William M. Kelley - US grants

[unreadable] DESCRIPTION (provided by applicant): 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.

Neuropsychological and functional neuroimaging studies have suggested that specific regions of frontal and medial temporal cortex are engaged during episodic memory formation. Further, there is specialization across these regions such that verbal materials appear to preferentially engage left regions while nonverbal materials primarily engage right regions. These hemispheric differences likely reflect lateralization of the verbal and nonverbal processing mechanisms used to memorize different kinds of information. An open question, however, has been how each of these regions specifically contributes to the formation of a memory. The overall goal of the proposed research is to characterize the involvement of specific brain regions in episodic memory formation using functional magnetic resonance imaging (fMRI). Specifically, experiments are proposed to better understand the contributions of dorsal frontal cortex and the hippocampal formation to aspects of episodic encoding. Experiments are proposed to: (1) better characterize the contributions of left and right dorsal frontal cortex during memory encoding, and (2) better understand the functional role of the hippocampal formation during memory encoding. For example, does left dorsal frontal activity reflect access to phonological information (i.e. a verbal label) or more general semantic information? Is the right-sided `nonverbal' activity specific to visually-presented materials, or can it be evoked for materials presented in other sensory modalities (e.g. sounds)? Is hippocampal activity more sensitive to the novelty of individual items or the relationship between items? A series of fMRI studies will address these issues. Taken together, these studies will provide important insights into the specific cognitive operations engaged by frontal and medial temporal brain regions during memory formation. Such insight may ultimately aid in the development of more effective cognitive rehabilitation strategies for the treatment of brain injury.

Understanding the nature of self is central to many areas of psychology, and evidence from multiple domains suggests that information about one's self is processed in a substantially different manner than information about others. For example, information about the perceiver receives preferential attention, such as when people hear their names across noisy rooms. There is also a selective memory advantage for stimuli evaluated with reference to the self, as when a listener remembers words better if asked about how well the words described him or herself as compared to someone else. Initial studies have identified a number of central midline brain structures, notably the medial prefrontal cortex, posterior cingulate cortex, and ventral anterior cingulate cortex that are active in various aspects of self-representation. For instance, people differ in how they view themselves, with some people generally favorable (i.e., those with high self-esteem) and others generally more negative (low self-esteem). With support from the National Science Foundation, Dr. William Kelley and colleagues at Dartmouth College will use functional magnetic resonance imaging (fMRI) and anatomy-based diffusion tensor imaging (DTI) to examine individual differences in how people process information about the self. An innovative feature of this research is the use of a hybrid state-item brain imaging design that allows for an independent assessment of how temporary changes in mood influence the way that individuals evaluate themselves on a moment-to-moment basis. Individual differences in brain patterns for well-known perceptual effects (e.g., flicker fusion for visually presented checker-board patterns) will be compared with more self-related tasks (e.g., judging the relevance of words to describe a person). Here, there must be individual differences, so contrasting those differences with what should be fairly stable patterns will allow a better sense of what the imaging results can tell us.

This line of inquiry will provide insights into the brain regions that support a unified representation of self. A better understanding of the specific roles of brain regions involved in the mental representation of self should aid in understanding variations in self, such as age-related changes in self-awareness and how various disease processes might affect how people process information about the self. This research will also explore the effectiveness of hybrid brain imaging designs for studying the beneficial effects of social and affective components of human cognition. The current project helps to enhance and sustain an interdisciplinary collaboration between social psychology, affective neuroscience, and cognitive neuroscience that has been developing at Dartmouth College. It does so by a training program in which undergraduate and graduate students in the laboratories of the investigators receive training in multiple domains: social psychology, emotion, cognition, and neuroscience.

Project Summary How the self is experienced is central to healthy emotional functioning as well as many disturbances in psychological functioning. This competing renewal uses structural, functional, and resting-state neuroimaging, coupled with passive smartphone sensing technology and ecological momentary assessments, to examine the affective components of self. Understanding the factors that contribute to changes in the affective aspects of self that result from environmental stressors has the potential to provide important insights into the development of mental disorders and help identify individuals who might be in greatest need of early intervention or treatment. Research findings during the prior two award periods (R01 MH059282) revealed several key brain regions involved in processing information related to self. Moreover, we discovered that structural and functional connectivity between these regions and other brain regions known to be involved in emotional processes are associated with measures of self-affect. The overarching goal of this research is to examine how brain connectivity and activity is related to change in subjective distress and associated functional impairment. An exciting aspect of the proposed work is that we will take advantage of the university setting to follow a large cohort of participants over their four years of college to assess how changes in self- affect are predicted by relevant brain networks as well as how those networks change over time. Tasks assessing self-affect will be performed during scanning. Given that approximately 30% of participants are likely to develop a significant subjective distress, one goal is to examine whether there are biomarkers that predict these outcomes. Additional scanning studies will induce interpersonal distress to examine the temporary inductions of affect on task performance. This project will use recently developed applications of network analysis to assess resting state connectivity in brain circuitry and its relation to self-affect and health- relevant outcomes. The guiding hypothesis of this research is that individual differences in the integrity of these networks can predict individual differences in vulnerability to stress and their relation to self-affect. The specific aims of the study are: (1). Characterize neural networks that give rise to self-affect using diffusion tensor imaging, resting state functional connectivity, and task-related functional imaging. In addition, multivariate pattern analysis and representation similarity analysis will be used to classify participants as having high or low self-affect (e.g., self-esteem, depression, anxiety); (2). Examine how changes in self-affect that occur over time are reflected by changes within relevant brain networks and are predicted by baseline network connectivity; and (3). Examine how induced interpersonal distress impacts self-affect and related functional connectivity across networks. Understanding the factors that contribute to changes in self-affect that result from environmental stressors has the potential to provide important insights into the development of mental disorders and help identify individuals who might be in greatest need of early intervention or treatment.