Search Results (16)

This study examined spontaneous activity in children aged 3–11 years with specific language impairment (SLI) using an electroencephalogram (EEG). We compared SLI-diagnosed children with a normo-development group (ND). The signal complexity, multiscale entropy (MSE) and parameterized power spectral density (FOOOF) were analyzed, decomposing the PSD into its aperiodic (AP, proportional to 1/fx) and periodic (P) components. The results showed increases in complexity across scales in both groups. Although the topographic distributions were similar, children with SLI exhibited an increased AP component over a broad frequency range (13–45 Hz) in the medial regions. The P component showed differences in brain activity according to the frequency and region. At 9–12 Hz, ND presented greater central–anterior activity, whereas, in SLI, this was seen for posterior–central. At 33–36 Hz, anterior activity was greater in SLI than in ND. At 37–45 Hz, SLI showed greater activity than ND, with a specific increase in the left, medial and right regions at 41–45 Hz. These findings suggest alterations in the excitatory–inhibitory balance and impaired intra- and interhemispheric connectivity, indicating difficulties in neuronal modulation possibly associated with the cognitive and linguistic characteristics of SLI. Full article

Background/Objectives: Although specific language impairment (SLI) was thought to be a language impairment, recent studies suggest that it is also associated with domain-general and nonverbal deficits such as deficits in nonverbal working memory, visual short-term memory, executive functions, etc. This study aimed to examine if applied visual strategy when copying the Rey–Osterrieth complex figure (ROCF) correlates with language abilities in children with SLI. Methods: The sample consisted of 37 children diagnosed with SLI, divided into two groups based on the strategy used when copying ROCF. We used ROCF to assess perceptual organization and planning, and the Peabody Picture Vocabulary Test, Boston Naming Test, Token Test, Grammatical Judgment, The Children’s Grammar, and Global Articulation Test for language measurement. Univariate ANOVA was used for statistical analysis. Results: The results indicate that children who used a more mature strategy when copying ROCF achieved better results on tests used to assess grammar and articulation status. Conclusions: These results support the conclusion that there are neurocognitive mechanisms underlying both grammatical and visuospatial deficits. The obtained results suggest the importance of examining visual and visuospatial functions in children with SLI and the need for more comprehensive treatment of those children. Full article

Specific language impairment (SLI) is a developmental disorder with substantial genetic contributions. A genome-wide linkage analysis and homozygosity mapping were performed in five consanguineous families from Pakistan. The highest LOD scores of 2.49 at 12p11.22-q11.21 in family PKSLI-31 and 1.92 at 6p in family PKSLI-20 were observed. Homozygosity mapping showed a loss of heterozygosity on 1q25.3-q32.2 and 2q36.3-q37.3 in PKSLI-20. A loss of heterozygosity mapped, in PKSLI-31 and PKSLI-34 flanks, NFXL1 and CNTNAP2, which are genes previously identified in SLI. Our findings report novel SLI loci and corroborate previously reported SLI loci, indicating the utility of a family-based approach. Full article

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. Full article

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. Full article

This paper addresses the grammatical challenges associated with the development of clause complexity, focusing on the performance of a group of monolingual Spanish-speaking schoolchildren with Specific Language Impairment/Developmental Language Disorder (SLI/DLD) in a longitudinal corpus of oral narrative samples. The study examines the presence of interclause relations of subordination and equivalence (hypotaxis and parataxis) in language samples of two groups: an experimental group made up of 24 schoolchildren with SLI/DLD and a control group made up of 24 schoolchildren with typical development (TD). The results show that while both groups use parataxis as the most common relation between clauses in all school grades, there is a significant decrease in paratactic relations and a significant increase in hypotactic relations from first to fourth grade of primary education. Although the development patterns are highly similar, the SLI/DLD group shows greater difficulties in mastering more complex (hypotactic) relations in fourth grade compared to the control group, indicating that it is less sophisticated in the use of these types of complex relations. These findings suggest that focused support on the most complex structures is needed towards the fourth grade of primary education, given the demands of the school academic register from 6 and 7 years of age and the potential problems that the development of clause complexity can cause in school-age children. Full article

Individuals with specific language impairment (SLI) struggle with language acquisition despite average non-verbal intelligence and otherwise typical development. One SLI account focuses on grammar acquisition delay. The current study aimed to detect novel rare genetic variants associated with performance on a grammar assessment, the Test of Early Grammatical Impairment (TEGI), in English-speaking children. The TEGI was selected due to its sensitivity and specificity, consistently high heritability estimates, and its absence from all but one molecular genetic study. We performed whole exome sequencing (WES) in eight families with SLI (n = 74 total) and follow-up Sanger sequencing in additional unrelated probands (n = 146). We prioritized rare exonic variants shared by individuals with low TEGI performance (n = 34) from at least two families under two filtering workflows: (1) novel and (2) previously reported candidate genes. Candidate variants were observed on six new genes (PDHA2, PCDHB3, FURIN, NOL6, IQGAP3, and BAHCC1), and two genes previously reported for overall language ability (GLI3 and FLNB). We specifically suggest PCDHB3, a protocadherin gene, and NOL6 are critical for ribosome synthesis, as they are important targets of SLI investigation. The proposed SLI candidate genes associated with TEGI performance emphasize the utility of precise phenotyping and family-based genetic study. Full article

Evaluation of the rehabilitation efficacy may be an essential indicator of its further implementation and planning. The research aim is to examine whether the estimation of EEG correlates of auditory-verbal processing in a child with overlapping autism spectrum disorder (ASD) and specific language impairment (SLI) symptoms may be a predictor of the treatment efficacy in conditions when behavioral tests do not show improvement during the time course. The prospective case report reports follow-up results in a child aged 36 to 66 months. During continuous integrative therapy, autism risk index, cognitive, speech–language, sensory, and EEG correlates of auditory-verbal information processing are recorded in six test periods, and their mutual interrelation was analyzed. The obtained results show a high statistically significant correlation of all observed functions with EEG correlates related to the difference between the average mean values of theta rhythm in the left (F1, F3, F7) and right (F2, F4, F8) frontal region. The temporal dynamics of the examined processes point to the consistency of the evaluated functions increasing with time flow. These findings indicate that EEG correlates of auditory-verbal processing may be used to diagnose treatment efficacy in children with overlapping ASD and SLI. Full article

Language disorders are highly heritable and are influenced by complex interactions between genetic and environmental factors. Despite more than twenty years of research, we still lack critical understanding of the biological underpinnings of language. This review provides an overview of the genetic landscape of developmental language disorders (DLD), with an emphasis on the importance of defining the specific features (the phenotype) of DLD to inform gene discovery. We review the specific phenotype of DLD in the genetic literature, and the influence of historic variation in diagnostic inclusion criteria on researchers’ ability to compare and replicate genotype–phenotype studies. This review provides an overview of the recently identified gene pathways in populations with DLD and explores current state-of-the-art approaches to genetic analysis based on the hypothesised architecture of DLD. We will show how recent global efforts to unify diagnostic criteria have vastly increased sample size and allow for large multi-cohort metanalyses, leading the identification of a growing number of contributory loci. We emphasise the important role of estimating the genetic architecture of DLD to decipher underlying genetic associations. Finally, we explore the potential for epigenetics and environmental interactions to further unravel the biological basis of language disorders. Full article

Specific language impairment (SLI) is a common neurodevelopmental disorder (NDD) that displays high heritability estimates. Genetic studies have identified several loci, but the molecular basis of SLI remains unclear. With the aim to better understand the genetic architecture of SLI, we performed whole-exome sequencing (WES) in a single family (ID: 489; n = 11). We identified co-segregating rare variants in three new genes: BUD13, APLP2, and NDRG2. To determine the significance of these genes in SLI, we Sanger sequenced all coding regions of each gene in unrelated individuals with SLI (n = 175). We observed 13 additional rare variants in 18 unrelated individuals. Variants in BUD13 reached genome-wide significance (p-value < 0.01) upon comparison with similar variants in the 1000 Genomes Project, providing gene level evidence that BUD13 is involved in SLI. Additionally, five BUD13 variants showed cohesive variant level evidence of likely pathogenicity. Bud13 is a component of the retention and splicing (RES) complex. Additional supportive evidence from studies of an animal model (loss-of-function mutations in BUD13 caused a profound neural phenotype) and individuals with an NDD phenotype (carrying a CNV spanning BUD13), indicates BUD13 could be a target for investigation of the neural basis of language. Full article

Nonword repetition has been proposed as a diagnostic marker of developmental language disorder (DLD); however, the inconsistency in the ability of nonword repetition tasks (NRT) to identify children with DLD raises significant questions regarding its feasibility as a clinical tool. Research suggests that some of the inconsistency across NRT may be due to differences in the nature of the nonword stimuli. In this study, we compared children’s performance on NRT between two cohorts: the children in the Catalan–Spanish cohort (CS) were bilingual, and the children in the European Portuguese cohort (EP) were monolingual. NRT performance was assessed in both Spanish and Catalan for the bilingual children from Catalonia-Spain and in Portuguese for the monolingual children from Portugal. Results show that although the absolute performance differed across the two cohorts, with NRT performance being lower for the CS, in both Catalan and Spanish, as compared to the EP cohort in both, the cut-points for the likelihood ratios (LH) were similar across the three languages and mirror those previously reported in previous studies. However, the absolute LH ratio values for this study were higher than those reported in prior research due in part to differences in wordlikeness and frequency of the stimuli in the current study. Taken together, the findings from this study show that an NRT consisting of 3-, 4-, and 5-syllable nonwords, which varies in wordlikeness ratings, when presented in a random order accurately identifies and correctly differentiates children with DLD from TD controls the child is bilingual or monolingual. Full article

Organophosphate compounds (OPs) interfere with neurodevelopment and are neurotoxic for humans and animals. They are first biotransformed to the more toxic oxon form, and then hydrolyzed to specific metabolites by the enzyme paraoxonase/arylesterase, encoded by the gene PON1 located on human chr. 7q21.3. In autism spectrum disorder (ASD) and in attention-deficit/hyperactivity disorder (ADHD), a correlation between OP exposure and disease onset has been reported. In this case-control study, we aimed to replicate our previous work showing reduced levels of serum PON1 arylesterase activity in Italian and Caucasian-American ASD samples, and to extend our analysis to other neurodevelopmental disorders, namely ADHD and developmental language disorder (DLD), also known as specific language impairment (SLI). The arylesterase activity, measured using standard spectrophotometric methods, is significantly reduced in the ADHD, and not in the ASD sample compared with the controls. Our previous results seemingly stem from spuriously high arylesterase levels in the former control sample. Finally, genotyping SNPs rs705379 and rs662 using TDI-FP, a significant effect of rs705379 alleles on the serum arylesterase activity is observed in all of the subgroups tested, regardless of diagnosis, as well as a lack of association between PON1 gene polymorphisms and ASD/ADHD susceptibility in the Italian population. In summary, the serum arylesterase activity is reduced in children and adolescents with ADHD, and this reduction is not due to the functional PON1 gene variants assessed in this study. Based on previous literature, it may more likely reflect enhanced oxidative stress than specific genetic underpinnings. Full article

The aim of this work is to investigate how bilingual children perform with respect to monolingual children in a task eliciting direct object clitic pronouns in Italian. Clitic production is considered a good clinical marker for Italian monolingual children suffering from specific language impairment (SLI) (Bortolini et al. 2006). Moreover, this task is reported to be particularly challenging for early second language children (EL2), who are less accurate than their peers in this task (Vender et al. 2016). Even though the typology of errors committed by the two populations (non-impaired bilinguals and SLI children) is generally different, it can be difficult to keep them apart from each other and, as a consequence, to identify a language impairment in bilingual children. However, it has been suggested that the difficulties exhibited by EL2 children in clitic production are related to their competence in their L2 and that they should disappear as soon as their mastery of the L2 increases. To test this prediction, we assessed clitic production in a group of 31 bilingual children having Italian as their L2 (mean age 10;2), comparing their performance to that of a group of 33 Italian monolingual children (mean age 10;2). The bilingual children used their L1 on a daily basis, as assessed by means of a bilingual exposure questionnaire, and had on average eight years of exposure to Italian; moreover, they performed similarly to monolinguals in a receptive vocabulary task, indicating that their competence in Italian was good. Consistently with our predictions, we found that bilingual children performed very accurately in the clitic elicitation task, similarly to monolinguals, confirming that the deficits previously found in EL2 children were not related to bilingualism itself, but more likely to their still incomplete competence in Italian. Full article

Background: Child Spanish-speakers appear to use more null subjects than do adults. Null subject use, like the use of tense marking, is sensitive to discourse-pragmatics. Because tense marking has been used to identify child Spanish-speakers with specific language impairment (SLI) with near good sensitivity and specificity (89%), null subject use may as well, following the predictions of the Interface Deficit Hypothesis. We investigate the possibility that null subject occurrence may form part of a useful discriminant function for the identification of monolingual child Spanish-speakers diagnosed with specific language impairment. Methods: We evaluate the rate of null subject expression from spontaneous production data, together with results from independent measures of another discourse-sensitive construction, verb finiteness, in child Spanish. We perform a discriminant function analysis, using null subject expression as a target variable, among others, to classify monolingual child Spanish-speakers (N = 40) as SLI or as typically-developing (TD). Results: The SLI group is shown to have significantly higher scores than the TD group on null subject expression. Multiple discriminant functions, including the null subject variable with tense measures, and in combination with mean length of utterance in words (MLUw), are shown to provide good sensitivity and specificity (<90%) in the classification of children as SLI vs. TD. Conclusion: Our findings support the contention that null subject occurrence is a plausible reflection of the Interface Deficit of SLI for Spanish-speaking children. Full article

Reading and language disorders are common childhood conditions that often co-occur with each other and with other neurodevelopmental impairments. There is strong evidence that disorders, such as dyslexia and Specific Language Impairment (SLI), have a genetic basis, but we expect the contributing genetic factors to be complex in nature. To date, only a few genes have been implicated in these traits. Their functional characterization has provided novel insight into the biology of neurodevelopmental disorders. However, the lack of biological markers and clear diagnostic criteria have prevented the collection of the large sample sizes required for well-powered genome-wide screens. One of the main challenges of the field will be to combine careful clinical assessment with high throughput genetic technologies within multidisciplinary collaborations. Full article