Accumulated evidence suggests that multiple neurologic systems are aberrantly organized in individuals with developmental dyslexia, ranging from developmental anomalies of the neocortex to defects in lower level sensory systems. It is hypothesized that these anomalies are correlated, and further that they influence each other in a top-down manner. Specifically, we hypothesize that early focal neocortical injury sets into motion a cascade of events that results in the disruption of connectionally-related anatomic structures - a disruption that may in turn lead to defects in the function of fast components of primary sensory systems. The proposed set of experiments will explore the anatomic substrates of developmental dyslexia - a uniquely human disorder - with an animal model of neonatal focal neocortical damage. This animal model involves the induction of focal neuronal migration disorders by small freezing lesions to the developing cortical plate of the rat. These lesions result in the formation of an area of dysgenetic cortex resembling 4-layered microgyria, and are associated with fast component temporal processing deficits in this animal. It is the goal of this proposal to investigate how early neocortical damage might affect the organization of the developing brain connectionally and cytoarchitectonically, and how to ameliorate the anatomic effects of early brain injury. Specifically, we will attempt to determine (1) the effects of neonatal neocortical injury in different locations on neuronal connectivity of the rat, first by examining connections in adulthood and then by determining their formation developmentally; (2) the effects of neonatal neocortical injury on the volumetric and cellular morphometry of connectionally-related and - unrelated cortical and subcortical regions by measuring architectonic volume, neuronal size and density, and neuronal activation; (3) whether the reported amelioration of behavior by enrichment is associated with changes in the volumetric, connectional, and morphometric characteristics of the brain, and (4) the effects of age of lesion on the formation developmental cortical anomalies.
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