1. Al-Ayadhi L, Bhat RS, Alghamdi FA, Alhadlaq AS, El-Ansary A. Influence of Auditory Integrative Training on Casein Kinase 2 and Its Impact on Behavioral and Social Interaction in Children with Autism Spectrum Disorder. Current issues in molecular biology. 2023; 45(5): 4317-30.

Considerable disturbances in post-translational protein phosphorylation have recently been discovered in multiple neurological disorders. Casein kinase-2 (CK2) is a tetrameric Ser/Thr protein kinase that phosphorylates a large number of substrates and contributes in several cellular physiological and pathological processes. CK2 is highly expressed in the mammalian brain and catalyzes the phosphorylation of a large number of substrates that are crucial in neuronal or glial homeostasis and inflammatory signaling processes across synapses. In this study, we investigated the impact of auditory integration therapy (AIT) for the treatment of sensory processing abnormalities in autism on plasma CK2 levels. A total of 25 ASD children, aged between 5 and 12 years, were enrolled and participated in the present research study. AIT was performed for two weeks, for a period of 30 min, twice a day, with a 3 h interval between sessions. Before and after AIT, the Childhood Autism Rating Scale (CARS), Social Responsiveness Scale (SRS), and Short Sensory Profile (SSP) scores were calculated, and plasma CK2 levels were assayed using an ELISA test. The CARS and SRS indices of autism severity improved as a result of AIT, which could be related to the decreased level of plasma CK2. However, the mean value of the SSP scores was not significantly increased after AIT. The relationship between CK2 downregulation and glutamate excitotoxicity, neuro-inflammation, and leaky gut, as etiological mechanisms in ASD, was proposed and discussed. Further research, conducted on a larger scale and with a longer study duration, are required to assess whether the cognitive improvement in ASD children after AIT is related to the downregulation of CK2.

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2. Alhozyel E, Elbedour L, Balaum R, Meiri G, Michaelovski A, Dinstein I, Davidovitch N, Kerub O, Menashe I. Association Between Early Developmental Milestones and Autism Spectrum Disorder. Research on child and adolescent psychopathology. 2023.

Early diagnosis and treatment of autism spectrum disorder (ASD) has been shown to lead to better prognosis. Here, we examined the association of commonly measured early developmental milestones (DMs) with later diagnosis of ASD. We conducted a case-control study of 280 children with ASD (cases) and 560 typically developed children (controls) matched to cases by date of birth, sex, and ethnicity in a control/case ratio of 2:1. Both cases and controls were ascertained from all children whose development was monitored at mother-child health clinics (MCHCs) in southern Israel. DM failure rates during the first 18 months of life in three developmental categories (motor, social, and verbal) were compared between cases and controls. Conditional logistic regression models were used to assess the independent association of specific DMs with the risk of ASD, while adjusting for demographic and birth characteristics.Significant case-control differences in DM failure rates were observed as early as 3 months of age (p < 0.001), and these differences increased with age. Specifically, cases were 2.4 times more likely to fail ≥ 1 DM at 3 months (aOR = 2.39; 95%CI = 1.41-4.06), and 15.3 times more likely to fail ≥ 3 DMs at 18 months (aOR = 15.32; 95%CI = 7.75-30.28). The most notable DM-ASD association was observed for social DM failure at 9-12 months (aOR = 4.59; 95%CI = 2.59-8.13). Importantly, the sex or ethnicity of the participants did not affect these DM-ASD associations. Our findings highlight the potential role of DMs as early signs of ASD that could facilitate earlier referral and diagnosis of ASD.

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3. Briend F, Barantin L, Cléry H, Cottier JP, Bonnet-Brilhault F, Houy-Durand E, Gomot M. Glutamate levels of the right and left anterior cingulate cortex in autistics adults. Progress in neuro-psychopharmacology & biological psychiatry. 2023; 126: 110801.

BACKGROUND: The neurobiology of Autism Spectrum Disorder (ASD) is still unknown. Alteration in glutamate metabolism might translate into an imbalance of the excitation/inhibition equilibrium of cortical networks that in turn are related to autistic symptoms, but previous studies using voxel located in bilateral anterior cingulate cortex (ACC) failed to show abnormalities in total glutamate level. Due to the functional differences in the right and left ACC, we sought to determine whether a difference between right and left ACC glutamate levels could be found when comparing ASD patients and control subjects. METHODS: Using single-voxel proton magnetic resonance spectroscopy ((1)H-MRS), we analyzed the glutamate + glutamine (Glx) concentrations in the left and right ACC of 19 ASD patients with normal IQs and 25 matched control subjects. RESULTS: No overall group differences in Glx were shown, in the left ACC (p = 0.24) or in the right ACC (p = 0.11). CONCLUSIONS: No significant alterations in Glx levels were detected in the left and right ACC in high-functioning autistic adults. In the excitatory/inhibitory imbalance framework, our data reinforce the critical need to analyze the GABAergic pathway, for better understanding of basic neuropathology in autism.

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4. Brunt S, Sadikova E, Pappagianopoulos J, Mazurek MO. The impact of COVID-19 on receipt of health services among children with and without autism. Autism : the international journal of research and practice. 2023: 13623613231176930.

The COVID-19 pandemic disrupted doctor’s and dental visits, mental health treatments, and other special therapies for children across the United States. Prior research has found that autistic children were more likely to lack these services even before the pandemic, but they experienced more mental health and behavior problems with the onset of the pandemic, increasing the need for these services. This study analyzed data from before (2019) and after (2020) the onset of the pandemic to determine whether autistic children had even more severe disruptions in services after the pandemic started compared to nonautistic children. We found that autistic children were more likely to have unmet medical, dental, and mental health needs in both 2019 and 2020. Overall, children experienced increased disruptions from 2019 to 2020, but this did not differ by diagnosis. Our results suggest that there are persisting gaps in autistic children’s healthcare regardless of the pandemic. We discuss issues surrounding barriers to services for autistic children and issues surrounding virtual services, such as teletherapy. Future research should further explore how to reduce barriers to services for autistic children, including virtual and in-person services.

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5. Chen L, He X, Durrleman S. Acquisition of grammatical aspect by Mandarin-speaking preschool children with autism spectrum disorder. International journal of language & communication disorders. 2023.

BACKGROUND: Mandarin-speaking children with autism spectrum disorder (ASD) have difficulties producing aspect markers. The difficulties were explained in terms of pragmatic deficits since these children demonstrated strength in the comprehension of aspect markers using the Intermodal Preferential Looking (IPL) task. AIMS: To verify whether this dissociation between production and comprehension could be replicated using another technique to the IPL, and if all children with ASD show difficulties in the production of aspect markers. METHODS & PROCEDURES: A total of 34 children with ASD without cognitive delay, half with language impairment (ALI; mean age = 61.25 months old) and half with normal language (ALN, mean age = 61.52 months old), as well as 17 age-matched typically developing (TD) children (mean age = 61.38 months old) participated in a sentence-picture-matching task and a priming picture-description task to investigate their comprehension and production of Mandarin aspect markers zai-, -le and -zhe. OUTCOMES & RESULTS: In the comprehension task, children in the ALN group performed similarly to their TD peers, but those in the ALI group were less accurate on zai- and -le than TD children; children in all groups received higher accuracy when zai- was combined with Activity rather than Accomplishment verbs, and those in the ALI group was also more accurate when -le occurred with Achievement verbs, in contrast to Activity verbs. In the production task, children in the ALI group produced fewer targets and more irrelevant sentences with zai- than their TD peers, and they tended to produce bare verbs for -le and -zhe than TD children; children in all groups tended to combine zai- with Activity verbs, and those in the ALN group also tended to combine -le with Achievement verbs. CONCLUSIONS & IMPLICATIONS: The comprehension and production of Mandarin aspect markers by children with ASD are linked to general language abilities, and interactions between lexical and grammatical aspect. Patterns of performance are similar to those of TD peers only for the subgroup with spared global language, while pragmatic deficits are pervasive throughout the spectrum. Therefore, training on formal language, with a specific emphasis on aspectual rather than pragmatic abilities, may be more effective at enhancing the production of aspect markers. WHAT THIS PAPER ADDS: What is already known on this subject Mandarin-speaking children with ASD have difficulties producing aspect markers but demonstrate strengths in aspectual comprehension via the IPL task. Therefore, it has been proposed that their ‘specific’ difficulties in aspectual production should be ascribed to their pragmatic deficits. However, pragmatic deficits are highly pervasive in children with ASD while only a subgroup of children with ASD who are impaired in language development (children with ALI) show difficulties in producing tense/aspect morphology. Pursuing this reasoning, pragmatic deficits might not be the critical factor impacting the performance of children with ASD in aspectual production. What this study adds Children with ASD were divided into one group with ALI and the other with normal language (ALN). Results of a sentence-picture-matching and a priming picture-description task illustrated that both groups preserved the comprehension of Mandarin aspect markers zai-, -le and -zhe. However, children with ALI performed worse than age-matched TD children, while children with ALN demonstrated similar performance to TD children in aspectual production. These findings, coupled with the fact that pragmatic challenges affect individuals throughout the spectrum, suggest that general language abilities rather than pragmatics better explain the performance of children with ASD on aspectual production. What are the potential or actual clinical implications of this work? Since general language abilities rather than pragmatic deficits of children with ASD determine their performance on the production of aspect markers, direct training on the use of aspect markers or more global language therapy could benefit children with ASD in the production of aspect markers.

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6. Costa AN, Ferguson BJ, Hawkins E, Coman A, Schauer J, Ramirez-Celis A, Hecht PM, Bruce D, Tilley M, Talebizadeh Z, Van de Water J, Beversdorf DQ. The Relationship between Maternal Antibodies to Fetal Brain and Prenatal Stress Exposure in Autism Spectrum Disorder. Metabolites. 2023; 13(5).

Environmental and genetic factors contribute to the etiology of autism spectrum disorder (ASD), but their interaction is less well understood. Mothers that are genetically more stress-susceptible have been found to be at increased risk of having a child with ASD after exposure to stress during pregnancy. Additionally, the presence of maternal antibodies for the fetal brain is associated with a diagnosis of ASD in children. However, the relationship between prenatal stress exposure and maternal antibodies in the mothers of children diagnosed with ASD has not yet been addressed. This exploratory study examined the association of maternal antibody response with prenatal stress and a diagnosis of ASD in children. Blood samples from 53 mothers with at least one child diagnosed with ASD were examined by ELISA. Maternal antibody presence, perceived stress levels during pregnancy (high or low), and maternal 5-HTTLPR polymorphisms were examined for their interrelationship in ASD. While high incidences of prenatal stress and maternal antibodies were found in the sample, they were not associated with each other (p = 0.709, Cramér’s V = 0.051). Furthermore, the results revealed no significant association between maternal antibody presence and the interaction between 5-HTTLPR genotype and stress (p = 0.729, Cramér’s V = 0.157). Prenatal stress was not found to be associated with the presence of maternal antibodies in the context of ASD, at least in this initial exploratory sample. Despite the known relationship between stress and changes in immune function, these results suggest that prenatal stress and immune dysregulation are independently associated with a diagnosis of ASD in this study population, rather than acting through a convergent mechanism. However, this would need to be confirmed in a larger sample.

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7. English MCW, Maybery MT, Visser TAW. A review of behavioral evidence for hemispheric asymmetry of visuospatial attention in autism. Autism research : official journal of the International Society for Autism Research. 2023.

Most individuals show a small bias towards visual stimuli presented in their left visual field (LVF) that reflects right-hemispheric specialization of visuospatial functions. Moreover, this bias is altered by some neurodevelopmental disorders, suggesting they may be linked to changes in hemispheric asymmetry. To examine whether autism potentially alters hemispheric asymmetry, we conducted a systematic search of scientific databases to review existing literature on the link between autism and alterations in visuospatial bias. This search identified 13 publications that had explored this issue using a wide range of experimental designs and stimuli. Evidence of reduced LVF bias associated with autism was most consistent for studies examining attentional bias or preference measured using tasks such as line bisection. Findings for studies examining attentional performance (e.g., reaction time) were more equivocal. Further investigation is called for, and we make several recommendations for how this avenue of research can be extended.

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8. Fan Y, Li Y, Yang X, Zhang H, Wang B, Guan J, Gao J, Ma X, Liu Y. Generation and characterization of PBMCs-derived human induced pluripotent stem cell (iPSC) line SDQLCHi051-A from an autism spectrum disorder patient with compound CHD8 gene mutations. Stem cell research. 2023; 69: 103114.

CHD8 mutation is a case of genetic related autism spectrum disorder(ASD), In our research, We describe here the derivation of the iPSC line SDQLCHi051-A from a patient with autism spectrum disorder (ASD) due to two heterozygote mutations (c.6728G > A and c.3876 T > G) in the CHD8 gene. The resulting iPSC line has typical iPSCs characteristics, including pluripotency and trilineage differentiation hallmarks.

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9. Gray LJ, Durand H. Experiences of dysmenorrhea and its treatment among allistic and autistic menstruators: a thematic analysis. BMC women’s health. 2023; 23(1): 288.

BACKGROUND: Dysmenorrhea (i.e., period pain) is common and debilitating. Autistic people are known to experience pain differently, yet little is known about the menstrual pain experiences of autistic menstruators relative to non-autistic peers. This study aimed to explore the experience of period pain and treatment uptake for period pain among allistic and autistic populations. METHODS: This study used a qualitative design and opportunity sampling approach. Thirty-seven participants (of whom 17 were autistic) were interviewed via video-conferencing software using a semi-structured topic guide. Transcriptions of interviews were analysed using Braun and Clarke’s Reflexive Thematic Analysis. Data were initially analysed together for common themes. Autistic menstruators’ data was subsequently analysed separately to elucidate the unique experiences of this group. RESULTS: A total of six themes were constructed from the data. Initial analysis determined three themes related to experiences of period pain and treatment uptake in both allistic and autistic menstruators. Social perception of menstruation was discussed, highlighting the normalisation of pain, the taboo nature, and gendered experience of menstruation, contributing to untreated menstrual pain. Issues within menstrual healthcare were also shared, including experiences of ineffective treatment, dismissive interactions, and insufficient menstrual education. Impaired functionality was repeatedly highlighted, with menstruators detailing significant limitations to their usual functioning due to menstrual pain and ineffective treatment. Three further themes were constructed from separate analysis of data from autistic menstruators. Autistic menstruators discussed the impact of menstruation on their sensory experiences and needs, with many identifying overstimulation during menstruation. Social exclusion was discussed as a factor contributing to the experience of menstrual pain and poor treatment uptake. The final theme identified pain communication differences between autistic and allistic menstruators resulting in reports of ineffective treatment and challenges in healthcare interactions. CONCLUSIONS: Communication differences, sensory aspects, and social factors contributed to the experience of period pain and treatment uptake for autistic menstruators. The perception of menstruation within society was highlighted by allistic and autistic menstruators as influential to their pain experience and engagement with treatment. Functionality was significantly impacted by pain for this sample. The study highlights societal and healthcare factors that could be improved to ensure accessibility of support and treatment for menstrual issues.

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10. Hardman G, Zacharias J. Minimal-Access Atrial Septal Defect (ASD) Closure. Journal of cardiovascular development and disease. 2023; 10(5).

Progress towards the development and adoption of minimally invasive techniques in cardiac surgery has been slower than that seen in other surgical specialties. Congenital heart disease (CHD) patients represent an important population within cardiac disease, of which atrial septal defect (ASD) is one of the most common diagnoses. Management of ASD encompasses a range of minimal-access and minimally invasive approaches, including transcatheter device closure, mini-sternotomy, thoracotomy, video-assisted, endoscopic, and robotic approaches. In this article, we will discuss the pathophysiology of ASD, along with diagnosis, management, and indications for intervention. We will review the current evidence supporting minimally invasive and minimal-access surgical ASD closure in the adult and paediatric patient, highlighting peri-operative considerations and areas for further research.

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11. Katz J, Hunt J, Cammuso K, Moreno-De-Luca D. Development and Implementation of an Autism Spectrum and Intellectual Developmental Disorders Specialty Track Within Child and Adolescent Psychiatry Fellowship. Academic psychiatry : the journal of the American Association of Directors of Psychiatric Residency Training and the Association for Academic Psychiatry. 2023.

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12. Kundu K, Maharjan S, Saini LK, Gupta R. Sleep architecture is associated with core symptom severity in autism spectrum disorder: a few methodological observations. Sleep. 2023.

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13. Lincoln-Boyea B, Moultrie RR, Biesecker BB, Underwood M, Duparc M, Wheeler AC, Peay HL. Misunderstood terms and concepts identified through user testing of educational materials for fragile X premutation: « Not weak or fragile? ». Journal of genetic counseling. 2023.

Complicated genetic mechanisms and unpredictable health risks associated with the FMR1 premutation can result in challenges for patient education when the diagnosis is made in a newborn. From October 15, 2018, to December 10, 2021, North Carolina parents could obtain FMR1 premutation results about their newborns through a voluntary expanded newborn screening research study. The study provided confirmatory testing, parental testing, and genetic counseling. We developed web-based educational materials to augment information about fragile X premutation conveyed by a genetic counselor. Many genetics education materials are developed for the lay population. However, relatively little research is published on how well individuals understand these materials. We conducted three rounds of iterative user testing interviews to help refine web-based educational materials that support understanding and self-paced learning. The participants included 25 parents with a 2-year college degree or less and without a child identified with fragile X syndrome, premutation, or gray-zone allele. Content analysis of interview transcripts resulted in iterative changes and ultimately saturation of findings. Across all rounds of interviews, there were two terms that were commonly misunderstood (fragile and carrier) and two terms that elicited initial misconceptions that were overcome by participants. Many also had difficulty understanding the relationship between fragile X premutation and fragile X syndrome as well as appreciating the implications of having a « fragile X gene. » Website layout, formatting, and graphics also influenced comprehension. Despite iterative changes to the content, certain issues with understandability persisted. The findings support the need for user testing to identify misconceptions that may interfere with understanding and using genetic information. Here, we describe a process used to develop and refine evidence-based, understandable parental resources on fragile X premutation. Additionally, we provide recommendations to address ongoing educational challenges and discuss the potential impact of bias on the part of expert content developers.

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14. Nayar K, Katz L, Heinrich K, Berger N. Autism spectrum disorder and congenital heart disease: a narrative review of the literature. Cardiology in the young. 2023: 1-11.

Individuals born with congenital heart disease (CHD) are at an increased risk of developing neurodevelopmental disorders. Despite this, studies are limited in their investigation of autism spectrum disorder in the context of CHD. This review provides an overview of the literature examining autism spectrum disorder in CHD and discusses strengths, limitations, and future directions. Recent efforts have been made to extrapolate the association between CHD and symptoms of autism. Findings suggest that the core features of autism spectrum disorder are also implicated in children with CHD, namely social-cognitive weaknesses, pragmatic language differences, and social problems. Compared to norm-referenced samples, separate studies have identified divergent and overlapping neuropsychological profiles among both patient groups, yet there are no studies directly comparing the two groups. There is emerging evidence of prevalence rates of autism diagnosis in CHD showing an increased odds of having autism spectrum disorder among children with CHD relative to the general population or matched controls. There also appears to be genetic links to this overlap, with several genes identified as being tied to both CHD and autism. Together, research points to potentially shared underlying mechanisms contributing to the pathophysiology of neurodevelopmental, neuropsychological, and clinical traits in CHD and autism spectrum disorder. Future investigation delineating profiles across these patient populations can fill a significant gap in the literature and aid in treatment approaches to improve clinical outcomes.

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15. Peeters R, Premchand A, Tops W. Neuropsychological profile of children with Autism Spectrum Disorder and children with Developmental Language Disorder and its relationship with social communication. Applied neuropsychology Child. 2023: 1-11.

OBJECTIVE: The objective of this study was to probe neuropsychological mechanisms of social communication in children with Autism Spectrum Disorders (ASD) and children with Developmental Language Disorders (DLD). Due to overlap of symptoms that include social dysfunction, diagnostic boundaries between these two developmental disorders remain unclear. This study hypothesizes that these two groups of children differ in the characteristics and in the underlying mechanisms of their social issues. METHOD: This study examines a wide range of neuropsychological domains in search of a relationship with social communication. A total of 75 children with ASD and 26 children with DLD are included. A cross-battery assessment of neuropsychological functions is conducted, and social communication is evaluated using the Social Responsiveness Scale (SRS). RESULTS: The neuropsychological profile for the ASD group differs from the DLD group, with the former demonstrating higher scores on Visual Processing and Comprehension, whereas the DLD group scores higher on Fluid Reasoning, Visual Processing and Processing Speed. Correlation analysis reveals that the association between neuropsychological domains and social communication differs between the groups. DISCUSSION: Children with ASD and DLD clearly have distinctive neuropsychological profiles-their strengths and weaknesses are not equivalent. Such results motivate broad assessment of neuropsychological functions, as this assists in differentiating ASD from DLD for theragnostic purposes.

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16. Tromans S, Henley W, Summers I, Bilkey D, Datson J, Doherty N, Morpeth L, Benbow S, Jelbert R, Roy A, Watkins L, Perera B, Shazad S, Pender R, Alexander R, Laugharne R, Shankar R. The psychological and social impact of the digital self-support system ‘Brain in Hand’ on autistic people: prospective cohort study in England and Wales. BJPsych open. 2023; 9(3): e96.

BACKGROUND: Brain in Hand (BIH) is a UK-based digital self-support system for managing anxiety and social functioning. AIMS: To identify the impact of BIH on the psychological and social functioning of adults with autism. METHOD: Adults with diagnosed or suspected DSM-5 (level 1) autism, identified by seven NHS autism services in England and Wales, were recruited for a 12-week prospective mixed-methods cohort study. The primary quantitative outcome measures were the Health of the Nation Outcome Scales for People with Learning Disabilities (HONOS-LD) and the Hospital Anxiety and Depression Scale (HADS). Fisher’s exact test explored sociodemographic associations. Paired t-test was utilised for pre-post analysis of overall effectiveness of BIH. Multivariable linear regression models, univariable pre-post analysis, Wilcoxon signed-rank test, logistic regression analysis, Bonferroni correction and normative analysis were used to give confidence in changes identified. A thematic analysis of semi-structured exist interviews following Braun and Clarke’s six-step process of 10% of participants who completed the study was undertaken. RESULTS: Sixty-six of 99 participants completed the study. There was significant reduction in mean HONOS-LD scores, with 0.65 s.d. decrease in those who used BIH for 12 weeks. Significant positive changes were identified in HONOS-LD subdomains of ‘self-injurious behaviours’, ‘memory and orientation’, ‘communication problems in understanding’, ‘occupation and activities’ and ‘problems with relationship’. A significant reduction in the anxiety, but not depression, component of the HADS scores was identified. Thematic analysis showed high confidence in BIH. CONCLUSIONS: BIH improved anxiety and other clinical, social and functioning outcomes of adults with autism.

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17. Unruh KE, Bartolotti JV, McKinney WS, Schmitt LM, Sweeney JA, Mosconi MW. Functional connectivity of cortical-cerebellar networks in relation to sensorimotor behavior and clinical features in autism spectrum disorder. Cerebral cortex (New York, NY : 1991). 2023.

Sensorimotor issues are present in the majority of individuals with autism spectrum disorder (ASD) and are associated with core symptoms. The neural systems associated with these impairments remain unclear. Using a visually guided precision gripping task during functional magnetic resonance imaging, we characterized task-based connectivity and activation of cortical, subcortical, and cerebellar visuomotor networks. Participants with ASD (n = 19; ages 10-33) and age- and sex-matched neurotypical controls (n = 18) completed a visuomotor task at low and high force levels. Relative to controls, individuals with ASD showed reduced functional connectivity of right primary motor-anterior cingulate cortex and left anterior intraparietal lobule (aIPL)-right Crus I at high force only. At low force, increased caudate, and cerebellar activation each were associated with sensorimotor behavior in controls, but not in ASD. Reduced left aIPL-right Crus I connectivity was associated with more severe clinically rated ASD symptoms. These findings suggest that sensorimotor problems in ASD, particularly at high force levels, involve deficits in the integration of multimodal sensory feedback and reduced reliance on error-monitoring processes. Adding to literature positing that cerebellar dysfunction contributes to multiple developmental issues in ASD, our data implicate parietal-cerebellar connectivity as a key neural marker underlying both core and comorbid features of ASD.

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