Mechanisms of theta burst transcranial ultrasound induced plasticity in the human motor cortex

Yazan Shamli Oghli; Talyta Grippe; Tarun Arora; Tasnuva Hoque; Ghazaleh Darmani; Robert Chen

doi:10.1016/j.brs.2023.07.056

Mechanisms of theta burst transcranial ultrasound induced plasticity in the human motor cortex

Brain Stimul. 2023 Jul-Aug;16(4):1135-1143. doi: 10.1016/j.brs.2023.07.056. Epub 2023 Jul 29.

Authors

Yazan Shamli Oghli¹, Talyta Grippe², Tarun Arora³, Tasnuva Hoque², Ghazaleh Darmani², Robert Chen⁴

Affiliations

¹ Institute of Medical Science, University of Toronto, Toronto, Canada; Krembil Research Institute, University Health Network, Toronto, Canada; Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, United States.
² Krembil Research Institute, University Health Network, Toronto, Canada.
³ Krembil Research Institute, University Health Network, Toronto, Canada; Division of Clinical Neuroscience, Department of Neurology, Section for Clinical Neurophysiology, Oslo University Hospital, Oslo, Norway.
⁴ Institute of Medical Science, University of Toronto, Toronto, Canada; Krembil Research Institute, University Health Network, Toronto, Canada. Electronic address: robert.chen@uhn.ca.

PMID: 37524296
DOI: 10.1016/j.brs.2023.07.056

Abstract

Background: Transcranial ultrasound stimulation (TUS) is a novel non-invasive brain stimulation technique with high depth penetrance and spatial resolution. Theta-burst TUS (tbTUS) is a plasticity-inducing protocol which increases motor cortical excitability for up to 30 min following 80s of sonication. While this protocol may have therapeutic potential for the treatment of psychiatric and neurological disorders, the mechanisms of action of TUS remain unclear.

Objective: We conducted the first pharmacological study to examine the mechanisms of TUS in human primary motor cortex. By administering brain-active drugs with known mechanisms of action, we aimed to elucidate the mechanisms of tbTUS.

Methods: Fourteen healthy subjects participated in a within-subjects randomized, double-blind, cross-over study with five visits. At each visit, one of four study drugs (carbamazepine - Na⁺ channel blocker, nimodipine - L-type Ca²⁺ channel blocker, lorazepam - positive allosteric modulator of gamma-aminobutyric acid (GABA) type A receptor, dextromethorphan - N-methyl-d-aspartate receptor antagonist) or placebo was administered in random order, followed by tbTUS.

Results: The plasticity effects of tbTUS on motor cortex excitability measured by motor-evoked potential amplitudes elicited by transcranial magnetic stimulation were reduced by all study drugs compared to placebo.

Conclusion: tbTUS may induce NMDA-dependent synaptic plasticity since the effects are blocked by increased GABA_A receptor activities and voltage-gated Na⁺ and Ca²⁺ channels blockers. These results are consistent with the hypotheses that tbTUS induced long-term potentiation-like mechanisms and that TUS involves activation of mechanosensitive Na⁺ and Ca²⁺ channels. Alternatively, non-specific pharmacologically induced changes in excitatory/inhibitory balance might have interfered with the effects of tbTUS.

Keywords: Focused ultrasound; Neuroplasticity; Pharmacological mechanisms; Transcranial magnetic stimulation.

Publication types

Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Cross-Over Studies
Evoked Potentials, Motor / physiology
Humans
Long-Term Potentiation / physiology
Motor Cortex* / physiology
Neuronal Plasticity / physiology
Transcranial Magnetic Stimulation / methods

Abstract

Publication types

MeSH terms

Grants and funding