# Unveiling the mechanisms of ultrasound neuromodulation via spatially confined stimulation and temporally resolved recording

> **NIH NIH R01** · BOSTON UNIVERSITY (CHARLES RIVER CAMPUS) · 2020 · $654,740

## Abstract

Project Summary
Ultrasound has been explored as a modality to modulate nerves and muscles back in the 1920s. A number of
recent studies have demonstrated the feasibility of using ultrasound to stimulate peripheral nerves, spinal cord,
and brain. Yet, it has been difficult to determine whether ultrasound stimulation is via direct modulation of the
membrane voltage or via indirect synaptic or network pathways. In order to unveil the mechanisms of ultrasound
modulation, we formed a team of complementary expertise (Xue Han: neuroscience and technology; Ji-Xin
Cheng: imaging and opto-acoustic technology; Edward Boyden: neurotechnology). Specifically, we will deploy
and integrate three novel technologies that have been established in the co-PI's labs recently. First, we will use
a miniature fiber optoacoustic converter (FOC) (0.4 mm in dia.) that can be positioned inside the brain to deliver
localized ultrasound with an unprecedented sub-millimeter spatial resolution. Second, we will use cutting-edge
genetically encoded voltage sensors to quantify the effects of ultrasound stimulation on individual cells in the
brain at a temporal resolution of 1 millisecond that is beyond commonly used Ca2+ imaging. Third, we will deploy
submicron spatial resolution stimulated Raman scattering microscopy to map membrane voltage at threshold
and sub-threshold level to monitor membrane response to ultrasound at different regions of a single neuron.
Integrating these novel technologies with a large-scale imaging platform that allows simultaneous intracranial
local drug delivery, recently developed in the Han lab, we will perform a systematic analysis of the cellular and
the biophysical mechanisms of ultrasound stimulation at sub-cellular level in cultured primary neurons, and in
different brain regions of awake mice. Specifically, we will (1) examine the spatial response profile of individual
neurons in awake brains by FOC-based neurostimulation and large-scale Ca2+ imaging in vivo; (2) examine the
temporal response profile of individual neurons in awake brains by FOC-based neurostimulation and in vivo
voltage imaging with genetically encoded voltage sensors; and (3) examine the involvement of membrane
deformation and mechanosensitive channel activation in ultrasound neuromodulation. Our proposed studies will
deliver a systematic understanding of the spatiotemporal profiles of ultrasound neuromodulation in the brain, and
identify the causal role of membrane deformation and mechanosensitive channels. These new knowledge will
build a new foundation for rational design of ultrasound neuro-stimulators and for basic neuroscience research
as well as treatment of neurological disorders.

## Key facts

- **NIH application ID:** 9951137
- **Project number:** 5R01NS109794-03
- **Recipient organization:** BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)
- **Principal Investigator:** Ji-Xin Cheng
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $654,740
- **Award type:** 5
- **Project period:** 2018-09-30 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9951137

## Citation

> US National Institutes of Health, RePORTER application 9951137, Unveiling the mechanisms of ultrasound neuromodulation via spatially confined stimulation and temporally resolved recording (5R01NS109794-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9951137. Licensed CC0.

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