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 by which these regions interact to produce controlled behavior. The first set of experiments was designed to test the hypothesis that frontal cortex is hierarchically organized, with progressively more anterior regions processing higher-order representations. According to this hierarchical hypothesis, successive stages of processing lead to increased abstraction and complexity of representation along a posterior-anterior gradient across frontal cortex. This hypothesis will be tested with two paradigms and a variety of approaches: behavioral data from patients with focal PFC lesions, temporary lesions with 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 anterior part of lateral frontal cortex, a region implicated in higher cognition about which relatively little is known. Based on preliminary data, we have argued that this region is involved in the joint consideration of multiple relationships between mental representations - a general function that can be used to compare, evaluate, or integrate across concepts, or to coordinate several ongoing mental processes. A variety of complementary techniques will be used to test whether anterior lateral frontal cortex is sensitive to the need to consider multiple relations between items. Basic knowledge about the functional organization of frontal cortex gained from these proposed studies is of central clinical significance, and can provide substantial insights into the nature of a large number of neurological disorders associated with the frontal lobe dysfunction, such as stroke, traumatic brain injury, and degenerative brain diseases including Parkinson's, Alzheimer's Disease, and frontotemporal dementia.
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