Speech-coding and training-induced plasticity in auditory cortex of normal and dyslexia model rats

The ability to understand auditory stimuli and particularly speech sounds is a complex process involving many brain regions. Communication disorders are among the most common disabilities in the US and affect over 20% of the general population. Understanding the differences in the way the auditory cortex processes speech sounds in individuals with these disorders may elucidate the neural mechanisms behind these disorders and lead to more effective therapies. Dyslexia is the most common developmental language disorder and causes impairments in reading ability in spite of normal non-verbal IQ. Children with dyslexia have difficulty recognizing phonemes: the smallest segment of a word that, if changed, alters the meaning of the word. Dyslexic children also have altered neural responses to short auditory stimuli, such as phonemes or tones. Since humans with dyslexia have complex genetic profiles, the direct link between each of the dyslexia-associated genes and the auditory processing impairments seen in dyslexia cannot be studied in humans and requires the precise control available in animal models. In this dissertation, I document the cortical auditory firing impairments in rats with in utero RNAi of Kiaa0319 , the most well-studied candidate dyslexia gene. We document for the first time, that suppression of a candidate-dyslexia gene causes impaired phoneme processing in multiple auditory fields compared to normal controls. Many studies have shown that abnormal neural firing patterns lead to impairments in comparable behavior tasks. We report here that rats with RNAi of Kiaa0319 also have significant behavioral impairments on phoneme discrimination tasks. Extensive behavioral training can improve speech discrimination accuracy as well as restore neural firing properties to control levels. This result provides the first evidence for a possible neural mechanism that drives improvement in dyslexic children. Finally, in an effort to develop more biologically plausible analysis tools, we also report the development and testing of a new classifier which can use auditory cortex activity to locate and identify the evoking speech stimulus in real time. The results of these studies show that the variants in the candidate dyslexia gene KIAA0319 can cause neural and behavioral impairments in phoneme processing and provide new tools to investigate neural encoding of speech sounds in the normal and abnormal brain.