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Proper evaluation of the good and bad outcomes of a choice is a primary survival instinct, referred to as “rational” decision-making in humans.According to evidence revealed by scientists from the Massachusetts Institute of technology, this capacity becomes vulnerable following chronic stress, leading to wrong choices and high-risk behaviors.
One example of such cost-benefit conflict situations is deciding between a high paying job with long hours and a lower-paying position that allows for more free time.The researchers from MIT suggest that making decisions in such a situation – referred to as a cost-benefit conflict – is tremendously influenced by chronic stress.The paper appeared in Cell on November 16.
In their mice study, the scientists found that stressed animals were more likely to go for the high-risk, high-payoff option rather than the low-risk one.They also discovered that this abnormal decision making is caused by impairments of a specific brain circuit and that rational behavior could be restored by manipulating this circuit. “The exciting thing is that by performing this basic science, we identified a microcircuit of neurons in the striatum that could be manipulated to reverse the effects that stress has on this type of decision making,” says senior author Professor Ann Graybiel of MIT.Graybiel is also a member of the McGovern Institute for Brain Research.
If the same could be replicated in humans, the research team believes that it could help patients with disorders such as depression, anxiety, and addiction, which often go hand in hand with poor decision making. “To us, this is very promising, but we are also aware that so far these experiments have been conducted in rats and mice only,” noted Prof.Graybiel.
In the recent study, the MIT experts built on research they carried out two years back.In 2015, they first revealed the brain circuit involved in making decisions that surround cost-benefit analysis.The circuit starts at the prefrontal cortex (which is responsible for controlling moods) and extends to form clusters of neurons called striosomes, located in the striatum, a region that influences motivation, habit formation, and reward reinforcement.
In the 2015 study, the researchers trained mice to run through a maze in which they had to choose between two options that created a cost-benefit conflict situation.One possibility involved getting to highly concentrated chocolate milk, which rodents like, along with bright light, which they find irritating.The other arm of the maze was dimmer, but the chocolate milk was less concentrated.By using a technique called optogenetics to inhibit the connection between the cortical neurons and striosomes, the researchers discovered that the rodents’ preferences could be transformed from lower-risk with lower-payoff to high-risk/high-cost.
As for the subsequent study, the scientists conducted a similar experiment, only without optogenetic manipulations.Instead, they stressed the mice over a short period every day for two weeks.
Normal rats and mice that haven’t experienced stress were observed to go for the maze arm with dimmer light and weaker chocolate milk about half the time.And as the researchers increased the concentration of chocolate milk on the darker option, more animals began choosing that side.
When chronically stressed rodents were subjected to the same circumstances, however, they continued to choose the bright light/better chocolate milk option even as the concentration of chocolate milk was substantially increased on the dimmer side.This behavior was the same one that the scientists noted in rodents that had their prefrontal cortex-striosome circuit altered optogenetically. “The result is that the rodent ignores the steep cost and chooses the high reward,” said lead author Alexander Friedman, a scientist at McGovern Institute.
The MIT scientists suppose that this circuit integrates information about the good and bad aspects of possible choices, aiding the brain in making a rational decision.Ideally, when the circuit is turned on, the neurons in the prefrontal cortex activate particular neurons referred to as high firing interneurons, which in turn suppress striosome activity.
When the animals are subjected to chronic stress, these circuit dynamics get disrupted, causing the cortical neurons that inhibit the striosomes to fire too late.The striosomes then become overexcited.This phenomenon is what results in abnormal decision making. “In a way, this prior exposure to chronic stress influences the integration of good and bad,” Graybiel said, “It is as if the animals had lost the ability to balance between excitation and inhibition to settle on reasonable actions.”
The researchers discovered that once this stress-induced shift occurred, the effects stuck around for months.
They were able to restore normal behavior by making use of optogenetics to stimulate the high-firing interneurons, consequently suppressing the striosomes.This finding suggests that the prefrontal-striosome circuit doesn’t get damaged during stress, and is susceptible to manipulations that could restore normalcy in human patients. “It is possible that in the future we could target these interneurons to restore the excitation-inhibition balance,” says Friedman.