the target). In the prosaccade task, children with ASD were as accurate as TD children, yet faster to reach the stimulus. In the color visual search task, children with ASD were faster but less precise than TD children. In the categorical visual search, while TD children were more precise in orienting their gaze towards the face, children with ASD performed similarly in the two conditions; Time-to-target did not differ. Our results provide contradictory evidence regarding enhanced visual search ability in ASD: when considering response times, enhanced visual search performance was found in one task only, while when considering gaze precision no advantage was found. These three experiments demonstrate that the automatic saccadic system may function more rapidly in children with ASD. Nonetheless, a diminished sensitivity to bottom-up saliency and top-down influence might suppress this advantage in more complex visual environments. Autism Res 2019, 12: 212-224 © 2018 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Three experiments with no instructions were designed to assess oculomotor functions in children with Autism Spectrum Disorder (ASD). In a saccade task, children with ASD were faster than but as accurate as control children. In visual search tasks, accuracy and speed decreased with increasing complexity of visual environment. Children with ASD showed faster automatic visual orientation, but this might hinder exploratory behaviors, leading to difficulties in complex and social situations.

Background Faces are crucial social stimuli, eliciting automatic processing associated with increased physiological arousal in observers. The level of arousal can be indexed by pupil diameter (the 'Event-Related Pupil Dilation', ERPD). However, many parameters could influence the arousal evoked by a face and its social saliency (e.g. virtual vs. real, neutral vs. emotional, static vs. dynamic). A few studies have shown an atypical ERPD in autism spectrum disorder (ASD) patients using several kinds of faces but no study has focused on identifying which parameter of the stimulus is the most interfering with face processing in ASD. Methods In order to disentangle the influence of these parameters, we propose an original paradigm including stimuli along an ecological social saliency gradient: from static objects to virtual faces to dynamic emotional faces. This strategy was applied to 186 children (78 ASD and 108 typically developing (TD) children) in two pupillometric studies (22 ASD and 47 TD children in the study 1 and 56 ASD and 61 TD children in the study 2). Results Strikingly, the ERPD in ASD children is insensitive to any of the parameters tested: the ERPD was similar for objects, static faces or dynamic faces. On the opposite, the ERPD in TD children is sensitive to all the parameters tested: the humanoid, biological, dynamic and emotional quality of the stimuli. Moreover, ERPD had a good discriminative power between ASD and TD children: ASD had a larger ERPD than TD in response to virtual faces, while TD had a larger ERPD than ASD for dynamic faces. Conclusions This novel approach evidences an abnormal physiological adjustment to socially relevant stimuli in ASD.

Atypical sensory behaviours represent a core symptom of autism spectrum disorder (ASD). Investigating early visual processing is crucial to deepen our understanding of higher-level processes. Visual evoked potentials (VEPs) to pattern-reversal checkerboards were recorded in ASD children and age-matched controls. Peak analysis of the P100 component and two types of single-trial analyses were carried out. P100 amplitude was reduced in the ASD group, consistent with previous reports. The analysis of the proportion of trials with a positive activity in the latency range of the P100, measuring inter-trial (in)consistency, allowed identifying two subgroups of ASD participants: the first group, as control children, showed a high inter-trial consistency, whereas the other group showed an inter-trial inconsistency. Analysis of median absolute deviation of single-trial P100 (st-P100) latencies revealed an increased latency variability in the ASD group. Both single-trial analyses revealed increased variability in a subset of children with ASD. To control for this variability, VEPs were reconstructed by including only positive trials or trials with homogeneous st-P100 latencies. These control analyses abolished group differences, confirming that the reduced P100 amplitude results from increased inter-trial variability in ASD. This increased variability in ASD supports the neural noise theory. The existence of subgroups in ASD suggests that the neural response variability is not a genuine characteristic of the entire autistic spectrum, but rather characterized subgroups of children. Exploring the relationship between sensory responsiveness and inter-trial variability could provide more precise bioclinical profiles in children with ASD, and complete the functional diagnostic crucial for the development of individualized therapeutical projects.

Although ASD (Autism Spectrum Disorder) diagnosis requires the co-occurrence of socio-emotional deficits and inflexible behaviors, the interaction between these two domains remains unexplored. We used an emotional Wisconsin Card Sorting Test adapted to fMRI to explore this question. ASD and control participants matched a central card (a face) with one of four surrounding cards according to one of three rules: frame color, facial identity or expression. Feedback informed participants on whether to change or maintain the current sorting rule. For each rule, we modeled feedback onsets to change, switch (confirming the newly found rule) and maintenance events. “Bias error”, which measures participants’ willingness to switch, was larger in ASD participants for the emotional sorting rule. Brain activity to change events showed no group differences. In response to switch events significantly larger activity was observed for ASD participants in bilateral Inferior Parietal Sulci. Inflexibility in ASD appears characterized by the unwillingness to switch toward processing socio-emotional information, rather than a major disruption in cognitive flexibility. However, a larger activity to switch events in ASD highlights the need for a higher level of certainty before setting into a stable processing stage, which may be particularly detrimental in the highly changeable socio-emotional environment.

Voices transmit social signals through speech and/or prosody. Emotional prosody conveys key information about the emotional state of a speaker and is thus a crucial cue that one has to detect in order to develop efficient social communication. Previous studies in adults reported different brain responses to emotional than to neutral prosodic deviancy. The aim of this study was to characterize such specific emotional deviancy effects in school-age children. The mismatch negativity (MMN) and P3a evoked potentials, reflecting automatic change detection and automatic attention orienting, respectively, were obtained for neutral and emotional angry deviants in both school-age children (n = 26) and adults (n = 14). Shorter latencies were found for emotional than for neutral preattentional responses in both groups. However, whereas this effect was observed on the MMN in adults, it appeared in an early discriminative negativity preceding the MMN in children. A smaller P3a amplitude was observed for the emotional than for the neutral deviants at all ages. Overall, the brain responses involved in specific emotional change processing are already present during childhood, but responses have not yet reached an adult pattern. We suggest that these processing differences might contribute to the known improvement of emotional prosody perception between childhood and adulthood.

Autism and Autism Spectrum Disorder (ASD) cover a large variety of clinical profiles which share two main dimensions: social and communication impairment and repetitive behaviors or restricted interests, which are present during childhood. There is now no doubt that genetic factors are a major component in the etiology of autism but precise physiopathological pathways are still being investigated. Furthermore, developmental trajectories combined with compensatory mechanisms will lead to various clinical and neurophysiological profiles which together constitute this Autism Spectrum Disorder. To better understand the pathophysiology of autism, comprehension of key neurophysiological mechanisms and brain circuits underlying the different bioclinical profiles is thus crucial. To achieve this goal we propose a strategy which investigates different levels of information processing from sensory perception to complex cognitive processing, taking into account the complexity of the stimulus and whether it is social or non-social in nature. In order to identify different developmental trajectories and to take into account compensatory mechanisms, we further propose that such protocols should be carried out in individuals from childhood to adulthood representing a wide variety of clinical forms.

This chapter describes the putative representation of voices in human memory by looking at perceptual, acoustical, and cerebral correlates for the processing of speaker identity, gender, and age. Specifically, it outlines the factors that contribute to the variability in recognition accuracy for these speaker attributes, highlighting the importance of learning mechanisms. The chapter presents behavioural and neurological evidence for the notion that voices, similar to faces, are represented in memory relative to an average prototypical voice within a multidimensional acoustic space. While this account presents a useful framework to understand the neural coding of individual voices, it will take further research to elucidate how gender, age, and other speaker attributes are represented in this putative ‘voice space’. Furthermore, it remains to be determined whether and how the processing of various vocal cues may interact to shape everyday speaker perception.

Atypical visual exploration of both social and nonsocial scenes is often reported in Autism Spectrum Disorder (ASD) with less precise and longer saccades, potentially reflecting difficulties in oculomotor control. To assess a subset of oculomotor functions in ASD, 20 children with ASD and 21 age-matched typically developing (TD) children (2.6-11.5 years) partook in three tasks of increasing complexity, while no explicit instruction was provided: a prosaccade gap task, a color and a "categorical" visual search tasks (a face among butterflies and vice-versa). In addition to classical saccade metrics, we measured Distance error, (the distance between the target and the closest gaze position) and Time-to-target (the time taken to reach the target). In the prosaccade task, children with ASD were as accurate as TD children, yet faster to reach the stimulus. In the color visual search task, children with ASD were faster but less precise than TD children. In the categorical visual search, while TD children were more precise in orienting their gaze towards the face, children with ASD performed similarly in the two conditions; Time-to-target did not differ. Our results provide contradictory evidence regarding enhanced visual search ability in ASD: when considering response times, enhanced visual search performance was found in one task only, while when considering gaze precision no advantage was found. These three experiments demonstrate that the automatic saccadic system may function more rapidly in children with ASD. Nonetheless, a diminished sensitivity to bottom-up saliency and top-down influence might suppress this advantage in more complex visual environments. Autism Res 2019, 12: 212-224 © 2018 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Three experiments with no instructions were designed to assess oculomotor functions in children with Autism Spectrum Disorder (ASD). In a saccade task, children with ASD were faster than but as accurate as control children. In visual search tasks, accuracy and speed decreased with increasing complexity of visual environment. Children with ASD showed faster automatic visual orientation, but this might hinder exploratory behaviors, leading to difficulties in complex and social situations.

Gaze direction, a cue of both social and spatial attention, is known to modulate early neural responses to faces e.g. N170. However, findings in the literature have been inconsistent, likely reflecting differences in stimulus characteristics and task requirements. Here, we investigated the effect of task on neural responses to dynamic gaze changes: away and toward transitions (resulting or not in eye contact). Subjects performed, in random order, social (away/toward them) and non-social (left/right) judgment tasks on these stimuli. Overall, in the non-social task, results showed a larger N170 to gaze aversion than gaze motion toward the observer. In the social task, however, this difference was no longer present in the right hemisphere, likely reflecting an enhanced N170 to gaze motion toward the observer. Our behavioral and event-related potential data indicate that performing social judgments enhances saliency of gaze motion toward the observer, even those that did not result in gaze contact. These data and that of previous studies suggest two modes of processing visual information: a 'default mode' that may focus on spatial information; a 'socially aware mode' that might be activated when subjects are required to make social judgments. The exact mechanism that allows switching from one mode to the other remains to be clarified.

International audience; Detection of changes in facial emotional expressions is crucial to communicate and to rapidly and automatically process possible threats in the environment. Recent studies suggest that expression-related visual mismatch negativity (vMMN) reflects automatic processing of emotional changes. In the present study we used a controlled paradigm to investigate the specificity of emotional change-detection. In order to disentangle specific responses to emotional deviants from that of neutral deviants, we presented neutral expression as standard stimulus (p = 0.80) and both angry and neutral expressions as deviants (p = 0.10, each). In addition to an oddball sequence, an equiprobable sequence was presented, to control for refractoriness and low-level differences. Our results showed that in an early time window (100-200 ms), the controlled vMMN was greater than the oddball vMMN only for the angry deviant, suggesting the importance of controlling for refractoriness and stimulus physical features in emotion related studies. Within the controlled vMMN, angry and neutral deviants both elicited early and late peaks occurring at 140 and 310 ms, respectively, but only the emotional vMMN presented sustained amplitude after each peak. By directly comparing responses to emotional and neutral deviants, our study provides evidence of specific activity reflecting the automatic detection of emotional change. This differs from broader "visual" change processing, and suggests the involvement of two partially-distinct pre-attentional systems in the detection of changes in facial expressions.

International audience; Recovery of stress-induced structural alterations in Posttraumatic Stress Disorder (PTSD) remains largely unexplored. This study aimed to determine whether symptoms improvement is associated with GM density changes of brain structures involved in PTSD. Two groups of PTSD patients were involved in this study. The first group was treated with Eye Movement Desensitization and Reprocessing (EMDR) therapy and recovered from their symptoms (recovery group) (n = 11); Patients were scanned prior to therapy (T1), one week (T2) and five months after the end of therapy (T3). The second group included patients which followed a supportive therapy and remained symptomatic (wait-list group) (n = 7). They were scanned at three time-steps mimicking the same inter-scan intervals. T1-weighted images of anatomical structure were acquired using magnetic resonance imaging (MRI) prior to therapy (T1). Voxel-based morphometry (VBM) was used to characterize GM density evolution. GM density values showed a significant group-by-time interaction effect between T1 and T3 in prefrontal cortex areas. These interaction effects were driven by a GM density increase in the recovery group with respect to the wait-list group. Symptoms removal goes hand-in-hand with GM density enhancement of structures involved in emotional regulation.

International audience; Methods. 1120 subjects as well as a developmental phonagnosic subject (KH) along with age-matched controls performed the Glasgow Voice Memory Test, which assesses the ability to encode and immediately recognize, through an old/new judgment, both unfamiliar voices (delivered as vowels, making language requirements minimal) and bell sounds. The inclusion of non-vocal stimuli allows the detection of significant dissociations between the two categories (vocal vs non-vocal stimuli). Results. The distributions of accuracy and sensitivity scores (d') reflected a wide range of individual differences in voice recognition performance in the population. As expected, KH showed a dissociation between the recognition of voices and bell sounds, her performance being significantly poorer than matched controls for voices but not for bells. THE GLASGOW VOICE MEMORY TEST 2 Conclusion. By providing normative data of a large sample and by testing a developmental phonagnosic subject, we demonstrated that the Glasgow Voice Memory Test, available online and accessible from all over the world, can be a valid screening tool (~ 5 min) for a preliminary detection of potential cases of phonagnosia and of " super recognizers " for voices.

In this chapter we focus on the neural processes that occur in the mature healthy human brain in response to evaluating another’s social attention. We first examine the brain’s sensitivity to gaze direction of others, social attention (as typically indicated by gaze contact), and joint attention. Brain regions such as the superior temporal sulcus (STS), the amygdala, and the fusiform gyrus have been previously demonstrated to be sensitive to gaze changes, most frequently with functional magnetic resonance imaging (fMRI). Neurophysiological investigations, using electroencephalography (EEG) and magnetoencephalography (MEG), have identified event-related potentials (ERPs) such as the N170 that are sensitive to changes in gaze direction and head direction. We advance a putative model that explains findings relating to the neurophysiology of social attention , based mainly on our studies. This model proposes two brain modes of social information processing—a nonsocial “Default” mode and a social mode that we have named “Socially Aware”. In Default mode, there is an internal focus on executing actions to achieve our goals, as evident in studies in which passive viewing or tasks involving nonsocial judgments have been used. In contrast, Socially Aware mode is active when making explicit social judgments. Switching between these two modes is rapid and can occur via either top-down or bottom-up routes. From a different perspective, most of the literature, including our own studies, has focused on social attention phenomena as experienced from the first-person perspective, i.e., gaze changes or social attention directed at, or away from, the observer. However, in daily life we are actively involved in observing social interactions between others, where their social attention focus may not include us, or their gaze may not meet ours. Hence, changes in eye gaze and social attention are experienced from the third-person perspective. This area of research is still fairly small, but nevertheless important in the study of social and joint attention, and we discuss this very small literature briefly at the end of the chapter. We conclude the chapter with some outstanding questions, which are aimed at the main knowledge gaps in the literature.