DESCRIPTION (provided by applicant): Future-oriented thoughts occupy a prominent position in spontaneous mental activity. They serve an important adaptive function, in that they enable us to represent multiple hypothetical outcomes and act in light of those anticipated outcomes. A future-oriented thinking style has been linked with general wellbeing and correlates with optimism and resilience. Despite the importance of future thinking to psychology and other domains where beliefs about future outcomes are central to behavior, such as health and economics, our understanding of the cognitive and neural bases of future thinking is still in its infancy. Neuroimaging findings over te past five years have shown that thinking about the future engages a core set of brain regions that have traditionally been associated with episodic remembering. Such findings suggest a direct link between the ability to remember the past and to envision the future. However, neuroimaging evidence is correlational in nature, and causal inferences can only be drawn from lesion studies. Further, despite the fact that every future simulation, just like every lived experience, falls somewhere along an affective continuum, little is known about the interplay of emotion and memory in future thinking. Given the powerful influences of emotion on memory, the intriguing possibility of similar influences of emotion on future thinking merits study. The current proposal provides the first comprehensive, theoretically motivated analysis of future thinking in patients with amnesia secondary to medial temporal lobe (MTL) lesions. The first part of the proposal draws on insights from neuroimaging studies regarding hippocampally-mediated mechanisms of future thinking to define the scope of the future-thinking impairment in MTL amnesia and to identify interventions that may ameliorate the impairment. The second part of the proposal examines the interplay of emotion and memory in future thinking by (a) examining how emotion modulates hippocampally-mediated processes underlying future thinking; and (b) exploring how memory impairment affects emotional biases that are typically evident in future thinking. Given the role of the amygdala in the emotional modulation of memory, we focus on a comparison of the performance of patients with MTL lesions limited to the hippocampal complex and patients whose lesions extend beyond the hippocampal complex to include the amygdala. In the third part of the proposal, we evaluate the adaptive value of memory for future-oriented behavior by examining conditions in which MTL amnesia impacts decision making. The studies comprising this proposal provide a principled way to gauge the scope of the future thinking impairment that results from MTL lesions and a theoretically based approach to remediation. They also provide the first systematic exploration of how the emotional attributes of future thought modulate the MTL-associated impairment in future thinking. Finally, by revealing the impact of the MTL-associated memory impairment on future-oriented behaviors, these studies will shed novel light on the adaptive function of memory. We anticipate that these findings will have important implications for understanding impairments in future-oriented thought and behavior in a variety of neurological and psychiatric populations. !

PUBLIC HEALTH RELEVANCE: Memory impairment is a significant problem in a wide range of neurological and psychiatric illnesses that affect Veterans, including traumatic brain injury, dementia, depression, and schizophrenia. Although severe memory impairment in isolation is rare, the study of such impairment in amnesia provides a window onto the consequences of memory deficits in more prevalent disorders in which multiple cognitive abilities, including memory, are implicated. Memory problems have long been recognized as a major cognitive impediment in their own right. Recent evidence that memory problems may also contribute to impairments in future-oriented thought and behavior suggests that the impact of memory impairment may extend well beyond what was appreciated previously. Future-oriented behaviors are necessary for optimal health decisions, successful functional integration, and general wellbeing. Thus, a better understanding of the scope and potential amelioration of the future thinking deficit in amnesia will have far-reaching implications for Veterans' healthcare.