Systematic examination of low-intensity ultrasound parameters on human motor cortex excitability and behaviour

  1. Anton Fomenko  Is a corresponding author
  2. Kai-Hsiang Stanley Chen
  3. Jean-François Nankoo
  4. James Saravanamuttu
  5. Yanqiu Wang
  6. Mazen El-Baba
  7. Xue Xia
  8. Shakthi Sanjana Seerala
  9. Kullervo Hynynen
  10. Andres M Lozano  Is a corresponding author
  11. Robert Chen  Is a corresponding author
  1. University of Toronto, Canada
  2. National Taiwan University, Taiwan
  3. Toronto Western Hospital, Canada
  4. Sunnybrook Research Institute, Canada

Abstract

Low-intensity transcranial ultrasound (TUS) can non-invasively modulate human neural activity. We investigated how different fundamental sonication parameters influence the effects of TUS on the motor cortex (M1) of 16 healthy subjects by probing cortico-cortical excitability and behaviour. A low-intensity 500 kHz TUS transducer was coupled to a transcranial magnetic stimulation (TMS) coil. TMS was delivered 10 ms before the end of TUS to the left M1 hotspot of the first dorsal interosseous muscle. Varying acoustic parameters (pulse repetition frequency, duty cycle and sonication duration) on motor-evoked potential amplitude were examined. Paired-pulse measures of cortical inhibition and facilitation, and performance on a visuomotor task was also assessed. TUS safely suppressed TMS-elicited motor cortical activity, with longer sonication durations and shorter duty cycles when delivered in a blocked paradigm. TUS increased GABAA-mediated short-interval intracortical inhibition and decreased reaction time on visuomotor task but not when controlled with TUS at near-somatosensory threshold intensity.

Data availability

Data used for this study are included in the manuscript and supporting files.Files for 3D printing the stimulating devices and custom MATLAB scripts used for stimulation have been deposited into a cited GitHub repository.

Article and author information

Author details

  1. Anton Fomenko

    Krembil Research Institute, University of Toronto, Toronto, Canada
    For correspondence
    anton.fomenko@uhnresearch.ca
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4131-6784
  2. Kai-Hsiang Stanley Chen

    Neurology, National Taiwan University, Taiwan, Taiwan
    Competing interests
    The authors declare that no competing interests exist.
  3. Jean-François Nankoo

    Krembil Research Institute, University of Toronto, Toronto, Canada
    Competing interests
    The authors declare that no competing interests exist.
  4. James Saravanamuttu

    Krembil Research Institute, University of Toronto, Toronto, Canada
    Competing interests
    The authors declare that no competing interests exist.
  5. Yanqiu Wang

    Krembil Research Institute, University of Toronto, Toronto, Canada
    Competing interests
    The authors declare that no competing interests exist.
  6. Mazen El-Baba

    Krembil Research Institute, University of Toronto, Toronto, Canada
    Competing interests
    The authors declare that no competing interests exist.
  7. Xue Xia

    Toronto Western Hospital, Toronto, Canada
    Competing interests
    The authors declare that no competing interests exist.
  8. Shakthi Sanjana Seerala

    Focused Ultrasound Group, Sunnybrook Research Institute, Toronto, Canada
    Competing interests
    The authors declare that no competing interests exist.
  9. Kullervo Hynynen

    Focused Ultrasound Group, Sunnybrook Research Institute, Toronto, Canada
    Competing interests
    The authors declare that no competing interests exist.
  10. Andres M Lozano

    Krembil Research Institute, University of Toronto, Toronto, Canada
    For correspondence
    lozano@uhnresearch.ca
    Competing interests
    The authors declare that no competing interests exist.
  11. Robert Chen

    Toronto Western Hospital, Toronto, Canada
    For correspondence
    robert.chen@uhn.ca
    Competing interests
    The authors declare that no competing interests exist.

Funding

Canadian Institutes of Health Research (Banting and Best Doctoral Award)

  • Anton Fomenko

Canadian Institutes of Health Research (Foundation Grant,FDN 154292)

  • Robert Chen

University of Manitoba (Clinician Investigator Program)

  • Anton Fomenko

Canada Research Chairs (Neuroscience)

  • Andres M Lozano

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

Reviewing Editor

  1. Laura Dugué, Uni­ver­sité de Paris, France

Ethics

Human subjects: All patients gave written informed consent and the protocol was approved by the UHN Research Ethics Board (Protocol #18-5082) in accordance with the Declaration of Helsinki on the use of human subjects in experiments.

Version history

  1. Received: December 16, 2019
  2. Accepted: November 24, 2020
  3. Accepted Manuscript published: November 25, 2020 (version 1)
  4. Version of Record published: December 10, 2020 (version 2)

Copyright

© 2020, Fomenko 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.

Metrics

  • 4,658
    views
  • 625
    downloads
  • 68
    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. Anton Fomenko
  2. Kai-Hsiang Stanley Chen
  3. Jean-François Nankoo
  4. James Saravanamuttu
  5. Yanqiu Wang
  6. Mazen El-Baba
  7. Xue Xia
  8. Shakthi Sanjana Seerala
  9. Kullervo Hynynen
  10. Andres M Lozano
  11. Robert Chen
(2020)
Systematic examination of low-intensity ultrasound parameters on human motor cortex excitability and behaviour
eLife 9:e54497.
https://doi.org/10.7554/eLife.54497

Share this article

https://doi.org/10.7554/eLife.54497

Further reading

    1. Neuroscience
    Geoffroy Delamare, Yosif Zaki ... Claudia Clopath
    Short Report

    Representational drift refers to the dynamic nature of neural representations in the brain despite the behavior being seemingly stable. Although drift has been observed in many different brain regions, the mechanisms underlying it are not known. Since intrinsic neural excitability is suggested to play a key role in regulating memory allocation, fluctuations of excitability could bias the reactivation of previously stored memory ensembles and therefore act as a motor for drift. Here, we propose a rate-based plastic recurrent neural network with slow fluctuations of intrinsic excitability. We first show that subsequent reactivations of a neural ensemble can lead to drift of this ensemble. The model predicts that drift is induced by co-activation of previously active neurons along with neurons with high excitability which leads to remodeling of the recurrent weights. Consistent with previous experimental works, the drifting ensemble is informative about its temporal history. Crucially, we show that the gradual nature of the drift is necessary for decoding temporal information from the activity of the ensemble. Finally, we show that the memory is preserved and can be decoded by an output neuron having plastic synapses with the main region.

    1. Cell Biology
    2. Neuroscience
    Alexandra Stavsky, Leonardo A Parra-Rivas ... Daniel Gitler
    Short Report

    The cytosolic proteins synucleins and synapsins are thought to play cooperative roles in regulating synaptic vesicle (SV) recycling, but mechanistic insight is lacking. Here, we identify the synapsin E-domain as an essential functional binding-partner of α-synuclein (α-syn). Synapsin E-domain allows α-syn functionality, binds to α-syn, and is necessary and sufficient for enabling effects of α-syn at synapses of cultured mouse hippocampal neurons. Together with previous studies implicating the E-domain in clustering SVs, our experiments advocate a cooperative role for these two proteins in maintaining physiologic SV clusters.