Robert Maxwell Chapman - US grants

The general objective is to advance understanding of brain activity and information processing by studying the relationships between neurophysiological and behavioral measures. Both magnetic field and electrical potential data will be obtained in research on brain activity recording, short-term memory, and linguistic information processing. Based on experimental results in information processing and cognitive psychology, electrophysiological experiments have been designed to correlate Electroencephalogram (EEG) and Magnetoencephalogram (MEG) with cognitive functions and to identify meaningful components of the electrical brain activity. The experiments are organized around electrical recording of brain activity during specific tasks dependent on controlled stimuli. Approaches toward systematic, robust and efficient MEG and EEG measurement and evaluation are emphasized, including Event-Related Potentials and extended applications of the Relative Covariance method that combines simultaneously obtained electrical potential and magnetic field measurements. These techniques have potential significance for clinical assessment as well as experimental studies in memory and linguistic processing. The research has relevance in neuropsychology, neurology, psychology, vision and biopsychology.

[unreadable] DESCRIPTION (provided by applicant): Based on brain Event-Related Potentials (ERP) obtained under tasks with designed memory demands, the aim is to improve understanding and foster early interventions by 1) developing non-invasive brain activity marker(s) for Alzheimer's disease (AD) early in its course, and 2) predicting with such marker(s) which patients with mild cognitive impairment (MCI) will go on to develop Alzheimer's disease. About half of MCI patients develop AD within a few years. The overall goal is to determine early enough which patients might benefit from interventions and to understand better the brain functions altered in these diseases. We record ERP's while participants perform two simple cognitive tasks. In each of these tasks, ERP components differ under conditions which demand different use of memory and processing resources. The two tasks are (1) a number-letter paradigm that involves comparisons of numbers or of letters within each trial of 4 sequential stimuli (working memory); and (2) a pattern paradigm which involves symmetry judgments of visual patterns, some of which are repeated over trials (implicit memory). The research entails comparison of tasks-related ERPs of MCI patients, AD patients early in the course of AD, and appropriately aged controls. Multivariate statistics are used to measure the ERP components and to develop functions that discriminate among the subject groups and predict AD among the MCI patients. [unreadable] [unreadable]

DESCRIPTION (provided by applicant): To promote the success of clinical trials testing interventions for Alzheimer's disease (AD), it is imperative that researchers establish proper subject enrollment and measure the clinical efficacy of the treatment. Brain Event-Related Potentials (ERPs), which are obtained while subjects do tasks with designed perceptual/cognitive demands, offer a noninvasive method of measuring brain activity affected by AD that, once developed, can be implemented for clinical and research use without special equipment or special expertise. In conjunction with sophisticated multivariate analytic techniques, temporal ERPs have been shown to detect AD and predict AD progression in individuals with pre-clinical form of the disease. Our aim is to expand the study of ERPs to incorporate both their temporal and spatial properties in novel and innovative composite measures to: 1) define and refine the AD subject population to improve proper subject enrollment in clinical trials even in predementia AD, and 2) develop measures of brain activity that can detect change in subjects over time in order to gauge the effects of AD treatments. Using a cognitive paradigm known to elicit ERPs representative of memory encoding and retrieval, stimulus expectancy, and executive functioning, we will collect ERPs from AD patients early in the course of the disorder, MCI patients (a sizeable percentage of whom develop AD within a few years), and normal elderly. We will then apply new multivariate techniques, including Two-step Spatiotemporal Principal Components Analysis and Parallel Factors Analysis to define and measure the underlying spatiotemporal components of the ERPs, in order to combine both the temporal waveforms of the ERPs and their spatial distributions into useful composite measures. These spatiotemporal ERP measures will be linearly combined into discriminant functions that can be used to make group assignments with a quantitative measure of confidence in each subject's assignment through posterior probabilities of group membership. This technique will also be studied to detect change over time by reanalyzing group placements longitudinally. If successful, these ERP measures and multivariate methods will provide important tools for improving the validity of clinical trials while addressing the difficult barrie of empirically and quantitatively combining spatial and temporal ERP measures for use in evaluating AD across its course.

PROJECT SUMMARY This research addresses concerns in an NIH PAR, ?Emotional Function in Normal Aging and/or MCI and AD/ADRD?. It expands on foundational research in order to clarify the trajectories of change in emotional processing and linked neurobiological factors in adults who are aging normally, as well as in individuals with Mild Cognitive Impairment (MCI) and Alzheimer?s disease (AD). Its goals focus on 1) normative maturational shifts in emotional processing, and 2) how dysfunction in the integrative neural-behavioral mechanisms of emotional function manifest in MCI and the early stages of AD/ADRD. We propose to study brain Event- Related Potentials (ERPs) in the context of affective processing of word stimuli based on the classic, quantitative three-dimensional theory of affective (emotional) meaning developed by C.E. Osgood. Can the emotional changes which accompany aging be elucidated by brain ERPs measured during processing of affective word stimuli? What are the relationships among our ERP and behavioral measures and our neuropsychological measures of cognitive ability and neuropsychiatric assessments of affect and emotion? These questions will be studied in young adults, in elderly with normal cognition, and in like-aged individuals afflicted with MCI and early-stage AD. In addition, we will examine how affective meaning in ERPs change in MCI/early-stage AD when compared with like-aged normal elderly. Also studied will be the effects of gender differences on affective meaning ERP measures both in the aging analyses and the cognitive impairment analyses of MCI/AD. Our experimental design builds on a strong, empirically-supported framework of affective processing and emphasizes the affective differences within Osgood?s model. Multivariate analysis methods will be utilized, including separately studying combinations of ERP components related to particular connotative word classes for men and for women.