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

Version 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.

Metrics

  • 922
    Page views
  • 142
    Downloads
  • 5
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.

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)

  1. Valentina Borghesani
  2. Corby L Dale
  3. Sladjana Lukic
  4. Leighton BN Hinkley
  5. Michael Lauricella
  6. Wendy Shwe
  7. Danielle Mizuiri
  8. Susanna Honma
  9. Zachary Miller
  10. Bruce L Miller
  11. John F Houde
  12. Maria Luisa Gorno-Tempini
  13. Srikantan Nagarajan
(2021)
Neural dynamics of semantic categorization in semantic variant of Primary Progressive Aphasia
eLife 10:e63905.
https://doi.org/10.7554/eLife.63905

Share this article

https://doi.org/10.7554/eLife.63905

Further reading

    1. Neuroscience
    Olgerta Asko, Alejandro Omar Blenkmann ... Anne-Kristin Solbakk
    Research Article Updated

    Orbitofrontal cortex (OFC) is classically linked to inhibitory control, emotion regulation, and reward processing. Recent perspectives propose that the OFC also generates predictions about perceptual events, actions, and their outcomes. We tested the role of the OFC in detecting violations of prediction at two levels of abstraction (i.e., hierarchical predictive processing) by studying the event-related potentials (ERPs) of patients with focal OFC lesions (n = 12) and healthy controls (n = 14) while they detected deviant sequences of tones in a local–global paradigm. The structural regularities of the tones were controlled at two hierarchical levels by rules defined at a local (i.e., between tones within sequences) and at a global (i.e., between sequences) level. In OFC patients, ERPs elicited by standard tones were unaffected at both local and global levels compared to controls. However, patients showed an attenuated mismatch negativity (MMN) and P3a to local prediction violation, as well as a diminished MMN followed by a delayed P3a to the combined local and global level prediction violation. The subsequent P3b component to conditions involving violations of prediction at the level of global rules was preserved in the OFC group. Comparable effects were absent in patients with lesions restricted to the lateral PFC, which lends a degree of anatomical specificity to the altered predictive processing resulting from OFC lesion. Overall, the altered magnitudes and time courses of MMN/P3a responses after lesions to the OFC indicate that the neural correlates of detection of auditory regularity violation are impacted at two hierarchical levels of rule abstraction.

    1. Neuroscience
    Nada Kojovic, Sezen Cekic ... Marie Schaer
    Research Article Updated

    Atypical deployment of social gaze is present early on in toddlers with autism spectrum disorders (ASDs). Yet, studies characterizing the developmental dynamic behind it are scarce. Here, we used a data-driven method to delineate the developmental change in visual exploration of social interaction over childhood years in autism. Longitudinal eye-tracking data were acquired as children with ASD and their typically developing (TD) peers freely explored a short cartoon movie. We found divergent moment-to-moment gaze patterns in children with ASD compared to their TD peers. This divergence was particularly evident in sequences that displayed social interactions between characters and even more so in children with lower developmental and functional levels. The basic visual properties of the animated scene did not account for the enhanced divergence. Over childhood years, these differences dramatically increased to become more idiosyncratic. These findings suggest that social attention should be targeted early in clinical treatments.