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Resting State Network Modularity Along the Prodromal Late Onset Alzheimer's Disease Continuum

34 Pages Posted: 4 Sep 2018 First Look: Under Review

See all articles by Joey Contreras

Joey Contreras

USC-Keck School of Medicine ; Indiana University - Department of Radiology and Imaging Sciences

Andrea Avena-Koenigsberger

Indiana University Bloomington - Department of Psychological and Brain Sciences

Shannon L. Risacher

Indiana University Purdue University Indianapolis (IUPUI) - Center for Neuroimaging

John D. West

Indiana University - Department of Radiology and Imaging Sciences

Eileen Tallman

Indiana University - Department of Radiology and Imaging Sciences

Brenna C. McDonald

Indiana University - Department of Radiology and Imaging Sciences

Martin R. Farlow

Indiana University - Indiana Alzheimer Disease Center

Liana G. Apostolova

Indiana University - Department of Radiology and Imaging Sciences

Joaquin Goñi

Indiana University - Department of Radiology and Imaging Sciences

Mario Dzemidzic

Indiana University - Department of Radiology and Imaging Sciences

Yu-Chien Wu

Indiana University - Department of Radiology and Imaging Sciences

Daniel Kessler

University of Michigan at Ann Arbor - Department of Psychology

Lucas Jeub

Indiana University - School of Informatics, Computing and Engineering

Santo Fortunato

Indiana University - School of Informatics, Computing and Engineering

Andrew J. Saykin

Indiana University Purdue University Indianapolis (IUPUI) - Center for Neuroimaging

Olaf Sporns

Indiana University Bloomington - Department of Psychological and Brain Sciences

Abstract

Alzheimer's disease is considered a disconnection syndrome, motivating the use of brain network measures to detect changes in whole-brain resting-state functional connectivity (FC). We investigated changes in FC within and among resting state networks (RSN) across four different stages in the Alzheimer's disease continuum, and examining two independent cohorts of individuals (84 and 58 individuals, respectively) each comprising control, subjective cognitive decline, mild cognitive impairment and Alzheimer's dementia groups. For each participant, FC was computed as a matrix of Pearson correlations between pairs of time series from 278 gray matter brain regions. We determined significant differences in FC modular organization with two distinct approaches, network contingency analysis and multiresolution consensus clustering. Network contingency analysis identified RSN sub-blocks that differed significantly across clinical groups. Multiresolution consensus clustering identified differences in the stability of modules across multiple spatial scales. Significant modules were further test for statistical association with average memory and executive function cognitive scores. Across both analysis approaches in both participant cohorts the findings converged on a pattern of FC that varied systematically with diagnosis within the frontoparietal network (FP) and between the FP network and default mode network (DMN). Disturbances of modular organization were manifest as greater internal coherence of the FP network and stronger coupling between FP and DMN, resulting in less segregation of these two networks. Our findings suggest that the pattern of interactions within and between specific RSNs holds potential as a new biomarker predictive of clinical progression along the Alzheimer's disease spectrum.

Suggested Citation

Contreras, Joey and Avena-Koenigsberger, Andrea and Risacher, Shannon L. and West, John D. and Tallman, Eileen and McDonald, Brenna C. and Farlow, Martin R. and Apostolova, Liana G. and Goñi, Joaquin and Dzemidzic, Mario and Wu, Yu-Chien and Kessler, Daniel and Jeub, Lucas and Fortunato, Santo and Saykin, Andrew J. and Sporns, Olaf, Resting State Network Modularity Along the Prodromal Late Onset Alzheimer's Disease Continuum (September 1, 2018). NICL-18-847, Available at SSRN: https://ssrn.com/abstract=3242823 or http://dx.doi.org/10.2139/ssrn.3242823

Joey Contreras

USC-Keck School of Medicine ( email )

Los Angeles, CA 90089
United States

Indiana University - Department of Radiology and Imaging Sciences ( email )

340 W 10th St #6200
Indianapolis, IN 46202
United States

Andrea Avena-Koenigsberger

Indiana University Bloomington - Department of Psychological and Brain Sciences ( email )

Bloomington, ID 47405
United States

Shannon L. Risacher

Indiana University Purdue University Indianapolis (IUPUI) - Center for Neuroimaging ( email )

Indianapolis, ID 46202
United States

John D. West

Indiana University - Department of Radiology and Imaging Sciences

340 W 10th St #6200
Indianapolis, IN 46202
United States

Eileen Tallman

Indiana University - Department of Radiology and Imaging Sciences ( email )

340 W 10th St #6200
Indianapolis, IN 46202
United States

Brenna C. McDonald

Indiana University - Department of Radiology and Imaging Sciences

340 W 10th St #6200
Indianapolis, IN 46202
United States

Martin R. Farlow

Indiana University - Indiana Alzheimer Disease Center

340 W 10th St #6200
Indianapolis, IN 46202
United States

Liana G. Apostolova

Indiana University - Department of Radiology and Imaging Sciences

340 W 10th St #6200
Indianapolis, IN 46202
United States

Joaquin Goñi

Indiana University - Department of Radiology and Imaging Sciences

340 W 10th St #6200
Indianapolis, IN 46202
United States

Mario Dzemidzic

Indiana University - Department of Radiology and Imaging Sciences

340 W 10th St #6200
Indianapolis, IN 46202
United States

Yu-Chien Wu

Indiana University - Department of Radiology and Imaging Sciences

340 W 10th St #6200
Indianapolis, IN 46202
United States

Daniel Kessler

University of Michigan at Ann Arbor - Department of Psychology

Ann Arbor, MI 48109
United States

Lucas Jeub

Indiana University - School of Informatics, Computing and Engineering

107 S Indiana Ave
100 South Woodlawn
Bloomington, IN 47405
United States

Santo Fortunato

Indiana University - School of Informatics, Computing and Engineering

107 S Indiana Ave
100 South Woodlawn
Bloomington, IN 47405
United States

Andrew J. Saykin

Indiana University Purdue University Indianapolis (IUPUI) - Center for Neuroimaging ( email )

Indianapolis, ID 46202
United States

Olaf Sporns (Contact Author)

Indiana University Bloomington - Department of Psychological and Brain Sciences ( email )

Bloomington, ID 47405
United States

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