1. Neuroscience
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Neural dynamics of semantic categorization in semantic variant of Primary Progressive Aphasia

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Cite this article as: eLife 2021;10:e63905 doi: 10.7554/eLife.63905

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

  1. Valentina Borghesani

    Neurology, University of California, San Francisco, San Francisco, United States
    For correspondence
    valentina.borghesani@ucsf.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7909-8631
  2. Corby L Dale

    Radiology, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Sladjana Lukic

    Radiology, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Leighton BN Hinkley

    Radiology, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Michael Lauricella

    Neurology, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Wendy Shwe

    Neurology, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Danielle Mizuiri

    Radiology, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Susanna Honma

    Radiology, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Zachary Miller

    Neurology, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
  10. Bruce L Miller

    Department of Neurology, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
  11. John F Houde

    Radiology, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
  12. Maria Luisa Gorno-Tempini

    Department of Neurology, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
  13. Srikantan Nagarajan

    Department of Neurology, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.

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).

Reviewing Editor

  1. Chris I Baker, National Institute of Mental Health, National Institutes of Health, United States

Publication history

  1. Received: October 10, 2020
  2. Accepted: June 21, 2021
  3. Accepted Manuscript published: June 22, 2021 (version 1)
  4. Version of Record published: June 29, 2021 (version 2)

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.

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