# Investigating the role of nucleus accumbens delta signaling in loss of control

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2022 · $393,438

## Abstract

Project Summary/Abstract
Binge eating disorder is the most common eating disorder afflicting up to 10% of US adults. It is characterized
by recurring episodes of eating large sums with a sense of loss of control. Preclinical studies have implicated
dysregulation of the nucleus accumbens (NAc) in loss of control eating. To provide a deeper understanding as
to how the NAc underlies LOC eating in humans, we leverage data from an early feasibility trial entitled
Responsive Neurostimulation for Loss of Control Eating (NCT03868670). This UH3 study aims to examine the
safety, feasibility, and preliminary efficacy of responsive neurostimulation of the NAc for LOC eating. Two
subjects are currently enrolled and successfully underwent bilateral surgical implantation of the responsive
neurostimulation system (NeuroPace, Inc.) into the NAc. Both subjects are undergoing responsive DBS guided
by NAc delta (2-4Hz) oscillations (i.e. “delta-responsive DBS”) and have exhibited less LOC (primary endpoint).
A supplement to enroll the 4 additional subjects is under FDA review. Here, we intend to characterize the role
of NAc delta signaling in human LOC eating behaviors. Preliminary data suggests that ventral NAc delta power
and bilateral connectivity elevate during anticipatory and LOC-like cravings states, specific to palatable foods.
Futhermore, delta power and ventral bilateral NAc connectivity are reduced following delta-responsive DBS,
and that this effect is sensitive to stimulation parameter optimization. Our central hypothesis suggests the NAc
as a key region in LOC eating, and that aberrant delta signaling underlies LOC eating. As such, we predict that
delta-responsive DBS acts on LOC behaviors through a rescue of the NAc’s aberrant delta signaling. Our aims
are to determine how NAc delta power and connectivity can differentiate LOC eating from normal eating, and
identify neural underpinnings of behavioral response to NAc delta-responsive DBS. As LOC is common to all
binges and is a transdiagnostic feature of many mental health disorders, this work will provide invaluable
insight relevant to much of Psychiatry.

## Key facts

- **NIH application ID:** 10426696
- **Project number:** 1R01MH124760-01A1
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Casey Harrison Halpern
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $393,438
- **Award type:** 1
- **Project period:** 2022-03-07 → 2027-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10426696

## Citation

> US National Institutes of Health, RePORTER application 10426696, Investigating the role of nucleus accumbens delta signaling in loss of control (1R01MH124760-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10426696. Licensed CC0.

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