Journal Article

The inner fluctuations of the brain in presymptomatic Frontotemporal Dementia: The chronnectome fingerprint

Masellis, Mario, Neason, Mollie, Thonberg, Hakan, Cosseddu, Maura, Rossor, Martin, Calhoun, Vince D., Flanagan, Toby, Prix, Catharina, Archetti, Silvana, Antonell, Anna, Binetti, Giuliano, Galimberti, Daniela, Mitchell, Sara, Finger, Elizabeth, Duro, Diana, Warren, Jason, Levin, Johannes, Fox, Nick, Tagliavini, Fabrizio, Gabilondo, Alazne, Balasa, Mircea, Rosa-Neto, Pedro, Otto, Markus, Black, Sandra, Meeter, Lieke, Bras, Jose, Vandenbulcke, Mathieu, Sanchez-Valle, Raquel, Ferreira, Carlos, Mead, Simon, Rohrer, Jonathan D., Shafei, Rachelle, van Swieten, John, Pievani, Michela, Maruta, Carolina, Tábuas-Pereira, Miguel, Vandenberghe, Rik, Lladó, Albert, Rogaeva, Ekaterina, Anderl-Straub, Sarah, Santana, Isabel, Arighi, Andrea, Greaves, Caroline, Synofzik, Matthis, Jelic, Vesna, Santiago, Beatriz, Freedman, Morris, Nicholas, Jennifer, Fenoglio, Chiara, Scarpini, Elio, Ducharme, Simon, Villanua, Jorge, Giaccone, Giorgio, Vandamme, Philip, Papma, Janne, van Minkelen, Rick, Padovani, Alessandro, Redaelli, Veronica, Guerreiro, Rita, Heller, Carolin, Bruffaerts, Rose, Ghidoni, Roberta, Hoegen, Tobias, Borroni, Barba

2019

Overview

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. •Frontotemporal Dementia is preceded by a long period of subtle brain changes.•Time-varying dynamic connectivity can unveiled underappreciated brain details.•Presymptomatic Frontotemporal Dementia exhibits a reduced dynamic fluidity.•Frontotemporal Dementia showed a selective vulnerability of specific brain regions.•At the very early stage Frontotemporal Dementia is affecting brain as global system.

• Publisher: Elsevier Inc,Elsevier Limited
• Subject: Adult / Age / Brain / Brain mapping / C9orf72 / Chronnectome / Clinical trials / Cognitive ability / Connectome - methods / Dementia / Dementia disorders / Dynamic brain functional connectivity / Female / Fluidity / Frontotemporal dementia / Frontotemporal Dementia - diagnostic imaging / Frontotemporal Dementia - genetics / Frontotemporal Dementia - physiopathology / Functional magnetic resonance imaging / Granulin / Heterozygote / Humans / Magnetic Resonance Imaging / Male / Microtuble associate protein tau / Middle Aged / Mutation / Nerve Net - diagnostic imaging / Nerve Net - physiopathology / Neural networks / Neuroimaging / NMR / Nuclear magnetic resonance / Prodromal Symptoms / resting-state fMRI / Studies / Synchronization / Time Factors