Functional connectivity in the first year of life in infants at-risk for autism: a preliminary near-infrared spectroscopy study

Background: Autism spectrum disorder (ASD) has been called a “developmental disconnection syndrome,” however the majority of the research examining connectivity in ASD has been conducted exclusively with older children and adults. Yet, prior ASD research suggests that perturbations in neurodevelopmental trajectories begin as early as the first year of life. Prospective longitudinal studies of infants at risk for ASD may provide a window into the emergence of these aberrant patterns of connectivity. The current study employed functional connectivity near-infrared spectroscopy (NIRS) in order to examine the development of intra- and inter-hemispheric functional connectivity in high- and low-risk infants across the first year of life. Methods: NIRS data were collected from 27 infants at high risk for autism (HRA) and 37 low-risk comparison (LRC) infants who contributed a total of 116 data sets at 3-, 6-, 9-, and 12-months. At each time point, HRA and LRC groups were matched on age, sex, head circumference, and Mullen Scales of Early Learning scores. Regions of interest (ROI) were selected from anterior and posterior locations of each hemisphere. The average time course for each ROI was calculated and correlations for each ROI pair were computed. Differences in functional connectivity were examined in a cross-sectional manner. Results: At 3-months, HRA infants showed increased overall functional connectivity compared to LRC infants. This was the result of increased connectivity for intra- and inter-hemispheric ROI pairs. No significant differences were found between HRA and LRC infants at 6- and 9-months. However, by 12-months, HRA infants showed decreased connectivity relative to LRC infants. Conclusions: Our preliminary results suggest that atypical functional connectivity may exist within the first year of life in HRA infants, providing support to the growing body of evidence that aberrant patterns of connectivity may be a potential endophenotype for ASD

Memory, learning and language in autism spectrum disorder

Background and aims: The ‘dual-systems’ model of language acquisition has been used by Ullman and colleagues to explain patterns of strength and weakness in the language of higher-functioning people with autism spectrum disorder (ASD). Specifically, intact declarative/explicit learning is argued to compensate for a deficit in non-declarative/implicit procedural learning, constituting an example of the so-called ‘see-saw’ effect. Ullman and Pullman (2015) extended their argument concerning a see-saw effect on language in ASD to cover other perceived anomalies of behaviour, including impaired acquisition of social skills. The aim of this paper is to present a critique of Ullman and colleagues’ claims, and to propose an alternative model of links between memory systems and language in ASD. Main contribution: We argue that a 4-systems model of learning, in which intact semantic and procedural memory are used to compensate for weaknesses in episodic memory and perceptual learning, can better explain patterns of language ability across the autistic spectrum. We also argue that attempts to generalise the ‘impaired implicit learning/spared declarative learning’ theory to other behaviours in ASD are unsustainable. Conclusions: Clinically significant language impairments in ASD are under-researched, despite their impact on everyday functioning and quality of life. The relative paucity of research findings in this area lays it open to speculative interpretation which may be misleading. Implications: More research is need into links between memory/learning systems and language impairments across the spectrum. Improved understanding should inform therapeutic intervention, and contribute to investigation of the causes of language impairment in ASD with potential implications for prevention

Defining language impairments in a subgroup of children with autism spectrum disorder

Autism spectrum disorder (ASD) is diagnosed on the basis of core impairments in pragmatic language skills, which are found across all ages and subtypes. In contrast, there is significant heterogeneity in language phenotypes, ranging from nonverbal to superior linguistic abilities, as defined on standardized tests of vocabulary and grammatical knowledge. The majority of children are verbal but impaired in language, relative to age-matched peers. One hypothesis is that this subgroup has ASD and co-morbid specific language impairment (SLI). An experiment was conducted comparing children with ASD to children with SLI and typically developing controls on aspects of language processing that have been shown to be impaired in children with SLI: repetition of nonsense words. Patterns of performance among the children with ASD and language impairment were similar to those with SLI, and contrasted with the children with ASD and no language impairment and typical controls, providing further evidence for the hypothesis that a subgroup of children with ASD has co-morbid SLI. The findings are discussed in the context of brain imaging studies that have explored the neural bases of language impairment in ASD and SLI, and overlap in the genes associated with elevated risk for these disorders.M01 RR00533 - NCRR NIH HHS; R01 DC10290 - NIDCD NIH HHS; U19 DC03610 - NIDCD NIH HH

Neural Processing of Repetition and Non-Repetition Grammars in 7- and 9-Month-Old Infants

An essential aspect of infant language development involves the extraction of meaningful information from a continuous stream of auditory input. Studies have identified early abilities to differentiate auditory input along various dimensions, including the presence or absence of structural regularities. In newborn infants, frontal and temporal regions were found to respond differentially to these regularities (Gervain et al., 2008), and in order to examine the development of this abstract rule learning we presented 7- and 9-month-old infants with syllables containing an ABB pattern (e.g., “balolo”) or an ABC pattern (e.g., “baloti”) and measured activity in left and right lateral brain regions using near-infrared spectroscopy (NIRS). While prior newborn work found increases in oxyhemoglobin (oxyHb) activity in response to ABB blocks as compared to ABC blocks in anterior regions, 7- and 9-month-olds showed no differentiation between grammars in oxyHb. However, changes in deoxyhemoglobin (deoxyHb) pointed to a developmental shift, whereby 7-month-olds showed deoxyHb responding significantly different from zero for ABB blocks, but not ABC blocks, and 9-month-olds showed the opposite pattern, with deoxyHb responding significantly different from zero for the ABC blocks but not the ABB blocks. DeoxyHb responses were more pronounced over anterior regions. A grammar by time interaction also illustrated that during the early blocks, deoxyHb was significantly greater to ABC than in later blocks, but there was no change in ABB activation over time. The shift from stronger activation to ABB in newborns (Gervain et al., 2008) and 7-month-olds in the present study to stronger activation to ABC by 9-month-olds here is discussed in terms of changes in stimulus salience and novelty preference over the first year of life. The present discussion also highlights the importance of future work exploring the coupling between oxyHb and deoxyHb activation in infant NIRS studies

Changing the perspective on early development of Rett syndrome

We delineated the achievement of early speech-language milestones in 15 young children with Rett syndrome (MECP2 positive) in the first two years of life using retrospective video analysis. By contrast to the commonly accepted concept that these children are normal in the pre-regression period, we found markedly atypical development of speech-language capacities, suggesting a paradigm shift in the pathogenesis of Rett syndrome and a possible approach to its early detection

When prototypes are not best: Judgments made by children with autism

The current study used a factorial comparison experimental design to investigate conflicting findings on prototype effects shown by children with autism (Klinger & Dawson, 2001; Molesworth, Bowler, & Hampton, 2005). The aim was to see whether children with high –functioning autism could demonstrate prototype effects via categorization responses and whether failure to do so was related to difficulty understanding ambiguous task demands. Two thirds of the autism group did show an effect. The remainder, a sub-group defined by performance on a control task, did not. The discussion focuses on the influence of heterogeneity within the autism group and the ability to resolve ambiguity on task performance. Finally, an alternative experimental design is recommended for further research into these issues

Atypical audiovisual speech integration in infants at risk for autism

The language difficulties often seen in individuals with autism might stem from an inability to integrate audiovisual information, a skill important for language development. We investigated whether 9-month-old siblings of older children with autism, who are at an increased risk of developing autism, are able to integrate audiovisual speech cues. We used an eye-tracker to record where infants looked when shown a screen displaying two faces of the same model, where one face is articulating/ba/and the other/ga/, with one face congruent with the syllable sound being presented simultaneously, the other face incongruent. This method was successful in showing that infants at low risk can integrate audiovisual speech: they looked for the same amount of time at the mouths in both the fusible visual/ga/− audio/ba/and the congruent visual/ba/− audio/ba/displays, indicating that the auditory and visual streams fuse into a McGurk-type of syllabic percept in the incongruent condition. It also showed that low-risk infants could perceive a mismatch between auditory and visual cues: they looked longer at the mouth in the mismatched, non-fusible visual/ba/− audio/ga/display compared with the congruent visual/ga/− audio/ga/display, demonstrating that they perceive an uncommon, and therefore interesting, speech-like percept when looking at the incongruent mouth (repeated ANOVA: displays x fusion/mismatch conditions interaction: F(1,16) = 17.153, p = 0.001). The looking behaviour of high-risk infants did not differ according to the type of display, suggesting difficulties in matching auditory and visual information (repeated ANOVA, displays x conditions interaction: F(1,25) = 0.09, p = 0.767), in contrast to low-risk infants (repeated ANOVA: displays x conditions x low/high-risk groups interaction: F(1,41) = 4.466, p = 0.041). In some cases this reduced ability might lead to the poor communication skills characteristic of autism

Spatial contrast sensitivity in adolescents with autism spectrum disorders

Adolescents with autism spectrum disorders (ASD) and typically developing (TD) controls underwent a rigorous psychophysical assessment that measured contrast sensitivity to seven spatial frequencies (0.5-20 cycles/degree). A contrast sensitivity function (CSF) was then fitted for each participant, from which four measures were obtained: visual acuity, peak spatial frequency, peak contrast sensitivity, and contrast sensitivity at a low spatial frequency. There were no group differences on any of the four CSF measures, indicating no differential spatial frequency processing in ASD. Although it has been suggested that detail-oriented visual perception in individuals with ASD may be a result of differential sensitivities to low versus high spatial frequencies, the current study finds no evidence to support this hypothesis