Joëlle Malvy

Interaction and imitation deficits from infancy to 4 years of age in children with autism A pilot study based on videotapes

The present study investigated the influence of developmental level on interaction and imitation in infants and young children with autism on the basis of family videos and filmed consultation. The sample comprised 18 children with autism divided into groups according to their developmental quotient (DQ > 50 and DQ < 50). A quantitative evaluation was performed on video observations at four periods (10-12 months, 16-18 months, 24-26 months, after 4 years) using scales appropriate for the evaluation of interaction and imitation impairments. The findings showed that, at a very early age, infants later diagnosed as having autistic disorder show different intensities of interaction and imitation deficits according to developmental level.

Metabolomics Study of Urine in Autism Spectrum Disorders Using a Multiplatform Analytical Methodology

Autism spectrum disorder (ASD) is a neurodevelopmental disorder with no clinical biomarker. The aims of this study were to characterize a metabolic signature of ASD and to evaluate multiplatform analytical methodologies in order to develop predictive tools for diagnosis and disease follow-up. Urine samples were analyzed using (1)H and (1)H-(13)C NMR-based approaches and LC-HRMS-based approaches (ESI+ and ESI- on HILIC and C18 chromatography columns). Data tables obtained from the six analytical modalities on a training set of 46 urine samples (22 autistic children and 24 controls) were processed by multivariate analysis (orthogonal partial least-squares discriminant analysis, OPLS-DA). The predictions from each of these OPLS-DA models were then evaluated using a prediction set of 16 samples (8 autistic children and 8 controls) and receiver operating characteristic curves. Thereafter, a data fusion block-scaling OPLS-DA model was generated from the 6 best models obtained for each modality. This fused OPLS-DA model showed an enhanced performance (R(2)Y(cum) = 0.88, Q(2)(cum) = 0.75) compared to each analytical modality model, as well as a better predictive capacity (AUC = 0.91, p-value = 0.006). Metabolites that are most significantly different between autistic and control children (p < 0.05) are indoxyl sulfate, N-α-acetyl-l-arginine, methyl guanidine, and phenylacetylglutamine. This multimodality approach has the potential to contribute to find robust biomarkers and characterize a metabolic phenotype of the ASD population.

Urinary p-cresol is elevated in young French children with autism spectrum disorder: a replication study

Abstract The aromatic compound p-cresol (4-methylphenol) has been found elevated in the urines of Italian autistic children up to 8 years of age. The present study aims at replicating these initial findings in an ethnically distinct sample and at extending them by measuring also the three components of urinary p-cresol, namely p-cresylsulfate, p-cresylglucuronate and free p-cresol. Total urinary p-cresol, p-cresylsulfate and p-cresylglucuronate were significantly elevated in 33 French autism spectrum disorder (ASD) cases compared with 33 sex- and age-matched controls (p < 0.05). This increase was limited to ASD children aged ≤8 years (p < 0.01), and not older (p = 0.17). Urinary levels of p-cresol and p-cresylsulfate were associated with stereotypic, compulsive/repetitive behaviors (p < 0.05), although not with overall autism severity. These results confirm the elevation of urinary p-cresol in a sizable set of small autistic children and spur interest into biomarker roles for p-cresol and p-cresylsulfate in autism.

A Brief Clinical Scale for the Early Evaluation of Imitation Disorders in Autism

Many authors have described a deficit of imitation of gestures and of symbolic and affective tasks in infants and young children with autism. This deficit is paradoxically associated with echolalia (atypical verbal imitation) and echopraxia (atypical gesture imitation) which in themselves appear to be excessive imitation. We have developed a brief clinical scale, the Imitation Disorders Evaluation scale (IDE scale), to evaluate these different early features of imitation disorders in autism. The present article reports (1) the validation study (inter- rater reliability, factor analysis) of the IDE scale carried out with a population of 30 infants and young children with autism aged from 10 to 46 months, and (2) the results of a follow-up study in which this scale was applied to a group of young children with autism (from 30 to 46 months) over 9 months’ treatment. Factor analysis provided two factors: factor 1, called ‘deficient imitation’, comprising six items describing a deficit of facial, gestural, vocal and affective imitation; and factor 2, called ‘atypical imitation’, including echolalia, echopraxia and variability of imitation. The descriptive results of the follow-up study emphasize the sensitivity of the IDE scale for assessment of improvement in imitation disorders of early autism.

Behaviour profiles in a population of infants later diagnosed as having autistic disorder.

Abstract.In order to complement findings in the field of early autism and in the context of our studies on the quantitative neurobiological evaluation of patients with autism, we studied a large population of infants later diagnosed as having autistic disorder, using multivariate descriptive statistical methods. The population included 74 infants between six and 35 months, evaluated with the Infant Behavioural Summarised Evaluation (IBSE) scale. Thirteen of the 33 items of the IBSE scale were selected according to previous studies on older patients with autistic disorder. Correspondence analysis was applied to these 13 items, followed by a classical cluster analysis. This procedure permitted the identification of four different profiles which were distinguished on the basis of five main behaviours: activity, auditory perception, sensorimotility, eye contact and use of objects. These profiles are similar to those identified in older children with autism. This study provides an objective description of early clinical markers of the heterogeneity in autism and thus contributes to the description of the onset of autistic disorder. It identified more precise clinical subtyping which will be valuable for future bioclinical studies.

Attitudes of the autism community to early autism research

Investigation into the earliest signs of autism in infants has become a significant sub-field of autism research. This work invokes specific ethical concerns such as use of ‘at-risk’ language, communicating study findings to parents and the future perspective of enrolled infants when they reach adulthood. This study aimed to ground this research field in an understanding of the perspectives of members of the autism community. Following focus groups to identify topics, an online survey was distributed to autistic adults, parents of children with autism and practitioners in health and education settings across 11 European countries. Survey respondents (n = 2317) were positively disposed towards early autism research, and there was significant overlap in their priorities for the field and preferred language to describe infant research participants. However, there were also differences including overall less favourable endorsement of early autism research by autistic adults relative to other groups and a dislike of the phrase ‘at-risk’ to describe infant participants, in all groups except healthcare practitioners. The findings overall indicate that the autism community in Europe is supportive of early autism research. Researchers should endeavour to maintain this by continuing to take community perspectives into account.

Production and comprehension of French wh-questions by children with autism spectrum disorder: A comparative study with specific language impairment: CORRIGENDUM

The nature of structural language difficulties in children with autism spectrum disorder (ASD) was explored in a comparative study with specific language impairment (SLI) through investigation of the frequently reported ASD weakness in receptive skills relative to expressive skills. Twenty French-speaking children with ASD aged 6 to 12 were compared to age-matched children with SLI on production and comprehension of wh-questions. The two groups displayed similar effects of the complexity of the different wh-strategies. In the ASD group (as in the SLI group), these effects were not greater in comprehension compared to production; moreover, nonverbal ability (which varied from normal to impaired) was not related to language performance. Observed ASD-SLI differences are argued to largely be due to ASD pragmatic deficits, rather than to a qualitative difference in structural language skills.

Emotional prosodic change detection in autism Spectrum disorder: an electrophysiological investigation in children and adults

BackgroundAutism spectrum disorder (ASD) is characterized by atypical behaviors in social environments and in reaction to changing events. While this dyad of symptoms is at the core of the pathology along with atypical sensory behaviors, most studies have investigated only one dimension. A focus on the sameness dimension has shown that intolerance to change is related to an atypical pre-attentional detection of irregularity. In the present study, we addressed the same process in response to emotional change in order to evaluate the interplay between alterations of change detection and socio-emotional processing in children and adults with autism.MethodsBrain responses to neutral and emotional prosodic deviancies (mismatch negativity (MMN) and P3a, reflecting change detection and orientation of attention toward change, respectively) were recorded in children and adults with autism and in controls. Comparison of neutral and emotional conditions allowed distinguishing between general deviancy and emotional deviancy effects. Moreover, brain responses to the same neutral and emotional stimuli were recorded when they were not deviants to evaluate the sensory processing of these vocal stimuli.ResultsIn controls, change detection was modulated by prosody: in children, this was characterized by a lateralization of emotional MMN to the right hemisphere, and in adults, by an earlier MMN for emotional deviancy than for neutral deviancy. In ASD, an overall atypical change detection was observed with an earlier MMN and a larger P3a compared to controls suggesting an unusual pre-attentional orientation toward any changes in the auditory environment. Moreover, in children with autism, deviancy detection depicted reduced MMN amplitude. In addition in children with autism, contrary to adults with autism, no modulation of the MMN by prosody was present and sensory processing of both neutral and emotional vocal stimuli appeared atypical.ConclusionsOverall, change detection remains altered in people with autism. However, differences between children and adults with ASD evidence a trend toward normalization of vocal processing and of the automatic detection of emotion deviancy with age.

Pragmatic versus structural difficulties in the production of pronominal clitics in French-speaking children with autism spectrum disorder

Background and aims Impaired production of third person accusative pronominal clitics is a signature of language impairment in French-speaking children. It has been found to be a prominent and persistent difficulty in children and adolescents with specific language impairment. Previous studies have reported that many children with autism spectrum disorder also have low performance on these clitics. However, it remains unclear whether these difficulties in children with autism spectrum disorder are due to structural language impairment or to pragmatic deficits. This is because pragmatics skills, notoriously weak in children with autism spectrum disorder, are also needed for appropriate use of pronouns. Use of pronouns without clear referents and difficulty with discourse pronouns (first and second person), which require taking into account the point of view of one’s interlocutor (perspective shifting), have frequently been reported for autism spectrum disorder. Methods We elicited production of nominative, reflexive and accusative third and first person pronominal clitics in 19 verbal children with autism spectrum disorder (aged 6–12, high and low functioning, with structural language impairment, or with normal language) and 19 age-matched children with specific language impairment. If pragmatics is behind difficulties on these elements, performance on first-person clitics would be expected to be worse than performance on third person clitics, since it requires perspective shifting. Furthermore, worse performance for first person clitics was expected in the children with autism spectrum disorder compared to the children with specific language impairment, since weak pragmatics is an integral part of impairment in the former, but not in the latter. More generally, different error patterns would be expected in the two groups, if the source of difficulty with clitics is different (a pragmatic deficit vs. a structural language deficit). Results Similar patterns of relative difficulties were found in the autism spectrum disorder language impairment and specific language impairment groups, with third person accusative clitics being produced at lower rates than first-person pronouns and error patterns being essentially identical. First-person pronouns did not pose particular difficulties in the children with autism spectrum disorder (language impairment or normal language) with respect to third-person pronouns or to the children with specific language impairment. Performance was not related to nonverbal intelligence in the autism spectrum disorder group. Conclusions The elicitation task used in this study included explicit instruction, and focus on perspective shifting (both visual and verbal), allowing for potential pragmatic effects to be controlled. Moreover, the task elicited a variety of types of clitics in morphosyntactic contexts of varying complexity, providing ample opportunities for employment of perspective shifting, which may have also curtailed perseveration of third person over first person. These properties of the task allowed for the grammatical nature of children’s difficulties with third-person accusative clitics to emerge unambiguously. Implications Assessment of structural language abilities in children with autism spectrum disorder requires careful consideration of task demands. The influence of pragmatic abilities on structural language performance can be circumvented by making the pragmatic demands of the task explicit and salient. Filtering out this potential influence on structural language performance is fundamental to understanding language profiles in children with autism spectrum disorder and thus which children could benefit from which kinds of language intervention.

A strategic plan to identify key neurophysiological mechanisms and brain circuits in autism

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.