Anorexia Nervosa and the Motivational Brain

Anorexia nervosa is a serious mental disorder that manifests with an intense fear of weight gain and a disturbed body image. This can lead to severe diet restrictions or other behaviors like purging, excessive-exercise regimen, or extensive physical activity in an attempt to maintain weight loss.

Anorexia nervosa and the mesolimbic reward system

Cataloging factors believed responsible for anorexia nervosa yields a lengthy list that includes genetic, developmental, and neurobiological influences. The mesolimbic pathway, also referred to as the reward pathway, is a system that connects several brain regions involved in the regulation of reward response; or to put it differently, it regulates how we respond in the presence of something that is rewarding, like food or sex, for example. So, it should not be surprising that studies often point to changes in the mesolimbic system when describing the brain’s involvement in anorexia nervosa.

This is true of a recent study [1] by a group at the Semel Institute for Neuroscience and Human Behavior at UCLA. By using functional magnetic resonance imaging (fMRI) to compare activity in the brain of adolescent participants experiencing anorexia nervosa versus those without, the group discovered poor functional and structural connections within the mesolimbic reward system of those with anorexia nervosa. This discovery supports the idea that anorexia nervosa may be a disconnectivity syndrome characterized by disrupted (functional and circuit) interactions within relevant brain networks, particularly in this case the mesolimbic reward system.

The study compared 32 adolescent females with anorexia nervosa versus 28 healthy controls. Reward-motivation response was examined in an fMRI while participants completed a monetary-reward task.

Before the scans, participants were told that they were going to play a game in which they could win $10 for correct responses. At the beginning of each session, a color image was presented. Participants were instructed to push the right or left button to guess whether the image belonged in “group 1” or “group 2.” After selection, there was a short pause before participants received feedback on whether their guess was correct or incorrect, consequently receiving or not receiving the reward.

The chance of receiving a reward in each session was in fact random (50/50 chance of being correct). The goal was simply to measure the brain’s response to the reward. Several brain regions were examined, but given the well-established important role of the mesolimbic dopamine system for motivational reward, special attention was given to the mesolimbic system.

The mesolimbic system is comprised of various nodes. One primary node in the middle of the brain sends dopamine to a recipient node towards the front. As is true for most structures in the brain, there are two sets of structures, one residing in each side of the brain or brain hemisphere. The study found that presenting a reward to a healthy participant activated the primary node, the recipient node, and its connections. An inverse relationship was also discovered between the activation of the nodes with the speed of reward-seeking. The stronger the nodes’ activation, the faster participants would perform the selection task that might lead to a reward.

What is particularly telling, however, about those with anorexia nervosa was the significant reduction in functional connectivity between the primary and recipient node in the right side of their brain during the task. Also, unlike healthy participants, the speed of reward-seeking showed no relationship with activity in the mesolimbic nodes or in their connections for those with anorexia nervosa, suggesting a potential neural and behavioral “decoupling” in those with anorexia nervosa as they experience reward motivation. Subsequent analyses also revealed fewer fiber connections between the primary and recipient node in the right side of the brain for participants with anorexia nervosa, which might help explain the observed disconnect on the right side of their mesolimbic path.

Identifying the causes of anorexia nervosa

Anorexia nervosa occurs in approximately 1% of women and 0.3% of men, and onsets during the teenage years or in the early 20s. Whether anorexia nervosa is the result of sociocultural, developmental, or biological influences, or a combination of these, is a question of great interest and one that undergoes great scrutiny by members of the scientific community.

Undoubtedly, the findings in this study support the biological aspects of the disorder’s etiology. The emphasis on the reward pathway is interesting, in part, because those with anorexia nervosa do not necessarily regard food as tasting bad or lack a need for food. In fact, patients in the binge-purge subtype of the disorder, unlike the restrictive subtype, find themselves eating large amounts of food in a short period of time before purging. So, the role of the mesolimbic dopamine system in this disorder may go beyond its modulation of motivational reward and into other realms of the brain-behavior connection, but clearly reward regulation by dopamine is at least one factor that is impacted by this disorder. The dopamine model of anorexia nervosa would argue that this disorder is, at least partly, the result of aberrant dopamine processing [2]. The findings in this fMRI study lend further credibility to this model. Finally, another issue that often arises while interpreting studies like this one is whether brain changes observed in participants with anorexia nervosa resulted from the disorder or whether the changes in the brain system are the cause of the disorder. This is an understandably difficult issue to resolve.

Anorexia Nervosa Essential Reads

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Anorexia Nervosa: Addressing the Bugs in the System

So while a cure for anorexia nervosa is proving elusive, work like the one described here brings us closer to a better understanding of the neurobiological underpinnings responsible for the manifestation of this disorder, as well as other eating disorders, which impact millions of people.