Sex differences in early language delay and in developmental language disorder.

Developmental language disorder (DLD) is a neurodevelopmental condition, occurring in about 3% to 7% of preschoolers, that can impair communication and negatively impact educational and social attainments, in spite of adequate neurological, cognitive, emotional, social development, and educational opportunities for language learning. Significant risk factors for DLD are male sex, familial history of early language delay, low parental education, and various perinatal factors. A strong sex effect with a higher prevalence of language delay and DLD in males than in females has been consistently reported. Neurobiological and environmental risk factors, interacting with each other, are probably responsible for the phenotypic expression of DLD. The aim of this brief review is to further the knowledge of the role of sex in early language delay and DLD by analyzing the evidence from four significant sources: epidemiological studies, studies on twins, family aggregation studies, and studies on sex chromosome trisomies. Data pertaining only to sex differences (biological and physiological characteristics of females and males) will be analyzed. Studies on family aggregations and twins confirm the role of genetic factors and of sex in determining language abilities and disabilities, but genes alone do not determine outcomes. Sex chromosome trisomies represent a unique example of the relationship between a genetic alteration and a language disorder. Clarification of how sex acts in determining DLD could provide new information on early risk factors and, thus, contribute to improve diagnosis and clinical management.

Evidence for a Pathogenic Role of CSMD1 in Childhood Apraxia of Speech.

Childhood apraxia of speech (CAS) is a pediatric motor speech disorder. The genetic etiology of this complex neurological condition is not yet well understood, although some genes have been linked to it. We describe the case of a boy with a severe and persistent motor speech disorder, consistent with CAS, and a coexisting language impairment.Whole exome sequencing in our case revealed a de novo and splicing mutation in the CSMD1 gene.

Vowel variability and contrast in Childhood Apraxia of Speech: acoustics and articulation.

Phoneme production may be affected by limited speech motor control in Childhood Apraxia of Speech (CAS), with a general instability of acoustic targets across multiple repetitions of speech stimuli. This acoustic and Ultrasound Tongue Imaging (UTI) study shows that increased variability and reduction of contrast in vowel production is found in native Italian speakers with CAS, particularly as far as the height dimension is concerned. The data suggest that vowel production should play a major role in CAS diagnosis and treatment. Moreover, this study shows that a combined acoustic and articulatory approach allows direct observation of lingual dynamics together with an estimation of changes in the acoustic dimension. The two dimensions are shown not to correspond in a straightforward way in the speech of children with CAS, and encourage consideration of articulatory compensation strategies aimed at saving the acoustic identity of vowels.

Morphosyntactic weaknesses in Developmental Language Disorder: the role of structure and agreement configurations.

Agreement is a morphosyntactic dependency which is sensitive to the hierarchical structure of the clause and is constrained by the structural distance that separates the elements involved in this relation. In this paper we present two experiments, providing new evidence that Italian-speaking children with Developmental Language Disorder (DLD), as well as Typically Developing (TD) children, are sensitive to the same hierarchical and locality factors that characterise agreement in adult grammars. This sensitivity holds even though DLD children show accrued difficulties in more complex agreement configurations. In the first experiment, a forced-choice task was used to establish whether children are more affected in the computation of S-V agreement when an element intervenes hierarchically or linearly in the agreement relation: DLD children are more subject to attraction errors when the attractor intervenes hierarchically, indicating that DLD children discriminate between hierarchical and linear configurations. The second experiment, also conducted through a forced-choice task, shows that the computation of agreement in DLD children is more 'fragile' than in TD children (and also in children with a primary impairment in the phonological domain), in that it is more sensitive to the factors of complexity identified in Moscati and Rizzi's (2014) typology of agreement configurations. To capture the agreement pattern found in DLD children, we put forth a novel hypothesis: the Fragile Computation of Agreement Hypothesis. Its main tenet is that DLD children make use of the same grammatical operations employed by their peers, as demonstrated in Experiment 1, but difficulties increase as a function of the complexity of the agreement configuration.

Training RAN or reading? A telerehabilitation study on developmental dyslexia.

Rehabilitation procedures recommended for developmental dyslexia (DD) are still not fully defined, and only few studies directly compare different types of training. This study compared a training (Reading Trainer) working on the reading impairment with one (Run the RAN) working on the rapid automatized naming (RAN) impairment, one of the main cognitive deficits associated with DD. Two groups of DD children (N = 45) equivalent for age, sex, full IQ, and reading speed were trained either by Reading Trainer (n = 21) or by Run the RAN (n = 24); both trainings required an intensive home exercise, lasting 3 months. Both trainings showed significant improvements in reading speed and accuracy of passages and words. Bypassing the use of alphanumeric stimuli, but empowering the cognitive processes underlying reading, training RAN may be a valid tool in children with reading difficulties opening new perspectives for children with severe impairments or, even, at risk of reading difficulties.

Telerehabilitation in developmental dyslexia: methods of implementation and expected results.

BACKGROUND: Developmental Dyslexia is a disorder, highly frequent in the school population, for which the recommended rehabilitation procedures are not well defined. This study aimed to automatize reading decoding skills by using an innovative system for rehabilitation, based on a telerehabilitation method. It requires an intensive home-exercise with the supervision, by web, of the clinician. The study had three main aims: to diffuse knowledge on new methods for rehabilitation of reading difficulties; to verify whether an intensive and simplified exercise, targeted to the automation of reading, is suitable for different subgroups of dyslexic children; to define the treatment effects on basic cognitive functions underlying reading. METHODS: Twenty-five children, grouped according to the neuropsychological and anamnestic profiles, took part to the treatment by the software Reading Trainer®. RESULTS: Both speed and accuracy of reading decoding increased significantly after treatment, independently from the functional neuropsychological profile or the history of oral language delay. These changes were specific to decoding and not associated with improvements in reading comprehension or spelling skills. However, there was a "cascade effect" of the treatment efficacy on those basic cognitive functions considered precursors of the ability to read, with significant improvements in rapid lexical access, phonological processing and visual attention. CONCLUSIONS: This study provides information on the efficacy of new tools for telerehabilitation of specific reading disorders.

A longitudinal study of lexical and grammar development in deaf Italian children provided with early cochlear implantation.

OBJECTIVE: A growing number of studies on deaf children with cochlear implant (CI) document a significant improvement in receptive and expressive language skills after implantation, even if they show language delay when compared with normal-hearing peers. Data on language acquisition in CI Italian children are still scarce and limited to only certain aspects of language. The purpose of this study is to prospectively describe the trajectories of language development in early CI Italian children, with particular attention to the transition from first words to combinatorial speech and to acquisition of complex grammar in a language with rich morphology, such as Italian. DESIGN: Six children, with profound prelingual deafness, provided with CI, between 16 and 24 months of age were prospectively assessed and followed over a mean period of up to 34.8 months postimplant. During follow-up, each child received between four to five individual language evaluations through a combination of indirect procedures (parent reports of early lexical and grammar development) and direct ones (administration of standardized receptive and expressive language tests with Italian norms and collection of spontaneous language samples). RESULTS: In relation to chronological age, the acquisition of expressive vocabulary was delayed. However, considering the duration of hearing experience, most CI participants showed an earlier start and faster growth of expressive rather than receptive vocabulary in comparison with typically developing children. This quite atypical result persisted right up until the end of the follow-up. The acquisition of expressive grammar was delayed relative to chronological age, though all but one CI participant achieved the expected grammar level after approximately 3 years of CI use. In addition, the rate of grammar acquisition was not homogeneous during development, showing two different paces: one comparable with normal hearing in the transition from holophrastic to primitive combinatorial speech and a much slower one to attain more advanced levels of morphosyntactic control. CONCLUSION: From a rehabilitative viewpoint, our results suggest the importance of implementing rehabilitation in lexical comprehension, even when expressive vocabulary appears to be within normal range. Moreover, assessment of language acquisition in CI Italian children should focus on those grammar aspects that are more vulnerable to early acoustic deprivation (such as free and bound morphology) to ensure enhanced language therapy planning.

Sex/Gender Differences in the Language Profiles of Italian Children with Autism Spectrum Disorder: A Retrospective Study.

Sex/gender (S/G) differences in ASD language profiles have been poorly investigated. The present study aims to explore whether male (M) and female (F) children with ASD and with normal non-verbal cognitive abilities differ in their linguistic profiles. A sample of 76 Italian children with ASD (range: 4.9-8 years), including 50 Ms and 26 Fs, was retrospectively recruited. Language profiles were analyzed using standardized tests for the evaluation of receptive and expressive vocabulary as well as grammar. Grammatical comprehension was the most impaired domain compared to the other language measures in both M and F children. Comparing language profiles between S/G, Fs showed significantly better scores than Ms in grammatical production (p = 0.002), and Ms showed better active negative sentence comprehension (p = 0.035). Moreover, comparing the language profiles between Ms and Fs with a receptive disorder, Fs had significantly worse grammatical comprehension and better grammatical production than Ms. Even among children without a receptive disorder, Fs had significantly higher grammatical production scores. The S/G differences in language profile, particularly better expressive language in Fs than Ms, can partially contribute to the delayed ASD diagnosis or underdiagnosis of Fs without intellectual disability. Finally, the results document the importance of accurately investigating both expressive and receptive abilities in children with ASD.

Sleep disturbances in specific learning disorders: a qualitative and quantitative investigation.

BACKGROUND: The literature reports a significant association between sleep disorders and learning disabilities. Nevertheless, not all children with learning disorders have sleep alterations, and which sleep characteristics are associated with which learning difficulty is still unknown. The study aimed at acquiring new information on the relation between sleep disturbances or habits and the learning profiles of children with a specific learning disorder (SLD). METHODS: The Sleep Disturbance Scale for Children (SDSC) and an actigraph (the FitBit-Flex, FB-F) were used in 26 and 16 SLD children respectively; all children were also assessed for learning skills. RESULTS: Although parents' reports at the SDSC did not differentiate SLD from typical readers, the awakening, respiratory and arousal disturbances at the SDSC correlated with sleep duration at the FB-F. Sleep alterations at the FB-F actigraph characterize SLD with literacy difficulties: children with reading decoding difficulties showed shorter minimum amount of sleep than typical children, and severe SLDs showed shorter maximum sleep duration and a higher number of awakenings in comparison to SLDs with mild learning deficits. CONCLUSIONS: Mild alterations in the amount, duration and quality of sleep may characterize children with learning disorders and actigraphy proves to be a useful tool in starting the individual monitoring of sleep in these populations.

Specific Learning Disabilities and Emotional-Behavioral Difficulties: Phenotypes and Role of the Cognitive Profile.

Specific Learning Disabilities (SLD) are often associated with emotional-behavioral problems. Many studies highlighted a greater psychopathological risk in SLD, describing both internalizing and externalizing problems. The aims of this study were to investigate the emotional-behavioral phenotype through the Child Behavior Checklist (CBCL), and evaluate the mediating role of background and cognitive characteristics on the relationship between CBCL profile and learning impairment in children and adolescents with SLD. One hundred and twenty-one SLD subjects (7-18 years) were recruited. Cognitive and academic skills were assessed, and parents completed the questionnaire CBCL 6-18. The results showed that about half of the subjects manifested emotional-behavioral problems with a prevalence of internalizing symptoms, such as anxiety and depression, over externalizing ones. Older children showed greater internalizing problems than younger ones. Males have greater externalizing problems compared to females. A mediation model analysis revealed that learning impairment is directly predicted by age and familiarity for neurodevelopmental disorders and indirectly via the mediation of the WISC-IV/WAIS-IV Working Memory Index (WMI) by the CBCL Rule-Breaking Behavior scale. This study stresses the need to combine the learning and neuropsychological assessment with a psychopathological evaluation of children and adolescents with SLD and provides new interpretative insights on the complex interaction between cognitive, learning, and emotional-behavioral phenotypes.

Evaluating benefits of cochlear implantation in deaf children with additional disabilities.

OBJECTIVES: Cochlear-implanted deaf children having additional disabilities may develop speech perception and language skills at a slower pace than their implanted peers without such disorders. Nevertheless, it has been shown that, even for these special cases, cochlear implantation (CI) provides benefits for a larger range of neuropsychological functions including social and relational skills. These benefits are frequently mentioned by parents, but rarely objectively measured by tests. This article presents a new evaluation tool aimed at assessing the global benefits offered by CI in these special cases. DESIGN: The new tool has been designed as a closed-format questionnaire, divided into five areas. It is based on observing the frequency of preselected behaviors in daily activities, which imply specific social, neuropsychological, and perceptual skills. The questionnaire has been presented to the parents of 50 deaf children with additional disabilities, before and at least 6 months after CI. RESULTS: The data show significant improvements in all investigated areas. However, not all skills improve in the same way, and only those skills related to language and communication correlate positively with time after implantation. The present article further discusses changes in skills for which parents have higher expectations, such as the preferred communication mode, speech intelligibility, and the ability to communicate on the telephone. CONCLUSIONS: The questionnaire has a simple-to-use format, and it has been proven to be sufficiently sensitive for the detection of changes in each examined area. Because the questionnaire is based on observed behaviors, it can be used even when other existing tests involve tasks that are too complex for these children.

Differences and Commonalities in Children with Childhood Apraxia of Speech and Comorbid Neurodevelopmental Disorders: A Multidimensional Perspective.

Childhood apraxia of speech (CAS) is a motor speech disorder often co-occurring with language impairment and complex neurodevelopmental disorders. A cohort of 106 children with CAS associated to other neurodevelopmental disorders underwent a multidimensional investigation of speech and language profiles, chromosome microarray analysis and structural brain magnetic resonance (MR). Our aim was to compare the clinical profiles of children with CAS co-occurring with only language impairment with those who, in addition to language impairment, had other neurodevelopmental disorders. Expressive grammar was impaired in the majority of the sample in the context of similar alterations of speech, typical of the core symptoms of CAS. Moreover, children with complex comorbidities also showed more severe and persistent receptive language deficits. About 25% of the participants harbored copy number variations (CNVs) already described in association to neurodevelopmental disorders. CNVs occurred more frequently in children with complex comorbidities. MR structural/signal alterations were found in a small number of children and were of uncertain pathogenic significance. These results confirm that CAS needs multidimensional diagnostic and clinical management. The high frequency of language impairment has important implications for early care and demands a personalized treatment approach in which speech and language goals are consistently integrated.

Relationship among Connectivity of the Frontal Aslant Tract, Executive Functions, and Speech and Language Impairment in Children with Childhood Apraxia of Speech.

Childhood apraxia of speech (CAS) is a subtype of motor speech disorder usually co-occurring with language impairment. A supramodal processing difficulty, involving executive functions (EFs), might contribute to the cognitive endophenotypes and behavioral manifestations. The present study aimed to profile the EFs in CAS, investigating the relationship between EFs, speech and language severity, and the connectivity of the frontal aslant tract (FAT), a white matter tract involved in both speech and EFs. A total of 30 preschool children with CAS underwent speech, language, and EF assessments and brain MRIs. Their FAT connectivity metrics were compared to those of 30 children without other neurodevelopmental disorders (NoNDs), who also underwent brain MRIs. Alterations in some basic EF components were found. Inhibition and working memory correlated with speech and language severity. Compared to NoND children, a weak, significant reduction in fractional anisotropy (FA) in the left presupplementary motor area (preSMA) FAT component was found. Only speech severity correlated and predicted FA values along with the FAT in both of its components, and visual-spatial working memory moderated the relationship between speech severity and FA in the left SMA. Our study supports the conceptualization of a composite and complex picture of CAS, not limited to the speech core deficit, but also involving high-order cognitive skills.

Implicit learning in children with Childhood Apraxia of Speech.

BACKGROUND: Childhood Apraxia of Speech is a severe and persistent clinical subtype of Speech Sound Disorder. Given the difficulties in the acquisition, programming and control of the movements underlying speech and the slowdown in a wide range of non-linguistic skills, the difficulty in implicit learning of sequential information could play a role in the disorder, contributing to understand its etiopathological mechanisms and behavioral manifestations. AIMS: The present study was aimed at investigating implicit learning in children with Childhood Apraxia of Speech. METHODS AND PROCEDURES: Twenty-five children with Childhood Apraxia of Speech, aged between 4 and 12 years, were matched for IQ and age to a control group of 25 typically developing children. Implicit learning of participants was assessed by Serial Reaction Time Task. OUTCOME AND RESULTS: Children with Childhood Apraxia of Speech did not show implicit learning, as documented by the absence of differences between reaction times in the sequenced block and the random block, usually considered as a measure of implicit learning effect. CONCLUSION AND IMPLICATIONS: Our results underline an implicit learning deficit in children with Childhood Apraxia of Speech, supporting the concept of a disorder not only confined to the speech domain, but also involving non-linguistic skills, in a composite and complex picture.

How many functional brains in developmental dyslexia? When the history of language delay makes the difference.

BACKGROUND: Clinical manifestations of developmental dyslexia (DD) are greatly variable, suggesting complex underlying mechanisms. It was recently advanced that the characteristics of DD in Italian, a language with shallow orthography, are influenced by a positive history for language delay. OBJECTIVE: We explored this hypothesis by studying in Italian individuals with DD (i) the brain representation of phonological processing with functional magnetic resonance imaging and (ii) the correlation between the patterns of activation and the presence/absence of previous language delay. METHOD: Thirteen individuals with DD and 13 controls participated in the functional magnetic resonance imaging experiment consisting of a rhyme-generation task. RESULTS: Individuals with DD showed a reduced activation of phonological processing areas of the left hemisphere, such as the middle frontal gyrus, the precuneus, and the inferior parietal lobule, and in particular the superior temporal gyrus. Furthermore, patients with a history of language delay had reduced activation in the left inferior and medial frontal gyrus, that was associated with worse reading and phonological accuracy than patients with normal language development. CONCLUSIONS: Neurofunctional profiles of Italian individuals with DD are correlated to the history of language delay, suggesting that the relatively better behavioral profiles observed in individuals without a history of language delay are associated with a major activation of frontal networks normally involved in phonological working memory.

Neural Changes Induced by a Speech Motor Treatment in Childhood Apraxia of Speech: A Case Series.

We report a case series of children with childhood apraxia of speech, by describing behavioral and white matter microstructural changes following 2 different treatment approaches.Five children with childhood apraxia of speech were assigned to a motor speech treatment (PROMPT) and 5 to a language, nonspeech oral motor treatment. Speech assessment and brain MRI were performed pre- and post-treatment. The ventral (tongue/larynx) and dorsal (lips) corticobulbar tracts were reconstructed in each subject. Mean fractional anisotropy and mean diffusivity were extracted. The hand corticospinal tract was assessed as a control pathway. In both groups speech improvements paralleled changes in the left ventral corticobulbar tract fractional anisotropy. The PROMPT treated group also showed fractional anisotropy increase and mean diffusivity decrease in the left dorsal corticobulbar tract. No changes were detected in the hand tract. Our results may provide preliminary support to the possible neurobiologic effect of a multimodal speech motor treatment in childhood apraxia of speech.

Neurodevelopmental disorders in children with severe to profound sensorineural hearing loss: a clinical study.

AIM: The effects of sensorineural hearing loss (SNHL) are often complicated by additional disabilities, but the epidemiology of associated disorders is not clearly defined. The aim of this study was to evaluate the frequency and type of additional neurodevelopmental disabilities in a sample of children with SNHL and to investigate the relation between these additional disabilities and the aetiology of deafness. METHOD: One hundred children with severe/profound SNHL (60 males, 40 females; mean age 5 y 7 mo, SD 3 y 6 mo, range 8 mo-16 y) were investigated using a diagnostic protocol including neurodevelopmental, genetic, neurometabolic, and brain magnetic resonance imaging (MRI) assessment. RESULTS: Forty-eight per cent of the sample exhibited one or more additional disabilities, with cognitive, behavioural-emotional, and motor disorders being the most frequent. The risk of additional disabilities varied according to the type of aetiology. Thirty-seven out of 80 individuals with available MRIs showed signal abnormalities, in particular brain malformations (46%) and white matter abnormalities (54%). Frequency and type of disability were associated with aetiology (p=0.015) and MRI data (p<0.001). INTERPRETATION: A multidimensional evaluation, including aetiological, neurodevelopmental, and MRI investigation, is needed for planning therapeutic intervention, such as cochlear implantation in children with severe to profound hearing impairment. The aetiology of deafness is a relevant risk indicator for the presence of an associated disorder.

Adaptive Working Memory Training Can Improve Executive Functioning and Visuo-Spatial Skills in Children With Pre-term Spastic Diplegia.

Pre-term spastic diplegia (pSD) due to periventricular leukomalacia is a form of cerebral palsy in which weaknesses in executive functions are reported beyond the core visuo-spatial deficits. The study aimed at improving executive functioning and visuo-spatial skills with an evidence-based training focused on working memory in children with pSD. The intervention study followed a stepped wedge design. 19 children with pSD (11 female and 8 male; age range: 4;1-13;1 years), mild to moderate upper limb impairment and Verbal Intelligence Quotient (VIQ) >80 participated to the study. The children were trained with a home-based adaptive working memory training (CogMed®) over a 5-week period. The primary outcome measure was the CogMed Improvement index; pre- and post-test explorative neuropsychological assessment was conducted with a subset of tests from the NEPSY-II battery. Working memory training in children with pSD significantly improved trained working memory abilities (CogMed indices) as well as non-trained skills, such as visuo-spatial skills, inhibition of automatic responses and phonological processing. The results suggest that standard rehabilitation schedules for children with pSD should be integrated with trainings on executive functions.

Autism Spectrum Disorder and Childhood Apraxia of Speech: Early Language-Related Hallmarks across Structural MRI Study.

Autism Spectrum Disorder (ASD) and Childhood Apraxia of Speech (CAS) are developmental disorders with distinct diagnostic criteria and different epidemiology. However, a common genetic background as well as overlapping clinical features between ASD and CAS have been recently reported. To date, brain structural language-related abnormalities have been detected in both the conditions, but no study directly compared young children with ASD, CAS and typical development (TD). In the current work, we aim: (i) to test the hypothesis that ASD and CAS display neurostructural differences in comparison with TD through morphometric Magnetic Resonance Imaging (MRI)-based measures (ASD vs. TD and CAS vs. TD); (ii) to investigate early possible disease-specific brain structural patterns in the two clinical groups (ASD vs. CAS); (iii) to evaluate predictive power of machine-learning (ML) techniques in differentiating the three samples (ASD, CAS, TD). We retrospectively analyzed the T1-weighted brain MRI scans of 68 children (age range: 34-74 months) grouped into three cohorts: (1) 26 children with ASD (mean age ± standard deviation: 56 ± 11 months); (2) 24 children with CAS (57 ± 10 months); (3) 18 children with TD (55 ± 13 months). Furthermore, a ML analysis based on a linear-kernel Support Vector Machine (SVM) was performed. All but one brain structures displayed significant higher volumes in both ASD and CAS children than TD peers. Specifically, ASD alterations involved fronto-temporal regions together with basal ganglia and cerebellum, while CAS alterations are more focused and shifted to frontal regions, suggesting a possible speech-related anomalies distribution. Caudate, superior temporal and hippocampus volumes directly distinguished the two conditions in terms of greater values in ASD compared to CAS. The ML analysis identified significant differences in brain features between ASD and TD children, whereas only some trends in the ML classification capability were detected in CAS as compared to TD peers. Similarly, the MRI structural underpinnings of two clinical groups were not significantly different when evaluated with linear-kernel SVM. Our results may represent the first step towards understanding shared and specific neural substrate in ASD and CAS conditions, which subsequently may contribute to early differential diagnosis and tailoring specific early intervention.

Grammatical Comprehension in Italian Children with Autism Spectrum Disorder.

Language deficits represent one of the most relevant factors that determine the clinical phenotype of children with autism spectrum disorder (ASD). The main aim of the research was to study the grammatical comprehension of children with ASD. A sample of 70 well-diagnosed children (60 boys and 10 girls; aged 4.9-8 years) were prospectively recruited. The results showed that language comprehension is the most impaired language domain in ASD. These findings have important clinical implications, since the persistence of grammatical receptive deficits may have a negative impact on social, adaptive and learning achievements. As for the grammatical profiles, persistent difficulties were found during the school-age years in morphological and syntactic decoding in children with relatively preserved cognitive and expressive language skills. These data and the lack of a statistically significant correlation between the severity of ASD symptoms and language skills are in line with the DSM-5 (Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition) perspective that considers the socio-communication disorder as a nuclear feature of ASD and the language disorder as a specifier of the diagnosis and not as a secondary symptom anymore. The presence of receptive difficulties in school-age ASD children with relatively preserved non-verbal cognitive abilities provides important hints to establish rehabilitative treatments.