Fundamentally distinct types of regret may be altered in depression (IMAGE)
Caption
Mice were trained to navigate a maze to work for food rewards while on a limited time budget. Mice had to make cost-benefit decisions to accept or reject offers to wait in line for a reward depending on how expensive the cost was (i.e., how long they had to wait). The length of the wait was signaled by the pitch of a tone. Sometimes, mice would make economic mistakes atypical relative to their usual choices by rejecting low-cost offers (type I violations). Other times, mice would conversely accept high-cost offers (type II violations). On the trial following these mistakes, particularly when encountering worse offers, signals in the brain have been shown to represent alternative actions the animals could have taken, serving as a neural signature of counterfactual processing and the basis of regret. These events subsequently bias animals to overcompensate and make future decisions they typically would not. Mount Sinai researchers found that these different economic scenarios tap into fundamentally distinct forms of regret processing that are independently disrupted in an animal model used for the study of depression. Stress-susceptible mice were hypersensitive to type I regret while also insensitive to type II regret, unlike healthy animals. They also discovered that the function of the CREB gene, implicated in human depression and known to promote either resilience vs susceptibility to stress in two distinct brain regions, the medial prefrontal cortex (mPFC) or nucleus accumbens (NAc), regulated sensitivity to these two different types of regret.
Credit
Brian Sweis, Mount Sinai Health System
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