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Functional network resilience to pathology in presymptomatic genetic frontotemporal dementia

2019· article· en· W2907921626 on OpenAlexafffund
Timothy Rittman, Robin Borchert, Simon Jones, John C. van Swieten, Barbara Borroni, Daniela Galimberti, Mario Masellis, Maria Carmela Tartaglia, Caroline Graff, Fabrizio Tagliavini, Giovanni B. Frisoni, Robert Laforce, Elizabeth Finger, Alexandre de Mendonça, Sandro Sorbi, Jonathan D. Rohrer, James B. Rowe, Sónia Afonso, Maria Rosário Almeida, Sarah Anderl‐Straub, Christin Andersson, Anna Antonell, Silvana Archetti, Andrea Arighi, Mircea Balasa, Myriam Barandiarán, Núria Bargalló, Benjamin Bender, Luisa Benussi, Valentina Bessi, Giuliano Binetti, Sandra E. Black, Martina Bocchetta, Sergi Borrego‐Écija, José Brás, Rose Bruffaerts, Paola Caroppo, David M. Cash, Miguel Castelo‐Branco, Rhian S. Convery, Thomas Cope, Maura Cosseddu, María de Arriba, Giuseppe Di Fede, Zigor Díaz, Katrina M. Dick, Diana Duro, Chiara Fenoglio, Camilla Ferrari, Catarina B. Ferreira, Toby Flanagana, Nick C. Fox, Morris Freedman, Giorgio Fumagalli, Alazne Gabilondo, Roberto Gasparotti, Serge Gauthier, Stefano Gazzina, Roberta Ghidoni, Giorgio Giaccone, Ana Gorostidi, Caroline Greaves, Rita Guerreiro, Carolin Heller, Tobias Hoegen, Begoña Indakoetxea, Vesna Jelić, Lize C. Jiskoot, Hans‐Otto Karnath, Ron Keren, Maria João Leitão, Albert Lladó, Gemma Lombardi, Sandra Loosli, Carolina Maruta, Simon Mead, Lieke Meeter, Gabriel Miltenberger, Rick van Minkelen, Sara Mitchell, Benedetta Nacmias, Mollie Neason, Jennifer Nicholas, Linn Öijerstedt, Jaume Olives, Alessandro Padovani, Jessica Panman, Janne M. Papma, Michela Pievani, Yolande A.L. Pijnenburg, Enrico Premi, Sara Prioni, Catharina Prix, Rosa Rademakers, Veronica Redaelli, Ekaterina Rogaeva, Pedro Rosa‐Neto, Giacomina Rossi, Martin Rosser, Beatriz Santiago, Elio Scarpini, Sonja Schönecker, Elisa Semler, Rachelle Shafei, Christen Shoesmith, Miguel Tábuas‐Pereira, Mikel Tainta, Ricardo Taipa, David F. Tang‐Wai, David L. Thomas, Håkan Thonberg, Carolyn Timberlake, Pietro Tiraboschi, Mathieu Vandenbulcke, Michele Veldsman, Ana Verdelho, Jorge Villanúa, Jason D. Warren, Carlo Wilke, Ione Woollacott, Elisabeth Wlasich, Henrik Zetterberg, Miren Zulaica

Bibliographic record

VenueNeurobiology of Aging · 2019
Typearticle
Languageen
FieldNeuroscience
TopicFunctional Brain Connectivity Studies
Canadian institutionsWestern UniversityUniversité LavalOccupational Cancer Research CentreHealth Sciences CentreUniversity of TorontoSunnybrook Health Science Centre
FundersDepartment of Family and Community Medicine, University of TorontoFonds de recherche du Québec – Nature et technologiesMedical Research CouncilFonds de Recherche du Québec - SantéFonds de recherche du QuébecMinistero della SaluteUniversity of TorontoEnte Cassa di Risparmio di FirenzeBrain Research TrustWolfson FoundationOntario Ministry of Health and Long-Term CareUniversity of CambridgeParkinson's UKZonMwNIHR Cambridge Biomedical Research CentreAlzheimer's Research FoundationNational Institute for Health and Care ResearchSunnybrook Research InstituteWellcome TrustCanadian Institutes of Health ResearchWellcome
KeywordsFrontotemporal dementiaC9orf72DementiaNeuroscienceAtrophyFrontotemporal lobar degenerationCognitionPsychologyMedicinePathologyDisease

Abstract

fetched live from OpenAlex

The presymptomatic phase of neurodegenerative diseases are characterized by structural brain changes without significant clinical features. We set out to investigate the contribution of functional network resilience to preserved cognition in presymptomatic genetic frontotemporal dementia. We studied 172 people from families carrying genetic abnormalities in C9orf72, MAPT, or PGRN. Networks were extracted from functional MRI data and assessed using graph theoretical analysis. We found that despite loss of both brain volume and functional connections, there is maintenance of an efficient topological organization of the brain's functional network in the years leading up to the estimated age of frontotemporal dementia symptom onset. After this point, functional network efficiency declines markedly. Reduction in connectedness was most marked in highly connected hub regions. Measures of topological efficiency of the brain's functional network and organization predicted cognitive dysfunction in domains related to symptomatic frontotemporal dementia and connectivity correlated with brain volume loss in frontotemporal dementia. We propose that maintaining the efficient organization of the brain's functional network supports cognitive health even as atrophy and connectivity decline presymptomatically.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.001
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.164
Threshold uncertainty score0.571

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.018
GPT teacher head0.238
Teacher spread0.220 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

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Citations65
Published2019
Admission routes2
Has abstractyes

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