Search

Purpose Childhood onset speech fluency disorder (stuttering) is possibly related to dopaminergic dysfunction. Mesencephalic hyperechogenicity (ME) detected by transcranial ultrasound (TCS) might be seen as an indirect marker of dopaminergic dysfunction. We here determined whether adults who stutter since childhood (AWS) show ME. Methods We performed TCS in ten AWS and ten matched adults who never stuttered. We also assessed motor performance in finger tapping and in the 25 Foot Walking test. Results Compared to controls, AWS showed enlarged ME on either side. Finger tapping was slower in AWS. Walking cadence, i.e., the ratio of number of steps by time, tended to be higher in AWS than in control participants. Discussion The results demonstrate a motor deficit in AWS linked to dopaminergic dysfunction and extending beyond speech. Since iron deposits evolve in childhood and shrink thereafter, ME might serve as an easily quantifiable biomarker helping to predict the risk of persistency in children who stutter.

Additional file 2. Kruskal Wallis Test results for the differentiation of lung cancer subtypes using ADC-ratio.

Highlights • Multi-domain profiles advance retrospective prediction of emergent literacy. • DCDC2 and KIAA0319 risk variants influence emergent spelling skills. • Combined DYX2 and auditory brainstem measures enhance predictive model fits. • Additional benefit of preliterate phonological awareness on predictive power., Literacy acquisition is impaired in children with developmental dyslexia resulting in lifelong struggle to read and spell. Proper diagnosis is usually late and commonly achieved after structured schooling started, which causes delayed interventions. Legascreen set out to develop a preclinical screening to identify children at risk of developmental dyslexia. To this end we examined 93 preliterate German children, half of them with a family history of dyslexia and half of them without a family history. We assessed standard demographic and behavioral precursors of literacy, acquired saliva samples for genotyping, and recorded speech-evoked brainstem responses to add an objective physiological measure. Reading and spelling was assessed after two years of structured literacy instruction. Multifactorial regression analyses considering demographic information, genotypes, and auditory brainstem encoding, predicted children’s literacy skills to varying degrees. These predictions were improved by adding the standard psychometrics with a slightly higher impact on spelling compared to reading comprehension. Our findings suggest that gene-brain-behavior profiling has the potential to determine the risk of developmental dyslexia. At the same time our results imply the need for a more sophisticated assessment to fully account for the disparate cognitive profiles and the multifactorial basis of developmental dyslexia.

Children lay the foundation for later academic achievement by acquiring core mathematical abilities in the first school years. Neural reorganization processes associated with individual differences in early mathematical learning, however, are still poorly understood. To fill this research gap, we followed a sample of 5-6-year-old children longitudinally to the end of second grade in school (age 7–8 years) combining magnetic resonance imaging (MRI) with comprehensive behavioral assessments. We report significant links between the rate of neuroplastic change of cortical surface anatomy, and children's early mathematical skills. In particular, most of the behavioral variance (about 73%) of children's visuospatial abilities was explained by the change in cortical thickness in the right superior parietal cortex. Moreover, half of the behavioral variance (about 55%) of children's arithmetic abilities was explained by the change in cortical folding in the right intraparietal sulcus. Additional associations for arithmetic abilities were found for cortical thickness change of the right temporal lobe, and the left middle occipital gyrus. Visuospatial abilities were related to right precentral and supramarginal thickness, as well as right medial frontal gyrus folding plasticity. These effects were independent of other individual differences in IQ, literacy and maternal education. Our findings highlight the critical role of cortical plasticity during the acquisition of fundamental mathematical abilities.\ud \ud

Mathematical ability is heritable and related to several genes expressing proteins in the brain. It is unknown, however, which intermediate neural phenotypes could explain how these genes relate to mathematical ability. Here, we examined genetic effects on cerebral cortical volume of 3-6-year-old children without mathematical training to predict mathematical ability in school at 7-9 years of age. To this end, we followed an exploration sample (n = 101) and an independent replication sample (n = 77). We found that ROBO1, a gene known to regulate prenatal growth of cerebral cortical layers, is associated with the volume of the right parietal cortex, a key region for quantity representation. Individual volume differences in this region predicted up to a fifth of the behavioral variance in mathematical ability. Our findings indicate that a fundamental genetic component of the quantity processing system is rooted in the early development of the parietal cortex.

Persistent developmental stuttering (PDS) disrupts speech fluency in about 1% of adults. Although many models of speech production assume an intact sensory feedback from the speech organs to the brain, very little is actually known about the integrity of their sensory representation in PDS. Here, we studied somatosensory evoked potentials (SEPs) in adults who stutter (AWS), with the aim of probing the integrity of sensory pathways. In addition, we tested the processing of dual sensory input to address a putative link between stuttering and focal dystonia. In 15 AWS (aged 15–55 years; three females) and 14 matched fluent speaking adults (ANS), we recorded SEPs at C50 and C60 induced by stimulating separately or simultaneously the tongue or the cheek at the corner of the mouth. We determined latencies (N13, P19, and N27) and peakto- peak amplitudes (N13-P19, P19-N27). We divided amplitudes from simultaneous stimulation by the sum of those from separate stimulation. Amplitude ratios did not differ between groups, indicating normal processing of dual sensory input. This does not support a clinical analogy between focal dystonia and persistent stuttering. SEP latencies as a measure of transmission speed in sensory pathways were significantly shorter in stuttering subjects than in fluent speaking participants, however, this might have been related to a trend for a height difference between groups, and was not confirmed in a replication dataset. In summary, we did not find evidence for dystonia-like sensory overflow of tongue representations in AWS. Open-Access-Publikationsfonds 2019 peerReviewed

Background\ud Dyslexia is a specific learning disorder affecting reading and spelling abilities. Its prevalence is ~5% in German‐speaking individuals. Although the etiology of dyslexia largely remains to be determined, comprehensive evidence supports deficient phonological processing as a major contributing factor. An important prerequisite for phonological processing is auditory discrimination and, thus, essential for acquiring reading and spelling skills. The event‐related potential Mismatch Response (MMR) is an indicator for auditory discrimination capabilities with dyslexics showing an altered late component of MMR in response to auditory input.\ud Methods\ud In this study, we comprehensively analyzed associations of dyslexia‐specific late MMRs with genetic variants previously reported to be associated with dyslexia‐related phenotypes in multiple studies comprising 25 independent single‐nucleotide polymorphisms (SNPs) within 10 genes.\ud Results\ud First, we demonstrated validity of these SNPs for dyslexia in our sample by showing that additional inclusion of a polygenic risk score improved prediction of impaired writing compared with a model that used MMR alone. Secondly, a multifactorial regression analysis was conducted to uncover the subset of the 25 SNPs that is associated with the dyslexia‐specific late component of MMR. In total, four independent SNPs within DYX1C1 and ATP2C2 were found to be associated with MMR stronger than expected from multiple testing. To explore potential pathomechanisms, we annotated these variants with functional data including tissue‐specific expression analysis and eQTLs. \ud Conclusion\ud Our findings corroborate the late component of MMR as a potential endophenotype for dyslexia and support tripartite relationships between dyslexia‐related SNPs, the late component of MMR and dyslexia.

Dyslexia is a severe disorder in the acquisition of reading and writing. Several studies investigated the role of genetics for reading, writing and spelling ability in the general population. However, many of the identified SNPs were not analysed in case-control cohorts. Here, we investigated SNPs previously linked to reading or spelling ability in the general population in a German case-control cohort. Furthermore, we characterised these SNPs for functional relevance with in silico methods and meta-analysed them with previous studies. A total of 16 SNPs within five genes were included. The total number of risk alleles was higher in cases than in controls. Three SNPs were nominally associated with dyslexia: rs7765678 within DCDC2, and rs2038137 and rs6935076 within KIAA0319. The relevance of rs2038137 and rs6935076 was further supported by the meta-analysis. Functional profiling included analysis of tissue-specific expression, annotations for regulatory elements and effects on gene expression levels (eQTLs). Thereby, we found molecular mechanistical implications for 13 of all 16 included SNPs. SNPs associated in our cohort showed stronger gene-specific eQTL effects than non-associated SNPs. In summary, our results validate SNPs previously linked to reading and spelling in the general population in dyslexics and provide insights into their putative molecular pathomechanisms.

Background: Recent studies suggest that neurobiological anomalies are already detectable in pre-school children with a family history of developmental dyslexia (DD). However, there is a lack of longitudinal studies showing a direct link between those differences at a preliterate age and the subsequent literacy difficulties seen in school. It is also not clear whether the prediction of DD in pre-school children can be significantly improved when considering neurobiological predictors, compared to models based on behavioral literacy precursors only. Methods: We recruited 53 pre-reading children either with (N=25) or without a family risk of DD (N=28). Quantitative T1 MNI data and literacy precursor abilities were assessed at kindergarten age. A subsample of 35 children was tested for literacy skills either one or two years later, that is, either in first or second grade. Results: The group comparison of quantitative T1 measures revealed significantly higher T1 intensities in the left anterior arcuate fascicle (AF), suggesting reduced myelin concentration in preliterate children at risk of DD. A logistic regression showed that DD can be predicted significantly better (p=.024) when neuroanatomical differences between groups are used as predictors (80%) compared to a model based on behavioral predictors only (63%).The Wald statistic confirmed that the T1 intensity of the left AF is a statistically significant predictor of DD (p

Dyslexia is a developmental disorder characterized by severe problems in the acquisition of reading and writing skills. It has a strong neurobiological basis. Genetic influence is estimated at 5070%. One of the central problems with dyslexia is its late diagnosis, normally not before the end of the 2nd grade, resulting in the loss of several years for early therapy. Currently, research is focusing on the development of early tests for dyslexia, which may be based on EEG and genetics. Our aim was to determine the acceptance of such a future test among parents. We conducted a representative survey in Germany with 1000 parents of children aged 37 years, with and without experience of dyslexia. 88.7% of the parents supported the introduction of an early test for dyslexia based on EEG and genetics; 82.8% would have their own children tested, and 57.9% were willing to pay for the test if health insurance did not cover the costs. Test acceptance was significantly higher if par ents had prior experience with dyslexia. The perceived benefits of such a test were early recognition and remediation and, preventing deficits. Concerns regarded the precision of the test, its potentially stigmatizing effect and its costs. The high overall support for the test leads to the conclusion that parents would accept a test for dyslexia based on EEG and genetics.