Disrupted interhemispheric communication in primary progressive aphasia: a multimodal MRI study of homotopic connectivity.

The two hemispheres of the brain are strongly connected both structurally and functionally, and disruptions to interhemispheric communication can have significant cognitive and behavioral consequences. While alterations to interhemispheric structural and/or functional connectivity have been reported in many neurological conditions, this issue has been scarcely addressed in Primary Progressive Aphasia (PPA). PPA is a neurogenerative syndrome primarily involving (left-)lateralized gray matter atrophy and typically categorized into three variants - logopenic, non-fluent, and semantic. Here we examined interhemispheric, homotopic structural and functional connectivity in 72 individuals from the three variants and age-matched controls. Structural connectivity (SC) was calculated from diffusion-weighted MRI and functional connectivity (FC) from resting-state fMRI. Both resulting connectomes were based on the same atlas of homotopic parcels. We asked: 1) Are patterns of abnormal homotopic SC and/or FC shared across PPA variants? 2) How are the FC changes related to underlying structural changes to white and gray matter? We found, first, that average homotopic SC was reduced in all variants and was related to greater behavioral disease severity. By contrast, for homotopic FC, the three variants displayed distinct patterns. Second, direct FC-SC comparisons established that, across variants, the FC and SC changes were distinct from one another and were largely dissociated from gray matter atrophy. In sum, the structural connectivity between the two hemispheres weakens in PPA with disease progression. However, the uncoupling of FC from underlying structural changes indicates that these changes reflect complex patterns of functional re-organization of interhemispheric communication in response to the disease.