MEG biomarker of Alzheimer's disease: Absence of a prefrontal generator during auditory sensory gating

• Published in: Human brain mapping 2017-10, Vol.38 (10), p.5180-5194
• Main Authors: Josef Golubic, Sanja, Aine, Cheryl J., Stephen, Julia M., Adair, John C., Knoefel, Janice E., Supek, Selma
• Format: Article
• Language: English
• Subjects: Acoustic Stimulation; Activation; Aged; Aged, 80 and over; Alzheimer Disease - diagnosis; Alzheimer Disease - diagnostic imaging; Alzheimer Disease - physiopathology; Alzheimer Disease - psychology; Alzheimer's disease; Auditory perception; Auditory Perception - physiology; auditory sensory gating; biomarker; Biomarkers; Brain; Cluster Analysis; dementia; Female; Gating; Generators; Humans; Localization; Magnetic Resonance Imaging; Magnetoencephalography; Male; Middle Aged; mild cognitive impairment; Neurodegenerative diseases; neuroimaging; Neuropsychological Tests; preclinical Alzheimer's disease; prefrontal cortex; Prefrontal Cortex - diagnostic imaging; Prefrontal Cortex - physiopathology; Principal Component Analysis; Rey–Osterreith complex figure test; Sensitivity; Sensitivity analysis; Sensitivity and Specificity; Sensory Gating - physiology; Signal Processing, Computer-Assisted; Topology
• ISSN: 1065-9471; 1097-0193
• DOI: 10.1002/hbm.23724

Magnetoencephalography (MEG), a direct measure of neuronal activity, is an underexplored tool in the search for biomarkers of Alzheimer's disease (AD). In this study, we used MEG source estimates of auditory gating generators, nonlinear correlations with neuropsychological results, and multivariate analyses to examine the sensitivity and specificity of gating topology modulation to detect AD. Our results demonstrated the use of MEG localization of a medial prefrontal (mPFC) gating generator as a discrete (binary) detector of AD at the individual level and resulted in recategorizing the participant categories in: (1) controls with mPFC generator localized in response to both the standard and deviant tones; (2) a possible preclinical stage of AD participants (a lower functioning group of controls) in which mPFC activation was localized to the deviant tone only; and (3) symptomatic AD in which mPFC activation was not localized to either the deviant or standard tones. This approach showed a large effect size (0.9) and high accuracy, sensitivity, and specificity (100%) in identifying symptomatic AD patients within a limited research sample. The present results demonstrate high potential of mPFC activation as a noninvasive biomarker of AD pathology during putative preclinical and clinical stages. Hum Brain Mapp 38:5180–5194, 2017. © 2017 Wiley Periodicals, Inc.