Perturbations of language network connectivity in primary progressive aphasia.

Aphasias are caused by disruption in structural integrity and interconnectivity within a large-scale distributed language network. We investigated the distribution and behavioral consequences of altered functional connectivity in three variants of primary progressive aphasia (PPA). The goal was to clarify relationships among atrophy, resting connectivity, and the resulting behavioral changes in 73 PPA and 33 control participants. Three core regions of the left perisylvian language network: the inferior frontal gyrus (IFG), middle temporal gyrus (MTG), and anterior temporal lobe (ATL) were evaluated in agrammatic (PPA-G), logopenic (PPA-L), and semantic (PPA-S) PPA variants. All PPA groups showed decreased connectivity between IFG and MTG. The PPA-S group also showed additional loss of connectivity strength between ATL and the other language regions. Decreased connectivity between the IFG and MTG nodes in PPA-G remained significant even when controlled for the effect of atrophy. In the PPA group as a whole, IFG-MTG connectivity strength correlated with repetition and grammar scores, whereas MTG-ATL connectivity correlated with picture naming and single-word comprehension. There was no significant change in the connectivity of homologous regions in the right hemisphere. These results show that language impairments in PPA are associated with perturbations of functional connectivity within behaviorally concordant components of the language network. Altered connectivity in PPA may reflect not only the irreversible loss of cortical components indexed by atrophy, but also the dysfunction of remaining neurons.