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Role of a candidate-dyslexia gene on rapid auditory processing; insights from comparing a preclinical model to children
Poster B9 in Poster Session B, Friday, October 25, 10:00 - 11:30 am, Great Hall 4
Tracy M Centanni1,2, Logun Gunderson2, Vishal Thakkar2, Monica Parra2, Brad Wilkes1; 1University of Florida, 2Texas Christian University
Despite the knowledge that dyslexia is the most common neurodevelopmental disorder, affecting up to 15% of the population, the interventions that exist do not help all readers achieve fluency. Dyslexia is a polygenic disorder, influenced by several genes that are often non-overlapping across individuals. It is therefore exceedingly difficult to evaluate the role of individual candidate-dyslexia genes on neural plasticity in humans. One of the most well-studied genes implicated in dyslexia is DCDC2, a gene involved in early brain development, amongst other functions throughout the lifespan. In children with dyslexia, this gene is associated with reading speed, working memory, and differences in brain volume. Prior work utilizing rodent models with Dcdc2 manipulation also reported poor working memory and anatomical differences. Our own prior work suggested that this gene may impair rapid perceptual processing, specifically of speech sounds, and may interfere with neural plasticity during training. The first goal of the current study was to expand this work and probe the effects of this gene on 1) anatomy, 2) rapid auditory perception, and 3) plasticity using a novel knockout rat model. Rats with homozygous or heterozygous knockout and their wild-type littermate controls were trained on a rapid speech sound discrimination task previously developed and validated by our group. Auditory evoked potentials were recorded in response to tones and broad band noise burst trains in rats following training (N = 25 across the genotype groups) and in a group of age-matched naïve controls (N = 22 across the genotype groups). Brain tissue was then fixed and extracted prior to undergoing anatomical and diffusion-weighted 17.6T MRI. While we did not observe a specific rapid perception deficit following Dcdc2 knockout, there is an effect of this gene on neural development and response to training. To evaluate the potential translational value of this work, we compared these data to a sample of children with dyslexia, in which rapid stimulus perception was measured and DCDC2 was genotyped. A sample of children between 7-12 years old with (N = 33) and without (N = 33) dyslexia were recruited. Following assessment, they completed several tasks of rapid stimulus processing, including rapid auditory perception (of tones, speech, and consonant-vowel-consonant sounds), rapid visual perception (of letters and shapes), and a visuo-spatial working memory task. All tasks were based on previously validated and published protocols. Saliva samples were mailed to the lab and several variants of interest on DCDC2 were genotyped. In children with dyslexia, we observed a specific deficit in reaction times without a corresponding accuracy hit, in line with the preclinical data. We will highlight the effects of genotype on neural plasticity for tones and noise burst trains and effects of training on the brain in the preclinical model and suggest future directions for translational research into the role of this gene in dyslexia. These findings will be discussed in the context of what we know about this gene in humans with dyslexia and how these preclinical findings may inform our future studies of non-responders to intervention.
Topic Areas: Disorders: Developmental, Genetics