Neural ensemble dynamics in dorsal motor cortex during speech in people with paralysis

  1. Sergey D Stavisky  Is a corresponding author
  2. Francis R Willett
  3. Guy H Wilson
  4. Brian A Murphy
  5. Paymon Rezaii
  6. Donald T Avansino
  7. William D Memberg
  8. Jonathan P Miller
  9. Robert F Kirsch
  10. Leigh R Hochberg
  11. A Bolu Ajiboye
  12. Shaul Druckmann
  13. Krishna V Shenoy
  14. Jaimie M Henderson
  1. Stanford University, United States
  2. Case Western Reserve University, United States
  3. University Hospitals Cleveland Medical Center, United States
  4. Brown University, United States

Abstract

Speaking is a sensorimotor behavior whose neural basis is difficult to study with single neuron resolution due to the scarcity of human intracortical measurements. We used electrode arrays to record from the motor cortex 'hand knob' in two people with tetraplegia, an area not previously implicated in speech. Neurons modulated during speaking and during non-speaking movements of the tongue, lips, and jaw. This challenges whether the conventional model of a 'motor homunculus' division by major body regions extends to the single-neuron scale. Spoken words and syllables could be decoded from single trials, demonstrating the potential of intracortical recordings for brain-computer interfaces to restore speech. Two neural population dynamics features previously reported for arm movements were also present during speaking: a component that was mostly invariant across initiating different words, followed by rotatory dynamics during speaking. This suggests that common neural dynamical motifs may underlie movement of arm and speech articulators.

Data availability

The sharing of the raw human neural data is restricted due to the potential sensitivity of this data. These data are available upon request to the senior authors (K.V.S. or J.M.H.). To respect the participants' expectation of privacy, a legal agreement between the researcher's institution and the BrainGate consortium would need to be set up to facilitate the sharing of these datasets. Processed data is provided as source data, and analysis code is available at https://github.com/sstavisk/speech_in_dorsal_motor_cortex_eLife_2019.

Article and author information

Author details

  1. Sergey D Stavisky

    Department of Neurosurgery, Stanford University, Stanford, United States
    For correspondence
    sergey.stavisky@gmail.com
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5238-0573
  2. Francis R Willett

    Department of Neurosurgery, Stanford University, Stanford, United States
    Competing interests
    No competing interests declared.
  3. Guy H Wilson

    Neurosciences Program, Stanford University, Stanford, United States
    Competing interests
    No competing interests declared.
  4. Brian A Murphy

    Department of Biomedical Engineering, Case Western Reserve University, Cleveland, United States
    Competing interests
    No competing interests declared.
  5. Paymon Rezaii

    Department of Neurosurgery, Stanford University, Stanford, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4803-0853
  6. Donald T Avansino

    Department of Neurosurgery, Stanford University, Stanford, United States
    Competing interests
    No competing interests declared.
  7. William D Memberg

    Department of Biomedical Engineering, Case Western Reserve University, Cleveland, United States
    Competing interests
    No competing interests declared.
  8. Jonathan P Miller

    Department of Neurosurgery, University Hospitals Cleveland Medical Center, Cleveland, United States
    Competing interests
    No competing interests declared.
  9. Robert F Kirsch

    Department of Biomedical Engineering, Case Western Reserve University, Cleveland, United States
    Competing interests
    No competing interests declared.
  10. Leigh R Hochberg

    School of Engineering and Carney Institute for Brain Science, Brown University, Providence, United States
    Competing interests
    Leigh R Hochberg, The MGH Translational Research Center has clinical research support agreements with Paradromics and Synchron Med, for which L.R.H provides consultative input.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0261-2273
  11. A Bolu Ajiboye

    Department of Biomedical Engineering, Case Western Reserve University, Cleveland, United States
    Competing interests
    No competing interests declared.
  12. Shaul Druckmann

    Department of Neurobiology, Stanford University, Stanford, United States
    Competing interests
    No competing interests declared.
  13. Krishna V Shenoy

    Department of Electrical Engineering, Stanford University, Stanford, United States
    Competing interests
    Krishna V Shenoy, is a consultant for Neuralink Corp. and on the scientific advisory boards of CTRL-Labs Inc., MIND-X Inc., Inscopix Inc., and Heal Inc.
  14. Jaimie M Henderson

    Department of Neurosurgery, Stanford University, Stanford, United States
    Competing interests
    Jaimie M Henderson, is a consultant for Neuralink Corp.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3276-2267

Funding

ALS Association Milton Safenowitz Postdoctoral Fellowship (17-PDF-364)

  • Sergey D Stavisky

National Institute of Neurological Disorders and Stroke (5U01NS098968-02)

  • Leigh R Hochberg
  • Jaimie M Henderson

Howard Hughes Medical Institute

  • Krishna V Shenoy

National Institute on Deafness and Other Communication Disorders (R01DC009899)

  • Leigh R Hochberg

NSF GRFP (DGE - 1656518)

  • Guy H Wilson

Regina Casper Stanford Graduate Fellowship

  • Guy H Wilson

Office of Research and Development, Rehabilitation R&D Service, Department of Veterans Affairs (A2295R)

  • Leigh R Hochberg

Office of Research and Development, Rehabilitation R&D Service, Department of Veterans Affairs (B6453R)

  • Leigh R Hochberg

A. P. Giannini Foundation Postdoctoral Research Fellowship

  • Sergey D Stavisky

Wu Tsai Neurosciences Institute Interdisciplinary Scholar Award

  • Sergey D Stavisky

Larry and Pamela Garlick Foundation

  • Krishna V Shenoy
  • Jaimie M Henderson

Samuel and Betsy Reeves

  • Krishna V Shenoy
  • Jaimie M Henderson

National Institute on Deafness and Other Communication Disorders (R01DC014034)

  • Jaimie M Henderson

Office of Research and Development, Rehabilitation R&D Service, Department of Veterans Affairs (N9288C)

  • Leigh R Hochberg

Executive Committee on Research of Massachusetts General Hospital

  • Leigh R Hochberg

Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD077220)

  • Robert F Kirsch

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

Ethics

Human subjects: The two participants in this study were enrolled in the BrainGate2 Neural Interface System pilot clinical trial (ClinicalTrials.gov Identifier: NCT00912041). The overall purpose of the study is to obtain preliminary safety information and demonstrate proof of principle that an intracortical brain-computer interface can enable people with tetraplegia to communicate and control external devices. Permission for the study was granted by the U.S. Food and Drug Administration under an Investigational Device Exemption (Caution: Investigational device. Limited by federal law to investigational use). The study was also approved by the Institutional Review Boards of Stanford University Medical Center (protocol #20804), Brown University (#0809992560), University Hospitals of Cleveland Medical Center (#04-12-17), Partners HealthCare and Massachusetts General Hospital (#2011P001036), and the Providence VA Medical Center (#2011-009). Both participants gave informed consent to the study and publications resulting from the research, including consent to publish photographs and audiovisual recordings of them.

Copyright

This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

Metrics

  • 6,236
    views
  • 946
    downloads
  • 83
    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. Sergey D Stavisky
  2. Francis R Willett
  3. Guy H Wilson
  4. Brian A Murphy
  5. Paymon Rezaii
  6. Donald T Avansino
  7. William D Memberg
  8. Jonathan P Miller
  9. Robert F Kirsch
  10. Leigh R Hochberg
  11. A Bolu Ajiboye
  12. Shaul Druckmann
  13. Krishna V Shenoy
  14. Jaimie M Henderson
(2019)
Neural ensemble dynamics in dorsal motor cortex during speech in people with paralysis
eLife 8:e46015.
https://doi.org/10.7554/eLife.46015

Share this article

https://doi.org/10.7554/eLife.46015

Further reading

    1. Neuroscience
    Jacob A Miller
    Insight

    When navigating environments with changing rules, human brain circuits flexibly adapt how and where we retain information to help us achieve our immediate goals.

    1. Neuroscience
    Franziska Auer, Katherine Nardone ... David Schoppik
    Research Article

    Cerebellar dysfunction leads to postural instability. Recent work in freely moving rodents has transformed investigations of cerebellar contributions to posture. However, the combined complexity of terrestrial locomotion and the rodent cerebellum motivate new approaches to perturb cerebellar function in simpler vertebrates. Here, we adapted a validated chemogenetic tool (TRPV1/capsaicin) to describe the role of Purkinje cells — the output neurons of the cerebellar cortex — as larval zebrafish swam freely in depth. We achieved both bidirectional control (activation and ablation) of Purkinje cells while performing quantitative high-throughput assessment of posture and locomotion. Activation modified postural control in the pitch (nose-up/nose-down) axis. Similarly, ablations disrupted pitch-axis posture and fin-body coordination responsible for climbs. Postural disruption was more widespread in older larvae, offering a window into emergent roles for the developing cerebellum in the control of posture. Finally, we found that activity in Purkinje cells could individually and collectively encode tilt direction, a key feature of postural control neurons. Our findings delineate an expected role for the cerebellum in postural control and vestibular sensation in larval zebrafish, establishing the validity of TRPV1/capsaicin-mediated perturbations in a simple, genetically tractable vertebrate. Moreover, by comparing the contributions of Purkinje cell ablations to posture in time, we uncover signatures of emerging cerebellar control of posture across early development. This work takes a major step towards understanding an ancestral role of the cerebellum in regulating postural maturation.