# Low intensity focused ultrasound: a new paradigm for depression and anxiety

> **NIH NIH U01** · OCEAN STATE RESEARCH INSTITUTE, INC. · 2022 · $583,140

## Abstract

PROJECT SUMMARY/ABSTRACT
Current treatments for depression and anxiety are often limited by partial efficacy and significant side effects.
These disorders constitute serious public health challenges due to significant burden of illness, and the lack of
more effective treatments contributes to substantial suicide risks. To address these unmet needs, non-invasive
brain stimulation is a circuit-based treatment with minimal side effects; it is clinically available for major
depression and obsessive-compulsive disorder, with evidence for efficacy in anxiety and posttraumatic stress
disorder. One of the core brain regions involved in these disorders, among others, is the amygdala, with its
critical role in salience detection and emotion processing. This region demonstrates pathological activation in
nearly all depressive and anxiety disorders, and pathological activity changes with successful treatment. Yet,
because the amygdala is distal to the cortical surface it is not directly accessible with current technologies. Our
challenge is to find a way to focally and non-invasively modulate the amygdala, with the broader hypothesis
that direct engagement will yield treatments with superior clinical outcomes.
 Low intensity pulsed focused ultrasound (LIFU) applies non-invasive acoustic energy to safely
modulate neural activity in translational models and non-human primates. Unlike transcranial magnetic or
electrical stimulation and related technologies, LIFU is able to directly and focally modulate activity within deep
brain structures. LIFU can safely modulate human somatosensory and motor cortex and safely suppress
thalamic activity; recent data indicates it can suppress amygdala activity. Furthermore, an MRI-compatible
LIFU system is now available (Brainsonix, Inc. LA, USA), thus permitting simultaneous fMRI-LIFU experiments.
These factors create a compelling argument to develop LIFU as a treatment for depression and anxiety by
testing whether it can safely modulate the amygdala.
 To set the stage for future clinical trials, we must first test how LIFU engages the amygdala in patients
with depression and anxiety. In accordance with the U01 RFA, we propose several pilot experiments. We will
systematically assess safety (Aim 1) as we evaluate spatial specificity of target engagement, using online and
offline approaches (Aims 2-3) using a randomized, anatomically controlled, experimental design, and explore
the impact of LIFU on clinical symptoms. We obtained an Investigational Device Exemption (IDE) from the FDA
for this proposal as it is written.
 If successful, this first-in-human proposal will provide the necessary data to support a broad and
programmatic research focus on clinically applied LIFU for depression and anxiety. Resulting data will inform
future studies, including improvement of individual-level modeling for LIFU, informing optimal targets to
engage, refinement of LIFU shams, and evaluating effects of varied LIFU parameters or multiple sessi...

## Key facts

- **NIH application ID:** 10414943
- **Project number:** 5U01MH123427-02
- **Recipient organization:** OCEAN STATE RESEARCH INSTITUTE, INC.
- **Principal Investigator:** Noah Stephen Philip
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $583,140
- **Award type:** 5
- **Project period:** 2021-06-01 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10414943

## Citation

> US National Institutes of Health, RePORTER application 10414943, Low intensity focused ultrasound: a new paradigm for depression and anxiety (5U01MH123427-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10414943. Licensed CC0.

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