Human Neocortical Neurosolver (HNN), a new software tool for interpreting the cellular and network origin of human MEG/EEG data

  1. Samuel A Neymotin  Is a corresponding author
  2. Dylan S Daniels
  3. Blake Caldwell
  4. Robert A McDougal
  5. Nicholas T Carnevale
  6. Mainak Jas
  7. Christopher I Moore
  8. Michael L Hines
  9. Matti Hämäläinen
  10. Stephanie R Jones  Is a corresponding author
  1. Brown University, United States
  2. Yale University, United States
  3. Massachusetts General Hospital, United States

Abstract

Magneto- and electro-encephalography (MEG/EEG) non-invasively record human brain activity with millisecond resolution providing reliable markers of healthy and disease states. Relating these macroscopic signals to underlying cellular- and circuit-level generators is a limitation that constrains using MEG/EEG to reveal novel principles of information processing or to translate findings into new therapies for neuropathology. To address this problem, we built Human Neocortical Neurosolver (HNN, https://hnn.brown.edu) software. HNN has a graphical user interface designed to help researchers and clinicians interpret the neural origins of MEG/EEG. HNN's core is a neocortical circuit model that accounts for biophysical origins of electrical currents generating MEG/EEG. Data can be directly compared to simulated signals and parameters easily manipulated to develop/test hypotheses on a signal's origin. Tutorials teach users to simulate commonly measured signals, including event related potentials and brain rhythms. HNN's ability to associate signals across scales makes it a unique tool for translational neuroscience research.

Data availability

All source-code, model parameters, and associated data are provided in a permanent public-accessible repository on github (https://github.com/jonescompneurolab/hnn).

Article and author information

Author details

  1. Samuel A Neymotin

    Department of Neuroscience, Brown University, Providence, United States
    For correspondence
    samuel.neymotin@nki.rfmh.org
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3646-5195
  2. Dylan S Daniels

    Department of Neuroscience, Brown University, Providence, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Blake Caldwell

    Department of Neuroscience, Brown University, Providence, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6882-6998
  4. Robert A McDougal

    Department of Neuroscience, Yale University, New Haven, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6394-3127
  5. Nicholas T Carnevale

    Department of Neuroscience, Yale University, New Haven, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Mainak Jas

    Athinoula A Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Christopher I Moore

    Department of Neuroscience, Brown University, Providence, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4534-1602
  8. Michael L Hines

    Department of Neuroscience, Yale University, New Haven, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Matti Hämäläinen

    Athinoula A Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, United States
    Competing interests
    The authors declare that no competing interests exist.
  10. Stephanie R Jones

    Department of Neuroscience, Brown University, Providence, United States
    For correspondence
    Stephanie_Jones@brown.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6760-5301

Funding

National Institute of Biomedical Imaging and Bioengineering (BRAIN Award 5-R01-EB022889-02)

  • Samuel A Neymotin
  • Dylan S Daniels
  • Blake Caldwell
  • Robert A McDougal
  • Nicholas T Carnevale
  • Mainak Jas
  • Christopher I Moore
  • Michael L Hines
  • Matti Hämäläinen
  • Stephanie R Jones

National Institute of Biomedical Imaging and Bioengineering (BRAIN Award Supplement R01EB022889-02S1)

  • Samuel A Neymotin
  • Dylan S Daniels
  • Blake Caldwell
  • Robert A McDougal
  • Nicholas T Carnevale
  • Mainak Jas
  • Christopher I Moore
  • Michael L Hines
  • Matti Hämäläinen
  • Stephanie R Jones

National Institute on Deafness and Other Communication Disorders (5-R01DC012947-07)

  • Samuel A Neymotin

Army Research Office (W911NF-19-1-0402)

  • Samuel A Neymotin

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication. The views and conclusions contained in this document are those of the authorsand should not be interpreted as representing the official policies, either expressed or implied, of the Army Research Office or the U.S. Government. The U.S. Government is authorized to reproduce and distribute reprints for Government purposes notwithstanding any copyright notation herein.

Copyright

© 2020, Neymotin 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

  • 7,188
    views
  • 920
    downloads
  • 76
    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. Samuel A Neymotin
  2. Dylan S Daniels
  3. Blake Caldwell
  4. Robert A McDougal
  5. Nicholas T Carnevale
  6. Mainak Jas
  7. Christopher I Moore
  8. Michael L Hines
  9. Matti Hämäläinen
  10. Stephanie R Jones
(2020)
Human Neocortical Neurosolver (HNN), a new software tool for interpreting the cellular and network origin of human MEG/EEG data
eLife 9:e51214.
https://doi.org/10.7554/eLife.51214

Share this article

https://doi.org/10.7554/eLife.51214

Further reading

    1. Neuroscience
    Mathias Guayasamin, Lewis R Depaauw-Holt ... Ciaran Murphy-Royal
    Research Article

    Early-life stress can have lifelong consequences, enhancing stress susceptibility and resulting in behavioural and cognitive deficits. While the effects of early-life stress on neuronal function have been well-described, we still know very little about the contribution of non-neuronal brain cells. Investigating the complex interactions between distinct brain cell types is critical to fully understand how cellular changes manifest as behavioural deficits following early-life stress. Here, using male and female mice we report that early-life stress induces anxiety-like behaviour and fear generalisation in an amygdala-dependent learning and memory task. These behavioural changes were associated with impaired synaptic plasticity, increased neural excitability, and astrocyte hypofunction. Genetic perturbation of amygdala astrocyte function by either reducing astrocyte calcium activity or reducing astrocyte network function was sufficient to replicate cellular, synaptic, and fear memory generalisation associated with early-life stress. Our data reveal a role of astrocytes in tuning emotionally salient memory and provide mechanistic links between early-life stress, astrocyte hypofunction, and behavioural deficits.

    1. Neuroscience
    Alessandro Piccin, Anne-Emilie Allain ... Angelo Contarino
    Research Article

    Substance-induced social behavior deficits dramatically worsen the clinical outcome of substance use disorders; yet, the underlying mechanisms remain poorly understood. Herein, we investigated the role for the corticotropin-releasing factor receptor 1 (CRF1) in the acute sociability deficits induced by morphine and the related activity of oxytocin (OXY)- and arginine-vasopressin (AVP)-expressing neurons of the paraventricular nucleus of the hypothalamus (PVN). For this purpose, we used both the CRF1 receptor-preferring antagonist compound antalarmin and the genetic mouse model of CRF1 receptor-deficiency. Antalarmin completely abolished sociability deficits induced by morphine in male, but not in female, C57BL/6J mice. Accordingly, genetic CRF1 receptor-deficiency eliminated morphine-induced sociability deficits in male mice. Ex vivo electrophysiology studies showed that antalarmin also eliminated morphine-induced firing of PVN neurons in male, but not in female, C57BL/6J mice. Likewise, genetic CRF1 receptor-deficiency reduced morphine-induced firing of PVN neurons in a CRF1 gene expression-dependent manner. The electrophysiology results consistently mirrored the behavioral results, indicating a link between morphine-induced PVN activity and sociability deficits. Interestingly, in male mice antalarmin abolished morphine-induced firing in neurons co-expressing OXY and AVP, but not in neurons expressing only AVP. In contrast, in female mice antalarmin did not affect morphine-induced firing of neurons co-expressing OXY and AVP or only OXY, indicating a selective sex-specific role for the CRF1 receptor in opiate-induced PVN OXY activity. The present findings demonstrate a major, sex-linked, role for the CRF1 receptor in sociability deficits and related brain alterations induced by morphine, suggesting new therapeutic strategy for opiate use disorders.