Study lifts veil on brain’s executive function

The “CEO” in your brain appears to be concerned more about the consequences of your actions than how hard they are to produce.

That is the implication of a detailed study of the neuronal activity in a critical area of the brain, called the anterior cingulate cortex (ACC), published in the Oct. 3 issue of the journal Science. It is the latest in a series of experiments that are beginning to lift the veil on the brain’s “executive function” – how it monitors its own performance so that it can regulate behavior. Many cognitive scientists feel that the ACC may be at the heart of this higher order system.

Brown, JoshuaJoshua Brown, WUSTL research associate in psychology in Arts & Sciences, is co-author of a study of the brain’s executive function published in the Oct. 3 issue of the journal Science.

He offers the comments below to explain his role in the research and its relation to other ongoing research at Washington University.

We’ve all experienced the satisfaction of a goal achieved, or an unexpected windfall like finding a $20 bill lying in the street. On the other hand, we’ve all had the feeling of disappointment when, despite our best efforts, things don’t work out as we intended. It may be a relationship, or it may be trying to catch a bus or a plane. Sometimes we just know things won’t work out before the failure actually happens, and sometimes a failure is totally unexpected. How do we know that something isn’t going to work out as we intend, or that it didn’t work out? How do we recognize success as a result of effort versus an unexpected windfall?

We investigated a specific area in the brains of macaque monkeys called the anterior cingulate cortex (ACC) and found individual cells that process this information.

The ACC isn’t the only part of the brain that processes these kinds of signals, but the finding is important, because the ACC plays a key role in disorders such as schizophrenia and obsessive-compulsive disorder in humans.

Other research here at Washington University suggests how the ACC uses these signals to help people control their actions. For example, if a task is difficult or the task requirements change frequently, the ACC seems to help people slow down and be more careful. Similarly, we have evidence from other investigators that the ACC may drive someone to try a different problem-solving approach altogether when the current approach isn’t working. Previous work from other labs suggested that too much ACC activity leads people to try to correct a problem that doesn’t exist, such as repeatedly checking to see whether the lights were turned off at night even when you already know they are turned off. This is a fundamental characteristic of obsessive-compulsive disorder. On the other hand, if the ACC doesn’t function properly as it should, it can diminish a person’s ability to recognize their own mistakes and correct them or at least acknowledge them. A lot of evidence suggests that this kind of dysfunction is a key factor in mental illnesses such as schizophrenia. The significance of this work is that it reveals how certain brain cells in these areas actually process and represent signals corresponding to awareness of the consequences of one’s own actions.

Another exciting aspect of this study is that as we learn how the brain cells process this information, we at Washington University are also working to combine that with the tremendous speed of today’s computers and actually program a computer to simulate how the brain processes information and monitors its own behavior, using the technology of neural networks. This may reveal more about how the brain functions improperly in neuropsychiatric disorders such as obsessive-compulsive disorder and schizophrenia.

Researchers found the ACC responds to discrepancies between a person’s intentions and what actually occurs when actions are performed, providing new support for one popular theory on its function. But they did not find evidence of neural activity in the ACC when the brain is forced to change course in mid-action, as predicted by another popular theory.

“The broad question is, ‘How does the brain monitor and control intentional actions.’ Our research indicates that it does so by monitoring the consequences of such actions, not the actions themselves,” says Jeffrey Schall, Ingram Professor of Neuroscience and director of Vanderbilt’s Center for Integrative and Cognitive Neuroscience. He directed the study with doctoral student Shigehiko Ito, post-doctoral fellow Veit Stuphorn, and Joshua Brown, a research associate at Washington University.

Brown adds that “the ACC isn’t the only part of the brain that processes these kinds of signals, but this finding is important because the ACC plays a key role in disorders such as schizophrenia and obsessive-compulsive disorder in humans. Other research here at Washington University suggests how the ACC uses these signals to help people control their actions.”

The researchers investigated the ACC through detailed studies measuring the response of hundreds of individual neurons in the ACC of macaque monkeys as the animals performed a task that required self-control. Macaques serve as the primary animal model for higher cognitive function.

The monkeys were trained to look at a visual target displayed in different positions on a computer screen, unless they received a stop signal. They were taught not to look at the target after receiving such a signal. The monkeys’ eye movements were tracked with enough precision so that they could be correlated with neuronal activity. The monkeys were trained by rewarding them with squirts of juice when they correctly followed instructions.

By requiring the monkeys to inhibit a movement after their brain had begun preparing to execute it, Schall and his colleagues created situations that isolated different types of neural signals. By recording in the ACC while the monkeys responded to these situations, the researchers successfully identified neurons that signaled discrepancies between intentions and actions, what the researchers refer to as errors.

“The elegance of this paper is that they were able to sort out different cognitive components or behavioral components that might be driving neural activity in the cingulate,” says Tomas Paus of McGill University, a neuroscientist who was not involved in the study but also investigates this part of the brain.

This methodology allowed the researchers to determine whether activity in the anterior cingulate signaled that the action deviated from what the monkey had intended or signaled that the consequences of the action differed from what he anticipated. “We had a few trials where he did the right movement but we didn’t give him juice. We found that many of these neurons also fired following the absence of reinforcement,” says Schall. In these trials the monkey’s action was correct but the consequence was unexpected. If the ACC were monitoring the actions alone, the neurons would not have responded.

The researchers also found that there was an appreciable time lag in the responses of the neurons in the anterior cingulate compared to that of neurons in another part of the frontal lobe, the supplementary eye field – an area that Schall and coworkers had previously shown to contain neurons signaling success, errors and degree of difficulty in eye-tracking tasks.

“This delay makes it unlikely that the purpose of the error detection that we discovered in the ACC is to correct actions as they take place,” said Schall.

An influential theory about ACC function has suggested that the brain is sensitive to the conflict that arises when tasks are too complex and subjects are being asked to do more than they can without making errors. Schall’s earlier work on the supplementary eye field found neurons signaling this conflict, but they failed to find neurons signaling conflict alone in the ACC. This observation is at odds with certain functional brain imaging studies in humans.

The anterior cingulate cortex, shown in red, may help the brain monitor and control intentional actions.

These results do not mean that the ACC does not also monitor conflicts, Schall cautions. Virtually all of the human measurements have been made using tasks that involve button pushing or other manual tasks, rather than eye movements. The ACC has no direct connections to the areas of the brain that control the eyes but it does have direct connections to those that control the muscles in the hands and arms. So hand movements may be controlled differently than eye movements. There is also the possibility that the ACC in humans may function differently than it does in monkeys.

“These results are telling us that things are not as simple as some people have thought,” says Paus, who adds that we won’t really be able to tie these signals back to cognitive functions until researchers can go beyond the current stage of simply recording brain activities to that of actually inducing changes in brain activity – either through the administration of drugs or electrical stimulation to small groups of neurons – and observing the changes in behavior that result.

The research was funded by grants from the National Institute for Mental Health, the National Eye Institute, McKnight Endowment Fund for Neuroscience and the Deutscheforschungs Gemeinschaft.