Speech sound processing deficits and training-induced neural plasticity in rats with dyslexia gene knockdown.

Tracy M Centanni,Joseph J Loturco,Anne M Booker,Fuyi Chen,Michael P Kilgard,Andrew M Sloan,Robert L Rennaker,Crystal T Engineer

doi:10.1371/journal.pone.0098439

Tracy M Centanni, Joseph J Loturco + Show 6 more

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https://doi.org/10.1371/journal.pone.0098439

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Abstract

In utero RNAi of the dyslexia-associated gene Kiaa0319 in rats (KIA-) degrades cortical responses to speech sounds and increases trial-by-trial variability in onset latency. We tested the hypothesis that KIA- rats would be impaired at speech sound discrimination. KIA- rats needed twice as much training in quiet conditions to perform at control levels and remained impaired at several speech tasks. Focused training using truncated speech sounds was able to normalize speech discrimination in quiet and background noise conditions. Training also normalized trial-by-trial neural variability and temporal phase locking. Cortical activity from speech trained KIA- rats was sufficient to accurately discriminate between similar consonant sounds. These results provide the first direct evidence that assumed reduced expression of the dyslexia-associated gene KIAA0319 can cause phoneme processing impairments similar to those seen in dyslexia and that intensive behavioral therapy can eliminate these impairments.

Highlights

Dyslexia is the most common developmental language disorder and affects approximately 7% of the population [1,2]
Since ADHD and dyslexia have high comorbidity in humans, we evaluated response latency across groups to ensure that RNA interference (RNAi) of Kiaa0319 did not cause hyperactivity
Though on the first day of training, KIA- animals responded significantly faster, the groups were not significantly different on any other training day (Figure S2B). These results suggest that the assumed in utero knockdown of Kiaa0319 does not cause significant hyperactivity, impulsivity, motor problems, or difficulty hearing speech sounds

Summary

Introduction

Dyslexia is the most common developmental language disorder and affects approximately 7% of the population [1,2] Individuals with this disorder have normal nonverbal intelligence, but score more than a standard deviation below their peers on reading tests [1,3,4]. The observation that variants in KIAA0319 impair speech evoked cortical activity [21] and cause poor speech perception and reading ability [19,22] is consistent with the earlier hypothesis that phonological processing is a core deficit in dyslexia [23,24,25,26,27,28,29,30]. Kiaa0319 RNAi duplicates corpus callosum abnormalities in dyslexia [23,32,33] without changing body weight or the volume of the cortex and hippocampus [34]

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