Spontaneous low frequency BOLD signal variations from resting-state fMRI are decreased in Alzheimer disease

PLoS One. 2017 Jun 5;12(6):e0178529. doi: 10.1371/journal.pone.0178529. eCollection 2017.

Abstract

Previous studies have demonstrated altered brain activity in Alzheimer's disease using task based functional MRI (fMRI), network based resting-state fMRI, and glucose metabolism from 18F fluorodeoxyglucose-PET (FDG-PET). Our goal was to define a novel indicator of neuronal activity based on a first-order textural feature of the resting state functional MRI (RS-fMRI) signal. Furthermore, we examined the association between this neuronal activity metric and glucose metabolism from 18F FDG-PET. We studied 15 normal elderly controls (NEC) and 15 probable Alzheimer disease (AD) subjects from the AD Neuroimaging Initiative. An independent component analysis was applied to the RS-fMRI, followed by template matching to identify neuronal components (NC). A regional brain activity measurement was constructed based on the variation of the RS-fMRI signal of these NC. The standardized glucose uptake values of several brain regions relative to the cerebellum (SUVR) were measured from partial volume corrected FDG-PET images. Comparing the AD and NEC groups, the mean brain activity metric was significantly lower in the accumbens, while the glucose SUVR was significantly lower in the amygdala and hippocampus. The RS-fMRI brain activity metric was positively correlated with cognitive measures and amyloid β1-42 cerebral spinal fluid levels; however, these did not remain significant following Bonferroni correction. There was a significant linear correlation between the brain activity metric and the glucose SUVR measurements. This proof of concept study demonstrates that this novel and easy to implement RS-fMRI brain activity metric can differentiate a group of healthy elderly controls from a group of people with AD.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / cerebrospinal fluid*
  • Alzheimer Disease / diagnosis
  • Alzheimer Disease / physiopathology
  • Amygdala / metabolism*
  • Amygdala / physiopathology
  • Amyloid beta-Peptides / cerebrospinal fluid
  • Case-Control Studies
  • Cerebellum / metabolism*
  • Cerebellum / physiopathology
  • Databases, Factual
  • Female
  • Fluorodeoxyglucose F18 / administration & dosage
  • Hippocampus / metabolism*
  • Hippocampus / physiopathology
  • Humans
  • Magnetic Resonance Imaging / methods*
  • Male
  • Nucleus Accumbens / metabolism*
  • Nucleus Accumbens / physiopathology
  • Peptide Fragments / cerebrospinal fluid
  • Positron-Emission Tomography
  • Radiopharmaceuticals / administration & dosage

Substances

  • Amyloid beta-Peptides
  • Peptide Fragments
  • Radiopharmaceuticals
  • amyloid beta-protein (1-42)
  • Fluorodeoxyglucose F18

Grants and funding

This study was funded by the Canadian Institute of Health Research (www.cihr-irsc.gc.ca/) with grant CSE 133350. Data collection and sharing for this project was funded by the Alzheimer's Disease Neuroimaging Initiative (National Institutes of Health Grant U01 AG024904) and DOD ADNI (Department of Defense award number W81XWH-12-2-0012). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: AbbVie, Alzheimer’s Association; Alzheimer’s Drug Discovery Foundation; Araclon Biotech; BioClinica, Inc.; Biogen; Bristol-Myers Squibb Company; CereSpir, Inc.; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; EuroImmun; F. Hoffmann-La Roche Ltd and its affiliated company Genentech, Inc.; Fujirebio; GE Healthcare; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development LLC.; Lumosity; Lundbeck; Merck & Co., Inc.; Meso Scale Diagnostics, LLC.; NeuroRx Research; Neurotrack Technologies; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Takeda Pharmaceutical Company; and Transition Therapeutics. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (www.fnih.org). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer's Disease Cooperative Study at the University of California, San Diego. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of Southern California. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.