Affiliations : The Douglas Institute, McGill, Canada
Journal reference: DOI: 10.1172/JCI138532
Summary: Do you know the difference between goal directed behaviours versus habits? In this study Dr Favier explores whether an imbalance between those two behaviours could be one of the central causes behind eating disorders.
Eating disorders such as anorexia nervosa, bulimia nervosa or binge eating disorder are severe psychiatric illnesses. Anorexia nervosa is difficult to treat, particularly in adults, and has the highest mortality rate of all mental disorders. Anorexia nervosa includes persistent restriction of food intake (restrictive-only) or binge eating followed by purging, whereas bulimia nervosa or binge eating disorder involve consumption of a large amount of food in a short period of time, accompanied by a loss of control over eating. Eating disorders are frequently associated with a lack of cognitive flexibility, aberrant reward processing or obsessive-compulsive disorder. The inability to interrupt behavior despite negative consequences in patients with eating disorders alludes a common basis with compulsive disorders. Currently, there is an unmet need for specific biological treatment for eating disorders.
In humans or other animals, every action reflects a balance between two types of reward-based learning: goal-directed behaviors and habits (or habitual behaviors). Goal-directed behaviors are observed when individuals are engaged in reaching a specific objective. In this case, action selection is governed by its outcome. Goal-directed behaviors are characterized by active deliberation of future consequences and adaptive flexibility to changing environments. Habits on the other hand emerge from goal-directed learning when behaviors become automated due to repetition. Habits are driven by environmental stimuli and they are independent from the outcome. They are shaped by past experience, and are characterized by efficiency and inflexibility. Automaticity has major benefits as it allows the brain to free up attentional and decision-making resources (called cognitive resources). Let’s take the example of someone that is learning to drive a car. At the beginning, the young driver has to assimilate a range of procedures (speed adjustment, wheel control, etc…). Progressively however and with repetition, all these actions become habits, allowing the experienced pilot to have more cognitive resources to adapt to unexpected events (e.g. someone crossing the road…). However, automaticity can also be detrimental, underlying the development of maladaptive habits, which in the extreme can result in compulsive behaviors.
In our study, we questioned whether an imbalance between goal-directed behaviors and habits could be a central cause of eating disorders, as already described in other compulsive disorders.
First, using a computer-based neurocognitive task that evaluates habit formation in humans, we found that a subgroup of patients with restrictive anorexia nervosa was more prone to habitual behavior than healthy individuals. In addition, the tendency for habits of these restrictive anorexic patients was correlated with their poor cognitive flexibility.
In order to decipher the brain basis of dysregulated habit formation and its involvement in maladaptive eating, we also used mice models. In the brain, a structure called the striatum is a key hub for the regulation of goal-directed and habitual behaviors. While the dorsomedial striatum (caudate in humans) is crucial for the acquisition of flexible goal-directed behaviors, the dorsolateral striatum (putamen in humans) modulates rigid habitual behaviors. To communicate, brain cells (neurons) use small molecules named neurotransmitters. It is well-known that a specific neurotransmitter, dopamine, is a pivotal regulator of the transition from goal-directed behaviors to habits. Other types of neurons, called striatal cholinergic interneurons are also major modulators of striatal functions. Striatal cholinergic interneurons have the remarkable ability to use 2 types of neurotransmitters, acetylcholine and glutamate. It was recently found that acetylcholine and glutamate released by striatal cholinergic interneurons differentially affect dopamine transmission in the ventral striatum. However, how individual neurotransmitters (acetylcholine or glutamate) released by striatal cholinergic interneurons impact the transition between goal-directed behaviors and habits, and therefore potentially influence maladaptive eating was still obscure.
We showed that inactivating acetylcholine release from striatal cholinergic interneurons, impaired behavioral flexibility, facilitated habit formation and consequently caused mice to be more susceptible to maladaptive eating. Specific deletion of acetylcholine release from striatal cholinergic interneurons in the dorsomedial striatum was sufficient to promote maladaptive eating. In parallel, we observed that dopamine efflux was decreased in the dorsomedial striatum but remained unchanged in the dorsolateral striatum of our genetic mice model. This observation points to the possibility that an uneven dopamine transmission in striatal compartments could underlie excessive habit formation and maladaptive eating. Indeed, increasing acetylcholine efflux with a pharmacological treatment called donepezil, or dopamine efflux with a pharmacological treatment called L-DOPA, abolished the self-starvation phenotype of acetylcholine-depleted mice in the activity-based anorexia model.
In total, our work reveals mechanisms underlying vulnerability to maladaptive eating and identify striatal acetylcholine/glutamate co-transmission as a potential target to correct excessive habitual behavior and pathological eating. Our data pave the way to the identification of a specific subgroup of eating disorders patients and suggest innovative targeted therapies for the treatment of these patients.