The Role of Hub and Spoke Regions in Theory of Mind in Early Alzheimer's Disease and Frontotemporal Dementia

Abstract

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 < 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.

Keywords: 18F-FDG-PET; Alzheimer’s disease; brain network; dementia; frontotemporal dementia; mild cognitive impairment; neurodegenerative diseases; neuroimaging; social cognition; theory of mind.

Figure 1

RMET ROIs according to Molenberghs et al. (2016) (RMET = Reading the Mind in the Eyes task; R = right; L = left; ROIs = regions of interest). Legend: green = R/L cingulate gyrus; cyan = R/L inferior frontal gyrus; blue = R/L superior frontal gyrus; violet = R/L middle frontal gyrus; yellow = R/L middle temporal gyrus; purple = left precentral gyrus; red = R/L superior temporal gyrus.

Figure 2

ROIs involved in the RMET network within the two patient groups. (A) bvFTD group. (B) MCI–AD group (RMET = Reading the Mind in the Eyes task; R = right; L = left; bvFTD = behavioral variant of frontotemporal dementia). Legend: green = R/L cingulate gyrus; cyan = R/L inferior frontal gyrus; blue = R/L superior frontal gyrus; violet = R/L middle frontal gyrus; yellow = R/L middle temporal gyrus; purple = left precentral gyrus; red = R/L superior temporal gyrus.