Deep-brain electrophysiology of reward and craving in obesity

• Deep-brain recordings in a patient with severe obesity showed that Mounjaro and Zepbound (GLP-1 receptor agonists) briefly quieted craving-related circuits.¹
• Obsessive thoughts about food disappeared as the medication quieted the nucleus accumbens, the brain’s reward hub.¹
• The work illustrates direct electrophysiology of human reward circuitry in a clinical context.^{1 1}

Gardner updates

• Deep-brain recordings in a patient with severe obesity showed that Mounjaro and Zepbound briefly quieted craving circuits and nucleus accumbens activity. ¹
• Obsessive thoughts about food disappeared as the medication quieted the brain’s reward hub. ¹

Weekly enrichment (2026-07-20)

• This is a single-participant case report (“Participant 3,” a 60-year-old woman with severe treatment-resistant obesity, type-2 diabetes and persistent food noise) drawn from a four-participant early-feasibility trial, published in Nature Medicine (Choi et al., 2025; DOI 10.1038/s41591-025-04035-5).^{2 3}
• Intracranial EEG electrodes were implanted in the nucleus accumbens (NAc) using the NeuroPace Responsive Neurostimulation (RNS) System under FDA Investigational Device Exemption G180079 (University of Pennsylvania IRB 850489), the same device class used in epilepsy and Parkinson’s care.^{3 4}
• Tirzepatide (Mounjaro/Zepbound), a dual GLP-1/GIP receptor agonist, was titrated to its maximum dose; on full dose the participant reported no food preoccupation and NAc craving-related activity was quiet.^{2 3}
• The suppression was temporary: after roughly five months the previously silent NAc low-frequency activity and intense food noise returned, showing the drug’s effect on loss-of-control eating was not durable.^{2 3}
• The three trial participants not taking tirzepatide consistently showed heightened NAc activity and frequent food preoccupation, supporting the interpretation that the drug—not the surgery—drove the suppression seen in Participant 3.^{2 3}
• The craving biomarker is a NAc delta-theta (low-frequency) oscillation that rises specifically before food fixation and binge urges and is absent during ordinary pre-meal hunger.^{3 5}
• In the earlier two-patient pilot (Nature Medicine, 2022), electrophysiologically-guided responsive NAc DBS over 6 months cut loss-of-control eating frequency by 80% and 87% in the two subjects, alongside weight loss.⁵
• For scope: binge eating disorder affects more than 3 million people in the US and up to ~60% of people with obesity report “food noise”; the authors caution current GLP-1/GIP drugs are not FDA-approved for food preoccupation and are “not optimized” in their current form.^{2 3}

Footnotes

1. https://www.sciencedaily.com/releases/2025/12/251208052534.htm ↩ ↩² ↩³ ↩⁴ ↩⁵ ↩⁶

2. https://www.sciencedaily.com/releases/2025/12/251208052534.htm ↩ ↩² ↩³ ↩⁴ ↩⁵

3. https://www.nature.com/articles/s41591-025-04035-5 ↩ ↩² ↩³ ↩⁴ ↩⁵ ↩⁶ ↩⁷

4. https://clinicaltrials.gov/study/NCT03868670 ↩

5. https://www.nature.com/articles/s41591-022-01941-w ↩ ↩²