Dr. Casey Halpern, head of Functional and Stereotactic Neurosurgery at Penn Medicine. | https://www.pennmedicine.org/providers/profile/casey-halpern
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Patient Daily Report | Sep 7, 2023

Chief study author: 'These findings underscore that some individuals' brains can be fundamentally different in regions that increase the risk for obesity'

Researchers from the Perelman School of Medicine have found a direct correlation between disrupted connections in brain circuits responsible for memory and appetite regulation and an individual's body mass index. The connection is especially strong in patients who have experienced disordered or excessive eating habits that can contribute to obesity and binge eating disorders (BED), an Aug. 30 University of Pennsylvania news release said.

"These findings underscore that some individuals' brains can be fundamentally different in regions that increase the risk for obesity," said the senior author, Dr. Casey Halpern, an associate professor of neurosurgery and Chief of Stereotactic and Functional Neurosurgery at Penn Medicine and the Corporal Michael J. Crescenz Veterans Affairs Medical Center. "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," Dr. Halpern said, "but the therapeutic equivalent of an electrician that can make right these connections inside their brain."

The study's findings were published on Aug. 30 in the research journal Nature.

Obese individuals exhibited compromised connectivity between the dorsolateral hippocampus (dlHPC) and the lateral hypothalamus (LH), potentially affecting their capacity to manage emotional reactions when anticipating enjoyable meals or indulgent treats, the news release on the research paper said.

The dlHPC is situated in the brain region responsible for memory processing, while the LH is positioned in the brain region responsible for maintaining bodily equilibrium, known as homeostasis, the news release said. Earlier studies established a connection between impaired function in the human hippocampus and conditions like obesity and eating disorders such as BED. However, aside from imaging methods like MRI, investigating the role of the hippocampus in individuals with obesity and eating disorders has proven challenging, the news release said.

Researchers were able to conduct the study by examining patients whose brain activity was already under electrical monitoring in the epilepsy monitoring unit. They recorded brain activity as patients anticipated and subsequently consumed a chocolate milkshake. Their observations revealed that both the dlHPC and the LH became active simultaneously when participants anticipated the milkshake. In individuals with obesity, researchers observed that the dysfunction of this hypothalamus-hippocampus circuit was directly correlated with their BMI.

To strengthen the confirmation of this connection, Halpern's team used a method known as "brain clearing" to examine brain tissue. This technique revealed the presence of melanin-concentrating hormone (MCH), a hormone responsible for regulating feeding behavior and typically produced in the LH. The team identified the presence of MCH specifically within the dlHPC, establishing a conclusive link between these two brain regions.

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