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Neuropsychological evidence of multi-domain network hubs in the human thalamus

  1. Kai Hwang  Is a corresponding author
  2. James M Shine
  3. Joel Bruss
  4. Daniel Tranel
  5. Aaron Boes
  1. University of Iowa, United States
  2. The University of Sydney, Australia
Research Article
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Cite this article as: eLife 2021;10:e69480 doi: 10.7554/eLife.69480


Hubs in the human brain support behaviors that arise from brain network interactions. Previous studies have identified hub regions in the human thalamus that are connected with multiple functional networks. However, the behavioral significance of thalamic hubs has yet to be established. Our framework predicts that thalamic subregions with strong hub properties are broadly involved in functions across multiple cognitive domains. To test this prediction, we studied human patients with focal thalamic lesions in conjunction with network analyses of the human thalamocortical functional connectome. In support of our prediction, lesions to thalamic subregions with stronger hub properties were associated with widespread deficits in executive, language, and memory functions, whereas lesions to thalamic subregions with weaker hub properties were associated with more limited deficits. These results highlight how a large-scale network model can broaden our understanding of thalamic function for human cognition.

Data availability

We have made all code and lesion-derived measures used in the manuscript freely available on github (https://github.com/kaihwang/LTH), including neuropsych assessment outcome, derivatives from lesion analyses, data used for functional connectivity analyses, and mRNA expression analyses. Functional connectivity analyses utilized publicly available datasets (Holmes et al., 2015; Nooner et al., 2012). The only data that we cannot post without restrictions are each patient's clinical MRI data and lesion data. Patients were enrolled into the Iowa Lesion Patient Registry the past few decades, and most did not consent to post their clinical MRI data publicly. To gain access to those data, the interested party will have to contact the PI of the lesion registry, Dr. Dan Tranel, and the corresponding author of this project, Dr. Kai Hwang. The user will require to sign a data use agreement. This institutional policy was designed to ensure the appropriate use of the data for academic and not commercial purposes. A study plan of the proposed research will have to be submitted, and we will work with the interested party to obtain the necessary IRB approval from both institutions.

The following previously published data sets were used
    1. Homes et al
    (2015) Brain Genomics Superstruct Project
    Brain Genomics Superstruct Project initial data release with structural, functional, and behavioral measures.
    1. Nooner et al
    (2012) NKI-Rockland sample
    The enhanced Nathan Kline Institute-Rockland Sample (NKI-RS).

Article and author information

Author details

  1. Kai Hwang

    Psychological and Brain Sciences, University of Iowa, Iowa City, United States
    For correspondence
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1064-7815
  2. James M Shine

    The University of Sydney, Sydney, Australia
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1762-5499
  3. Joel Bruss

    Psychological and Brain Sciences, University of Iowa, Iowa City, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Daniel Tranel

    University of Iowa, Iowa, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Aaron Boes

    Psychological and Brain Sciences, University of Iowa, Iowa City, United States
    Competing interests
    The authors declare that no competing interests exist.


National Institutes of Health (R01MH122613)

  • Kai Hwang
  • Daniel Tranel
  • Aaron Boes

National Institutes of Health (RO1MH117772)

  • James M Shine

National Institutes of Health (P50MH094258)

  • Daniel Tranel

Kiwanis Neuroscience Research Foundation

  • Daniel Tranel

National Institutes of Health (R01NS114405)

  • Aaron Boes

National Institutes of Health (R21MH120441)

  • Aaron Boes

National Health and Medical Research Council (GNT1156536)

  • James M Shine

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.


Human subjects: All participants gave written informed consent, and the study was approved by the University of Iowa Institutional Review Board (protocol #200105018).

Reviewing Editor

  1. Jörn Diedrichsen, University of Western Ontario, Canada

Publication history

  1. Received: April 16, 2021
  2. Accepted: September 30, 2021
  3. Accepted Manuscript published: October 8, 2021 (version 1)


© 2021, Hwang 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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