Virtual brain simulations reveal network-specific parameters in neurodegenerative dementias

Anita Monteverdi; Fulvia Palesi; Michael Schirner; Francesca Argentino; Mariateresa Merante; Alberto Redolfi; Francesca Conca; Laura Mazzocchi; Stefano F Cappa; Matteo Cotta Ramusino; Alfredo Costa; Anna Pichiecchio; Lisa M Farina; Viktor Jirsa; Petra Ritter; Claudia A M Gandini Wheeler-Kingshott; Egidio D'Angelo

doi:10.3389/fnagi.2023.1204134

Virtual brain simulations reveal network-specific parameters in neurodegenerative dementias

Front Aging Neurosci. 2023 Jul 28:15:1204134. doi: 10.3389/fnagi.2023.1204134. eCollection 2023.

Authors

Anita Monteverdi¹, Fulvia Palesi², Michael Schirner^{3

4

5

6

7}, Francesca Argentino², Mariateresa Merante², Alberto Redolfi⁸, Francesca Conca⁹, Laura Mazzocchi¹⁰, Stefano F Cappa^{9

11}, Matteo Cotta Ramusino¹², Alfredo Costa^{2

12}, Anna Pichiecchio^{2

10}, Lisa M Farina⁹, Viktor Jirsa¹³, Petra Ritter^{3

4

5

6

7}, Claudia A M Gandini Wheeler-Kingshott^{1

2

14}, Egidio D'Angelo^{1

2}

Affiliations

¹ Unit of Digital Neuroscience, IRCCS Mondino Foundation, Pavia, Italy.
² Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy.
³ Berlin Institute of Health, Charité - Universitätsmedizin Berlin, Berlin, Germany.
⁴ Department of Neurology with Experimental Neurology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt Universität zu Berlin, Berlin, Germany.
⁵ Bernstein Focus State Dependencies of Learning and Bernstein Center for Computational Neuroscience, Berlin, Germany.
⁶ Einstein Center for Neurosciences Berlin, Berlin, Germany.
⁷ Einstein Center Digital Future, Berlin, Germany.
⁸ Laboratory of Neuroinformatics, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy.
⁹ IRCCS Mondino Foundation, Pavia, Italy.
¹⁰ Advanced Imaging and Artificial Intelligence Center, IRCCS Mondino Foundation, Pavia, Italy.
¹¹ University Institute of Advanced Studies (IUSS), Pavia, Italy.
¹² Unit of Behavioral Neurology, IRCCS Mondino Foundation, Pavia, Italy.
¹³ Institut de Neurosciences des Systèmes, INSERM, INS, Aix Marseille University, Marseille, France.
¹⁴ NMR Research Unit, Queen Square Multiple Sclerosis Centre, Department of Neuroinflammation, UCL Queen Square Institute of Neurology, London, United Kingdom.

Abstract

Introduction: Neural circuit alterations lay at the core of brain physiopathology, and yet are hard to unveil in living subjects. The Virtual Brain (TVB) modeling, by exploiting structural and functional magnetic resonance imaging (MRI), yields mesoscopic parameters of connectivity and synaptic transmission.

Methods: We used TVB to simulate brain networks, which are key for human brain function, in Alzheimer's disease (AD) and frontotemporal dementia (FTD) patients, whose connectivity and synaptic parameters remain largely unknown; we then compared them to healthy controls, to reveal novel in vivo pathological hallmarks.

Results: The pattern of simulated parameter differed between AD and FTD, shedding light on disease-specific alterations in brain networks. Individual subjects displayed subtle differences in network parameter patterns that significantly correlated with their individual neuropsychological, clinical, and pharmacological profiles.

Discussion: These TVB simulations, by informing about a new personalized set of networks parameters, open new perspectives for understanding dementias mechanisms and design personalized therapeutic approaches.

Keywords: Alzheimer’s disease; brain dynamics; excitatory/inhibitory balance; frontotemporal dementia; resting-state networks; virtual brain modeling.

Grants and funding

The work performed at the IRCCS Mondino Foundation was supported by the Italian Ministry of Health (RC2022-RC2024). The work performed at the University of Pavia was supported by H2020 Research and Innovation Action Grants Human Brain Project 785907 and 945539 (SGA2 and SGA3) to ED’A, FP, and PR. Moreover, the project was supported by the MNL Project “Local Neuronal Microcircuits” of the Centro Fermi (Rome, Italy), #NEXTGENERATIONEU (NGEU) and funded by the Ministry of University and Research (MUR), the National Recovery and Resilience Plan (NRRP), project IR00011-EBRAINS-Italy to ED’A; Horizon2020 [Research and Innovation Action Grants Human Brain Project 945539 (SGA3)], BRC (#BRC704/CAP/CGW), MRC (#MR/S026088/1), Ataxia UK to CW-K; PR acknowledges Digital Europe Grant TEF-Health #101100700; H2020 Research and Innovation Action Grant Human Brain Project (ICEI 800858, EOSC VirtualBrainCloud 82642, AISN 101057655); H2020 Research Infrastructures Grant (EBRAINS-PREP 101079717, EBRAIN-Health 101058516); H2020 European Innovation Council (PHRASE 101058240); H2020 European Research Council Grant (ERC BrainModes 683049); JPND ERA PerMed PatternCog 2522FSB904; Berlin Institute of Health and Foundation Charité; Johanna Quandt Excellence Initiative; and German Research Foundation (SFB 1436, project ID 425899996; SFB 1315, project ID 327654276; SFB 936, project ID 178316478; and SFB-TRR 295, project ID 424778381).