Dyslexia risk gene relates to representation of sound in the auditory brainstem

Abstract

Dyslexia is a reading disorder with strong associations with KIAA0319 and DCDC2. Both genes play a functional role in spike time precision of neurons. Strikingly, poor readers show an imprecise encoding of fast transients of speech in the auditory brainstem. Whether dyslexia risk genes are related to the quality of sound encoding in the auditory brainstem remains to be investigated. Here, we quantified the response consistency of speech-evoked brainstem responses to the acoustically presented syllable [da] in 159 genotyped, literate and preliterate children. When controlling for age, sex, familial risk and intelligence, partial correlation analyses associated a higher dyslexia risk loading with KIAA0319 with noisier responses. In contrast, a higher risk loading with DCDC2 was associated with a trend towards more stable responses. These results suggest that unstable representation of sound, and thus, reduced neural discrimination ability of stop consonants, occurred in genotypes carrying a higher amount of KIAA0319 risk alleles. Current data provide the first evidence that the dyslexia-associated gene KIAA0319 can alter brainstem responses and impair phoneme processing in the auditory brainstem. This brain-gene relationship provides insight into the complex relationships between phenotype and genotype thereby improving the understanding of the dyslexia-inherent complex multifactorial condition.

Neural Noise Hypothesis of Developmental Dyslexia

“…An increasing number of studies have investigated the function of RD risk genes in animal models [2–13], and the neurobiological and behavioral consequences of RD risk variants in humans [14–31], motivating the need for a synthesis of these findings, especially as they relate to emerging avenues of human research on the role of neurochemistry [32] and neural oscillations [33–36] in RD. We present a timely integration of diverse lines of current research linking some of the key neural and behavioral deficits associated with RD to basic neural processes.…”

“…An important test for our hypothesis is whether similar loss of response consistency is present in humans carrying RD risk alleles. In the only study [31] to examine association between RD risk genes and the consistency of human neural responses to auditory stimuli, KIAA0391 risk alleles were associated with less consistent auditory brainstem responses (ABRs) in preliterate children. In the same study, DCDC2 risk alleles were associated with a trend towards more stable ABRs.…”

Neural Noise Hypothesis of Developmental Dyslexia

“…An important test for our hypothesis is whether similar loss of response consistency is present in humans carrying RD risk alleles. In the only study [31] to examine the association between RD risk genes and the consistency of human neural responses to auditory stimuli, KIAA0391 risk alleles were associated with less-consistent auditory brainstem responses (ABRs) in preliterate children. In the same study, DCDC2 risk alleles were associated with a trend towards more stable ABRs.…”

“…An increasing number of studies have investigated the function of RD risk genes in animal models [2][3][4][5][6][7][8][9][10][11][12][13], and the neurobiological and behavioral consequences of genetic RD risk variants in humans [14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31], motivating the need for a synthesis of these findings, especially because they relate to emerging avenues of human research on the role of neurochemistry [32] and neural oscillations [33][34][35][36] in RD. Here, we present a timely integration of diverse lines of current research linking some of the key neural and behavioral deficits associated with RD to basic neural processes.…”

Towards Language Independent Detection of Dyslexia with a Web-based Game

“…A recent study found evidence that dyslexia-associated genes are related to the encoding of sounds in the auditory brainstem [18].However, there are musicians with dyslexia which scored better on auditory perception tests than the general population [17]. At the same time, these participants score worse on tests of auditory working memory, i.e., the ability to keep a sound in mind for seconds.…”