Mieke Verfaellie - US grants

[unreadable] DESCRIPTION (provided by applicant): This project examines associative memory (i.e., memory for the link or relation among different events or items) in patients with amnesia due to lesions of the medial temporal lobes or diencephalon. To date, studies of implicit and explicit memory in amnesia have focused largely on item memory. By providing an information processing analysis of amnesic patients' performance on tasks of associative memory, we hope to provide further insight into the nature of the memory processes that are impaired and preserved in amnesia. The first section of this proposal focuses on amnesics' implicit memory for novel associations. We propose to systematically investigate amnesics' performance across a range of implicit memory tasks in which new associative priming occurs at a perceptual and at a conceptual level, and in which associations are formed within-domain and across-domain. Comparison of amnesics' performance across these tasks will allow us to assess the validity of the notion that amnesia reflects a general deficit in relational memory. The second section of the proposal focuses on amnesics' explicit memory for novel associations. We evaluate whether amnesics' recognition memory for associative information is disproportionately impaired in comparison to their recognition memory for item information. We also examine whether amnesics are differentially impaired on associative memory tasks that vary in their underlying processing demands. These studies are aimed at assessing the validity of the notion that amnesics' impairment in associative recognition is due to a disproportionate impairment in recollection. Converging evidence from these two lines of study should provide important insights into the nature of associative memory and its status in amnesia. By specifying the nature of the memory processes that allow the establishment and retrieval of different forms of novel associations, this project will further our understanding of the form of memory that is critical for remembering relational information.

DESCRIPTION (adapted from investigator's abstract): Computation models of memory storage have recently gained increased popularity because they account for a variety of findings observed in patients with human amnesia. These models also lead to two predictions regarding the pattern of deficits seen in patients with semantic dementia. This application requires six months of support to test these predictions in a well characterized sample of semantic dementia patients followed at the Medical Research Council in Cambridge, England. The first two studies use both explicit and implicit probes of memory to test the prediction that semantic dementia patients should show better preservation of semantic knowledge acquired in recent time periods than in more remote time periods. The second two studies test the prediction that new learning is intact in these patients when the need for semantic elaboration at encoding is minimized. These studies examine the status of two qualitatively different processes than can mediate new learning, namely recollection and familiarity. Taken together with the existing findings in patients with amnesia, these studies of patients with semantic dementia will provide a powerful test of current models of memory storage in the human brain.

This program proposal requests continued support for the Boston University Memory Disorders Research Center. This Center is dedicated to the study of memory disorders and their neurological underpinnings in brain-injured adults. Three major theses link the five components of this project. First is the belief that memory disorders can be understood in terms of a breakdown of specific components of information processing, the exact nature of which may be determined by the severity and etiology of a patient's memory disorder. Second, a better understanding of amnesics' preserved capabilities ought to guide mnemonic retraining. Third, elucidating the neurological underpinnings of processing requires an understanding of the systems of brain interaction. The first component (Verbal Memory) of this project focuses on patients' on-line analysis of verbal material; then on the ability to utilize this analysis after a retention interval and, finally, on the ability to learn across multiple episodes. The second component (Perceptual Memory) follows a similar approach to study memory for visual, nonverbalizable, material. On-line analysis is investigated, followed by retention based on features and ultimately upon learning skills. The third component (Case Studies) utilizes individual cases to investigate in detail how information processing and retention may be disrupted. These cases often provide insights into memory performance overshadowed in group studies. Component four (Physiological) explores autonomic indices of orienting as an independent indicant of processing. The final component (Assessment) is concerned with the development of procedures that allow differentiation of patient groups based on processing and memory abilities. In concert with the five research components, two Core Center components are designed to contribute to and support the research endeavors of these projects. The first (Clinical Core) provides a complete neurological (including MRI) and neuropsychological profile on each memory disordered patient prior to inclusion in an investigation. The second (Administrative Core) provides a support staff for the operation of the Center and the educational, consultant and collaborative features of the Center. The interactions between the investigators from the five investigative components supported by the core programs constitute the fabric of our Center.

[unreadable] DESCRIPTION (provided by applicant): This proposal represents a systematic investigation of the effects of repetition on learning and memory in amnesic patients. Although it is clear that repetition provides one of the most powerful methods to enhance memory in amnesia, little is known about the kinds of repetition that are most beneficial, and the mechanisms by which different forms of repetition have their effect. The present studies are guided by a framework that distinguishes between a fast learning system mediated by the medial temporal lobes and a slow learning system mediated by neocortex, and are based on the assumption that repetition has distinct effects in each of these systems. The first section of the proposal examines repetition in the fast medial temporal learning system by evaluating the operation in amnesic patients of three different mechanisms thought to contribute to repetition effects in individuals with intact memory function, namely (1) encoding; (2) time in working memory; and (3) study-phase retrieval. We predict that these mechanisms will be impaired in individuals with amnesia, but that conditions can be created that minimize these impairments, thus optimizing their performance. The second section of the proposal concerns the effects of repetition in the slow neocortical learning system. Little is known about the nature and characteristics of repetition in the slow learning system, because previous studies have failed to isolate the contribution of slow neocortical learning from that of fast medial temporal learning. Here we make use of a novel paradigm that allows assessment of the slow neocortical learning system in isolation and test the hypothesis that such learning is intact in amnesic patients. We also examine how various encoding and retrieval conditions affect repetition-based slow learning, with the aim of uncovering how such learning can be optimized in amnesic patients. A better understanding of the ways in which repetition operates within the fast and the slow learning systems will elucidate the operation of these memory systems and will provide a theoretical basis for the development of specific strategies aimed at enhancing distinct forms of memory in amnesia. [unreadable] [unreadable] [unreadable]

DESCRIPTION (provided by applicant): One of the most exciting developments in memory research over the past five years is the discovery of a link between the ability to remember the past and the ability to envision the future. The bulk of the supporting evidence for this link comes from neuroimaging studies in normal cognition, which demonstrate that thinking about the future engages a core set of brain structures that have traditionally been associated with episodic remembering. These findings have inspired new ways of thinking about the function of episodic memory, re- casting its purpose as one of facilitating the generation or simulation of alternative future scenarios in the service of planning and decision-making. A limitation of neuroimaging studies, however, is that they cannot address the necessity of activated brain areas for task performance; such information must come from studies of patients with lesions to candidate brain areas. Thus, an important source of evidence about the functional link between memory and future thinking comes from amnesic individuals, who have lesions to medial- temporal lobe structures and consequent impairments in episodic memory. To date, such research has been limited to a handful of studies predominated by examination of individual cases. The present proposal represents a systematic investigation of the relationship between memory and future thinking in amnesia, using both behavioral and neuroimaging techniques. The first part of the proposal comprises a series of behavioral experiments aimed at: elucidating the nature and extent of the future thinking impairment in amnesia; testing alternative theories about the cognitive mechanisms that characterize hippocampal contributions to future thinking; and exploring ways to ameliorate the future thinking impairment in amnesia. The second part of the proposal represents the first examination in amnesia of the default network, a constellation of brain areas that have been implicated in future thinking in normal cognition. These neuroimaging studies will allow us to examine whether impairments in future thinking in amnesia are associated with reduced connectivity and/or activation in regions of the default network that have previously been linked to future thinking. Further, these studies will elucidate the effect of a focal lesion in one part of the default network (the medial temporal lobe) on the correlated activity among other structures within the default network. The studies comprising this proposal have the potential to deepen our understanding of the cognitive and neural underpinnings of future thought, to provide important constraints on theories of future thinking and its relation to episodic memory, and to shape interventional approaches to a variety of clinical disorders in which future thinking is implicated. PUBLIC HEALTH RELEVANCE: Recent research has revealed a link between the ability to remember the past and the ability to envision the future. In this study, we will investigate the relationship between memory and future thinking in amnesic individuals, who have marked deficits in remembering the past. Our findings may shape interventional approaches to a variety of clinical disorders in which memory and future thinking may be implicated.