Brain Activity Study Reveals How Weight-Loss Medications Reduce Food Cravings
A groundbreaking study has uncovered how tirzepatide, marketed under the brand names Mounjaro and Zepbound, affects brain patterns linked to obsessive thoughts about eating. Scientists tracked electrical signals in the brain of an individual struggling with severe weight issues and constant intrusive thoughts about food after they started the medication.
This research marks the first time scientists have used direct brain electrode measurements to observe how these popular weight-loss medications—which work by mimicking GLP-1 hormones—influence neural activity in humans, particularly regarding intense food desires.
According to Amber Alhadeff, a neuroscience researcher at Philadelphia’s Monell Chemical Senses Center, the approach of identifying a distinct brain signature for food obsession and then studying how medications alter it represents an excellent research strategy.
An Unexpected Discovery
The research team, led by Casey Halpern, a neurosurgeon-scientist at the University of Pennsylvania, wasn’t initially investigating obesity medications. Their original aim was to test whether deep brain stimulation—a treatment involving mild electrical currents delivered directly to brain tissue—could help reduce compulsive eating in people with obesity who hadn’t benefited from other interventions like weight-loss surgery.
The study involved implanting electrodes in the nucleus accumbens, a brain region central to reward processing. This area also contains GLP-1 receptors, making it relevant to how these hormones influence reward responses, explains Christian Hölscher, a neuroscientist based in Zhengzhou, China. These electrodes can both monitor electrical activity and provide stimulation when necessary, and are already used clinically for certain epilepsy cases.
Identifying the Pattern
During testing with the first two participants, researchers noticed that periods of intense food preoccupation coincided with increased low-frequency electrical activity in the brain. This discovery suggested these changes could function as a quantifiable indicator of compulsive food urges.
The third study participant, a woman aged 60, had recently begun high-dose tirzepatide treatment for type 2 diabetes management when she received her electrode implant. Halpern noted they seized this fortunate circumstance given the significant interest surrounding these medications.
Dramatic Changes Observed
Over subsequent months while on the medication, the participant’s urges to overeat completely disappeared. Halpern described the striking absence of food obsession in someone with an extensive history of cravings and food preoccupation. Equally remarkable was the profound quieting of electrical activity detected in the nucleus accumbens that preceded this behavioral change.
However, between five and seven months post-implantation, researchers detected the same type of brain activity previously associated with food compulsion beginning to increase. They questioned whether this signaled an impending return of the obsessive thoughts. Their concerns proved accurate—the neural pattern emerged before the actual return of food cravings and episodes of uncontrolled eating.
Implications and Future Directions
Despite occurring in just one individual, Alhadeff finds the temporal relationship between the neural marker and the return of food obsession quite convincing, though she emphasizes the need for validation in additional participants.
Notably, the participant remained on tirzepatide when her cravings resurfaced, suggesting possible tolerance development to this particular medication effect. Hölscher proposes that GLP-1 receptors in that brain region might become less responsive to the drug over time.
Halpern expresses hope that these findings will motivate pharmaceutical companies to develop medications specifically targeting food obsession. He points out that current drugs are primarily optimized for weight reduction, which appears to temporarily help people with these intrusive thoughts but may not provide lasting relief.
Reference:
Choi, W., Nho, Y., Qiu, L., Chang, A., Campos, G., Seilheimer, R. L., Wilent, W. B., Bakalov, D., Firdous, N., Kerr, M., Joshi, D., Maze, G., Topalovic, U., Batista, D., Suthana, N., Amaro, A., Hayes, M. R., Cajigas, I., Cristancho, M., . . . Halpern, C. H. (2025). Brain activity associated with breakthrough food preoccupation in an individual on tirzepatide. Nature. https://doi.org/10.1038/s41591-025-04035-5