Multi-modal investigation of transcranial ultrasound-induced neuroplasticity of the human motor cortex

Nardin Samuel; Ke Zeng; Irene E Harmsen; Mandy Yi Rong Ding; Ghazaleh Darmani; Can Sarica; Brendan Santyr; Artur Vetkas; Aditya Pancholi; Anton Fomenko; Vanessa Milano; Kazuaki Yamamoto; Utpal Saha; Richard Wennberg; Nathan C Rowland; Robert Chen; Andres M Lozano

doi:10.1016/j.brs.2022.10.001

Multi-modal investigation of transcranial ultrasound-induced neuroplasticity of the human motor cortex

Brain Stimul. 2022 Nov-Dec;15(6):1337-1347. doi: 10.1016/j.brs.2022.10.001. Epub 2022 Oct 11.

Authors

Nardin Samuel¹, Ke Zeng², Irene E Harmsen³, Mandy Yi Rong Ding⁴, Ghazaleh Darmani², Can Sarica¹, Brendan Santyr¹, Artur Vetkas⁵, Aditya Pancholi¹, Anton Fomenko⁶, Vanessa Milano¹, Kazuaki Yamamoto¹, Utpal Saha², Richard Wennberg⁷, Nathan C Rowland⁸, Robert Chen⁹, Andres M Lozano¹⁰

Affiliations

¹ Toronto Western Hospital, Division of Neurosurgery, University of Toronto, Toronto, Ontario, Canada.
² Krembil Research Institute, University Health Network, Toronto, Ontario, Canada.
³ Toronto Western Hospital, Division of Neurosurgery, University of Toronto, Toronto, Ontario, Canada; Krembil Research Institute, University Health Network, Toronto, Ontario, Canada.
⁴ Krembil Research Institute, University Health Network, Toronto, Ontario, Canada; Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada.
⁵ Toronto Western Hospital, Division of Neurosurgery, University of Toronto, Toronto, Ontario, Canada; Department of Neurosurgery, Tartu University Hospital, University of Tartu, Estonia.
⁶ Division of Neurosurgery, University of Manitoba, Winnipeg, Manitoba, Canada.
⁷ Mitchell Goldhar MEG Unit, Toronto Western Hospital, University Health Network, Toronto, Ontario, Canada; Division of Neurology, Toronto Western Hospital, University Health Network, University of Toronto, Toronto, Ontario, Canada.
⁸ Department of Neurosurgery, Medical University of South Carolina, Charleston, SC, USA.
⁹ Krembil Research Institute, University Health Network, Toronto, Ontario, Canada; Division of Neurology, Toronto Western Hospital, University Health Network, University of Toronto, Toronto, Ontario, Canada.
¹⁰ Toronto Western Hospital, Division of Neurosurgery, University of Toronto, Toronto, Ontario, Canada; Krembil Research Institute, University Health Network, Toronto, Ontario, Canada. Electronic address: lozano@uhnresearch.ca.

PMID: 36228977
DOI: 10.1016/j.brs.2022.10.001

Abstract

Introduction: There is currently a gap in accessibility to neuromodulation tools that can approximate the efficacy and spatial resolution of invasive methods. Low intensity transcranial focused ultrasound stimulation (TUS) is an emerging technology for non-invasive brain stimulation (NIBS) that can penetrate cortical and deep brain structures with more focal stimulation compared to existing NIBS modalities. Theta burst TUS (tbTUS, TUS delivered in a theta burst pattern) is a novel repetitive TUS protocol that can induce durable changes in motor cortex excitability, thereby holding promise as a novel neuromodulation tool with durable effects.

Objective: The aim of the present study was to elucidate the neurophysiologic effects of tbTUS motor cortical excitability, as well on local and global neural oscillations and network connectivity.

Methods: An 80-s train of active or sham tbTUS was delivered to the left motor cortex in 15 healthy subjects. Motor cortical excitability was investigated through transcranial magnetic stimulation (TMS)-elicited motor-evoked potentials (MEPs), short-interval intracortical inhibition (SICI), and intracortical facilitation (ICF) using paired-pulse TMS. Magnetoencephalography (MEG) recordings during resting state and an index finger abduction-adduction task were used to assess oscillatory brain responses and network connectivity. The correlations between the changes in neural oscillations and motor cortical excitability were also evaluated.

Results: tbTUS to the motor cortex results in a sustained increase in MEP amplitude and decreased SICI, but no change in ICF. MEG spectral power analysis revealed TUS-mediated desynchronization in alpha and beta spectral power. Significant changes in alpha power were detected within the supplementary motor cortex (Right > Left) and changes in beta power within bilateral supplementary motor cortices, right basal ganglia and parietal regions. Coherence analysis revealed increased local connectivity in motor areas. MEP and SICI changes correlated with both local and inter-regional coherence.

Conclusion: The findings from this study provide novel insights into the neurophysiologic basis of TUS-mediated neuroplasticity and point to the involvement of regions within the motor network in mediating this sustained response. Future studies may further characterize the durability of TUS-mediated neuroplasticity and its clinical applications as a neuromodulation strategy for neurological and psychiatric disorders.

Keywords: Low-intensity focused ultrasound; Magnetoencephalography (MEG); Neuroplasticity; Transcranial magnetic stimulation (TMS).

MeSH terms

Evoked Potentials, Motor / physiology
Humans
Magnetoencephalography
Motor Cortex* / diagnostic imaging
Motor Cortex* / physiology
Neural Inhibition / physiology
Neuronal Plasticity
Parietal Lobe
Transcranial Magnetic Stimulation / methods