Distinct neurophysiology during nonword repetition in logopenic and non-fluent variants of primary progressive aphasia.

Overlapping clinical presentations in primary progressive aphasia (PPA) variants present challenges for diagnosis and understanding pathophysiology, particularly in the early stages of the disease when behavioral (speech) symptoms are not clearly evident. Divergent atrophy patterns (temporoparietal degeneration in logopenic variant lvPPA, frontal degeneration in nonfluent variant nfvPPA) can partially account for differential speech production errors in the two groups in the later stages of the disease. While the existing dogma states that neurodegeneration is the root cause of compromised behavior and cortical activity in PPA, the extent to which neurophysiological signatures of speech dysfunction manifest independent of their divergent atrophy patterns remain unknown. We test the hypothesis that nonword deficits in lvPPA and nfvPPA arise from distinct patterns of neural oscillations that are unrelated to atrophy. We use a novel structure-function imaging approach integrating magnetoencephalographic imaging of neural oscillations during a non-word repetition task with voxel-based morphometry-derived measures of gray matter volume to isolate neural oscillation abnormalities independent of atrophy. We find reduced beta band neural activity in left temporal regions associated with the late stages of auditory encoding unique to patients with lvPPA and reduced high-gamma neural activity over left frontal regions associated with the early stages of motor preparation in patients with nfvPPA. Neither of these patterns of reduced cortical oscillations was explained by cortical atrophy in our statistical model. These findings highlight the importance of structure-function imaging in revealing neurophysiological sequelae in early stages of dementia when neither structural atrophy nor behavioral deficits are clinically distinct.