Different patterns of functional network reorganization across the variants of primary progressive aphasia: a graph-theoretic analysis.

Primary progressive aphasia (PPA) is a neurodegenerative syndrome with three main variants (nonfluent, logopenic, semantic) that are identified primarily based on language deficit profiles and are associated with neurotopographically distinct atrophic patterns. We used a graph-theoretic analytic approach to examine changes in functional network properties measured with resting-state fMRI in all three PPA variants compared with age-matched healthy controls. All three variants showed a more segregated network organization than controls. To better understand the changes underlying the increased segregation, we examined the distribution of functional "hubs". We found that while all variants lost hubs in the left superior frontal and parietal regions, new hubs were recruited in different areas across the variants. In particular, both logopenic and semantic variants recruited significant numbers of hubs in the right hemisphere. Importantly, these functional characteristics could not be fully explained by local volume changes. These findings indicate that patterns of functional connectivity can serve as further evidence to distinguish the PPA variants, and provide a basis for longitudinal studies and for investigating treatment effects. This study also highlights the utility of graph-theoretic approaches in understanding the brain's functional reorganization in response to neurodegenerative disease.