Default Mode Network quantitative diffusion and resting‐state functional magnetic resonance imaging correlates in sporadic Creutzfeldt‐Jakob disease

Grey matter involvement is a well‐known feature in sporadic Creutzfeldt–Jakob disease (sCJD), yet precise anatomy‐based quantification of reduced diffusivity is still not fully understood. Default Mode Network (DMN) areas have been recently demonstrated as selectively involved in sCJD, and functiona...

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Published inHuman brain mapping Vol. 43; no. 13; pp. 4158 - 4173
Main Authors Paoletti, Matteo, Caverzasi, Eduardo, Mandelli, Maria Luisa, Brown, Jesse A., Henry, Roland G., Miller, Bruce L., Rosen, Howard J., DeArmond, Stephen J., Bastianello, Stefano, Seeley, William W., Geschwind, Michael D.
Format Journal Article
LanguageEnglish
Published Hoboken, USA John Wiley & Sons, Inc 01.09.2022
Subjects
Autopsies
Autopsy
Biomarkers
Brain - diagnostic imaging
Brain - pathology
CJD
Creutzfeldt-Jakob disease
Creutzfeldt-Jakob Syndrome - diagnostic imaging
Creutzfeldt-Jakob Syndrome - pathology
Default Mode Network
Diffusion Magnetic Resonance Imaging - methods
Diffusivity
DMN
fMRI
Functional magnetic resonance imaging
Humans
Magnetic Resonance Imaging
mean diffusivity
Medical imaging
MRI
Prion protein
resting‐state
sporadic Jakob–Creutzfeldt disease
Subgroups
Substantia grisea
fMRI
DMN
MRI
sporadic Jakob-Creutzfeldt disease
MD
CJD
mean diffusivity
resting-state
Online AccessGet full text
ISSN1065-9471
1097-0193
1097-0193
DOI10.1002/hbm.25945

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Abstract Grey matter involvement is a well‐known feature in sporadic Creutzfeldt–Jakob disease (sCJD), yet precise anatomy‐based quantification of reduced diffusivity is still not fully understood. 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‐parametric MRI approach. Specifically, grey matter mean diffusivity of 37 subjects with sCJD was compared with that of 30 age‐matched healthy controls with a group‐wise 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 (n = 27, 73%). We also assessed resting‐state functional connectivity of both ventral and dorsal components of DMN in a subset of subject with a rs‐fMRI dataset available (n = 17). 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‐inferior 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. In our study we explored quantitatively the diffusivity of grey matter and resting‐state functional connectivity in a cohort of sporadic Creutzfeldt‐Jakob subjects and found an involvement of areas included in the Default Mode Network. Combined quantitative diffusivity and functional data at rest may provide useful novel insights in the understanding of prion diseases.
AbstractList Grey matter involvement is a well‐known feature in sporadic Creutzfeldt–Jakob disease (sCJD), yet precise anatomy‐based quantification of reduced diffusivity is still not fully understood. 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‐parametric MRI approach. Specifically, grey matter mean diffusivity of 37 subjects with sCJD was compared with that of 30 age‐matched healthy controls with a group‐wise 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 ( n  = 27, 73%). We also assessed resting‐state functional connectivity of both ventral and dorsal components of DMN in a subset of subject with a rs‐fMRI dataset available ( n  = 17). 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‐inferior 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.
Grey matter involvement is a well-known feature in sporadic Creutzfeldt-Jakob disease (sCJD), yet precise anatomy-based quantification of reduced diffusivity is still not fully understood. 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-parametric MRI approach. Specifically, grey matter mean diffusivity of 37 subjects with sCJD was compared with that of 30 age-matched healthy controls with a group-wise 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 (n = 27, 73%). We also assessed resting-state functional connectivity of both ventral and dorsal components of DMN in a subset of subject with a rs-fMRI dataset available (n = 17). 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-inferior 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.Grey matter involvement is a well-known feature in sporadic Creutzfeldt-Jakob disease (sCJD), yet precise anatomy-based quantification of reduced diffusivity is still not fully understood. 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-parametric MRI approach. Specifically, grey matter mean diffusivity of 37 subjects with sCJD was compared with that of 30 age-matched healthy controls with a group-wise 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 (n = 27, 73%). We also assessed resting-state functional connectivity of both ventral and dorsal components of DMN in a subset of subject with a rs-fMRI dataset available (n = 17). 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-inferior 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.
Grey matter involvement is a well-known feature in sporadic Creutzfeldt-Jakob disease (sCJD), yet precise anatomy-based quantification of reduced diffusivity is still not fully understood. 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-parametric MRI approach. Specifically, grey matter mean diffusivity of 37 subjects with sCJD was compared with that of 30 age-matched healthy controls with a group-wise 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 (n = 27, 73%). We also assessed resting-state functional connectivity of both ventral and dorsal components of DMN in a subset of subject with a rs-fMRI dataset available (n = 17). 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-inferior 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.
Grey matter involvement is a well‐known feature in sporadic Creutzfeldt–Jakob disease (sCJD), yet precise anatomy‐based quantification of reduced diffusivity is still not fully understood. 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‐parametric MRI approach. Specifically, grey matter mean diffusivity of 37 subjects with sCJD was compared with that of 30 age‐matched healthy controls with a group‐wise 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 (n = 27, 73%). We also assessed resting‐state functional connectivity of both ventral and dorsal components of DMN in a subset of subject with a rs‐fMRI dataset available (n = 17). 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‐inferior 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. In our study we explored quantitatively the diffusivity of grey matter and resting‐state functional connectivity in a cohort of sporadic Creutzfeldt‐Jakob subjects and found an involvement of areas included in the Default Mode Network. Combined quantitative diffusivity and functional data at rest may provide useful novel insights in the understanding of prion diseases.
Grey matter involvement is a well‐known feature in sporadic Creutzfeldt–Jakob disease (sCJD), yet precise anatomy‐based quantification of reduced diffusivity is still not fully understood. 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‐parametric MRI approach. Specifically, grey matter mean diffusivity of 37 subjects with sCJD was compared with that of 30 age‐matched healthy controls with a group‐wise 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 (n = 27, 73%). We also assessed resting‐state functional connectivity of both ventral and dorsal components of DMN in a subset of subject with a rs‐fMRI dataset available (n = 17). 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‐inferior 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.
Grey matter involvement is a well‐known feature in sporadic Creutzfeldt–Jakob disease (sCJD), yet precise anatomy‐based quantification of reduced diffusivity is still not fully understood. 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‐parametric MRI approach. Specifically, grey matter mean diffusivity of 37 subjects with sCJD was compared with that of 30 age‐matched healthy controls with a group‐wise 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 ( n  = 27, 73%). We also assessed resting‐state functional connectivity of both ventral and dorsal components of DMN in a subset of subject with a rs‐fMRI dataset available ( n  = 17). 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‐inferior 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. In our study we explored quantitatively the diffusivity of grey matter and resting‐state functional connectivity in a cohort of sporadic Creutzfeldt‐Jakob subjects and found an involvement of areas included in the Default Mode Network. Combined quantitative diffusivity and functional data at rest may provide useful novel insights in the understanding of prion diseases.
Author Henry, Roland G.
Paoletti, Matteo
Mandelli, Maria Luisa
DeArmond, Stephen J.
Miller, Bruce L.
Geschwind, Michael D.
Brown, Jesse A.
Rosen, Howard J.
Seeley, William W.
Caverzasi, Eduardo
Bastianello, Stefano
AuthorAffiliation 4 Department of Brain and Behavioral Sciences University of Pavia Pavia Italy
1 Memory and Aging Center, Department of Neurology, Weill Institute for Neuroscience University of California San Francisco San Francisco California USA
6 Department of Radiology and Biomedical Imaging University of California San Francisco San Francisco California USA
7 Department of Pathology University of California San Francisco California USA
5 Graduate Group in Bioengineering University of California San Francisco San Francisco California USA
3 Weill Institute for Neurosciences, Department of Neurology University of California San Francisco San Francisco California USA
2 Department of Neuroradiology IRCCS Mondino Foundation Pavia Italy
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CitedBy_id crossref_primary_10_1002_acn3_51739
crossref_primary_10_1587_transinf_2022EDL8049
crossref_primary_10_1212_CON_0000000000001248
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IngestDate Thu Aug 21 17:55:45 EDT 2025
Fri Sep 05 11:48:40 EDT 2025
Sat Jul 26 02:29:56 EDT 2025
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IsDoiOpenAccess true
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Issue 13
Keywords fMRI
DMN
MRI
sporadic Jakob-Creutzfeldt disease
MD
CJD
mean diffusivity
resting-state
Language English
License Attribution-NonCommercial
2022 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.
This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
LinkModel DirectLink
MergedId FETCHMERGED-LOGICAL-c5095-d85ac16176f67e7b2358fd3a03bb8126f420719226fa9164f15fc48b9d4a79243
Notes Funding information
Matteo Paoletti and Eduardo Caverzasi contributed equally to this work.
Larry L. Hillblom Foundation Hellman Family Foundation; Michael J. Homer Family Fund; National Institutes of Health (NIH), Grant/Award Numbers: R01 AG031189, R56AG055619, R01AG062562, P30AG062422, UL1RR024131, UL1TR000004, R01AG032289
ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 14
content type line 23
Funding information Larry L. Hillblom Foundation Hellman Family Foundation; Michael J. Homer Family Fund; National Institutes of Health (NIH), Grant/Award Numbers: R01 AG031189, R56AG055619, R01AG062562, P30AG062422, UL1RR024131, UL1TR000004, R01AG032289
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0000-0002-8232-7562
0000-0001-9281-7402
0000-0002-0350-0460
OpenAccessLink https://proxy.k.utb.cz/login?url=https://onlinelibrary.wiley.com/doi/abs/10.1002%2Fhbm.25945
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PublicationTitle Human brain mapping
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Snippet Grey matter involvement is a well‐known feature in sporadic Creutzfeldt–Jakob disease (sCJD), yet precise anatomy‐based quantification of reduced diffusivity...
Grey matter involvement is a well-known feature in sporadic Creutzfeldt-Jakob disease (sCJD), yet precise anatomy-based quantification of reduced diffusivity...
SourceID pubmedcentral
proquest
pubmed
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wiley
SourceType Open Access Repository
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StartPage 4158
SubjectTerms Autopsies
Autopsy
Biomarkers
Brain - diagnostic imaging
Brain - pathology
CJD
Creutzfeldt-Jakob disease
Creutzfeldt-Jakob Syndrome - diagnostic imaging
Creutzfeldt-Jakob Syndrome - pathology
Default Mode Network
Diffusion Magnetic Resonance Imaging - methods
Diffusivity
DMN
fMRI
Functional magnetic resonance imaging
Humans
Magnetic Resonance Imaging
mean diffusivity
Medical imaging
MRI
Prion protein
resting‐state
sporadic Jakob–Creutzfeldt disease
Subgroups
Substantia grisea
Title Default Mode Network quantitative diffusion and resting‐state functional magnetic resonance imaging correlates in sporadic Creutzfeldt‐Jakob disease
URI https://onlinelibrary.wiley.com/doi/abs/10.1002%2Fhbm.25945
https://www.ncbi.nlm.nih.gov/pubmed/35662331
https://www.proquest.com/docview/2701325401
https://www.proquest.com/docview/2673598848
https://pubmed.ncbi.nlm.nih.gov/PMC9374887
Volume 43
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