Type 2 diabetes may quietly alter the brain in ways that mimic early Alzheimer’s, weakening reward perception and memory signals in a key brain area called the anterior cingulate cortex (ACC).
In a rat study, diabetic animals still behaved normally but processed rewarding locations differently, showing dulled communication between the hippocampus and ACC. This change could explain links between diabetes, mood disorders, and neurodegeneration – and may point to new treatment targets.
Type 2 Diabetes and Brain Disorders
The high comorbidity of type 2 diabetes (T2D) with psychiatric or neurodegenerative disorders points to a need for understanding what links these diseases. A potential link is the anterior cingulate cortex (ACC). The ACC supports behaviors related to cognition and emotions and is involved in some T2D-associated diseases, like mood disorders and Alzheimer’s disease (AD). James Hyman and colleagues, from the University of Nevada, Las Vegas, used a rat model of T2D that affects only males to explore whether diabetes affects ACC activity and behavior. Their work is featured in JNeurosci’s Computational Properties of the Prefrontal Cortex Special Collection.
Investigating the ACC’s Role in T2D
The researchers examined ACC activity and behavior as male rats sought rewards in a cognitively demanding maze. All rats pursued rewards, but areas where rewards were received were less salient to those with T2D; these rats had weaker ACC reward signals in these locations and did not stay there long. The researchers pinpointed the weakened reward signal to a dampened input into ACC from the hippocampus, which is involved in spatial memory.
“We think the hippocampus tells the rat where it is in the maze, and the ACC tells the rat what it is doing and that it’s getting a reward. These things should come together and make the rat remember it was just in a special, rewarding location, but this doesn’t happen with the ones that have T2D,” says Hyman.
This study highlights the close relationship T2D has with reward and spatial processing. According to the authors, the hippocampus-to-ACC projection may be worth exploring as a treatment target for mood disorders to which the ACC is already linked.
Hyman also emphasizes that because this projection contributes to mild cognitive impairment preceding AD, “Diabetes may be altering the brain similarly to early stages of AD. AD goes undetected for decades because our brains are good at finding ways to adapt. Before diagnosis, people behave normally despite having changes in information processing. We even observed that in this study! Diabetic rats still went to receive the reward, but their experience differed compared to healthy animals.”
Reference: “ACC reward location information is carried by hippocampal theta synchrony and suppressed in a Type 2 Diabetes model.” by Guncha Bhasin, Emmanuel Flores, Lauren A. Crew, Ryan A. Wirt, Andrew A. Ortiz, Jefferson W. Kinney and James M. Hyman, 23 March 2025, Journal of Neuroscience.
DOI: 10.1523/JNEUROSCI.1546-24.2025
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