The pupil: a window on social automatic processing in autism spectrum disorder children.

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.

Eye Movement Monitoring and Maturation of Human Face Exploration.

OBJECTIVE: The aim of this study was to characterize ocular exploration of neutral and emotional faces in the typical development of a child. SUBJECTS AND METHOD: In this eye-tracking study, visual exploration of faces (with neutral or emotional expressions: happiness or sadness) was characterized in a population of 52 children (24 girls and 28 boys from 4 to 15 years of age) and 44 adults (22 women and 22 men from 18 to 35 years of age). The time spent on the eyes, nose and mouth of the faces was measured. RESULTS: All participants spent more time on the eyes (13%) rather than the nose and mouth (6%). The youngest participants spent less time exploring the eyes than the older participants, suggesting the progressive establishment of interest in these informative regions of the face during maturation. This process seemed to occur later in females (7-9 years) than males (4-6 years). CONCLUSION: These results confirm the importance of the eye area and the capacity of this region to capture attention. In addition, this study shows that the exploration of this region increases with age and is lower among girls aged 4-6 years compared with boys of the same age.

An odor identification approach based on event-related pupil dilation and gaze focus.

Olfactory disorders constitute a potential marker of many diseases and are considered valuable clues to the diagnosis and evaluation of progression for many disorders. The most commonly used test for the evaluation of impairments of olfactory identification requires the active participation of the subject, who must select the correct name of the perceived odor from a list. An alternative method is required because speech may be impaired or not yet learned in many patients. As odor identification is known to be facilitated by searching for visual clues, we aimed to develop an objective, vision-based approach for the evaluation of odor identification. We used an eye tracking method to quantify pupillary and ocular responses during the simultaneous presentation of olfactory and visual stimuli, in 39 healthy participants aged from 19 to 77years. Odor presentation triggered an increase in pupil dilation and gaze focus on the picture corresponding to the odor presented. These results suggest that odorant stimuli increase recruitment of the sympathetic system (as demonstrated by the reactivity of the pupil) and draw attention to the visual clue. These results validate the objectivity of this method.

Subjective and physiological emotional response in euthymic bipolar patients: a pilot study.

The euthymic phase of bipolar disorders may be associated with residual emotional and/or subsyndromal symptoms. The aim of this study was to compare subjective and physiologic emotional response to negative, neutral and positive emotion eliciting pictures between euthymic bipolar patients (n=26) and healthy controls (n=30). We evaluated emotional response using an emotional induction method with emotional pictures from the International Affective Picture System. We measured subjective emotional response with the Self-Assessment Manikin and physiological emotional response by measuring pupil size. No difference was found between euthymic bipolar patients and controls regarding subjective emotional response. However, upon viewing positive pictures, pupil dilation was significantly lower in euthymic bipolar patients compared to controls. This finding suggests that euthymic bipolar phase may be associated with reduced physiologic emotional response to positive valence, which is consistent with a more general negative emotional bias or can be understood as a residual emotional subsyndromal symptom.

Event-related potential and eye tracking evidence of the developmental dynamics of face processing.

Although the wide neural network and specific processes related to faces have been revealed, the process by which face-processing ability develops remains unclear. An interest in faces appears early in infancy, and developmental findings to date have suggested a long maturation process of the mechanisms involved in face processing. These developmental changes may be supported by the acquisition of more efficient strategies to process faces (theory of expertise) and by the maturation of the face neural network identified in adults. This study aimed to clarify the link between event-related potential (ERP) development in response to faces and the behavioral changes in the way faces are scanned throughout childhood. Twenty-six young children (4-10 years of age) were included in two experimental paradigms, the first exploring ERPs during face processing, the second investigating the visual exploration of faces using an eye-tracking system. The results confirmed significant age-related changes in visual ERPs (P1, N170 and P2). Moreover, an increased interest in the eye region and an attentional shift from the mouth to the eyes were also revealed. The proportion of early fixations on the eye region was correlated with N170 and P2 characteristics, highlighting a link between the development of ERPs and gaze behavior. We suggest that these overall developmental dynamics may be sustained by a gradual, experience-dependent specialization in face processing (i.e. acquisition of face expertise), which produces a more automatic and efficient network associated with effortless identification of faces, and allows the emergence of human-specific social and communication skills.

Back to basic: do children with autism spontaneously look at screen displaying a face or an object?

Eye-tracking studies on exploration of faces and objects in autism provided important knowledge but only in a constraint condition (chin rest, total time looking at screen not reported), without studying potential differences between subjects with autism spectrum disorder (ASD) and controls in spontaneous visual attention toward a screen presenting these stimuli. This study used eye tracking to compare spontaneous visual attention to a screen displaying a face or an object between children with autism and controls in a nonconstraint condition and to investigate the relationship with clinical characteristics in autism group. Time exploring screen was measured during passive viewing of static images of faces or objects. Autistic behaviors were assessed by the CARS and the BSE-R in autism group. In autism group, time exploring face screen and time exploring object screen were lower than in controls and were not correlated with degree of distractibility. There was no interaction between group and type of image on time spent exploring screen. Only time exploring face screen was correlated with autism severity and gaze impairment. Results highlight particularities of spontaneous visual attention toward a screen displaying faces or objects in autism, which should be taken into account in future eye-tracking studies on face exploration.

Can pupil size and pupil responses during visual scanning contribute to the diagnosis of autism spectrum disorder in children?

The purpose of this study was to determine whether baseline pupil size and pupil responses during visual scanning with eye-tracking technology could discriminate children with autism spectrum disorder (ASD) from mental age-matched and chronological age-matched controls. To this end, we used stimuli consisting in still color photographs presented centrally to the participant's midline on a stimulus monitor. Each child was presented with a series of neutral faces, virtual faces (avatars) and different objects, separated by black slides. We recorded the mean pupil size and pupil size changes over time in each of the three categories of stimuli and during exposure to the black slides. Fifty-seven children participated in study (19 ASD, mean age 118 months; 19 mental age-matched controls, mean age 87 months; and 19 chronological age-matched controls, mean age 118 months). We compared the baseline pupil size and pupil responses during visual scanning among the three diagnostic groups. During the presentation of slides, the mean pupil size in the ASD group was clearly smaller than in the MA-matched and CA-matched groups. Discriminate analysis of pupil size during the presentation of black slides and slides with visual stimuli successfully predicted group membership in 72% of the participants. Group membership was correctly classified in 89% of the participants in the ASD group, in 63% in the MA-matched group and in 63% in the CA-matched group. These potential biomarkers may contribute to our understanding of the differences in neurological development in the brain in autism and could prove useful as indicators of ASD.

Preserved subcortical volumes and cortical thickness in women with sexual abuse-related PTSD.

Posttraumatic stress disorder (PTSD) has been frequently associated with volumetric reductions of grey matter structures (e.g. hippocampus and anterior cingulate), but these results remain controversial, especially in female non-combat-related samples. The present study aimed at exploring whole-brain structures in women with sexual abuse-related PTSD on the basis of cortical and subcortical structure comparisons to a matched pair sample that was well-controlled. Seventeen young women who had experienced sexual abuse and who had a diagnosis of chronic PTSD based on the Clinician Administered PTSD Scale for DSM-IV and 17 healthy controls individually matched for age and years of education were consecutively recruited. Both groups underwent structural magnetic resonance imaging and psychiatric assessment of the main disorders according to Axis I of DSM-IV. The resulting scans were analyzed using automated cortical and subcortical volumetric quantifications. Compared with controls, PTSD subjects displayed normal global and regional brain volumes and cortical thicknesses. Our results indicate preserved subcortical volumes and cortical thickness in a sample of female survivors of sexual abuse with PTSD. The authors discuss potential differences between neural mechanisms of sexual abuse-related PTSD and war-related PTSD.

Atypical activation of the mirror neuron system during perception of hand motion in autism.

Disorders in the autism spectrum are characterized by deficits in social and communication skills such as imitation, pragmatic language, theory of mind, and empathy. The discovery of the "mirror neuron system" (MNS) in macaque monkeys may provide a basis from which to explain some of the behavioral dysfunctions seen in individuals with autism spectrum disorders (ASD).We studied seven right-handed high-functioning male autistic and eight normal subjects (TD group) using functional magnetic resonance imaging during observation and execution of hand movements compared to a control condition (rest). The between group comparison of the contrast [observation versus rest] provided evidence of a bilateral greater activation of inferior frontal gyrus during observation of human motion than during rest for the ASD group than for the TD group. This hyperactivation of the pars opercularis (belonging to the MNS) during observation of human motion in autistic subjects provides strong support for the hypothesis of atypical activity of the MNS that may be at the core of the social deficits in autism.

Exploration of core features of a human face by healthy and autistic adults analyzed by visual scanning.

Autism is a neurodevelopmental disorder characterized by disorders in social interaction and emotional reciprocity which can be explained by impairments of the ability to understand the mental states of others ("theory of mind") and recognition of facial expressions. These impairments may be related to the difficulties with face recognition characteristic of this disorder. Face perception plays a critical role in the development of social interaction and understanding of the internal emotional state of others. It depends on initial oculomotor exploration. The aim of this study was to quantify ocular behaviour in 11 adults with autism and 23 healthy subjects (15-35 years) while exploring neutral faces and faces expressing an emotion using an eye tracking method. The strategy used to explore faces was also studied. All subjects spent significantly more time on the eye region than on the rest of the face. However, subjects with autism spent less time on the eye region than healthy subjects. The latter used a strategy based on their own eye dominance when exploring faces. All healthy subjects significantly began their exploration of a face by looking at the eye in the contralateral visual field to their dominant eye. This strategy seemed to be impaired in patients with autism. To conclude, these results contrast with earlier reports regarding the lack of interest in the eye region in patients with autism, and demonstrate for the first time that perception of the face is dependent on eye dominance.

Impaired cortical activation in autistic children: is the mirror neuron system involved?

The inability to imitate becomes obvious early in autistic children and seems to contribute to learning delay and to disorders of communication and contact. Posture, motility and imitation disorders in autistic syndrome might be the consequence of an abnormality of sensori-motor integration, related to the visual perception of movement, and could reflect impairment of the mirror neuron system (MNS). We compared EEG activity during the observation of videos showing actions or still scenes in 14 right-handed autistic children and 14 right-handed, age- and gender-matched control children (3 girls and 11 boys, aged 5 years 3 months-7 years 11 months). We showed desynchronisation of the EEG in the motor cerebral cortex and the frontal and temporal areas during observation of human actions in the group of healthy children. No such desynchronisation was found in autistic children. Moreover, inversion of the pattern of hemispheric activation was found in autistic children, with increased cortical activity in the right hemisphere in the posterior region, including the centro-parietal and temporo-occipital sites. These results are in agreement with the hypothesis of impairment of the mirror neuron system in autistic disorder.

Impairment of a cortical event-related desynchronisation during a bimanual load-lifting task in children with autistic disorder.

In autism, the abilities of communication are affected, associated with abnormalities of cognitive, sensorial and motor development. In a previous study based on a load-lifting task, we showed impairment of anticipation in children with autism as evidenced by kinematics and eletromyographic recordings [Neurosci. Lett. 348 (2003) 17]. In the present study, we assessed the cortical counterparts of the use of anticipatory postural adjustments in a group of control children and in a group of children with autism. The tasks required maintaining a stable forearm position despite imposed or voluntary lifting of an object placed either on the controlateral forearm or on a support. We investigated the differences between the two groups of children on the Event-Related Desynchronisation (ERD) which precedes movement onset in adults [Electroencephalogr. Clin. Neurophysiol. 46 (1979) 138]. Electroencephalogram (EEG) power evolution of a 6-8-Hz frequency band was averaged before and after imposed or voluntary movement onset. EEG reactivity of control and autistic children did not differ during the imposed unloading condition, but significant differences appeared in the voluntary unloading situations. Before lifting the object, control children showed an ERD above the left motor areas. An ERD also occurred above the right motor areas when the object was placed on their forearm. This indicates that the ERD can also translate the use of anticipatory postural adjustments. By contrast, children with autism did not show an ERD in the two voluntary situations. This suggests a central deficit of anticipation in both postural and motor control in children with autism.

Motor control and children with autism: deficit of anticipatory function?

This study aims at investigating how do anticipatory postural adjustments develop in children with autism, during a bimanual load-lifting task that required maintaining the stabilisation of the forearm despite imposed or voluntary unloading. Elbow angle and electromyographic were recorded on the child forearm supporting the load. The forearm stabilisation was as good in children with autism as in the control group. However, in children with autism, the latencies for both kinematics and muscular events indicated an increase of the duration of unloading. These results indicate the use of a feedback rather than a feed-forward mode of control. Impairments in both the building of internal representations and the mastering of timing parameters, could explain the deficient postural anticipation reported in children with autism.

Investigation of whole blood and urine monoamines in autism.

Levels of serotonin (5-HT), dopamine (DA), norepinephrine (NE) and epinephrine (E) were determined in the whole blood and urine of 23 children with autism and compared to those of normal children. Very significant group effects (low whole blood 5-HT, high urinary 5-HT and high NE+E in autism) and age effects (urinary 5-HT and DA decrease with age) were found. Moreover, the urinary DA and the whole blood E levels were correlated with clinical findings. The results suggest a maturation defect of noradrenergic systems, possibly disturbed dopaminergic and serotoninergic metabolism, and a functional imbalance among these neurotransmitters in autism.