Molecular Autism最新文献

Background: Sensory processing requires selectivity to salient sensory input. Many autistic individuals report different sensory processing, which has been associated with altered sensory selectivity. The locus-coeruleus norepinephrine (LC-NE) system modulates the neuronal gain of sensory input, which represents a neurophysiological mechanism of sensory selectivity. In autistic individuals, we hypothesized that LC-NE tonic upregulation reduces sensory selectivity and underlies different sensory processing.

Methods: Autistic (n = 139) and non-autistic (n = 98) individuals were assessed during a passive auditory oddball task with pupillometry and electroencephalography. For every trial, a baseline pupil size (BPS) assessed LC-NE tonic activity that coincides with current arousal, while a stimulus-evoked pupillary response (SEPR) assessed LC-NE phasic activity that estimated sensory selectivity. Electroencephalography assessed amplitudes of mismatch negativity (MMN-amp) that estimated pre-attentive change detection as a brain-activity readout of sensory selectivity. Measures were modeled between groups within the task by combining Frequentist and Bayesian approaches.

Results: Across groups, higher BPS was associated with more negative MMN-amp to standards and oddballs. A more negative MMN-amp to standards was associated with a higher SEPR to standards. Controlling for these associations, autistic versus non-autistic individuals showed a higher SEPR in response to standards. In addition, a positive association of BPS and SEPR to standards was specific to autistic individuals. With task progression, autistic versus non-autistic individuals showed a higher initial increase and subsequently steeper decrease of BPS. This was supported by Bayesian posterior distribution estimates.

Limitations: A short trial duration required concatenating trials to epochs and applying a linear-time invariant filter to capture the slow pupil changes. Without an LC-NE manipulation, we cannot rule out that pupil changes are evoked by other cortical pathways than the LC-NE.

Conclusions: Across groups, LC-NE tonic upregulation is emphasized as a general mechanism that un-specifically increases pre-attentive change detection to all sensory stimuli, which then increases sensory selectivity to frequent stimuli. In autistic individuals, different sensory processing is characterized by increased sensory selectivity to frequent stimuli. This is likely caused by an LC-NE tonic upregulation. It associates autistic sensory processing with increased arousal upregulation that increases sensory selectivity to inconspicuous auditory information.

Background: Little is known about how autistic children's brains process language during real-world "social contexts," despite the fact that challenges with language, communication, and social interaction are core features of Autism Spectrum Disorder (ASD).

Methods: We investigated the neural bases of language processing during social and non-social contexts in a sample of autistic and neurotypical (NT) preschool-aged children, 3-6 years old, living in the United States. Functional near-infrared spectroscopy was used to measure children's brain response to "live language" spoken by a live experimenter during an in-person social context (i.e., book reading) and "recorded language" played via an audio recording during a non-social context (i.e., screen time). We examined within-group and between-group differences in the strength and localization of brain response to live language and recorded language, as well as correlations between children's brain response to live language versus recorded language and their language skills, as measured by the Preschool Language Scales.

Results: In the NT group, brain response to live language was greater than brain response to recorded language in the right temporal parietal junction (TPJ). In the ASD group, the strength of brain response did not differ between conditions in any brain regions of interest after correction for multiple comparisons. Children who showed a greater difference in right TPJ brain response to live language versus recorded language had higher language skills; this significant correlation was driven by the ASD group.

Limitations: Findings should be considered preliminary until they are replicated in a larger sample.

Conclusions: Group level findings indicate that for NT children, but not autistic children, the right TPJ responds more strongly to live language presented during a social context compared to recorded language presented during a non-social context. However, individual differences in how the right TPJ responds to language during social versus non-social contexts may help to explain why language skills are so variable across children on the autism spectrum.

Background: Despite advancements in neonatal care, premature infants remain at increased risk for cognitive and socio-emotional difficulties, collectively referred to as the preterm behavioral phenotype. A particular aspect of this phenotype is atypical social orienting, characterized by reduced attention towards socially relevant information, similar to what has been reported for autism spectrum disorder.

Methods: We monitored a cohort of prematurely born children from birth. At five years of age, we administered a series of frequency-tagging electroencephalography (EEG) paradigms to investigate their neural sensitivity to social cues, i.e., sensitivity for faces and voices. Frequency-tagging EEG utilizes fast periodic stimulation to elicit synchronized brain responses measurable in the frequency domain. In the preterm (N = 66) and in a matched full-term control group (N = 32), we applied two multi-input frequency-tagging EEG paradigms, simultaneously presenting streams of social and non-social stimuli, each tagged at different presentation rates. In the visual domain, we presented streams of faces and houses. In the auditory domain, we presented streams of voices and object sounds. We used linear mixed models to investigate the effects of group and stimulus type.

Results: All children showed an implicit social bias towards faces and voices. Compared to full-term peers, preterm preschoolers showed intact neural tuning to faces, but diminished neural tuning to voices, in particular in the speech-sensitive 3.70 Hz frequency band.

Limitations: The preterm group was highly heterogeneous in terms of gestational age and consisted of healthy preterm preschoolers. Moreover, the used paradigms are artificial and may not fully capture neural tuning in naturalistic social interactions.

Conclusions: The diminished neural response to voices in the preterm children may potentially reflect the effects of atypical auditory exposure and premature visual exposure in the NICU environment or altered social experiences early in life. These findings contribute to our understanding of the socio-emotional and communicative development in preterm populations and may aid in identifying children at risk for psychopathology or subclinical socio-emotional difficulties.

Background: Theory of mind (ToM) is fundamental for social interactions, allowing individuals to appreciate that others have their own mental states. Children and youth with neurodevelopmental conditions (e.g., autism, attention-deficit hyperactivity disorder (ADHD), and obsessive-compulsive disorder (OCD)) often show differences in ToM abilities compared to their neurotypical (NT) peers. Given the phenotypic heterogeneity and overlap associated with these conditions, this motivates a transdiagnostic investigation of ToM across neurodevelopmental conditions.

Methods: Five hundred and fifty-five participants (5-22 years; 193 ADHD, 189 autism, 33 OCD, and 140 NT) were recruited via the Province of Ontario Neurodevelopmental Disorders network. To measure ToM, participants completed the Social Attribution Task (SAT), where participants attribute social stories to videos of moving shapes. The Animation Index (ability to attribute social stories to the videos) and Pertinence Index (how pertinent the attributions are) were calculated from the descriptions. Three analyses were performed: (1) a case-control analysis, comparing the SAT indices amongst the diagnostic groups, (2) a univariate dimensional analysis, examining associations with phenotypic variables (e.g., full-scale IQ, verbal IQ, and social communication difficulties), (3) and a multivariate analysis (partial least squares) that identifies a latent space that describes the associations between the SAT and phenotypic measures.

Results: There were no between-group differences in the Animation Index, but the Pertinence Index was significantly lower in autism compared to the other diagnostic categories. Phenotypic variables (full-scale IQ, verbal IQ, and social communication difficulties) were found to be significantly associated with SAT performance across groups, and explained more variance than the diagnostic categories. In the multivariate analysis, the phenotypic variables contributed more strongly to the identified latent component compared to the diagnostic categories.

Limitations: The verbal requirement of the SAT limited the inclusion of non-verbal participants, while the overall cognitive demand limited the participation of those with lower IQs. Additionally, our OCD group was significantly smaller than the other groups, which may have limited our ability to detect OCD-specific effects.

Conclusions: In a large sample, we found that transdiagnostic measures, such as IQ and social communication difficulties, are related to SAT abilities across neurodivergent and neurotypical children and youth and better describe differences in SAT performance compared to the individual diagnostic categories. Although poorer performance on ToM tasks has been classically associated with autism, this study highlights that transdiagnostic, phenotypic variables are a stronger predictor of SAT perform

Background: Autistic communities in Europe continue to face difficulties accessing services despite increasing rates of autism diagnosis in recent years.

Methods: To investigate autistic people's access to services in Europe and reasons for unsuccessful access, we conducted the ACCESS-EU survey comprising of 2322 formally diagnosed autistic people and family carers living within the European Union (EU) and the United Kingdom (UK). The survey also examined age group (adult vs. child) and gender (male vs. female) differences in results.

Results: Overall, autistic people reported access to therapy (33.38%), mental health (29.89%), educational (27.05%), medical (34.28%), financial (26.66%), needs assessment (14.90%), information/referral (14.73%), social care (14.43%), employment (7.54%), housing (6.80%), legal (3.96%), helpline (3.40%) and other services (0.26%), and most (≥ 57.61%) had waited up to 6 months from referral to access most services. Several respondents were also unable to access therapeutic (13.53%), mental health (11.90%), autism diagnostic (5.92%), needs assessment (8.32%), financial (9.62%), educational (8.10%), social care (7.39%), information/referral (6.14%), medical (7.28%), housing (5.92%), employment (5.43%), legal (3.42%), and helpline services (2.34%). Reasons cited by respondents for their unsuccessful service access included service unavailability (23.08%), service unsuitability or participant ineligibility (20.04%), long waitlists (17.42%), service unaffordability (11.80%), and rejection from service due to autism diagnosis (9.87%), along with other reasons not listed in the survey (18.42%). Significant age group and gender differences were observed for successful access to services, waiting time, unsuccessful access and reasons for unsuccessful access. Among the five most represented countries in the survey-the UK (33.33%), Spain (14.04%), Poland (13.87%), France (11.07%) and Germany (6.03%)-overall service access was most inconsistent in Poland and the UK, highest in Germany and Spain but poorest in France.

Limitations: Issues related to survey presentation such as the languages in which the survey was conducted and the phrasing of some questions should be considered, as well as issues regarding subjectivity and ambiguity of data analysis such as translation of non-English responses into English.

Conclusions: Our findings suggest that service access among autistic people in Europe is inconsistent. Significant improvement to current policies is required to enhance access to services across Europe.

Background: Humans form almost instantaneous impressions of everyone they encounter. These impressions set the first tone for how they approach and interact with others. Research on impression formation unveiled that impressions formed by autistic and non-autistic people are often less favourable when rating an autistic person. This effect is partly explainable by differences in motion dynamics.

Methods: In this preregistered study, we systematically assessed impressions formed by 27 autistic and 36 non-autistic comparison observers when watching videos showing silent interactions between either two non-autistic or between an autistic and a non-autistic person. We used an eye tracker to capture their gaze patterns while observing these interactions. Of each dyadic interaction, video vignettes with high and vignettes with low interpersonal synchrony of movement (IPS_mov) were extracted using Motion Energy Analysis so that we could investigate the effects of interpersonal synchrony and diagnosis, respectively.

Results: Interactions were rated less favourably when the observed dyad included an autistic adult. Additionally, interactions showing low IPS_mov were rated less favourably than interactions showing high IPS_mov, regardless of dyad type. Both autistic and comparison observers rated interactions of non-autistic dyads and high IPS_mov interactions more favourably. Gaze patterns revealed differences between autistic and comparison observers, but no differences due to IPS_mov or dyad type. Furthermore, dwell times to hands predicted ratings.

Limitations: In this study, we investigated specific influences on impression formation, specifically interpersonal synchrony of movement and autism. There are many more potentially interesting aspects of individuals that impact impression formation, such as facial expressiveness, gaze behaviour and linguistic content of conversations, which should be investigated systematically and in a controlled fashion in future research.

Conclusions: Extending research on autism and impression formation to dyadic interactions, this study reveals that motion dynamics play a role in how pleasant interactions are perceived. Autistic-involved interactions were rated lower, despite observers being unaware of the dyad type and only watching people's outlines. Future research should identify conversational aspects driving lower ratings of mixed dyads, potentially considering the effect of hand dwell times on ratings. Autistic and comparison observers showed different gaze patterns despite similar ratings, confirming distinct social information processing.

Background: Autism and attention deficit hyperactivity disorder (ADHD) are two highly heterogeneous neurodevelopmental conditions with variable underlying neurobiology. Imaging studies have yielded varied results, and it is now clear that there is unlikely to be one characteristic neuroanatomical profile of either condition. Parsing this heterogeneity could allow us to identify more homogeneous subgroups, either within or across conditions, which may be more clinically informative. This has been a pivotal goal for neurodevelopmental research using both clinical and neuroanatomical features, though results thus far have again been inconsistent with regards to the number and characteristics of subgroups.

Methods: Here, we use population modelling to cluster a multi-site dataset based on global and regional centile scores of cortical thickness, surface area and grey matter volume. We use HYDRA, a novel semi-supervised machine learning algorithm which clusters based on differences to controls and compare its performance to a traditional clustering approach.

Results: We identified distinct subgroups within autism and ADHD, as well as across diagnosis, often with opposite neuroanatomical alterations relatively to controls. These subgroups were characterised by different combinations of increased or decreased patterns of morphometrics. We did not find significant clinical differences across subgroups.

Limitations: Crucially, however, the number of subgroups and their membership differed vastly depending on chosen features and the algorithm used, highlighting the impact and importance of careful method selection.

Conclusions: We highlight the importance of examining heterogeneity in autism and ADHD and demonstrate that population modelling is a useful tool to study subgrouping in autism and ADHD. We identified subgroups with distinct patterns of alterations relative to controls but note that these results rely heavily on the algorithm used and encourage detailed reporting of methods and features used in future studies.

Background: The prevalence of autism spectrum disorder (ASD), a common developmental disorder, has surged in recent years. Accordingly, the identification and early management of possible risk factors can diminish ASD incidence.

Aim: To determine the prevalence and severity of idiopathic ASD in Egyptian children aged 12 months to 12 years, and to identify the epidemiological, sociodemographic, and environmental risk factors contributing to this disorder.

Methods: This study comprised 41,640 children from the main eight geographic areas in Egypt. It was conducted through four phases: household screening, facility-based screening for high-risk children, diagnosis confirmation, and risk factor assessment.

Results: The prevalence of ASD as confirmed by the criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) and the Childhood Autism Rating Scale (CARS) was 1.1% (455 out of 41,640), with significant geographic variability. Urban areas had a significantly higher prevalence than rural areas. Children aged 3-6 years showed the highest prevalence at 1.5%. Boys were four times more affected than girls, with prevalence rates of 1.7% and 0.4%, respectively. Significant risk factors included: a history of convulsions (AOR = 4.7; 95% CI: 3.3-6.79), low birth weight (AOR = 2.08; 95% CI: 1.54-2.79), prolonged stays in neonatal intensive care unit (NICU) longer than two days (AOR = 1.91; 95% CI: 1.46-2.49) and maternal health problems during pregnancy (AOR = 1.66; 95% CI:1.36-1.95). Regarding severity, 45% of diagnosed children had moderate ASD, 39% had severe ASD, and 16% had mild ASD. Female gender and older age were significant predictors of greater ASD severity.

Conclusion: ASD prevalence in Egypt is comparable to other Middle Eastern countries. Policymakers should utilize these findings to design targeted public health interventions aimed at early detection, management, and prevention of ASD progression.