14Centre référent pour le diagnostic des troubles du langage et des apprentissages, Département de pédiatrie, CHU Nord, Grenoble, France; Background: The relationship between phoneme awareness, rapid automatized naming (RAN), verbal short-term/working memory (ST/WM) and diagnostic category is investigated in control and dyslexic children, and the extent to which this depends on orthographic complexity. Methods: General cognitive, phonological and literacy skills were tested in 1,138 control and 1,114 dyslexic children speaking six different languages spanning a large range of orthographic complexity (Finnish, Hungarian, German, Dutch, French, English). Results: Phoneme deletion and RAN were strong concurrent predictors of developmental dyslexia, while verbal ST/WM and general verbal abilities played a comparatively minor role. In logistic regression models, more participants were classified correctly when orthography was more complex. The impact of phoneme deletion and RAN-digits was stronger in complex than in less complex orthographies. Conclusions: Findings are largely consistent with the literature on predictors of dyslexia and literacy skills, while uniquely demonstrating how orthographic complexity exacerbates some symptoms of dyslexia.

No abstract

Dyslexia is one of the most common learning disorders affecting about 5% of all school-aged children. It has been shown that event-related potential measurements reveal differences between dyslexic children and age-matched controls. This holds particularly true for mismatch negativity (MMN), which reflects automatic speech deviance processing and is altered in dyslexic children. We performed a whole-genome association analysis in 200 dyslexic children, focusing on MMN measurements. We identified rs4234898, a marker located on chromosome 4q32.1, to be significantly associated with the late MMN component. This association could be replicated in an independent second sample of 186 dyslexic children, reaching genome-wide significance in the combined sample (P = 5.14eÀ08). We also found an association between the late MMN component and a two-marker haplotype of rs4234898 and rs11100040, one of its neighboring single nucleotide polymorphisms (SNPs). In the combined sample, this marker combination withstands correction for multiple testing (P = 6.71eÀ08). Both SNPs lie in a region devoid of any protein-coding genes; however, they both show significant association with mRNA-expression levels of SLC2A3 on chromosome 12, the predominant facilitative glucose transporter in neurons. Our results suggest a possible transregulation effect on SLC2A3, which might lead to glucose deficits in dyslexic children and could explain their attenuated MMN in passive listening tasks.

The main diagnostic criterion for developmental dyslexia (DD) in transparent orthographies is a remarkable reading speed deficit, which is often accompanied by spelling difficulties. These deficits have been traced back to both deficits in orthographic and phonological processing. For a better understanding of the reading speed deficit in DD it is necessary to clarify which processing steps are degraded in children with DD during reading. In order to address this question the present study used EEG to investigate three reading related ERPs: the N170, N400 and LPC. Twenty-nine children without DD and 52 children with DD performed a phonological lexical decision (PLD)—task, which tapped both orthographic and phonological processing. Children were presented with words, pseudohomophones, pseudowords and false fonts and had to decide whether the presented stimulus sounded like an existing German word or not. Compared to control children, children with DD showed deficits in all the investigated ERPs. Firstly, a diminished mean area under the curve for the word material-false font contrasts in the time window of the N170 was observed, indicating a reduced degree of print sensitivity; secondly, N400 amplitudes, as suggested to reflect the access to the orthographic lexicon and grapheme-phoneme conversion, were attenuated; and lastly, phonological access as indexed by the LPC was degraded in children with DD. Processing differences dependent on the linguistic material in children without DD were observed only in the LPC, suggesting that similar reading processes were adopted independent of orthographic familiarity. The results of this study suggest that effective treatment should include both orthographic and phonological training. Furthermore, more longitudinal studies utilizing the same task and stimuli are needed to clarify how these processing steps and their time course change during reading development.

The aim of the present study was to characterize the EEG response pattern specific for tonic pain which is an experimental pain model resembling clinical pain more closely than phasic pain. Tonic experimental pain was produced by a series of heat pulses 1 degree C above pain threshold over 10 min. A series of heat pulses 0.3 degree C below pain threshold and a constant temperature of 37 degrees C served as non-painful heat control and as baseline condition, respectively. The level of attention was experimentally manipulated by instruction and by a distraction task. Twenty male, pain-free subjects had to rate the sensation intensity and sensation unpleasantness during thermal stimulation. Furthermore, a German version of the McGill Pain Questionnaire was to be filled out after tonic painful heat stimulation. The EEG was recorded via 10 leads according to 10/20 convention. Power density was calculated for the usual frequency bands. The ratings showed that tonic painful heat was experienced clearly distinct from tonic non-painful heat. An EEG response pattern emerged characterized by a rather generalized increased delta(2) activity, a left-biased fronto-temporally diminished theta activity, a fronto-temporal decrease in the alpha(1) activity and a left-sided temporal increase in the beta(1) activity. This observation agrees well with the findings of others. However, there was no evidence in our data that these EEG changes are specific to tonic heat pain as opposed to changes observed during tonic non-painful heat stimulation. Accordingly, the repeatedly reported EEG patterns are also likely to be produced by other forms of strong somatosensory stimuli and to be not specific for pain.

It has been repeatedly shown that mismatch negativity (MMN), an event related potential measurement, reveals differences between dyslexic children and age-matched controls. MMN reflects the automatic detection of deviance between a stream of incoming sounds presented to the passive listener, and deficits in MMN (i.e. attenuated amplitudes) have been especially reported in dyslexia for detecting differences between speech sounds (e.g./ba/vs./da/). We performed an association analysis in 200 dyslexic children. This analysis focused on two MMN components, an early MMN (188-300 ms) and a late MMN (300-710 ms), and the dyslexia candidate genes KIAA0319 and DCDC2 on chromosome 6. Additionally, we imputed rare variants located in this region based on the 1000 genomes project. We identified four rare variants that were significantly associated with the late MMN component. For three of these variants, which were in high LD to each other, genotyping confirmed the association signal. Our results point to an association between late MMN and rare variants in a candidate gene region for dyslexia.

Dyslexia affects 5–10% of school-aged children and is therefore one of the most common learning disorders. Research on auditory event related potentials (AERP), particularly the mismatch negativity (MMN) component, has revealed anomalies in individuals with dyslexia to speech stimuli. Furthermore, candidate genes for this disorder were found through molecular genetic studies. A current challenge for dyslexia research is to understand the interaction between molecular genetics and brain function, and to promote the identification of relevant endophenotypes for dyslexia. The present study examines MMN, a neurophysiological correlate of speech perception, and its potential as an endophenotype for dyslexia in three groups of children. The first group of children was clinically diagnosed with dyslexia, whereas the second group of children was comprised of their siblings who had average reading and spelling skills and were therefore “unaffected” despite having a genetic risk for dyslexia. The third group consisted of control children who were not related to the other groups and were also unaffected. In total, 225 children were included in the study. All children showed clear MMN activity to/da/−/ba/contrasts that could be separated into three distinct MMN components. Whilst the first two MMN components did not differentiate the groups, the late MMN component (300–700 ms) revealed significant group differences. The mean area of the late MMN was attenuated in both the dyslexic children and their unaffected siblings in comparison to the control children. This finding is indicative of analogous alterations of neurophysiological processes in children with dyslexia and those with a genetic risk for dyslexia, without a manifestation of the disorder. The present results therefore further suggest that the late MMN might be a potential endophenotype for dyslexia.

There is strong evidence that auditory processing plays a major role in the etiology of dyslexia. Auditory temporal processing of non-speech stimuli, speech perception, and phonological awareness have been shown to be influential in reading and spelling development. However, the relationship between these variables remains unclear. In order to analyze the influence of these three auditory processing levels on spelling, 19 dyslexic and 15 control children were examined. Significant group differences were found for all speech variables, but not for any non-speech variable. Structural equation modeling resulted in a fairly simple model with direct paths to the respective next lower level. One additional path from preattentive speech processing to spelling had to be included in order to improve the model fit. These results strengthen the role of speech and phonological processing for the etiology in dyslexia.