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@ARTICLE{Strain:165167,
      author       = {Strain, Jeremy F and Brier, Matthew R and Tanenbaum, Aaron
                      and Gordon, Brian A and McCarthy, John E and Dincer, Aylin
                      and Marcus, Daniel S and Chhatwal, Jasmeer P and
                      Graff-Radford, Neill R and Day, Gregory S and la Fougère,
                      Christian and Perrin, Richard J and Salloway, Stephen and
                      Schofield, Peter R and Yakushev, Igor and Ikeuchi, Takeshi
                      and Vöglein, Jonathan and Morris, John C and Benzinger,
                      Tammie L S and Bateman, Randall J and Ances, Beau M and
                      Snyder, Abraham Z},
      collaboration = {Network, Dominantly Inherited Alzheimer},
      title        = {{C}ovariance-based vs. correlation-based functional
                      connectivity dissociates healthy aging from {A}lzheimer
                      disease.},
      journal      = {NeuroImage},
      volume       = {261},
      issn         = {1053-8119},
      address      = {Orlando, Fla.},
      publisher    = {Academic Press},
      reportid     = {DZNE-2022-01469},
      pages        = {119511},
      year         = {2022},
      abstract     = {Prior studies of aging and Alzheimer disease have evaluated
                      resting state functional connectivity (FC) using either
                      seed-based correlation (SBC) or independent component
                      analysis (ICA), with a focus on particular functional
                      systems. SBC and ICA both are insensitive to differences in
                      signal amplitude. At the same time, accumulating evidence
                      indicates that the amplitude of spontaneous BOLD signal
                      fluctuations is physiologically meaningful. We
                      systematically compared covariance-based FC, which is
                      sensitive to amplitude, vs. correlation-based FC, which is
                      not, in affected individuals and controls drawn from two
                      cohorts of participants including autosomal dominant
                      Alzheimer disease (ADAD), late onset Alzheimer disease
                      (LOAD), and age-matched controls. Functional connectivity
                      was computed over 222 regions of interest and group
                      differences were evaluated in terms of components projected
                      onto a space of lower dimension. Our principal observations
                      are: (1) Aging is associated with global loss of resting
                      state fMRI signal amplitude that is approximately uniform
                      across resting state networks. (2) Thus, covariance FC
                      measures decrease with age whereas correlation FC is
                      relatively preserved in healthy aging. (3) In contrast,
                      symptomatic ADAD and LOAD both lead to loss of spontaneous
                      activity amplitude as well as severely degraded correlation
                      structure. These results demonstrate a double dissociation
                      between age vs. Alzheimer disease and the amplitude vs.
                      correlation structure of resting state BOLD signals.
                      Modeling results suggest that the AD-associated loss of
                      correlation structure is attributable to a relative increase
                      in the fraction of locally restricted as opposed to widely
                      shared variance.},
      keywords     = {Aging / Alzheimer Disease: diagnostic imaging / Brain:
                      physiology / Healthy Aging / Humans / Magnetic Resonance
                      Imaging: methods / Aging (Other) / Autosomal dominant
                      Alzheimer disease (Other) / Covariance (Other) / Late onset
                      Alzheimer disease (Other) / Resting-state functional
                      connectivity (Other)},
      cin          = {Tübingen common},
      ddc          = {610},
      cid          = {I:(DE-2719)6000018},
      pnm          = {353 - Clinical and Health Care Research (POF4-353)},
      pid          = {G:(DE-HGF)POF4-353},
      typ          = {PUB:(DE-HGF)16},
      pmc          = {pmc:PMC9750733},
      pubmed       = {pmid:35914670},
      doi          = {10.1016/j.neuroimage.2022.119511},
      url          = {https://pub.dzne.de/record/165167},
}