The virtual aging brain: Causal inference supports interhemispheric dedifferentiation in healthy aging
Mario Lavanga,
Johanna Stumme,
Bahar Hazal Yalcinkaya,
Jan Fousek,
Christiane Jockwitz,
Hiba Sheheitli,
Nora Bittner,
Meysam Hashemi,
Spase Petkoski,
Svenja Caspers,
Viktor Jirsa
Affiliations
Mario Lavanga
Institut de Neurosciences des Systèmes (INS), Inserm, Aix-Marseille University, Marseille 13005, France
Johanna Stumme
Institute of Neuroscience and Medicine (INM-1), Research Centre Jülich, Jülich, Germany; Institute for Anatomy I, Medical Faculty & University Hospital Düsseldorf, Heinrich-Heine University Düsseldorf, Düsseldorf, Germany
Bahar Hazal Yalcinkaya
Institut de Neurosciences des Systèmes (INS), Inserm, Aix-Marseille University, Marseille 13005, France
Jan Fousek
Institut de Neurosciences des Systèmes (INS), Inserm, Aix-Marseille University, Marseille 13005, France
Christiane Jockwitz
Institute of Neuroscience and Medicine (INM-1), Research Centre Jülich, Jülich, Germany; Institute for Anatomy I, Medical Faculty & University Hospital Düsseldorf, Heinrich-Heine University Düsseldorf, Düsseldorf, Germany
Hiba Sheheitli
Institut de Neurosciences des Systèmes (INS), Inserm, Aix-Marseille University, Marseille 13005, France
Nora Bittner
Institute of Neuroscience and Medicine (INM-1), Research Centre Jülich, Jülich, Germany; Institute for Anatomy I, Medical Faculty & University Hospital Düsseldorf, Heinrich-Heine University Düsseldorf, Düsseldorf, Germany
Meysam Hashemi
Institut de Neurosciences des Systèmes (INS), Inserm, Aix-Marseille University, Marseille 13005, France
Spase Petkoski
Institut de Neurosciences des Systèmes (INS), Inserm, Aix-Marseille University, Marseille 13005, France
Svenja Caspers
Institute of Neuroscience and Medicine (INM-1), Research Centre Jülich, Jülich, Germany; Institute for Anatomy I, Medical Faculty & University Hospital Düsseldorf, Heinrich-Heine University Düsseldorf, Düsseldorf, Germany
Viktor Jirsa
Institut de Neurosciences des Systèmes (INS), Inserm, Aix-Marseille University, Marseille 13005, France; Corresponding author.
The mechanisms of cognitive decline and its variability during healthy aging are not fully understood, but have been associated with reorganization of white matter tracts and functional brain networks. Here, we built a brain network modeling framework to infer the causal link between structural connectivity and functional architecture and the consequent cognitive decline in aging. By applying in-silico interhemispheric degradation of structural connectivity, we reproduced the process of functional dedifferentiation during aging. Thereby, we found the global modulation of brain dynamics by structural connectivity to increase with age, which was steeper in older adults with poor cognitive performance. We validated our causal hypothesis via a deep-learning Bayesian approach. Our results might be the first mechanistic demonstration of dedifferentiation during aging leading to cognitive decline.
