Disinhibition of the orbitofrontal cortex biases goal-directed behaviour 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 behaviour. Here, we reveal a novel role for the lOFC in the cognitive control of behaviour in obesity. Goal-directed behaviour is biased in obesity such that in obese animals, actions are no longer influenced by 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 behaviour. Conversely, pharmacological or optogenetic restoration of inhibitory neurotransmission in the lOFC of obese mice reinstates flexible, goal-directed behaviour. Our results indicate that obesity hinders an individual’s ability to make value representations about rewards, which in turn may influence how individuals make decisions in an obesogenic environment.