{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Strain JF"],"funding":["NCATS NIH HHS","NIBIB NIH HHS","NIA NIH HHS","Medical Research Council","NINR NIH HHS","NINDS NIH HHS"],"pagination":["119511"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9750733"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["261"],"pubmed_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."],"journal":["NeuroImage"],"pubmed_title":["Covariance-based vs. correlation-based functional connectivity dissociates healthy aging from Alzheimer disease."],"pmcid":["PMC9750733"],"funding_grant_id":["R01 AG052550","R01 NR014449","MR/009076/1","UL1 TR002345","K01 AG053474","UF1 AG032438","R01 NR012657","P01 AG036694","UL1 TR000448","R01 NR012907","P30 NS098577","P30 NS048056","MR/L023784/1","R25 NS090978","P30 AG066444","P01 NS080675","R01 EB009352","P01 AG026276","R01 AG062667","P01 AG003991"],"pubmed_authors":["McCarthy JE","Chhatwal JP","Salloway S","Dominantly Inherited Alzheimer Network","Day GS","Ikeuchi T","Bateman RJ","Ances BM","Graff-Radford NR","Snyder AZ","Morris JC","Marcus DS","Gordon BA","Tanenbaum A","Yakushev I","la Fougere C","Schofield PR","Strain JF","Brier MR","Voglein J","Perrin RJ","Benzinger TLS","Dincer A"],"additional_accession":[]},"is_claimable":false,"name":"Covariance-based vs. correlation-based functional connectivity dissociates healthy aging from Alzheimer disease.","description":"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.","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Nov","modification":"2025-04-18T16:31:50.603Z","creation":"2025-04-07T03:47:13.686Z"},"accession":"S-EPMC9750733","cross_references":{"pubmed":["35914670"],"doi":["10.1016/j.neuroimage.2022.119511"]}}