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

Research output: Contribution to journalArticleAcademicpeer-review

6 Citations (Scopus)


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 18 F-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 18 F-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 < 0.001), while the impact of hubs damage on ToM performance was independent from the integrity of spokes (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.

Original languageEnglish
Article number544
Issue number3
Publication statusPublished - 1 Mar 2022


  • Alzheimer’s disease
  • Brain network
  • Dementia
  • Frontotemporal dementia
  • Mild cognitive impairment
  • Neurodegenerative diseases
  • Neuroimaging
  • Social cognition
  • Theory of mind

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