Pharmacological Mechanisms of Low-intensity Focused Ultrasound for Motor Cortex Neuroplasticity

Summary

Low-intensity focused ultrasound (LIFUS) has been shown to be an effective and safe non-invasive brain stimulation technique, capable of reaching greater brain depth and a greater spatial resolution than other brain stimulation tools. Its use as a potential clinical tool for treatment of neurological disorders is reliant on an understanding of its mechanisms of action. Although it has been shown to induce immediate (online) and prolonged (offline) changes in plasticity in the motor cortex, researchers have not studied its effects on neurotransmitter receptors and ion channels responsible for neuronal signaling in humans. The purpose of this study is to explore the effects of online and offline LIFUS stimulation in tandem with administration of various brain-active drugs, to elucidate the effects of this technique on specific cortical receptors and channels. 20 healthy, screened subjects will be recruited to participate in 5 sessions in-lab. Each session will represent the double-blinded administration of four known and studied pharmacological agents known to safely induce changes in the motor cortex, as well as a placebo. Investigators will use carbamazepine (sodium channel blocker), lorazepam (GABAA positive allosteric modulator), nimodipine (calcium channel blocker), and dextromethorphan (glutamate N-Methyl-D-aspartate receptor antagonist). Single- and paired-pulse transcranial magnetic stimulation (TMS) measures will be recorded for online LIFUS before and after drug intervention, and induction of offline LIFUS during placebo will be compared with its induction following the various drug interventions. Investigators predict that due to the differential effects of online and offline LIFUS on motor parameters, the mechanisms in which it alters the receptors and channels of interest will also be differentially modulated.

Conditions

• Low Intensity Focussed Ultrasound

Interventions

DRUG

Carbamazepine

600 mg reconstituted as one table. Administered once

DRUG

Lorazepam

2.5 mg mg reconstituted as one table. Administered once

DRUG

Dextromethorphan

150 mgmg reconstituted as one table. Administered once

DRUG

Nimodipine

30 mg reconstituted as one table. Administered once

DRUG

Placebo

Administered once

Sponsors & Collaborators

• University Health Network, Toronto

  lead OTHER

Principal Investigators

• Robert Chen, MBBS · University Health Network, Toronto

Study Design

Allocation

NA

Purpose

BASIC_SCIENCE

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Max Age

65 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2021-05-25

Primary Completion

2022-07-10

Completion

2026-05-31

Countries

• Canada

Study Locations