Development and standardization of the DALI-DAB (dyslexia assessment for languages of India - dyslexia assessment battery).

A majority of Indian schoolchildren are biliterate in that they acquire literacy in at least two language systems, necessitating dyslexia assessment in both. The DALI-DAB assesses risk for dyslexia by evaluating reading ability and literacy-learning potential through a battery including literacy tests (letter and word reading, spelling, nonword reading, reading comprehension), and mediator skills (phonological awareness, processing automaticity and executive fluency, oral language) in multiple languages. DALI-DAB was developed in three languages - English, Hindi, and Marathi - and standardized on a sample of 1013 children. Reliability analyses revealed high internal consistency (α > 0.8) in most tests in all three languages. Low standard error of measurement values supported DALI-DAB score stability over repeated testing. Construct validity was variously reinforced through, (i) selection of culture-referenced, research-based tests, (ii) approval of test materials by schoolteachers (face validity) and (iii) grade-correlated performance increases on all DALI-DAB tests, besides robust correlations between (iv) literacy and mediator skill test scores (p < .001, concurrent validity), (v) equivalent tests across languages (p < .01, convergent validity), and (vi) DALI-DAB and WJ III ACH literacy scores (p < .01, criterion validity), in contrast to (vii) low correlation between DALI-DAB and WJ III ACH math scores (p > .05, discriminant validity). Overall, the DALI-DAB represents the first standardized dyslexia assessment tool for bilingual-biliterate children.

Autistic traits and individual brain differences: functional network efficiency reflects attentional and social impairments, structural nodal efficiencies index systemising and theory-of-mind skills.

BACKGROUND: Autism is characterised not only by impaired social cognitive 'empathising' but also by superior rule-based 'systemising'. These cognitive domains intertwine within the categorical diagnosis of autism, yet behavioural genetics suggest largely independent heritability, and separable brain mechanisms. We sought to determine whether quantitative behavioural measures of autistic traits are dimensionally associated with structural and functional brain network integrity, and whether brain bases of autistic traits vary independently across individuals. METHODS: Thirty right-handed neurotypical adults (12 females) were administered psychometric (Social Responsiveness Scale, Autism Spectrum Quotient and Systemising Quotient) and behavioural (Attention Network Test and theory-of-mind reaction time) measures of autistic traits, and structurally (diffusion tensor imaging) and functionally (500 s of 2 Hz eyes-closed resting fMRI) derived graph-theoretic measures of efficiency of information integration were computed throughout the brain and within subregions. RESULTS: Social impairment was positively associated with functional efficiency (r = .47, p = .006), globally and within temporo-parietal and prefrontal cortices. Delayed orienting of attention likewise was associated with greater functional efficiency (r = - .46, p = .0133). Systemising was positively associated with global structural efficiency (r = .38, p = 0.018), driven specifically by temporal pole; theory-of-mind reaction time was related to structural efficiency (r = - .40, p = 0.0153) within right supramarginal gyrus. LIMITATIONS: Interpretation of these relationships is complicated by the many senses of the term 'connectivity', including functional, structural and computational; by the approximation inherent in group functional anatomical parcellations when confronted with individual variation in functional anatomy; and by the validity, sensitivity and specificity of the several survey and experimental behavioural measures applied as correlates of brain structure and function. CONCLUSIONS: Functional connectivities highlight distributed networks associated with domain-general properties such as attentional orienting and social cognition broadly, associating more impaired behaviour with more efficient brain networks that may reflect heightened feedforward information flow subserving autistic strengths and deficits alike. Structural connectivity results highlight specific anatomical nodes of convergence, reflecting cognitive and neuroanatomical independence of systemising and theory-of-mind. In addition, this work shows that individual differences in theory-of-mind related to brain structure can be measured behaviourally, and offers neuroanatomical evidence to pin down the slippery construct of 'systemising' as the capacity to construct invariant contextual associations.

A pilot Indian family-based association study between dyslexia and Reelin pathway genes, DCDC2 and ROBO1, identifies modest association with a triallelic unit TAT in the gene RELN.

Dyslexia is a neurodevelopmental disorder that manifests as a reading disability despite normal intelligence and adequate educational opportunity. Twin and family studies have indicated a genetic component, while genome-wide studies have implicated a number of susceptibility genes, most of which have direct or indirect roles in neuronal migration. Reelin (RELN) has important biological functions facilitating migration of neurons. Polymorphisms in RELN have been implicated in related disorders like autism and schizophrenia but have not been examined in dyslexia. We hypothesized that not only RELN, but its interactors in the neuronal migration pathway may play roles in the etiology of dyslexia. Twenty two functional variants across six RELN signalling genes (RELN, VLDLR, APOER2, DAB1, LIS1 and NDEL1) and two dyslexia candidate genes (DCDC2 and ROBO1) were analyzed for association in twenty six nuclear and three extended families with individuals affected with dyslexia. Univariate association analysis was suggestive of association (puncorrected = 0.01) with rs362746 in RELN which however did not withstand Bonferroni corrections (pcorrected = 0.21). Multimarker tests indicated significant association (p = 0.037), based on which we tested for haplotype associations. Although there were no significant haplotypic associations, we found that a three marker unit with rs3808039 and rs2072403 flanking and independently in linkage disequilibrium with rs362746 was significantly overtransmitted (risk allelic combination - TAT) to dyslexia affected individuals in the sample (p = 0.002). Our results suggest preliminary evidence for a new potential risk variant in the RELN locus for dyslexia.

Ancestral Variations of the PCDHG Gene Cluster Predispose to Dyslexia in a Multiplex Family.

Dyslexia is a heritable neurodevelopmental disorder characterized by difficulties in reading and writing. In this study, we describe the identification of a set of 17 polymorphisms located across 1.9Mb region on chromosome 5q31.3, encompassing genes of the PCDHG cluster, TAF7, PCDH1 and ARHGAP26, dominantly inherited with dyslexia in a multi-incident family. Strikingly, the non-risk form of seven variations of the PCDHG cluster, are preponderant in the human lineage, while risk alleles are ancestral and conserved across Neanderthals to non-human primates. Four of these seven ancestral variations (c.460A>C [p.Ile154Leu], c.541G>A [p.Ala181Thr], c.2036G>C [p.Arg679Pro] and c.2059A>G [p.Lys687Glu]) result in amino acid alterations. p.Ile154Leu and p.Ala181Thr are present at EC2: EC3 interacting interface of γA3-PCDH and γA4-PCDH respectively might affect trans-homophilic interaction and hence neuronal connectivity. p.Arg679Pro and p.Lys687Glu are present within the linker region connecting trans-membrane to extracellular domain. Sequence analysis indicated the importance of p.Ile154, p.Arg679 and p.Lys687 in maintaining class specificity. Thus the observed association of PCDHG genes encoding neural adhesion proteins reinforces the hypothesis of aberrant neuronal connectivity in the pathophysiology of dyslexia. Additionally, the striking conservation of the identified variants indicates a role of PCDHG in the evolution of highly specialized cognitive skills critical to reading.

Fronto-temporal connectivity is preserved during sung but not spoken word listening, across the autism spectrum.

Co-occurrence of preserved musical function with language and socio-communicative impairments is a common but understudied feature of Autism Spectrum Disorders (ASD). Given the significant overlap in neural organization of these processes, investigating brain mechanisms underlying speech and music may not only help dissociate the nature of these auditory processes in ASD but also provide a neurobiological basis for development of interventions. Using a passive-listening functional magnetic resonance imaging paradigm with spoken words, sung words and piano tones, we found that 22 children with ASD, with varying levels of functioning, activated bilateral temporal brain networks during sung-word perception, similarly to an age and gender-matched control group. In contrast, spoken-word perception was right-lateralized in ASD and elicited reduced inferior frontal gyrus (IFG) activity which varied as a function of language ability. Diffusion tensor imaging analysis reflected reduced integrity of the left hemisphere fronto-temporal tract in the ASD group and further showed that the hypoactivation in IFG was predicted by integrity of this tract. Subsequent psychophysiological interactions revealed that functional fronto-temporal connectivity, disrupted during spoken-word perception, was preserved during sung-word listening in ASD, suggesting alternate mechanisms of speech and music processing in ASD. Our results thus demonstrate the ability of song to overcome the structural deficit for speech across the autism spectrum and provide a mechanistic basis for efficacy of song-based interventions in ASD.