Intranasal Immunotherapy with M2 Macrophage Secretome Ameliorates Language Impairments and Autistic-like Behavior in Children.

Background/Objectives: The intranasal delivery of various neurotropic substances is considered a new attractive therapeutic approach for treating neuropathologies associated with neuroinflammation and altered regeneration. Specific language impairment (SLI) that arises as a result of damage to the cortical speech zones during the developmental period is one of the most common problems in preschool children, and it is characterized by persistent difficulties in the acquisition, understanding, and use of language. This study's objective is to evaluate the efficacy and safety of intranasal immunotherapy using the M2 macrophage secretome as a rich source of immunoregulatory and neurotrophic factors for the treatment of severe language impairment in children. Methods: Seventy-one children (54 boys and 17 girls, aged 3 to 13 years) were recruited to participate in a clinical trial (NCT04689282) in two medical centers. The children were examined before, 1 month after, and 6 months after the start of therapy. In the vast majority of children (55/71), language impairment was associated with autistic-like symptoms and attention deficit hyperactivity disorder (ADHD). Results: Daily intranasal inhalations of M2 macrophage-conditioned medium (for 30 days) were well tolerated and led to a decrease in the severity of language impairments, autistic-like behavior, and ADHD symptoms. The clinical effect appeared within a month after the first procedure and persisted or intensified during a 6-month follow-up. Two-thirds of the children showed a clear clinical improvement, while the rest had less pronounced improvement. Conclusions: Thus, the use of the M2 macrophage secretome and its intranasal delivery is safe, well tolerated, and clinically effective in children with severe language impairments.

Language and reading in attention-deficit/hyperactivity disorder and comorbid attention-deficit/hyperactivity disorder + developmental language disorder.

Background: The current study sought to examine whether psycholinguistic assessments could discriminate children and adolescents with developmental language disorder (DLD) from those with attention-deficit/hyperactivity disorder (ADHD; combined or inattentive subtype) and comorbid DLD + ADHD. Methods: The Clinical Evaluation of Language Fundamentals-Screening Test (CELFST; Wiig et al., 2013), the Comprehensive Test of Phonological Processing (nonword repetition subtest; Wagner et al., 2013), and the Test of Word Reading Efficiency (sight word and phonemic decoding subtests; Torgesen et al., 2012) were examined in 441 children and adolescents between 6 and 16 years of age. Results: The presence of a language disorder (with or without ADHD) predicted poor performance across tasks. Children and adolescents with ADHD (combined vs. inattentive) only significantly differed in sight word reading, in favor of those with combined type. Measures of reading efficiency could distinguish between the two types of ADHD, but not between other groups. Interestingly, scores on the standard language screener were no worse for children with ADHD + DLD than children with DLD only. Conclusions: The combination of comorbid ADHD + DLD did not appear to be associated with lower language abilities, sight word reading, or phonemic decoding relative to DLD alone. Reading efficiency was effective in discriminating between ADHD subtypes. These findings offer valuable insights into differential diagnosis and the identification of comorbidity.

Language growth in verbal autistic children from 5 to 11 years.

To examine predictors and growth in language for verbal autistic and non-autistic children with/without low language from 4 to 11 years. Receptive and expressive language trajectories were compared in a community sample of 1026 children at ages 5, 7, and 11 years, across four groups: two autistic groups; one with and one without low language; and two non-autistic groups; one with and one without low language. Groups were delineated on baseline assessment at 4 years. Non-autistic and autistic children with low language had lower mean expressive language scores than the non-autistic typical language group (22.26 and 38.53 units lower, respectively, p < 0.001), yet demonstrated faster language growth across 5 to 11 years (p < 0.001 and p = 0.002, respectively). Both groups without low language had similar mean expressive language scores (p = 0.864) and a comparable rate of growth (p = 0.645). Language at 4 years was the only consistent predictor of language at 11 years for autistic children. Results were similar for receptive language in all analyses except there was no significant difference in rate of progress (slope) for the autistic with low language group compared with the typical language group (p = 0.272). Findings suggest early language ability, rather than a diagnosis of autism, is key to determining language growth and outcomes at 11 years in verbal children. Furthermore, children with low language showed developmental acceleration compared with same age peers.

Beta Spectral Power during Passive Listening in Preschool Children with Specific Language Impairment.

INTRODUCTION: Children with specific language impairment (SLI) have difficulties in different speech and language domains. Electrophysiological studies have documented that auditory processing in children with SLI is atypical and probably caused by delayed and abnormal auditory maturation. During the resting state, or different auditory tasks, children with SLI show low or high beta spectral power, which could be a clinical correlate for investigating brain rhythms. METHODS: The aim of this study was to examine the electrophysiological cortical activity of the beta rhythm while listening to words and nonwords in children with SLI in comparison to typical development (TD) children. The participants were 50 children with SLI, aged 4 and 5 years, and 50 age matched TD children. The children were divided into two subgroups according to age: (1) children 4 years of age; (2) children 5 years of age. RESULTS: The older group differed from the younger group in beta auditory processing, with increased values of beta spectral power in the right frontal, temporal, and parietal regions. In addition, children with SLI have higher beta spectral power than TD children in the bilateral temporal regions. CONCLUSION: Complex beta auditory activation in TD and SLI children indicates the presence of early changes in functional brain connectivity.

Natural language acquisition and gestalt language processing: A critical analysis of their application to autism and speech language therapy.

Background and Aim: Recently, there has been a lot of interest surrounding the term gestalt language processor (GLP) which is associated with Natural Language Acquisition (NLA): a protocol intended to support the language development of autistic people. In NLA, delayed echolalia is presumed raw source material that GLPs use to acquire language in a stage-like progression from delayed echolalia to spontaneous speech. The aim of this article is to evaluate NLA in light of relevant literatures to allow scrutiny of NLA claims. Main contributions: First, we review the notion of gestalt language and situate it in the broader literature on language styles to update understanding of its significance. We then review the links from gestalt language processing to autism and identify definitional and conceptual problems and clarify the construct 'episodic memory'. We discuss the 'raw material view of delayed echolalia' and identify theoretical and empirical shortcomings. Finally, we review Blanc's language stages and their accompanying assessment and language support recommendations and challenge their validity. Conclusions & Implications: The term 'gestalt language processor' is definitionally and conceptually troubled, the assertion that autistic people are GLPs is misleading and unhelpful, and evidence is lacking that GLP represents a legitimate clinical entity. The theoretical basis of NLA lacks empirical support. NLA stages are implausible and their accompanying assessment and support recommendations lack justification. We recommend the use of alternate, individualized, theoretically-sound, evidence-based, neurodiversity-affirming supports that are sensitive and responsive to the heterogeneity that defines autism.

Assessment of Executive Functions in Children with Sensorineural Hearing Loss and in Children with Specific Language Impairment: Preliminary Reports.

Executive functions (EFs) are related abilities, associated with the frontal lobes functions, that allow individuals to modify behavioral patterns when they become unsatisfactory. The aim of this study was to assess EFs in children with sensorineural hearing loss (SNHL) and in children with "specific language impairment" (SLI), compared with a control group of children with normal development, to identify specific skill deficits. Three groups of preschool children aged between 2 and 6 years were assessed: 19 children with normal hearing, cognitive, and language development, 10 children with SNHL, and 20 children with SLI. The FE-PS 2-6 Battery was used for the assessment of preschool EFs, supplemented with the Modified Bell Test for the analysis of selective attention. Statistically significant differences were found between the two experimental groups and the control one, regarding the investigated skills. Children with SNHL showed a clear deficit in flexibility, whereas children with SLI had greater problems in self-regulation and management of waiting for gratification. Selective attention was found to be deficient in all three groups, with no statistically significant differences. This study shows that the skills investigated were found to be deficient in both SNHL and SLI patients. It is essential to start targeted exercises based on specific deficient skills as part of the rehabilitation program. It is of great importance to understand the consequences of EF deficit in preschool children to achieve an accurate diagnosis and carry out customized rehabilitation programs.

NR4A2 as a Novel Target Gene for Developmental and Epileptic Encephalopathy: A Systematic Review of Related Disorders and Therapeutic Strategies.

The NR4A2 gene encodes an orphan transcription factor of the steroid-thyroid hormone-retinoid receptor superfamily. This review focuses on the clinical findings associated with the pathogenic variants so far reported, including three unreported cases. Also, its role in neurodegenerative diseases, such as Parkinson's or Alzheimer's disease, is examined, as well as a brief exploration on recent proposals to develop novel therapies for these neurological diseases based on small molecules that could modulate NR4A2 transcriptional activity. The main characteristic shared by all patients is mild to severe developmental delay/intellectual disability. Moderate to severe disorder of the expressive and receptive language is present in at least 42%, while neuro-psychiatric issues were reported in 53% of patients. Movement disorders, including dystonia, chorea or ataxia, are described in 37% patients, although probably underestimated because of its frequent onset in late adolescence-young adulthood. Finally, epilepsy was surprisingly present in 42% of patients, being drug-resistant in three of them. The age at onset varied widely, from five months to twenty-six years, as did the classification of epilepsy, which ranged from focal epilepsy to infantile spasms or Lennox-Gastaut syndrome. Accordingly, we propose that NR4A2 should be considered as a first-tier target gene for the genetic diagnosis of developmental and epileptic encephalopathy.

THE USE OF CLASSIFIERS IN VIETNAMESE IN TYPICAL AND ATYPICAL LANGUAGE DEVELOPMENT.

The acquisition of numeral classifiers and their associated syntactic structures has been documented and studied in a broad range of East and Southeast Asian languages among typically-developing (TD) young speakers. However, little research has considered how classifiers are acquired by children with developmental language disorder (DLD). The current paper compares and analyzes the development of numeral classifier patterns among a set of Vietnamese speakers, TD and DLD, studied over three years, from kindergarten to second grade. The investigation highlights differences in the performance of children with TD and DLD and describes the areas of classifier use that seem to be most challenging. Children with DLD produced more errors of classifier omission in kindergarten, showed more random alternations in representational forms, and delays in the development of three element classifier structures. Findings are discussed in terms of future directions in the study of classifier use in Vietnamese speakers with DLD.

Language impairment in sporadic and familial (type 8) amyotrophic lateral sclerosis: A comparative study.

INTRODUCTION/AIMS: Language is frequently affected in patients with sporadic amyotrophic lateral sclerosis (sALS), with reduced performance in naming, syntactic comprehension, grammatical expression, and orthographic processing. However, the language profile of patients with familial type 8 ALS (ALS8), linked to p.P56S VAPB mutation, remains unclear. We investigated language in patients with ALS8 by examining their auditory comprehension and verbal production. METHODS: We included three groups of participants: (1) patients with sALS (n = 20), (2) patients with familial ALS8 (n = 22), and (3) healthy controls (n = 21). The groups were matched for age, sex, and education level. All participants underwent a comprehensive language battery, including the Boston Diagnostic Aphasia Examination, the reduced Token test, letter fluency, categorical fluency (animals), word definition from the Cambridge Semantic Memory Research Battery, and a narrative discourse analysis. Participants also were evaluated using Addenbrooke's Cognitive Exam-Revised Version, the Hospital Anxiety and Depression Scale, and the ALS Functional Rating Scale-Revised. RESULTS: Compared to controls, sALS and ALS8 patients had impaired performance on oral (syntactic and phonological processing) comprehension and inappropriate discourse cohesion. sALS and ALS8 did not differ in any language measure. There was no correlation between language scores and functional and psychiatric scales. DISCUSSION: ALS8 patients exhibit language deficits that are independent of motor features. These findings are consistent with the current evidence suggesting that ALS8 has prominent non-motor features.

Exploring Spanish writing abilities of children with developmental language disorder in expository texts.

Introduction: Numerous studies have shown that children with developmental language disorder (DLD), in addition to oral language difficulties, exhibit impaired writing abilities. Their texts contain problems in grammar, organization, cohesion, and length of written output. However, most of these studies have been conducted with English speakers. English is characterized by complex phonological structure, opaque orthography, poor morphology and strict word order. The aim of this research is to observe the writing abilities of children with DLD in a language with simple phonological structure, transparent orthography, rich morphology and flexible word order like Spanish in the production of expository texts. Methods: Twenty-six children with DLD (mean age in months = 128.85) and 26 age-and sex-matched typically developing (TD) children (mean age in months = 124.61) wrote an expository text about their favorite animal. Results: In order to analyze how the two groups plan and encode written texts, we looked at word frequency and sentence structure, grammatical complexity and lexical density, and omissions and errors. Compared to the TD group, the children with DLD omitted more content words; made more errors with functional words, verb conjugation and inflectional morphemes, and made a large number of spelling errors. Moreover, they wrote fewer words, fewer sentences, and less structurally and lexically complex texts. Discussion: These results show that children with DLD who speak a transparent orthography language such as Spanish also have difficulties in most language areas when producing written texts. Our findings should be considered when planning and designing interventions.

Sentence production and sentence repetition in autistic adolescents and young adults: Linguistic sensitivity to finiteness-marking.

Purpose: Despite the clinical utility of sentence production and sentence repetition to identify language impairment in autism, little is known about the extent to which these tasks are sensitive to potential dialectal variation. One promising method is strategic scoring (Oetting et al., 2016), which has good clinical utility for identifying language impairment in nonautistic school-age children across dialects of English. This report applies strategic scoring to analyze sentence repetition and sentence production in autistic adolescents and adults. Method: Thirty-one diverse autistic adolescents and adults with language impairment (ALI; n=15) and without language impairment (ASD; n=16) completed the Formulated Sentences and Recalling Sentences subtests of the Clinical Evaluation of Language Fundamentals-5th Ed (Wiig et al., 2013). Descriptive analyses and regression evaluated effects of scoring condition, group, and scoring condition by group on outcomes, as well as group differences in finiteness-marking across utterances and morphosyntactic structures. Results: Strategic and unmodified item-level scores were essentially constant on both subtests and significantly lower in the ALI than the ASD group. Only group predicted item-level scores. Group differences were limited to: percent grammatical utterances on Formulated Sentences and percent production of overt structures combined on Sentence Repetition (ALI < ASD). Discussion: Findings support the feasibility of strategic scoring for sentence production and sentence repetition to identify language impairment and indicate that potential dialectal variation in finiteness-marking did not confound outcomes in this sample. To better understand the clinical utility of strategic scoring, replication with a larger sample varying in age and comparisons with dialect-sensitive measures are needed.

Secondary language impairment in posterior cortical atrophy: insights from sentence repetition.

Introduction: Posterior cortical atrophy (PCA) is a neurodegenerative syndrome characterized by progressive impairment in visuospatial and perceptual function linked to atrophy of the occipito-parietal cortex. Besides the salient visual impairment, several studies have documented subtle changes in language may also be present. Sentence repetition is a highly constrained linguistic task involving multiple linguistic and cognitive processes and have been shown to be impaired in other AD spectrum disorders, with little consensus on its relevance in PCA. This aim of this study was to further delineate the linguistic and cognitive features of impaired language in PCA using a sentence repetition task. Method: Seven PCA patients and 16 healthy controls verbally repeated 16 sentences from the Boston Diagnostic Aphasia Examination. Responses were transcribed orthographically and coded for accuracy (percentage accuracy; percentage Correct Information Units; Levenshtein Distance) and for temporal characteristics (preparation duration (ms); utterance duration (ms); silent pause duration (ms); speech duration (ms); dysfluency duration (ms)). The potential modulating effects of attentional control and working memory capacity were explored. Results: PCA patients showed lower overall accuracy with retained semantic content of the sentences, and lower phonological accuracy. Temporal measures revealed longer preparation and utterance duration for PCA patients compared to controls, alongside longer speech duration but comparable dysfluency duration. PCA patients also showed comparable silent pause duration to controls. Attentional control, measured using the Hayling sentence completion task, predicted accuracy of sentence repetition. Discussion: The findings suggest that sentence repetition is impaired in PCA and is characterized by phonological, response planning and execution difficulties, underpinned in part by attentional control mechanisms. The emerging profile of language impairment in PCA suggests vulnerability of similar cognitive systems to other Alzheimer's syndromes, with subtle differences in clinical presentation.

FLP: Factor lattice pattern-based automated detection of Parkinson's disease and specific language impairment using recorded speech.

BACKGROUND: Timely detection of neurodevelopmental and neurological conditions is crucial for early intervention. Specific Language Impairment (SLI) in children and Parkinson's disease (PD) manifests in speech disturbances that may be exploited for diagnostic screening using recorded speech signals. We were motivated to develop an accurate yet computationally lightweight model for speech-based detection of SLI and PD, employing novel feature engineering techniques to mimic the adaptable dynamic weight assignment network capability of deep learning architectures. MATERIALS AND METHODS: In this research, we have introduced an advanced feature engineering model incorporating a novel feature extraction function, the Factor Lattice Pattern (FLP), which is a quantum-inspired method and uses a superposition-like mechanism, making it dynamic in nature. The FLP encompasses eight distinct patterns, from which the most appropriate pattern was discerned based on the data structure. Through the implementation of the FLP, we automatically extracted signal-specific textural features. Additionally, we developed a new feature engineering model to assess the efficacy of the FLP. This model is self-organizing, producing nine potential results and subsequently choosing the optimal one. Our speech classification framework consists of (1) feature extraction using the proposed FLP and a statistical feature extractor; (2) feature selection employing iterative neighborhood component analysis and an intersection-based feature selector; (3) classification via support vector machine and k-nearest neighbors; and (4) outcome determination using combinational majority voting to select the most favorable results. RESULTS: To validate the classification capabilities of our proposed feature engineering model, designed to automatically detect PD and SLI, we employed three speech datasets of PD and SLI patients. Our presented FLP-centric model achieved classification accuracy of more than 95% and 99.79% for all PD and SLI datasets, respectively. CONCLUSIONS: Our results indicate that the proposed model is an accurate alternative to deep learning models in classifying neurological conditions using speech signals.

Comprehension of Ditransitive Constructions in Mandarin-Speaking Children with Developmental Language Disorder and Children with Autism Spectrum Disorder Plus Language Impairment.

This study examined and compared the comprehension of Mandarin ditransitive constructions in children with developmental language disorder (DLD) and children with autism spectrum disorder plus language impairment (ALI). Eighteen children with DLD, 17 children with ALI, and 27 age-matched typically developing (TDA) children, participated in a sentence-picture matching task on four patterns of Mandarin ditransitive constructions. Both children with DLD and children with ALI received significantly lower accuracy than TDA children in general and their most common errors were thematic role reversals. However, while children with ALI evinced a generalized deficit in all four patterns, only the comprehension of S1 (Subj. + Vgei + IO + DO) and S3 (Subj. + gei + IO + V + DO) was affected in children with DLD, with that of S2 (Subj. + V + DO + gei + IO) and S4 (Subj. + V + IO + DO) preserved in this population. Additionally, thematic role reversal errors were more dominant in children with DLD than in children with ALI who also committed a relatively higher proportion of Wrong Theme and No Recipient errors. It is concluded that the primary deficit of children with DLD lies in representing dependent relationships between the arguments and the verb as involved in thematic role assignment, but this is less critical in children with ALI, with their performance on the comprehension task possibly also related to other factors associated with the condition. To enhance the development of ditransitive constructions, intervention efforts for children with DLD and children with ALI could focus on strengthening the connection between each argument and its thematic role.

Sleep quality relates to language impairment in children with autism spectrum disorder without intellectual disability.

OBJECTIVES: This study aimed to identify sleep quality profiles of children with autism spectrum disorder (ASD), to compare these profiles with those of typically developing (TD) children, and to verify whether there are differences between them in terms of language skills. METHODS: We evaluated the sleep quality and language skills of 47 children with ASD without intellectual disability (ID) and 32 children with TD. Using a hierarchical cluster analysis, we identified two sleep quality ASD profiles (poor and good). We then performed a series of MANCOVAs and ANOVAs to compare the sleep quality and language skills of the two ASD clusters and the TD group. RESULTS: A main group effect (TD, "poor" cluster, and "good" cluster) was found in the total sleep quality and all its dimensions. Significant differences were revealed between the "good" and "poor" clusters in the total structural language score (F1,46 = 10.75, p < 0.001) and three of its subscales (speech: F1,46 = 9.19, p < 0.001; syntax, F1,46 = 8.61, p = 0.001; coherence: F1,46 = 11.36, p < 0.001); the total pragmatic language score (F1,46 = 7.00, p = 0.001) and three of its subscales (inappropriate initiation: F1,46 = 8.02, p = 0.001; use of context: F1,46 = 8.07, p = 0.001; nonverbal communication: F1,46 = 7.35, p = 0.001); and the social relations score (F1,46 = 9.97, p = 0.003). CONCLUSIONS: Sleep quality in children with ASD (especially a subgroup) is worse than in children with TD. There is an association between sleep quality and language skills, both at the pragmatic and structural levels.

Language outcomes in children who underwent surgery for the removal of a posterior fossa tumor: A systematic review.

BACKGROUND: Children who underwent posterior fossa tumor removal may have spoken or written language impairments. The present systematic review synthesized the literature regarding the language outcomes in this population. Benefits of this work were the identification of shortcomings in the literature and a starting point toward formulating guidelines for postoperative language assessment. METHODS: A systematic literature search was conducted, identifying studies with patients who had posterior fossa surgery before 18 years of age. Included studies were narratively synthesized to understand language outcomes by language function (e.g., phonology, morphosyntax) at a group and individual level. Furthermore, the influence of several mediators (e.g., postoperative cerebellar mutism syndrome (pCMS), tumor type) was investigated. A critical evaluation of the language assessment tools was conducted. RESULTS: The narrative synthesis of 66 studies showed that a broad spectrum of language impairments has been described, characterized by a large interindividual heterogeneity. Patients younger at diagnosis, receiving treatment for a high-grade tumor and/or radiotherapy and diagnosed with pCMS seemed more prone to impairment. Several gaps in language assessment remain, such as a baseline preoperative assessment and the assessment of pragmatics and morphosyntax. Further, there were important methodological differences in existing studies which complicated our ability to accurately guide clinical practice. CONCLUSION: Children who had posterior fossa surgery seem to be at risk for postoperative language impairment. These results stress the need for language follow-up in posterior fossa tumor survivors.

A Rare Cause of Intellectual Disability.

A seven-year-old female was followed in a developmental clinic from the age of nine months due to delayed psychomotor development. The first physical examination showed a newborn with irritability and a large anterior fontanelle. A transfontanellar ultrasound was performed, revealing mild enlargement of the lateral and third ventricles. Head circumference remained below the third percentile until the age of five months, then rose to the third percentile. Developmental milestones were globally delayed, with expressive language being more severely affected and axial hypotonia with appendicular hypertonia on neurological examination. Subsequent medical observation revealed deep-set eyes, mildly up-slanted palpebral fissures, a high nasal bridge with a broad nasal tip, a thin upper lip, widely spaced teeth, retrognathia, and a slight pectus excavatum. Genetic investigation revealed the diagnosis, with whole-exome sequencing consistent with the genetic diagnosis of autosomal dominant mental retardation type 7 (MRD7). All patients diagnosed with MRD7 have a development delay detected at a young age and, typically, a mild to severe intellectual disability later in life. All individuals present language impairment, especially in verbal expression. Motor development is typically affected by gait disturbances and generalized hypertonia, which are noted early in life. Microcephaly is a prominent feature of this syndrome, present in over 90% of the cases. The most common findings in MRD7 (microcephaly and intellectual disability) have a broad differential diagnosis. Some disorders have multiple findings in common with MRD7, such as Angelman syndrome (AS), MECP2 disorders, or Mowat-Wilson syndrome (MWS). MRD7 is a rare genetic syndrome characterized by developmental delay/intellectual disability, microcephaly, autism spectrum disorder, behavior problems, typical facial features, and seizures. Early intervention is more likely to be effective and potentially change a child's developmental path. Small gains early in life could represent a significant difference in the children's future autonomy.

Hypomethylation of Wnt signaling regulator genes in developmental language disorder.

Background: Developmental language disorder (DLD) is a neurodevelopmental disorder. Considering the pivotal role of epigenetics in neurodevelopment, we examined any altered DNA methylation between DLD and control subjects. Materials & methods: We looked into genome-wide methylation differences between DLD and control groups. The findings were validated by quantitative PCR (qPCR). Results: In the DLD group, differential methylation of CpG sites was observed in the Wnt signaling regulator genes APCDD1, AMOTL1, LRP5, MARK2, TMEM64, TRABD2B, VEPH1 and WNT2B. Hypomethylation of APCDD1, LRP5 and WNT2B was confirmed by qPCR. Conclusion: This is the first report associating Wnt signaling with DLD. The findings are relevant in the light of the essential role of Wnt in myelination, and of the altered myelination in DLD.

Developmental language disorder (DLD), previously called specific language impairment, is a neurodevelopmental disorder affecting approximately 7% of school-age children. Affected children fail to develop normal speech and language skills; this is a major public health concern as it adversely impacts their communication, academic and social skills. Human brain development is complex, and the accurate temporal and spatial regulation of the expression of multiple genes is essential for proper brain development. Epigenetic factors such as DNA methylation can modulate gene expression without altering the DNA sequence and are considered key regulators of the expression of genes involved in neurodevelopment. We examined any genome-wide methylation differences between children with DLD and control subjects. The findings were validated by real-time qPCR. The DLD group showed differential methylation of CpG sites in several Wnt signaling regulator genes (APCDD1, AMOTL1, LRP5, MARK2, TMEM64, TRABD2B, VEPH1, WNT2B) compared with the control group. Among these, hypomethylation of APCDD1, LRP5 and WNT2B was confirmed by qPCR. This is the first report associating Wnt signaling with DLD. The findings are relevant in the light of the essential role of Wnt in neuronal myelination and the altered myelination in DLD revealed by magnetic resonance imaging.

Selective short-term memory impairment for verbalizable visual objects in children with Developmental Language Disorder.

BACKGROUND: Developmental language disorder (DLD) affects the ability to acquire and make use of native language. Possible underlying cognitive mechanisms are related to memory functions. AIMS: The aim was examination of the relationship between visual short-term memory of objects as well as audiovisual short-term memory, and particular nonverbal and language abilities. METHODS AND PROCEDURES: The study included 7-9-year-old children with DLD and matched control group. Participants completed the Language Development Test, the Stanford-Binet IQ scale (SB5), and two short-term memory tasks: immediate recall of the visually presented pictograms and immediate recall of audiovisually presented sequences of syllables. OUTCOMES AND RESULTS: The results revealed diminished levels of short-term visual memory for objects as well as audiovisual memory in children with DLD. However, there were no group differences in the control task of WM. CONCLUSIONS AND IMPLICATIONS: Results supported the idea of diminished abilities in children with DLD to perform mental operations on verbalizable visual objects. Importantly non-verbal working memory ability, which cannot easily be supported by verbal representations, is at typical levels. This suggests that verbalization ability should be taken into account in the assessment of seemingly non-verbal cognitive functions among children with DLD.