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Poster A30, Wednesday, November 8, 10:30 – 11:45 am, Harborview and Loch Raven Ballrooms

Distinct spatiotemporal patterns of neuronal functional connectivity in primary progressive aphasia variants

Kamalini Ranasinghe1, Leighton Hinkley1, Alexander Beagle1, Danielle Mizuiri1, Susanne Honma1, Ariane Welch1, Isabel Hubbard1, Maria Luisa Mandelli1, Zachary Miller1, Coleman Garret1, Alice La1, Adam Boxer1, John Houde1, Bruce Miller1, Keith Vossel1, Maria Luisa Gorno-Tempini1, Srikantan Nagarajan1;1University of California San Francisco

Primary progressive aphasia (PPA) is a syndrome characterized by progressive loss of language abilities with three main phenotypic clinical presentations, including logopenic (lvPPA), non-fluent/agrammatic (nfvPPA), and semantic (svPPA) variants. Previous imaging studies have shown unique anatomic impacts within language networks in each variant. However, direct measures of spontaneous neuronal activity and functional integrity of these impacted neural networks in PPA are lacking. The aim of this study was to characterize the spatial and temporal patterns of resting state neuronal synchronizations in PPA syndromes. We hypothesized that resting state brain oscillations will show unique deficits within language networks in each variant of PPA. We examined 39 PPA patients including lvPPA (n = 14, age = 61±9), nfvPPA (n = 12, age = 71±8) and svPPA (n = 13, age = 65±7) using magnetoencephalographic imaging, compared to a control group that was matched in age and gender to each PPA subgroup (n = 20, age = 65±5). Each patient underwent a complete clinical evaluation including a comprehensive battery of language tests. We examined the whole-brain resting state functional connectivity as measured by imaginary coherence in each patient group compared to the control cohort, in three frequency oscillation bands—delta-theta (2 - 8 Hz); alpha (8 - 12Hz); and beta (12 - 30Hz). We found that within the left hemisphere, each PPA variant shows a distinct pattern of functional connectivity deficits in alpha and beta frequency oscillations. Specifically, we found significant reductions of neuronal synchrony within the left posterior temporal and occipital cortices in lvPPA patients, within the left inferior frontal cortex in nfvPPA patients, and within the left temporo-parietal junction in svPPA patients. lvPPA patients further showed significant hypersynchrony of delta-theta frequency band within bilateral medial frontal and posterior parietal cortices. Importantly, the distinct spatiotemporal characteristics of MEGI-derived functional connectivity patterns reliably discriminated PPA variants (linear discriminant function analysis, overall correct classification of 95%). We also found distinct patterns of regional spectral power in each PPA variant. The functional connectivity deficits showed consistently robust effects when corrected for cortical volumes loss. In contrast, the spectral power differences showed partial dependencies on cortical volumes. Collectively, these results demonstrate neural signatures of network specific, regional, neuronal dysfunction in each PPA variant. The unique spatiotemporal patterns of neuronal synchrony in subgroups signify diverse neurophysiological disruptions and pathological underpinnings of the language network in each PPA variant.

Topic Area: Language Disorders

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