Anhedonia: In search of pleasure

What do chocolate, TV and sports have in common? Apart from the fact that if you overindulge in the former two, you had better pick up the latter, all three also bring us a great deal of pleasure. Pleasure is essential to our well-being. It points us to the activities that are good for our survival, such as eating, socializing or sex, and makes us feel great when we are doing them, so much that we want to pursue them sometimes even at a great cost.

The importance of pleasure becomes obvious when we stop feeling it. The diminished ability to experience pleasure is called anhedonia, and it is a core symptom of depression. For a very long time, we thought that people with anhedonia have reduced capacity to like, i.e. feel less when they are doing something enjoyable, but recent research has shown that it might not be as simple as that.

Liking is not the main problem in anhedonia

Liking, in the context of neuroscience, refers to the level of pleasure we feel when we enjoy something. Animal studies suggests that it arises from small hedonic hot spots located mainly in the subcortical regions of the brain, such as the nucleus accumbens or ventral pallidum. However, we might need the cortical regions, such as orbitofrontal cortex or anterior cinguate cortex, to be consciously aware of the feeling (Thomsen et al., 2015).

How do such hot spots look like? They are small and sensitive to opioids and endocannabinoids (brain-grown cousins of morphine and marijuana). Although the hot spot in a rat nucleus accumbens takes up only about 1 mm3 (10% of the nucleus), when it is injected with morphine, it doubles the rat’s pleasure – at least according to its facial expression.

In humans, liking is measured by self-report questionnaires. They often list traditionally pleasurable activities, such as drinking tea or hanging out with friends, and ask how much you enjoy them. In these questionnaires, depressed individuals report much lower levels pleasure than healthy people, which originally led to the belief that anhedonia is caused by impairments in liking. However, when the volunteers were asked to rate the pleasantness of sweet water solution in real time, there was no difference between people with depression and others. Yet the neuroimagining studies show that when depressed people receive rewards, their ventral striatum (brain region consisting of nucleus accumbens and olfactory tubercle) is less active.

What to take home from this? Anhedonia, or at least depression, might impair the brain regions involved in liking, but that does not seem to affect the subjective feeling of pleasure during consumption of rewards. Instead, it seems to affect the way we think about past or future pleasure. To put it simply, people with anhedonia like chocolate as much as anybody else, but when they are not eating it they think they like it less.

Wanting and anticipantion of pleasure is impaired

When we are thinking about future or hypothetical rewards, it is all about wanting rather than liking. In a very simplified view: wanting is what we predict our liking is going to be traded off against the predicted costs, such as money, effort or time. Wanting makes us pursue desirable rewards even though it might take considerable effort.

Generally, people want what they like and like what they want but wanting and liking are two separate processes that can be dissociated behaviourally and also neurologically. This was first proven 15 years ago by Aharon et al.. He showed heterosexual men pictures of males and females and asked them to rate them for their attractiveness. In a follow-up task, they were shown these images once again. If they wanted to view the images for longer, they had to keep clicking (i.e. exert effort). While the men rated the female and male pictures as equally attractive, only the female pictures made them click.

Although wanting and liking share many brain regions, such as the nucleus accumbens and ventral pallidum, the wanting network is much larger, and involves additional areas including the ventral tegmental area or lateral hypothalamus. These brain regions are closely related to dopaminergic network, and it is indeed the dopamine stimulation that has the biggest and most exclusive impact on wanting. For example, mice depleted of dopamine will choose standard food rather treats if they have to climb over an obstacle to get to the treats. In contrast, mice injected with amphetamine, a powerful stimulant of dopamine, eat more food but do not seem to be liking it any more than other mice. So dopamine enhances wanting but not liking. Parkinson‘s patients are particularly interesting in this respect. Parkinson‘s disease kills dopamine producing cells in the brain. While, the patients often lack the motivation to pursue rewards or goals, they still report the same levels of pleasure as other people.

Although the research into wanting has increased over the past decade, there are still very few studies comparing wanting in the healthy and depressed population. The ones that do exist seem to suggest that people with depression are less likely to exert higher effort for greater rewards and are satisfied with less rewarding options, similar to the mice with depleted dopamine. This might explain why people with anhedonia lose interest in things they used to enjoy. However, we do not yet know whether this is because they underestimate future rewards, overestimate related effort or whether it is a combination of both. Nonetheless, neuroimaging studies seem to suggest that at least reward anticipation might be impaired in anhedonia as depressed people have diminished activity in the nucleus accumbens when they wait for a reward compared to healthy people.

People with anhedonia learn less from pleasurable experiences

Reward learning creates a bridge between wanting and liking, as it indexes the things we have enjoyed in the past and that are therefore worth pursuing. It allows us to learn and subsequently remember what we like and enables us to update our preferences over time.

Reward learning is probably the most widely studied component of pleasure processing, as it is easy to simulate it in the lab. In reward based tasks, participants have to either learn which of previously unknown options has higher odds of reward or they have to track the size of a reward over time. In both cases, dopamine-driven activation in ventral striatum reflects reward prediction errors, that is the difference between what you got and what you had expected. This is considered a key marker of learning – the more you know about an option, the closer will your expectation match the actual reward and the reward prediction error will get smaller.

Studies suggests that people with depression, and especially those with anhedonia, are less sensitive to reward odds. In a task when one option is more likely to yield rewards than the other, it takes them longer to identify it and they select it less frequently.  This is supported by neuroimagining data that show reduced learning signal in ventral striatum. So depressed (and especially anhedonic) people learn slower about rewards around them and might be less likely to recall pleasurable experiences, which explains why they report to feel less pleasure or interest when they are asked about their past or prospective activities.

What comes next?

To conclude, people with anhedonia seem to experience pleasure similar to other people but they are less likely to anticipate and remember every day pleasures, and are less willing to pursue them, especially if that requires a lot of effort or investment. These findings could be particularly beneficial for pharmacological research into a treatment for anhedonia as there is no drug known to alleviate it at the moment.

However, there are still some issues that need to be ironed out before we can start a meaningful search for a new medication. Probably the most pressing one, at least in my opinion, is the lack of studies in the anhedonic population. So far, studies about anhedonia were mostly carried out in depressed people, neglecting whether participants actually have the symptom or not. Even though anhedonia is common in depression, not all people who have depression are also anhedonic. Although interchanging one for the other makes it easier to find participants, it introduces variability through uncontrolled inter-individual differences to the results. At this early stage, such lack of control might considerably slow down the research. Hence, the research should focus on people with anhedonia, or we might potentially forego the chance to follow a promising lead for a treatment of this thoroughly unpleasant disorder.

References:

Aharon, I., Etcoff, N., Ariely, D., Chabris, C., O’Connor, E. and Breiter, H. (2001). Beautiful Faces Have Variable Reward Value. Neuron, 32(3), pp.537-551.

Thomsen, K.R., Whybrow, P. and Kringelbach, M. (2015). Reconceptualizing anhedonia: novel perspectives on balancing the pleasure networks in the human brain. Front. Behav. Neurosci., 9.

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