Early trajectories and moderators of autistic language profiles: A longitudinal study in preschoolers.

LAY ABSTRACT: Language development can greatly vary among autistic children. Children who struggle with language acquisition often face many challenges and experience lower quality of life. However, little is known about the early language trajectories of autistic preschoolers and their moderators. Autistic language can be stratified into three profiles. Language unimpaired experience little to no language difficulties; language impaired show significant difficulties in language; minimally verbal never develop functional language. In this study, we used a longitudinal sample of preschoolers with autism and with typical development (aged 1.5-5.7 years). We replicated the three language profiles through a data-driven approach. We also found that different factors modulated the language outcome within each group. For instance, non-verbal cognition at age 2.4 moderated the participants' attribution to each language profile. Moreover, early intervention moderated verbal outcome in the language impaired profile. In conclusion, we provided a detailed description of how autistic preschoolers acquire language, and what factors might influence their trajectories. Our findings could inspire more personalized intervention for early autistic language difficulties.

Prosodic signatures of ASD severity and developmental delay in preschoolers.

Atypical prosody in speech production is a core feature of Autism Spectrum Disorder (ASD) that can impact everyday life communication. Because the ability to modulate prosody develops around the age of speech acquisition, it might be affected by ASD symptoms and developmental delays that emerge at the same period. Here, we investigated the existence of a prosodic signature of developmental level and ASD symptom severity in a sample of 74 autistic preschoolers. We first developed an original diarization pipeline to extract preschoolers' vocalizations from recordings of naturalistic social interactions. Using this novel approach, we then found a robust voice quality signature of ASD developmental difficulties in preschoolers. Furthermore, some prosodic measures were associated with one year later outcome in participants who had not acquired speech yet. Altogether, our results highlight the potential benefits of automatized diarization algorithms and prosodic metrics for digital phenotyping in psychiatry, helping clinicians establish early diagnosis and prognosis.

Measuring social orienting in preschoolers with autism spectrum disorder using cartoons stimuli.

Altered social orienting (SO) was proposed as the primary source of socio-communicative difficulties in autism spectrum disorder (ASD). Eye-tracking studies generally confirm a decreased SO in ASD population. However, SO has been scarcely investigated using minimally social stimuli such as cartoons. The extent to which SO might be decreased when watching cartoons is therefore unknown. Yet, it could allow for malleable and child-friendly paradigms that could be sensitive to early atypical visual preference. In this study, 90 preschoolers with ASD (age = 3.19 ± 0 .88) and 20 TD (age = 2.95 ± 1.26) watched two eye-tracking preference tasks. One Realistic task, displaying children dancing versus geometric shapes moving repetitively and a Cartoon task, displaying social and non-social cartoon stimuli with similar movements. We measured SO percentage along with refined visual exploration parameters and compared those of ASD children to TDs. In addition, we investigated their relations with behavioral measures such as symptom severity, developmental and adaptive levels. We evidenced a decreased SO percentage in ASD compared to TD children when watching the Realistic task but not the Cartoon task. We did not identify any other between groups differences. However, we identified several correlations between eye-tracking measures and developmental as well as adaptive measures within the Cartoon task. Together, our results support a preferential orientation of children with autism towards repetitively moving shapes but no decreased SO when measured with minimally social stimuli. Nonetheless, when investigating finer visual exploration parameters, even socially simple stimuli elicited atypical gaze patterns related to early developmental delay.

Distinct Patterns of Cognitive Outcome in Young Children With Autism Spectrum Disorder Receiving the Early Start Denver Model.

Evidence-based, early intervention significantly improves developmental outcome in young children with autism. Nonetheless, there is high interindividual heterogeneity in developmental trajectories during the therapy. It is established that starting intervention as early as possible results in better developmental outcomes. But except for younger age at start, there is no clear consensus about behavioral characteristics that could provide a reliable individual prediction of a child's developmental outcome after receiving an early intervention. In this study, we analyze developmental trajectories of preschoolers with autism who received 2 years of intervention using the Early Start Denver Model (ESDM) approach in Geneva, Switzerland in an individual setting (n = 55, aged 28.7 ± 5.1 months with a range of 15-42). Our aim was to identify early predictors of response to intervention. We applied a cluster analysis to distinguish between 3 groups based on their cognitive level at intake, and rates of cognitive change over the course of intervention. The first group of children only had a mild cognitive delay at intake and nearly no cognitive delay by the end of intervention (Higher Cognitive at baseline: HC). The children in the two other groups all presented with severe cognitive delay at baseline. However, they had two very different patterns of response to intervention. The majority significantly improved developmental scores over the course of intervention (Optimal Responders: OptR) whereas a minority of children showed only modest improvement (Minimal Responders: MinR). Further analyses showed that children who ended up having an optimal 2-year intervention outcome (OptR) were characterized by higher adaptive functioning at baseline combined with rapid developmental improvement during the first 6 months of intervention. Inversely, less significant progress by the sixth month of intervention was associated with a less optimal response to treatment (MinR).

Downregulation of the schizophrenia risk-gene Dgcr2 alters early microcircuit development in the mouse medial prefrontal cortex.

Alterations in the generation, migration and integration of different subtypes of neurons in the medial prefrontal cortex (mPFC) microcircuit could play an important role in vulnerability to schizophrenia. Using in vivo cell-type specific manipulation of pyramidal neurons (PNs) progenitors, we aim to investigate the role of the schizophrenia risk-gene DiGeorge Critical Region 2 (Dgcr2) on cortical circuit formation in the mPFC of developing mice. This report describes how Dgcr2 knock down in upper-layer PNs impacts the functional maturation of PNs and interneurons (INs) in the mPFC. First, we demonstrate that Dgcr2 knock-down disrupts laminar positioning, dendritic morphology and excitatory activity of upper-layer PNs. Interestingly, inhibitory activity is also modified in Dgcr2 knock-down PNs, suggesting a broader microcircuit alteration involving interneurons. Further analyses show that the histological maturation of parvalbumin (PV) INs is not dramatically impaired, thus implying that other INs subtypes might be at play in the reported microcircuit alteration. Overall, this study unravels how local functional deficits of the early postnatal development of the mPFC can be induced by Dgcr2 knock-down in PNs.

Altered Gray-White Matter Boundary Contrast in Toddlers at Risk for Autism Relates to Later Diagnosis of Autism Spectrum Disorder.

BACKGROUND: Recent neuroimaging studies have highlighted differences in cerebral maturation in individuals with autism spectrum disorder (ASD) in comparison to typical development. For instance, the contrast of the gray-white matter boundary is decreased in adults with ASD. To determine how gray-white matter boundary integrity relates to early ASD phenotypes, we used a regional structural MRI index of gray-white matter contrast (GWC) on a sample of toddlers with a hereditary high risk for ASD. MATERIALS AND METHODS: We used a surface-based approach to compute vertex-wise GWC in a longitudinal cohort of toddlers at high-risk for ASD imaged twice between 12 and 24 months (n = 20). A full clinical assessment of ASD-related symptoms was performed in conjunction with imaging and again at 3 years of age for diagnostic outcome. Three outcome groups were defined (ASD, n = 9; typical development, n = 8; non-typical development, n = 3). RESULTS: ASD diagnostic outcome at age 3 was associated with widespread increases in GWC between age 12 and 24 months. Many cortical regions were affected, including regions implicated in social processing and language acquisition. In parallel, we found that early onset of ASD symptoms (i.e., prior to 18-months) was specifically associated with slower GWC rates of change during the second year of life. These alterations were found in areas mainly belonging to the central executive network. LIMITATIONS: Our study is the first to measure maturational changes in GWC in toddlers who developed autism, but given the limited size of our sample results should be considered exploratory and warrant further replication in independent and larger samples. CONCLUSION: These preliminary results suggest that ASD is linked to early alterations of the gray-white matter boundary in widespread brain regions. Early onset of ASD diagnosis constitutes an independent clinical parameter associated with a specific corresponding neurobiological developmental trajectory. Altered neural migration and/or altered myelination processes potentially explain these findings.