This study examines whether the cognitive and affective components of self-reflection can be dissociated using functional magnetic resonance imaging. Using a simple paradigm in which subjects judged the personal relevance of personality characteristics that were either favorable (e.g., “honest”) or unfavorable (e.g., “lazy”, we found that distinct neural circuits in adjacent regions of the prefrontal cortex subserve cognitive and emotional aspects of self-reflection. The medial prefrontal cortex responded only to material that was self-descriptive, and this did not differ as a function of the valence of the trait. When material was judged to be self-relevant, the valence of the material was resolved in an adjacent region of ventral anterior cingulate. The nature of self is one of the most enduring questions in science, and researchers are now beginning to be able to decompose the neural operations that give rise to a unitary sense of self.

Researchers have long debated whether knowledge about the self is unique in terms of its functional anatomic representation within the human brain. In the context of memory function, knowledge about the self is typically remembered better than other types of semantic information. But why does this memorial effect emerge? Extending previous research on this topic (see Craik et al., 1999), the present study used event-related functional magnetic resonance imaging to investigate potential neural substrates of self-referential processing. Participants were imaged while making judgments about trait adjectives under three experimental conditions (self-relevance, other-relevance, or case judgment). Relevance judgments, when compared to case judgments, were accompanied by activation of the left inferior frontal cortex and the anterior cingulate. A separate region of the medial prefrontal cortex was selectively engaged during self-referential processing. Collectively, these findings suggest that self-referential processing is functionally dissociable from other forms of semantic processing within the human brain.

Neuroimaging studies have suggested that specific regions of the frontal and medial temporal cortex are engaged during memory formation. Further, there is specialization across these regions such that verbal materials appear to preferentially engage the left regions while nonverbal materials primarily engage the right regions. An open question, however, has been to what extent frontal regions contribute to successful memory formation. The present study investigates this question using a reversible lesion technique known as the Wada test. Patients memorized words and unfamiliar faces while portions of their left and right hemispheres were temporarily anesthetized with sodium amytal. Subsequent memory tests revealed that faces were remembered better than words following left-hemisphere anesthesia, whereas words were remembered better than faces following right-hemisphere anesthesia. Importantly, inspection of the circulation affected by the amytal further suggests that these memory impairments did not result from direct anesthetization of the medial temporal regions. Taken in the context of the imaging findings, these results suggest that frontal regions may also contribute to memory formation in normal performance.