Disrupted Connections Between Memory and Appetite May Explain Obesity

New research finds impaired connections between the dorsolateral hippocampus (diHPC) and the lateral hypothalamus (LH) in people with obesity, which may impact their ability to control or regulate emotional responses around food.

"These findings underscore that some individual's brains can be fundamentally different in regions that increase the risk for obesity," said senior author Casey Halpern, MD, Associate Professor of Neurosurgery and Chief of Stereotactic and Functional Neurosurgery at the University of Pennsylvania in Philadelphia. "Conditions like disordered eating and obesity are a lot more complicated than simply managing self-control and eating healthier. What these individuals need is not more willpower, but the therapeutic equivalent of an electrician that can make right these connections inside their brain."

Previous research based on imaging techniques has found an association with loss of function in the human hippocampus in individuals with obesity and related eating disorders. For this study, published in Nature, researchers sought to explore the relationship further, analyzing the differences in the brain activity and tissue of those with obesity.

Participants in the study were already being monitored electrically in the Epilepsy Monitoring Unit of Penn Medicine. Researchers observed the patients' brain activity as they anticipated and then received a chocolate milkshake. They found that the diHPC and LH were activated simultaneously as the participants anticipated receiving the milkshake. To confirm their findings, researchers used stimulation techniques, which indicated that the diHPC and LH, in particular, exhibited strong connectivity. 

In addition, researchers found that in those with obesity, the severity of the hypothalamus-hippocampus circuit’s impairment was directly proportional to body mass index (BMI). Investigators validated these findings using a technique known as "brain clearing" to analyze brain tissue.

According to the study’s authors, these results indicate a connection between the functioning of the hippocampus and obesity, which could lead to more targeted interventions for the condition.

"The hippocampus has never been targeted to treat obesity or the disordered eating that can sometimes cause obesity," said Halpern. "We hope to be able to use this research to both identify which individuals who are likely to develop obesity later in life and to develop novel therapies -- both invasive and not -- to help improve function of this critical circuit that seems to go awry in patients who are obese."