# FOCUS: FUNCTIONAL OPTICAL IMAGING FEEDBACK-CONTROLLED CELLULAR-LEVEL ULTRASOUND STIMULATION

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2020 · $677,502

## Abstract

PROJECT SUMMARY/ABSTRACT
Although neurotechnologies are rapidly advancing, we lack a noninvasive, cell-type specific, and
spatiotemporally regulated neuromodulation tool, which would radically change neuroscience research and
enable clinically noninvasive brain stimulation with high spatiotemporal precision. The objective of this study is
to develop a noninvasive, cell-type specific, imaging feedback-controlled neuromodulation tool that we call
Functional Optical Imaging Feedback-Controlled Cellular-Level Ultrasound Stimulation (FOCUS).
FOCUS uses a tripartite methodology: starting with ultrasound-mediated gene delivery to noninvasively deliver
a viral vector encoding an ultrasound-sensitive ion channel to specific neuronal cells, followed by ultrasound
stimulation to noninvasively activate the ion channel and modulate the brain activity, followed by online feedback
control of the ultrasound stimulation parameters based on optical imaging of brain activity. Guided by strong
preliminary data, the objective will be accomplish by pursuing four specifics aims: (1) Evaluate and select
mechanosensitive ion channels suitable for activating neurons by ultrasound; (2) Optimize ultrasound gene
delivery to achieve noninvasive, localized, efficient delivery of AAVs; (3) Develop and optimize FOCUS for
noninvasive causal manipulation of brain activity; and (4) Demonstrate FOCUS in controlling animal behavior in
awake mice by manipulating brain circuits. The proposed FOCUS tool is innovative and transformative because
it addresses key limitations of current state-of-the-art neuromodulation tools, and opens new horizons in
neuroscience and neuroengineering. FOCUS offers the following innovative features: truly noninvasive, easily
scalable to large animals, cell-type specific, and neuroimaging-feedback control. The proposed research is
significant because it directly addresses the central goal of RFA-MH-17-240 by providing the neuroscience
community with a long awaited tool that is transformative and has the potential to become the next frontier in
neuromodulation.

## Key facts

- **NIH application ID:** 9942504
- **Project number:** 5R01MH116981-03
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Hong Chen
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $677,502
- **Award type:** 5
- **Project period:** 2018-08-23 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9942504

## Citation

> US National Institutes of Health, RePORTER application 9942504, FOCUS: FUNCTIONAL OPTICAL IMAGING FEEDBACK-CONTROLLED CELLULAR-LEVEL ULTRASOUND STIMULATION (5R01MH116981-03). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9942504. Licensed CC0.

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