What’s the difference between you and a rat? The list is unsurprisingly long but now, we can cross a universal human experience — feelings of regret — off of it.

A new study shows for the first time that rats regret bad decisions and learn from them. In addition to existentialist suggestions of a rat’s regret — and what that takes away from, or adds to, being “human” — the study is highly relevant to basic brain research. Researchers demonstrated that we can tap into complex internal states of rodents if we hone in on the right behavior and the right neurons. There is a significant literature on what brain regions are representative of certain states, like reward predictions and value calculations, but the study, powered by a novel behavioral test, is able to put together such discrete behavioral correlates into a “rat” definition of regret.

Finding better animal models of human behavior constitute a long-standing challenge in neuroscience: It has been difficult to authentically recapitulate mental states in animal models of neuropsychiatric disorders: For example, an attempt to model depression in rodents can often go no further than relatively coarse approximations of the core symptoms like guilt or sadness, which often translates to behaviors like social avoidance or anhedonia in rodents. The inability to efficiently approach the questions of mental abnormalities is a major problem. Depression is currently ranked as the leading cause of disability globally, and it’s estimated that by 2020, depression will lead 1.5 million people to end their lives by suicide.

Now, thanks to a simple yet well-conceived series of experiments by Steiner and Redish, a compound behavior like regret is fully open to investigation. The investigators use a spatial decision-making set-up called “Restaurant Row”: an arena with four zones where four different flavors of food (banana, cherry, chocolate or unflavored) are introduced in sequence. Every time a rat entered a zone, it encountered a random length of delay and a tone before receiving the reward: the pitch of the tone indicated the delay the rat had to wait before receiving a reward (a higher pitch representing a longer delay). The delay counted down, with each subsequent second indicated by a lower pitch tone. Rats were trained to go one zone to next over a period of on hour. So, upon entering a zone, a rat knew what flavor of reward it was getting and how long it had to wait for it.

Each of the four rats used in the experiment demonstrated a preference for a different flavor: One, for example, preferred banana over cherry, meaning that it was willing to wait longer for banana than for cherry. This was termed the rat’s ‘threshold’: A 20 seconds cherry threshold for Rat A means that Rat A is, on average, willing to wait 20 seconds for the cherry flavor.

Researchers then define an regret-inducing situation in terms of these thresholds. If a rat leaves a particular flavor zone before the threshold and ends up waiting above the threshold for the next zone, this is then said to induce regret. For example, consider a rat that prefers banana over cherry: Say it is willing to wait for banana for 25 seconds, and for cherry only for 10 seconds. Then say this rat, in a given session, opts to wait for banana for 15 seconds and leaves before getting the reward, and then moves to the cherry zone. Since its cherry threshold is 10 seconds, if the rat ends up waiting longer than 10 seconds, this induced regret because the rat should have stayed with the banana. Regret is then an expensive missed opportunity. Rats showed both a behavioral sign of regret (turning and looking at the missed high-value reward) and were then more willing to wait for a reward following regret-inducing instances, indicating that they learned from their mistake.

Investigators examined the neural correlates of regret: Prior to starting the Restaurant Row sessions, they implanted electrodes into two regions implicated in neural calculations of reward, value and prediction of expected value: the orbitofrontal cortex (OFC) and ventral Striatum (vStr). Then they coupled these neural recordings with specific instances during the session, including the zone entries, reward deliveries, and regret-inducing situations.

A fascinating conclusion of these recordings revealed a subtle subtext of human regret that is mirrored in rats. Studies of regret in humans show that people regret miscalculated actions more than the missed outcomes — i.e a gambler feels more regret over misplaying a hand than over how much money she lost.
In an effort to see if rats had a similar cognitive structure of regret, investigators first examined the neural activity signatures in the OFC and vStr in two separate instances: when a rat entered a zone and when it received a reward. When compared to the activity signatures at the moment of regret (based on when a rat turned and looked at the missed opportunity), it was the signature of zone, not of the reward, that lit up in the respective brain regions: Rats regret having skipped the zone more than having not received the reward.

The study is rare in that it illuminates new internal states in rodents; it promises future efforts to explore other complex behaviors in rodents, which could further inform better animal models of behavior. With each such effort that unravels the parallels between the behaviors of humans and those of other mammals, we inch ever closer to a better picture what it means to act, feel and be human.