No two children have the same genetic profile, save for monozygotic twins. Few speech and communication disorders are due to a single gene. This branch of my program currently focuses on dyslexia and aims to determine how each candidate gene contributes to the broader phenotype. Rats are surprisingly good at discriminating human speech sounds on the basis of initial consonant, middle vowel, and speaker identity or gender. Their thresholds on these tasks in background noise, spectral or temporal degradation, and at various speeds match what we see in humans. This behavioral control, along with the ability to manipulate individual genes and record directly from cortex, makes rats a good model to begin unpacking the role of individual dyslexia genes.
The candidate dyslexia gene KIAA0319 is involved in neural migration but its role in causing dyslexia is unknown. Previous work has suggested that some individuals with dyslexia may have auditory processing impairments (Shulte-Korne et al., 1999). To evaluate whether this gene alters the basic perception of sound, we recorded auditory cortex responses to speech and non-speech sounds in rats with RNA interference of this gene. We found that reduced expression of the rat homolog of KIAA0319 (Kiaa0319) causes the brain to respond with inconsistent timing to the onset of auditory stimuli and causes speech sound identification deficits in rats. Following behavioral training, however, neural variability and consonant encoding precision in these animals returned to control levels, demonstrating the presence of plasticity even in a genetically manipulated model.
- TM Centanni, F Chen, CT Engineer, AB Booker, RL Rennaker, JJ LoTurco, MP Kilgard (2014). Speech sound processing deficits and training-induced neural plasticity in rats with dyslexia gene knockdown, PLOS one; 9(5): e98439. doi: 10.1371/journal.pone.0098439.
- TM Centanni, AB Booker, AM Sloan, F Chen, BJ Maher, RS Carraway, N Khodaparast, JJ LoTurco, MP Kilgard (2014). Knockdown of the Dyslexia-Associated Gene Kiaa0319 Impairs Temporal Responses to Speech Stimuli in Rat Primary Auditory Cortex, Cerebral Cortex; 24(7): 1753-66.
Another gene commonly associated with dyslexia is DCDC2. This gene is also involved in neural migration and is located right next to KIAA0319 on chromosome 6. To determine whether this gene has a similar role in auditory processing, we evaluated several groups of rats with in utero RNAi of the rat homolog of this gene (Dcdc2). In contrast to Kiaa0319, suppression of Dcdc2 did not cause neural inconsistency nor did it cause impaired phoneme discrimination in quiet or in background noise. Instead, these rats had a severe impairment in discrimination of rapidly presented speech. This impairment could not be accounted for by phase locking in primary auditory areas, suggesting that this impairment is due to some abnormality in a higher cortical region.
- TM Centanni, AB Booker, F Chen, AM Sloan, RS Carraway, RL Rennaker, JJ LoTurco, MP Kilgard (2016). Knockdown of dyslexia-gene Dcdc2 interferes with rapid speech sound discrimination. The Journal of Neuroscience. 36(17):4895:4906.