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.

Reviewing Editor

  1. Tamar R Makin, University College London, United Kingdom

Version history

  1. Received: February 14, 2019
  2. Accepted: November 14, 2019
  3. Accepted Manuscript published: December 10, 2019 (version 1)
  4. Version of Record published: January 10, 2020 (version 2)

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

  • 5,693
    Page views
  • 853
    Downloads
  • 42
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, Scopus, PubMed Central.

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
    Maureen van der Grinten, Jaap de Ruyter van Steveninck ... Yağmur Güçlütürk
    Tools and Resources

    Blindness affects millions of people around the world. A promising solution to restoring a form of vision for some individuals are cortical visual prostheses, which bypass part of the impaired visual pathway by converting camera input to electrical stimulation of the visual system. The artificially induced visual percept (a pattern of localized light flashes, or ‘phosphenes’) has limited resolution, and a great portion of the field’s research is devoted to optimizing the efficacy, efficiency, and practical usefulness of the encoding of visual information. A commonly exploited method is non-invasive functional evaluation in sighted subjects or with computational models by using simulated prosthetic vision (SPV) pipelines. An important challenge in this approach is to balance enhanced perceptual realism, biologically plausibility, and real-time performance in the simulation of cortical prosthetic vision. We present a biologically plausible, PyTorch-based phosphene simulator that can run in real-time and uses differentiable operations to allow for gradient-based computational optimization of phosphene encoding models. The simulator integrates a wide range of clinical results with neurophysiological evidence in humans and non-human primates. The pipeline includes a model of the retinotopic organization and cortical magnification of the visual cortex. Moreover, the quantitative effects of stimulation parameters and temporal dynamics on phosphene characteristics are incorporated. Our results demonstrate the simulator’s suitability for both computational applications such as end-to-end deep learning-based prosthetic vision optimization as well as behavioral experiments. The modular and open-source software provides a flexible simulation framework for computational, clinical, and behavioral neuroscientists working on visual neuroprosthetics.

    1. Neuroscience
    Simon Lui, Ashleigh K Brink, Laura H Corbit
    Research Article

    Extinction is a specific example of learning where a previously reinforced stimulus or response is no longer reinforced, and the previously learned behaviour is no longer necessary and must be modified. Current theories suggest extinction is not the erasure of the original learning but involves new learning that acts to suppress the original behaviour. Evidence for this can be found when the original behaviour recovers following the passage of time (spontaneous recovery) or reintroduction of the reinforcement (i.e. reinstatement). Recent studies have shown that pharmacological manipulation of noradrenaline (NA) or its receptors can influence appetitive extinction; however, the role and source of endogenous NA in these effects are unknown. Here, we examined the role of the locus coeruleus (LC) in appetitive extinction. Specifically, we tested whether optogenetic stimulation of LC neurons during extinction of a food-seeking behaviour would enhance extinction evidenced by reduced spontaneous recovery in future tests. LC stimulation during extinction trials did not change the rate of extinction but did serve to reduce subsequent spontaneous recovery, suggesting that stimulation of the LC can augment reward-related extinction. Optogenetic inhibition of the LC during extinction trials reduced responding during the trials where it was applied, but no long-lasting changes in the retention of extinction were observed. Since not all LC cells expressed halorhodopsin, it is possible that more complete LC inhibition or pathway-specific targeting would be more effective at suppressing extinction learning. These results provide further insight into the neural basis of appetitive extinction, and in particular the role of the LC. A deeper understanding of the physiological bases of extinction can aid development of more effective extinction-based therapies.