Stability of motor representations after paralysis

  1. Charles Guan  Is a corresponding author
  2. Tyson Aflalo  Is a corresponding author
  3. Carey Y Zhang
  4. Elena Amoruso
  5. Emily R Rosario
  6. Nader Pouratian
  7. Richard A Andersen
  1. California Institute of Technology, United States
  2. University College London, United Kingdom
  3. Casa Colina Hospital and Centers for Healthcare, United States
  4. University of California, Los Angeles, United States

Abstract

Neural plasticity allows us to learn skills and incorporate new experiences. What happens when our lived experiences fundamentally change, such as after a severe injury? To address this question, we analyzed intracortical population activity in the posterior parietal cortex (PPC) of a tetraplegic adult as she controlled a virtual hand through a brain-computer interface (BCI). By attempting to move her fingers, she could accurately drive the corresponding virtual fingers. Neural activity during finger movements exhibited robust representational structure similar to fMRI recordings of able-bodied individuals' motor cortex, which has previously been shown to reflect able-bodied usage patterns. The finger representational structure was consistent throughout multiple sessions, even though the structure contributed to BCI decoding errors. Within individual BCI movements, the representational structure was dynamic, first resembling muscle activation patterns and then resembling the anticipated sensory consequences. Our results reveal that motor representations in PPC reflect able-bodied motor usage patterns even after paralysis, and BCIs can re-engage these representations to restore lost motor functions.

Data availability

Data is available on the BRAIN Initiative DANDI Archive at https://dandiarchive.org/dandiset/000147

The following data sets were generated
The following previously published data sets were used

Article and author information

Author details

  1. Charles Guan

    Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, United States
    For correspondence
    cguan@caltech.edu
    Competing interests
    The authors declare that no competing interests exist.
  2. Tyson Aflalo

    Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, United States
    For correspondence
    taflalo@caltech.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0101-2455
  3. Carey Y Zhang

    Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Elena Amoruso

    Institute of Cognitive Neuroscience, University College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  5. Emily R Rosario

    Casa Colina Hospital and Centers for Healthcare, Pomona, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Nader Pouratian

    5David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Richard A Andersen

    Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, United States
    Competing interests
    The authors declare that no competing interests exist.

Funding

National Eye Institute (R01EY015545)

  • Charles Guan
  • Tyson Aflalo
  • Emily R Rosario
  • Nader Pouratian
  • Richard A Andersen

National Eye Institute (UG1EY032039)

  • Charles Guan
  • Tyson Aflalo
  • Emily R Rosario
  • Nader Pouratian
  • Richard A Andersen

Tianqiao and Chrissy Chen Brain-machine Interface Center at Caltech

  • Tyson Aflalo
  • Richard A Andersen

Boswell Foundation

  • Richard A Andersen

Amazon AI4Science Fellowship

  • Charles Guan

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

Ethics

Human subjects: All procedures were approved by the California Institute of Technology, Casa Colina Hospital and Centers for Healthcare, and the University of California, Los Angeles Institutional Review Boards. NS consented to the surgical procedure as well as to the subsequent clinical studies after understanding their nature, objectives, and potential risks.

Copyright

© 2022, Guan 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.

Download links

Share this article

https://doi.org/10.7554/eLife.74478

Further reading

    1. Neuroscience
    Ulrike Pech, Jasper Janssens ... Patrik Verstreken
    Research Article

    The classical diagnosis of Parkinsonism is based on motor symptoms that are the consequence of nigrostriatal pathway dysfunction and reduced dopaminergic output. However, a decade prior to the emergence of motor issues, patients frequently experience non-motor symptoms, such as a reduced sense of smell (hyposmia). The cellular and molecular bases for these early defects remain enigmatic. To explore this, we developed a new collection of five fruit fly models of familial Parkinsonism and conducted single-cell RNA sequencing on young brains of these models. Interestingly, cholinergic projection neurons are the most vulnerable cells, and genes associated with presynaptic function are the most deregulated. Additional single nucleus sequencing of three specific brain regions of Parkinson’s disease patients confirms these findings. Indeed, the disturbances lead to early synaptic dysfunction, notably affecting cholinergic olfactory projection neurons crucial for olfactory function in flies. Correcting these defects specifically in olfactory cholinergic interneurons in flies or inducing cholinergic signaling in Parkinson mutant human induced dopaminergic neurons in vitro using nicotine, both rescue age-dependent dopaminergic neuron decline. Hence, our research uncovers that one of the earliest indicators of disease in five different models of familial Parkinsonism is synaptic dysfunction in higher-order cholinergic projection neurons and this contributes to the development of hyposmia. Furthermore, the shared pathways of synaptic failure in these cholinergic neurons ultimately contribute to dopaminergic dysfunction later in life.

    1. Neuroscience
    Gergely F Turi, Sasa Teng ... Yueqing Peng
    Research Article

    Synchronous neuronal activity is organized into neuronal oscillations with various frequency and time domains across different brain areas and brain states. For example, hippocampal theta, gamma, and sharp wave oscillations are critical for memory formation and communication between hippocampal subareas and the cortex. In this study, we investigated the neuronal activity of the dentate gyrus (DG) with optical imaging tools during sleep-wake cycles in mice. We found that the activity of major glutamatergic cell populations in the DG is organized into infraslow oscillations (0.01–0.03 Hz) during NREM sleep. Although the DG is considered a sparsely active network during wakefulness, we found that 50% of granule cells and about 25% of mossy cells exhibit increased activity during NREM sleep, compared to that during wakefulness. Further experiments revealed that the infraslow oscillation in the DG was correlated with rhythmic serotonin release during sleep, which oscillates at the same frequency but in an opposite phase. Genetic manipulation of 5-HT receptors revealed that this neuromodulatory regulation is mediated by Htr1a receptors and the knockdown of these receptors leads to memory impairment. Together, our results provide novel mechanistic insights into how the 5-HT system can influence hippocampal activity patterns during sleep.