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Neuromodulation with single-element transcranial focused ultrasound in human thalamus.

Authors: Legon W, Ai L, Bansal P, Mueller JK

Transcranial focused ultrasound (tFUS) has proven capable of stimulating cortical tissue in humans. tFUS confers high spatial resolutions with deep focal lengths and as such, has the potential to noninvasively modulate neural targets deep to the cortex in humans. We test the ability of single-element tFUS to noninvasively modulate unilateral thalamus in humans. Participants (N = 40) underwent either tFUS or sham neuromodulation targeted at the unilateral sensory thalamus that contains the ventro-posterior lateral (VPL) nucleus of thalamus. Somatosensory evoked potentials (SEPs) were recorded from scalp electrodes contralateral to median nerve stimulation. Activity of the unilateral sensory thalamus was indexed by the P14 SEP generated in the VPL nucleus and cortical somatosensory activity by subsequent inflexions of the SEP and through time/frequency analysis. Participants also under went tactile behavioral assessment during either the tFUS or sham condition in a separate experiment. A detailed acoustic model using computed tomography (CT) and magnetic resonance imaging (MRI) is also presented to assess the effect of individual skull morphology for single-element deep brain neuromodulation in humans. tFUS targeted at unilateral sensory thalamus inhibited the amplitude of the P14 SEP as compared to sham. There is evidence of translation of this effect to time windows of the EEG commensurate with SI and SII activities. These results were accompanied by alpha and beta power attenuation as well as time-locked gamma power inhibition. Furthermore, participants performed significantly worse than chance on a discrimination task during tFUS stimulation.

Introduction

Purpose Transcranial ultrasound stimulation
Study Objective To test whether single‑element transcranial focused ultrasound can noninvasively modulate the human unilateral sensory thalamus (VPL), as measured by somatosensory evoked potentials and behavioral assessments.
Animal model / Human subject Homo sapiens (human); strain: N/A; age: 18-37 years old; sex: 14 male, 26 female
Disease model Healthy
MRI or image guidance method CT- and MRI-based acoustic modeling (computed tomography and magnetic resonance imaging used to guide/assess targeting)
Targeted brain region(s) Thalamus

Outcomes and Safety

Summary of Outcomes Unilateral single-element tFUS targeting the sensory (VPL) thalamus suppressed the P14 somatosensory evoked potential, produced downstream SI/SII EEG changes, and impaired tactile discrimination performance compared to sham.
Safety-related matter No adverse physical safety events or harms are reported in the abstract; however, tFUS produced a behavioral effect, with participants performing significantly worse than chance on a tactile discrimination task during stimulation.

Brain Region

Ultrasound Parameters

Ultrasound instrument Custom-designed focused ultrasound transducer (Ultran Group, Inc.)
FUS Frequency 500 kHz
FUS Intensity 14.56 W/cm2 (Free water); 7.03 W/cm2 (through human temporal bone)
FUS Pressure 137.79 kPa
FUS Mode pulsed
Pulse duration 0.36 ms
Duration of a single FUS session 1 hour
Focal Characteristics focal depth: None; focal length: 70.92 mm; aperture size: 63 mm
Treatment frequency single

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