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Default Mode Network (DMN) areas have been recently demonstrated as selectively involved in sCJD, and functional connectivity has never been investigated in prion diseases. We analyzed the grey matter involvement using a quantitatively multi\u2010parametric MRI approach. Specifically, grey matter mean diffusivity of 37 subjects with sCJD was compared with that of 30 age\u2010matched healthy controls with a group\u2010wise approach. Differences in mean diffusivity were also examined between the cortical (MM(V)1, MM(V)2C, and VV1) and subcortical (VV2 and MV2K) subgroups of sCJD for those with autopsy data available (<jats:italic>n<\/jats:italic>\u00a0=\u00a027, 73%). We also assessed resting\u2010state functional connectivity of both ventral and dorsal components of DMN in a subset of subject with a rs\u2010fMRI dataset available (<jats:italic>n<\/jats:italic>\u00a0=\u00a017). Decreased diffusivity was predominantly present in posterior cortical regions of the DMN, but also outside of the DMN in temporal areas and in a few limbic and frontal areas, in addition to extensive deep nuclei involvement. Both subcortical and cortical sCJD subgroups showed decreased diffusivity subcortically, whereas only the cortical type expressed significantly decreased diffusivity cortically, mainly in parietal, occipital, and medial\u2010inferior temporal cortices bilaterally. Interestingly, we found abnormally increased connectivity in both dorsal and ventral components of the DMN in sCJD subjects compared with healthy controls. The significance and possible utility of functional imaging as a biomarker for tracking disease progression in prion disease needs to be explored further.<\/jats:p>","DOI":"10.1002\/hbm.25945","type":"journal-article","created":{"date-parts":[[2022,6,6]],"date-time":"2022-06-06T09:37:37Z","timestamp":1654508257000},"page":"4158-4173","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Default Mode Network quantitative diffusion and resting\u2010state functional magnetic resonance imaging correlates in sporadic Creutzfeldt\u2010Jakob disease"],"prefix":"10.1002","volume":"43","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1221-7747","authenticated-orcid":false,"given":"Matteo","family":"Paoletti","sequence":"first","affiliation":[{"name":"Memory and Aging Center, Department of Neurology, Weill Institute for Neuroscience University of California San Francisco  San Francisco California USA"},{"name":"Department of Neuroradiology IRCCS Mondino Foundation  Pavia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0350-0460","authenticated-orcid":false,"given":"Eduardo","family":"Caverzasi","sequence":"additional","affiliation":[{"name":"Weill Institute for Neurosciences, Department of Neurology University of California San Francisco  San Francisco California USA"},{"name":"Department of Brain and Behavioral Sciences University of Pavia  Pavia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2518-2520","authenticated-orcid":false,"given":"Maria Luisa","family":"Mandelli","sequence":"additional","affiliation":[{"name":"Memory and Aging Center, Department of Neurology, Weill Institute for Neuroscience University of California San Francisco  San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3139-9451","authenticated-orcid":false,"given":"Jesse A.","family":"Brown","sequence":"additional","affiliation":[{"name":"Memory and Aging Center, Department of Neurology, Weill Institute for Neuroscience University of California San Francisco  San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8232-7562","authenticated-orcid":false,"given":"Roland G.","family":"Henry","sequence":"additional","affiliation":[{"name":"Weill Institute for Neurosciences, Department of Neurology University of California San Francisco  San Francisco California USA"},{"name":"Graduate Group in Bioengineering University of California San Francisco  San Francisco California USA"},{"name":"Department of Radiology and Biomedical Imaging University of California San Francisco  San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2152-4220","authenticated-orcid":false,"given":"Bruce L.","family":"Miller","sequence":"additional","affiliation":[{"name":"Memory and Aging Center, Department of Neurology, Weill Institute for Neuroscience University of California San Francisco  San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9281-7402","authenticated-orcid":false,"given":"Howard J.","family":"Rosen","sequence":"additional","affiliation":[{"name":"Memory and Aging Center, Department of Neurology, Weill Institute for Neuroscience University of California San Francisco  San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen J.","family":"DeArmond","sequence":"additional","affiliation":[{"name":"Department of Pathology University of California  San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Bastianello","sequence":"additional","affiliation":[{"name":"Department of Neuroradiology IRCCS Mondino Foundation  Pavia Italy"},{"name":"Department of Brain and Behavioral Sciences University of Pavia  Pavia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1410-2027","authenticated-orcid":false,"given":"William W.","family":"Seeley","sequence":"additional","affiliation":[{"name":"Memory and Aging Center, Department of Neurology, Weill Institute for Neuroscience University of California San Francisco  San Francisco California USA"},{"name":"Department of Pathology University of California  San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2861-3776","authenticated-orcid":false,"given":"Michael D.","family":"Geschwind","sequence":"additional","affiliation":[{"name":"Memory 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