John W. McCrary

EP Component Identification and Measurement by Principal Components-Analysis

Between the acquisition of Evoked Potential (EP) data and their interpretation lies a major problem: What to measure? An approach to this kind of problem is outlined here in terms of Principal Components Analysis (PCA). An important second theme is that experimental manipulation is important to functional interpretation. It would be desirable to have a system of EP measurement with the following characteristics: (1) represent the data in a concise, parsimonous way; (2) determine EP components from the data without assuming in advance any particular waveforms for the components; (3) extract components which are independent of each other; (4) measure the amounts (contributions) of various components in observed EPs; (5) use measures that have greater reliability than measures at any single time point or peak; and (6) identify and measure components that overlap in time. PCA has these desirable characteristics. Simulations are illustrated. PCAs beauty also has some warts that are discussed. In addition to discussing the usual two-mode model of PCA, an extension of PCA to a three-mode model is described that provides separate parameters for (1) waveforms over time, (2) coefficients for spatial distribution, and (3) scores telling the amount of each component in each EP. PCA is compared with more traditional approaches. Some biophysical considerations are briefly discussed. Choices to be made in applying PCA are considered. Other issues include misallocation of variance, overlapping components, validation, and latency changes.

Behavioral and neural analyses of connotative meaning: Word classes and rating scales☆

Abstract Behavioral (semantic differential) and neural (Evoked Potentials, EPs) responses were related to connotative meaning. The approach was based on Osgoods semantic analyses and dimensions of Evaluation (E), Potency (P), and Activity (A). The experimental variables were (1) the semantic class of the stimulus word (E+, E-, P+, P-, A+, A-) and (2) the dimension of the semantic scale (E, P, A) which the subject used to rate the stimulus words. These variables were experimentally combined such that on each trial the subject used a designated semantic scale to judge a specified stimulus word while brain activity was recorded. Using multivariate analyses, the effects on the EPs of stimulus word class, scale dimension, and their interaction were analyzed. The EP effects of stimulus word class were similar whether the subjects were merely saying the words or rating the words on a variety of semantic scales. Different EPs were found for six word classes, three semantic scale dimensions, and the 18 groups formed by their combination. The success rates in EP identification of (1) word class and (2) scale dimension did not depend on whether these two kinds of semantic variables involved the same or different semantic dimensions. The two kinds of semantic effects in EPs were largely independent. The behavioral data supported Osgoods results and showed that our subjects were appropriately processing the semantic information. The common analyses of data from all subjects suggest the universality of the connotative EP effects across individuals. This parallels, at the neural level, the universality of the connotative dimensions found at the behavioral level by semantic differential ratings. The EP effects imply that the neural representation of meaning is similar in different individuals.

Predicting conversion from mild cognitive impairment to Alzheimer's disease using neuropsychological tests and multivariate methods.

Behavioral markers measured through neuropsychological testing in mild cognitive impairment (MCI) were analyzed and combined in multivariate ways to predict conversion to Alzheimers disease (AD) in a longitudinal study of 43 MCI patients. The test measures taken at a baseline evaluation were first reduced to underlying components (principal component analysis, PCA), and then the component scores were used in discriminant analysis to classify MCI individuals as likely to convert or not. When empirically weighted and combined, episodic memory, speeded executive functioning, recognition memory (false and true positives), visuospatial memory processing speed, and visuospatial episodic memory were together strong predictors of conversion to AD. These multivariate combinations of the test measures achieved through the PCA were good, statistically significant predictors of MCI conversion to AD (84% accuracy, 86% sensitivity, and 83% specificity). Importantly, the posterior probabilities of group membership that accompanied the binary prediction for each participant indicated the confidence of the prediction. Most of the participants (81%) were in the highly confident probability bins (.70–1.00), where the obtained prediction accuracy was more than 90%. The strength and reliability of this multivariate prediction method were tested by cross-validation and randomized resampling.

Brain responses related to semantic meaning

Evoked Potentials from electroencephalogram (EEG) recording were averaged to many visually presented word stimuli whose semantic meanings were specified along Osgoods semantic dimensions of Evaluation, Potency, and Activity [Miron & Osgood, 1966, in R. B. Cattell (Ed.), Handbook of multivariate experimental psychology, Chicago: Rand-McNally; Osgood, 1971, Journal of Social Issues, 27, 5–63; Osgood, May, & Miron, 1975, Cross-cultural universals of affective meaning, Urbana, Ill.: University of Illinois Press]. Multivariate analyses classified the Evoked Potentials to six semantic classes with success rates more than twice chance expectation. The pattern of brain activity related to the six semantic classes was similar for (i) two sets of words, (ii) 10 subjects used to develop the analyses, and (iii) an added, new subject.

Women have Farther to Fall: Gender Differences Between Normal Elderly and Alzheimer's Disease in Verbal Memory Engender Better Detection of Alzheimer's Disease in Women

We analyzed verbal episodic memory learning and recall using the Logical Memory (LM) subtest of the Wechsler Memory Scale-III to determine how gender differences in AD compare to those seen in normal elderly and whether or not these differences impact assessment of AD. We administered the LM to both an AD and a Control group, each comprised of 21 men and 21 women, and found a large drop in performance from normal elders to AD. Of interest was a gender interaction whereby the womens scores dropped 1.6 times more than the mens did. Control women on average outperformed Control men on every aspect of the test, including immediate recall, delayed recall, and learning. Conversely, AD women tended to perform worse than AD men. Additionally, the LM achieved perfect diagnostic accuracy in discriminant analysis of AD versus Control women, a statistically significantly higher result than for men. The results indicate the LM is a more powerful and reliable tool in detecting AD in women than in men.

Diagnosis of Alzheimer's disease using neuropsychological testing improved by multivariate analyses

Neuropsychological assessment aids in the diagnosis of Alzheimers disease (AD) by objectively establishing cognitive impairment from standardized tests. We present new criteria for diagnosis that use weighted combined scores from multiple tests. Our method employs two multivariate analyses: principal components analysis (PCA) and discriminant analysis. PCA (N = 216 participants) created more interpretable cognitive dimensions by resolving 49 test measures in our neuropsychological battery to 13 component scores for each participant. The component scores were used to build discriminant functions that classified each participant as either an early-stage AD (N = 55) or normal elderly (N = 78). Our discriminant function performed with high accuracy, sensitivity, and specificity (nearly all >90%) in the development, a cross-validation, and a new-subjects validation. When contrasted to two different traditional empirical methods for diagnosis (using cutscores and defining AD as falling below 5% on two or more test domains), our results suggested that the multivariate method was superior in classification (approximately 20% more accurate).

Distribution of Latent Components Related to Information Processinga

Endogeneous components of evoked potentials (EPs) are commonly defined by their correlation with internal stimulus processing mechanisms and their independence of the physical stimulus characteristics (Donchin er al., 1978). In the present study, we investigated evoked potentials recorded during performance on an information processing task. In previous studies, latent components have been identified which were related to attention, relevance of the stimulus and the probability of occurrence of a task-relevant stimulus (Chapman et al., 1978; 1979). We were interested not only in the temporal characteristics of components of the evoked potentials but also in their spatial distribution on the scalp. Therefore, EEG recordings were obtained simultaneously from 16 scalp locations. In order to investigate the relationship of central projections of the visual field to the evoked potential components, we also varied the stimulus location on the retina.

Cognitive Dimensions in Alzheimer’s Disease, Mild Cognitive Impairment, and Normal Elderly: Developing a Common Metric

The aim of this research was to assess similarity in cognitive factor structures underlying neuropsychological test performance of elders belonging to three clinical groups: Alzheimers disease (AD), Mild Cognitive Impairment (MCI), and normal elderly. We administered a battery of neuropsychological tests to 214 elderly participants in the groups. First, the underlying cognitive structure of a Combined-Set of AD, MCI, and Control subjects was determined by Principal Components Analysis (PCA), including quantitative relationships (loadings) between the test measures and the factors. The PCA resolved 17 neuropsychological test measures into 6 interpretable factors, accounting for 78% of the variance. This cognitive structure was compared with separate cognitive structures from an AD-Set, an MCI-Set, and a Control-Set (different individuals in each set) in additional PCA using Procrustes factor rotation. Analysis of congruence coefficients between each set and the Combined-Set by a bootstrapping statistical procedure supported the factor invariance hypothesis. These close similarities across groups in their underlying neuropsychological dimensions support the use of a common metric system (the factor structure of a Combined-Set) for measuring neuropsychological factors in all these elderly individuals.

Hemispheric Differences in Evoked Potentials to Relevant and Irrelevant Visual Stimuli

Since the early days of averaging evoked potentials (EPs) in man, the importance of cognitive variables, as well as stimulus variables, has been recognized (e.g., Chapman and Bragdon, 1964). Using an experimental design which involves processing number and letter stimuli, we have been studying EP effects related to a variety of cognitive operations (Chapman, 1965, 1966, 1969a, 1969b, 1973, 1974a, 1974b, 1977, in press; Chapman et al., in press (a); Chapman et al. in press (b). Most of our analyses have been for the CPZ scalp location (recorded monopolar on the midline one-third of the distance from Cz to Pz; reference was linked ear- lobes). It is of interest to study the cognitive effects at other sites, with a particular focus on the question of hemispheric differences and parietal-occipital differences.

C145 as a Short-Latency Electrophysiological Index of Cognitive Compensation in Alzheimer's Disease

Brain plasticity and cognitive compensation in the elderly are of increasing interest, and Alzheimers disease (AD) offers an opportunity to elucidate how the brain may overcome damage. We provide neurophysiological evidence of a short-latency event-related potential (ERP) component (C145) linked to stimulus relevancy that may reflect cognitive compensation in early-stage AD. Thirty-six subjects with early-stage, mild AD and 36 like-aged normal elderly (controls) had their EEG recorded while performing our Number-Letter task, a cognitive/perceptual paradigm that manipulates stimulus relevancies. ERP components, including C145, were extracted from ERPs using principal components analysis. C145 amplitudes and spatial distributions were compared among controls, AD subjects with high performance on the Number-Letter task, and AD subjects with low performance. Compared to AD subjects, control subjects showed enhanced C145 processing of visual stimuli in the occipital region where differential processing of relevant stimuli occurred. AD high performers recruited central brain areas in processing task relevancy. Controls and AD low performers did not show a significant task relevancy effect in these areas. We conclude that short-latency ERP components can detect electrophysiological differences in early-stage AD that reflect altered cognition. Differences in C145 amplitudes between AD and normal elderly groups regarding brain locations and types of task effects suggest compensatory mechanisms can occur in the AD brain to overcome loss of normal functionality, and this early compensation may have a profound effect on the cognitive efficiency of AD individuals.