Daniel Schacter - US grants

Memory impairments and subjectivecomplaints of memory loss are among the most common features of cognitive aging. The long-term goals of this project are to facilitate understanding the effects of aging on memory processes, and to provide a basis for developing techniques and interventions that can enhance memory functions of older adults in their everyday lives. The proposed experiments will contribute to these goals by clarifying the effects of aging on source memory (remembering when and where previous experiences occurred)and false memory (inaccuraterecollections). The first specific aim is to evaluate the hypothesis that older adults can use a "distinctiveness heuristic" [unreadable]a strategy whereby participants demand access to distinctive recollections to support a positive memory decision - to reduce robust false recognition effects that are observed after participants study lists of semantically related words or categorized pictures. Experiments 1-6test this hypothesis by manipulating conditions that do or do not allow participants to rely on a distinctiveness heuristic to reduce false recognition. The second specific aim is to extend the distinctiveness heuristic hypothesis to other forms of false recognition. This objective will be accomplished by examining the effects of distinctive encoding in a paradigm where false memory effects are created by repeating new items on a recognition test (Experiments 7-10), and by testing the hypothesis that younger adults will show greater "false recognition reversal" than older adults because the effect depends on memory processes that are impaired in older adults, and cannot be produced by invoking a distinctiveness heuristic (Experiment11-13). The third specific aim is to characterize source memory in older adults and examine its role in the generation and suppression of false memories. To do so, we assess the hypothesis that memory for partial source information is preserved in older adults and can provide a basis for using the distinctiveness heuristic (Experiments 14-16), and also evaluate whether older adults can use a likelihood heuristic to reduce source memory errors (Experiment 17). The fourth specific aim [unreadable] to evaluate the contribution of conceptual information to age-related increases in false recognition of categorized pictures and novel patterns [unreadable]will be accomplished by attempting to interfere with verbal labeling (Experiment 18) and by manipulating the presence or absence of verbal labels for novel visual patterns (Experiment 19). Taken together, the proposed studies will provide new insights into memory distortions that accompany aging and what can be done to minimize them. 3ERFORMANCE SITE(S) (organization, city, state) Harvard University: Cambridge, MA KEY PERSONNEL. See instructions on page 11. Use continuationpages as neededto provide the requiredinformation in the format shown below. Name Organization Role on Project Daniel L. Schacter Harvard University P.I. Chad S.Dodson Harvard University Post-Doctoral Researcher PHS 398(Rev.5/95) Page 2 B B Number pages consecutively at the bottom throughout the application. Do not use suffixes such as 3a, 3b. CC Principal Investj^Br/Program Director (Last, first, middle): ^^Bhacter, Daniel L. Type the name of the principal investigator/program direcraPIFthe top of eachprinted pageand each continuation page. (Fortype specifications, see instructions on page 6.) RESEARCH GRANT TABLE OF CONTENTS Page Numbers Face Page 1 Description,

Memory for a recent event can be expressed through explicit recollection or inferred from priming effects that need not involve intentional recollection of any previous experience. The latter kind of memory has been referred to as implicit memory. The goals of this project are to deepen and broaden our knowledge of implicit memory, to evaluate empirically relevant theoretical ideas put forward by the investigators, and to bring together ideas and findings concerning the nature of memory and perception. The experiments focus on priming of novel visual objects, and test the idea that such priming effects are mediated by a presemantic structural description system that represents information about the global relations among parts of objects. A total of 30 experiments and subexperiments are proposed. In Experiments 1a/b-2a/b, priming is examined with a possible/impossible object decision test, and predictions made by the structural description system hypothesis concerning the differential effects of semantic and structural encoding on implicit and explicit memory are evaluated. Experiments 3a/b-4a/b explore conditions under which priming of impossible objects may be obtained. Experiments 5-14 elucidate the nature of the structural descriptions underlying object decision priming using a new type of object decision task, and introduce new analytic paradigms that test the idea that the structural description system represents relations among parts with respect to an object's principal axis. Experiments 15-21 examine object priming in patients with organic amnesia, and provide tests of ideas concerning the neural locus of priming. The proposed research will enrich our knowledge of normal memory processes and also have important implications for understanding preserved and impaired memory functions following brain damage.

Visual mental imagery helps people to perform a host of tasks, including remembering events, spatial reasoning, and language comprehension. The images produced in the service of these activities are the result of a complex information processing system. This system can be conceptualized as being composed of a set of distinct "processing subsystems," each of which performs a specific cognitive operation (e.g., shifting the orientation of an imaged object, activating stored visual memories to create an image, encoding the relative location of part of the imaged object). The research described here makes use of a theory of these processing subsystems that draws on concepts from artificial intelligence and facts about the neurological substrate of high.level vision. The research will characterize the relative efficacy of eleven of these subsystems in the elderly, compared to younger adults. The primary aim of the research is to discover whether certain subsystems are, relative to other subsystems, selectively more effective in senescence. The research aims to disprove the idea that cognitive aging can be understood solely in terms of "generalized slowing," showing that slowing with age differs for different subsystems. If so, then strategies that make use of relatively effective subsystems should be more useful for elderly people than strategies that rely on ineffective subsystems. The experiments designed here are a step toward using contemporary theory from cognitive neuroscience and techniques of task analysis from cognitive science to design new tests for cognitive efficiency in the senescence.

DESCRIPTION (Applicant's Abstract): Memory is a critical component of human cognition, with major implications for everyday life and mental health. However, memory is not a unitary or monolithic entity, but instead consists of a variety of dissociable processes and systems. The proposed experiments use positron emission tomography in an attempt to map the component process and systems involved in explicit memory (conscious recollection of previous experiences) and implicit memory (nonconscious effects of past experiences on subsequent behavior and performance). Within the domain of explicit memory, preliminary data suggest that the hippocampal formation is sometimes associated with the conscious recollection of recent experiences -- successful remembering of an event -- as opposed to strategic efforts to retrieve a recent event. Experiments 1-3 examine this possibility, and also explore the role of prefrontal cortex in explicit retrieval, by using experimental manipulations that provide a basis for distinguishing between, and characterizing the nature of, processes involved in successful remembering on the one hand and effortful retrieval attempts on the other. These experiments also examine the types of retrieved information that are associated with hippocampal blood flow increases, and also explore the role of medial temporal and frontal regions in illusory memories. Experiments 4-6 investigate implicit memory, focusing on the neuroanatomical correlates of visual and auditory priming. These experiments test specific hypotheses about the neural basis of priming that are generated by a theoretical framework developed by the principal investigator. Previous research has revealed that preserved priming and other implicit memory abilities in amnesic patients can provide a basis for developing effective rehabilitation strategies that have significant effects on patients' everyday lives. The proposed studies will provide new information about the neuroanatomical correlates of implicit memory and thereby contribute to the further development of rehabilitation efforts.

DESCRIPTION: (Adapted from the Investigator's Abstract) Memory is a critical component of human cognition, with major implications for everyday life and mental health. A key feature of human memory concerns the encoding processes that play a crucial role in the formation of enduring recollections. The proposed experiments use recently developed event-related functional magnetic resonance imaging techniques in an attempt to map structures and processes that underly encoding of new memories, and to test specific hypothesis concerning the nature of encoding. The first specific aim is to characterize the functional anatomy associated with different levels of encoding, and test hypotheses concerning the involvement of specific brain regions in particular forms of encoding. Preliminary results suggest that levels of activity within the left prefrontal cortex and parahippocampal cortex during encoding predict whether verbal experiences will be subsequently remembered or forgotten. Experiments 1-5 examine different types and levels of encoding operations in an attempt to expand our knowledge of the brain processes and systems that contribute to the formation of verbal memories. Several of these experiments examine the contributions of visual imagery, phonological encoding, and relational or associative information to the formation of new memories, whereas others examine such fundamental issues as the relation between attention and memory. The second specific aim is to test hypotheses concerning the generality of the contributions of parahippocampal cortex to memory encoding by varying the nature of the materials to-be encoded. Experiments 6-7 examine this issue using nonverbal materials: pictures and melodies. The third specific aim is to test hypotheses about the consequences of encoding of previously exposed stimuli for further encoding of those stimuli. These experiments will help to create new links between studies of encoding and related work on how repetition benefits learning, and how people detect changes to objects in their environments. Previous research has revealed that encoding processes play a key role in mental disorders such as depression, and are crucial in efforts to rehabilitate memory deficits are brain damage. The proposed studies will provide new information about the neuroanatomical bases of encoding processes and thereby contribute to the further development of rehabilitation efforts.

DESCRIPTION (provided by applicant): Memory is a critical component of human cognition, and has major implications for everyday life and mental health. The long-term goals of this project are to increase our understanding of critical encoding and retrieval processes, and to help explain why memory is sometimes inaccurate, by using recently developed event-related functional magnetic resonance imaging techniques. The first 2 specific aims focus on basic aspects of encoding and retrieval, whereas the next 3 focus on memory distortion. The first specific aim is to characterize the functional anatomy of encoding, and test hypotheses concerning the involvement of specific brain regions in encoding variability, repetition priming, and response learning effects. Experiments 1-2 examine encoding manipulations that improve or impair subsequent memory, using techniques that link brain activity during encoding with later memory performance. The 2nd specific aim is to test hypotheses concerning the role of prefrontal cortex in specific aspects of strategic retrieval, which we do in Experiments 3 and 4 by manipulating the usefulness of recollective retrieval strategies. The 3rd specific aim is to characterize the neural underpinnings of true and false memory by testing the hypotheses that true memory, more than false memory, involves reactivation of sensory cortices involved in perceptual encoding, and that sensory reactivation reflects the influence of priming, a form of implicit memory. Experiments 5-10 accomplish this objective by comparing true and false memories, and conscious versus nonconscious recognition, for visual shapes, patterns, and objects. The 4th specific aim is to characterize encoding processes that result in memory errors in which people falsely recognize similar objects as the same ones they previously studied. Experiments 11-12 accomplish these objectives by using experimental procedures that relate particular encoding events to later true and false recognition. The 5th specific aim is to link work on memory distortion with research concerning perception of objects and scenes. Experiments 13 and 14 evaluate hypotheses regarding the role played by regions of parahippocampal cortex involved in contextual associations in false recognition of objects, and Experiment 15 examines the role of this region in boundary extension, where people "remember" aspects of a scene that were not presented in a photograph but are likely to have been present just beyond its borders. The proposed studies will increase our understanding of how memories are constructed, and will also contribute to efforts to improve memory.

DESCRIPTION (provided by applicant): This plan for Graduate Training in Psychology and Neuroimaging rests on multidisciplinary collaborations between 23 faculty members in the Psychology Department at Harvard University and the Athinoula A. Martinos Center for Biomedical Imaging at the Massachusetts General Hospital. The training program aims to prepare a new generation of scientists whose graduate training concentrates on linking human brain function to cognitive processing through neuroimaging research. Functional magnetic resonance imaging (fMRI), magnetoencephalography (MEG), electroencephalography (EEG), positron emission tomography (PET), and near-infrared spectrography (NIRS) have emerged as central tools in cognitive neuroscience. By training students to use these neuroimaging methods effectively, our goal is to equip them with the means to answer questions about the neural bases of mental processing with technological competence. A demanding 5-year program of graduate training is proposed to meet this goal. Although the emphasis is on traditional cognitive psychology, it will be readily possible for trainees to address issues of cognitive development, social cognition and psychopathology. Each student will be admitted into a program in the psychology department and will be expected to fulfill the requirements of that specific program, including first-year, second-year and Ph.D. thesis research projects. In addition, every trainee will take two team-taught courses in their first two years: a course in Cognition, Brain and Behavior (taught by all the training faculty in psychology and faculty in cognitive psychology at the Martinos Center) and an intensive introduction to functional brain imaging (taught by training and other faculty from the Martinos Center). In subsequent years, trainees will take a research seminar jointly taught by all faculty. Students will explore particular areas of cognitive and brain function in depth, develop skills for crafting experiments that dissect specific cognitive functions, present their research, and interact with other trainees in the program. The goal of these requirements is to impart knowledge that is broad and deep, both about the human brain and about the cognitive functions that it performs. Throughout their training, students will be co-advised by one Harvard Psychology and one Martinos Center faculty.