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

Hum Brain Mapp. 2017 Oct;38(10):5180-5194. doi: 10.1002/hbm.23724. Epub 2017 Jul 17.

Abstract

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.

Keywords: Alzheimer's disease; Rey-Osterreith complex figure test; auditory sensory gating; biomarker; dementia; magnetoencephalography; mild cognitive impairment; neuroimaging; preclinical Alzheimer's disease; prefrontal cortex.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acoustic Stimulation
  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / diagnosis*
  • Alzheimer Disease / diagnostic imaging
  • Alzheimer Disease / physiopathology*
  • Alzheimer Disease / psychology
  • Auditory Perception / physiology*
  • Cluster Analysis
  • Female
  • Humans
  • Magnetic Resonance Imaging
  • Magnetoencephalography*
  • Male
  • Middle Aged
  • Neuropsychological Tests
  • Prefrontal Cortex / diagnostic imaging
  • Prefrontal Cortex / physiopathology*
  • Principal Component Analysis
  • Sensitivity and Specificity
  • Sensory Gating / physiology*
  • Signal Processing, Computer-Assisted