Multi-level evidence of an allelic hierarchy of USH2A variants in hearing, auditory processing and speech/language outcomes.
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ABSTRACT:
SUBMITTER: Perrino PA
PROVIDER: S-EPMC7170883 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Recent insight into the genetic bases for autism spectrum disorder, dyslexia, stuttering, and language disorders suggest that neurogenetic approaches may also reveal at least one etiology of auditory processing disorder (APD). A person with an APD typically has difficulty understanding speech in background noise despite having normal pure-tone hearing sensitivity. The estimated prevalence of APD may be as high as 10% in the pediatric population, yet the causes are unknown and have not been explored by molecular or genetic approaches. The aim of our study was to determine the heritability of frequency and temporal resolution for auditory signals and speech recognition in noise in 96 identical or fraternal twin pairs, aged 6-11 years. Measures of auditory processing (AP) of non-speech sounds included backward masking (temporal resolution), notched noise masking (spectral resolution), pure-tone frequency discrimination (temporal fine structure sensitivity), and nonsense syllable recognition in noise. We provide evidence of significant heritability, ranging from 0.32 to 0.74, for individual measures of these non-speech-based AP skills that are crucial for understanding spoken language. Identification of specific heritable AP traits such as these serve as a basis to pursue the genetic underpinnings of APD by identifying genetic variants associated with common AP disorders in children and adults.
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Project description:Hearing loss with increasing age adversely affects the ability to understand speech, an effect that results partly from reduced audibility. The aims of this study were to establish whether aging reduces speech intelligibility for listeners with normal audiograms, and, if so, to assess the relative contributions of auditory temporal and cognitive processing. Twenty-one older normal-hearing (ONH; 60-79 years) participants with bilateral audiometric thresholds ? 20 dB HL at 0.125-6 kHz were matched to nine young (YNH; 18-27 years) participants in terms of mean audiograms, years of education, and performance IQ. Measures included: (1) identification of consonants in quiet and in noise that was unmodulated or modulated at 5 or 80 Hz; (2) identification of sentences in quiet and in co-located or spatially separated two-talker babble; (3) detection of modulation of the temporal envelope (TE) at frequencies 5-180 Hz; (4) monaural and binaural sensitivity to temporal fine structure (TFS); (5) various cognitive tests. Speech identification was worse for ONH than YNH participants in all types of background. This deficit was not reflected in self-ratings of hearing ability. Modulation masking release (the improvement in speech identification obtained by amplitude modulating a noise background) and spatial masking release (the benefit obtained from spatially separating masker and target speech) were not affected by age. Sensitivity to TE and TFS was lower for ONH than YNH participants, and was correlated positively with speech-in-noise (SiN) identification. Many cognitive abilities were lower for ONH than YNH participants, and generally were correlated positively with SiN identification scores. The best predictors of the intelligibility of SiN were composite measures of cognition and TFS sensitivity. These results suggest that declines in speech perception in older persons are partly caused by cognitive and perceptual changes separate from age-related changes in audiometric sensitivity.
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Project description:Defects in USH2A cause both isolated retinal disease and Usher syndrome (ie, retinal disease and deafness). To gain insights into isolated/nonsyndromic USH2A retinopathy, we screened USH2A in 186 probands with recessive retinal disease and no hearing complaint in childhood (discovery cohort) and in 84 probands with recessive retinal disease (replication cohort). Detailed phenotyping, including retinal imaging and audiological assessment, was performed in individuals with two likely disease-causing USH2A variants. Further genetic testing, including screening for a deep-intronic disease-causing variant and large deletions/duplications, was performed in those with one likely disease-causing change. Overall, 23 of 186 probands (discovery cohort) were found to harbour two likely disease-causing variants in USH2A. Some of these variants were predominantly associated with nonsyndromic retinal degeneration ('retinal disease-specific'); these included the common c.2276?G>T, p.(Cys759Phe) mutation and five additional variants: c.2802?T>G, p.(Cys934Trp); c.10073?G>A, p.(Cys3358Tyr); c.11156?G>A, p.(Arg3719His); c.12295-3?T>A; and c.12575?G>A, p.(Arg4192His). An allelic hierarchy was observed in the discovery cohort and confirmed in the replication cohort. In nonsyndromic USH2A disease, retinopathy was consistent with retinitis pigmentosa and the audiological phenotype was variable. USH2A retinopathy is a common cause of nonsyndromic recessive retinal degeneration and has a different mutational spectrum to that observed in Usher syndrome. The following model is proposed: the presence of at least one 'retinal disease-specific' USH2A allele in a patient with USH2A-related disease results in the preservation of normal hearing. Careful genotype-phenotype studies such as this will become increasingly important, especially now that high-throughput sequencing is widely used in the clinical setting.
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Project description:Purpose Clinicians depend on the accuracy of research in the speech, language, and hearing sciences to improve assessment and treatment of patients with communication disorders. Although this work has contributed to great advances in clinical care, common statistical misconceptions remain, which deserve closer inspection in the field. Challenges in applying and interpreting traditional statistical methods with behavioral data from humans have led to difficulties with replication and reproducibility in other allied scientific fields, including psychology and medicine. The importance of research in our fields of study for advancing science and clinical care for our patients means that the choices of statistical methods can have far-reaching, real-world implications. Method The goal of this article is to provide an overview of fundamental statistical concepts and methods that are used in the speech, language, and hearing sciences. Results We reintroduce basic statistical terms such as the p value and effect size, as well as recommended procedures for model selection and multiple comparisons. Conclusions Research in the speech, language, and hearing sciences can have a profound positive impact on the lives of individuals with communication disorders, but the validity of scientific findings in our fields is enhanced when data are analyzed using sound statistical methods. Misunderstanding or misinterpretation of basic statistical principles may erode public trust in research findings. Recommendations for practices that can help minimize the likelihood of errors in statistical inference are provided. Supplemental Material https://doi.org/10.23641/asha.7849223.
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Project description:Under the predictive coding hypothesis, specific spatiotemporal patterns of cortical activation are postulated to occur during sensory processing as expectations generate feedback predictions and prediction errors generate feedforward signals. Establishing experimental evidence for this information flow within cortical hierarchy has been difficult, especially in humans, due to spatial and temporal limitations of non-invasive measures of cortical activity. This study investigated cortical responses to auditory novelty using the local/global deviant paradigm, which engages the hierarchical network underlying auditory predictive coding over short ('local deviance'; LD) and long ('global deviance'; GD) time scales. Electrocorticographic responses to auditory stimuli were obtained in neurosurgical patients from regions of interest (ROIs) including auditory, auditory-related and prefrontal cortex. LD and GD effects were assayed in averaged evoked potential (AEP) and high gamma (70-150?Hz) signals, the former likely dominated by local synaptic currents and the latter largely reflecting local spiking activity. AEP LD effects were distributed across all ROIs, with greatest percentage of significant sites in core and non-core auditory cortex. High gamma LD effects were localized primarily to auditory cortex in the superior temporal plane and on the lateral surface of the superior temporal gyrus (STG). LD effects exhibited progressively longer latencies in core, non-core, auditory-related and prefrontal cortices, consistent with feedforward signaling. The spatial distribution of AEP GD effects overlapped that of LD effects, but high gamma GD effects were more restricted to non-core areas. High gamma GD effects had shortest latencies in STG and preceded AEP GD effects in most ROIs. This latency profile, along with the paucity of high gamma GD effects in the superior temporal plane, suggest that the STG plays a prominent role in initiating novelty detection signals over long time scales. Thus, the data demonstrate distinct patterns of information flow in human cortex associated with auditory novelty detection over multiple time scales.
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Project description:IMPORTANCE Hearing loss (HL) in children can be deleterious to their speech and language development. The standard of practice has been early provision of hearing aids (HAs) to moderate these effects; however, there have been few empirical studies evaluating the effectiveness of this practice on speech and language development among children with mild-to-severe HL. OBJECTIVE To investigate the contributions of aided hearing and duration of HA use to speech and language outcomes in children with mild-to-severe HL. DESIGN, SETTING, AND PARTICIPANTS An observational cross-sectional design was used to examine the association of aided hearing levels and length of HA use with levels of speech and language outcomes. One hundred eighty 3- and 5-year-old children with HL were recruited through records of Universal Newborn Hearing Screening and referrals from clinical service providers in the general community in 6 US states. INTERVENTIONS All but 4 children had been fitted with HAs, and measures of aided hearing and the duration of HA use were obtained. MAIN OUTCOMES AND MEASURES Standardized measures of speech and language ability were obtained. RESULTS Measures of the gain in hearing ability for speech provided by the HA were significantly correlated with levels of speech (?179?=?0.20; P?=?.008) and language: ?155?=?0.21; P?=?.01) ability. These correlations were indicative of modest levels of association between aided hearing and speech and language outcomes. These benefits were found for children with mild and moderate-to-severe HL. In addition, the amount of benefit from aided hearing interacted with the duration of HA experience (Speech: F4,161?=?4.98; P?<?.001; Language: F4,138?=?2.91; P?<?.02). Longer duration of HA experience was most beneficial for children who had the best aided hearing. CONCLUSIONS AND RELEVANCE The degree of improved hearing provided by HAs was associated with better speech and language development in children. In addition, the duration of HA experience interacted with the aided hearing to influence outcomes. These results provide support for the provision of well-fitted HAs to children with HL. In particular, the findings support early HA fitting and HA provision to children with mild HL.
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Project description:Purpose:There is a growing interest in speech intelligibility and auditory perception of deaf children. The aim of the present study was to compare speech intelligibility and auditory perception of pre-school children with Hearing Aid (HA), Cochlear Implant (CI), and Typical Hearing (TH). Methods:The research design was descriptive-analytic and comparative. The participants comprised 75 male pre-school children aged 4-6 years in the 2017-2018 from Tehran, Iran. The participants were divided into three groups, and each group consisted of 25 children. The first and second groups were respectively selected from pre-school children with HA and CI using the convenience sampling method, while the third group was selected from pre-school children with TH by random sampling method. All children completed Speech Intelligibility Rating and Categories of Auditory Performance Questionnaires. Results:The findings indicated that the mean scores of speech intelligibility and auditory perception of the group with TH were significantly higher than those of the other groups (P < 0.0001). The mean scores of speech intelligibility in the group with CI did not significantly differ from those of the group with HA (P < 0.38). Also, the mean scores of auditory perception in the group with CI were significantly higher than those of the group with HA (P < 0.002). Conclusion:The results showed that auditory perception in children with CI was significantly higher than children with HA. This finding highlights the importance of cochlear implantation at a younger age and its significant impact on auditory perception in deaf children.
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