# Noninvasive modulation of deep brain circuits for treatment-resistant depression

> **NIH NIH R61** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2024 · $967,781

## Abstract

Current interventions for depression lack the capability to directly, precisely, and noninvasively engage the
deep brain circuits at the core of the illness. We have developed a non-significant-risk, MRI-compatible,
individually-targeted, ultrasonic neuromodulation device that can stimulate deep circuits in humans
noninvasively with a precision previously achievable only with surgically implanted electrodes. This R61/R33
project will evaluate the potential for this novel device to engage deep brain targets and modulate mood
symptoms in individuals with treatment-resistant depression. The R61 phase will demonstrate target
engagement by delivering low-intensity ultrasound to the subcallosal cingulate during functional magnetic
resonance imaging. This phase aims to evaluate the intensity dependence, target specificity, and tolerability
of this neuromodulation intervention. If predefined go/no-go criteria are met, the R33 phase will then evaluate
the short-term effects of subcallosal cingulate neuromodulation using a randomized sham-controlled study
design. The aims of this phase are to examine the associations between target engagement, short-term mood
changes, and immediate changes in brain functional connectivity. The R33 also aims to evaluate tolerability
and feasibility of a subsequent efficacy trial. This project will address an unmet need by providing new,
noninvasive, circuit-directed treatment options for patients with treatment-resistant depression. Because this
ultrasonic neuromodulation device offers access to deep brain structures with a unique combination of
flexibility, precision, and noninvasiveness, the proposed work is expected to have broader positive impacts for
understanding and treating other disorders of deep brain circuits.

## Key facts

- **NIH application ID:** 10786600
- **Project number:** 1R61MH134943-01
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** Jan Kubanek
- **Activity code:** R61 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $967,781
- **Award type:** 1
- **Project period:** 2024-06-01 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10786600

## Citation

> US National Institutes of Health, RePORTER application 10786600, Noninvasive modulation of deep brain circuits for treatment-resistant depression (1R61MH134943-01). Retrieved via AI Analytics 2026-07-01 from https://api.ai-analytics.org/grant/nih/10786600. Licensed CC0.

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