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.

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.

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

  • 5,204
    views
  • 699
    downloads
  • 97
    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
    Christine Ahrends, Mark W Woolrich, Diego Vidaurre
    Tools and Resources

    Predicting an individual’s cognitive traits or clinical condition using brain signals is a central goal in modern neuroscience. This is commonly done using either structural aspects, such as structural connectivity or cortical thickness, or aggregated measures of brain activity that average over time. But these approaches are missing a central aspect of brain function: the unique ways in which an individual’s brain activity unfolds over time. One reason why these dynamic patterns are not usually considered is that they have to be described by complex, high-dimensional models; and it is unclear how best to use these models for prediction. We here propose an approach that describes dynamic functional connectivity and amplitude patterns using a Hidden Markov model (HMM) and combines it with the Fisher kernel, which can be used to predict individual traits. The Fisher kernel is constructed from the HMM in a mathematically principled manner, thereby preserving the structure of the underlying model. We show here, in fMRI data, that the HMM-Fisher kernel approach is accurate and reliable. We compare the Fisher kernel to other prediction methods, both time-varying and time-averaged functional connectivity-based models. Our approach leverages information about an individual’s time-varying amplitude and functional connectivity for prediction and has broad applications in cognitive neuroscience and personalised medicine.

    1. Neuroscience
    Simonas Griesius, Amy Richardson, Dimitri Michael Kullmann
    Research Article

    Non-linear summation of synaptic inputs to the dendrites of pyramidal neurons has been proposed to increase the computation capacity of neurons through coincidence detection, signal amplification, and additional logic operations such as XOR. Supralinear dendritic integration has been documented extensively in principal neurons, mediated by several voltage-dependent conductances. It has also been reported in parvalbumin-positive hippocampal basket cells, in dendrites innervated by feedback excitatory synapses. Whether other interneurons, which support feed-forward or feedback inhibition of principal neuron dendrites, also exhibit local non-linear integration of synaptic excitation is not known. Here, we use patch-clamp electrophysiology, and two-photon calcium imaging and glutamate uncaging, to show that supralinear dendritic integration of near-synchronous spatially clustered glutamate-receptor mediated depolarization occurs in NDNF-positive neurogliaform cells and oriens-lacunosum moleculare interneurons in the mouse hippocampus. Supralinear summation was detected via recordings of somatic depolarizations elicited by uncaging of glutamate on dendritic fragments, and, in neurogliaform cells, by concurrent imaging of dendritic calcium transients. Supralinearity was abolished by blocking NMDA receptors (NMDARs) but resisted blockade of voltage-gated sodium channels. Blocking L-type calcium channels abolished supralinear calcium signalling but only had a minor effect on voltage supralinearity. Dendritic boosting of spatially clustered synaptic signals argues for previously unappreciated computational complexity in dendrite-projecting inhibitory cells of the hippocampus.