Differentiation of human telencephalic progenitor cells into MSNs by inducible expression of Gsx2 and Ebf1.

Medium spiny neurons (MSNs) are a key population in the basal ganglia network, and their degeneration causes a severe neurodegenerative disorder, Huntington's disease. Understanding how ventral neuroepithelial progenitors differentiate into MSNs is critical for regenerative medicine to develop specific differentiation protocols using human pluripotent stem cells. Studies performed in murine models have identified some transcriptional determinants, including GS Homeobox 2 (Gsx2) and Early B-cell factor 1 (Ebf1). Here, we have generated human embryonic stem (hES) cell lines inducible for these transcription factors, with the aims of (i) studying their biological role in human neural progenitors and (ii) incorporating TF conditional expression in a developmental-based protocol for generating MSNs from hES cells. Using this approach, we found that Gsx2 delays cell-cycle exit and reduces Pax6 expression, whereas Ebf1 promotes neuronal differentiation. Moreover, we found that Gsx2 and Ebf1 combined overexpression in hES cells achieves high yields of MSNs, expressing Darpp32 and Ctip2, in vitro as well in vivo after transplantation. We show that hES-derived striatal progenitors can be transplanted in animal models and can differentiate and integrate into the host, extending fibers over a long distance.

Sox2 conditional mutation in mouse causes ataxic symptoms, cerebellar vermis hypoplasia, and postnatal defects of Bergmann glia.

Sox2 is a transcription factor active in the nervous system, within different cell types, ranging from radial glia neural stem cells to a few specific types of differentiated glia and neurons. Mutations in the human SOX2 transcription factor gene cause various central nervous system (CNS) abnormalities, involving hippocampus and eye defects, as well as ataxia. Conditional Sox2 mutation in mouse, with different Cre transgenes, previously recapitulated different essential features of the disease, such as hippocampus and eye defects. In the cerebellum, Sox2 is active from early embryogenesis in the neural progenitors of the cerebellar primordium; Sox2 expression is maintained, postnatally, within Bergmann glia (BG), a differentiated cell type essential for Purkinje neurons functionality and correct motor control. By performing Sox2 Cre-mediated ablation in the developing and postnatal mouse cerebellum, we reproduced ataxia features. Embryonic Sox2 deletion (with Wnt1Cre) leads to reduction of the cerebellar vermis, known to be commonly related to ataxia, preceded by deregulation of Otx2 and Gbx2, critical regulators of vermis development. Postnatally, BG is progressively disorganized, mislocalized, and reduced in mutants. Sox2 postnatal deletion, specifically induced in glia (with GLAST-CreERT2), reproduces the BG defect, and causes (milder) ataxic features. Our results define a role for Sox2 in cerebellar function and development, and identify a functional requirement for Sox2 within postnatal BG, of potential relevance for ataxia in mouse mutants, and in human patients.

Preventive motor training but not progenitor grafting ameliorates cerebellar ataxia and deregulated autophagy in tambaleante mice.

Treatment options for degenerative cerebellar ataxias are currently very limited. A large fraction of such disorders is represented by hereditary cerebellar ataxias, whose familiar transmission facilitates an early diagnosis and may possibly allow to start preventive treatments before the onset of the neurodegeneration and appearance of first symptoms. In spite of the heterogeneous aetiology, histological alterations of ataxias often include the primary degeneration of the cerebellar cortex caused by Purkinje cells (PCs) loss. Thus, approaches aimed at replacing or preserving PCs could represent promising ways of disease management. In the present study, we compared the efficacy of two different preventive strategies, namely cell replacement and motor training. We used tambaleante (tbl) mice as a model for progressive ataxia caused by selective loss of PCs and evaluated the effectiveness of the preventive transplantation of healthy PCs into early postnatal tbl cerebella, in terms of PC replacement and functional preservation. On the other hand, we investigated the effects of motor training on PC survival, cerebellar circuitry and their behavioral correlates. Our results demonstrate that, despite a good survival rate and integration of grafted PCs, the adopted grafting protocol could not alleviate the ataxic symptoms in tbl mice. Conversely, preventive motor training increases PCs survival with a moderate positive impact on the motor phenotype.

Sonic hedgehog patterning during cerebellar development.

The morphogenic factor sonic hedgehog (Shh) actively orchestrates many aspects of cerebellar development and maturation. During embryogenesis, Shh signaling is active in the ventricular germinal zone (VZ) and represents an essential signal for proliferation of VZ-derived progenitors. Later, Shh secreted by Purkinje cells sustains the amplification of postnatal neurogenic niches: the external granular layer and the prospective white matter, where excitatory granule cells and inhibitory interneurons are produced, respectively. Moreover, Shh signaling affects Bergmann glial differentiation and promotes cerebellar foliation during development. Here we review the most relevant functions of Shh during cerebellar ontogenesis, underlying its role in physiological and pathological conditions.

Transcranial Direct Current Stimulation in neurogenetic syndromes: new treatment perspectives for Down syndrome?

This perspective review aims to explore the potential neurobiological mechanisms involved in the application of transcranial Direct Current Stimulation (tDCS) for Down syndrome (DS), the leading cause of genetically-based intellectual disability. The neural mechanisms underlying tDCS interventions in genetic disorders, typically characterized by cognitive deficits, are grounded in the concept of brain plasticity. We initially present the neurobiological and functional effects elicited by tDCS applications in enhancing neuroplasticity and in regulating the excitatory/inhibitory balance, both associated with cognitive improvement in the general population. The review begins with evidence on tDCS applications in five neurogenetic disorders, including Rett, Prader-Willi, Phelan-McDermid, and Neurofibromatosis 1 syndromes, as well as DS. Available evidence supports tDCS as a potential intervention tool and underscores the importance of advancing neurobiological research into the mechanisms of tDCS action in these conditions. We then discuss the potential of tDCS as a promising non-invasive strategy to mitigate deficits in plasticity and promote fine-tuning of the excitatory/inhibitory balance in DS, exploring implications for cognitive treatment perspectives in this population.

Psychiatric Comorbidities in Children and Adolescents with High-Functioning Autism Spectrum Disorder: A Study on Prevalence, Distribution and Clinical Features in an Italian Sample.

This study investigated the prevalence and distribution of psychiatric comorbidities in a group of 472 children and adolescents with ASD aged 3-18 years. We examined differences in age, sex, IQ, adaptive skills, and ASD symptom severity by comparing participants with ASD (ASD group) with participants with ASD and a psychiatric disorder (ASD/PSY group). Overall, 32.2% of participants had a comorbid psychiatric condition. Attention deficit/hyperactivity disorder (ADHD) was the most frequent diagnosis among preschoolers (20.4%); among school-age children, ADHD and anxiety/obsessive-compulsive disorders were the most frequent conditions (21% and 10.6%, respectively); finally, adolescents exhibit higher prevalence of anxiety/obsessive-compulsive disorders (21.8%). The ASD/PSY group showed a higher percentage of males, they were older and showed lower adaptive skills than the group with ASD; moreover, their mothers exhibited higher stress levels than mothers of participants in the ASD group. The comparison between age groups in participants within ASD/PSY group revealed that preschoolers had lower IQ than school-age children and adolescents, and worse adaptive skills, more repetitive behaviors, and restricted interests than adolescents. This study highlights the importance of an accurate diagnosis of psychiatric comorbidities in children and adolescents with ASD, also considering individual and family impairment.

Talkitt: toward a new instrument based on artificial intelligence for augmentative and alternative communication in children with down syndrome.

Introduction: Individuals with Down syndrome (DS) often exhibit a severe speech impairment, with important consequences on language intelligibility. For these cases, the use of Augmentative Alternative Communication instruments, that increase an individual's communication abilities, becomes crucial. Talkitt is a mobile application created by Voiceitt Company, exploiting speech recognition technology and artificial intelligence models to translate in real-time unintelligible sounds into clear words, allowing individuals with language production impairment to verbally communicate in real-time. Methods: The study evaluated the usability and satisfaction related to the Talkitt application use, as well as effects on adapted behavior and communication, of participants with DS. A final number of 23 individuals with DS, aged 5.54 to 28.9 years, participated in this study and completed 6 months of training. The application was trained to consistently recognize at least 20 different unintelligible words (e.g., nouns and/or short phrases)/person. Results: Results revealed good usability and high levels of satisfaction related to the application use. Moreover, we registered improvement in linguistic abilities, particularly naming. Discussion: These results paves the road for a potential role of Talkitt application as a supportive and rehabilitative tool for DS.

Sleep and behavioral problems in Down syndrome: differences between school age and adolescence.

Background: Individuals with Down syndrome (DS) are at risk of developing sleep problems. In spite of the well-established knowledge on the presence of sleep difficulties in DS individuals and the associated emotional and behavioral problems, less is known about the possible differences in the kind of associations between sleep and emotional/behavioral problems across different age ranges. Methods: In this retrospective study, we included 289 participants with DS aged 6-18 years with the aims to explore differences in the distribution of sleep problems between specific age groups (school age vs. adolescence) and to identify specific age-based associations between sleep problems and emotional/behavioral problems. Results: Some differences in the distribution of sleep problems have emerged between age groups. Moreover, differences in the patterns of association between emotional/behavioral difficulties and sleep problems-in particular, sleep-related breathing difficulties and parasomnias-have been observed. However, sleep-wake transition disorders and excessive daily somnolence appear to be related to emotional and behavioral problems (both internalizing and externalizing), in general, across school age and adolescence. Discussion: These results remark the importance of appropriate neuropsychiatric and psychological evaluation taking into account the age-specific needs and features of individuals with DS.

Emotional and behavioral features associated with subclinical hypothyroidism in children and adolescents with Down syndrome.

Background: Subclinical hypothyroidism (SH) is particularly frequent in individuals with Down syndrome (DS). Despite the amount of evidence suggesting SH is associated with psychopathological symptoms and sleep problems in general population, poor is known about the emotional and behavioral features associated with SH in children with DS. Objective: The first aim of the current study was to investigate differences in emotional and behavioral profiles between a group of children with DS exhibiting co-occurring SH and a group of age and BMI-matched children with DS without co-occurring SH. The second aim of the present study was to investigate differences in sleep disturbances between these groups. Methods: We included in this retrospective study 98 participants with DS aged 3-18 years with the aim to explore differences in emotional/behavioral problems as well as in sleep difficulties between children with DS with or without co-occurring SH. Results: Participants with co-occurring SH exhibited significantly higher scores at several scales of the Conners' Parent Rating Scales Long Version - Revised. However, they did not exhibit more sleep problems than control group. Conclusion: These results provide specific indications for psychological and neuropsychiatric evaluation of children with DS with suspected or diagnosed SH, highlighting the importance of a multidisciplinary approach in clinical care for children and adolescents with DS.

The efficacy of non-invasive brain stimulation in the treatment of children and adolescents with Anorexia Nervosa: study protocol of a randomized, double blind, placebo-controlled trial.

BACKGROUND: Current psychological and pharmacological treatments for Anorexia Nervosa (AN) provide only moderate effective support, and there is an urgent need for research to improve therapies, especially in developing age. Non-invasive brain stimulation has suggested to have the potential to reducing AN symptomatology, via targeting brain alterations, such as hyperactivity of right prefrontal cortex (PFC). We suppose that transcranial direct current stimulation (tDCS) to the PFC may be effective in children and adolescents with AN. METHODS: We will conduct a randomized, double blind, add-on, placebo-controlled trial to investigate the efficacy of tDCS treatment on clinical improvement. We will also investigate brain mechanisms and biomarkers changes acting in AN after tDCS treatment. Eighty children or adolescent with AN (age range 10-18 years) will undergo treatment-as-usual including psychiatric, nutritional and psychological support, plus tDCS treatment (active or sham) to PFC (F3 anode/F4 cathode), for six weeks, delivered three times a week. Psychological, neurophysiological and physiological measures will be collected at baseline and at the end of treatment. Participants will be followed-up one, three, six months and one year after the end of treatment. Psychological measures will include parent- and self-report questionnaires on AN symptomatology and other psychopathological symptoms. Neurophysiological measures will include transcranial magnetic stimulation (TMS) with electroencephalography and paired pulse TMS and repetitive TMS to investigate changes in PFC connectivity, reactivity and plasticity after treatment. Physiological measures will include changes in the functioning of the endogenous stress response system, body mass index (BMI) and nutritional state. DISCUSSION: We expect that tDCS treatment to improve clinical outcome by reducing the symptoms of AN assessed as changes in Eating Disorder Risk composite score of the Eating Disorder Inventory-3. We also expect that at baseline there will be differences between the right and left hemisphere in some electrophysiological measures and that such differences will be reduced after tDCS treatment. Finally, we expect a reduction of endogenous stress response and an improvement in BMI and nutritional status after tDCS treatment. This project would provide scientific foundation for new treatment perspectives in AN in developmental age, as well as insight into brain mechanisms acting in AN and its recovery. Trial registration The study was registered at ClinicalTrials.gov (ID: NCT05674266) and ethical approval for the study was granted by the local research ethics committee (process number 763_OPBG_2014).

Parenting Stress in Mothers of Children and Adolescents with Down Syndrome.

Parenting stress has deleterious effects on parents, children, and overall family functioning. Parents of children with intellectual disability, including Down Syndrome (DS), show higher levels of parenting stress than parents of typically developing children. This research aimed to (i) evaluate parenting stress levels in a group of mothers of youths with DS using a parent-report questionnaire, (ii) identify children's individual and clinical features associated with maternal stress, and (iii) identify specific situational life/demographics factors related to maternal stress. Seventy-eight youths with DS underwent a neuropsychological evaluation, whereas mothers completed questionnaires for the assessment of parenting stress and of the child's emotional and behavioral problems. We found that Parent-Child Difficult Interaction was the domain with the highest percentage of clinical scores (39.7%). Both internalizing and externalizing problems correlated with maternal stress, as well as autistic symptoms. The levels of maternal stress were not associated with any socio-demographic variable. After controlling for child-related correlates of maternal stress and for mothers' age and education level, unemployed mothers exhibited higher levels of parental distress than employed mothers. The present study highlights that unemployment is related with parenting stress and potentially amenable to policy interventions supporting parents in combining work and family care.

Parental perspectives on the quality of life of children with Down syndrome.

Down Syndrome (DS) is the most common chromosome abnormality and the most frequent cause of developmental delay/intellectual disabilities in children. Although the investigation of the quality of life (QoL) is crucial in children with DS, relatively poor attention has been paid to this topic. The current study aimed to evaluate parent-reported QoL in a group of children with DS and identify children's individual and clinical features associated with different levels of QoL. We included in the study 73 children with DS (5-12 years) and investigated the parent-reported levels of QoL by means of the Pediatric Quality of Life Inventory. Cognitive level and the presence of behavioral difficulties were also evaluated. The overall parent-reported QoL of children with DS was high; emotional functioning was the domain with the highest level of QoL. Moreover, parents perceived low levels of QoL in children who exhibited low IQ, worse analogical reasoning, worse adaptive skills, more frequent challenging behaviors, more ritualistic/sameness behavior and more autistic symptoms. No differences emerged for family variables, namely parental education and employment, between the two groups with high and low QoL, as perceived by parents. The understanding of cognitive and behavioral factors - such as analogical reasoning, socio-communication abilities and challenging behaviors - related with different degrees of QoL in children with DS is crucial for the development of effective strategies to promote the improvement of the QoL.

Delusion of Pregnancy in Down Syndrome: Two Case Reports.

Individuals with intellectual disability (ID) are more vulnerable to psychotic disorder and schizophrenia than the general population. However, psychotic symptoms have not been widely described in this population. Here, we deeply investigated the cases of two young women with ID and Down syndrome (DS) who developed a delusion of pregnancy, a rare condition defined as a fixed belief of being pregnant despite factual evidence to the contrary. The assessment included psychopathological and neuropsychological examination, as well as the evaluation of cognitive and adaptive functioning. In these cases, delusion manifested as a psychotic symptom of a cyclothymic disorder (case 1) or as an independent delusional disorder (case 2). However, some similarities emerged: both women exhibited good pre-morbid adaptive functioning and family history of psychiatric disorders; moreover, in both cases delusion emerged in association with an external trigger. Difficulties in verbally expressing one's thoughts and beliefs were found, as well as poor abstract reasoning skills that may have affected the ability to deeply conceptualize the delusional idea itself. These findings may provide crucial insights into the clinical manifestation of psychosis in individuals with DS and underscore the importance of a routine psychological and neuropsychological follow-up to provide prompt and adequate intervention.

Understanding the Effects of Transcranial Electrical Stimulation in Numerical Cognition: A Systematic Review for Clinical Translation.

Atypical development of numerical cognition (dyscalculia) may increase the onset of neuropsychiatric symptoms, especially when untreated, and it may have long-term detrimental social consequences. However, evidence-based treatments are still lacking. Despite plenty of studies investigating the effects of transcranial electrical stimulation (tES) on numerical cognition, a systematized synthesis of results is still lacking. In the present systematic review (PROSPERO ID: CRD42021271139), we found that the majority of reports (20 out of 26) showed the effectiveness of tES in improving both number (80%) and arithmetic (76%) processing. In particular, anodal tDCS (regardless of lateralization) over parietal regions, bilateral tDCS (regardless of polarity/lateralization) over frontal regions, and tRNS (regardless of brain regions) strongly enhance number processing. While bilateral tDCS and tRNS over parietal and frontal regions and left anodal tDCS over frontal regions consistently improve arithmetic skills. In addition, tACS seems to be more effective than tDCS at ameliorating arithmetic learning. Despite the variability of methods and paucity of clinical studies, tES seems to be a promising brain-based treatment to enhance numerical cognition. Recommendations for clinical translation, future directions, and limitations are outlined.

Assessment of oppositional defiant disorder and oppositional behavior in children and adolescents with Down syndrome.

Introduction: Children and adolescents with intellectual disability (ID) exhibit higher rates of oppositional defiant disorder (ODD) than typically developing (TD) peers. However, studies focusing on the investigation of ODD prevalence in youth with Down syndrome (DS) are still limited. Methods: The current study aimed to investigate the prevalence of ODD clinical and subclinical symptoms in a group of 101 youth with DS (63 boys, 38 girls) ranging in age from 6 to 18 years. Moreover, the prevalence of ODD symptoms, as detected by means of three parent-report questionnaires, was compared with that detected by a semi-structured psychopathological interview, namely, the Schedule for Affective Disorders and Schizophrenia for School Aged Children Present and Lifetime (K-SADS) Version Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-5). Results: We found that 17% of participants met diagnostic criteria for ODD on the K-SADS, whereas 24% exhibited subclinical symptoms. Results also suggest good specificity of Swanson, Nolan, and Pelham-IV Rating Scale (SNAP-IV), Conners' Parent Rating Scales Long Version (CPRS) and Child Behavior Checklist (CBCL) in detecting ODD symptoms. The investigation of the agreement in the prevalence rates of clinical and subclinical symptoms of ODD between K-SADS and the parent-report questionnaires indicated CPRS as the parent-report questionnaire with the best agreement with K-SADS. Discussion: This study provides support for the use of parent-report questionnaires to assess ODD symptoms in children and adolescents with DS by evaluating their levels of agreement with a semi-structured psychopathological interview. In particular, our results suggest that CPRS could be considered a suitable screening tool for ODD clinical and subclinical symptoms in youth with DS.

Sleep and behavioral problems in preschool-age children with Down syndrome.

Sleep is a major concern, especially in people with Down Syndrome (DS). Beyond Obstructive Sleep Apnea, a number of other sleep difficulties have been reported in children with DS, such as delayed sleep onset, night-time awakenings, and early morning awakenings. The detrimental effect of sleep difficulties seems to contribute to and exacerbate the cognitive and behavioral outcomes of DS. Although the screening for sleep disorders is recommended early in age in DS, only a few studies have evaluated the sleep profile in preschool-age children with DS. The aim of the current study was to assess the association between sleep disturbances and behavioral problems in a group of preschool-age children with DS, by means of a feasible and easy-to-administer parent-report questionnaires. Seventy-one preschool-age children with DS, ranging in age from 3 to 5.11 years, were included in this retrospective study. Sleep disturbances were evaluated by means of the Sleep Disturbance Scale for Children, while emotional and behavioral problems by means of the Child Behavior Checklist. Sleep breathing disorders were the most frequent sleep difficulties reported by parents. Moreover, children with clinical scores in total sleep problems exhibited elevation of psychopathological symptoms, namely Total problems, Affective problems, Anxiety problems, Pervasive Developmental Problems, and Attention Deficit/Hyperactivity Problems. The identification of the broader connection between sleep difficulties and emotional and behavioral problems in preschool-age children with DS leads to important considerations for intervention.

Cerebellar Agenesis and Bilateral Polimicrogyria Associated with Rare Variants of CUB and Sushi Multiple Domains 1 Gene (CSMD1): A Longitudinal Neuropsychological and Neuroradiological Case Study.

Cerebellar agenesis is an extremely rare condition characterized by a near complete absence of the cerebellum. The pathogenesis and molecular basis remain mostly unknown. We report the neuroradiological, molecular, neuropsychological and behavioral characterization of a 5-year-old girl, with cerebellar agenesis associated with parietal and peri-Sylvian polymicrogyria, followed-up for 10 years at four time points. Whole exome sequencing identified two rare variants in CSMD1, a gene associated with neurocognitive and psychiatric alterations. Mild intellectual impairment, cerebellar ataxia and deficits in language, memory and executive functions, with relatively preserved adaptive and psychopathological domains, were initially showed. Phonological awareness and verbal memory declined at 11 years of age, and social and anxiety problems emerged. Adaptive and psychopathological characteristics dramatically worsened at 15 years. In summary, the developmental clinical outcome showed impairment in multiple cognitive functions in childhood, with a progressive decline in cognitive and adaptive abilities and the emergence of psychopathological symptoms in adolescence. The observed phenotype could be the result of a complex interplay between cerebellar abnormality, brain malformation and the relations with CSMD1 variants. These findings may provide insights into the developmental clinical outcomes of a co-occurrence between rare brain malformation and rare genetic variants associated to neurodevelopmental disorders.

Sensory Processing Disorders in Children and Adolescents: Taking Stock of Assessment and Novel Therapeutic Tools.

Sensory processing disorders (SPDs) can be described as difficulty detecting, modulating, interpreting, and/or responding to sensory experiences. Because SPDs occur in many individuals with autism spectrum disorder and in other populations with neurodevelopmental disorders, it is important to distinguish between typical and atypical functioning in sensory processes and to identify early phenotypic markers for developing SPDs. This review considers different methods for diagnosing SPDs to outline a multidisciplinary approach useful for developing valid diagnostic measures. In particular, the advantages and limitations of the most commonly used tools in assessment of SPDs, such as caregiver reports, clinical observation, and psychophysical and neuroimaging studies, will be reviewed. Innovative treatment methods such as neuromodulation techniques and virtual reality will also be suggested.

Characterization of Sleep Disturbances in Children and Adolescents with Down Syndrome and Their Relation with Cognitive and Behavioral Features.

Despite sleep disturbances are common among youths with Down syndrome (DS), the cognitive and behavioral features associated with sleep problems have not yet been studied extensively. The present study investigated the presence of sleep disturbances in a group of children and adolescents with DS and their cognitive and behavioral correlates. Seventy-one children and adolescents with DS underwent a neuropsychological evaluation, whereas parents completed questionnaires for the screening of the child's sleep, emotional and behavioral problems. We found no association between sleep disturbances and sex, nonverbal IQ, nor adaptive abilities. However, we found that age was positively associated with disorders in initiating and maintaining sleep (DIMS) and disorders of excessive somnolence (DOES), while body mass index was related with DOES. We also detected a relationship between visual-motor integrations and DIMS, as well as multiple associations between sleep disturbances and psychopathological and behavioral problems, mainly externalizing symptoms. The present study provided a detailed characterization of sleep problems in relation to several features of youths with DS. The proper identification of sleep disturbances profile in the DS population could support the process of clinical evaluation, in particular for psychopathological aspects.

Implicit and Explicit Memory in Youths with High-Functioning Autism Spectrum Disorder: A Case-Control Study.

Individuals with autism spectrum disorder (ASD) usually manifest heterogeneous impairments in their higher cognitive functions, including their implicit memory (IM) and explicit memory (EM). However, the findings on IM and EM in youths with ASD remain debated. The aim of this study was to clarify such conflicting results by examining IM and EM using two comparable versions of the Serial Reaction Time Task (SRTT) in the same group of children and adolescents with ASD. Twenty-five youths with high-functioning ASD and 29 age-matched and IQ-matched typically developing youths undertook both tasks. The ability to implicitly learn the temporal sequence of events across the blocks in the SRTT was intact in the youths with ASD. When they were tested for EM, the participants with ASD did not experience a significant reduction in their reaction times during the blocks with the previously learned sequence, suggesting an impairment in EM. Moreover, the participants with ASD were less accurate and made more omissions than the controls in the EM task. The implications of these findings for the establishment of tailored educational programs for children with high-functioning ASD are discussed.