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March 14, 2023; 100 (11) Research Article

Advanced Brain Age and Chronic Poststroke Aphasia Severity

Natalie Busby, Janina Wilmskoetter, Ezequiel Gleichgerrcht, Chris Rorden, Rebecca Roth, Roger Newman-Norlund, Argye Elizabeth Hillis, Simon S. Keller, Christophe de Bezenac, Sigfus Kristinsson, Julius Fridriksson, Leonardo Bonilha
First published December 16, 2022, DOI: https://doi.org/10.1212/WNL.0000000000201693
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Article Information

vol. 100 no. 11 e1166-e1176
DOI: 
https://doi.org/10.1212/WNL.0000000000201693
PubMed: 
36526425
Published By: 
Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology
Print ISSN: 
0028-3878
Online ISSN: 
1526-632X
History: 
  • Received May 16, 2022
  • Accepted in final form October 31, 2022
  • First Published December 16, 2022.

Article Versions

Copyright & Usage: 
© 2022 American Academy of Neurology

Author Disclosures

    1. Natalie Busby, PhD,
    2. Janina Wilmskoetter, PhD,
    3. Ezequiel Gleichgerrcht, MD, PhD,
    4. Chris Rorden, PhD,
    5. Rebecca Roth, BA,
    6. Roger Newman-Norlund, PhD,
    7. Argye Elizabeth Hillis, MD, MA,
    8. Simon S. Keller, PhD,
    9. Christophe de Bezenac, PhD,
    10. Sigfus Kristinsson, PhD,
    11. Julius Fridriksson, PhD and
    12. Leonardo Bonilha, MD, PhD
  1. Natalie Busby, PhD,
    2. Scientific Advisory Boards:

    1. None

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. None

    Editorial Boards:

    1. NONE

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. NONE

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. NONE

    Research Support, Government Entities:

    1. NONE

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. None

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  2. Janina Wilmskoetter, PhD,
    3. Scientific Advisory Boards:

    1. None

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. None

    Editorial Boards:

    1. NONE

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. NONE

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. NONE

    Research Support, Government Entities:

    1. (1) NIH/NIDCD U01DC017521, Co-Investigator, 2022(2) NIH/NIDCD P50DC014664-06A1, Co-Investigator, 2022(3) NIH/NIDCD P50DC014664-06A1, Co-Investigator, 2022

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. None

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  3. Ezequiel Gleichgerrcht, MD, PhD,
    4. Scientific Advisory Boards:

    1. None

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. None

    Editorial Boards:

    1. NONE

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. NONE

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. NONE

    Research Support, Government Entities:

    1. NONE

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. None

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  4. Chris Rorden, PhD,
    5. Scientific Advisory Boards:

    1. None

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. None

    Editorial Boards:

    1. NONE

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. NONE

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. NONE

    Research Support, Government Entities:

    1. P50 DC014664 4/1/2016-3/31/2020 $11,394,899, Role Project Leader: Neuroimaging Core and Project 3R01 DC009659 10/1/2015-10/5/2019 $1,829,676, Role co-IR21 DC014170 05/2015-04/2017 $275,000, Role co-IR01 DC014021 10/6/2014-5/31/2019 $1,381,525, Role co-IU01 DC011739 Fridriksson (PI) 7/1/2012-6/31/2017 $1,381,525, Role co-ISouth Carolina SmartState Endowed Chair of Neuroimaging, Role PI

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. None

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  5. Rebecca Roth, BA,
    6. Scientific Advisory Boards:

    1. None

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. None

    Editorial Boards:

    1. NONE

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. NONE

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. NONE

    Research Support, Government Entities:

    1. NONE

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. None

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  6. Roger Newman-Norlund, PhD,
    7. Scientific Advisory Boards:

    1. None

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. None

    Editorial Boards:

    1. NONE

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. NONE

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. NONE

    Research Support, Government Entities:

    1. NONE

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. None

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  7. Argye Elizabeth Hillis, MD, MA,
    8. Scientific Advisory Boards:

    1. Unpaid member of the Scientific Advisory Board, SnyderCenter for Aphasia Life Enhancement

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. None

    Editorial Boards:

    1. Stroke, Associate Editor, 2014-2020; Deputy Editor (present); Aphasiology, Associate Editor, 2008-2022, Practice Update Neurology, Associate Editor, 2015-present

    Patents:

    1. NONE

    Publishing Royalties:

    1. Handbook of Adult Language Disorders, Taylor & Francis, 2015-2020

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. NONE

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. NONE

    Research Support, Government Entities:

    1. (1) NIDCD RO1 DC05375 2003-current, PI(2) P50 DC014664, PI of project 2 and PI of clinical core, 2016-current(3)NIDCD, R01DC015466, PI, 2017-current(4)NINDS, R25NS06572, PI, 2009-present(5) NHLBI R01HL144751 Co-I 2021-present

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. Serves on the Board of Directors of the World Stroke Organization (unpaid)

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  8. Simon S. Keller, PhD,
    9. Scientific Advisory Boards:

    1. None

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. None

    Editorial Boards:

    1. NONE

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. NONE

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. NONE

    Research Support, Government Entities:

    1. NONE

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. None

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  9. Christophe de Bezenac, PhD,
    10. Scientific Advisory Boards:

    1. None

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. None

    Editorial Boards:

    1. NONE

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. NONE

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. NONE

    Research Support, Government Entities:

    1. NONE

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. None

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  10. Sigfus Kristinsson, PhD,
    11. Scientific Advisory Boards:

    1. None

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. None

    Editorial Boards:

    1. NONE

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. NONE

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. NONE

    Research Support, Government Entities:

    1. NONE

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. None

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  11. Julius Fridriksson, PhD and
    12. Scientific Advisory Boards:

    1. None

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. None

    Editorial Boards:

    1. ssociate Editor:Neurobiology of Language

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. NONE

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. PI on two NIH grants. Co-I on several other NIH grants.

    Research Support, Government Entities:

    1. NONE

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. None

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  12. Leonardo Bonilha, MD, PhD
    13. Scientific Advisory Boards:

    1. None

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. None

    Editorial Boards:

    1. I am part of the editorial board of Epilepsy and Behavior. I do not receive financial compensation for this role.

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. NONE

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. NONE

    Research Support, Government Entities:

    1. R01DC014021 (NIH/NIDCD)Bonilha (PI) 07/01/2014 – 07/01/2024Brain Connectivity Supporting Language Recovery in Aphasia. Major Goal: To investigate how residual structural connectivity enables recovery from aphasia in individuals who suffered a stroke.Role: PIU01DC017521 (NIH/NIDCD)Bonilha (MPI) 01/01/2019– 01/01/2024Speech Entrainment for Aphasia Recovery (SpARc).Major Goal: Phase II clinical trial to determine effect sizes and optimal dose of speech entrainment to treat non-fluent aphasia.Role: Corresponding MPIR01NS110347(NIH/NINDS)Bonilha (MPI) 07/01/2019 – 07/01/2024Predicting Epilepsy Surgery Outcomes Using Neural Network Architecture.Major Goal: To evaluate the relationship between neuronal network abnormalities and surgical outcomes in temporal lobe epilepsy.Role: Corresponding MPIP50 DC014664 (NIH/NIDCD)Fridriksson (PI) 04/14/2016 – 04/14/2021Center for the Study of Aphasia Recovery (C-STAR) P50 DC014664Major Goal: To evaluate mechanisms associated with language impairment and recovery after brain injury. (Co-Investigator).

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. None

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  1. From the Departments of Communication Sciences and Disorders (N.B., J.F.), and Psychology (C.R., R.N.N.), University of South Carolina, Columbia; Department of Health and Rehabilitation Sciences (J.W., E.G., S.K., J.F.), Medical University of South Carolina, Charleston; Department of Neurology (R.R., L.B.), Emory University, Atlanta, GA; Department of Neurology (A.E.H.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Pharmacology and Therapeutics (S.S.K., C.d.B.), Institute of Systems, Molecular and Integrative Biology, University of Liverpool, United Kingdom; The Walton Centre NHS Foundation Trust (S.S.K., C.d.B.), Liverpool, United Kingdom.
  1. Correspondence
    Dr. Busby hethern{at}mailbox.sc.edu
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