Networks Disrupted in Linguistic Variants of Frontotemporal Dementia

Abstract

The non-fluent/agrammatic variant of primary progressive aphasia (nfvPPA) and semantic variant (svPPA) of frontotemporal dementia (FTD) are neurodegenerative diseases. Previous works have shown alterations of fractional anisotropy (FA) and mean diffusivity (MD) from diffusion tensor images (DTIs). This manuscript is aimed at using DTI images to build a global tractography and to identify atrophy patterns of white matter in each variant. Twenty patients with svPPA, 20 patients with nfvPPA, 26 patients with behavioral variant of FTD (bvFTD) and, 33 controls were included. An analysis based on the connectivity of structural networks showed changes in FA and MD in svPPA and nfvPPA with respect to bvFTD. Much damage in the internal networks of the left temporal lobe was found in svPPA patients; in contrast, patients with nfvPPA showed atrophy in networks from the basal ganglia to motor and premotor areas. Those findings support the dual stream model of speech and language.

Keywords: diffusion tensor imaging; fractional anisotropy; frontotemporal dementia; primary progressive aphasia; structural connectivity; white matter.

Figure 1

General pipeline of DTI processing and matrix construction.

Figure 2

Atrophic networks in linguistic variants and bvFTD with respect to controls. Top figures show changes in fractional anisotropy (FA) and bottom show changes in mean diffusivity (MD). The figure shows alterations overlaid on a 3D template in the Montreal Neurological Institute's standard space in neurological convention.

Figure 3

Atrophic networks in the svPPA variant with respect to bvFTD. The labels from Brainnetome represent the nodes and the edges show the changes in FA and MD. Only the edges with changes are shown. The whole list of the nodes with the names is located in Supplementary Data. The left of the figure shows alterations overlaid on a 3D template in the Montreal Neurological Institute's standard space in neurological convention. The right side shows the same results displayed in 2D with the names of nodes in the Brainnetome Atlas and displayed at p < 0.05.

Figure 4

Atrophic networks in the nfvPPA variant regarding bvFTD, the labels from Brainnetome represents the nodes, and the edges show the changes in FA and MD. Only the edges with changes are shown. The whole list of the nodes with the names is located in Supplementary Data. The left side of the figure shows alterations overlaid on a 3D template in the Montreal Neurological Institute's standard space in neurological convention. The right side shows the same results displayed in 2D with the names of nodes in the Brainnetome Atlas and displayed at p<0.05.

Figure 5

Atrophic networks in PPA variants. The labels from Brainnetome represent the nodes and the edges show the changes in FA and MD, only the edges with changes are shown. The whole list of the nodes with the names is located in Supplementary Data. The left side of the figure shows alterations overlaid on a 3D template in the Montreal Neurological Institute's standard space in neurological convention. The right side shows the same results displayed in 2D with the names of nodes in the Brainnetome Atlas and displayed at p < 0.05.

Figure 6

Comparisons of gray matter between controls and primary progressive variants. Each tile shows significant regions (correction by threshold-free cluster enhancement, p < 0.05, permutations: 8000) VBM analysis. Green: gray matter atrophy in svPPA, Purple: gray matter atrophy in nfvPPA. The table of main locations and their labels and coordinates can be found in Supplementary Data (Tables S1, S2).

Figure 7

Comparisons of gray matter between behavioral variants and primary progressive variants. Each tile shows significant regions (correction by threshold-free cluster enhancement, p < 0.05, permutations: 8000) VBM analysis. (A) Regions with atrophy at linguistic variants regarding bvFTD. Blue: gray matter with changes in nfvPPa; Red: gray matter with changes in svPPA; Pink: gray matter with changes in svPPA and nfvPPA. (B) Gray matter changes in svPPA regarding nfvPPA. (C) Gray matter changes in nfvPPA regarding svPPA. The table of main locations and their labels and coordinates can be found in Supplementary Data.