Kirk R. Daffner, M.D. - US grants

Orienting to novelty plays a critical role in directing attention and guiding behavior in normal individuals and is disrupted in many disease states. Yet, little is known about the neural substrate of novelty seeking. The proposed research will investigate the neuroanatomical and electrophysiological underpinning of responses to novel stimuli. Non-brain damaged subjects will be studied to determine the link between early stages of C.N.S. responses to novel stimuli using electrophysiological recordings (as measured by the "novelty" P300) and subsequent stages of information processing and behavioral responses (as measured by subject-controlled stimulus exposure durations). Patients with strokes will be studied to investigate the impact of focal lesions on electrophysiological and behavioral components of novelty seeking and to determine if the frontal cortex plays an essential role in this activity. All subjects will be studied in 1) an Event-Related potential (ERP) Laboratory using specifically designed visual stimuli to evoke different electrophysiological responses and behavioral reactions and 2) an Eye movement Laboratory using visual stimuli to elicit exploratory eye movements. Stroke patients will undergo magnetic resonance imaging (MRI) with 3 dimensional surface reconstruction of the lesion site to precisely delineate the location of structural brain damage.

DESCRIPTION: (provided by applicant) Attention to novel events facilitates adaptation to a changing environment and may increase engagement with one?s surroundings and enhance cognitive abilities. Despite its importance, there has been limited study of age- and disease-related changes in how the brain processes novel events. Based on the PI?s research, a provisional model of a neurally-based novelty processing system is presented. Building upon this work, the proposed research will investigate age-related changes in the novelty P3 response and subsequent allocation of attention to novel stimuli (as measured by viewing durations) in order to elucidate the relationship between responsiveness to novelty and different patterns of cognitive aging. The research aims to distinguish between changes in response to novelty that appear to be inevitable (observed with even the most successful cognitive aging), changes that are most commonly seen with usual cognitive aging, and changes that are associated with the most frequent degenerative disease of the brain (Alzheimer?s disease). A carefully designed series of experiments will test hypotheses about: 1) age-related changes in response to novelty among groups of cognitively high performing individuals; 2) differences in response to novelty between cognitively high and mid performing older individuals; 3) age-related changes in response to novelty among groups of individuals that differ in level of cognitive performance; 4) differences in response to novelty between cognitively normal individuals and cognitively impaired ones (with mild Alzheimer?s disease); and 5) the relationship between the novelty P3 response and subsequent attention to novel events in the laboratory and level of engagement in daily activities. These integrative functional and cognitive neuroscientific studies will extend previous work on the neurology of attention to novel events and provide new insights into the ways in which this fundamental aspect of human behavior is related to normal aging and disease.

[unreadable] DESCRIPTION (provided by applicant): As increasing numbers of Americans are living to advanced ages, understanding what allows individuals to maintain meaningful levels of intellectual functioning and independence has become a major public health concern. The primary goal of the proposed research is to investigate the ways in which information processing of cognitively `successful' older adults differs from that of cognitively less successful ones. Event-related potential (ERP) indices of sensory-perceptual encoding, selective attention, and capacity- limited controlled processing will be measured. This will provide an opportunity to evaluate competing theories about cognitive aging that differ in terms of which information processing operations are hypothesized to be most important to age-related changes in cognition. Our proposal emphasizes novelty processing because increased responsiveness to novelty may not only be a reflection of successful cognitive aging, but also help to promote it. In the proposed study, individuals from 18 to over 90 years old will be divided into cognitively high and cognitively average performers based on age-appropriate neuropsychological test norms. A carefully planned set of ERP experiments will examine the extent to which groups varying in cognitive status differ in age-related changes in novelty processing under conditions that manipulate demands on 1) capacity-limited controlled processing (Aim 1), 2) context-appropriate resource allocation (Aim 2), and 3) selective attention to task-relevant events (Aim 3). Aim 1 will be addressed by comparing responses to novel stimuli under single vs. dual-task conditions. Aim 2 will be addressed by comparing responses to novelty under conditions that vary whether novel stimuli serve as distracters or potentially meaningful events. Aim 3 will be addressed by comparing responses to salient stimuli under attend vs. ignore conditions. Our work will provide important insights into 1) the extent to which age-related differences between cognitively high and average performing adults are due to a decline in information processing capacity that begins earlier in the lifespan for average performers; 2) the extent to which the magnitude of age-related differences between cognitively high and average performing adults differ across various stages of information processing; 3) the extent to which members of different age and cognitive groups are able to vary their response to novel events depending on the context in which they occur; and 4) the extent to which ERP indices of sensory-perceptual encoding, selective attention, and capacity-limited controlled processing can differentially account for the variance in age-related changes in neuropsychological performance. In summary, the proposed research will provide an opportunity to elucidate factors that are fundamental to successful cognitive aging, an endeavor that is critical to this important field of study. PUBLIC HEALTH RELEVANCE: The proposed research will investigate factors that contribute to successful cognitive aging, a topic of major importance to public health as an increasing number of Americans are living to advanced ages. We will study age-related changes in brain wave activity in individuals from 18 to over 90 years old who vary in their level of intellectual functioning. We aim to identify underlying mechanisms that allow people to remain active and high functioning throughout adulthood. [unreadable] [unreadable] [unreadable]