Dyslexia and language learning disorders have been separately associated with both alterations in neocortical function and with focal neocortical malformations. Similar developmental malformations in animal models have been associated with alterations in behavioral and neurophysiological responses to auditory stimuli. A remaining question is how are focal cortical malformations causally related to these impairments. The overall hypothesis of this project is that focal cortical malformations, such as microgyria and ectopias, alter cortical excitability during critical periods in development and, thereby, disrupt the normal pattern of synaptic plasticity necessary to establish normal circuitry and sensory processing. We propose to use electrophysiology to determine how focal cortical malformations alter the pattern of synaptic plasticity in sensory neocortex and how this altered plasticity leads to disrupted cortical responses to sensory stimuli. In particular, we will determine the time course of plasticity alterations, shown in preliminary data to occur in auditory neocortex. We will determine whether changes in synaptic plasticity occur in visual cortex, too. We will determine whether there is a gender difference in response to malformations. Finally, we will determine whether alterations in auditory sensory experience, deprivation, and enrichment modify the shift in cortical plasticity that is altered by microgyria. Results from this study may lead to insight into the pathophysiology associated with neocortical malformations and may suggest methods of intervention to limit the development of neurological impairments caused by focal neocortical malformations.
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