Page 92 - MEGIN Book Of Abstracts - 2023

Neural dynamics of semantic categorization in Reduced synchrony in alpha oscillations during life
semantic variant of primary progressive aphasia predicts post mortem neurofibrillary tangle density
(2021) in early-onset and atypical Alzheimer's disease
(2021)
Borghesani, V; Dale, C L; Lukic, S; Hinkley, Lbn;
Lauricella, M; Shwe, W; Mizuiri, D; Honma, S; Miller, Z; Ranasinghe, Kamalini G; Petersen, Cathrine; Kudo,
Miller, B; Houde, J F; Gorno-Tempini, M L; Nagarajan, S S Kiwamu; Mizuiri, Danielle; Rankin, Katherine P;
Rabinovici, Gil D; Gorno-Tempini, Maria Luisa; Seeley,
Memory and Aging Center, Department of Neurology, Univer- William W; Spina, Salvatore; Miller, Bruce L; Vossel, Keith;
sity of California, San Francisco, San Francisco, United States; Grinberg, Lea T; Nagarajan, Srikantan S
Department of Radiology and Biomedical Imaging, Univer-
sity of California, San Francisco, San Francisco, United States; Memory and Aging Center, Department of Neurology, Uni-
Department of Otolaryngology, University of California, San versity of California San Francisco, San Francisco, California,
Francisco, San Francisco, United States; Department of Neu- USA; Medical Imaging Business Center, Ricoh Company, Ltd.,
rology, Dyslexia Center University of California, San Francisco, Kanazawa, Japan; Department Radiology & Biomedical Im-
San Francisco, United States aging, University of California San Francisco, San Francisco,
California, USA; Department of Pathology, University of Cali-
ABSTRACT Semantic representations are processed fornia, San Francisco, San Francisco, California, USA; Mary S.
along a posterior-to-anterior gradient reflecting a shift Easton Center for Alzheimer's Disease Research, Department
from perceptual (e.g., it has eight legs) to conceptual of Neurology, David Geffen School of Medicine, University of
(e.g., venomous spiders are rare) information. One criti- California Los Angeles, Los Angeles, California, USA; Depart-
cal region is the anterior temporal lobe (ATL): patients ment of Pathology, LIM22, University of Sao Paulo, Sao Paulo,
with semantic variant primary progressive aphasia Brazil
(svPPA), a clinical syndrome associated with ATL
neurodegeneration, manifest a deep loss of semantic INTRODUCTION Neurophysiological manifestations
knowledge. We test the hypothesis that svPPA patients selectively associated with amyloid beta and tau depo-
perform semantic tasks by over-recruiting areas impli- sitions in Alzheimer's disease (AD) are useful network
cated in perceptual processing. We compared MEG re- biomarkers to identify peptide specific pathological
cordings of svPPA patients and healthy controls during processes. The objective of this study was to validate
a categorization task. While behavioral performance the associations between reduced neuronal synchrony
did not differ, svPPA patients showed indications of within alpha oscillations and neurofibrillary tangle
greater activation over bilateral occipital cortices and (NFT) density in autopsy examination, in patients with
superior temporal gyrus, and inconsistent engagement AD.
of frontal regions. These findings suggest a pervasive
reorganization of brain networks in response to ATL METHODS In a well-characterized clinicopathological
neurodegeneration: the loss of this critical hub leads to cohort of AD patients (n = 13), we quantified neuro-
a dysregulated (semantic) control system, and defective nal synchrony within alpha (8-12 Hz) and delta-theta
semantic representations are seemingly compensated (2-8 Hz) oscillations, using magnetoencephalography
via enhanced perceptual processing. during the disease course, within six selected neocorti-
cal and hippocampal regions, including angular gyrus,
Keywords: anterior temporal lobe, human, magnetoen- superior temporal gurus, middle frontal gyrus, primary
cephalography, neuroscience, primary progressive apha- motor cortex, CA1, and subiculum, and correlated these
sia, semantic categorization, semantic dementia, semantic with regional NFT density quantified at histopathologi-
variant ppa cal examination.

eLife (2021), Vol. 10 (34155973) (4 citations)

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