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The effect of transcranial ultrasound pulse repetition frequency on sustained inhibition in the human primary motor cortex: A double-blind, sham-controlled study.

Authors: Zadeh AK, Raghuram H, Shrestha S, Kibreab M, Kathol I, Martino D, Pike GB, Pichardo S, Monchi O

Non-invasive brain stimulation techniques such as transcranial magnetic stimulation and transcranial direct current stimulation hold promise for inducing brain plasticity. However, their limited precision may hamper certain applications. In contrast, Transcranial Ultrasound Stimulation (TUS), known for its precision and deep brain targeting capabilities, requires further investigation to establish its efficacy in producing enduring effects for treating neurological and psychiatric disorders. To investigate the enduring effects of different pulse repetition frequencies (PRF) of TUS on motor corticospinal excitability. T1-, T2-weighted, and zero echo time magnetic resonance imaging scans were acquired from 21 neurologically healthy participants for neuronavigation, skull reconstruction, and the performance of transcranial ultrasound and thermal modelling. The effects of three different TUS PRFs (10, 100, and 1000 Hz) with a constant duty cycle of 10 % on corticospinal excitability in the primary motor cortex were assessed using TMS-induced motor evoked potentials (MEPs). Each PRF and sham condition was evaluated on separate days, with measurements taken 5-, 30-, and 60-min post-TUS. A significant decrease in MEP amplitude was observed with a PRF of 10 Hz (p = 0.007), which persisted for at least 30 min, and with a PRF of 100 Hz (p = 0.001), lasting over 60 min. However, no significant changes were found for the PRF of 1000 Hz and the sham conditions. This study highlights the significance of PRF selection in TUS and underscores its potential as a non-invasive approach to reduce corticospinal excitability, offering valuable insights for future clinical applications.

Introduction

Purpose Transcranial ultrasound stimulation (TUS)
Study Objective To determine how different transcranial ultrasound pulse repetition frequencies affect sustained inhibition in the human primary motor cortex in a double-blind, sham-controlled study.
Animal model / Human subject Homo sapiens (human); strain: N/A; age: Not specified; sex: Not specified
Disease model healthy
MRI or image guidance method GE Healthcare 3T MR750W system (GE, Waukesha, WI, USA)
Targeted brain region(s) Primary Motor Cortex
Cargo name and characteristics Not specified in the provided text.
Route of administration Not applicable (no drug or cargo administered)

Outcomes and Safety

Summary of Outcomes Transcranial ultrasound at specific pulse repetition frequencies produced sustained inhibition of excitability in the human primary motor cortex compared with sham stimulation.
Duration of biological effect not reported
Safety-related matter No safety issues or adverse effects are mentioned in the provided text.

Brain Region

Ultrasound Parameters

Ultrasound instrument 128-element-custom-made phased array ultrasound transuder (H317, Sonic Concepts, WA, USA)
FUS Frequency 250 KHz
FUS Intensity ISPPA = 5 W/cm2; ISPTA = 0.5 W/cm2
FUS Pressure Not reported
FUS Mode pulsed
Pulse duration Not reported
Duration of a single FUS session 120 seconds (2 minutes)
Focal Characteristics 7 mm diameter, 45 mm length at 6 dB; 5.1 mm diameter, 30.28 mm length at 3 dB
Treatment frequency multiple sessions

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