Arthur P. Shimamura - US grants

social perception; memory disorders; neuropsychology; aging; memory; neuropsychological tests; human old age (65+); human middle age (35-64); young adult human (21-34); brain disorders; brain injury; Alzheimer's disease; human subject;

9319103 IVRY Theories of object recognition in psychology, physiology, and even computer science have concerned themselves with feature analysis, where features may be line segments, colors, spatial frequencies, etc. According to these theories, recognizing an object involves detecting the features of that object. For example, the features round, shiny, and red might signal an apple. Recently, however, Treisman and her colleagues have pointed out that correct feature registration is not sufficient for veridical object recognition. When many different objects are present, as they are in most natural scenes, observers must not only correctly register the features, but also correctly bind the features into separate objects. Treisman and other have shown that under conditions of a brief exposure, observers will report "illusory conjunctions," or precepts in which they correctly identify the visual features, but combine them incorrectly. For example, an individual briefly presented a red X and a green O would perceive the X as green in some laboratory conditions on up to 30% of the trials. In most circumstances, our visual systems combine features of objects seemingly without error or effort, making the process of feature integration difficult to study. By studying errors in this feature binding process under laboratory conditions (i.e., illusory conjunctions), we can test different theories of feature integration. Unfortunately, the study of feature binding has been hampered for three reasons. First, most theories have been specified in a vague or informal manner. Second, theories have not been formulated in a format that allows a direct test between them. Finally, there has been considerable disagreement on how to measure illusory conjunctions. Many of the widely used methods of measuring feature binding from the occurrence of illusory conjunctions confound feature registration with feature binding. Preliminary research has led to the development of a mathematical model that add resses the above three issues, as well as to the development of a new theory of feature binding, based on probabilistic multidimensional modeling and on the psychophysics of location perception. The 15 experiments to be performed fall into four categories: (1) The formal theory will be tested by varying stimulus values (e.g., color of items) systematically and seeing how they affect parameters of the mathematical model, adjusting the model if necessary. (2) Cognitive variables such as attention will be varied and the effect of these variables on feature integration estimated separately. (3) Different theories of feature binding will be compared directly. (4) The analytic method and formal analysis will be extended to new experimental paradigms, in order to make it as useful as possible to other investigators. ***

The primary focus of the proposed research will be to study the biological basis of implicit memory function. Specifically, patients with unilateral neocortical lesions will be assessed on a variety of implicit memory tests. Subjects will include patients with dorsolateral prefrontal lesions, patients with temporal-parietal lesions, and patients with occipital lesions. Various tests of implicit memory (e.g., tests of perceptual, lexical, and semantic priming) and various stimulus material (e.g., verbal, nonverbal) will be used to determine patterns of impairment on these tests in patients with neocortical lesions. It is predicted that secondary sensory areas (e.g., prestriate occipital areas) will be critical for perceptual priming, temporal-parietal associational areas will be critical for lexical priming, and frontal areas will be critical for semantic priming.

The broad objective of the proposed research program is to assess the contribution of the frontal lobes to human memory. Behavioral analyses of neurological patients will be used to provide an understanding of neural systems underlying cognitive function. In the proposed studies, patients with frontal lobe lesions will be evaluated on a variety of memory and cognitive measures. Recently, the role of the frontal lobes in human memory and cognition has been studied rather extensively. Advances in the field have been attained by progress in human functional neuroimaging techniques, in cognitive analyses of patients with frontal lobe lesions, and in neurobehavioral analyses of animal models. These advances have led to the hypothesis that the frontal lobes contribute to "working memory"-that is, the on-line monitoring and controlling of information processing. The proposed research program will assess a theoretical framework that attempts to refine and extend the notion of working memory. It is suggested that the prefrontal cortex acts as a dynamic filtering mechanism that gates and ultimately controls stimulus encoding and memory activation. Damage to this mechanism results in a failure to filter inappropriate stimulus features, memories, and response decisions. In the proposed studies, patients with lesions of the dorsolateral prefrontal cortex will be evaluated on a variety of tests that tap aspects of attention and memory. These patients will be compared to neurologically intact control subjects and to other neurological patients (e.g., patients with orbital prefrontal lesions or temporal-parietal lesions). Central research questions include the following: What is the relationship between memory and other cognitive disorders observed in patients with frontal lobe lesions? At what stage or stages of memory processing do the frontal lobes appear to make significant contributions-stimulus encoding, access to semantic memory, memory storage, memory retrieval? As a result of an impairment in gating or selection, are patients with frontal lobe lesions more susceptible to interference from irrelevant or extraneous information?

DESCRIPTION: (provided by applicant) The broad objective of the research program is to assess the role of the orbitofrontal cortex in emotional control. In recent years, the field of affective neuroscience has been advanced significantly by progress in human functional neuroimaging techniques, in behavioral analyses of neurological patients and in theoretical analyses integrating cognitive and emotional function. These advances have led to the view that the orbitofrontal cortex contributes to a variety of functions, including inhibitory control, reward-feedback expectancy, decision making under high risk, and social awareness. In the proposed research program, a four-pronged analysis will be applied. This analysis will include: 1) neuropsychological assessment of patients with frontal lobe lesions, 2) functional magnetic resonance imaging (fMRI), 3) electrophysiological recording of event-related potentials (ERPs), and 4) development of novel behavioral tests to assess cognitive function associated with emotional control. A theoretical framework, dynamic filtering theory, will be used to guide the research program. It is suggested that the prefrontal cortex acts as a filtering or gating mechanism that controls many aspects of information processing, including stimulus encoding, memory activation, response decision, and emotion. Different regions within the prefrontal cortex monitor and control different aspects of mental function. It is proposed that the orbitofrontal cortex is involved in the monitoring and control of affect and arousal. The advantage of this theoretical framework is that findings and research in the analysis of dorsolateral. prefrontal function can be applied to the analysis of orbitofrontal function. This cognitive neuroscience approach will attempt to provide an understanding of the biological underpinnings of drug abuse. In particular, issues of inhibitory control, reward-feedback analysis, and decision making will be considered in light of issues related to drug abuse, such as compulsions, cue-induced cravings, risk taking behavior.

Two brain regions--the Medial temporal cortex and prefrontal cortex--contribute prominently to aspects of human learning, storage, and retrieval. It is generally viewed that the medial temporal cortex is critical for the establishment and storage of new memories. The prefrontal cortex is involved in controlling and monitoring information that is to be stored or retrieved from memory. The specific aim of this project is to define and characterize more succinctly the functional contributions of these two brain regions and determine how they interact with each other and with memory representations stored in posterior cortical (associational) areas. Specifically, the proposal will focus n the analysis of medial temporal and prefrontal function in terms of the storage and binding of novel representations, proactive interference, and novelty encoding. One unique aspect of human memory is the establishment of complex representations--such as memory for episodic events or for newly learned semantic knowledge. Such representations can be formed, stored and often retrieved in a facile manner. The binding of such representations is proposed to be a key role of the medial temporal cortex. With respect to learning and remembering, prefrontal function serves to make this binding mechanism more efficient by selecting and maintaining appropriate encoding and retrieval strategies. For example, successful learning and retrieval depends of the ability to select relevant information and filter irrelevant information (e.g., reducing proactive interference). In addition, memory processes and be made more efficient by marking distinctive or novel events and disregarding familiar or usual ones. It is proposed that executive control processes associated with prefrontal cortex facilitate efficient memory processes by filtering irrelevant neural activity and selecting relevant (i.e., distinctive or novel) activity. In the proposed research, patients with medial temporal lesions and patients with frontal lobe lesions will be assessed on a variety of memory paradigms. Related studies using functional neuroimaging methods (fMRI, ERP) are proposed to define the dynamic relation between medial temporal and prefrontal activity.

The ability to call to mind past experiences and events is the essence of human memory. Our understanding of this process often called episodic retrieval has been advanced by neuroimaging studies, particularly those involving functional magnetic resonance imaging (fMRI). Brain regions involved in episodic retrieval can be analyzed by measuring activity during successful retrieval of a memory. Two prominent regions have been linked to episodic retrieval the parietal cortex and the prefrontal cortex. Although the role of the prefrontal cortex in memory has been studied extensively, there is less detail about the role of the parietal cortex. With support from the National Science Foundation, Dr. Arthur P. Smimamura of the University of California, Berkeley, will use fMRI to study brain activity during episodic retrieval. Three other tasks will be compared with episodic retrieval of word lists: visuospatial processing (seeing letter strings to the right or left of a target), working memory (remembering the location of visual targets), and semantic retrieval (recalling an experimentally determined piece of information). By having such an array of processes, the role of the parietal cortex in episodic memory should become clear.

Research has recently focused on the dynamics between brain regions, rather than the activity in just one region. Moreover, past investigations have keyed on a particular cognitive process, such as episodic memory or visuospatial attention and their neural correlates, without considering how such processes interact. In the present research program, the contribution of the parietal cortex will be assessed across a variety of tasks, and the degree to which brain responses across these tasks overlap will be investigated. By this analysis, it is hoped that the neural dynamics underlying episodic retrieval will be revealed and clarified. Such insights will help us understand the workings of everyday memory and perhaps to help overcome their loss.