A connectional hub in the rostral anterior cingulate cortex links areas of emotion and cognitive control

  1. Wei Tang
  2. Saad Jbabdi
  3. Ziyi Zhu
  4. Michiel Cottaar
  5. Giorgia Grisot
  6. Julia F Lehman
  7. Anastasia Yendiki
  8. Suzanne N Haber  Is a corresponding author
  1. McLean Hospital / Harvard Medical School, United States
  2. University of Oxford, United Kingdom
  3. University of Rochester School of Medicine, United States
  4. Massachusetts General Hospital, United States

Abstract

We investigated afferent inputs from all areas in the frontal cortex (FC) to different subregions in the rostral anterior cingulate cortex (rACC). Using retrograde tracing in macaque monkeys, we quantified projection strength by counting retrogradely labeled cells in each FC area. The projection from different FC regions varied across injection sites in strength, following different spatial patterns. Importantly, a site at the rostral end of the cingulate sulcus stood out as having strong inputs from many areas in diverse FC regions. Moreover, it was at the integrative conjunction of three projection trends across sites. This site marks a connectional hub inside the rACC that integrates FC inputs across functional modalities. Tractography with monkey diffusion magnetic resonance imaging (dMRI) located a similar hub region comparable to the tracing result. Applying the same tractography method to human dMRI data, we demonstrated that a similar hub can be located in the human rACC.

Data availability

All data analysed during this study are included in the manuscript and supporting files. FreeSurfer label files have been provided for Figure 8A.

The following previously published data sets were used

Article and author information

Author details

  1. Wei Tang

    Basic Neuroscience Division, McLean Hospital / Harvard Medical School, Belmont, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Saad Jbabdi

    Centre for Functional MRI of the Brain, Department of Clinical Neurology, University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  3. Ziyi Zhu

    Department of Pharmacology and Physiology, University of Rochester School of Medicine, Rochester, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Michiel Cottaar

    Centre for Functional MRI of the Brain, Department of Clinical Neurology, University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  5. Giorgia Grisot

    Athinoula A Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4349-1201
  6. Julia F Lehman

    Department of Pharmacology and Physiology, University of Rochester School of Medicine, Rochester, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Anastasia Yendiki

    Athinoula A Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Suzanne N Haber

    Department of Pharmacology and Physiology, University of Rochester School of Medicine, Rochester, United States
    For correspondence
    Suzanne_Haber@urmc.rochester.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5237-1941

Funding

National Institute of Mental Health (MH106435)

  • Wei Tang
  • Ziyi Zhu
  • Julia F Lehman
  • Suzanne N Haber

National Institute of Mental Health (MH045573)

  • Wei Tang
  • Ziyi Zhu
  • Julia F Lehman
  • Suzanne N Haber

Medical Research Council (MR/L009013/1)

  • Saad Jbabdi

National Institute of Mental Health (U01-MH109589)

  • Michiel Cottaar

NIH Blueprint for Neuroscience Research (U01-MH093765)

  • Giorgia Grisot
  • Anastasia Yendiki

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

Ethics

Animal experimentation: All nonhuman primate experiments were performed in accordance with the Institute of Laboratory Animal Resources Guide for the Care and Use of Laboratory Animals and approved by the University Committee on Animal Resources at University of Rochester (Protocol Number UCAR-2008-122R).

Human subjects: The human data were obtained from the publicly available Human Connectome Project database. All procedures conformed to ethical standards approved by the Institutional Review Board of Partners Healthcare. All human subjects have provided written informed consent.

Reviewing Editor

  1. David Badre, Brown University, United States

Publication history

  1. Received: November 19, 2018
  2. Accepted: June 18, 2019
  3. Accepted Manuscript published: June 19, 2019 (version 1)
  4. Version of Record published: July 11, 2019 (version 2)

Copyright

© 2019, Tang 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

  • 3,389
    Page views
  • 471
    Downloads
  • 33
    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. Wei Tang
  2. Saad Jbabdi
  3. Ziyi Zhu
  4. Michiel Cottaar
  5. Giorgia Grisot
  6. Julia F Lehman
  7. Anastasia Yendiki
  8. Suzanne N Haber
(2019)
A connectional hub in the rostral anterior cingulate cortex links areas of emotion and cognitive control
eLife 8:e43761.
https://doi.org/10.7554/eLife.43761

Further reading

    1. Neuroscience
    Nataliia Kozhemiako et al.
    Research Article

    Motivated by the potential of objective neurophysiological markers to index thalamocortical function in patients with severe psychiatric illnesses, we comprehensively characterized key non-rapid eye movement (NREM) sleep parameters across multiple domains, their interdependencies, and their relationship to waking event-related potentials and symptom severity. In 72 schizophrenia (SCZ) patients and 58 controls, we confirmed a marked reduction in sleep spindle density in SCZ and extended these findings to show that fast and slow spindle properties were largely uncorrelated. We also describe a novel measure of slow oscillation and spindle interaction that was attenuated in SCZ. The main sleep findings were replicated in a demographically distinct sample, and a joint model, based on multiple NREM components, statistically predicted disease status in the replication cohort. Although also altered in patients, auditory event-related potentials elicited during wake were unrelated to NREM metrics. Consistent with a growing literature implicating thalamocortical dysfunction in SCZ, our characterization identifies independent NREM and wake EEG biomarkers that may index distinct aspects of SCZ pathophysiology and point to multiple neural mechanisms underlying disease heterogeneity. This study lays the groundwork for evaluating these neurophysiological markers, individually or in combination, to guide efforts at treatment and prevention as well as identifying individuals most likely to benefit from specific interventions.

    1. Medicine
    2. Neuroscience
    Guido I Guberman et al.
    Research Article

    Background: The heterogeneity of white matter damage and symptoms in concussion has been identified as a major obstacle to therapeutic innovation. In contrast, most diffusion MRI (dMRI) studies on concussion have traditionally relied on group-comparison approaches that average out heterogeneity. To leverage, rather than average out, concussion heterogeneity, we combined dMRI and multivariate statistics to characterize multi-tract multi-symptom relationships.

    Methods: Using cross-sectional data from 306 previously-concussed children aged 9-10 from the Adolescent Brain Cognitive Development Study, we built connectomes weighted by classical and emerging diffusion measures. These measures were combined into two informative indices, the first representing microstructural complexity, the second representing axonal density. We deployed pattern-learning algorithms to jointly decompose these connectivity features and 19 symptom measures.

    Results: Early multi-tract multi-symptom pairs explained the most covariance and represented broad symptom categories, such as a general problems pair, or a pair representing all cognitive symptoms, and implicated more distributed networks of white matter tracts. Further pairs represented more specific symptom combinations, such as a pair representing attention problems exclusively, and were associated with more localized white matter abnormalities. Symptom representation was not systematically related to tract representation across pairs. Sleep problems were implicated across most pairs, but were related to different connections across these pairs. Expression of multi-tract features was not driven by sociodemographic and injury-related variables, as well as by clinical subgroups defined by the presence of ADHD. Analyses performed on a replication dataset showed consistent results.

    Conclusions: Using a double-multivariate approach, we identified clinically-informative, cross-demographic multi-tract multi-symptom relationships. These results suggest that rather than clear one-to-one symptom-connectivity disturbances, concussions may be characterized by subtypes of symptom/connectivity relationships. The symptom/connectivity relationships identified in multi-tract multi-symptom pairs were not apparent in single-tract/single-symptom analyses. Future studies aiming to better understand connectivity/symptom relationships should take into account multi-tract multi-symptom heterogeneity.

    Funding: financial support for this work from a Vanier Canada Graduate Scholarship from the Canadian Institutes of Health Research (GIG), an Ontario Graduate Scholarship (SS), a Restracomp Research Fellowship provided by the Hospital for Sick Children (SS), an Institutional Research Chair in Neuroinformatics (MD), as well as a Natural Sciences and Engineering Research Council CREATE grant (MD).