# Modulating ventral striatal activity and connectivity with transcranial focused ultrasound as a putative novel intervention for cocaine use disorder

> **NIH NIH UG3** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2024 · $700,219

## Abstract

ABSTRACT. Cocaine use disorder (CUD) is highly debilitating and common, but without established treatments.
Individuals with CUD show elevated activity to cocaine cues in the ventral striatum (VS), a key region in the
prefrontal cortex-striatal reward network (RNet) supporting reward valuation, other RNet regions, and the dorsal
anterior cortex-insula salience network (SN). This pattern of elevated activity is positively associated with craving
and years of cocaine use. Carefully-monitored studies show that transcranial focused ultrasound (tFUS) is a safe
intervention that has the advantage over other neuromodulation techniques of being able to target deep
subcortical structures, such as the VS. tFUS is thus a promising intervention for CUD, and other neurological
and psychiatric disorders characterized by abnormally elevated subcortical activity. Yet, no studies have
determined whether the VS can be modulated by tFUS. We propose a proof-of-concept study targeting the VS
with tFUS, as a promising way to develop new device-based interventions for individuals with CUD, in accord
with PAR-20-279. Our first goal is to determine that VS engagement by tFUS is possible (UG3 phase) in 25
healthy volunteers (aged 18-45 years; VS tFUS [and same hemisphere sham] laterality counterbalanced across
participants). We will use a reward task that reliably activates the VS to reward prediction error (PE), the
difference between the expected and actual reward, in healthy individuals, where greater VS activity to reward
PE is associated with higher levels of impulsive decision-making, a behavioral trait predisposing to substance
use disorders. Greater VS activity to reward PE in healthy individuals is thus a neural marker of substance use
disorder risk, as well as a target for tFUS. We will then (UH3 phase) perform a sham-controlled trial to determine
the effects of VS tFUS on neural responses to cocaine cues and cocaine craving in 40 individuals with CUD. In
UG3, we aim: 1. To determine in healthy individuals target engagement of the VS by tFUS, and the duration and
tolerability of the intervention. We will measure: a) how VS tFUS vs. sham tFUS impacts VS activity and VS-
RNet and VS-SN functional connectivity (FC) to reward PE with fMRI; and b) if it has lingering effects on neural
network measures, and adverse effects. tFUS positioning and delivery will be guided by neuronavigation and
individualized simulation of the US field of stimulation; 2. To finalize all regulatory approvals for UH3, including
protocol approval by the University of Pittsburgh Institutional Review Board, and an Investigational Device
Exemption by the FDA, for tFUS use in individuals with CUD. In UH3, we aim: 3. To determine the effects of VS
vs. sham tFUS on neural responses to cocaine cues and cocaine craving in individuals with CUD. We will
measure: a) how VS tFUS vs. sham tFUS affects VS activity and VS- RNet and SN FC to cocaine cues; and b)
if these neural changes are associated with c...

## Key facts

- **NIH application ID:** 10884616
- **Project number:** 1UG3DA060431-01
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Fabio Ferrarelli
- **Activity code:** UG3 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $700,219
- **Award type:** 1
- **Project period:** 2024-06-15 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10884616

## Citation

> US National Institutes of Health, RePORTER application 10884616, Modulating ventral striatal activity and connectivity with transcranial focused ultrasound as a putative novel intervention for cocaine use disorder (1UG3DA060431-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10884616. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*