TY - JOUR
T1 - The inner fluctuations of the brain in presymptomatic Frontotemporal Dementia
T2 - The chronnectome fingerprint
AU - Genetic FTD Initiative, GENFI
AU - Premi, Enrico
AU - Calhoun, Vince D.
AU - Diano, Matteo
AU - Gazzina, Stefano
AU - Cosseddu, Maura
AU - Alberici, Antonella
AU - Archetti, Silvana
AU - Paternicò, Donata
AU - Gasparotti, Roberto
AU - van Swieten, John
AU - Galimberti, Daniela
AU - Sanchez-Valle, Raquel
AU - Laforce, Robert
AU - Moreno, Fermin
AU - Synofzik, Matthis
AU - Graff, Caroline
AU - Masellis, Mario
AU - Tartaglia, Maria Carmela
AU - Rowe, James
AU - Vandenberghe, Rik
AU - Finger, Elizabeth
AU - Tagliavini, Fabrizio
AU - de Mendonça, Alexandre
AU - Santana, Isabel
AU - Butler, Chris
AU - Ducharme, Simon
AU - Gerhard, Alex
AU - Danek, Adrian
AU - Levin, Johannes
AU - Otto, Markus
AU - Frisoni, Giovanni
AU - Cappa, Stefano
AU - Sorbi, Sandro
AU - Padovani, Alessandro
AU - Rohrer, Jonathan D.
AU - Borroni, Barbara
N1 - Publisher Copyright:
© 2019
PY - 2019/4/1
Y1 - 2019/4/1
N2 - Frontotemporal Dementia (FTD) is preceded by a long period of subtle brain changes, occurring in the absence of overt cognitive symptoms, that need to be still fully characterized. Dynamic network analysis based on resting-state magnetic resonance imaging (rs-fMRI) is a potentially powerful tool for the study of preclinical FTD. In the present study, we employed a “chronnectome” approach (recurring, time-varying patterns of connectivity) to evaluate measures of dynamic connectivity in 472 at-risk FTD subjects from the Genetic Frontotemporal dementia research Initiative (GENFI) cohort. We considered 249 subjects with FTD-related pathogenetic mutations and 223 mutation non-carriers (HC). Dynamic connectivity was evaluated using independent component analysis and sliding-time window correlation to rs-fMRI data, and meta-state measures of global brain flexibility were extracted. Results show that presymptomatic FTD exhibits diminished dynamic fluidity, visiting less meta-states, shifting less often across them, and travelling through a narrowed meta-state distance, as compared to HC. Dynamic connectivity changes characterize preclinical FTD, arguing for the desynchronization of the inner fluctuations of the brain. These changes antedate clinical symptoms, and might represent an early signature of FTD to be used as a biomarker in clinical trials.
AB - Frontotemporal Dementia (FTD) is preceded by a long period of subtle brain changes, occurring in the absence of overt cognitive symptoms, that need to be still fully characterized. Dynamic network analysis based on resting-state magnetic resonance imaging (rs-fMRI) is a potentially powerful tool for the study of preclinical FTD. In the present study, we employed a “chronnectome” approach (recurring, time-varying patterns of connectivity) to evaluate measures of dynamic connectivity in 472 at-risk FTD subjects from the Genetic Frontotemporal dementia research Initiative (GENFI) cohort. We considered 249 subjects with FTD-related pathogenetic mutations and 223 mutation non-carriers (HC). Dynamic connectivity was evaluated using independent component analysis and sliding-time window correlation to rs-fMRI data, and meta-state measures of global brain flexibility were extracted. Results show that presymptomatic FTD exhibits diminished dynamic fluidity, visiting less meta-states, shifting less often across them, and travelling through a narrowed meta-state distance, as compared to HC. Dynamic connectivity changes characterize preclinical FTD, arguing for the desynchronization of the inner fluctuations of the brain. These changes antedate clinical symptoms, and might represent an early signature of FTD to be used as a biomarker in clinical trials.
KW - C9orf72
KW - Chronnectome
KW - Dynamic brain functional connectivity
KW - Frontotemporal dementia
KW - Granulin
KW - Microtuble associate protein tau
KW - Mutation
KW - resting-state fMRI
UR - http://www.scopus.com/inward/record.url?scp=85061078895&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85061078895&partnerID=8YFLogxK
U2 - 10.1016/j.neuroimage.2019.01.080
DO - 10.1016/j.neuroimage.2019.01.080
M3 - Article
C2 - 30716457
AN - SCOPUS:85061078895
SN - 1053-8119
VL - 189
SP - 645
EP - 654
JO - NeuroImage
JF - NeuroImage
ER -