1. Neuroscience
Download icon

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
Tools and Resources
  • Cited 5
  • Views 2,859
  • Annotations
Cite this article as: eLife 2020;9:e51214 doi: 10.7554/eLife.51214

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.

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.

Reviewing Editor

  1. Arjen Stolk, Donders Centre for Cognitive Neuroimaging, Netherlands

Publication history

  1. Received: August 20, 2019
  2. Accepted: January 22, 2020
  3. Accepted Manuscript published: January 22, 2020 (version 1)
  4. Version of Record published: February 13, 2020 (version 2)

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

  • 2,859
    Page views
  • 429
    Downloads
  • 5
    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)

Download citations (links to download the citations from this article in formats compatible with various reference manager tools)

Open citations (links to open the citations from this article in various online reference manager services)

Further reading

    1. Chromosomes and Gene Expression
    2. Neuroscience
    Alicia Tapias et al.
    Research Article Updated

    Brain homeostasis is regulated by the viability and functionality of neurons. HAT (histone acetyltransferase) and HDAC (histone deacetylase) inhibitors have been applied to treat neurological deficits in humans; yet, the epigenetic regulation in neurodegeneration remains elusive. Mutations of HAT cofactor TRRAP (ransformation/translation domain-associated protein) cause human neuropathies, including psychosis, intellectual disability, autism, and epilepsy, with unknown mechanism. Here we show that Trrap deletion in Purkinje neurons results in neurodegeneration of old mice. Integrated transcriptomics, epigenomics, and proteomics reveal that TRRAP via SP1 conducts a conserved transcriptomic program. TRRAP is required for SP1 binding at the promoter proximity of target genes, especially microtubule dynamics. The ectopic expression of Stathmin3/4 ameliorates defects of TRRAP-deficient neurons, indicating that the microtubule dynamics is particularly vulnerable to the action of SP1 activity. This study unravels a network linking three well-known, but up-to-date unconnected, signaling pathways, namely TRRAP, HAT, and SP1 with microtubule dynamics, in neuroprotection.

    1. Neuroscience
    Lawrence Huang et al.
    Tools and Resources

    Fluorescent calcium indicators are often used to investigate neural dynamics, but the relationship between fluorescence and action potentials (APs) remains unclear. Most APs can be detected when the soma almost fills the microscope's field of view, but calcium indicators are often used to image populations of neurons, necessitating a large field of view, generating fewer photons per neuron, and compromising AP detection. Here we characterized the AP-fluorescence transfer function in vivo for 48 layer 2/3 pyramidal neurons in primary visual cortex, with simultaneous calcium imaging and cell-attached recordings from transgenic mice expressing GCaMP6s or GCaMP6f. While most APs were detected under optimal conditions, under conditions typical of population imaging studies only a minority of 1AP and 2AP events were detected (often <10% and ~20-30%, respectively), emphasizing the limits of AP detection under more realistic imaging conditions.