A neural oscillations perspective on phonological development and phonological processing in developmental dyslexia

Children’s ability to reflect upon and manipulate the sounds in words (’phonological awareness’) develops as part of natural language acquisition, supports reading acquisition, and develops further as reading and spelling are learned. Children with developmental dyslexia typically have impairments in phonological awareness. Many developmental factors contribute to individual differences in phonological development. One important source of individual differences may be the child’s sensory/neural processing of the speech signal from an amplitude modulation (~ energy or intensity variation) perspective, which may affect the quality of the sensory/neural representations (’phonological representations’) that support phonological awareness. During speech encoding, brain electrical rhythms (oscillations, rhythmic variations in neural excitability) re-calibrate their temporal activity to be in time with rhythmic energy variations in the speech signal. The accuracy of this neural alignment or ’entrainment’ process is related to speech intelligibility. Recent neural studies demonstrate atypical oscillatory function at slower rates in children with developmental dyslexia. Potential relations with the development of phonological awareness by children with dyslexia are discussed.Medical Research Council, G0400574 and G090237

Persistent cAMP-Signals Triggered by Internalized G-Protein–Coupled Receptors

Real-time monitoring of G-protein-coupled receptor (GPCR) signaling in native cells suggests that the receptor for thyroid stimulating hormone remains active after internalization, challenging the current model for GPCR signaling

Atypical neural synchronization to speech envelope modulations in dyslexia

A fundamental deficit in the synchronization of neural oscillations to temporal information in speech could underlie phonological processing problems in dyslexia. In this study, the hypothesis of a neural synchronization impairment is investigated more specifically as a function of different neural oscillatory bands and temporal information rates in speech. Auditory steady-state responses to 4, 10, 20 and 40 Hz modulations were recorded in normal reading and dyslexic adolescents to measure neural synchronization of theta, alpha, beta and low-gamma oscillations to syllabic and phonemic rate information. In comparison to normal readers, dyslexic readers showed reduced non-synchronized theta activity, reduced synchronized alpha activity and enhanced synchronized beta activity. Positive correlations between alpha synchronization and phonological skills were found in normal readers, but were absent in dyslexic readers. In contrast, dyslexic readers exhibited positive correlations between beta synchronization and phonological skills. Together, these results suggest that auditory neural synchronization of alpha and beta oscillations is atypical in dyslexia, indicating deviant neural processing of both syllabic and phonemic rate information. Impaired synchronization of alpha oscillations in particular demonstrated to be the most prominent neural anomaly possibly hampering speech and phonological processing in dyslexic readers

The relation between neurofunctional and neurostructural determinants of phonological processing in pre-readers

Phonological processing skills are known as the most robust cognitive predictor of reading ability. Therefore, the neural determinants of phonological processing have been extensively investigated by means of either neurofunctional or neurostructural techniques. However, to fully understand how the brain represents and processes phonological information, there is need for studies that combine both methods. The present study applies such a multimodal approach with the aim of investigating the pre-reading relation between neural measures of auditory temporal processing, white matter properties of the reading network and phonological processing skills. We administered auditory steady-state responses, diffusion-weighted MRI scans and phonological awareness tasks in 59 pre-readers. Our results demonstrate that a stronger rightward lateralization of syllable-rate (4 Hz) processing coheres with higher fractional anisotropy in the left fronto-temporoparietal arcuate fasciculus. Both neural features each in turn relate to better phonological processing skills. As such, the current study provides novel evidence for the existence of a pre-reading relation between functional measures of syllable-rate processing, structural organization of the arcuate fasciculus and cognitive precursors of reading development. Moreover, our findings demonstrate the value of combining different neural techniques to gain insight in the underlying neural systems for reading (dis)ability

A longitudinal study investigating neural processing of speech envelope modulation rates in children with (a family risk for) dyslexia

Recent evidence suggests that a fundamental deficit in the synchronization of neural oscillations to temporal information in speech may underlie phonological processing problems in dyslexia. Since previous studies were performed cross-sectionally in school-aged children or adults, developmental aspects of neural auditory processing in relation to reading acquisition and dyslexia remain to be investigated. The present longitudinal study followed 68 children during development from pre-reader (5 years old) to beginning reader (7 years old) and more advanced reader (9 years old). Thirty-six children had a family risk for dyslexia and 14 children eventually developed dyslexia. EEG recordings of auditory steady-state responses to 4 and 20 Hz modulations, corresponding to syllable and phoneme rates, were collected at each point in time. Our results demonstrate an increase in neural synchronization to phoneme-rate modulations around the onset of reading acquisition. This effect was negatively correlated with later reading and phonological skills, indicating that children who exhibit the largest increase in neural synchronization to phoneme rates, develop the poorest reading and phonological skills. Accordingly, neural synchronization to phoneme-rate modulations was found to be significantly higher in beginning and more advanced readers with dyslexia. We found no developmental effects regarding neural synchronization to syllable rates, nor any effects of a family risk for dyslexia. Altogether, our findings suggest that the onset of reading instruction coincides with an increase in neural responsiveness to phoneme-rate modulations, and that the extent of this increase is related to (the outcome of) reading development. Hereby, dyslexic children persistently demonstrate atypically high neural synchronization to phoneme rates from the beginning of reading acquisition onwards

A DTI tractography study in pre-readers at risk for dyslexia

In adults and school-aged children, phonological aspects of reading seem to be sustained by left dorsal regions, while ventral regions seem to be involved in orthographic word recognition. Yet, given that the brain reorganises during reading acquisition, it is unknown when and how these reading routes emerge and whether neural deficits in dyslexia predate reading onset. Using diffusion MRI in 36 pre-readers with a family risk for dyslexia (FRD + ) and 35 well matched pre-readers without a family risk (FRD - ), our results show that phonological predictors of reading are sustained bilaterally by both ventral and dorsal tracts. This suggests that a dorsal and left-hemispheric specialisation for phonological aspects of reading, as observed in adults, is presumably gradually formed throughout reading development. Second, our results indicate that FRD + pre-readers display mainly white matter differences in left ventral tracts. This suggests that atypical white matter organisation previously found in dyslexic adults may be causal rather than resulting from a lifetime of reading difficulties, and that the location of such a deficit may vary throughout development. While this study forms an important starting point, longitudinal follow-up of these children will allow further investigation of the dynamics between emerging literacy development and white matter connections

Oncogenic mutations in the thyrotropin receptor of autonomously functioning thyroid nodules in the Japanese population.

OBJECTIVE: Constitutively activating mutations of the thyrotropin receptor (TSHR) have been found in the majority of autonomously functioning thyroid nodules (AFTNs) in European patients. The reported frequency of these mutations varies among reports but amounts to 50-80%. To date, only one such mutation responsible for AFTNs has been identified in the Japanese population and the pathogenic role of such mutations in Japanese AFTNs has been questioned. In the present study, we evaluated the frequency of activating mutations in the TSHR and G(alpha)s in 10 Japanese AFTNs. DESIGN: Genomic DNA was extracted from fresh frozen tissue. The TSHR and the almost entire sequence of the gene coding for the alpha subunit of Gs have been amplified and sequenced. RESULTS: In sequence analysis, four mutations in the TSHR (T632A, I486M, M453T and L512R) were found. To complete our analysis, we searched mutations in the gene coding for the alpha subunit of Gs, in the samples negative for TSHR mutations. In one case a mutation (R201H) affecting GTPase activity was found. CONCLUSIONS: If we focus on the solitary nodules, we obtain the same mutation proportion as in European patients (70%). The absence of TSHR and G(alpha)s mutations in a significant proportion of autonomous adenomas in multinodular goiters suggests that other causes may also play a role in the genesis of these lesions.Journal ArticleResearch Support, Non-U.S. Gov'tinfo:eu-repo/semantics/publishe