# Ultrasonic Neuromodulation: From Mechanism To Optimal Application

> **NIH NIH R00** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2020 · $247,330

## Abstract

Entirely noninvasive neuromodulation achieved using low-intensity focused ultrasound (US) is one of
the most exciting frontiers in neuroscience today. US is emerging as a new way of stimulating specific regions
of the brain noninvasively through the skull of animals and humans. In comparison to other noninvasive
alternatives such as transcranial magnetic stimulation (TMS) or transcranial electrical stimulation (tDCS, tACS),
US propagates deep into the brain while also retaining a sharp spatial focus. TMS is currently used to treat
neuropathic pain and major depressive disorder. US will provide a much more focused alternative, with fewer
side effects, to treat these disorders. The method may also be used as a noninvasive and focused alternative
to deep brain stimulation (DBS). However, it is unknown how US stimulates neurons and what stimulus
parameters researchers and clinicians should use to achieve optimal stimulation.
The principal investigator (PI) has a background in neural engineering, including pharmacological
neuromodulation and electrophysiology. To elucidate the mechanism of US neuromodulation and to work
toward optimal stimulation, the PI will pursue training through the K99 Pathway to Independence Award
mechanism at Stanford University. He has three faculty members with expertise in diverse aspects of US
neuromodulation as mentors.
In the mentored phase, the PI and colleagues will identify which neurons and ion channels are
activated by US using a small invertebrate (C. elegans) as a model. Using this animal, the PI will also rapidly
establish the set of optimal stimulation parameters. In a translational part of the training, the PI, within an
interdisciplinary team at Stanford, will build on these findings to determine optimal stimulus parameters in a
large mammal (sheep). To do so, they will ultrasonically stimulate a deep brain structure, verify the US focus
using MR imaging, and record EEG responses. This work will also establish safety threshold at which there is
no detectable tissue damage. The training will teach the PI five skills essential to attain independence. He will
learn how to i) conduct mechanistic investigations at the circuit level ii) perform US stimulation in large animals
iii) mentor a student to conduct US experiments iv) establish collaborations and v) present findings.
In the independent phase, the PI and his students will apply this training. They will build on the optimal
stimulus and safety data to devise optimal stimulation protocols in species with which the PI worked previously:
macaque monkeys and humans. The monkey will serve to optimize the effectiveness and validate the safety of
the approach before it will be advanced to humans.
Together, this research will elucidate how US activates neurons, and provide a set of US parameters
that activates neurons efficiently. It is expected that this knowledge will provide a new tool to study the function
of neural circuits and open doors for clinical application...

## Key facts

- **NIH application ID:** 9999699
- **Project number:** 5R00NS100986-04
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** Jan Kubanek
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $247,330
- **Award type:** 5
- **Project period:** 2017-04-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9999699

## Citation

> US National Institutes of Health, RePORTER application 9999699, Ultrasonic Neuromodulation: From Mechanism To Optimal Application (5R00NS100986-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9999699. Licensed CC0.

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