1. Baizer JS. Neuroanatomy of autism: what is the role of the cerebellum?. Cereb Cortex. 2024; 34(13): 94-103.

Autism (or autism spectrum disorder) was initially defined as a psychiatric disorder, with the likely cause maternal behavior (the very destructive « refrigerator mother » theory). It took several decades for research into brain mechanisms to become established. Both neuropathological and imaging studies found differences in the cerebellum in autism spectrum disorder, the most widely documented being a decreased density of Purkinje cells in the cerebellar cortex. The popular interpretation of these results is that cerebellar neuropathology is a critical cause of autism spectrum disorder. We challenge that view by arguing that if fewer Purkinje cells are critical for autism spectrum disorder, then any condition that causes the loss of Purkinje cells should also cause autism spectrum disorder. We will review data on damage to the cerebellum from cerebellar lesions, tumors, and several syndromes (Joubert syndrome, Fragile X, and tuberous sclerosis). Collectively, these studies raise the question of whether the cerebellum really has a role in autism spectrum disorder. Autism spectrum disorder is now recognized as a genetically caused developmental disorder. A better understanding of the genes that underlie the differences in brain development that result in autism spectrum disorder is likely to show that these genes affect the development of the cerebellum in parallel with the development of the structures that do underlie autism spectrum disorder.

Lien vers le texte intégral (Open Access ou abonnement)

2. Baloyi O, Jarvis MA, Chironda G, Mbeje P, Ngcobo SJ, Gqaleni T, Mhlongo EM, Ngcobo WB, Brysiewicz P. Experiences of families with children diagnosed with Autism Spectrum Disorder in World Health Organization Afro-Regions: A scoping review. Nurs Health Sci. 2024; 26(2): e13123.

A scoping review on Autism Spectrum Disorder (ASD) and its impact on the families of affected children was undertaken due to insufficient information available on the diverse experiences impacting their lives. Using the Joanna Briggs Institute methodology, eligibility criteria were guided by Population (families), Concept (family experiences), and Context (African region). English-language articles were sought from a variety of databases and search engines. The publication date of the identified articles ranged from 2003 to 2021 with most published in 2020 (n = 10), and the majority using qualitative methodologies (n = 51). Most family members involved were parents (n = 51) and their ages ranged from 18 to 75 years. The families experienced various challenges related to their child with regard to education, healthcare, and the broader community including lack of support. Family coping strategies included believing in God, attending counseling sessions, adapting, and accepting the situation. Healthcare professionals should be prepared and positioned to educate families and siblings on various aspects of ASD. There is a need for active, continued research on families within most countries of World Health Organization Afro-region.

Lien vers le texte intégral (Open Access ou abonnement)

3. Canals J, Morales-Hidalgo P, Voltas N, Hernández-Martínez C. Prevalence of comorbidity of autism and ADHD and associated characteristics in school population: EPINED study. Autism Res. 2024.

Autism and attention deficit hyperactivity disorder (ADHD) comorbidity in the school population have been understudied. This study estimates its prevalence considering both parents’ and teachers’ reports and clinical diagnosis. Sociodemographic, clinical, and cognitive data were compared by diagnostic groups: autism, ADHD, autism and ADHD, subthreshold autism spectrum disorder (ASD), subthreshold ADHD, and children without neurodevelopmental conditions. Following a two-phase design, 3727 parents and teachers (1802 preschoolers, 1925 school-age children) participated in the first phase. Subsequently, 781 participants underwent individual assessment for DSM-5 diagnoses. The estimated prevalence of the comorbid diagnosis was 0.51% (0.28%-0.74%), with significant sex differences (0.16% girls, 0.89% boys). The cooccurrence of symptoms of autism and ADHD reported by parents or teachers was 3.2% and 2.6%, respectively. ADHD comorbidity was observed in 32.8% of autistic children and 31.4% of those with subthreshold ASD. ASD comorbidity was observed in 9.8% of children with ADHD and 5.7% of those with subthreshold ADHD. Comorbidity was reported by at least one informant in 95% of children. Only 15.8% of children with autism and ADHD had been previously diagnosed with both conditions. Early detection and accurate comorbidity diagnosis are crucial to address the clinical and socio-educational needs of these children.

Lien vers le texte intégral (Open Access ou abonnement)

4. Corbett BA, Muscatello RA, McGonigle T, Vandekar S, Burroughs C, Sparks S. Trajectory of depressive symptoms over adolescence in autistic and neurotypical youth. Mol Autism. 2024; 15(1): 18.

BACKGROUND: Adolescence coincides with a dramatic rise in the onset of psychiatric conditions including depression. Depression symptoms may be particularly prevalent and impairing for youth with autism spectrum disorder (ASD). While prior research suggests adolescence is associated with worsening depression symptoms for typically developing (TD) and autistic youth, it is unclear if they follow a similar course. METHOD: The study examined the trajectory of depressive symptoms in autistic and neurotypical youth over a 4-year longitudinal study using linear and logistic mixed effects models. In youth with clinically relevant depressive scores (t-score > 65), moderating factors (i.e., diagnosis, age, puberty, sex) were explored. During Year 1, the sample included 244 youth 10-to-13 years: 140 in the ASD group (36 females) and 104 in the TD group (46 females). RESULTS: Autistic youth had elevated depression scores compared to TD peers (p < 0.001) and females were higher than males in both groups (p = 0.001). There was significant diagnosis by age (p < 0.001) and diagnosis by pubertal stage (p < 0.05) interactions. In the ASD group, elevated depressive scores presented in early adolescence and decreased during middle adolescence and puberty, whereas the TD group showed the opposite trend with an increase in depression symptoms with advancing development. LIMITATIONS: Limitations include an unequal sex distribution (fewer females), non-representative autistic sample (e.g., cognition and race/ethnicity), and potential confound of the COVID-19 pandemic. CONCLUSIONS: Autistic youth present with higher rates of depressive symptoms early in development; yet, approaching middle adolescence and puberty, the symptom trajectory in the autistic youth declines coinciding with an increase in the TD youth. While group trajectories are divergent, they lead to similar levels of depression in late adolescence with higher symptoms in females. Findings suggest a period of quiescence in depressive symptomology influenced by biopsychosocial factors impacting affective profiles.

Lien vers le texte intégral (Open Access ou abonnement)

5. Degré-Pelletier J, Danis É, Thérien VD, Bernhardt B, Barbeau EB, Soulières I. Differential neural correlates underlying visuospatial versus semantic reasoning in autistic children. Cereb Cortex. 2024; 34(13): 19-29.

While fronto-posterior underconnectivity has often been reported in autism, it was shown that different contexts may modulate between-group differences in functional connectivity. Here, we assessed how different task paradigms modulate functional connectivity differences in a young autistic sample relative to typically developing children. Twenty-three autistic and 23 typically developing children aged 6 to 15 years underwent functional magnetic resonance imaging (fMRI) scanning while completing a reasoning task with visuospatial versus semantic content. We observed distinct connectivity patterns in autistic versus typical children as a function of task type (visuospatial vs. semantic) and problem complexity (visual matching vs. reasoning), despite similar performance. For semantic reasoning problems, there was no significant between-group differences in connectivity. However, during visuospatial reasoning problems, we observed occipital-occipital, occipital-temporal, and occipital-frontal over-connectivity in autistic children relative to typical children. Also, increasing the complexity of visuospatial problems resulted in increased functional connectivity between occipital, posterior (temporal), and anterior (frontal) brain regions in autistic participants, more so than in typical children. Our results add to several studies now demonstrating that the connectivity alterations in autistic relative to neurotypical individuals are much more complex than previously thought and depend on both task type and task complexity and their respective underlying cognitive processes.

Lien vers le texte intégral (Open Access ou abonnement)

6. Demircan K, Chillon TS, Jensen RC, Jensen TK, Sun Q, Bonnema SJ, Glintborg D, Bilenberg N, Andersen MS, Schomburg L. Maternal selenium deficiency during pregnancy in association with autism and ADHD traits in children: the Odense Child Cohort. Free Radic Biol Med. 2024.

BACKGROUND: Selenoproteins regulate pathways controlling neurodevelopment, e.g., redox signaling and thyroid hormone metabolism. However, studies investigating maternal selenium in relation to child neurodevelopmental disorders are scarce. METHODS: 719 mother-child pairs from the prospective population-based Odense Child Cohort study in Denmark were included. Three selenium biomarkers, i.e. concentrations of serum selenium, selenoprotein P (SELENOP), and activity of glutathione peroxidase 3 (GPX3), along with serum copper, zinc and iron were measured in early third trimester (at 28.9 +/- 0.8 weeks of pregnancy). ADHD and ASD traits in children were assessed systematically using the established Child Behaviour Checklist at 5 years of age, based on a Danish reference cohort with cut-off at 90(th) percentile. Multivariable regression models adjusted for biologically relevant confounders were applied. RESULTS: 155 of 719 (21.6%) children had ASD traits and 59 of 719 (8.2%) children had traits of ADHD at 5 years of age. In crude and adjusted models, all three selenium biomarkers associated inversely with ADHD traits. For ADHD, fully adjusted OR for 10 μg/L increment in selenium was 0.76 (95% CI 0.60, 0.94), for one mg/L increment in SELENOP was 0.73 (0.56, 0.95), and for 10 U/L increment in GPx3 was 0.93 (0.87,1.00). Maternal total selenium was inversely associated with child ASD traits, OR per 10 μg/L increment was 0.85 (0.74, 0,98). SELENOP and GPx3 were not associated with ASD traits. The associations were specific to selenium, as other trace elements such as copper, zinc, or iron were not associated with the outcomes. CONCLUSIONS: The results provide coherent evidence for selenium deficiency as a risk factor for ADHD and ASD traits in an environment with borderline supply, the causality of which should be elucidated in a randomized controlled trial.

Lien vers le texte intégral (Open Access ou abonnement)

7. Denusik L, Glista D, Servais M, Friesen J, Oram J, Cunningham BJ. « We were the best people to do the job »: Caregivers’ reported outcomes of a virtual caregiver-delivered program for autistic preschoolers. Autism Dev Lang Impair. 2024; 9: 23969415241244767.

BACKGROUND AND AIMS: Caregiver-delivered programs are a recommended best practice to support young autistic children. While research has extensively explored children’s outcomes quantitatively, minimal qualitative research has been conducted to understand caregivers’ perspectives of program outcomes for themselves and their children. Hearing directly from caregivers is an important step in ensuring these programs are meeting the needs of those who use them. This study explored caregivers’ perceived outcomes following one virtual caregiver-delivered program, The Hanen Centre’s More Than Words(®) (MTW) program. METHODS: This study was a secondary analysis of data from individual interviews conducted with 21 caregivers who had recently participated in a virtual MTW program. A hybrid codebook thematic analysis approach was taken to analyze the interview data. Program outcomes were coded and analyzed within the International Classification Functioning, Disability, and Health (ICF) framework. Additionally, caregivers completed an online survey and rated Likert Scale items about perceived program outcomes, which were analyzed descriptively. RESULTS: Five themes were identified: (1) caregivers learned new strategies to facilitate their child’s development, (2) caregivers developed a new mindset, (3) children gained functional communication skills, (4) caregiver-child relationships improved, and (5) caregivers gained a social and professional support network. These themes fell within four of five ICF framework components (activities, participation, personal factors, and environmental factors). No themes were identified under Body Structures and Functions. Survey results indicated most caregivers reported learning new communication strategies (n = 20, 95%), and identifying new teaching opportunities with their child (n = 21, 100%). CONCLUSIONS: Some reported outcomes, related to Activities and Participation, were consistent with previous reports in the literature on the MTW program. In line with previous research, caregivers learned strategies to support their child’s communication development. Contrary to previous quantitative studies, caregivers in this study rarely commented on gains in vocabulary and instead focused on gains in skills that positively impacted their child’s ability to engage in meaningful social interaction. Novel outcomes were identified within the Participation, Personal Factors, and Environmental Factors components of the ICF framework. IMPLICATIONS: Caregivers in this study identified important outcomes for themselves and their child that have not been the focus of prior research, suggesting it is important to integrate their perspectives in the development and evaluation of caregiver-delivered programs. Clinicians should include goals that address outcomes identified as important by caregivers, including those that address children’s Participation, and those that target caregivers’ Personal and Environmental Factors. Developers of caregiver-delivered programs could integrate identified goals to ensure they are meeting families’ needs.

Lien vers le texte intégral (Open Access ou abonnement)

8. Du L, Ye F, Gao W, Yang A, Luan J, Xu M, Lv K, Hu P, Liu B, Yu H, Wang Y, Huang W, Shu N, Ouyang G, Yin Q, Shmuel A, Wang Y, Zhang Q, Xu P, Ma G. Decreased brain iron deposition based on quantitative susceptibility mapping correlates with reduced neurodevelopmental status in children with autism spectrum disorder. Cereb Cortex. 2024; 34(13): 63-71.

To investigate potential correlations between the susceptibility values of certain brain regions and the severity of disease or neurodevelopmental status in children with autism spectrum disorder (ASD), 18 ASD children and 15 healthy controls (HCs) were recruited. The neurodevelopmental status was assessed by the Gesell Developmental Schedules (GDS) and the severity of the disease was evaluated by the Autism Behavior Checklist (ABC). Eleven brain regions were selected as regions of interest and the susceptibility values were measured by quantitative susceptibility mapping. To evaluate the diagnostic capacity of susceptibility values in distinguishing ASD and HC, the receiver operating characteristic (ROC) curve was computed. Pearson and Spearman partial correlation analysis were used to depict the correlations between the susceptibility values, the ABC scores, and the GDS scores in the ASD group. ROC curves showed that the susceptibility values of the left and right frontal white matter had a larger area under the curve in the ASD group. The susceptibility value of the right globus pallidus was positively correlated with the GDS-fine motor scale score. These findings indicated that the susceptibility value of the right globus pallidus might be a viable imaging biomarker for evaluating the neurodevelopmental status of ASD children.

Lien vers le texte intégral (Open Access ou abonnement)

9. Fatemi SH, Eschenlauer A, Aman J, Folsom TD, Chekouo T. Quantitative proteomics of dorsolateral prefrontal cortex reveals an early pattern of synaptic dysmaturation in children with idiopathic autism. Cereb Cortex. 2024; 34(13): 161-71.

Autism spectrum disorder (ASD) is a developmental disorder with a rising prevalence and unknown etiology presenting with deficits in cognition and abnormal behavior. We hypothesized that the investigation of the synaptic component of prefrontal cortex may provide proteomic signatures that may identify the biological underpinnings of cognitive deficits in childhood ASD. Subcellular fractions of synaptosomes from prefrontal cortices of age-, brain area-, and postmortem-interval-matched samples from children and adults with idiopathic ASD vs. controls were subjected to HPLC-tandem mass spectrometry. Analysis of data revealed the enrichment of ASD risk genes that participate in slow maturation of the postsynaptic density (PSD) structure and function during early brain development. Proteomic analysis revealed down regulation of PSD-related proteins including AMPA and NMDA receptors, GRM3, DLG4, olfactomedins, Shank1-3, Homer1, CaMK2α, NRXN1, NLGN2, Drebrin1, ARHGAP32, and Dock9 in children with autism (FDR-adjusted P < 0.05). In contrast, PSD-related alterations were less severe or unchanged in adult individuals with ASD. Network analyses revealed glutamate receptor abnormalities. Overall, the proteomic data support the concept that idiopathic autism is a synaptopathy involving PSD-related ASD risk genes. Interruption in evolutionarily conserved slow maturation of the PSD complex in prefrontal cortex may lead to the development of ASD in a susceptible individual.

Lien vers le texte intégral (Open Access ou abonnement)

10. Frye RE, Rincon N, McCarty PJ, Brister D, Scheck AC, Rossignol DA. Biomarkers of mitochondrial dysfunction in autism spectrum disorder: A systematic review and meta-analysis. Neurobiol Dis. 2024: 106520.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder affecting 1 in 36 children and is associated with physiological abnormalities, most notably mitochondrial dysfunction, at least in a subset of individuals. This systematic review and meta-analysis discovered 204 relevant articles which evaluated biomarkers of mitochondrial dysfunction in ASD individuals. Significant elevations (all p < 0.01) in the prevalence of lactate (17%), pyruvate (41%), alanine (15%) and creatine kinase (9%) were found in ASD. Individuals with ASD had significant differences (all p < 0.01) with moderate to large effect sizes (Cohen's d' ≥ 0.6) compared to controls in mean pyruvate, lactate-to-pyruvate ratio, ATP, and creatine kinase. Some studies found abnormal TCA cycle metabolites associated with ASD. Thirteen controlled studies reported mitochondrial DNA (mtDNA) deletions or variations in the ASD group in blood, peripheral blood mononuclear cells, lymphocytes, leucocytes, granulocytes, and brain. Meta-analyses discovered significant differences (p < 0.01) in copy number of mtDNA overall and in ND1, ND4 and CytB genes. Four studies linked specific mtDNA haplogroups to ASD. A series of studies found a subgroup of ASD with elevated mitochondrial respiration which was associated with increased sensitivity of the mitochondria to physiological stressors and neurodevelopmental regression. Lactate, pyruvate, lactate-to-pyruvate ratio, carnitine, and acyl-carnitines were associated with clinical features such as delays in language, social interaction, cognition, motor skills, and with repetitive behaviors and gastrointestinal symptoms, although not all studies found an association. Lactate, carnitine, acyl-carnitines, ATP, CoQ10, as well as mtDNA variants, heteroplasmy, haplogroups and copy number were associated with ASD severity. Variability was found across biomarker studies primarily due to differences in collection and processing techniques as well as the intrinsic heterogeneity of the ASD population. Several studies reported alterations in mitochondrial metabolism in mothers of children with ASD and in neonates who develop ASD. Treatments targeting mitochondria, particularly carnitine and ubiquinol, appear beneficial in ASD. The link between mitochondrial dysfunction in ASD and common physiological abnormalities in individuals with ASD including gastrointestinal disorders, oxidative stress, and immune dysfunction is outlined. Several subtypes of mitochondrial dysfunction in ASD are discussed, including one related to neurodevelopmental regression, another related to alterations in microbiome metabolites, and another related to elevations in acyl-carnitines. Mechanisms linking abnormal mitochondrial function with alterations in prenatal brain development and postnatal brain function are outlined. Given the multisystem complexity of some individuals with ASD, this review presents evidence for the mitochondria being central to ASD by contributing to abnormalities in brain development, cognition, and comorbidities such as immune and gastrointestinal dysfunction as well as neurodevelopmental regression. A diagnostic approach to identify mitochondrial dysfunction in ASD is outlined. From this evidence, it is clear that many individuals with ASD have alterations in mitochondrial function which may need to be addressed in order to achieve optimal clinical outcomes. The fact that alterations in mitochondrial metabolism may be found during pregnancy and early in the life of individuals who eventually develop ASD provides promise for early life predictive biomarkers of ASD. Further studies may improve the understanding of the role of the mitochondria in ASD by better defining subgroups and understanding the molecular mechanisms driving some of the unique changes found in mitochondrial function in those with ASD.

Lien vers le texte intégral (Open Access ou abonnement)

11. Hensel L, Lüdtke J, Brouzou KO, Eickhoff SB, Kamp D, Schilbach L. Noninvasive brain stimulation in autism: review and outlook for personalized interventions in adult patients. Cereb Cortex. 2024; 34(13): 8-18.

Noninvasive brain stimulation (NIBS) has been increasingly investigated during the last decade as a treatment option for persons with autism spectrum disorder (ASD). Yet, previous studies did not reach a consensus on a superior treatment protocol or stimulation target. Persons with ASD often suffer from social isolation and high rates of unemployment, arising from difficulties in social interaction. ASD involves multiple neural systems involved in perception, language, and cognition, and the underlying brain networks of these functional domains have been well documented. Aiming to provide an overview of NIBS effects when targeting these neural systems in late adolescent and adult ASD, we conducted a systematic search of the literature starting at 631 non-duplicate publications, leading to six studies corresponding with inclusion and exclusion criteria. We discuss these studies regarding their treatment rationale and the accordingly chosen methodological setup. The results of these studies vary, while methodological advances may allow to explain some of the variability. Based on these insights, we discuss strategies for future clinical trials to personalize the selection of brain stimulation targets taking into account intersubject variability of brain anatomy as well as function.

Lien vers le texte intégral (Open Access ou abonnement)

12. Kausel L, Michon M, Soto-Icaza P, Aboitiz F. A multimodal interface for speech perception: the role of the left superior temporal sulcus in social cognition and autism. Cereb Cortex. 2024; 34(13): 84-93.

Multimodal integration is crucial for human interaction, in particular for social communication, which relies on integrating information from various sensory modalities. Recently a third visual pathway specialized in social perception was proposed, which includes the right superior temporal sulcus (STS) playing a key role in processing socially relevant cues and high-level social perception. Importantly, it has also recently been proposed that the left STS contributes to audiovisual integration of speech processing. In this article, we propose that brain areas along the right STS that support multimodal integration for social perception and cognition can be considered homologs to those in the left, language-dominant hemisphere, sustaining multimodal integration of speech and semantic concepts fundamental for social communication. Emphasizing the significance of the left STS in multimodal integration and associated processes such as multimodal attention to socially relevant stimuli, we underscore its potential relevance in comprehending neurodevelopmental conditions characterized by challenges in social communication such as autism spectrum disorder (ASD). Further research into this left lateral processing stream holds the promise of enhancing our understanding of social communication in both typical development and ASD, which may lead to more effective interventions that could improve the quality of life for individuals with atypical neurodevelopment.

Lien vers le texte intégral (Open Access ou abonnement)

13. Kittridge C, Rob P, Fisher-Rogers A, Anis T, Attygalle U, Islam F, Sharma AN, Rodgers J. The development of the Helping your Anxious Child programme: a parent-mediated group intervention for parents of autistic children in South Asia. BJPsych Int. 2024; 21(2): 26-8.

Autistic children are at increased risk of experiencing a range of mental health difficulties, including anxiety. A number of intervention programmes are now available in high-income countries to support autistic children. However, to date there are no evidence-based interventions to support families of such children in South Asia. Based on consultations with clinicians, researchers and parents in Bangladesh and Sri Lanka, we developed a culturally tailored two-session skills-based group programme for parents whose autistic children present with anxiety. This paper describes the process of creating this programme, to be delivered by mental health professionals.

Lien vers le texte intégral (Open Access ou abonnement)

14. Kosmer K, Kulesza R. Cortical dysmorphology and reduced cortico-collicular projections in an animal model of autism spectrum disorder. Cereb Cortex. 2024; 34(13): 146-60.

Autism spectrum disorder is a neurodevelopmental disability that includes sensory disturbances. Hearing is frequently affected and ranges from deafness to hypersensitivity. In utero exposure to the antiepileptic valproic acid is associated with increased risk of autism spectrum disorder in humans and timed valproic acid exposure is a biologically relevant and validated animal model of autism spectrum disorder. Valproic acid-exposed rats have fewer neurons in their auditory brainstem and thalamus, fewer calbindin-positive neurons, reduced ascending projections to the midbrain and thalamus, elevated thresholds, and delayed auditory brainstem responses. Additionally, in the auditory cortex, valproic acid exposure results in abnormal responses, decreased phase-locking, elevated thresholds, and abnormal tonotopic maps. We therefore hypothesized that in utero, valproic acid exposure would result in fewer neurons in auditory cortex, neuronal dysmorphology, fewer calbindin-positive neurons, and reduced connectivity. We approached this hypothesis using morphometric analyses, immunohistochemistry, and retrograde tract tracing. We found thinner cortical layers but no changes in the density of neurons, smaller pyramidal and non-pyramidal neurons in several regions, fewer neurons immunoreactive for calbindin-positive, and fewer cortical neurons projecting to the inferior colliculus. These results support the widespread impact of the auditory system in autism spectrum disorder and valproic acid-exposed animals and emphasize the utility of simple, noninvasive auditory screening for autism spectrum disorder.

Lien vers le texte intégral (Open Access ou abonnement)

15. Krug MK, Takarae Y, Iosif AM, Solomon M. Decision-making under conditions of explicit risk and uncertainty in autistic and typically developing adolescents and young adults. Cereb Cortex. 2024; 34(13): 1-7.

Adolescence has been characterized as a period of risky and possibly suboptimal decision-making, yet the development of decision-making in autistic adolescents is not well understood. To investigate decision-making in autism, we evaluated performance on 2 computerized tasks capturing decision-making under explicit risk and uncertainty in autistic and non-autistic adolescents/young adults ages 12-22 years. Participants completed the Game of Dice Task (32 IQ-matched participant pairs) to assess decision-making under explicit risk and the modified Iowa Gambling Task (35 IQ-matched pairs) to assess decision-making under uncertainty. Autistic participants overall made riskier decisions than non-autistic participants on the Game of Dice Task, and the odds of making riskier decisions varied by age and IQ. In contrast, the autistic group showed comparable levels of learning over trial blocks to the non-autistic group on the modified Iowa Gambling Task. For both tasks, younger autistic participants performed poorer than their non-autistic counterparts, while group differences diminished in older ages. This age-related pattern suggests positive development during adolescence on risk assessment and decision-making in autism but also implies differential developmental trajectories between groups. These findings also suggest differential performance by the risk type, with additional complex influences of IQ and fluid cognition, which warrants further investigations.

Lien vers le texte intégral (Open Access ou abonnement)

16. Langhorne S, Uglik-Marucha N, Broadhurst C, Lieven E, Pearson A, Vitoratou S, Leadbitter K. The Knowledge of Autism Questionnaire-UK: Development and Initial Psychometric Evaluation. J Autism Dev Disord. 2024.

Tools to measure autism knowledge are needed to assess levels of understanding within particular groups of people and to evaluate whether awareness-raising campaigns or interventions lead to improvements in understanding. Several such measures are in circulation, but, to our knowledge, there are no psychometrically-validated questionnaires that assess contemporary autism knowledge suitable to the UK context. We aimed to produce a brief measure to assess between-respondent variability and within-respondent change over time. A pool of questionnaire items was developed and refined through a multi-stage iterative process involving autism experts and a lay sample. Attention was paid to face validity, clarity, consensus on correct responses, and appropriate difficulty levels. Initial validation data was obtained from a lay sample of 201 people. Difficulty and discrimination ability were assessed using item response theory and low-performing items were removed. Dimensionality was evaluated with exploratory factor analysis, which revealed a one-factor structure of the questionnaire. Further items were removed where they did not load strongly on their main factor. This process resulted in a final 14-item questionnaire called the Knowledge of Autism Questionnaire-UK. Internal consistency was satisfactory, and the final questionnaire was able to distinguish between parents of autistic people and those without an affiliation to autism. The KAQ-UK is a new, freely-available measure of autism knowledge that could be used to assess between-respondent variability and within-respondent change over time. Further evaluation and validation of its measurement properties are required.

Lien vers le texte intégral (Open Access ou abonnement)

17. Liu J, Girault JB, Nishino T, Shen MD, Kim SH, Burrows CA, Elison JT, Marrus N, Wolff JJ, Botteron KN, Estes AM, Dager SR, Hazlett HC, McKinstry RC, Schultz RT, Snyder AZ, Styner M, Zwaigenbaum L, Pruett JR, Jr., Piven J, Gao W. Atypical functional connectivity between the amygdala and visual, salience regions in infants with genetic liability for autism. Cereb Cortex. 2024; 34(13): 30-9.

The amygdala undergoes a period of overgrowth in the first year of life, resulting in enlarged volume by 12 months in infants later diagnosed with ASD. The overgrowth of the amygdala may have functional consequences during infancy. We investigated whether amygdala connectivity differs in 12-month-olds at high likelihood (HL) for ASD (defined by having an older sibling with autism), compared to those at low likelihood (LL). We examined seed-based connectivity of left and right amygdalae, hypothesizing that the HL and LL groups would differ in amygdala connectivity, especially with the visual cortex, based on our prior reports demonstrating that components of visual circuitry develop atypically and are linked to genetic liability for autism. We found that HL infants exhibited weaker connectivity between the right amygdala and the left visual cortex, as well as between the left amygdala and the right anterior cingulate, with evidence that these patterns occur in distinct subgroups of the HL sample. Amygdala connectivity strength with the visual cortex was related to motor and communication abilities among HL infants. Findings indicate that aberrant functional connectivity between the amygdala and visual regions is apparent in infants with genetic liability for ASD and may have implications for early differences in adaptive behaviors.

Lien vers le texte intégral (Open Access ou abonnement)

18. Liu M, Yu W, Xu D, Wang M, Peng B, Jiang H, Dai Y. Diagnosis for autism spectrum disorder children using T1-based gray matter and arterial spin labeling-based cerebral blood flow network metrics. Front Neurosci. 2024; 18: 1356241.

INTRODUCTION: Autism Spectrum Disorder (ASD) is a complex neurodevelopmental condition characterized by impairments in motor skills, communication, emotional expression, and social interaction. Accurate diagnosis of ASD remains challenging due to the reliance on subjective behavioral observations and assessment scales, lacking objective diagnostic indicators. METHODS: In this study, we introduced a novel approach for diagnosing ASD, leveraging T1-based gray matter and ASL-based cerebral blood flow network metrics. Thirty preschool-aged patients with ASD and twenty-two typically developing (TD) individuals were enrolled. Brain network features, including gray matter and cerebral blood flow metrics, were extracted from both T1-weighted magnetic resonance imaging (MRI) and ASL images. Feature selection was performed using statistical t-tests and Minimum Redundancy Maximum Relevance (mRMR). A machine learning model based on random vector functional link network was constructed for diagnosis. RESULTS: The proposed approach demonstrated a classification accuracy of 84.91% in distinguishing ASD from TD. Key discriminating network features were identified in the inferior frontal gyrus and superior occipital gyrus, regions critical for social and executive functions in ASD patients. DISCUSSION: Our study presents an objective and effective approach to the clinical diagnosis of ASD, overcoming the limitations of subjective behavioral observations. The identified brain network features provide insights into the neurobiological mechanisms underlying ASD, potentially leading to more targeted interventions.

Lien vers le texte intégral (Open Access ou abonnement)

19. McLellan J, Croen LA, Iosif AM, Ashwood P, Yoshida C, Berger K, Van de Water J. Differences in mid-gestational and early postnatal neonatal cytokines and chemokines are associated with patterns of maternal autoantibodies in the context of autism. Cereb Cortex. 2024; 34(13): 50-62.

Associations between maternal immune dysregulation (including autoimmunity and skewed cytokine/chemokine profiles) and offspring neurodevelopmental disorders such as autism have been reported. In maternal autoantibody-related autism, specific maternally derived autoantibodies can access the fetal compartment to target eight proteins critical for neurodevelopment. We examined the relationship between maternal autoantibodies to the eight maternal autoantibody-related autism proteins and cytokine/chemokine profiles in the second trimester of pregnancy in mothers of children later diagnosed with autism and their neonates’ cytokine/chemokine profiles. Using banked maternal serum samples from 15 to 19 weeks of gestation from the Early Markers for Autism Study and corresponding banked newborn bloodspots, we identified three maternal/offspring groups based on maternal autoantibody status: (1) mothers with autoantibodies to one or more of the eight maternal autoantibody-related autismassociated proteins but not a maternal autoantibody-related autism-specific pattern, (2) mothers with a known maternal autoantibody-related autism pattern, and (3) mothers without autoantibodies to any of the eight maternal autoantibody-related autism proteins. Using a multiplex platform, we measured maternal second trimester and neonatal cytokine/chemokine levels. This combined analysis aimed to determine potential associations between maternal autoantibodies and the maternal and neonatal cytokine/chemokine profiles, each of which has been shown to have implications on offspring neurodevelopment independently.

Lien vers le texte intégral (Open Access ou abonnement)

20. Mughal ZUN, Ahmed B, Rangwala BS, Rangwala HS, Fatima H, Ali M, Farah AA. Trofinetide receives FDA approval as first drug for Rett syndrome. Ann Med Surg (Lond). 2024; 86(5): 2382-5.

Lien vers le texte intégral (Open Access ou abonnement)

21. Nagai Y, Kirino E, Tanaka S, Usui C, Inami R, Inoue R, Hattori A, Uchida W, Kamagata K, Aoki S. Functional connectivity in autism spectrum disorder evaluated using rs-fMRI and DKI. Cereb Cortex. 2024; 34(13): 129-45.

We evaluated functional connectivity (FC) in patients with adult autism spectrum disorder (ASD) using resting-state functional MRI (rs-fMRI) and diffusion kurtosis imaging (DKI). We acquired rs-fMRI data from 33 individuals with ASD and 33 healthy controls (HC) and DKI data from 18 individuals with ASD and 17 HC. ASD showed attenuated FC between the right frontal pole (FP) and the bilateral temporal fusiform cortex (TFusC) and enhanced FC between the right thalamus and the bilateral inferior division of lateral occipital cortex, and between the cerebellar vermis and the right occipital fusiform gyrus (OFusG) and the right lingual gyrus, compared with HC. ASD demonstrated increased axial kurtosis (AK) and mean kurtosis (MK) in white matter (WM) tracts, including the right anterior corona radiata (ACR), forceps minor (FM), and right superior longitudinal fasciculus (SLF). In ASD, there was also a significant negative correlation between MK and FC between the cerebellar vermis and the right OFusG in the corpus callosum, FM, right SLF and right ACR. Increased DKI metrics might represent neuroinflammation, increased complexity, or disrupted WM tissue integrity that alters long-distance connectivity. Nonetheless, protective or compensating adaptations of inflammation might lead to more abundant glial cells and cytokine activation effectively alleviating the degeneration of neurons, resulting in increased complexity. FC abnormality in ASD observed in rs-fMRI may be attributed to microstructural alterations of the commissural and long-range association tracts in WM as indicated by DKI.

Lien vers le texte intégral (Open Access ou abonnement)

22. Peng X, Li T, Liu G, Ni W, Yi L. Enhanced neural synchronization during social communications between dyads with high autistic traits. Cereb Cortex. 2024; 34(13): 104-11.

Autism is characterized by atypical social communication styles. To investigate whether individuals with high autistic traits could still have effective social communication among each other, we compared the behavioral patterns and communication quality within 64 dyads of college students paired with both high, both low, and mixed high-low (HL) autistic traits, with their gender matched. Results revealed that the high-high (HH) autistic dyads exhibited atypical behavioral patterns during conversations, including reduced mutual gaze, communicational turns, and emotional sharing compared with the low-low and/or HL autistic dyads. However, the HH autistic dyads displayed enhanced interpersonal neural synchronization during social communications measured by functional near-infrared spectroscopy, suggesting an effective communication style. Besides, they also provided more positive subjective evaluations of the conversations. These findings highlight the potential for alternative pathways to effectively communicate with the autistic community, contribute to a deeper understanding of how high autistic traits influence social communication dynamics among autistic individuals, and provide important insights for the clinical practices for supporting autistic people.

Lien vers le texte intégral (Open Access ou abonnement)

23. Price T, Apostolopoulou T, Jones K. Virtually delivered cognitive behavioural therapy for avoidant restrictive food intake disorder (CBT-AR): a case study in an adult with elevated autistic traits. Eat Disord. 2024: 1-21.

Cognitive Behavioural Therapy for Avoidant and Restrictive Food Intake Disorder (CBT-AR; ARIFD) is a psychological treatment that targets many of the core symptoms of ARFID. Although a growing literature supports the efficacy of behavioural interventions for paediatric feeding and eating disorders, including ARFID, the applicability of these methods to adults remains undetermined. Telehealth delivery of CBT-AR in adults with autism has yet to be tested. With this study, we conduct a preliminary evaluation of CBT-AR delivered virtually to a 26-year-old white British female, with mixed ARFID and elevated autistic traits. She attended 23 remote CBT-AR sessions facilitated through a dedicated telehealth platform. Adjustments were made to accommodate her lived experience of neurodiversity. Using a pre-post treatment design, changes on measures of subjective goal attainment, eating-related and general psychosocial impairment, general anxiety, and depression were evaluated. Following treatment, the participant had made significant progress towards personally meaningful goals, with improvements observed in nutritional intake, general well-being, and reductions in eating-related psychosocial impairment and general anxiety. The results offer preliminary insights into acceptability and efficacy of virtual CBT-AR for neurodiverse individuals.

Lien vers le texte intégral (Open Access ou abonnement)

24. Rodrigues GD, Cordani R, Veneruso M, Chiarella L, Prato G, Ferri R, Carandina A, Tobaldini E, Nobili L, Montano N. Predominant cardiac sympathetic modulation during wake and sleep in patients with Rett syndrome. Sleep Med. 2024; 119: 188-91.

BACKGROUND: Rett syndrome (RTT) is a rare neurological disorder primarily associated with mutations in the methyl-CpG-binding protein 2 (MECP2) gene. The syndrome is characterized by cognitive, social, and physical impairments, as well as sleep disorders and epilepsy. Notably, dysfunction of the autonomic nervous system is a key feature of the syndrome. Although Heart Rate Variability (HRV) has been used to investigate autonomic nervous system dysfunction in RTT during wakefulness, there is still a significant lack of information regarding the same during sleep. Therefore, our aim was to investigate cardiovascular autonomic modulation during sleep in subjects with RTT compared to an age-matched healthy control group (HC). METHOD: A complete overnight polysomnographic (PSG) recording was obtained from 11 patients with Rett syndrome (all females, 10 ± 4 years old) and 11 HC (all females, 11 ± 4 years old; p = 0.48). Electrocardiogram and breathing data were extracted from PSG and divided into wake, non-REM, and REM sleep stages. Cardiac autonomic control was assessed using symbolic non-linear heart rate variability analysis. The symbolic analysis identified three patterns: 0 V% (sympathetic), 2UV%, and 2LV% (vagal). RESULTS: The 0 V% was higher in the RTT group than in the HC group during wake, non-REM, and REM stages (p < 0.01), while the 2LV and 2UV% were lower during wake and sleep stages (p < 0.01). However, the 0 V% increased similarly from the wake to the REM stage in both RTT and HC groups. CONCLUSIONS: Therefore, the sympatho-vagal balance shifted towards sympathetic predominance and vagal withdrawal during wake and sleep in RTT, although cardiac autonomic dynamics were preserved during sleep.

Lien vers le texte intégral (Open Access ou abonnement)

25. Ronconi L, Cantiani C, Riva V, Franchin L, Bettoni R, Gori S, Bulf H, Valenza E, Facoetti A. Infants’ reorienting efficiency depends on parental autistic traits and predicts future socio-communicative behaviors. Cereb Cortex. 2024; 34(13): 40-9.

Attentional reorienting is dysfunctional not only in children with autism spectrum disorder (ASD), but also in infants who will develop ASD, thus constituting a potential causal factor of future social interaction and communication abilities. Following the research domain criteria framework, we hypothesized that the presence of subclinical autistic traits in parents should lead to atypical infants’ attentional reorienting, which in turn should impact on their future socio-communication behavior in toddlerhood. During an attentional cueing task, we measured the saccadic latencies in a large sample (total enrolled n = 89; final sample n = 71) of 8-month-old infants from the general population as a proxy for their stimulus-driven attention. Infants were grouped in a high parental traits (HPT; n = 23) or in a low parental traits (LPT; n = 48) group, according to the degree of autistic traits self-reported by their parents. Infants (n = 33) were then longitudinally followed to test their socio-communicative behaviors at 21 months. Results show a sluggish reorienting system, which was a longitudinal predictor of future socio-communicative skills at 21 months. Our combined transgenerational and longitudinal findings suggest that the early functionality of the stimulus-driven attentional network-redirecting attention from one event to another-could be directly connected to future social and communication development.

Lien vers le texte intégral (Open Access ou abonnement)

26. Simpson A, Tallur KK, Chin RFM, Yong K, Stone J. Autism spectrum disorder in children and young people with FND. J Psychosom Res. 2024; 182: 111681.

Lien vers le texte intégral (Open Access ou abonnement)

27. Vakilzadeh G, Maseko BC, Bartely TD, McLennan YA, Martínez-Cerdeño V. Increased number of excitatory synapsis and decreased number of inhibitory synapsis in the prefrontal cortex in autism. Cereb Cortex. 2024; 34(13): 121-8.

Previous studies in autism spectrum disorder demonstrated an increased number of excitatory pyramidal cells and a decreased number of inhibitory parvalbumin+ chandelier interneurons in the prefrontal cortex of postmortem brains. How these changes in cellular composition affect the overall abundance of excitatory and inhibitory synapses in the cortex is not known. Herein, we quantified the number of excitatory and inhibitory synapses in the prefrontal cortex of 10 postmortem autism spectrum disorder brains and 10 control cases. To identify excitatory synapses, we used VGlut1 as a marker of the presynaptic component and postsynaptic density protein-95 as marker of the postsynaptic component. To identify inhibitory synapses, we used the vesicular gamma-aminobutyric acid transporter as a marker of the presynaptic component and gephyrin as a marker of the postsynaptic component. We used Puncta Analyzer to quantify the number of co-localized pre- and postsynaptic synaptic components in each area of interest. We found an increase in the number of excitatory synapses in upper cortical layers and a decrease in inhibitory synapses in all cortical layers in autism spectrum disorder brains compared with control cases. The alteration in the number of excitatory and inhibitory synapses could lead to neuronal dysfunction and disturbed network connectivity in the prefrontal cortex in autism spectrum disorder.

Lien vers le texte intégral (Open Access ou abonnement)

28. Wang H, Jing H, Yang J, Liu C, Hu L, Tao G, Zhao Z, Shen N. Identifying autism spectrum disorder from multi-modal data with privacy-preserving. Npj Ment Health Res. 2024; 3(1): 15.

The application of deep learning models to precision medical diagnosis often requires the aggregation of large amounts of medical data to effectively train high-quality models. However, data privacy protection mechanisms make it difficult to perform medical data collection from different medical institutions. In autism spectrum disorder (ASD) diagnosis, automatic diagnosis using multimodal information from heterogeneous data has not yet achieved satisfactory performance. To address the privacy preservation issue as well as to improve ASD diagnosis, we propose a deep learning framework using multimodal feature fusion and hypergraph neural networks for disease prediction in federated learning (FedHNN). By introducing the federated learning strategy, each local model is trained and computed independently in a distributed manner without data sharing, allowing rapid scaling of medical datasets to achieve robust and scalable deep learning predictive models. To further improve the performance with privacy preservation, we improve the hypergraph model for multimodal fusion to make it suitable for autism spectrum disorder (ASD) diagnosis tasks by capturing the complementarity and correlation between modalities through a hypergraph fusion strategy. The results demonstrate that our proposed federated learning-based prediction model is superior to all local models and outperforms other deep learning models. Overall, our proposed FedHNN has good results in the work of using multi-site data to improve the performance of ASD identification.

Lien vers le texte intégral (Open Access ou abonnement)

29. Wang Y, Cao R, Chakravarthula PN, Yu H, Wang S. Atypical neural encoding of faces in individuals with autism spectrum disorder. Cereb Cortex. 2024; 34(13): 172-86.

Individuals with autism spectrum disorder (ASD) experience pervasive difficulties in processing social information from faces. However, the behavioral and neural mechanisms underlying social trait judgments of faces in ASD remain largely unclear. Here, we comprehensively addressed this question by employing functional neuroimaging and parametrically generated faces that vary in facial trustworthiness and dominance. Behaviorally, participants with ASD exhibited reduced specificity but increased inter-rater variability in social trait judgments. Neurally, participants with ASD showed hypo-activation across broad face-processing areas. Multivariate analysis based on trial-by-trial face responses could discriminate participant groups in the majority of the face-processing areas. Encoding social traits in ASD engaged vastly different face-processing areas compared to controls, and encoding different social traits engaged different brain areas. Interestingly, the idiosyncratic brain areas encoding social traits in ASD were still flexible and context-dependent, similar to neurotypicals. Additionally, participants with ASD also showed an altered encoding of facial saliency features in the eyes and mouth. Together, our results provide a comprehensive understanding of the neural mechanisms underlying social trait judgments in ASD.

Lien vers le texte intégral (Open Access ou abonnement)

30. Wang Y, Guo D, Wang M, Hu M, Zhu D, Yu Q, Li Z, Zhang X, Ding R, Zhao M, He P. Correction: Community-based integrated care for patients with diabetes and depression (CIC-PDD): study protocol for a cluster randomized controlled trial. Trials. 2024; 25(1): 295.

Lien vers le texte intégral (Open Access ou abonnement)

31. Xie X, Zhou R, Fang Z, Zhang Y, Wang Q, Liu X. Seeing beyond words: Visualizing autism spectrum disorder biomarker insights. Heliyon. 2024; 10(9): e30420.

OBJECTIVE: This study employs bibliometric and visual analysis to elucidate global research trends in Autism Spectrum Disorder (ASD) biomarkers, identify critical research focal points, and discuss the potential integration of diverse biomarker modalities for precise ASD assessment. METHODS: A comprehensive bibliometric analysis was conducted using data from the Web of Science Core Collection database until December 31, 2022. Visualization tools, including R, VOSviewer, CiteSpace, and gCLUTO, were utilized to examine collaborative networks, co-citation patterns, and keyword associations among countries, institutions, authors, journals, documents, and keywords. RESULTS: ASD biomarker research emerged in 2004, accumulating a corpus of 4348 documents by December 31, 2022. The United States, with 1574 publications and an H-index of 213, emerged as the most prolific and influential country. The University of California, Davis, contributed significantly with 346 publications and an H-index of 69, making it the leading institution. Concerning journals, the Journal of Autism and Developmental Disorders, Autism Research, and PLOS ONE were the top three publishers of ASD biomarker-related articles among a total of 1140 academic journals. Co-citation and keyword analyses revealed research hotspots in genetics, imaging, oxidative stress, neuroinflammation, gut microbiota, and eye tracking. Emerging topics included « DNA methylation, » « eye tracking, » « metabolomics, » and « resting-state fMRI. » CONCLUSION: The field of ASD biomarker research is dynamically evolving. Future endeavors should prioritize individual stratification, methodological standardization, the harmonious integration of biomarker modalities, and longitudinal studies to advance the precision of ASD diagnosis and treatment.

Lien vers le texte intégral (Open Access ou abonnement)

32. Yin Z, Ding X, Zhang X, Wu Z, Wang L, Xu X, Li G. Early autism diagnosis based on path signature and Siamese unsupervised feature compressor. Cereb Cortex. 2024; 34(13): 72-83.

Autism spectrum disorder has been emerging as a growing public health threat. Early diagnosis of autism spectrum disorder is crucial for timely, effective intervention and treatment. However, conventional diagnosis methods based on communications and behavioral patterns are unreliable for children younger than 2 years of age. Given evidences of neurodevelopmental abnormalities in autism spectrum disorder infants, we resort to a novel deep learning-based method to extract key features from the inherently scarce, class-imbalanced, and heterogeneous structural MR images for early autism diagnosis. Specifically, we propose a Siamese verification framework to extend the scarce data, and an unsupervised compressor to alleviate data imbalance by extracting key features. We also proposed weight constraints to cope with sample heterogeneity by giving different samples different voting weights during validation, and used Path Signature to unravel meaningful developmental features from the two-time point data longitudinally. We further extracted machine learning focused brain regions for autism diagnosis. Extensive experiments have shown that our method performed well under practical scenarios, transcending existing machine learning methods and providing anatomical insights for autism early diagnosis.

Lien vers le texte intégral (Open Access ou abonnement)