Neural dynamics of semantic categorization in semantic variant of Primary Progressive Aphasia
- University of California, San Francisco, United States
Abstract
Semantic representations are processed along a posterior-to-anterior gradient reflecting a shift from perceptual (e.g., it has eight legs) to conceptual (e.g., venomous spiders are rare) information. One critical region is the anterior temporal lobe (ATL): patients with semantic variant primary progressive aphasia (svPPA), a clinical syndrome associated with ATL neurodegeneration, manifest a deep loss of semantic knowledge. We test the hypothesis that svPPA patients perform semantic tasks by over-recruiting areas implicated in perceptual processing. We compared MEG recordings of svPPA patients and healthy controls during a categorization task. While behavioral performance did not differ, svPPA patients showed indications of greater activation over bilateral occipital cortices and superior temporal gyrus, and inconsistent engagement of frontal regions. These findings suggest a pervasive reorganization of brain networks in response to ATL neurodegeneration: the loss of this critical hub leads to a dysregulated (semantic) control system, and defective semantic representations are seemingly compensated via enhanced perceptual processing.
Data availability
The sensitive nature of patients' data and our current ethics protocol do not permit open data sharing. However, anonymized, pre-processed, group-level data used to generate the figures have been uploaded to NeuroVault [https://neurovault.org/collections/FTKQLDFP/]. The clinical and neuroimaging data used in the current paper are available from the Senior Author (S.N.), upon formal request indicating name and affiliation of the researcher as well as a brief description of the use that will be done of the data. All requests will undergo UCSF regulated procedure thus require submission of a Material Transfer Agreement (MTA) which can be found at https://icd.ucsf.edu/material-transfer-and-data-agreements No commercial use would be approved.
Article and author information
Author details
Valentina Borghesani
Funding
National Institute of Health (R01NS050915)
- Maria Luisa Gorno-Tempini
Global Brain Health Institute
- Maria Luisa Gorno-Tempini
University of California Office of the President (MRP-17-454755)
- Srikantan Nagarajan
National Institute of Health (K24DC015544)
- Maria Luisa Gorno-Tempini
National Institute of Health (R01NS100440)
- John F Houde
National Institute of Health (R01DC013979)
- Srikantan Nagarajan
National Institute of Health (R01DC176960)
- Srikantan Nagarajan
National Institute of Health (R01DC017091)
- Srikantan Nagarajan
National Institute of Health (R01EB022717)
- Srikantan Nagarajan
National Institute of Health (R01AG062196)
- Srikantan Nagarajan
Larry Hillblom Foundation
- Maria Luisa Gorno-Tempini
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Human subjects: The study was approved by the UCSF Committee on Human Research and all subjects provided written informed consent.(IRB # 11-05249).
Copyright
© 2021, Borghesani et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Metrics
-
- 1,033
- views
-
- 164
- downloads
-
- 5
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Neural dynamics of semantic categorization in semantic variant of Primary Progressive Aphasia
eLife 10:e63905.
https://doi.org/10.7554/eLife.63905
Further reading
-
- Evolutionary Biology
- Neuroscience
The first complete 3D reconstruction of the compound eye of a minute wasp species sheds light on the nuts and bolts of size reduction.
-
- Neuroscience
Early-life stress can have lifelong consequences, enhancing stress susceptibility and resulting in behavioural and cognitive deficits. While the effects of early-life stress on neuronal function have been well-described, we still know very little about the contribution of non-neuronal brain cells. Investigating the complex interactions between distinct brain cell types is critical to fully understand how cellular changes manifest as behavioural deficits following early-life stress. Here, using male and female mice we report that early-life stress induces anxiety-like behaviour and fear generalisation in an amygdala-dependent learning and memory task. These behavioural changes were associated with impaired synaptic plasticity, increased neural excitability, and astrocyte hypofunction. Genetic perturbation of amygdala astrocyte function by either reducing astrocyte calcium activity or reducing astrocyte network function was sufficient to replicate cellular, synaptic, and fear memory generalisation associated with early-life stress. Our data reveal a role of astrocytes in tuning emotionally salient memory and provide mechanistic links between early-life stress, astrocyte hypofunction, and behavioural deficits.
