Indra Kraft

Genetic dyslexia risk variant is related to neural connectivity patterns underlying phonological awareness in children

Phonological awareness is the best-validated predictor of reading and spelling skill and therefore highly relevant for developmental dyslexia. Prior imaging genetics studies link several dyslexia risk genes to either brain-functional or brain-structural factors of phonological deficits. However, coherent evidence for genetic associations with both functional and structural neural phenotypes underlying variation in phonological awareness has not yet been provided. Here we demonstrate that rs11100040, a reported modifier of SLC2A3, is related to the functional connectivity of left fronto-temporal phonological processing areas at resting state in a sample of 9- to 12-year-old children. Furthermore, we provide evidence that rs11100040 is related to the fractional anisotropy of the arcuate fasciculus, which forms the structural connection between these areas. This structural connectivity phenotype is associated with phonological awareness, which is in turn associated with the individual retrospective risk scores in an early dyslexia screening as well as to spelling. These results suggest a link between a dyslexia risk genotype and a functional as well as a structural neural phenotype, which is associated with a phonological awareness phenotype. The present study goes beyond previous work by integrating genetic, brain-functional and brain-structural aspects of phonological awareness within a single approach. These combined findings might be another step towards a multimodal biomarker for developmental dyslexia.

Predicting early signs of dyslexia at a preliterate age by combining behavioral assessment with structural MRI.

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<.05). CONCLUSIONS Our longitudinal results provide evidence for the hypothesis that neuroanatomical anomalies in children with a family risk of DD are related to subsequent problems in acquiring literacy. Particularly, solid white matter organization in the left anterior arcuate fascicle seems to play a pivotal role.

Cortical differences in preliterate children at familiar risk of dyslexia are similar to those observed in dyslexic readers.

Sir, We thank Indra Kraft and colleagues (2015) for their insightful letter commenting on our recent report in Brain . We agree with the authors in their assessment that, while longitudinal studies are invaluable for disentangling cause and effect in neurodevelopmental disorders, such studies are unfortunately rare because of many practical difficulties. And because of such difficulties, longitudinal studies such as ours often end up with final sample sizes that are relatively low compared to cross-sectional studies. As the authors correctly identified, one of the risks of studies with a smaller sample size is that there is an increased chance of type II errors. One way to ameliorate this is to examine effect sizes in conjunction with statistical significance. In our study, the effect sizes of pre-reading differences were remarkably large (effect sizes >2, calculated as Cohen’s d, reported in the …

Lexical learning in mild aphasia: Gesture benefit depends on patholinguistic profile and lesion pattern

Gestures accompany speech and enrich human communication. When aphasia interferes with verbal abilities, gestures become even more relevant, compensating for and/or facilitating verbal communication. However, small-scale clinical studies yielded diverging results with regard to a therapeutic gesture benefit for lexical retrieval. Based on recent functional neuroimaging results, delineating a speech-gesture integration network for lexical learning in healthy adults, we hypothesized that the commonly observed variability may stem from differential patholinguistic profiles in turn depending on lesion pattern. Therefore we used a controlled novel word learning paradigm to probe the impact of gestures on lexical learning, in the lesioned language network. Fourteen patients with chronic left hemispheric lesions and mild residual aphasia learned 30 novel words for manipulable objects over four days. Half of the words were trained with gestures while the other half were trained purely verbally. For the gesture condition, rootwords were visually presented (e.g., Klavier, [piano]), followed by videos of the corresponding gestures and the auditory presentation of the novel words (e.g., /krulo/). Participants had to repeat pseudowords and simultaneously reproduce gestures. In the verbal condition no gesture-video was shown and participants only repeated pseudowords orally. Correlational analyses confirmed that gesture benefit depends on the patholinguistic profile: lesser lexico-semantic impairment correlated with better gesture-enhanced learning. Conversely largely preserved segmental-phonological capabilities correlated with better purely verbal learning. Moreover, structural MRI-analysis disclosed differential lesion patterns, most interestingly suggesting that integrity of the left anterior temporal pole predicted gesture benefit. Thus largely preserved semantic capabilities and relative integrity of a semantic integration network are prerequisites for successful use of the multimodal learning strategy, in which gestures may cause a deeper semantic rooting of the novel word-form. The results tap into theoretical accounts of gestures in lexical learning and suggest an explanation for the diverging effect in therapeutical studies advocating gestures in aphasia rehabilitation.

Dyslexia risk gene relates to representation of sound in the auditory brainstem

Highlights • Previous studies associate poor reading with unstable speech-evoked brainstem responses.• DCDC2 and KIAA0319 risk alleles form a strong genetic link with developmental dyslexia.• Genetic burden with KIAA0319 risk is related to unstable speech-evoked brainstem responses.• Genetic burden with DCDC2 risk is related to intact speech-evoked brainstem responses.• Revealed brain-gene relationships may inform the multifactorial pathophysiology of dyslexia.

High acceptance of an early dyslexia screening test involving genetic analyses in Germany

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 50–70%. 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 3–7 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 parents 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.

ATP2C2 and DYX1C1 are putative modulators of dyslexia-related MMR

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.