The broad goal of Project 1 is to advance understanding of the organization of lateral frontal cortex,both in terms of the regional distinctions that define its functional topography and the principles bywhich these regions interact to produce controlled behavior. The first set of experiments wasdesigned to test the hypothesis that frontal cortex is hierarchically organized, with progressively moreanterior regions processing higher-order representations. According to this hierarchical hypothesis,successive stages of processing lead to increased abstraction and complexity of representation alonga posterior-anterior gradient across frontal cortex. This hypothesis will be tested with two paradigmsand a variety of approaches: behavioral data from patients with focal PFC lesions, temporary lesionswith transcranial magnetic stimulation, intracortical recordings in humans prior to epilepsy surgery,and fMRI studies in adults and children. The second set of experiments focuses on the most anteriorpart of lateral frontal cortex, a region implicated in higher cognition about which relatively little isknown. Based on preliminary data, we have argued that this region is involved in the jointconsideration of multiple relationships between mental representations - a general function that canbe used to compare, evaluate, or integrate across concepts, or to coordinate several ongoing mentalprocesses. A variety of complementary techniques will be used to test whether anterior lateral frontalcortex is sensitive to the need to consider multiple relations between items. Basic knowledge aboutthe functional organization of frontal cortex gained from these proposed studies is of central clinicalsignificance, and can provide substantial insights into the nature of a large number of neurologicaldisorders associated with the frontal lobe dysfunction, such as stroke, traumatic brain injury, anddegenerative brain diseases including Parkinson's, Alzheimer's Disease, and frontotemporaldementia.
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