ABSTRACT
Previous work has suggested that evoked potential analysis might allow the detection of subjects with new-onset Alzheimer's disease, which would be useful clinically and personally. Here, it is described how subjects with new-onset Alzheimer's disease have been differentiated from healthy, normal subjects to 100% accuracy, based on the back-projected independent components (BICs) of the P300 peak at the electroencephalogram electrodes in the response to an oddball, auditory-evoked potential paradigm. After artifact removal, clustering, selection, and normalization processes, the BICs were classified using a neural network, a Bayes classifier, and a voting strategy. The technique is general and might be applied for presymptomatic detection and to other conditions and evoked potentials, although further validation with more subjects, preferably in multicenter studies is recommended.
Subject(s)
Alzheimer Disease/diagnosis , Cerebral Cortex , Cognitive Dysfunction/diagnosis , Electroencephalography/methods , Event-Related Potentials, P300 , Evoked Potentials, Auditory , Neural Networks, Computer , Aged , Alzheimer Disease/physiopathology , Cerebral Cortex/physiopathology , Cognitive Dysfunction/physiopathology , Event-Related Potentials, P300/physiology , Evoked Potentials, Auditory/physiology , Female , Humans , Male , Models, TheoreticalABSTRACT
The objective was to characterize the non-oscillatory independent components (ICs) of the auditory event-related potential (ERP) waveform of an oddball task for normal and newly diagnosed Alzheimer's disease (AD) subjects, and to seek biomarkers for AD. Single trial ERP waveforms were analysed using independent components analysis (ICA) and k-means clustering. Two stages of clustering depended upon the magnitudes and latencies, and the scalp topographies of the non-oscillatory back-projected ICs (BICs) at electrode Cz. The electrical current dipole sources of the BICs were located using Low Resolution Electromagnetic Tomography (LORETA). Generally 3-10 BICs, of different latencies and polarities, occurred in each trial. Each peak was associated with positive and negative BICs. The trial-to-trial variations in their relative numbers and magnitudes may explain the variations in the averaged ERP reported, and the delay in the averaged P300 for AD patients. The BIC latencies, topographies and electrical current density maximum locations varied from trial-to-trial. Voltage foci in the BIC topographies identify the BIC source locations. Since statistical differences were found between the BICs in healthy and AD subjects, the method might provide reliable biomarkers for AD, if these findings are reproduced in a larger study, independently of other factors influencing the comparison of the two populations. The method can extract artefact- and EEG-free single trial ERP waveforms, offers improved ERP averages by selecting the trials on the basis of their BICs, and is applicable to other evoked potentials, conditions and diseases.
