The Role of Hub and Spoke Regions in Theory of Mind in Early Alzheimer’s Disease and Frontotemporal Dementia
Beatrice Orso,
Luigi Lorenzini,
Dario Arnaldi,
Nicola Girtler,
Andrea Brugnolo,
Elisa Doglione,
Pietro Mattioli,
Erica Biassoni,
Federico Massa,
Enrico Peira,
Matteo Bauckneht,
Maria I. Donegani,
Silvia Morbelli,
Flavio Nobili,
Matteo Pardini
Affiliations
Beatrice Orso
Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), University of Genoa, Largo Daneo 3, 16132 Genoa, Italy
Luigi Lorenzini
Department of Radiology and Nuclear Medicine, Amsterdam UMC Location VuMC, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The Netherlands
Dario Arnaldi
Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), University of Genoa, Largo Daneo 3, 16132 Genoa, Italy
Nicola Girtler
Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), University of Genoa, Largo Daneo 3, 16132 Genoa, Italy
Andrea Brugnolo
Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), University of Genoa, Largo Daneo 3, 16132 Genoa, Italy
Elisa Doglione
IRCCS Ospedale Policlinico S. Martino, Largo Rosanna Benzi 10, 16132 Genoa, Italy
Pietro Mattioli
Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), University of Genoa, Largo Daneo 3, 16132 Genoa, Italy
Erica Biassoni
Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), University of Genoa, Largo Daneo 3, 16132 Genoa, Italy
Federico Massa
Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), University of Genoa, Largo Daneo 3, 16132 Genoa, Italy
Enrico Peira
National Institute of Nuclear Physics (INFN), Genoa Section, Via Dodecaneso 33, 16146 Genoa, Italy
Matteo Bauckneht
IRCCS Ospedale Policlinico S. Martino, Largo Rosanna Benzi 10, 16132 Genoa, Italy
Maria I. Donegani
IRCCS Ospedale Policlinico S. Martino, Largo Rosanna Benzi 10, 16132 Genoa, Italy
Silvia Morbelli
IRCCS Ospedale Policlinico S. Martino, Largo Rosanna Benzi 10, 16132 Genoa, Italy
Flavio Nobili
Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), University of Genoa, Largo Daneo 3, 16132 Genoa, Italy
Matteo Pardini
Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), University of Genoa, Largo Daneo 3, 16132 Genoa, Italy
Theory of mind (ToM, the ability to attribute mental states to others) deficit is a frequent finding in neurodegenerative conditions, mediated by a diffuse brain network confirmed by 18F-FDG-PET and MR imaging, involving frontal, temporal and parietal areas. However, the role of hubs and spokes network regions in ToM performance, and their respective damage, is still unclear. To study this mechanism, we combined ToM testing with brain 18F-FDG-PET imaging in 25 subjects with mild cognitive impairment due to Alzheimer’s disease (MCI–AD), 24 subjects with the behavioral variant of frontotemporal dementia (bvFTD) and 40 controls. Regions included in the ToM network were divided into hubs and spokes based on their structural connectivity and distribution of hypometabolism. The hubs of the ToM network were identified in frontal regions in both bvFTD and MCI–AD patients. A mediation analysis revealed that the impact of spokes damage on ToM performance was mediated by the integrity of hubs (p p < 0.001). Our findings support the theory that a key role is played by the hubs in ToM deficits, suggesting that hubs could represent a final common pathway leading from the damage of spoke regions to clinical deficits.
