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Poster B24, Tuesday, August 20, 2019, 3:15 – 5:00 pm, Restaurant Hall

Dyslexia risk children with different forms of ROBO1 gene differ in their cortical representation of new phonological word forms

Anni Nora1, Hanna Renvall1, Miia Ronimus2, Heikki Lyytinen3, Juha Kere4, Riitta Salmelin1;1Department of Neuroscience and Biomedical Engineering, and Aalto Neuroimaging, Aalto University, 2Niilo Mäki Institute, Jyväskylä, Finland, 3Jyväskylä University, Finland, 4Karolinska Institutet, Stockholm

Dyslexia, or reading disorder, is the most common learning disability world-wide, affecting 5-10% of school-age children and ranging from mild to severe. The underlying problems lie in phonological processing and learning. Several dyslexia candidate genes have been identified, with effects on brain structure. However, few studies have examined the effects of these genes on brain function in phonological processing. One of these genes, ROBO1, is an axon guidance gene that controls the development of the corpus callosum and has been linked to white and grey matter volume of the posterior corpus callosum and parietal cortices. ROBO1 is also implicated in pseudoword repetition performance, auditory response strength and interaction of the left and right cortices in auditory processing. Therefore, it is a good candidate gene for identifying different subgroups of dyslexics who might differ in phonological processing and learning, and in the interplay of the left and right auditory cortices that underlies the development of phonological processing. To tap the underlying phonological problems, we utilized pseudoword repetition, which has been shown to be an efficient paradigm in dissociating between dyslexic and non-reading-impaired individuals. Children on the first grade of elementary school, with high risk for dyslexia, were identified based on their performance in learning letter-sound-correspondences in a version of the GraphoGame and invited to further cognitive and reading tests, genetic mapping and brain imaging sessions. The control group consisted of children from the same classrooms. The participants were 28 dyslexia risk and 20 control children, with equal sex and age distribution in the two groups. Based on identification of the ROBO1 (3p12) gene allele in snp rs6770755 (GG vs AA/GA), the dyslexia risk group was further divided in half into two haplotype subgroups. We measured cortical responses with magnetoencephalography (MEG) while the children performed delayed overt repetition of four-syllable pseudowords. Half of the word forms were repeated four times during the first session and again on the following day, along with new words. Learning of the repeated pseudowords, without meanings attached, was measured with repetition and recognition accuracy. The dyslexia risk children improved in the overt repetition but were poorer in explicit recognition of the recurring word forms, despite showing normal-range nonverbal intelligence and associative learning task performance similar to the control group. In the auditory cortices, only the control group showed reduced left temporal activation for recurring pseudowords 400-800 ms after word onset, possibly related to more efficient left-hemispheric phonological processing and better explicit memory for the newly-learned word forms. Both groups showed a similar effect in the right temporal areas. In the comparison of different haplotype groups, dyslexics with the risk haplotype (AA/GA) did not show systematic cortical effects. In contrast, the GG-type children showed a right-hemispheric reduction of activation for the recurring word forms. Dyslexia risk children with this genotype may thus be able to compensate for the deficient left-hemispheric phonological memory with right-hemispheric processes. The results are unique in highlighting the interplay of the left and right auditory cortices in phonological development and dyslexia.

Themes: Language Genetics, Disorders: Developmental
Method: Functional Imaging

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