1. Pathway to Independence – an interview with Marcella Birtele. Development;2024 (Aug 15);151(16)

Marcella Birtele completed her PhD in Malin Parmar’s lab at Lund University, Sweden, where her project involved characterising stem cell-derived dopaminergic neurons with the long-term goal of transplanting these neurons into patients with Parkinson’s disease. She is now a postdoc at the University of Southern California, USA, where she has been using cortical organoids to explore the role of autism spectrum disorder-associated genes in neural development. Marcella was selected as one of our 2024 PI fellows, a group of researchers who will be supported by Development’s Pathway to Independence Programme as they aim to secure independent positions. We spoke to Marcella to hear why she decided to apply to the programme, and how the research questions she hopes to address with her own lab will bridge her previous neurodegeneration and neural development studies.

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2. Binder MS, Escobar I, Xu Y, Sokolov AM, Zhang L, Bordey A. Reducing filamin A restores cortical synaptic connectivity and early social communication following cellular mosaicism in ASD pathways. J Neurosci;2024 (Aug 20)

Communication in the form of non-verbal, social vocalization, or crying is evolutionary conserved in mammals and is impaired early in human infants that are later diagnosed with autism spectrum disorder (ASD). Defects in infant vocalization have been proposed as an early sign of ASD that may exacerbate ASD development. However, the neural mechanisms associated with early communicative deficits in ASD are not known. Here, we expressed a constitutively active mutant of Rheb (Rheb(S16H)), which is known to upregulate two ASD core pathways, mTOR complex 1 (mTORC1) and ERK1/2, in layer (L) 2/3 pyramidal neurons of the neocortex of mice of either sex. We found that cellular mosaic expression of Rheb(S16H) in L2/3 pyramidal neurons altered the production of isolation calls from neonatal mice. This was accompanied by an expected misplacement of neurons and dendrite overgrowth, along with an unexpected increase in spine density and length, which was associated with increased excitatory synaptic activity. This contrasted with the known decrease in spine density in Rheb(S16H) neurons of one-month-old mice. Reducing the levels of the actin crosslinking and adaptor protein filamin A (FLNA), known to be increased downstream of ERK1/2, attenuated dendrite overgrowth and fully restored spine properties, synaptic connectivity, and the production of pup isolation calls. These findings suggest that upper-layer cortical pyramidal neurons contribute to communicative deficits in a condition known to affect two core ASD pathways and that these mechanisms are regulated by FLNA.Significance Statement An infant’s cry is a form of evolutionarily conserved social communication that is altered in ASD and has been proposed as an early sign of ASD. However, the neural substrate of early communicative deficits is not known. We show that cellular mosaic expression of a constitutively active Rheb, known to upregulate two core ASD pathways, selectively in upper-layer neocortical pyramidal neurons, alters the production of pup isolation calls and synaptic connectivity. These defects were prevented by reducing the expression of the adaptor protein FLNA. This underscores the importance of a specific neuronal substrate responsible for communicative deficits and its regulation by FLNA.

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3. Brennan J, Ward OF, Tomeny TS, Davis TE, 3rd. A Systematic Review of Parental Self-Efficacy in Parents of Autistic Children. Clin Child Fam Psychol Rev;2024 (Aug 19)

Parental self-efficacy (PSE) assesses a parent’s expectations and beliefs about their ability to effectively parent their child. PSE has implications for a parent’s well-being, parenting practices, mental health, the parent-child relationship, and child adjustment. While PSE has been extensively examined within the broader parenting literature, the examination of PSE specifically for parents of autistic children has gained increasing attention in recent years. The following systematic review aimed to investigate the role of PSE for parents of autistic children by examining variables that predict PSE or are predicted by PSE in relation to how they align with the broader parenting literature and are unique to autism. Utilizing PRISMA guidelines, peer-reviewed articles were included if (a) participants included caregivers of autistic children, (b) at least one quantitative outcome measure of PSE was utilized, and (c) the role of PSE was examined as an outcome, predictor, or variable in an explanatory model. A total of 53 studies were included in the review and the role of PSE was examined regarding family (e.g., parental characteristics, parent stress, well-being, and support) and child factors (e.g., autism symptomology, problem behaviors, interventions). Several themes emerged including a positive relationship between PSE and support, and a negative relationship between PSE and parenting stress, parent mental health outcomes (e.g., anxiety, depression), and autism symptomology. Findings were compared to the broader parenting and PSE literature to examine how increased considerations and challenges (e.g., child problem behaviors, social impairment, and caregiver strain) associated with raising an autistic child might impact PSE.

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4. Doornaert EE, El-Cheikh Mohamad A, Johal G, Allman B, Möhrle D, Schmid S. Not a deficit, just different – Prepulse inhibition disruptions in autism depend on startle stimulus intensities. eNeuro;2024 (Aug 19)

Sensory processing disruptions are a core symptom of autism spectrum disorder (ASD) and other neurological disorders. The acoustic startle response and prepulse inhibition (PPI) are common metrics used to assess disruptions in sensory processing and sensorimotor gating in clinical studies and animal models. However, often there are inconsistent findings on ASD-related PPI deficits across different studies. Here, we used a novel method for assessing changes in startle and PPI in rodents, using the Cntnap2 knockout (KO) rat model for neurodevelopmental disorder/ASD that has consistently shown PPI disruptions in past studies. We discovered that not only sex and prepulse intensity but also the intensity of the startle stimulus, profoundly impacts whether PPI deficits are evident in the Cntnap2 KO rat or not. We show that rats do not universally exhibit a PPI deficit, instead impaired PPI is contingent on specific testing conditions. Notably, at lower startle stimulus intensities, Cntnap2 KO rats not only demonstrated intact PPI but also exhibited evidence of enhanced PPI compared to their wildtype counterparts. This finding emphasizes the importance of considering specific testing conditions when evaluating startle and PPI in the context of ASD and other neuropsychiatric conditions and might explain some of the inconsistencies between different studies.Significance Statement The present study extends traditional approaches to evaluating sensory processing using startle and PPI by showing that startle and PPI disruptions are contingent upon specific testing parameters. Compared to conventional PPI testing where only prepulse levels and interstimulus intervals might vary, we here show that animals consistently reported to have PPI deficits do not have a general sensorimotor gating deficit, but intact, and potentially even enhanced, PPI at lower startle intensities. This has a widespread impact on PPI testing and the interpretation of PPI results, given the broad use in animal models of various neurodevelopmental conditions, alongside the translational relevance to clinical settings.

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5. Estrugo Y, Bar Yehuda S, Bauminger-Zviely N. Motor, cognitive, and socio-cognitive mechanisms explaining social skills in autism and typical development. Autism Res;2024 (Aug 19)

Challenges in social functioning are considered a core criterion for diagnosing autism. Although motor skills, executive functioning (EF), and theory of mind (ToM) abilities independently affect social challenges and are interconnected, these abilities’ shared contribution to the explanation of social functioning in autism remains under-investigated. To address this disparity, we examined the motor, EF, and ToM abilities of 148 autistic and non-autistic youth (ages 6-16 years), evaluating these variables’ impact on social ability and their interconnections. Our mediation model exploring the contribution of motor, EF, and ToM skills explained 85% of the variance in social functioning (Social Responsiveness Scale-SRS-2). Analysis yielded a direct path from study group to SRS-2-social (typically developing-TD > autistic) and two main parallel indirect joint paths: (a) Group ➔ motor ➔ EF ➔ SRS-2-social; and (b) Group ➔ motor ➔ ToM ➔ SRS-2-social. In two secondary indirect paths, autistic children showed lower motor skills, which in turn explained their higher EF and/or ToM impairment, which in turn explained their higher social skills impairment. Put differently, our results suggest that better EF and TOM proficiency may compensate for poorer motor skills. Findings also indicated that the collective impact of motor, EF, and ToM skills on social functioning, along with the mediating role played by EF and ToM on the social-motor linkage, may contribute to understanding individual differences in the social functioning of autistic children. These conclusions call for the inclusion of motor, EF, and ToM activities into daily practices to facilitate social functioning.

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6. Frigerio A, Knight T, Rella R, Sinigaglia E, Camussi E, Montali L. Experiences of parenting for autistic children in Australia and Italy: a qualitative cross-cultural comparison. Front Psychol;2024;15:1409234.

INTRODUCTION: Parents vary in their gradual adaptation to the demands of caring for an autistic child. Their experiences can be positive, negative, or a combination of both, depending on the severity of the cases and various personal and social factors. Cross-cultural comparisons can aid in understanding how contextual factors, such as the availability of social and health services, and cultural factors, such as family relationships and the distribution of care burden, may influence the caregiving experience. However, there is a limited amount of cross-cultural research on this topic, which is almost exclusively quantitative. AIMS AND METHODS: From an ecocultural perspective, our interview-based study aimed to explore the experiences of Australian (15) and Italian (11) parents of autistic children living in their respective countries. RESULTS: The analysis identified three main themes. Life through autism, autism through life: coexisting with an unexpected life partner, Parenting autistic children: reorganization of parents’ subjectivity and familiar dynamics, and The unseen side of disability: autism communities between inclusion and segregation. DISCUSSION: Our comparative approach reveals both commonalities and differences between the two groups of participants. The similarities support features previously identified in the literature: the emotional and physical burden on parents and the positive impact on parental identity. The differences relate to the diagnostic process, interactions with health professionals, the impact of autism on family dynamics and parental perspectives, and the role assigned to siblings. Despite facing similar challenges, these differences reveal how Italian and Australian parents articulate different understandings linked to social and cultural differences.

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7. Hanzel M, Fernando K, Maloney SE, Horn Z, Gong S, Mätlik K, Zhao J, Pasolli HA, Heissel S, Dougherty JD, Hull C, Hatten ME. Mice lacking Astn2 have ASD-like behaviors and altered cerebellar circuit properties. Proc Natl Acad Sci U S A;2024 (Aug 20);121(34):e2405901121.

Astrotactin 2 (ASTN2) is a transmembrane neuronal protein highly expressed in the cerebellum that functions in receptor trafficking and modulates cerebellar Purkinje cell (PC) synaptic activity. Individuals with ASTN2 mutations exhibit neurodevelopmental disorders, including autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), learning difficulties, and language delay. To provide a genetic model for the role of the cerebellum in ASD-related behaviors and study the role of ASTN2 in cerebellar circuit function, we generated global and PC-specific conditional Astn2 knockout (KO and cKO, respectively) mouse lines. Astn2 KO mice exhibit strong ASD-related behavioral phenotypes, including a marked decrease in separation-induced pup ultrasonic vocalization calls, hyperactivity, repetitive behaviors, altered behavior in the three-chamber test, and impaired cerebellar-dependent eyeblink conditioning. Hyperactivity and repetitive behaviors are also prominent in Astn2 cKO animals, but they do not show altered behavior in the three-chamber test. By Golgi staining, Astn2 KO PCs have region-specific changes in dendritic spine density and filopodia numbers. Proteomic analysis of Astn2 KO cerebellum reveals a marked upregulation of ASTN2 family member, ASTN1, a neuron-glial adhesion protein. Immunohistochemistry and electron microscopy demonstrate a significant increase in Bergmann glia volume in the molecular layer of Astn2 KO animals. Electrophysiological experiments indicate a reduced frequency of spontaneous excitatory postsynaptic currents (EPSCs), as well as increased amplitudes of both spontaneous EPSCs and inhibitory postsynaptic currents in the Astn2 KO animals, suggesting that pre- and postsynaptic components of synaptic transmission are altered. Thus, ASTN2 regulates ASD-like behaviors and cerebellar circuit properties.

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8. Harrison AJ, Madison M, Naqvi N, Bowman K, Campbell J. The development of the Autism Stigma and Knowledge Questionnaire, Second edition (ASK-Q-2), through a cross-cultural psychometric investigation. Autism;2024 (Aug 20):13623613241270916.

The Autism Stigma and Knowledge Questionnaire (ASK-Q) was developed to assess autism knowledge across cultural contexts. The current study aimed to examine cultural equivalence of the measure using a large, international database. These analyses identified 18 items in need of examination for removal or revision. A team of autism experts recommended several additional changes to reduce stigma and increase cross-cultural sensitivity and accuracy of the items on the measure. These changes resulted in a briefer measure with maintained statistical support.

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9. Kamensek T, Iarocci G, Oruc I. Atypical daily visual exposure to faces in adults with autism spectrum disorder. Curr Biol;2024 (Aug 20)

Expert face processes are refined and tuned through a protracted development. Exposure statistics of the daily visual experience of neurotypical adults (the face diet) show substantial exposure to familiar faces. People with autism spectrum disorder (ASD) do not show the same expertise with faces as their non-autistic counterparts. This may be due to an impoverished visual experience with faces, according to experiential models of autism. Here, we present the first empirical report on the day-to-day visual experience of the faces of adults with ASD. Our results, based on over 360 h of first-person perspective footage of daily exposure, show striking qualitative and quantitative differences in the ASD face diet compared with those of neurotypical observers, which is best characterized by a pattern of reduced and atypical exposure to familiar faces in ASD. Specifically, duration of exposure to familiar faces was lower in ASD, and faces were viewed from farther distances and from viewpoints that were biased toward profile pose. Our results provide strong evidence that individuals with ASD may not be getting the experience needed for the typical development of expert face processes.

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10. Kotowska M, Kołodziej M, Szajewska H, Łukasik J. The impact of probiotics on core autism symptoms – a systematic review and meta-analysis of randomized clinical trials. Clin Nutr ESPEN;2024 (Aug 20)

BACKGROUND & AIMS: Studies have shown evidence of gut dysbiosis in individuals with autism spectrum disorder (ASD). Various microbiome-modifying treatments, including probiotics, have been proposed. This review systematically assessed the evidence on the effects of probiotics on core autism symptoms in children with ASD. METHODS: We performed a comprehensive literature search in Medline, Embase, CENTRAL, PsycInfo, and clinical trial registries, up to March 2023, and updated on January 10, 2024. Randomized controlled trials (RCTs) of parallel-group and cross-over designs were eligible. The population included individuals below 20 years of age diagnosed with ASD. Trials evaluating the effects of probiotics (any strain or dose) compared to placebo, no treatment, or another intervention were included. The outcomes of interest included the core autism symptoms: deficits in social skills, communication skills, and restricted, repetitive behaviors. No language restrictions were applied. Studies were excluded if an additional active compound was administered. The risk of bias was assessed using the Revised Cochrane Risk of Bias tool (RoB 2). This review was registered in PROSPERO (CRD42023393000). RESULTS: In total, 12 RCTs assessing 630 participants were included. A borderline significant beneficial effect of probiotics on core ASD symptoms was found (8 RCTs, mean difference -0.21; 95% CI -0.39 to -0.03). Subgroup analysis according to study type showed a significant positive effect in parallel group trials (6 RCTs, mean difference -0.26; 95% CI -0.48 to -0.05). The pooled effect estimates for the other outcomes didn’t reveal significant differences between the groups. Importantly, the risk of bias was high in nine studies. CONCLUSIONS: Available data do not provide high-quality evidence supporting the use of probiotics for ASD symptoms in children.

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11. McKinnon I, Whitehouse E, Harris M, Ciausu V, McCarthy J, Sheehan R. A UK-wide survey of community forensic services for adults with intellectual disability and/or autism. BJPsych Open;2024 (Aug 20);10(5):e148.

BACKGROUND: Specialist forensic community teams for people with intellectual disability and/or autism have been developed, but little is known about their extent and delivery. AIMS: To describe specialist forensic community teams for people with intellectual disability and/or autism across the UK. METHOD: An online survey was sent to representatives of each UK Trust/Health Board providing adult mental health and/or intellectual disability services. Questions covered the availability, structure and activities of specialist community forensic services. Quantitative data were summarised and associations between access to specialist forensic teams and care were tested with Chi-squared tests. Thematic analysis of free-text survey responses was used to understand the challenges of providing community forensic mental health services for this group. RESULTS: A total of 49 out of 78 (63%) eligible Trusts/Health Boards responded, of which 25 (51%) had access to a specialist forensic community team. Teams operated either as part of a single Trust/Board (n = 13) or over a larger regional footprint (n = 12). The availability of specialist forensic community teams was associated with better access to offence-related interventions (χ(2) = 15.1002, P < 0.005) and co-production of patient care plans (χ(2) = 7.8726, P = 0.005). Respondents reported a wide variation in availability, expertise and perceived quality of community services. The availability of secure and generic in-patient beds, commissioning and legal barriers were also significant challenges in providing appropriate care. CONCLUSIONS: Coverage of specialist community forensic teams is not universal. There are indications that such teams are associated with improved care processes, but further work is needed to establish longer-term outcomes and the optimal model of care.

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12. Montoya CN, Ishler KJ, Obeid R, Payner J, Berg KA. « Glimmers of hope and good things »: Positive aspects of caregiving to autistic adolescents and young adults. Autism;2024 (Aug 19):13623613241272050.

We wanted to explore the positive, or rewarding, experiences of caregivers who were caring for older adolescents or young autistic adults. We surveyed 174 caregivers, asking questions about how they dealt with stressors, the support they had from people in their lives, and the different behaviors of the autistic youth they care for. Using an existing measure, as well as an open-ended question, we asked caregivers about the most rewarding aspects of caring for their youth. When examining survey responses, we found that caregivers who reported receiving more help and support from their autistic youth also reported more positive aspects related to caregiving. In response to our study’s open-ended question, caregivers talked about the reward of seeing their youth grow and progress (e.g. learning new skills, reaching new milestones), described positive aspects of the relationship with their youth (e.g. sharing a special bond), and reflected on their own learning and personal growth as caregivers and people. Our findings highlight the positive, or rewarding, aspects of caregiving for autistic adolescents and young adults. This work will inform future work studying positive aspects of caring for autistic individuals and how this may impact caregivers’ psychological well-being.

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13. Santomauro DF, Hedley D, Sahin E, Brugha TS, Naghavi M, Vos T, Whiteford HA, Ferrari AJ, Stokes MA. The global burden of suicide mortality among people on the autism spectrum: A systematic review, meta-analysis, and extension of estimates from the Global Burden of Disease Study 2021. Psychiatry Res;2024 (Aug 20);341:116150.

We aimed to quantify the risk, mortality, and burden of suicide among autistic persons. We searched PubMed, Embase, and PsycINFO on 5(th) April 2023 for sources reporting the relative risk (RR) of suicide or suicide attempt among autistic persons (PROSPERO registration: CRD42021265313). Autism spectrum prevalence and suicide mortality and years of life lost (YLLs), were sourced from the Global Burden of Disease Study 2021. RRs pooled via meta-regression and health metrics estimates were used to estimate the excess suicide mortality and YLLs among autistic persons. We sourced 983 unique studies of which ten studies met inclusion criteria, consisting of 10.4 million persons. The pooled RR for suicide for autistic persons was 2·85 (95% UI: 2·05-4·03), which was significantly higher for autistic females than autistic males. No evidence of publication bias was detected via inspection of funnel plot and Egger’s test. Globally, we estimated 13 400 excess suicide deaths among autistic persons in 2021, equating to 1·8% of all suicide deaths and 621 000 excess YLLs. Studies were limited in number and geographical coverage. Effective suicide prevention strategies for autistic persons may substantially reduce the fatal burden of suicides globally and reduce the health burden experienced within this population.

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14. Shang C, Xie W, Zeng J, Osman N, Sun C, Zou M, Wang J, Wu L. E-Health Family Interventions for Parents of Children With Autism Aged 0-6 Years: A Scoping Review. Psychiatry Investig;2024 (Aug 20)

OBJECTIVE: Autism spectrum disorder (ASD) is a neurodevelopmental disorder with onset in infancy. Early intervention is critical to improve the prognosis for these children. E-health interventions have tremendous potential. This review aimed to determine the status and effectiveness of family interventions for parents of children aged 0-6 years with ASD in the context of e-health. METHODS: The review methodology was guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews. PubMed, Web of Science, and China National Knowledge Infrastructure were searched from inception to June 2022. The searches were limited to children with ASD of the age range between 0 and 6 years. We collated the available information and used descriptive statistics to analyze the synthesized data. RESULTS: Our initial search identified 3,672 articles, of which 30 studies met the inclusion criteria. The 30 articles selected were released between 2012 and 2022. All articles are in English. Most articles reviewed were from high-income countries (27/30, 90.0%), especially from the United States (16/30, 53.3%). Four major themes emerged from the 30 studies that matched the inclusion criteria, as follows: 1) type of e-health interventions, 2) duration of interventions, 3) clinical aspects of e-health interventions, and 4) evidence for intervention effectiveness, looking into the positive, negative, and mixed findings of previous studies. CONCLUSION: These findings suggest that a wide variety of e-health interventions may actually help support both children with ASD aged 0-6 years and their parents.

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15. Shom S, Saha S, Chatterjee M, Sinha S, Mukhopadhyay K. Indian ASD probands with 25(OH)D and vitamin D binding protein deficiency exhibited higher severity. Sci Rep;2024 (Aug 20);14(1):19242.

The severity of autism spectrum disorder (ASD) shows wide variations, though the reason remains unclear. Vitamin D (VitD) deficiency is considered a risk factor for ASD and its supplementation was reported to reduce symptom severity. Since VitD, either synthesized in the skin or absorbed from the food, is transported to the liver by the vitamin D binding protein (DBP), we have analyzed DBP genetic polymorphisms [rs7041 (A/C), rs4588 (G/T), and rs3755967 (C/T)] affecting DBP function [Case = 411; Control = 397], levels of plasma 25(OH)D and DBP [Case = 25; Control = 26], and DBP mRNA expression [Case = 74; Control = 44] in a group of Indo-Caucasoid ASD probands and neurotypical subjects. ASD probands with rs7041’CC’, rs4588 ‘TT’, and rs3755967 ‘TT’ genotypes exhibited higher scores for a few traits. Scores for Imitation and Listening response were also higher in the presence of the « A-T » haplotype (rs7041-rs4588). Plasma 25(OH)D and DBP levels as well as DBP mRNA expressions were significantly lower in the ASD probands as compared to the neurotypical subjects. We infer that DBP deficiency, in the presence of risk genetic variants, could be one of the reasons for the reported 25(OH)D deficiency of the ASD probands.

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16. Stefanou ME, Dundon NM, Bestelmeyer PEG, Biscaldi M, Smyrnis N, Klein C. The dissociating effects of fear and disgust on multisensory integration in autism: evidence from evoked potentials. Front Neurosci;2024;18:1390696.

BACKGROUND: Deficits in Multisensory Integration (MSI) in ASD have been reported repeatedly and have been suggested to be caused by altered long-range connectivity. Here we investigate behavioral and ERP correlates of MSI in ASD using ecologically valid videos of emotional expressions. METHODS: In the present study, we set out to investigate the electrophysiological correlates of audiovisual MSI in young autistic and neurotypical adolescents. We employed dynamic stimuli of high ecological validity (500 ms clips produced by actors) that depicted fear or disgust in unimodal (visual and auditory), and bimodal (audiovisual) conditions. RESULTS: We report robust MSI effects at both the behavioral and electrophysiological levels and pronounced differences between autistic and neurotypical participants. Specifically, neurotypical controls showed robust behavioral MSI for both emotions as seen through a significant speed-up of bimodal response time (RT), confirmed by Miller’s Race Model Inequality (RMI), with greater MSI effects for fear than disgust. Adolescents with ASD, by contrast, showed behavioral MSI only for fear. At the electrophysiological level, the bimodal condition as compared to the unimodal conditions reduced the amplitudes of the visual P100 and auditory P200 and increased the amplitude of the visual N170 regardless of group. Furthermore, a cluster-based analysis across all electrodes revealed that adolescents with ASD showed an overall delayed and spatially constrained MSI effect compared to controls. CONCLUSION: Given that the variables we measured reflect attention, our findings suggest that MSI can be modulated by the differential effects on attention that fear and disgust produce. We also argue that the MSI deficits seen in autistic individuals can be compensated for at later processing stages by (a) the attention-orienting effects of fear, at the behavioral level, and (b) at the electrophysiological level via increased attentional effort.

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17. Tseng YL, Lee CH, Chiu YN, Tsai WC, Wang JS, Wu WC, Chien YL. Characterizing Autism Spectrum Disorder Through Fusion of Local Cortical Activation and Global Functional Connectivity Using Game-Based Stimuli and a Mobile EEG System. IEEE Trans Neural Syst Rehabil Eng;2024;32:3026-3035.

The deficit in social interaction skills among individuals with autism spectrum disorder (ASD) is strongly influenced by personal experiences and social environments. Neuroimaging studies have previously highlighted the link between social impairment and brain activity in ASD. This study aims to develop a method for assessing and identifying ASD using a social cognitive game-based paradigm combined with electroencephalo-graphy (EEG) signaling features. Typically developing (TD) participants and autistic preadolescents and teenagers were recruited to participate in a social game while 12-channel EEG signals were recorded. The EEG signals underwent preprocessing to analyze local brain activities, including event-related potentials (ERPs) and time-frequency features. Additionally, the global brain network’s functional connectivity between brain regions was evaluated using phase-lag indices (PLIs). Subsequently, machine learning models were employed to assess the neurophysiological features. Results indicated pronounced ERP components, particularly the late positive potential (LPP), in parietal regions during social training. Autistic preadolescents and teenagers exhibited lower LPP amplitudes and larger P200 amplitudes compared to TD participants. Reduced theta synchronization was also observed in the ASD group. Aberrant functional connectivity within certain time intervals was noted in the ASD group. Machine learning analysis revealed that support-vector machines achieved a sensitivity of 100%, specificity of 91.7%, and accuracy of 95.8% as part of the performance evaluation when utilizing ERP and brain oscillation features for ASD characterization. These findings suggest that social interaction difficulties in autism are linked to specific brain activation patterns. Traditional behavioral assessments face challenges of subjectivity and accuracy, indicating the potential use of social training interfaces and EEG features for cognitive assessment in ASD.

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18. Xiong W, Li X, Huang X, Xu J, Qu Z, Su Y, Li Y, Han Y, Cui T, Zhang X. Impaired motor and social skill development in infancy predict high autistic traits in toddlerhood. Neuroscience;2024 (Aug 20);558:114-121.

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder. Early diagnosis in the critical period is important for ASD children. Recent studies of neurodevelopmental behavioral features and joint attention in high-risk infants showed there are some special cues which can distinguish ASD from typical development infant. But the findings of high-risk population may not be applicable to the general population. It is necessary to « analogically » study the potential warning traits of ASD in infancy in the general population. We did a nested case-control study from June 2019 to November 2022 in Tianjin, China, including 76 general infants whom completed the neurodevelopmental evaluation, the Checklist for Autism in Toddlers-23 (CHAT-23) screening, and eye tracking task. Social behavior quotient in infancy was negatively correlated to CHAT-23 total scores in toddlerhood. Social behavior quotient in infancy was positively correlated to initiating joint attention in toddlerhood. Regression model showed that high fine motor scale and social behaviour scale quotient in infancy were associated with an decreased risk of the total score of CHAT-23 ≥ 2 in toddlerhood. The Receiver operating characteristic curve showed the social behaviour in infancy alone and the combination of fine motor and social behaviour in infancy contributed to auxiliary diagnosis of higher level of autistic traits in toddlerhood. These findings suggest that Impaired development of fine motor and social behavior in infancy are potential warning features of high autistic traits in general population.

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19. Zahedi E, Sadr SS, Sanaeierad A, Hosseini M, Roghani M. Acetyl-l-carnitine alleviates valproate-induced autism-like behaviors through attenuation of hippocampal mitochondrial dysregulation. Neuroscience;2024 (Aug 20);558:92-104.

This study aimed to evaluate the potential benefits of acetyl-L-carnitine (ALCAR) in the context of valproate-induced autism. After prenatal exposure to valproate (VPA; 600 mg/kg, i.p.) on embryonic day 12.5, followed by ALCAR treatment (300 mg/kg on postnatal days 21-49, p.o.), assessment of oxidative stress, mitochondrial membrane potential (MMP), mitochondrial biogenesis, parvalbumin interneurons, and hippocampal volume was conducted. These assessments were carried out subsequent to the evaluation of autism-like behaviors. Hippocampal analysis of oxidative factors (reactive oxygen species and malondialdehyde) and antioxidants (superoxide dismutase, catalase, and glutathione) revealed a burden of oxidative stress in VPA rats. Additionally, mitochondrial biogenesis and MMP were elevated, while the number of parvalbumin interneurons decreased. These changes were accompanied by autism-like behaviors observed in the three-chamber maze, marble burring test, and Y-maze, as well as a learning deficit in the Barnes maze. In contrast, administrating ALCAR attenuated behavioral deficits, reduced oxidative stress, improved parvalbumin-positive neuronal population, and properly modified MMP and mitochondrial biogenesis. Collectively, our results indicate that oral administration of ALCAR ameliorates autism-like behaviors, partly through its targeting oxidative stress and mitochondrial biogenesis. This suggests that ALCAR may have potential benefits ASD managing.

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20. Zilkha N, Chuartzman SG, Fishman R, Ben-Dor S, Kimchi T. Maternal high-fat or low-protein diets promote autism-related behavior and altered social behavior within groups in offspring male mice. Sci Rep;2024 (Aug 20);14(1):19227.

Maternal malnutrition has been associated with neurodevelopmental deficits and long-term implications on the offspring’s health and behavior. Here, we investigated the effects of maternal low-protein diet (LPD) or obesity-inducing maternal high-fat diet (HFD) on dyadic social interactions, group organization and autism-related behaviors in mice. We found that maternal HFD induced an autism-related behavioral phenotype in the male offspring, including a robust decrease in sociability, increased aggression, cognitive rigidity and repetitive behaviors. Maternal LPD led to a milder yet significant effect on autism-related symptoms, with no effects on olfactory-mediated social behavior. Under naturalistic conditions in a group setting, this manifested in altered behavioral repertoires, increased magnitude in dominance relations, and reduced interactions with novel social stimuli in the HFD male offspring, but not in the LPD offspring. Finally, we found HFD-induced transcriptomic changes in the olfactory bulbs of the male offspring. Together, our findings show that maternal malnutrition induces long-lasting effects on aggression and autism-related behaviors in male offspring, and potential impairments in brain regions processing chemosensory signals.

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