Leighton B.N. Hinkley,Zachary A. Miller, Megan M. Cahill Thompson, Kamalini Ranasinghe, Danielle Mizuiri, Coleman Garrett, Susanne Honma,Bruce Miller, Keith Vossel, John F. Houde, Maria Luisa Gorno-Tempini, Srikantan S. Nagarajan, Ph.D.
Background Primary progressive aphasia (PPA), a syndrome characterized by progressive loss of language function, is clinically organized into three distinct variants: non-fluent (nfvPPA), logopenic (lvPPA) and semantic (svPPA) sub-types. Each variant is associated with a specific pattern of cortical atrophy and language deficits. While anomia is a feature common across these subtypes, little is known about variant specific brain region abnormalities subserving object naming deficits (from visual perception to object recognition, retrieval, speech preparation and production). Here, we use MEG imaging to identify impairments in stages of cortical oscillatory dynamics during a picture naming task in each PPA variant.
Method MEG data was collected using a 275-channel whole head biomagnetometer (CTF; Port Coquitlam, BC) during a picture naming task with overt speech production from both patients with nfvPPA, lvPPA and age-matched healthy controls. During MEG scanning, subjects participated in a picture naming task where subjects were presented on a screen a picture of an object and were instructed to name the object into a microphone. Response-locked datasets were reconstructed in source space using adaptive spatial filtering techniques implemented in NUTMEG in the beta (12-30Hz) frequency band prior to response onset. Laterality index (LI) was computed as an activation ratio between the left and right hemispheres within frontal ROIs involved in language production.
Results: Prior to speech onset (0ms) induced changes in beta power progressed from the occipital to temporal/parietal and left frontal lobes. Significant reduction in beta power (compared to healthy controls, p<0.05 FDR) was observed in the lvPPA patients in three regions in the left hemisphere: fusiform (300ms pre-response), posterior temporal lobe (STG/ITG; 200ms pre-response) and post-central gyrus (PoCG; 100ms pre-response) and one region in the right hemisphere: right MFG (100 ms pre-response). In contrast in patients with nfvPPA, the only significant difference in beta activity (p<0.05 FDR) was identified in late stage activity over the left PoCG (100ms pre-response). LI for the lvPPA cohort was significantly reducted (p<0.05) when compared to either the healthy control or nfvPPA cohort. The nfvPPA group and healthy controls were no different in LI (p>0.05).
Discussion: Our findings demonstrate that object naming deficits in lvPPA and nfvPPA originate from different mechanisms. In lvPPA, impoverished activation in earlier stages of the object naming pathway (fusiform, STG/ITG) lead to a failure to activate the PoCG during naming. Activation over the right hemisphere may act as a compensatory mechanism for speech production in the presence of cortical atrophy and underactivity in lvPPA. In nfvPPA, naming deficits originate from reduced activation in the PoCG alone, with preserved magnitude and timing of activity in the earlier stages of the object naming pathway. The findings demonstrate that MEG imaging can provide important distinctions between different stages in the speech production pathway that may discriminate between lvPPA and nfvPPA.