Identifying Dyslexia: Link between Maze Learning and Dyslexia Susceptibility Gene, DCDC2, in Young Children

Abstract

Dyslexia is a common learning disability that affects processing of written language despite adequate intelligence and educational background. If learning disabilities remain untreated, a child may experience long-term social and emotional problems, which influence future success in all aspects of their life. Dyslexia has a 60% heritability rate, and genetic studies have identified multiple dyslexia susceptibility genes (DSGs). DSGs, such as <i>DCDC2</i>, are consistently associated with the risk and severity of reading disability (RD). Altered neural connectivity within temporoparietal regions of the brain is associated with specific variants of DSGs in individuals with RD. Genetically altering DSG expression in mice results in visual and auditory processing deficits as well as neurophysiological and neuroanatomical disruptions. Previously, we demonstrated that learning deficits associated with RD can be translated across species using virtual environments. In this 2-year longitudinal study, we demonstrate that performance on a virtual Hebb-Williams maze in pre-readers is able to predict future reading impairment, and the genetic risk strengthens, but is not dependent on, this relationship. Due to the lack of oral reporting and use of letters, this easy-to-use tool may be particularly valuable in a remote working environment as well as working with vulnerable populations such as English language learners.

Orthographic Depth May Influence the Degree of Severity of Maze Learning Performance in Children at Risk for Reading Disorder

“…The virtual maze environment and analysis software used to test participants were created using the Unreal Development Kit and Java, respectively, and run on a Dell PC. Previous research from our laboratory suggests that type of computer and/or graphics card did not influence study outcomes [50, 51]. Mazes were displayed at a resolution of 1,600 × 900 in full screen mode.…”

“…Mazes were completed in succession, with 2-min distractor tasks between each maze. We previously demonstrated that the type of distractor task (e.g., puzzle, children’s movie, and reading measure) had no effects on maze performance [50]. The majority of participants completed all reading measures and maze tasks within a single 45-min session, with reading measures conducted between maze tasks.…”

“…Genetic risk was defined as presence of allele 5, microdeletion, and/or ARHQ score ≥0.40. LR was calculated based on PE scores across trials 1–4 [50, 84]. LR represented the degree of PE changed across trials (T): LR = ([PE T1 – PE T2 ] + [PE T2 – PE T3 ] + [PE T3 – PE T4 ])/3.…”

“…In our own research, we have shown that mice with a deletion of exon 2 of dcdc2 have impaired performance on a maze learning task [67], that this behavior could be translated across species using a virtual maze environment [51], that reading impairment was associated with poor maze learning performance in children between 5 and 12 years of age [50, 51], and that genetic risk for RD strengthens the relationship between reading ability and maze performance [50]. However, our research was based on native English-speaking children, and it is unclear whether the results from these studies could be broadly applied to children from other language orthographies.…”

“…Allele 5 is associated with severe RD, allele 6 with severe language impairment, and both disorders are present when the two alleles are combined (i.e., 5_6). Recently, we demonstrated that genetic risk for RD, either based on high familial risk, READ1 allele 5, and/or the microdeletion, was associated with impaired performance on a virtual maze learning task in young children (pre-readers and readers) with reading impairment [50]. A link between reading ability, genetic risk, and this goal-driven activity, which could be translated across species [51], suggests a possible novel approach to early identification of reading impairment.…”