Disinhibition of the orbitofrontal cortex biases decision-making in obesity

The lateral orbitofrontal cortex (lOFC) receives sensory information about food and integrates these signals with expected outcomes to guide future actions, and thus may play a key role in a distributed network of neural circuits that regulate feeding behavior. Here, we reveal a new role for the lOFC in the cognitive control of behavior in obesity. Food-seeking behavior is biased in obesity such that in male obese mice, behaviors are less flexible to changes in the perceived value of the outcome. Obesity is associated with reduced lOFC inhibitory drive and chemogenetic reduction in GABAergic neurotransmission in the lOFC induces obesity-like impairments in goal-directed behavior. Conversely, pharmacological or optogenetic restoration of inhibitory neurotransmission in the lOFC of obese mice reinstates flexible behavior. Our results indicate that obesity-induced disinhibition of the lOFC leads to a failure to update changes in the value of food with satiety, which in turn may influence how individuals make decisions in an obesogenic environment.

Automated summary

The lateral orbitofrontal cortex (lOFC) is involved in integrating sensory information about food and expected outcomes to regulate feeding behavior. In this study, it was found that the lOFC also plays a role in the cognitive control of behavior in obesity. Obesity leads to inflexible food-seeking behavior due to reduced inhibitory drive in the lOFC. Restoring inhibitory neurotransmission in the lOFC reinstates flexible behavior in obese mice. These findings suggest that obesity-induced disinhibition of the lOFC affects decision-making in an obesogenic environment.