Mapping the human subcortical auditory system using histology, post mortem MRI and in vivo MRI at 7T

  1. Kevin R Sitek  Is a corresponding author
  2. Omer Faruk Gulban  Is a corresponding author
  3. Evan Calabrese
  4. G Allan Johnson
  5. Agustin Lage-Castellanos
  6. Michelle Moerel
  7. Satrajit S Ghosh
  8. Federico de Martino
  1. Massachusetts Institute of Technology, United States
  2. Maastricht University, Netherlands
  3. Duke University, United States

Abstract

Studying the human subcortical auditory system non-invasively is challenging due to its small, densely packed structures deep within the brain. Additionally, the elaborate three-dimensional (3-D) structure of the system can be difficult to understand based on currently available 2-D schematics and animal models. We addressed these issues using a combination of histological data, post mortem magnetic resonance imaging (MRI), and in vivo MRI at 7 Tesla. We created anatomical atlases based on state-of-the-art human histology (BigBrain) and post mortem MRI (50 μm). We measured functional MRI (fMRI) responses to natural sounds and demonstrate that the functional localization of subcortical structures is reliable within individual participants who were scanned in two different experiments. Further, a group functional atlas derived from the functional data locates these structures with a median distance below 2mm. Using diffusion MRI tractography, we revealed structural connectivity maps of the human subcortical auditory pathway both in vivo (1050 μm isotropic resolution) and post mortem (200 μm isotropic resolution). This work captures current MRI capabilities for investigating the human subcortical auditory system, describes challenges that remain, and contributes novel, openly available data, atlases, and tools for researching the human auditory system.

Data availability

In vivo data are available on OpenNeuro: https://openneuro.org/datasets/ds001942Derivatives (including histology-based, post mortem MRI-based, and fMRI-based atlases) are available on the Open Science Framework: https://osf.io/c4m82/Analysis code, flowcharts, and other auxiliary files are available on Github: https://github.com/sitek/subcortical-auditory-atlas

The following data sets were generated

Article and author information

Author details

  1. Kevin R Sitek

    McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, United States
    For correspondence
    ksitek@mit.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2172-5786
  2. Omer Faruk Gulban

    Faculty of Psychology and Neuroscience, Maastricht University, Maastricht, Netherlands
    For correspondence
    faruk.gulban@maastrichtuniversity.nl
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7761-3727
  3. Evan Calabrese

    Center for In Vivo Microscopy, Duke University, Durham, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. G Allan Johnson

    Center for In Vivo Microscopy, Duke University, Durham, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Agustin Lage-Castellanos

    Faculty of Psychology and Neuroscience, Maastricht University, Maastricht, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  6. Michelle Moerel

    Faculty of Psychology and Neuroscience, Maastricht University, Maastricht, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  7. Satrajit S Ghosh

    McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5312-6729
  8. Federico de Martino

    Faculty of Psychology and Neuroscience, Maastricht University, Maastricht, Netherlands
    Competing interests
    The authors declare that no competing interests exist.

Funding

NWO (864-13-012)

  • Omer Faruk Gulban
  • Federico de Martino

National Institutes of Health (5R01EB020740)

  • Satrajit S Ghosh

National Institutes of Health (P41EB019936)

  • Satrajit S Ghosh

National Institutes of Health (5F31DC015695)

  • Kevin R Sitek

Eaton Peabody Laboratory at Mass Eye and Ear (Amelia Peabody Scholarship)

  • Kevin R Sitek

Harvard Brain Science Initiative (Travel Grant)

  • Kevin R Sitek

National Institutes of Health (P41EB015897)

  • G Allan Johnson

National Institutes of Health (1S10OD010683-01)

  • G Allan Johnson

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

Reviewing Editor

  1. Jonathan Erik Peelle, Washington University in St. Louis, United States

Ethics

Human subjects: The experimental procedures were approved by the ethics committee of the Faculty for Psychology and Neuroscience at Maastricht University (reference number: ERCPN-167_09_05_2016), and were performed in accordance with the approved guidelines and the Declaration of Helsinki. Written informed consent was obtained for every participant before conducting the experiments. All participants reported to have normal hearing, had no history of hearing disorder/impairments or neurological disease.

Version history

  1. Received: May 30, 2019
  2. Accepted: July 28, 2019
  3. Accepted Manuscript published: August 1, 2019 (version 1)
  4. Version of Record published: August 23, 2019 (version 2)

Copyright

© 2019, Sitek 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

  • 4,189
    views
  • 514
    downloads
  • 55
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

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. Kevin R Sitek
  2. Omer Faruk Gulban
  3. Evan Calabrese
  4. G Allan Johnson
  5. Agustin Lage-Castellanos
  6. Michelle Moerel
  7. Satrajit S Ghosh
  8. Federico de Martino
(2019)
Mapping the human subcortical auditory system using histology, post mortem MRI and in vivo MRI at 7T
eLife 8:e48932.
https://doi.org/10.7554/eLife.48932

Share this article

https://doi.org/10.7554/eLife.48932

Further reading

    1. Immunology and Inflammation
    2. Neuroscience
    Nicolas Aubert, Madeleine Purcarea ... Gilles Marodon
    Research Article

    CD4+CD25+Foxp3+ regulatory T cells (Treg) have been implicated in pain modulation in various inflammatory conditions. However, whether Treg cells hamper pain at steady state and by which mechanism is still unclear. From a meta-analysis of the transcriptomes of murine Treg and conventional T cells (Tconv), we observe that the proenkephalin gene (Penk), encoding the precursor of analgesic opioid peptides, ranks among the top 25 genes most enriched in Treg cells. We then present various evidence suggesting that Penk is regulated in part by members of the Tumor Necrosis Factor Receptor (TNFR) family and the transcription factor Basic leucine zipper transcription faatf-like (BATF). Using mice in which the promoter activity of Penk can be tracked with a fluorescent reporter, we also show that Penk expression is mostly detected in Treg and activated Tconv in non-inflammatory conditions in the colon and skin. Functionally, Treg cells proficient or deficient for Penk suppress equally well the proliferation of effector T cells in vitro and autoimmune colitis in vivo. In contrast, inducible ablation of Penk in Treg leads to heat hyperalgesia in both male and female mice. Overall, our results indicate that Treg might play a key role at modulating basal somatic sensitivity in mice through the production of analgesic opioid peptides.

    1. Neuroscience
    James Malkin, Cian O'Donnell ... Laurence Aitchison
    Research Article

    Biological synaptic transmission is unreliable, and this unreliability likely degrades neural circuit performance. While there are biophysical mechanisms that can increase reliability, for instance by increasing vesicle release probability, these mechanisms cost energy. We examined four such mechanisms along with the associated scaling of the energetic costs. We then embedded these energetic costs for reliability in artificial neural networks (ANNs) with trainable stochastic synapses, and trained these networks on standard image classification tasks. The resulting networks revealed a tradeoff between circuit performance and the energetic cost of synaptic reliability. Additionally, the optimised networks exhibited two testable predictions consistent with pre-existing experimental data. Specifically, synapses with lower variability tended to have (1) higher input firing rates and (2) lower learning rates. Surprisingly, these predictions also arise when synapse statistics are inferred through Bayesian inference. Indeed, we were able to find a formal, theoretical link between the performance-reliability cost tradeoff and Bayesian inference. This connection suggests two incompatible possibilities: evolution may have chanced upon a scheme for implementing Bayesian inference by optimising energy efficiency, or alternatively, energy-efficient synapses may display signatures of Bayesian inference without actually using Bayes to reason about uncertainty.