Marcia K. Johnson - US grants

Semantic memory refers to acquired generic knowledge, including knowledge of facts, concepts, and word meanings. Alzheimer's disease (AD) results in a progressive disruption in semantic memory that ultimately has a devastating effect on comprehension, memory for events, thinking, planning, and communicating. This proposal is directed at clarifying the nature of the disruption in semantic memory produced by AD. The project is guided by and intended to further develop a general cognitive architecture called MEM (Johnson, 1983, in press-a,b; Johnson & Hirst, in press). MEM is a theoretical framework for understanding both normal memory and disruption of function, for example, in delusions, confabulation, and amnesia. According to MEM, memory is organized at the most global functional level into two major systems, a perceptual memory system and a reflective memory system. In this framework, semantic memory is supported by both perceptual and reflective systems. The generalized cognitive deficits in AD are hypothesized to result from a disruption of the reflective system, especially a disruption of the ability of executive agendas to recruit other component reflective processes (cf. Nebes, 1989). Based on this characterization of AD, we expect that underlying structural relations among concepts (e.g., a dog, is an animal) and among attributes of concepts (e.g., cars have engines) may remain intact, but patients increasingly have a more difficult time using this information in cognitive tasks because reflective processes central to their use are disrupted. Experiments are proposed that assess the impact of AD on both the availability and use of semantic information of various types. Converging evidence will be obtained from several tasks, including verification of semantic relations (e.g., Is a sparrow a bird?), judgments of goodness or importance (e.g., Which is more central to the concept of a car, engine or hubcaps?), naming objects, and free association. These studies will also provide useful data for identifying the cognitive functions of brain areas damaged in AD (e.g., Van Hoesen & Damasio, 1987).

Compared to younger adults, older adults not only have difficulty remembering the content of information, but they also have problems in remembering the source (e.g., speaker, temporal or spatial context, modality) of information. The present project examines age-related differences in making source monitoring judgments and in remembering source-specifying attributes. The work is guided by a source monitoring framework (Johnson, Hastroudi, & Lindsay, 1993) and general memory model (Johnson, 1992; Johnson & Chalfonte, 1994; Johnson & Hirst, 1993) that identify relevant features of complex memories and describe central encoding and source monitoring processes. The proposed experiments assess the relative availability of certain features of memories, potential age differences in the binding of features into complex memories, and the contribution of different types of remembered information (e.g., perceptual, contextual and cognitive operations) to age differences in remembering source. We also examine whether age deficits in remembering source are dissociated from deficits in remembering content, and assess the impact of variables (e.g., repetition, specific combinations of features to be bound, amount of potential confusion among features, delay) on memory for content and source. Finally, we investigate the relations between performance on source memory tasks and neuropsychological tests sensitive to dysfunction in frontal, medial-temporal, and parietal brain regions. The findings from these experiments will help characterize the nature of age- related differences in forming and remembering complex events. Furthermore, the data and theoretical ideas generated from the empirical studies will provide constraints for developing a computer simulation model of age differences in encoding, reviving and making source judgments about complex memories. Devising assessment procedures for identifying and quantifying source monitoring deficits, correlating them with other indices (such as tests for frontal system deficits), and developing clinical remedial techniques for dealing with such deficits, will benefit from a more specific characterization of source monitoring situations and relevant memory attributes and processes.

Semantic memory refers to acquired generic knowledge, including knowledge of facts, concepts, and word meanings. Alzheimer's disease (AD) results in a progressive disruption in semantic memory that ultimately has a devastating effect on comprehension, memory for events, thinking, planning, and communicating. This proposal is directed at clarifying the nature of the disruption in semantic memory produced by AD. The project is guided by and intended to further develop a general cognitive architecture called MEM (Johnson, 1983, in press-a,b; Johnson & Hirst, in press). MEM is a theoretical framework for understanding both normal memory and disruption of function, for example, in delusions, confabulation, and amnesia. According to MEM, memory is organized at the most global functional level into two major systems, a perceptual memory system and a reflective memory system. In this framework, semantic memory is supported by both perceptual and reflective systems. The generalized cognitive deficits in AD are hypothesized to result from a disruption of the reflective system, especially a disruption of the ability of executive agendas to recruit other component reflective processes (cf. Nebes, 1989). Based on this characterization of AD, we expect that underlying structural relations among concepts (e.g., a dog, is an animal) and among attributes of concepts (e.g., cars have engines) may remain intact, but patients increasingly have a more difficult time using this information in cognitive tasks because reflective processes central to their use are disrupted. Experiments are proposed that assess the impact of AD on both the availability and use of semantic information of various types. Converging evidence will be obtained from several tasks, including verification of semantic relations (e.g., Is a sparrow a bird?), judgments of goodness or importance (e.g., Which is more central to the concept of a car, engine or hubcaps?), naming objects, and free association. These studies will also provide useful data for identifying the cognitive functions of brain areas damaged in AD (e.g., Van Hoesen & Damasio, 1987).

[unreadable] DESCRIPTION (provided by applicant): Our primary goal is understanding the cognitive processes underlying episodic memory, processes that associate (bind) features of events into complex memories (encoding), consolidate them over time, and revive and evaluate them later. Among the consequences of normal aging, one of the most distressing is the sense of losing access to specific details of episodic memories. Consider not being able to remember whether you already paid a bill or called in your prescription renewal or only thought about doing so. These problems are more common than more severe deficits, such as Alzheimer's Dementia; an even larger percentage of the population will experience these as the baby boomer population ages. Our research is directed at understanding the processes mediating episodic memory, and the ways that these processes break down in normal aging. The prefrontal cortex (PFC) plays a critical role in encoding daily events and subsequent memory for them. We have proposed that right PFC subserves relatively heuristic processes and that left PFC (or left and right together) subserves more systematic processes. We propose to test the hypothesis that age-related decrements in episodic memory involve PFC dysfunction that disrupts processes typically subserved by left PFC, or the interaction between left and right PFC, more than those subserved by right PFC. Our research is guided by the source monitoring framework (SMF), which provides an evolving organizational structure for summarizing current understanding of these processes and a basis for generating new hypotheses. This approach has helped clarify fundamental theoretical issues in memory, including the nature of age-related changes. This proposal requests funds to continue our cognitive/behavioral and functional magnetic resonance imaging (fMRI) research on these issues. The project has three main goals: (1) To further clarify the nature of cognitive processes subserving episodic memory and to specify the ways they are (and are not) likely to be affected by aging; (2) To further develop methods for assessing the qualitative characteristics of memories and models of the subjective experience of remembering, and to assess changes in subjective experience with age; and (3) To identify the neural bases of source monitoring processes and specify those most affected by aging. Devising assessment procedures for identifying and quantifying episodic memory deficits, correlating them with other indices (such as neuropsychological tests), and developing remedial techniques for dealing with such deficits, will benefit from a more specific characterization of source monitoring processes and changes in those processes and their neural substrates with age. [unreadable] [unreadable]

DESCRIPTION (provided by applicant): Normal aging is accompanied by reduced cognitive functioning that can have a broad impact on older adults'lives, including work, social interactions, and managing daily tasks such as finances. Perhaps one of the most common subjective complaints is problems with working memory and long term memory. A major factor contributing to such age-related decline is impaired functioning of the executive processes by which information is maintained and manipulated during higher-order cognitive activities such as comprehension, memory, decision-making and problem-solving. There is accumulating evidence converging on the critical role of prefrontal cortex (PFC) in the executive processes involved in such cognitive activities, and there is increasing evidence that PFC shows functional organization with respect to the processes engaged. There is also evidence that a primary role of PFC is to modulate activity in other brain regions, including those involved in initial perception and the encoding of enduring representations of experienced events. Aging disproportionately affects the PFC, compared to other brain regions, and structural, functional, and metabolic changes have been associated with cognitive dysfunction. There are a growing number of reports of positive correlations between older adults'cognitive performance and scores on cognitive tasks sensitive to executive function, and fMRI studies showing age-related differences in PFC and posterior area activity during cognitive tasks, including tasks assessing executive function. A common goal of investigators working on executive function is to characterize the functional organization of PFC with respect to individual processes, groups of related functions, and/or an area's role in modulating other areas during tasks requiring control. Yet, in spite of increasing interest in these topics, there is still little agreement on a single workable taxonomy of executive functions, how specific regions of frontal cortex map onto specific executive processes, or the dynamic networks that support them. One possible reason is that many of the laboratory tasks traditionally used to tap executive functions are complex---involving multiple component executive processes and subject to potential strategy differences across groups. The proposed project will thus use simple tasks to advance four broad aims: (1) To further specify the component cognitive processes involved in executive function;(2) To identify their neural bases, including functional networks between brain regions;(3) To assess how component processes and underlying neural activity are affected by aging;(4) To examine how individual differences in performance on measures of executive function relate to differences in patterns of brain activity (and connectivity) related to component executive processes. PUBLIC HEALTH RELEVANCE: Impaired executive functioning associated with normal aging can have a broad impact on older adults'productivity, physical health and general sense of well-being. With the expected increase in the aging population, normal age-related cognitive decline is a major public health issue. The aim of this project is to further characterize specific executive processes, their neural mechanisms, and the impact of aging on them;such information should aid the development of interventions and biomarkers to evaluate the efficacy of interventions.