1. Neuroscience

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
https://doi.org/10.7554/eLife.54497
Share this article
Cite this article
  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
  2. Download BibTeX
  3. Download .RIS

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.

Reviewing Editor

  1. Laura Dugué, Uni­ver­sité de Paris, France

Publication 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

  • 3,070
    Page views
  • 414
    Downloads
  • 23
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, Scopus, PubMed Central.

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

Categories and tags

Research organism

Further reading

    1. Neuroscience

    Flexible and efficient simulation-based inference for models of decision-making

    Jan Boelts et al.
    Research Advance Updated

    Inferring parameters of computational models that capture experimental data are a central task in cognitive neuroscience. Bayesian statistical inference methods usually require the ability to evaluate the likelihood of the model—however, for many models of interest in cognitive neuroscience, the associated likelihoods cannot be computed efficiently. Simulation-based inference (SBI) offers a solution to this problem by only requiring access to simulations produced by the model. Previously, Fengler et al. introduced likelihood approximation networks (LANs, Fengler et al., 2021) which make it possible to apply SBI to models of decision-making, but require billions of simulations for training. Here, we provide a new SBI method that is substantially more simulation efficient. Our approach, mixed neural likelihood estimation (MNLE), trains neural density estimators on model simulations to emulate the simulator, and is designed to capture both the continuous (e.g., reaction times) and discrete (choices) data of decision-making models. The likelihoods of the emulator can then be used to perform Bayesian parameter inference on experimental data using standard approximate inference methods like Markov Chain Monte Carlo sampling. We demonstrate MNLE on two variants of the drift-diffusion model and show that it is substantially more efficient than LANs: MNLE achieves similar likelihood accuracy with six orders of magnitude fewer training simulations, and is significantly more accurate than LANs when both are trained with the same budget. Our approach enables researchers to perform SBI on custom-tailored models of decision-making, leading to fast iteration of model design for scientific discovery.

    1. Computational and Systems Biology
    2. Neuroscience

    Information flows from hippocampus to auditory cortex during replay of verbal working memory items

    Vasileios Dimakopoulos et al.
    Research Article

    The maintenance of items in working memory (WM) relies on a widespread network of cortical areas and hippocampus where synchronization between electrophysiological recordings reflects functional coupling. We investigated the direction of information flow between auditory cortex and hippocampus while participants heard and then mentally replayed strings of letters in WM by activating their phonological loop. We recorded local field potentials from the hippocampus, reconstructed beamforming sources of scalp EEG, and – additionally in four participants – recorded from subdural cortical electrodes. When analyzing Granger causality, the information flow was from auditory cortex to hippocampus with a peak in the [4 8] Hz range while participants heard the letters. This flow was subsequently reversed during maintenance while participants maintained the letters in memory. The functional interaction between hippocampus and the cortex and the reversal of information flow provide a physiological basis for the encoding of memory items and their active replay during maintenance.

    1. Computational and Systems Biology
    2. Neuroscience

    Parallel processing, hierarchical transformations, and sensorimotor associations along the 'where' pathway

    Raymond Doudlah et al.
    Research Advance

    Visually guided behaviors require the brain to transform ambiguous retinal images into object-level spatial representations and implement sensorimotor transformations. These processes are supported by the dorsal 'where' pathway. However, the specific functional contributions of areas along this pathway remain elusive due in part to methodological differences across studies. We previously showed that macaque caudal intraparietal (CIP) area neurons possess robust three-dimensional (3D) visual representations, carry choice- and saccade-related activity, and exhibit experience-dependent sensorimotor associations (Chang et al., 2020b). Here, we used a common experimental design to reveal parallel processing, hierarchical transformations, and the formation of sensorimotor associations along the 'where' pathway by extending the investigation to V3A, a major feedforward input to CIP. Higher-level 3D representations and choice-related activity were more prevalent in CIP than V3A. Both areas contained saccade-related activity that predicted the direction/timing of eye movements. Intriguingly, the time-course of saccade-related activity in CIP aligned with the temporally integrated V3A output. Sensorimotor associations between 3D orientation and saccade direction preferences were stronger in CIP than V3A, and moderated by choice signals in both areas. Together, the results explicate parallel representations, hierarchical transformations, and functional associations of visual and saccade-related signals at a key juncture in the 'where' pathway.