Neural ensemble dynamics in dorsal motor cortex during speech in people with paralysis
- Stanford University, United States
- Case Western Reserve University, United States
- University Hospitals Cleveland Medical Center, United States
- 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
Jaimie M Henderson
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
-
- 6,180
- views
-
- 936
- downloads
-
- 80
- 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)
Neural ensemble dynamics in dorsal motor cortex during speech in people with paralysis
eLife 8:e46015.
https://doi.org/10.7554/eLife.46015
Further reading
-
- Neuroscience
The reward and novelty-related neuromodulator dopamine plays an important role in hippocampal long-term memory, which is thought to involve protein-synthesis-dependent synaptic plasticity. However, the direct effects of dopamine on protein synthesis, and the functional implications of newly synthesised proteins for synaptic plasticity, have not yet been investigated. We have previously reported that timing-dependent synaptic depression (t-LTD) can be converted into potentiation by dopamine application during synaptic stimulation (Brzosko et al., 2015) or postsynaptic burst activation (Fuchsberger et al., 2022). Here, we show that dopamine increases protein synthesis in mouse hippocampal CA1 neurons, enabling dopamine-dependent long-term potentiation (DA-LTP), which is mediated via the Ca2+-sensitive adenylate cyclase (AC) subtypes 1/8, cAMP, and cAMP-dependent protein kinase (PKA). We found that neuronal activity is required for the dopamine-induced increase in protein synthesis. Furthermore, dopamine induced a protein-synthesis-dependent increase in the AMPA receptor subunit GluA1, but not GluA2. We found that DA-LTP is absent in GluA1 knock-out mice and that it requires calcium-permeable AMPA receptors. Taken together, our results suggest that dopamine together with neuronal activity controls synthesis of plasticity-related proteins, including GluA1, which enable DA-LTP via a signalling pathway distinct from that of conventional LTP.
-
- Neuroscience
Insulin plays a critical role in maintaining metabolic homeostasis. Since metabolic demands are highly dynamic, insulin release needs to be constantly adjusted. These adjustments are mediated by different pathways, most prominently the blood glucose level, but also by feedforward signals from motor circuits and different neuromodulatory systems. Here, we analyze how neuromodulatory inputs control the activity of the main source of insulin in Drosophila – a population of insulin-producing cells (IPCs) located in the brain. IPCs are functionally analogous to mammalian pancreatic beta cells, but their location makes them accessible for in vivo recordings in intact animals. We characterized functional inputs to IPCs using single-nucleus RNA sequencing analysis, anatomical receptor expression mapping, connectomics, and an optogenetics-based ‘intrinsic pharmacology’ approach. Our results show that the IPC population expresses a variety of receptors for neuromodulators and classical neurotransmitters. Interestingly, IPCs exhibit heterogeneous receptor profiles, suggesting that the IPC population can be modulated differentially. This is supported by electrophysiological recordings from IPCs, which we performed while activating different populations of modulatory neurons. Our analysis revealed that some modulatory inputs have heterogeneous effects on the IPC activity, such that they inhibit one subset of IPCs, while exciting another. Monitoring calcium activity across the IPC population uncovered that these heterogeneous responses occur simultaneously. Certain neuromodulatory populations shifted the IPC population activity towards an excited state, while others shifted it towards inhibition. Taken together, we provide a comprehensive, multi-level analysis of neuromodulation in the insulinergic system of Drosophila.
