Consanguinity as a Risk Factor for Autism.

PURPOSE: Genetic and environmental risk factors associated with Autism Spectrum Disorders (ASD) continue to be a focus of research worldwide. Consanguinity, the cultural practice of marrying within a family, is common in cultures and societies of the Middle East, North Africa and parts of Asia. Consanguinity has been investigated as a risk factor for ASD in a limited number of studies, with mixed results. We employed registry and survey data from Qatar to evaluate the role of consanguinity as a risk factor for ASD. METHODS: Data were sourced from a national registry and a population-based survey of autism recently conducted in Qatar. We selected a sample of 891 children (mean age: 8.3 years) with (N = 361) or without (N = 530) ASD. Data on consanguinity and covariates were collected through questionnaires and interviews. RESULTS: The prevalence of consanguinity in the overall sample was 41.2% with no significant difference between cases and controls (42.1% vs 41.3%; p = .836). In adjusted multiple logistic regression analyses, consanguinity was not associated with risk of ASD (aOR = 1.065; 95% CI: .751-1.509; NS). CONCLUSION: Parental consanguinity was not associated with autism risk in our study. Replication in other populations with high rates of consanguineous unions is recommended.

Cross-Cultural Awareness and Attitudes Toward Threatened Animal Species.

The preservation of our planet's decreasing biodiversity is a global challenge. Human attitudes and preferences toward animals have profound impacts on conservation policies and decisions. To date, the vast majority of studies about human attitudes and concern toward animals have focused largely on western, educated, industrialized, rich and democratic (i.e., WEIRD) populations. In order to mitigate biodiversity loss globally, an understanding of how humans make decisions about animals from multicultural perspectives is needed. The present study examines familiarity, liking and endorsement of government protection amongst six broad cultural groups living in Qatar for five threatened animal species indigenous to the Arabian Gulf. Our findings highlight similarities and differences across cultures toward animals. Overall, familiarity did not predict endorsement for government protection after liking was accounted for. Liking, however, emerged as an important predictor of endorsement for government protection across cultures, although the degree of animal liking varied culturally. WEIRD and South East Asian participants showed similar and more positive attitudes toward animals compared to the other groups. Participants from the Arabian Gulf, Sub-Saharan Africa, Middle East and North Africa, and South Asia responded similarly toward the animals. Interestingly, the Arabian Gulf group demonstrated significantly less liking and protection endorsement for animals, including those animals which play an important role in their culture. This research highlights intriguing avenues for future research and points to liking as a possible universal human attitude toward animals that influences decision making about conservation across all cultures while suggesting applications for improving education.

Does the late positive component reflect successful reading acquisition? A longitudinal ERP study.

Developmental dyslexia is a reading disorder that is associated with deficits in phonological processing, where the exact neural basis for those processing deficits remains unclear. In particular, disagreement exists whether degraded phonological representations or an impaired access to the phonological representations causes these deficits. To investigate this question and to trace changes in neurophysiology during the process of reading acquisition, we designed a longitudinal study with event related potentials (ERPs) in children between kindergarten and second grade. We used an explicit word processing task to elicit the late positive component (LPC), which has been shown to reflect phonological processing. A brain-wide analysis of the LPC with an electrode-wise application of mixed effects models showed significantly attenuated amplitudes in the left temporo-parietal region in dyslexic children. Since these differences were only present in the word and not in the picture (i.e. control) condition, the attenuated amplitudes might reflect impaired access to the phonological representations of words. This was further confirmed by the longitudinal development, which showed a rapid increase in amplitude at the beginning of reading instruction and a decrease with continuing automatization, possibly pointing to a progression from grapheme-phoneme parsing to whole word reading. Our longitudinal study provides the first evidence that it is possible to detect neurophysiological differences in the LPC between children with dyslexia and control children in both preliterate and very early stages of reading acquisition, providing new insights about the neurophysiological development and a potential marker of later reading problems.

What does the brain of children with developmental dyslexia tell us about reading improvement? ERP evidence from an intervention study.

Intervention is key to managing developmental dyslexia (DD), but not all children with DD benefit from treatment. Some children improve (improvers, IMP), whereas others do not improve (non-improvers, NIMP). Neurobiological differences between IMP and NIMP have been suggested, but studies comparing IMP and NIMP in childhood are missing. The present study examined whether ERP patterns change with treatment and differ between IMP and NIMP. We investigated the ERPs of 28 children with DD and 25 control children (CON) while performing a phonological lexical decision (PLD) task before and after a 6-month intervention. After intervention children with DD were divided into IMP (n = 11) and NIMP (n = 17). In the PLD-task children were visually presented with words, pseudohomophones, pseudowords, and false fonts and had to decide whether the presented stimulus sounded like an existing German word or not. Prior to intervention IMP showed higher N300 amplitudes over fronto-temporal electrodes compared to NIMP and CON and N400 amplitudes were attenuated in both IMP and NIMP compared to CON. After intervention N300 amplitudes of IMP were comparable to those of CON and NIMP. This suggests that the N300, which has been related to phonological access of orthographic stimuli and integration of orthographic and phonological representations, might index a compensatory mechanism or precursor that facilitates reading improvement. The N400, which is thought to reflect grapheme-phoneme conversion or the access to the orthographic lexicon increased in IMP from pre to post and was comparable to CON after intervention. Correlations between N300 amplitudes pre, growth in reading ability and N400 amplitudes post indicated that higher N300 amplitudes might be important for reading improvement and increase in N400 amplitudes. The results suggest that children with DD, showing the same cognitive profile might differ regarding their neuronal profile which could further influence reading improvement.

Specific learning disorder: prevalence and gender differences.

Comprehensive models of learning disorders have to consider both isolated learning disorders that affect one learning domain only, as well as comorbidity between learning disorders. However, empirical evidence on comorbidity rates including all three learning disorders as defined by DSM-5 (deficits in reading, writing, and mathematics) is scarce. The current study assessed prevalence rates and gender ratios for isolated as well as comorbid learning disorders in a representative sample of 1633 German speaking children in 3rd and 4th Grade. Prevalence rates were analysed for isolated as well as combined learning disorders and for different deficit criteria, including a criterion for normal performance. Comorbid learning disorders occurred as frequently as isolated learning disorders, even when stricter cutoff criteria were applied. The relative proportion of isolated and combined disorders did not change when including a criterion for normal performance. Reading and spelling deficits differed with respect to their association with arithmetic problems: Deficits in arithmetic co-occurred more often with deficits in spelling than with deficits in reading. In addition, comorbidity rates for arithmetic and reading decreased when applying stricter deficit criteria, but stayed high for arithmetic and spelling irrespective of the chosen deficit criterion. These findings suggest that the processes underlying the relationship between arithmetic and reading might differ from those underlying the relationship between arithmetic and spelling. With respect to gender ratios, more boys than girls showed spelling deficits, while more girls were impaired in arithmetic. No gender differences were observed for isolated reading problems and for the combination of all three learning disorders. Implications of these findings for assessment and intervention of learning disorders are discussed.

Genetic analysis of dyslexia candidate genes in the European cross-linguistic NeuroDys cohort.

Dyslexia is one of the most common childhood disorders with a prevalence of around 5-10% in school-age children. Although an important genetic component is known to have a role in the aetiology of dyslexia, we are far from understanding the molecular mechanisms leading to the disorder. Several candidate genes have been implicated in dyslexia, including DYX1C1, DCDC2, KIAA0319, and the MRPL19/C2ORF3 locus, each with reports of both positive and no replications. We generated a European cross-linguistic sample of school-age children - the NeuroDys cohort - that includes more than 900 individuals with dyslexia, sampled with homogenous inclusion criteria across eight European countries, and a comparable number of controls. Here, we describe association analysis of the dyslexia candidate genes/locus in the NeuroDys cohort. We performed both case-control and quantitative association analyses of single markers and haplotypes previously reported to be dyslexia-associated. Although we observed association signals in samples from single countries, we did not find any marker or haplotype that was significantly associated with either case-control status or quantitative measurements of word-reading or spelling in the meta-analysis of all eight countries combined. Like in other neurocognitive disorders, our findings underline the need for larger sample sizes to validate possibly weak genetic effects.

The time course of reading processes in children with and without dyslexia: an ERP study.

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.

Separating mismatch negativity (MMN) response from auditory obligatory brain responses in school-aged children.

Mismatch negativity (MMN) overlaps with other auditory event-related potential (ERP) components. We examined the ERPs of 50 9- to 11-year-old children for vowels /i/, /y/ and equivalent complex tones. The goal was to separate MMN from obligatory ERP components using principal component analysis and equal probability control condition. In addition to the contrast of the deviant minus standard response, we employed the contrast of the deviant minus control response, to see whether the obligatory processing contributes to MMN in children. When looking for differences in speech deviant minus standard contrast, MMN starts around 112 ms. However, when both contrasts are examined, MMN emerges for speech at 160 ms whereas for nonspeech MMN is observed at 112 ms regardless of contrast. We argue that this discriminative response to speech stimuli at 112 ms is obligatory in nature rather than reflecting change detection processing.

Predictors of developmental dyslexia in European orthographies with varying complexity.

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.

Automatic integration of auditory and visual information is not simultaneous in Chinese.

ERP studies have revealed that for alphabetic languages letter/speech-sound integration develops with brain maturation and reading instruction over a relatively long period of time. Experienced adult readers associate letters and speech sounds automatically, as indexed by enhanced mismatch negativity (MMN) to simultaneously presented stimuli, but reveal attenuated MMN when the speech sound stimuli are presented with a delay. Chinese as a logographic language differs substantially from alphabetic languages and therefore integration processes might be characterized by unique timing mechanisms. In the present study, MMN was used to investigate the timing and automaticity of association between characters and lexical tones in adult native Chinese speakers. A character was presented simultaneously with a lexical tone, or with either a 100ms stimulus onset asynchrony (SOA) or a 200ms SOA in separate conditions. MMN was enhanced when the character and the lexical tone were presented with 100ms SOA, while no significant MMN enhancement was observed with simultaneous presentation or with 200ms SOA. These results suggest that the automatic association of characters and lexical tones in experienced Chinese adult readers requires more processing time than for alphabetic languages. These results highlight critical differences between fundamental reading processes across different writing systems. The neural differences between alphabetic and logographic languages for letter/character and speech-sound/tone integration need to be taken into consideration when considering past and future research on reading processes in these languages and especially for investigations of reading disorders, such as developmental dyslexia.

Evidence for the late MMN as a neurophysiological endophenotype 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.

N300 indexes deficient integration of orthographic and phonological representations in children with dyslexia.

In transparent orthographies, like German, children with developmental dyslexia (DD) are mainly characterized by a reading fluency deficit. The reading fluency deficit might be traced back to a scarce integration of orthographic and phonological representations. In order to address this question, the present study used EEG to investigate the N300, an ERP component which has been associated with the integration of orthographic and phonological representations. Twenty children without DD and 18 children with DD performed a phonological (P)-orthographic (O) matching task (P-O condition), which tapped the integration of orthographic and phonological representations. A control task was applied which did not require the integration of orthographic and phonological representations and consisted only of orthographic information (O-O condition). The O-O condition revealed a similar N300 distribution between groups with a bilateral activity over fronto-temporal electrodes. However, in the P-O condition N300 differentiated the 2 groups of children. The control group revealed greater activity over left fronto-temporal electrodes, whereas the N300 was distributed bilaterally in the group of children with DD suggesting deficient integration of orthographic and phonological representations. These findings might be related to the reading fluency deficit as it was also observed that better reading fluency was correlated with higher (r=-.36) and earlier peaking (r=-.33) N300 amplitudes in the left hemisphere and attenuated N300 amplitudes (r=.45) in the right hemisphere. Standardized low-resolution electromagnetic tomography analysis (sLORETA) revealed that children with DD rely more on right temporo-parietal brain areas compared to children without DD. Furthermore, in order to rule out that earlier deficient processes might influence the group differences found in the N300, we analyzed the N170 for group differences. We did not find significant differences between children without DD and children with DD. In conclusion the results suggest deficient integration of orthographic and phonological representations in dyslexia, as indexed by the N300, and further highlight how this activity is relevant for fluent reading.

Children with dyslexia reveal abnormal native language representations: evidence from a study of mismatch negativity.

Although a deficit perceiving phonemes, as indexed by the mismatch negativity (MMN), is apparent in developmental dyslexia (DD), studies have not yet addressed whether this deficit might be a result of deficient native language speech representations. The present study examines how a native-vowel prototype and an atypical vowel are discriminated by 9-year-old children with (n = 14) and without (n = 12) DD. MMN was elicited in all conditions in both groups. The control group revealed enhanced MMN to the native-vowel prototype in comparison to the atypical vowel. Children with DD did not show enhanced MMN amplitude to the native-vowel prototype, suggesting impaired tuning to native language speech representations. Furthermore, higher MMN amplitudes to the native-vowel prototype correlated with more advanced reading (r = - .47) and spelling skills (r = - .52).

An investigation of prototypical and atypical within-category vowels and non-speech analogues on cortical auditory evoked related potentials (AERPs) in 9 year old children.

The present study examined cortical auditory evoked related potentials (AERPs) for the P1-N250 and MMN components in children 9 years of age. The first goal was to investigate whether AERPs respond differentially to vowels and complex tones, and the second goal was to explore how prototypical language formant structures might be reflected in these early auditory processing stages. Stimuli were two synthetic within-category vowels (/y/), one of which was preferred by adult German listeners ("prototypical-vowel"), and analogous complex tones. P1 strongly distinguished vowels from tones, revealing larger amplitudes for the more difficult to discriminate but phonetically richer vowel stimuli. Prototypical language phoneme status did not reliably affect AERPs; however P1 amplitudes elicited by the prototypical-vowel correlated robustly with the ability to correctly identify two prototypical-vowels presented in succession as "same" (r=-0.70) and word reading fluency (r=-0.63). These negative correlations suggest that smaller P1 amplitudes elicited by the prototypical-vowel predict enhanced accuracy when judging prototypical-vowel "sameness" and increased word reading speed. N250 and MMN did not differentiate between vowels and tones and showed no correlations to behavioural measures.

Association of a rare variant with mismatch negativity in a region between KIAA0319 and DCDC2 in dyslexia.

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.

Clinical neurophysiology of visual and auditory processing in dyslexia: a review.

Neurophysiological studies on children and adults with dyslexia provide a deeper understanding of how visual and auditory processing in dyslexia might relate to reading deficits. The goal of this review is to provide an overview of research findings in the last two decades on motion related and contrast sensitivity visual evoked potentials and on auditory event related potentials to basic tone and speech sound processing in dyslexia. These results are particularly relevant for three important theories about causality in dyslexia: the magnocellular deficit hypothesis, the temporal processing deficit hypothesis and the phonological deficit hypothesis. Support for magnocellular deficits in dyslexia are primarily provided from evidence for altered visual evoked potentials to rapidly moving stimuli presented at low contrasts. Consistently ERP findings revealed altered neurophysiological processes in individuals with dyslexia to speech stimuli, but evidence for deficits processing certain general acoustic information relevant for speech perception, such as frequency changes and temporal patterns, are also apparent.

Auditory sensory memory and language abilities in former late talkers: a mismatch negativity study.

The present study investigated whether (a) a reduced duration of auditory sensory memory is found in late talking children and (b) whether deficits of sensory memory are linked to persistent difficulties in language acquisition. Former late talkers and children without delayed language development were examined at the age of 4 years and 7 months using mismatch negativity (MMN) with interstimulus intervals (ISIs) of 500 ms and 2000 ms. Additionally, short-term memory, language skills, and nonverbal intelligence were assessed. MMN mean amplitude was reduced for the ISI of 2000 ms in former late talking children both with and without persistent language deficits. In summary, our findings suggest that late talkers are characterized by a reduced duration of auditory sensory memory. However, deficits in auditory sensory memory are not sufficient for persistent language difficulties and may be compensated for by some children.

Variation in GRIN2B contributes to weak performance in verbal short-term memory in children with dyslexia.

A multi-marker haplotype within GRIN2B, a gene coding for a subunit of the ionotropic glutamate receptor, has recently been found to be associated with variation in human memory performance [de Quervain and Papassotiropoulos, 2006]. The gene locus is located within a region that has been linked to a phonological memory phenotype in a recent genome scan in families with dyslexia [Brkanac et al., 2008]. These findings may indicate the involvement of GRIN2B in memory-related aspects of human cognition. Memory performance is one of the cognitive functions observed to be disordered in dyslexia patients. We therefore investigated whether genetic variation in GRIN2B contributes to specific quantitative measures in a German dyslexia sample by genotyping 66 SNPs in its entire genomic region. We found supportive evidence that markers in intron 3 are associated with short-term memory in dyslexia, and were able to demonstrate that this effect is even stronger when only maternal transmission is considered. These results suggest that variation within GRIN2B may contribute to the genetic background of specific cognitive processes which are correlates of the dyslexia phenotype.