Brain circuit that controls decisions that induce high anxiety identified
Date:
May 28, 2015
Source:
Massachusetts Institute of Technology
Summary:
Some decisions arouse far more anxiety than others. Among the most anxiety-provoking are those that involve options with both positive and negative elements, such choosing to take a higher-paying job in a city far from family and friends, versus choosing to stay put with less pay.
Some decisions arouse far more anxiety than others. Among the most anxiety-provoking are those that involve options with both positive and negative elements, such choosing to take a higher-paying job in a city far from family and friends, versus choosing to stay put with less pay.
MIT researchers have now identified a neural circuit that appears to underlie decision-making in this type of situation, which is known as approach-avoidance conflict. The findings could help researchers to discover new ways to treat psychiatric disorders that feature impaired decision-making, such as depression, schizophrenia, and borderline personality disorder.
“In order to create a treatment for these types of disorders, we need to understand how the decision-making process is working,” says Alexander Friedman, a research scientist at MIT’s McGovern Institute for Brain Research and the lead author of a paper describing the findings in the May 28 issue of Cell.
Friedman and colleagues also demonstrated the first step toward developing possible therapies for these disorders: By manipulating this circuit in rodents, they were able to transform a preference for lower-risk, lower-payoff choices to a preference for bigger payoffs despite their bigger costs.
The paper’s senior author is Ann Graybiel, an MIT Institute Professor and member of the McGovern Institute. Other authors are postdoc Daigo Homma, research scientists Leif Gibb and Ken-ichi Amemori, undergraduates Samuel Rubin and Adam Hood, and technical assistant Michael Riad.
Making hard choices
The new study grew out of an effort to figure out the role of striosomes — clusters of cells distributed through the the striatum, a large brain region involved in coordinating movement and emotion and implicated in some human disorders. Graybiel discovered striosomes many years ago, but their function had remained mysterious, in part because they are so small and deep within the brain that it is difficult to image them with functional magnetic resonance imaging (fMRI).
Previous studies from Graybiel’s lab identified regions of the brain’s prefrontal cortex that project to striosomes. These regions have been implicated in processing emotions, so the researchers suspected that this circuit might also be related to emotion.
To test this idea, the researchers studied mice as they performed five different types of behavioral tasks, including an approach-avoidance scenario. In that situation, rats running a maze had to choose between one option that included strong chocolate, which they like, and bright light, which they don’t, and an option with dimmer light but weaker chocolate.
When humans are forced to make these kinds of cost-benefit decisions, they usually experience anxiety, which influences the choices they make. “This type of task is potentially very relevant to anxiety disorders,” Gibb says. “If we could learn more about this circuitry, maybe we could help people with those disorders.”
The researchers also tested rats in four other scenarios in which the choices were easier and less fraught with anxiety.
“By comparing performance in these five tasks, we could look at cost-benefit decision-making versus other types of decision-making, allowing us to reach the conclusion that cost-benefit decision-making is unique,” Friedman says.
Using optogenetics, which allowed them to turn cortical input to the striosomes on or off by shining light on the cortical cells, the researchers found that the circuit connecting the cortex to the striosomes plays a causal role in influencing decisions in the approach-avoidance task, but none at all in other types of decision-making.
When the researchers shut off input to the striosomes from the cortex, they found that the rats began choosing the high-risk, high-reward option as much as 20 percent more often than they had previously chosen it. If the researchers stimulated input to the striosomes, the rats began choosing the high-cost, high-reward option less often.
Paul Glimcher, a professor of physiology and neuroscience at New York University, describes the study as a “masterpiece” and says he is particularly impressed by the use of a new technology, optogenetics, to solve a longstanding mystery. The study also opens up the possibility of studying striosome function in other types of decision-making, he adds.
“This cracks the 20-year puzzle that [Graybiel] wrote — what do the striosomes do?” says Glimcher, who was not part of the research team. “In 10 years we will have a much more complete picture, of which this paper is the foundational stone. She has demonstrated that we can answer this question, and answered it in one area. A lot of labs will now take this up and resolve it in other areas.”
Emotional gatekeeper
The findings suggest that the striatum, and the striosomes in particular, may act as a gatekeeper that absorbs sensory and emotional information coming from the cortex and integrates it to produce a decision on how to react, the researchers say.
That gatekeeper circuit also appears to include a part of the midbrain called the substantia nigra, which has dopamine-containing cells that play an important role in motivation and movement. The researchers believe that when activated by input from the striosomes, these substantia nigra cells produce a long-term effect on an animal or human patient’s decision-making attitudes.
“We would so like to find a way to use these findings to relieve anxiety disorder, and other disorders in which mood and emotion are affected,” Graybiel says. “That kind of work has a real priority to it.”
In addition to pursuing possible treatments for anxiety disorders, the researchers are now trying to better understand the role of the dopamine-containing substantia nigra cells in this circuit, which plays a critical role in Parkinson’s disease and may also be involved in related disorders.
The research was funded by the National Institute of Mental Health, the CHDI Foundation, the Defense Advanced Research Projects Agency, the U.S. Army Research Office, the Bachmann-Strauss Dystonia and Parkinson Foundation, and the William N. and Bernice E. Bumpus Foundation.
Story Source:
The above story is based on materials provided by Massachusetts Institute of Technology. The original article was written by Anne Trafton. Note: Materials may be edited for content and length.
Journal Reference:
- Alexander Friedman, Daigo Homma, Leif G. Gibb, Ken-Ichi Amemori, Samuel J. Rubin, Adam S. Hood, Michael H. Riad, Ann M. Graybiel. A Corticostriatal Path Targeting Striosomes Controls Decision-Making under Conflict. Cell, 2015 DOI: 10.1016/j.cell.2015.04.049
Decision Making Process: Optogenetics Uncover Brain Network Involved In Emotional Choices
May 28, 2015 12:13 PM By Susan Scutti
During approach-avoidance conflicts, our brains access a specialized network involving the striosomes to help us make difficult and emotional decisions. Photo courtesy of Shutterstock.
You need more money, so you want a high-paid job, yet you know that would mean lots of hard work and probably late nights and weekends, too. Whenever a goal is both desirable and disagreeable, we experience a psychological conflict known as approach-avoidance. During these conflicts, our brains access a specialized network that helps us make difficult and emotional decisions, say MIT neuroscientists. This neural circuit begins and ends with striosomes.
What exactly are striosomes? These cell clusters are distributed through the striatum — a large brain region beneath the cerebral cortex that is involved in coordinating our movements to our motivations. Yet, striosomes are so small and lie so deep inside the brain, researchers find it difficult to image them with an fMRI. For this reason, they remain an undiscovered territory of the brain.
Previous studies from the lab of Dr. Ann Graybiel, an MIT professor and member of the McGovern Institute for Brain Research, identified regions of the brain’s prefrontal cortex that project to the striosomes. Because these regions helped process emotions, the researchers suspected the entire brain circuit might be related in some way to emotion. Importantly, in monkeys, decisions made during approach-avoidance conflicts selectively activate a subset of neurons in a medial prefrontal region that appears to correspond to the human zone targeting the striosomes.
Wanting to better understand this circuit and its function, the MIT team designed a series of experiments.
Discovering the Brain
The researchers studied rats as they performed five different types of behavioral tasks. The rodents’ choices were relatively simple in four of the settings, yet in one, the researchers constructed a more complex approach-avoidance scenario. During this maze-running task, the rats had to choose between two options: one that included strong chocolate (which they like) and a bright light (which they don’t like) and another option with dimmer light but weaker chocolate.
If we humans were to confront a similar approach-avoidance choice, we most likely would experience anxiety, which would influence our “cost-benefit analysis” and ultimately influence our decision.
Observing the response of the rats, the researchers added another dimension to these five revealing tasks. During some of the maze runs, the scientists turned cortical input to the rats’ striosomes on and off by shining light directly on the cortical cells — a neuromodulation method known as optogenetics.
By illuminating the rats’ decision-making processes, the researchers discovered the circuit connecting the cortex to the striosomes played a role during the approach-avoidance task, but in the four other tasks, the striosomes did not influence the decision-making process at all.
These findings suggest the striatum (and the striosomes in particular) may act as a mental gatekeeper, the researchers say. The striosomes absorb sensory and emotional information coming from the cortex and then integrate it to produce a decision.
This same circuit appears to include the substantia nigra, a midbrain region which has dopamine-containing cells. When activated by the striosomes, the researchers speculate, these substantia nigra cells produce a long-term effect on decision-making attitudes.
Ultimately, this research suggests new possibilities for relieving anxiety and other mood or emotional disorders. By better understanding the role of the dopamine-containing substantia nigra cells, the gang from MIT believe they also may learn how to ease the symptoms of Parkinson’s disease and related disorders.
Source: Friedman A, Homma D, Gibb LG, et al. A Corticostriatal Path Targeting Striosomes Controls Decision-Making under Conflict. Cell. 2015.
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