. 2019 Apr 1:189:645-654.

doi: 10.1016/j.neuroimage.2019.01.080. Epub 2019 Feb 1.

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

Enrico Premi¹, Vince D Calhoun², Matteo Diano³, Stefano Gazzina⁴, Maura Cosseddu⁴, Antonella Alberici⁴, Silvana Archetti⁵, Donata Paternicò⁴, Roberto Gasparotti⁶, John van Swieten⁷, Daniela Galimberti⁸, Raquel Sanchez-Valle⁹, Robert Laforce Jr¹⁰, Fermin Moreno¹¹, Matthis Synofzik¹², Caroline Graff¹³, Mario Masellis¹⁴, Maria Carmela Tartaglia¹⁵, James Rowe¹⁶, Rik Vandenberghe¹⁷, Elizabeth Finger¹⁸, Fabrizio Tagliavini¹⁹, Alexandre de Mendonça²⁰, Isabel Santana²¹, Chris Butler²², Simon Ducharme²³, Alex Gerhard²⁴, Adrian Danek²⁵, Johannes Levin²⁵, Markus Otto²⁶, Giovanni Frisoni²⁷, Stefano Cappa²⁸, Sandro Sorbi²⁹, Alessandro Padovani⁴, Jonathan D Rohrer³⁰, Barbara Borroni³¹; Genetic FTD Initiative, GENFI

Collaborators, Affiliations

Collaborators

Genetic FTD Initiative, GENFI:
Maria Rosario Almeida³², Sarah Anderl-Straub³³, Christin Andersson³⁴, Anna Antonell³⁵, Andrea Arighi³⁶, Mircea Balasa³⁵, Myriam Barandiaran³⁷, Nuria Bargalló³⁸, Robart Bartha³⁹, Benjamin Bender⁴⁰, Luisa Benussi⁴¹, Giuliano Binetti⁴¹, Sandra Black⁴², Martina Bocchetta⁴³, Sergi Borrego-Ecija³⁵, Jose Bras⁴³, Rose Bruffaerts¹⁷, Paola Caroppo⁴⁴, David Cash⁴³, Miguel Castelo-Branco⁴⁵, Rhian Convery⁴³, Thomas Cope⁴⁶, María de Arriba³⁷, Giuseppe Di Fede⁴⁴, Zigor Díaz⁴⁷, Katrina M Dick⁴³, Diana Duro⁴⁸, Chiara Fenoglio⁸, Carlos Ferreira⁴⁹, Catarina B Ferreira⁵⁰, Toby Flanagan⁵¹, Nick Fox⁴³, Morris Freedman⁵², Giorgio Fumagalli⁵³, Alazne Gabilondo³⁷, Serge Gauthier²³, Roberta Ghidoni⁴¹, Giorgio Giaccone⁴⁴, Ana Gorostidi³⁷, Caroline Greaves⁴³, Rita Guerreiro⁴³, Carolin Heller⁴³, Tobias Hoegen⁵⁴, Begoña Indakoetxea⁵⁵, Vesna Jelic⁵⁶, Lize Jiskoot⁷, Hans-Otto Karnath⁵⁷, Ron Keren⁵⁸, Maria João Leitão³², Albert Lladó³⁵, Gemma Lombardi⁵⁹, Sandra Loosli⁵⁴, Carolina Maruta⁶⁰, Simon Mead⁶¹, Lieke Meeter⁷, Gabriel Miltenberger⁵⁰, Rick van Minkelen⁶², Sara Mitchell⁴², Benedetta Nacmias⁵⁹, Mollie Neason⁴³, Jennifer Nicholas⁶³, Linn Öijerstedt⁶⁴, Jaume Olives³⁵, Jessica Panman⁷, Janne Papma⁷, Maximilian Patzig⁶⁵, Michela Pievani⁴¹, Sara Prioni⁴⁴, Catharina Prix⁵⁴, Rosa Rademakers⁶⁶, Veronica Redaelli⁴⁴, Tim Rittman⁴⁶, Ekaterina Rogaeva⁶⁷, Pedro Rosa-Neto⁶⁸, Giacomina Rossi⁴⁴, Martin Rossor⁴³, Beatriz Santiago²¹, Elio Scarpini³⁶, Elisa Semler³³, Rachelle Shafei⁴³, Christen Shoesmith⁶⁹, Miguel Tábuas-Pereira³², Mikel Tainta³⁷, David Tang-Wai⁵⁸, David L Thomas⁷⁰, Hakan Thonberg⁷¹, Carolyn Timberlake⁴⁶, Pietro Tiraboschi⁴⁴, Philip Vandamme⁷², Mathieu Vandenbulcke⁷³, Michele Veldsman⁷⁴, Ana Verdelho⁷⁵, Jorge Villanua⁷⁶, Jason Warren⁴³, Carlo Wilke⁷⁷, Henrik Zetterberg⁴³, Miren Zulaica³⁷

Affiliations

¹ Centre for Neurodegenerative Disorders, Neurology Unit, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy; Stroke Unit, Azienda Socio Sanitaria Territoriale Spedali Civili, Spedali Civili Hospital, Brescia, Italy.
² The Mind Research Network, Albuquerque, USA; Department of Electrical and Computer Engineering, University of New Mexico, Albuquerque, USA.
³ Department of Psychology, University of Turin, Turin, Italy; Department of Medical and Clinical Psychology, CoRPS - Center of Research on Psychology in Somatic Diseases, Tilburg University, the Netherlands.
⁴ Centre for Neurodegenerative Disorders, Neurology Unit, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.
⁵ Biotechnology Laboratory, Department of Diagnostic, Spedali Civili Hospital, Brescia, Italy.
⁶ Neuroradiology Unit, University of Brescia, Italy.
⁷ Department of Neurology, Erasmus Medical Center, Rotterdam, the Netherlands.
⁸ Department of Pathophysiology and Transplantation, "Dino Ferrari" Center, University of Milan, Fondazione Cà Granda, IRCCS Ospedale Maggiore Policlinico, Milan, Italy.
⁹ Neurology Department, Hospital Clinic, Institut d'Investigacions Biomèdiques, Barcelona, Spain.
¹⁰ Clinique Interdisciplinaire de Mémoire, Département des Sciences Neurologiques, CHU de Québec, Faculté de Médecine, Université Laval, QC, Canada.
¹¹ Department of Neurology, Hospital Universitario Donostia, San Sebastian, Gipuzkoa, Spain.
¹² Department of Cognitive Neurology, Center for Neurology, Hertie-Institute for Clinical Brain Research, Tübingen, Germany.
¹³ Karolinska Institutet, Department NVS, Center for Alzheimer Research, Division of Neurogenetics, Sweden.
¹⁴ LC Campbell Cognitive Neurology Research Unit, Sunnybrook Research Institute, Toronto, ON, Canada.
¹⁵ Toronto Western Hospital, Tanz Centre for Research in Neurodegenerative Disease, Toronto, ON, Canada.
¹⁶ Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.
¹⁷ Laboratory for Cognitive Neurology, Department of Neurosciences, KU Leuven, Leuven, Belgium.
¹⁸ Department of Clinical Neurological Sciences, University of Western Ontario, London, ON, Canada.
¹⁹ Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Istituto Neurologico Carlo Besta, Milan, Italy.
²⁰ Faculty of Medicine, University of Lisbon, Lisbon, Portugal.
²¹ Neurology Department, Centro Hospitalar e Universitário de Coimbra, Portugal.
²² Department of Clinical Neurology, University of Oxford, Oxford, UK.
²³ Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada.
²⁴ Institute of Brain, Behaviour and Mental Health, The University of Manchester, Withington, Manchester, UK.
²⁵ Neurologische Klinik und Poliklinik, Ludwig-Maximilians-Universität, Munich, German Center for Neurodegenerative Diseases (DZNE), Munich, Germany.
²⁶ Department of Neurology, University Hospital Ulm, Ulm, Germany.
²⁷ Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy; Memory Clinic and LANVIE-Laboratory of Neuroimaging of Aging, University Hospitals and University of Geneva, Geneva, Switzerland.
²⁸ Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy.
²⁹ Department of Neuroscience, Psychology, Drug Research and Child Health, University of Florence, Florence, Italy; Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) "Don Gnocchi", Florence, Italy.
³⁰ Dementia Research Centre, UCL Institute of Neurology, UK.
³¹ Centre for Neurodegenerative Disorders, Neurology Unit, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy. Electronic address: bborroni@inwind.it.
³² Centre of Neurosciences and Cell Biology, Universidade de Coimbra, Coimbra, Portugal.
³³ Ulm University, Ulm, Germany.
³⁴ Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
³⁵ Alzheimer's disease and Other Cognitive disorders Unit, Neurology Department, Hospital Clinic, Institut d'Investigacions Biomèdiques, Barcelona, Spain.
³⁶ Neurology Unit, Department of Physiopathology and Transplantation, Fondazione Cà Granda, Istituto di Ricovero e Cura a Carattere Scientifico Ospedale Policlinico, Milan, Italy.
³⁷ Neuroscience Area, Biodonostia Health Research Institute, Paseo Dr Begiristain sn, CP 20014, San Sebastian, Gipuzkoa, Spain.
³⁸ Radiology Department, Image Diagnosis Center, Hospital Clínic and Magnetic Resonance Image Core Facility, IDIBAPS, Barcelona, Spain.
³⁹ Department of Medical Biophysics, Robarts Research Institute, University of Western Ontario, London, Ontario, Canada.
⁴⁰ Department of Radiology, University of Tuebingen, Tuebingen, Germany.
⁴¹ Istituto di Ricovero e Cura a Carattere Scientifico Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy.
⁴² LC Campbell Cognitive Neurology Research Unit, Sunnybrook Research Institute, Toronto, Canada.
⁴³ Department of Neurodegenerative Disease, UCL Institute of Neurology, UK.
⁴⁴ Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Istituto Neurologico Carlo Besta, Milano, Italy.
⁴⁵ Neurology Department, Centro Hospitalar e Universitário de Coimbra, Instituto de Ciências Nucleares Aplicadas à Saúde (ICNAS), Portugal.
⁴⁶ University of Cambridge, UK.
⁴⁷ ITA Alzheimer, San Sebastian, Spain.
⁴⁸ Faculty of Medicine, Universidade de Coimbra, Coimbra, Portugal.
⁴⁹ Instituto Ciências Nucleares Aplicadas à Saúde, Universidade de Coimbra, Coimbra, Portugal.
⁵⁰ Faculty of Medicine, University of Lisbon, Portugal.
⁵¹ University of Manchester, UK.
⁵² Division of Neurology, Baycrest Centre for Geriatric Care, University of Toronto, Canada.
⁵³ Neurology Unit, Fondazione Cà Granda, Istituto di Ricovero e Cura a Carattere Scientifico Ospedale Policlinico, Milan, Italy; Department of Neuroscience, Psychology, Drug Research and Child Health, University of Florence, Florence, Italy.
⁵⁴ Department of Neurology, Ludwig-Maximilians-University Munich, Germany.
⁵⁵ Cognitive Disorders Unit, Department of Neurology, Donostia University Hospital, Paseo Dr Begiristain sn, CP 20014, San Sebastian, Gipuzkoa, Spain.
⁵⁶ Division of Clinical Geriatrics, Karolinska Institutet, Stockholm, Sweden.
⁵⁷ Section of Neuropsychology, Department of Cognitive Neurology, Center for Neurology & Hertie-Institute for Clinical Brain Research, Tübingen, Germany.
⁵⁸ University Health Network Memory Clinic, Toronto Western Hospital, Toronto, Canada.
⁵⁹ Department of Neuroscience, Psychology, Drug Research and Child Health, University of Florence, Florence, Italy.
⁶⁰ Lisbon Faculty of Medicine, Language Research Laboratory, Lisbon, Portugal.
⁶¹ MRC Prion Unit, Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London, UK.
⁶² Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, the Netherlands.
⁶³ The London School of Hygiene and Tropical Medicine, London, UK.
⁶⁴ Division of Neurogeriatrics, Karolinska Institutet, Stockholm, Sweden.
⁶⁵ Department of Neuroradiology, Ludwig-Maximilians-University Munich, Germany.
⁶⁶ Department of Neurosciences, Mayo Clinic, Jacksonville, FL, United States.
⁶⁷ Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Canada.
⁶⁸ Translational Neuroimaging Laboratory, McGill University, Montreal, Quebec, Canada.
⁶⁹ Department of Clinical Neurological Sciences, University of Western Ontario, London, Ontario, Canada.
⁷⁰ Neuroradiological Academic Unit, UCL Institute of Neurology, UK.
⁷¹ Center for Alzheimer Research, Division of Neurogeriatrics, Karolinska Institutet, Stockholm, Sweden.
⁷² Neurology Service, University Hospitals Leuven, Belgium; Laboratory for Neurobiology, VIB-KU Leuven Centre for Brain Research, Leuven, Belgium.
⁷³ Geriatric Psychiatry Service, University Hospitals Leuven, Belgium; Neuropsychiatry, Department of Neurosciences, KU Leuven, Leuven, Belgium.
⁷⁴ University of Oxford, UK.
⁷⁵ Department of Neurosciences, Santa Maria Hospital, University of Lisbon, Portugal.
⁷⁶ OSATEK Unidad de Donostia, San Sebastian, Gipuzkoa, Spain.
⁷⁷ Hertie Institute for Clinical Brain Research, University of Tuebingen, Tuebingen, Germany.

PMID: 30716457
PMCID: PMC6669888
DOI: 10.1016/j.neuroimage.2019.01.080

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

Enrico Premi et al. Neuroimage. 2019.

. 2019 Apr 1:189:645-654.

doi: 10.1016/j.neuroimage.2019.01.080. Epub 2019 Feb 1.

Authors

Collaborators

Genetic FTD Initiative, GENFI:
Maria Rosario Almeida³², Sarah Anderl-Straub³³, Christin Andersson³⁴, Anna Antonell³⁵, Andrea Arighi³⁶, Mircea Balasa³⁵, Myriam Barandiaran³⁷, Nuria Bargalló³⁸, Robart Bartha³⁹, Benjamin Bender⁴⁰, Luisa Benussi⁴¹, Giuliano Binetti⁴¹, Sandra Black⁴², Martina Bocchetta⁴³, Sergi Borrego-Ecija³⁵, Jose Bras⁴³, Rose Bruffaerts¹⁷, Paola Caroppo⁴⁴, David Cash⁴³, Miguel Castelo-Branco⁴⁵, Rhian Convery⁴³, Thomas Cope⁴⁶, María de Arriba³⁷, Giuseppe Di Fede⁴⁴, Zigor Díaz⁴⁷, Katrina M Dick⁴³, Diana Duro⁴⁸, Chiara Fenoglio⁸, Carlos Ferreira⁴⁹, Catarina B Ferreira⁵⁰, Toby Flanagan⁵¹, Nick Fox⁴³, Morris Freedman⁵², Giorgio Fumagalli⁵³, Alazne Gabilondo³⁷, Serge Gauthier²³, Roberta Ghidoni⁴¹, Giorgio Giaccone⁴⁴, Ana Gorostidi³⁷, Caroline Greaves⁴³, Rita Guerreiro⁴³, Carolin Heller⁴³, Tobias Hoegen⁵⁴, Begoña Indakoetxea⁵⁵, Vesna Jelic⁵⁶, Lize Jiskoot⁷, Hans-Otto Karnath⁵⁷, Ron Keren⁵⁸, Maria João Leitão³², Albert Lladó³⁵, Gemma Lombardi⁵⁹, Sandra Loosli⁵⁴, Carolina Maruta⁶⁰, Simon Mead⁶¹, Lieke Meeter⁷, Gabriel Miltenberger⁵⁰, Rick van Minkelen⁶², Sara Mitchell⁴², Benedetta Nacmias⁵⁹, Mollie Neason⁴³, Jennifer Nicholas⁶³, Linn Öijerstedt⁶⁴, Jaume Olives³⁵, Jessica Panman⁷, Janne Papma⁷, Maximilian Patzig⁶⁵, Michela Pievani⁴¹, Sara Prioni⁴⁴, Catharina Prix⁵⁴, Rosa Rademakers⁶⁶, Veronica Redaelli⁴⁴, Tim Rittman⁴⁶, Ekaterina Rogaeva⁶⁷, Pedro Rosa-Neto⁶⁸, Giacomina Rossi⁴⁴, Martin Rossor⁴³, Beatriz Santiago²¹, Elio Scarpini³⁶, Elisa Semler³³, Rachelle Shafei⁴³, Christen Shoesmith⁶⁹, Miguel Tábuas-Pereira³², Mikel Tainta³⁷, David Tang-Wai⁵⁸, David L Thomas⁷⁰, Hakan Thonberg⁷¹, Carolyn Timberlake⁴⁶, Pietro Tiraboschi⁴⁴, Philip Vandamme⁷², Mathieu Vandenbulcke⁷³, Michele Veldsman⁷⁴, Ana Verdelho⁷⁵, Jorge Villanua⁷⁶, Jason Warren⁴³, Carlo Wilke⁷⁷, Henrik Zetterberg⁴³, Miren Zulaica³⁷

Affiliations

¹ Centre for Neurodegenerative Disorders, Neurology Unit, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy; Stroke Unit, Azienda Socio Sanitaria Territoriale Spedali Civili, Spedali Civili Hospital, Brescia, Italy.
² The Mind Research Network, Albuquerque, USA; Department of Electrical and Computer Engineering, University of New Mexico, Albuquerque, USA.
³ Department of Psychology, University of Turin, Turin, Italy; Department of Medical and Clinical Psychology, CoRPS - Center of Research on Psychology in Somatic Diseases, Tilburg University, the Netherlands.
⁴ Centre for Neurodegenerative Disorders, Neurology Unit, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.
⁵ Biotechnology Laboratory, Department of Diagnostic, Spedali Civili Hospital, Brescia, Italy.
⁶ Neuroradiology Unit, University of Brescia, Italy.
⁷ Department of Neurology, Erasmus Medical Center, Rotterdam, the Netherlands.
⁸ Department of Pathophysiology and Transplantation, "Dino Ferrari" Center, University of Milan, Fondazione Cà Granda, IRCCS Ospedale Maggiore Policlinico, Milan, Italy.
⁹ Neurology Department, Hospital Clinic, Institut d'Investigacions Biomèdiques, Barcelona, Spain.
¹⁰ Clinique Interdisciplinaire de Mémoire, Département des Sciences Neurologiques, CHU de Québec, Faculté de Médecine, Université Laval, QC, Canada.
¹¹ Department of Neurology, Hospital Universitario Donostia, San Sebastian, Gipuzkoa, Spain.
¹² Department of Cognitive Neurology, Center for Neurology, Hertie-Institute for Clinical Brain Research, Tübingen, Germany.
¹³ Karolinska Institutet, Department NVS, Center for Alzheimer Research, Division of Neurogenetics, Sweden.
¹⁴ LC Campbell Cognitive Neurology Research Unit, Sunnybrook Research Institute, Toronto, ON, Canada.
¹⁵ Toronto Western Hospital, Tanz Centre for Research in Neurodegenerative Disease, Toronto, ON, Canada.
¹⁶ Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.
¹⁷ Laboratory for Cognitive Neurology, Department of Neurosciences, KU Leuven, Leuven, Belgium.
¹⁸ Department of Clinical Neurological Sciences, University of Western Ontario, London, ON, Canada.
¹⁹ Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Istituto Neurologico Carlo Besta, Milan, Italy.
²⁰ Faculty of Medicine, University of Lisbon, Lisbon, Portugal.
²¹ Neurology Department, Centro Hospitalar e Universitário de Coimbra, Portugal.
²² Department of Clinical Neurology, University of Oxford, Oxford, UK.
²³ Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada.
²⁴ Institute of Brain, Behaviour and Mental Health, The University of Manchester, Withington, Manchester, UK.
²⁵ Neurologische Klinik und Poliklinik, Ludwig-Maximilians-Universität, Munich, German Center for Neurodegenerative Diseases (DZNE), Munich, Germany.
²⁶ Department of Neurology, University Hospital Ulm, Ulm, Germany.
²⁷ Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy; Memory Clinic and LANVIE-Laboratory of Neuroimaging of Aging, University Hospitals and University of Geneva, Geneva, Switzerland.
²⁸ Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy.
²⁹ Department of Neuroscience, Psychology, Drug Research and Child Health, University of Florence, Florence, Italy; Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) "Don Gnocchi", Florence, Italy.
³⁰ Dementia Research Centre, UCL Institute of Neurology, UK.
³¹ Centre for Neurodegenerative Disorders, Neurology Unit, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy. Electronic address: bborroni@inwind.it.
³² Centre of Neurosciences and Cell Biology, Universidade de Coimbra, Coimbra, Portugal.
³³ Ulm University, Ulm, Germany.
³⁴ Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
³⁵ Alzheimer's disease and Other Cognitive disorders Unit, Neurology Department, Hospital Clinic, Institut d'Investigacions Biomèdiques, Barcelona, Spain.
³⁶ Neurology Unit, Department of Physiopathology and Transplantation, Fondazione Cà Granda, Istituto di Ricovero e Cura a Carattere Scientifico Ospedale Policlinico, Milan, Italy.
³⁷ Neuroscience Area, Biodonostia Health Research Institute, Paseo Dr Begiristain sn, CP 20014, San Sebastian, Gipuzkoa, Spain.
³⁸ Radiology Department, Image Diagnosis Center, Hospital Clínic and Magnetic Resonance Image Core Facility, IDIBAPS, Barcelona, Spain.
³⁹ Department of Medical Biophysics, Robarts Research Institute, University of Western Ontario, London, Ontario, Canada.
⁴⁰ Department of Radiology, University of Tuebingen, Tuebingen, Germany.
⁴¹ Istituto di Ricovero e Cura a Carattere Scientifico Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy.
⁴² LC Campbell Cognitive Neurology Research Unit, Sunnybrook Research Institute, Toronto, Canada.
⁴³ Department of Neurodegenerative Disease, UCL Institute of Neurology, UK.
⁴⁴ Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Istituto Neurologico Carlo Besta, Milano, Italy.
⁴⁵ Neurology Department, Centro Hospitalar e Universitário de Coimbra, Instituto de Ciências Nucleares Aplicadas à Saúde (ICNAS), Portugal.
⁴⁶ University of Cambridge, UK.
⁴⁷ ITA Alzheimer, San Sebastian, Spain.
⁴⁸ Faculty of Medicine, Universidade de Coimbra, Coimbra, Portugal.
⁴⁹ Instituto Ciências Nucleares Aplicadas à Saúde, Universidade de Coimbra, Coimbra, Portugal.
⁵⁰ Faculty of Medicine, University of Lisbon, Portugal.
⁵¹ University of Manchester, UK.
⁵² Division of Neurology, Baycrest Centre for Geriatric Care, University of Toronto, Canada.
⁵³ Neurology Unit, Fondazione Cà Granda, Istituto di Ricovero e Cura a Carattere Scientifico Ospedale Policlinico, Milan, Italy; Department of Neuroscience, Psychology, Drug Research and Child Health, University of Florence, Florence, Italy.
⁵⁴ Department of Neurology, Ludwig-Maximilians-University Munich, Germany.
⁵⁵ Cognitive Disorders Unit, Department of Neurology, Donostia University Hospital, Paseo Dr Begiristain sn, CP 20014, San Sebastian, Gipuzkoa, Spain.
⁵⁶ Division of Clinical Geriatrics, Karolinska Institutet, Stockholm, Sweden.
⁵⁷ Section of Neuropsychology, Department of Cognitive Neurology, Center for Neurology & Hertie-Institute for Clinical Brain Research, Tübingen, Germany.
⁵⁸ University Health Network Memory Clinic, Toronto Western Hospital, Toronto, Canada.
⁵⁹ Department of Neuroscience, Psychology, Drug Research and Child Health, University of Florence, Florence, Italy.
⁶⁰ Lisbon Faculty of Medicine, Language Research Laboratory, Lisbon, Portugal.
⁶¹ MRC Prion Unit, Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London, UK.
⁶² Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, the Netherlands.
⁶³ The London School of Hygiene and Tropical Medicine, London, UK.
⁶⁴ Division of Neurogeriatrics, Karolinska Institutet, Stockholm, Sweden.
⁶⁵ Department of Neuroradiology, Ludwig-Maximilians-University Munich, Germany.
⁶⁶ Department of Neurosciences, Mayo Clinic, Jacksonville, FL, United States.
⁶⁷ Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Canada.
⁶⁸ Translational Neuroimaging Laboratory, McGill University, Montreal, Quebec, Canada.
⁶⁹ Department of Clinical Neurological Sciences, University of Western Ontario, London, Ontario, Canada.
⁷⁰ Neuroradiological Academic Unit, UCL Institute of Neurology, UK.
⁷¹ Center for Alzheimer Research, Division of Neurogeriatrics, Karolinska Institutet, Stockholm, Sweden.
⁷² Neurology Service, University Hospitals Leuven, Belgium; Laboratory for Neurobiology, VIB-KU Leuven Centre for Brain Research, Leuven, Belgium.
⁷³ Geriatric Psychiatry Service, University Hospitals Leuven, Belgium; Neuropsychiatry, Department of Neurosciences, KU Leuven, Leuven, Belgium.
⁷⁴ University of Oxford, UK.
⁷⁵ Department of Neurosciences, Santa Maria Hospital, University of Lisbon, Portugal.
⁷⁶ OSATEK Unidad de Donostia, San Sebastian, Gipuzkoa, Spain.
⁷⁷ Hertie Institute for Clinical Brain Research, University of Tuebingen, Tuebingen, Germany.

PMID: 30716457
PMCID: PMC6669888
DOI: 10.1016/j.neuroimage.2019.01.080

Abstract

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.

Keywords: C9orf72; Chronnectome; Dynamic brain functional connectivity; Frontotemporal dementia; Granulin; Microtuble associate protein tau; Mutation; resting-state fMRI.

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Figures

**Figure 1.. The six connectivity patterns (CPs) resulting from the dynamic Functional Network Connectivity (dFNC) analysis.**
The six correlations’ matrix (among the 35 considered network components) are reported. The colorbar represents the direction and the strength of each correlation (red: positive correlation, blue: negative correlation).

Figure 2.. Meta-state dynamics through time, meta-state numbers, meta-state change points, and meta-state total distance in a representative mutation carrier and in a representative mutation non-carrier.
Meta-state dynamics through time (panel A), meta-state numbers (panel B), meta-state change points (panel C), and meta-state total distance (panel D) in a representative mutation non carrier (left column) and representative mutation carrier (right column). The colorbar represents the strength of probability to be in each meta-state. X-axis: the six connectivity patterns (Cps) are reported, from 1 to 6; Y-axis: time (seconds, after timecourse discretization in quartiles).

See this image and copyright information in PMC

References

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

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

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