Alterations in resting-state functional connectivity in primary progressive aphasia



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Primary progressive aphasia (PPA) is a neurodegenerative disorder affecting speech and language, which presents as three clinical variants: nonfluent PPA (nfvPPA), logopenic PPA (lvPPA), and semantic PPA (svPPA). PPA selectively targets dorsal left hemisphere regions involved in articulatory and phonological processing in nfvPPA and lvPPA and ventral lexical-semantic regions in svPPA. The aim of the current study was to investigate alterations in resting-state functional connectivity (RSFC) within key areas of dorsal and ventral language pathways in PPA relative to controls. We addressed this aim using a region of interest seed-based approach, with left hemisphere seeds located in: (1) the inferior frontal gyrus (IFG), (2) an area within the posterior Sylvian fissure at the temporo-parietal junction (SPT), and (3) the anterior temporal lobe (ATL). Participants included 22 patients with lvPPA, 32 patients with nfvPPA, 25 patients with svPPA and 39 healthy controls. Voxel-based morphometry (VBM) analysis was performed in order to identify areas of significant regional atrophy in patients. Subsequently, functional language networks were defined in healthy controls and in each patient group, and significant group differences in resting-state functional connectivity were determined after correction for gray matter volume. Results revealed reductions in connectivity among all patient groups for all seeded networks. Different patterns of RSFC alteration were also seen within each patient group. These findings provide evidence of selective functional and structural alterations in each of the clinical variants of PPA.