Communicating Emotion:Vocal Expression of Linguistic and Emotional Prosody in Children With Mild to Profound Hearing Loss Compared With That of Normal Hearing Peers

Objectives: Emotional prosody is known to play an important role in social communication. Research has shown that children with cochlear implants (CCIs) may face challenges in their ability to express prosody, as their expressions may have less distinct acoustic contrasts and therefore may be judged less accurately. The prosody of children with milder degrees of hearing loss, wearing hearing aids, has sparsely been investigated. More understanding of the prosodic expression by children with hearing loss, hearing aid users in particular, could create more awareness among healthcare professionals and parents on limitations in social communication, which awareness may lead to more targeted rehabilitation. This study aimed to compare the prosodic expression potential of children wearing hearing aids (CHA) with that of CCIs and children with normal hearing (CNH). Design: In this prospective experimental study, utterances of pediatric hearing aid users, cochlear implant users, and CNH containing emotional expressions (happy, sad, and angry) were recorded during a reading task. Of the utterances, three acoustic properties were calculated: fundamental frequency (F0), variance in fundamental frequency (SD of F0), and intensity. Acoustic properties of the utterances were compared within subjects and between groups. Results: A total of 75 children were included (CHA: 26, CCI: 23, and CNH: 26). Participants were between 7 and 13 years of age. The 15 CCI with congenital hearing loss had received the cochlear implant at median age of 8 months. The acoustic patterns of emotions uttered by CHA were similar to those of CCI and CNH. Only in CCI, we found no difference in F0 variation between happiness and anger, although an intensity difference was present. In addition, CCI and CHA produced poorer happy-sad contrasts than did CNH. Conclusions: The findings of this study suggest that on a fundamental, acoustic level, both CHA and CCI have a prosodic expression potential that is almost on par with normal hearing peers. However, there were some minor limitations observed in the prosodic expression of these children, it is important to determine whether these differences are perceptible to listeners and could affect social communication. This study sets the groundwork for more research that will help us fully understand the implications of these findings and how they may affect the communication abilities of these children. With a clearer understanding of these factors, we can develop effective ways to help improve their communication skills.</p

Characterization of the nasopharyngeal and middle ear microbiota in gastroesophageal reflux-prone versus gastroesophageal reflux non-prone children

Otitis media (OM) is one of the most common pediatric infections worldwide, but the complex microbiology associated with OM is poorly understood. Previous studies have shown an association between OM and gastroesophageal reflux (GER) in children. Therefore, in order to bridge the gap in our current understanding of the interaction between GER and OM, we investigated the nasopharyngeal and middle ear microbiota of children suffering from GER-associated OM and OM only, using culture-independent 16S rRNA gene sequencing. Middle ear fluid, nasopharyngeal swabs, and clinical data were collected as part of a prospective pilot study conducted at the Department of Otorhinolaryngology of the Erasmus MC-Sophia Children’s Hospital, Rotterdam, the Netherlands. A total of 30 children up to 12 years of age who suffered from recurrent acute otitis media (AOM) (5), chronic otitis media with effusion (OME) (23), or both (2), and who were listed for tympanostomy tube placement, were included in the study. Nine children were included in the GER-associated OM cohort and 21 in the OM-only cohort. We found no obvious effect of GER on the nasopharyngeal and middle ear microbiota between the two groups of children. However, our results highlight the need to assess the true role of Alloiococcus spp. and Turicella spp. in children presenting with a high prevalence of recurrent AOM and chronic OME

Structural brain differences in pre-adolescents who persist in and recover from stuttering

Background: Stuttering is a complex speech fluency disorder occurring in childhood. In young children, stuttering has been associated with speech-related auditory and motor areas of the brain. During transition into adolescence, the majority of children who stutter (75–80%) will experience remission of their symptoms. The current study evaluated brain (micro-)structural differences between pre-adolescents who persisted in stuttering, those who recovered, and fluently speaking controls. Methods: This study was embedded in the Generation R Study, a population-based cohort in the Netherlands of children followed from pregnancy onwards. Neuroimaging was performed in 2211 children (mean age: 10 years, range 8–12), of whom 20 persisted in and 77 recovered from stuttering. Brain structure (e.g., gray matter) and microstructure (e.g., diffusion tensor imaging) differences between groups were tested using multiple linear regression. Results: Pre-adolescents who persisted in stuttering had marginally lower left superior frontal gray matter volume compared to those with no history of stuttering (β −1344, 95%CI −2407;-280), and those who recovered (β −1825, 95%CI −2999;-650). Pre-adolescents who recovered, compared to those with no history of stuttering, had higher mean diffusivity in the forceps major (β 0.002, 95%CI 0.001;0.004), bilateral superior longitudinal fasciculi (β 0.001, 95%CI 0.000;0.001), left corticospinal tract (β 0.003, 95%CI 0.002;0.004), and right inferior longitudinal fasciculus (β 0.001, 95%CI 0.000;0.001). Conclusion: Findings suggest that relatively small difference in prefrontal gray matter volume is associated with persistent stuttering, and alterations in white matter tracts are apparent in individuals who recovered. The findings further strengthen the potential relevance of brain (micro-)structure in persistence and recovery from stuttering in pre-adolescents

Genome-wide association study for acute otitis media in children identifies FNDC1 as disease contributing gene

Acute otitis media (AOM) is among the most common pediatric diseases, and the most frequent reason for antibiotic treatment in children. Risk of AOM is dependent on environmental and host factors, as well as a significant genetic component. We identify genome-wide significance at a locus on 6q25.3 (rs2932989, P(meta)=2.15 × 10(−09)), and show that the associated variants are correlated with the methylation status of the FNDC1 gene (cg05678571, P=1.43 × 10(−06)), and further show it is an eQTL for FNDC1 (P=9.3 × 10(−05)). The mouse homologue, Fndc1, is expressed in middle ear tissue and its expression is upregulated upon lipopolysaccharide treatment. In this first GWAS of AOM and the largest OM genetic study to date, we identify the first genome-wide significant locus associated with AOM

Genome-wide association study for acute otitis media in children identifies FNDC1 as disease contributing gene

Acute otitis media (AOM) is among the most common pediatric diseases, and the most frequent reason for antibiotic treatment in children. Risk of AOM is dependent on environmental and host factors, as well as a significant genetic component. We identify genome-wide significance at a locus on 6q25.3 (rs2932989, Pmeta=2.15 × 10-09), and show that the associated variants are correlated with the methylation status of the FNDC1 gene (cg05678571, P=1.43 × 10-06), and further show it is an eQTL for FNDC1 (P=9.3 × 10-05). The mouse homologue, Fndc1, is expressed in middle ear tissue and its expression is upregulated upon lipopolysaccharide treatment. In this first GWAS of AOM and the largest OM genetic study to date, we identify the first genome-wide significant locus associated with AOM

Genome-wide analyses of individual differences in quantitatively assessed reading- and language-related skills in up to 34,000 people

The use of spoken and written language is a fundamental human capacity. Individual differences in reading- and language-related skills are influenced by genetic variation, with twin-based heritability estimates of 30 to 80% depending on the trait. The genetic architecture is complex, heterogeneous, and multifactorial, but investigations of contributions of single-nucleotide polymorphisms (SNPs) were thus far underpowered. We present a multicohort genome-wide association study (GWAS) of five traits assessed individually using psychometric measures (word reading, nonword reading, spelling, phoneme awareness, and nonword repetition) in samples of 13,633 to 33,959 participants aged 5 to 26 y. We identified genome-wide significant association with word reading (rs11208009, P = 1.098 × 10−8) at a locus that has not been associated with intelligence or educational attainment. All five reading-/language-related traits showed robust SNP heritability, accounting for 13 to 26% of trait variability. Genomic structural equation modeling revealed a shared genetic factor explaining most of the variation in word/nonword reading, spelling, and phoneme awareness, which only partially overlapped with genetic variation contributing to nonword repetition, intelligence, and educational attainment. A multivariate GWAS of word/nonword reading, spelling, and phoneme awareness maximized power for follow-up investigation. Genetic correlation analysis with neuroimaging traits identified an association with the surface area of the banks of the left superior temporal sulcus, a brain region linked to the processing of spoken and written language. Heritability was enriched for genomic elements regulating gene expression in the fetal brain and in chromosomal regions that are depleted of Neanderthal variants. Together, these results provide avenues for deciphering the biological underpinnings of uniquely human traits

Genome-wide analyses of individual differences in quantitatively assessed reading- and language-related skills in up to 34,000 people

The use of spoken and written language is a fundamental human capacity. Individual differences in reading- and language-related skills are influenced by genetic variation, with twin-based heritability estimates of 30 to 80% depending on the trait. The genetic architecture is complex, heterogeneous, and multifactorial, but investigations of contributions of single-nucleotide polymorphisms (SNPs) were thus far underpowered. We present a multicohort genome-wide association study (GWAS) of five traits assessed individually using psychometric measures (word reading, nonword reading, spelling, phoneme awareness, and nonword repetition) in samples of 13,633 to 33,959 participants aged 5 to 26 y. We identified genome-wide significant association with word reading (rs11208009, P = 1.098 × 10-8) at a locus that has not been associated with intelligence or educational attainment. All five reading-/language-related traits showed robust SNP heritability, accounting for 13 to 26% of trait variability. Genomic structural equation modeling revealed a shared genetic factor explaining most of the variation in word/nonword reading, spelling, and phoneme awareness, which only partially overlapped with genetic variation contributing to nonword repetition, intelligence, and educational attainment. A multivariate GWAS of word/nonword reading, spelling, and phoneme awareness maximized power for follow-up investigation. Genetic correlation analysis with neuroimaging traits identified an association with the surface area of the banks of the left superior temporal sulcus, a brain region linked to the processing of spoken and written language. Heritability was enriched for genomic elements regulating gene expression in the fetal brain and in chromosomal regions that are depleted of Neanderthal variants. Together, these results provide avenues for deciphering the biological underpinnings of uniquely human traits

Hypothesis-driven genome-wide association studies provide novel insights into genetics of reading disabilities

Peer reviewe

Genome-wide analyses of individual differences in quantitatively assessed reading- and language-related skills in up to 34,000 people

The use of spoken and written language is a fundamental human capacity. Individual differences in reading- and language-related skills are influenced by genetic variation, with twin-based heritability estimates of 30 to 80% depending on the trait. The genetic architecture is complex, heterogeneous, and multifactorial, but investigations of contributions of single-nucleotide polymorphisms (SNPs) were thus far underpowered. We present a multicohort genome-wide association study (GWAS) of five traits assessed individually using psychometric measures (word reading, nonword reading, spelling, phoneme awareness, and nonword repetition) in samples of 13,633 to 33,959 participants aged 5 to 26 y. We identified genome-wide significant association with word reading (rs11208009, P = 1.098 x 10(-8)) at a locus that has not been associated with intelligence or educational attainment. All five reading-/language-related traits showed robust SNP heritability, accounting for 13 to 26% of trait variability. Genomic structural equation modeling revealed a shared genetic factor explaining most of the variation in word/nonword reading, spelling, and phoneme awareness, which only partially overlapped with genetic variation contributing to nonword repetition, intelligence, and educational attainment. A multivariate GWAS of word/nonword reading, spelling, and phoneme awareness maximized power for follow-up investigation. Genetic correlation analysis with neuroimaging traits identified an association with the surface area of the banks of the left superior temporal sulcus, a brain region linked to the processing of spoken and written language. Heritability was enriched for genomic elements regulating gene expression in the fetal brain and in chromosomal regions that are depleted of Neanderthal variants. Together, these results provide avenues for deciphering the biological underpinnings of uniquely human traits.Peer reviewe

Heterozygous missense variants of LMX1A lead to nonsyndromic hearing impairment and vestibular dysfunction

Unraveling the causes and pathomechanisms of progressive disorders is essential for the development of therapeutic strategies. Here, we identified heterozygous pathogenic missense variants of LMX1A in two families of Dutch origin with progressive nonsyndromic hearing impairment (HI), using whole exome sequencing. One variant, c.721G > C (p.Val241Leu), occurred de novo and is predicted to affect the homeodomain of LMX1A, which is essential for DNA binding. The second variant, c.290G > C (p.Cys97Ser), predicted to affect a zinc-binding residue of the second LIM domain that is involved in protein–protein interactions. Bi-allelic deleterious variants of Lmx1a are associated with a complex phenotype in mice, including deafness and vestibular defects, due to arrest of inner ear development. Although Lmx1a mouse mutants demonstrate neurological, skeletal, pigmentation and reproductive system abnormalities, no syndromic features were present in the participating subjects of either family. LMX1A has previously been suggested as a candidate gene for intellectual disability, but our data do not support this, as affected subjects displayed normal cognition. Large variability was observed in the age of onset (a)symmetry, severity and progression rate of HI. About half of the affected individuals displayed vestibular dysfunction and experienced symptoms thereof. The late-onset progressive phenotype and the absence of cochleovestibular malformations on computed tomography scans indicate that heterozygous defects of LMX1A do not result in severe developmental abnormalities in humans. We propose that a single LMX1A wild-type copy is sufficient for normal development but insufficient for maintenance of cochleovestibular function. Alternatively, minor cochleovestibular developmental abnormalities could eventually lead to the progressive phenotype seen in the families