Background --Researchers have long debated whether knowledge about the self is unique in terms of its functional anatomic representation within the human brain. In experimental psychology, the debate has centered on two main issues. Is the self a unique cognitive structure? Does self-referential processing have some privileged status in the brain, or is it functionally equivalent to semantic processing about other classes of stimuli, such as cars, politicians, and Caribbean islands? Behaviorally, knowledge about the self is typically remembered better than other types of semantic information. But why does this memorial effect emerge? Our prior research shows that self-referential memory enhancement is associated with specific activation of medial prefrontal cortex. Specific Aims --The overall goal of the proposed research is to establish an interdisciplinary program involving research and training in social cognitive neuroscience. Working together, our team of cognitive neuroscientists and social psychologists will investigate potential neural substrates of self-referential processing using functional magnetic resonance imaging (fMRI). Methods --Experiments are proposed to better understand the contributions of regjons within prefrontal cortex to aspects of the mental representation of self. Specific studies will seek to: (1) better understand the neural basis for the memory enhancement afforded to material processed in a self-referential manner, (2) determine whether knowledge about the self shares the same neural architecture as knowledge about intimate others (e.g. a parent or best friend), and (3) identify potential differences in the functional anatomic representation of "self" across cultures that may place differential emphasis on the family as part of one's individual concept of self. A series of fMRI studies will address these issues. Significance --These studies will provide important insights into the specific cognitive operations engaged by brain regions during self-referential processing. Such insight may ultimately aid in the understanding and development of more effective cognitive rehabilitation strategies for the treatment of mood and personality disorders.