Systematic examination of low-intensity ultrasound parameters on human motor cortex excitability and behavior.

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 behavior. 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 GABA<sub>A</sub>-mediated short-interval intracortical inhibition and decreased reaction time on visuomotor task but not when controlled with TUS at near-somatosensory threshold intensity.

Introduction

Purpose Transcranial ultrasound stimulation

Study Objective To determine how varying sonication parameters of low-intensity transcranial ultrasound applied to the human primary motor cortex affect cortical excitability and visuomotor behavior.

Animal model / Human subject Human (Homo sapiens), strain: N/A, age: 29-59 years old, sex: 8 male; 10 female

Disease model Healthy

MRI or image guidance method TMS-guided (transducer coupled to TMS coil targeting the left M1 hotspot of the first dorsal interosseous muscle)

Targeted brain region(s) Primary Motor Cortex (M1)

Outcomes and Safety

Summary of Outcomes LITU applied to human M1 suppressed TMS-evoked motor-evoked potentials, increased GABAA-mediated short interval intracortical inhibition, and shortened visuomotor reaction time. Strongest effect under low duty cycles and longer snication time.

Safety-related matter No subjects reported any adverse effects, although two (13%) participants experienced a transient warm sensation at the sonication site after multiple experimental blocks. Neurological examinations after each visit were normal, supporting the safety profile of the pulsing schemes.

Brain Region

Ultrasound Parameters

Ultrasound instrument Custom 2-element annular array ultrasound transducer (Sonic Concepts)

FUS Frequency 500 kHz

FUS Intensity ISPTA: 0.69 W/cm2; ISPPA: 2.32 W/cm2

FUS Mode pulsed

Pulse duration 0.1-0.5 ms

Duration of a single FUS session 0.5 s

Focal Characteristics Focal depth: 30 mm; Focal length: 23 mm; Aperture size: 38 mm

Treatment frequency Multiple sessions

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