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All fields Title Creator / Publisher Keyword Year AND OR AND NOT All fields Title Creator / Publisher Keyword Year AND OR AND NOT All fields Title Creator / Publisher Keyword Year AND OR AND NOT All fields Title Creator / Publisher Keyword Year AND OR AND NOT All fields Title Creator / Publisher Keyword Year Sort by creator [A → Z]' creator [Z → A]' publishing year ↑ (asc)' publishing year ↓ (desc)' title [A → Z]' title [Z → A]' Simple Search Hits 1 – 4 of 4 1 Thalamo-cortical network hyperconnectivity in preclinical progranulin mutation carriers. Lee, Suzee E; Sias, Ana C; Kosik, Eena L. - : eScholarship, University of California, 2019 BASE Show details 2 Thalamo-cortical network hyperconnectivity in preclinical progranulin mutation carriers. Lee, Suzee E; Sias, Ana C; Kosik, Eena L; Flagan, Taru M; Deng, Jersey; Chu, Stephanie A; Brown, Jesse A; Vidovszky, Anna A; Ramos, Eliana Marisa; Gorno-Tempini, Maria Luisa; Karydas, Anna M; Coppola, Giovanni; Geschwind, Daniel H; Rademakers, Rosa; Boeve, Bradley F; Boxer, Adam L; Rosen, Howard J; Miller, Bruce L; Seeley, William W In: Lee, Suzee E; Sias, Ana C; Kosik, Eena L; Flagan, Taru M; Deng, Jersey; Chu, Stephanie A; et al.(2019). Thalamo-cortical network hyperconnectivity in preclinical progranulin mutation carriers. NeuroImage. Clinical, 22, 101751. doi:10.1016/j.nicl.2019.101751. UCLA: Retrieved from: http://www.escholarship.org/uc/item/6vv8g8qt (2019) Abstract: Mutations in progranulin (GRN) cause heterogeneous clinical syndromes, including behavioral variant frontotemporal dementia (bvFTD), primary progressive aphasia (PPA), corticobasal syndrome (CBS) and Alzheimer-type dementia (AD-type dementia). Human studies have shown that presymptomatic GRN carriers feature reduced connectivity in the salience network, a system targeted in bvFTD. Mice with homozygous deletion of GRN, in contrast, show thalamo-cortical hypersynchrony due to aberrant pruning of inhibitory synapses onto thalamo-cortical projection neurons. No studies have systematically explored the intrinsic connectivity networks (ICNs) targeted by the four GRN-associated clinical syndromes, or have forged clear links between human and mouse model findings. We compared 17 preclinical GRN carriers (14 "presymptomatic" clinically normal and three "prodromal" with mild cognitive symptoms) to healthy controls to assess for differences in cognitive testing and gray matter volume. Using task-free fMRI, we assessed connectivity in the salience network, a non-fluent variant primary progressive aphasia network (nfvPPA), the perirolandic network (CBS), and the default mode network (AD-type dementia). GRN carriers and controls showed similar performance on cognitive testing. Although carriers showed little evidence of brain atrophy, markedly enhanced connectivity emerged in all four networks, and thalamo-cortical hyperconnectivity stood out as a unifying feature. Voxelwise assessment of whole brain degree centrality, an unbiased graph theoretical connectivity metric, confirmed thalamic hyperconnectivity. These results show that human GRN disease and the prevailing GRN mouse model share a thalamo-cortical network hypersynchrony phenotype. Longitudinal studies will determine whether this network physiology represents a compensatory response as carriers approach symptom onset, or an early and sustained preclinical manifestation of lifelong progranulin haploinsufficiency. Keyword: Frontotemporal dementia; GRN; MRI; Progranulin; Thalamus URL: http://www.escholarship.org/uc/item/6vv8g8qt BASE Hide details 3 Thalamo-cortical network hyperconnectivity in preclinical progranulin mutation carriers. Lee, Suzee E; Sias, Ana C; Kosik, Eena L. - : eScholarship, University of California, 2019 BASE Show details 4 Thalamo-cortical network hyperconnectivity in preclinical progranulin mutation carriers Lee, Suzee E.; Sias, Ana C.; Kosik, Eena L.. - : Elsevier, 2019 BASE Show details

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