Why do individuals with Williams syndrome or Down syndrome fail the Weather Prediction Task?

Williams syndrome (WS) and Down syndrome (DS) are two neurodevelopmental disorders with distinct genetic origins characterized by mild to moderate intellectual disability. Individuals with WS or DS exhibit impaired hippocampus-dependent place learning and enhanced striatum-dependent spatial response learning. Here, we used the Weather Prediction Task (WPT), which can be solved using hippocampus- or striatum-dependent learning strategies, to determine whether individuals with WS or DS exhibit similar profiles outside the spatial domain. Only 10% of individuals with WS or DS solved the WPT. We further assessed whether a concurrent memory task could promote reliance on procedural learning to solve the WPT in individuals with WS but found that the concurrent task did not improve performance. To understand how the probabilistic cue-outcome associations influences WPT performance, and whether individuals with WS or DS can ignore distractors, we assessed performance using a visual learning task with differing reward contingencies, and a modified WPT with unpredictive cues. Both probabilistic feedback and distractors negatively impacted the performance of individuals with WS or DS. These findings are consistent with deficits in hippocampus-dependent learning and executive functions, and reveal the importance of congruent feedback and the minimization of distractors to optimize learning in these two populations.

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.

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).

Methylphenidate is more effective to improve inhibitory control and working memory compared to tDCS in children and adolescents with attention deficit/hyperactivity disorder: a proof-of-concept study.

Introduction: Attention-deficit/hyperactivity disorder (ADHD) is characterized by an inappropriate, pervasive and persistent pattern of inattention, hyperactivity, and/or impulsivity and associated with substantial functional impairment. Despite considerable advances in the understanding and management of ADHD, some patients do not respond well to methylphenidate (MPH), the first-choice pharmacological treatment. Over the past decades, among non-invasive brain stimulation techniques, transcranial direct current stimulation (tDCS) has proven to be an effective and safe technique to improve behavior and cognition in children with neurodevelopmental disorders, including ADHD, by modifying cortical excitability. However, the effect of tDCS has never been directly compared with that of the MPH. The present randomized sham-controlled trial evaluated the effect of a single session of anodal tDCS compared with the administration of a single dose of MPH in children and adolescents with ADHD. Methods: After completing baseline assessment (T0), 26 children and adolescents with ADHD were exposed to 3 conditions with a 24-h interval-sessions: (A) a single session of anodal tDCS over the left dorsolateral prefrontal cortex (DLPFC); (B) a single session of sham tDCS over the left DLPFC; (C) a single dose of MPH. Results: Our results showed that after administering a single dose of MPH, children and adolescents with ADHD improved inhibitory control and visual-spatial WM compared with baseline, anodal, and sham tDCS. However, a single session of active tDCS over the left DLPFC was not effective compared with either baseline or sham tDCS. Discussion: In conclusion, our protocol in ADHD involving a single tDCS session did not demonstrate consistent improvements in neurocognitive features compared with baseline, sham tDCS, or single MPH administration. Different protocols need to be developed to further test the effectiveness of tDCS in improving ADHD symptoms.

Anxiety, concerns and COVID-19: Cross-country perspectives from families and individuals with neurodevelopmental conditions.

Background: The COVID-19 pandemic had a major impact on the mental health and well-being of children with neurodevelopmental conditions (NDCs) and of their families worldwide. However, there is insufficient evidence to understand how different factors (e.g., individual, family, country, children) have impacted on anxiety levels of families and their children with NDCs developed over time. Methods: We used data from a global survey assessing the experience of 8043 families and their children with NDCs (mean of age (m) = 13.18 years, 37% female) and their typically developing siblings (m = 12.9 years, 45% female) in combination with data from the European Centre for Disease Prevention and Control, the University of Oxford, and the Central Intelligence Agency (CIA) World Factbook, to create a multilevel data set. Using stepwise multilevel modelling, we generated child-, family- and country-related factors that may have contributed to the anxiety levels of children with NDCs, their siblings if they had any, and their parents. All data were reported by parents. Results: Our results suggest that parental anxiety was best explained by family-related factors such as concerns about COVID-19 and illness. Children's anxiety was best explained by child-related factors such as children's concerns about loss of routine, family conflict, and safety in general, as well as concerns about COVID-19. In addition, anxiety levels were linked to the presence of pre-existing anxiety conditions for both children with NDCs and their parents. Conclusions: The present study shows that across the globe there was a raise in anxiety levels for both parents and their children with NDCs because of COVID-19 and that country-level factors had little or no impact on explaining differences in this increase, once family and child factors were considered. Our findings also highlight that certain groups of children with NDCs were at higher risk for anxiety than others and had specific concerns. Together, these results show that anxiety of families and their children with NDCs during the COVID-19 pandemic were predicted by very specific concerns and worries which inform the development of future toolkits and policy. Future studies should investigate how country factors can play a protective role during future crises.

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.

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.

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.

Effects of a short and intensive transcranial direct current stimulation treatment in children and adolescents with developmental dyslexia: A crossover clinical trial.

Developmental Dyslexia (DD) significantly interferes with children's academic, personal, social, and emotional functioning. Nevertheless, therapeutic options need to be further validated and tested in randomized controlled clinical trials. The use of transcranial direct current stimulation (tDCS) has been gaining ground in recent years as a new intervention option for DD. However, there are still open questions regarding the most suitable tDCS protocol for young people with DD. The current crossover study tested the effectiveness of a short and intensive tDCS protocol, including the long-term effects, as well as the influence of age and neuropsychological processes at baseline on reading improvements. Twenty-four children and adolescents with DD were randomly assigned to receive active tDCS during the first slot and sham tDCS during the second slot or vice versa. Five consecutive daily sessions of left anodal/right cathodal tDCS set at 1 mA for 20 min were administered over the parieto-occipital regions. Reading measures (text, high frequency word, low frequency word, and non-word lists) and neuropsychological measures (visual-spatial and verbal working memory, phoneme blending, and rapid automatized naming tasks) were collected before, immediately after, 1 week and 1 month later the treatment. Our results showed that only the active tDCS condition improved non-word reading speed immediately after and 1 month later the end of the treatment compared with baseline. In addition, the improvement in non-word reading speed was significantly correlated with age and with neuropsychological measures (verbal working memory and phoneme blending) at baseline but only in the active tDCS condition. The current crossover study contributed to enforce previous effects of tDCS, including long-term effects, on non-word reading speed and to understand the effect of age and neuropsychological processes on reading outcomes. Our findings showed that tDCS could be a low-cost and easy-to-implement treatment option with long-term effects for children and adolescents with DD.

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.

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.

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.

Comparing the Effect of Methylphenidate and Anodal tDCS on Inhibitory Control and Working-Memory in Children and Adolescents with Attention Deficit/Hyperactivity Disorder: A Study Protocol for a Randomized, within-Subject Trial.

Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by inappropriate levels of attention, hyperactivity, and impulsivity that interfere with individual functioning. The international guidelines recommend targeting ADHD-related neurochemical brain abnormalities by intervening via drug treatment, such as methylphenidate (MPH), as first choice. Drug treatments are usually associated with a huge amount of cost for families and the healthcare system, suspension for low compliance, poor long-term efficacy, and side effects. Transcranial direct current stimulation (tDCS) has been suggested as a possible noninvasive means to safely manipulate brain activity and, in turn, improve behavior and cognition in developmental ages. Several studies have shown that tDCS has the potential to improve ADHD-related cognitive deficits, but the effect of tDCS compared with MPH has never been evaluated. The aim of the present within-subject, sham-controlled, randomized proof-of-concept study is to demonstrate the positive effect of one-session anodal tDCS analogous to the MPH drug on inhibitory control and working memory in children and adolescents with ADHD. We strongly believe that this study protocol will serve to accelerate research into low-cost, drug-free, feasible interventions for ADHD.

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.

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.

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.

Boosting Numerical Cognition in Children and Adolescents with Mathematical Learning Disabilities by a Brain-Based Intervention: A Study Protocol for a Randomized, Sham-Controlled Clinical Trial.

Numbers are everywhere, and supporting difficulties in numerical cognition (e.g., mathematical learning disability (MLD)) in a timely, effective manner is critical for their daily use. To date, only low-efficacy cognitive-based interventions are available. The extensive data on the neurobiology of MLD have increased interest in brain-directed approaches. The overarching goal of this study protocol is to provide the scientific foundation for devising brain-based and evidence-based treatments in children and adolescents with MLD. In this double-blind, between-subject, sham-controlled, randomized clinical trial, transcranial random noise stimulation (tRNS) plus cognitive training will be delivered to participants. Arithmetic, neuropsychological, psychological, and electrophysiological measures will be collected at baseline (T0), at the end of the interventions (T1), one week (T2) and three months later (T3). We expect that tRNS plus cognitive training will significantly improve arithmetic measures at T1 and at each follow-up (T2, T3) compared with placebo and that such improvements will correlate robustly and positively with changes in the neuropsychological, psychological, and electrophysiological measures. We firmly believe that this clinical trial will produce reliable and positive results to accelerate the validation of brain-based treatments for MLD that have the potential to impact quality of life.

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.