BEHAVIOR: DEVELOPMENTAL CORTICAL INJURY /PROCESSING

Beth Israel Deaconess Medical Center, Boston MA

Investigators

Linked publications & trials

Abstract

DESCRIPTION (provided by applicant): The central hypothesis of the current Program Project application is that focal developmental malformations of cortex, such as induced microgyria, alter forebrain circuitry during critical periods of development thus disrupting perceptual and cognitive processing later in life. To test this hypothesis, we propose a series of studies that will explore relationships between neonatally induced cerebrocortical microgyria (similar to microgyria seen post mortem in the brains of dyslexics), rapid auditory processing deficits (as evidenced in clinically language-disabled populations), and cognitive and memory deficits (which may parallel higher-order processing anomalies seen in language disabled populations, e.g., in verbal/working memory). A connection between cerebrocortical microgyria and auditory processing deficits has been repeatedly demonstrated in a rat model, and a relationship between focal malformations of cortex and cognitive/memory deficits is supported by evidence that learning and memory indices are affected by cortical ectopias in mice. On a broader scale, we will address issues of causality using this rodent model. Assessment of causality represents in turn a major strength of animal models over human clinical and imaging studies, which are often restricted to correlational approaches (given ethical limitations on experimental intervention with humans). In using a rodent model, we can experimentally manipulate variables including parameters of early brain injury (i.e., timing, location and severity), as well as early hormonal, pharmacological and sensory exposure and can examine how these factors influence the relationship between early focal brain injury and various behavioral outcomes, both across development and in adulthood. An over-arching consideration in synthesizing collective data obtained will be to assess its compatibility with top-down versus bottom-up neurodevelopmental models, as well as to consider the possibility that portions of our findings will be consistent with both. At the conclusion of the proposed projects, we hope to have data regarding: how early focal injury of cortex developmentally propagates to other regions of cerebral cortex and other distal structures (such as thalamic nuclei); how such changes are functionally related to different patterns of processing deficits; how such changes are developmentally influenced by other factors such as hormonal exposure and sensory experience; and what developmental timeframes mediate this process. Such findings in turn may provide critical insights into neurobiological mechanisms that underlie some of the processing deficits associated with developmental disabilities of language.