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

Kamalini G. Ranasinghe, Leighton B. Hinkley, Alexander J. Beagle, Danielle Mizuiri, Susanne M. Honma, Ariane E. Welch, Isabel Hubbard, Maria Luisa Mandelli, Zachary A. Miller, Coleman Garrett, Alice La, Adam L. Boxer, John F. Houde, Bruce L. Miller, Keith A. Vossel, Maria Luisa Gorno-Tempini, Srikantan S. Nagarajan

Research output: Contribution to journalArticlepeer-review

40 Scopus citations


Primary progressive aphasia is a syndrome characterized by progressive loss of language abilities with three main phenotypic clinical presentations, including logopenic, non-fluent/agrammatic, and semantic 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 primary progressive aphasia are lacking. The aim of this study was to characterize the spatial and temporal patterns of resting state neuronal synchronizations in primary progressive aphasia syndromes. We hypothesized that resting state brain oscillations will show unique deficits within language network in each variant of primary progressive aphasia. We examined 39 patients with primary progressive aphasia including logopenic variant (n = 14, age = 61 - 9 years), non-fluent/agrammatic variant (n = 12, age = 71 - 8 years) and semantic variant (n = 13, age = 65 - 7 years) using magnetoencephalographic imaging, compared to a control group that was matched in age and gender to each primary progressive aphasia subgroup (n = 20, age = 65 - 5 years). 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 (8-12 Hz); beta (12-30 Hz). Each variant showed a distinct spatiotemporal pattern of altered functional connectivity compared to age-matched controls. Specifically, we found significant hyposynchrony of alpha and beta frequency within the left posterior temporal and occipital cortices in patients with the logopenic variant, within the left inferior frontal cortex in patients with the non-fluent/ agrammatic variant, and within the left temporo-parietal junction in patients with the semantic variant. Patients with logopenic variant primary progressive aphasia also showed significant hypersynchrony of delta-theta frequency within bilateral medial frontal and posterior parietal cortices. Furthermore, region of interest-based analyses comparing the spatiotemporal patterns of variantspecific regions of interest identified in comparison to age-matched controls showed significant differences between primary progressive aphasia variants themselves. We also found distinct patterns of regional spectral power changes in each primary progressive aphasia variant, compared to age-matched controls. Our results demonstrate neurophysiological signatures of network- specific neuronal dysfunction in primary progressive aphasia variants. The unique spatiotemporal patterns of neuronal synchrony signify diverse neurophysiological disruptions and pathological underpinnings of the language network in each variant.

Original languageEnglish (US)
Pages (from-to)2737-2751
Number of pages15
Issue number10
StatePublished - Oct 1 2017

Bibliographical note

Funding Information:
This study was supported by the National Institutes of Health grants: R01NS050915 (M.L.G.T.), K24DC015544 (M.L.G.T.), U01AG052943 (M.L.G.T.), F32AG050434-01A1 (K.G.R.), K23 AG038357 (K.A.V.), P50 AG023501 (B.L.M.), P01 AG19724 (B.L.M.), R21 NS76171 (S.S.N.), R01 DC010145 (J.F.H.), DC013979 (S.S.N.), R01 NS066654 (S.S.N.), R01 NS64060 (S.S.N.), R01 NS100440 (S.S.N.), 2R01AG038791-06A1 (A.L.B.), U54NS092089 (A.L.B.), National Science Foundation Grant BCS-1262297 (S.S.N.); a grant from John Douglas French Alzheimer’s Foundation (K.A.V.); a grant from Larry L. Hillblom Foundation, 2015-A-034-FEL (K.G.R.); University of California San Francisco Alzheimer’s Disease Research Center pilot project grant (K.A.V.); grants from the Alzheimer’s Association and made possible by Part the CloudTM,: (PCTRB-13-288476) (K.A.V.), ETAC-09-133596 (J.F.H.); and a gift from the S. D. Bechtel Jr. Foundation (.K.A.V), and a gift from Ricoh Inc. (S.S.N.). K.G.R., L.B.H., A.J.B., S.H., D.M., G.C., A.L., A.E.W., I.H., Z.A.M., M.L.M., M.L.G.T., A.L.B., K.A.V., S.S.N. and J.F.H. declare no competing financial interests relevant for this work. B.L.M. has the following disclosures: serves as Medical Director for the John Douglas French Foundation; Scientific Director for the Tau Consortium; Director/Medical Advisory Board of the Larry L. Hillblom Foundation; and Scientific Advisory Board Member for the National Institute for Health Research Cambridge Biomedical Research Centre and its subunit, the Biomedical Research Unit in Dementia, UK.

Publisher Copyright:
© The Author (2017).


  • dementia
  • magnetoencephalography
  • neural oscillations
  • primary progressive aphasia
  • resting state functional connectivity


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