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
-
- 6,154
- views
-
- 933
- 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
-
- Genetics and Genomics
- Neuroscience
Spinal muscular atrophy (SMA) is caused by mutations in the Survival Motor Neuron 1 (SMN1) gene. While traditionally viewed as a motor neuron disorder, there is involvement of various peripheral organs in SMA. Notably, fatty liver has been observed in SMA mouse models and SMA patients. Nevertheless, it remains unclear whether intrinsic depletion of SMN protein in the liver contributes to pathology in the peripheral or central nervous systems. To address this, we developed a mouse model with a liver-specific depletion of SMN by utilizing an Alb-Cre transgene together with one Smn2B allele and one Smn1 exon 7 allele flanked by loxP sites. Initially, we evaluated phenotypic changes in these mice at postnatal day 19 (P19), when the severe model of SMA, the Smn2B/- mice, exhibit many symptoms of the disease. The liver-specific SMN depletion does not induce motor neuron death, neuromuscular pathology or muscle atrophy, characteristics typically observed in the Smn2B/- mouse at P19. However, mild liver steatosis was observed, although no changes in liver function were detected. Notably, pancreatic alterations resembled that of Smn2B/-mice, with a decrease in insulin-producing β-cells and an increase in glucagon-producingα-cells, accompanied by a reduction in blood glucose and an increase in plasma glucagon and glucagon-like peptide (GLP-1). These changes were transient, as mice at P60 exhibited recovery of liver and pancreatic function. While the mosaic pattern of the Cre-mediated excision precludes definitive conclusions regarding the contribution of liver-specific SMN depletion to overall tissue pathology, our findings highlight an intricate connection between liver function and pancreatic abnormalities in SMA.
-
- Neuroscience
Childhood adversity is a strong predictor of developing psychopathological conditions. Multiple theories on the mechanisms underlying this association have been suggested which, however, differ in the operationalization of ‘exposure.’ Altered (threat) learning mechanisms represent central mechanisms by which environmental inputs shape emotional and cognitive processes and ultimately behavior. 1402 healthy participants underwent a fear conditioning paradigm (acquisition training, generalization), while acquiring skin conductance responses (SCRs) and ratings (arousal, valence, and contingency). Childhood adversity was operationalized as (1) dichotomization, and following (2) the specificity model, (3) the cumulative risk model, and (4) the dimensional model. Individuals exposed to childhood adversity showed blunted physiological reactivity in SCRs, but not ratings, and reduced CS+/CS- discrimination during both phases, mainly driven by attenuated CS+ responding. The latter was evident across different operationalizations of ‘exposure’ following the different theories. None of the theories tested showed clear explanatory superiority. Notably, a remarkably different pattern of increased responding to the CS- is reported in the literature for anxiety patients, suggesting that individuals exposed to childhood adversity may represent a specific sub-sample. We highlight that theories linking childhood adversity to (vulnerability to) psychopathology need refinement.
