(L) Study Shows Working Memory Is Driven By Prefrontal Cortex And Dopamine (2012)

December 18, 2012

redOrbit Staff & Wire Reports – Your Universe Online

One of the unique features of the human mind is its ability re-prioritize its goals and priorities as situations change and new information arises. This happens when you cancel a planned cruise because you need the money to repair your broke-down car, or when you interrupt your morning jog because your cell phone is ringing in your pocket.

In a new study published in the Proceedings of the National Academy of Sciences (PNAS), researchers from Princeton University say that they have discovered the mechanisms that control how our brains use new information to modify our existing priorities.

The team of researchers at Princeton’s Neuroscience Institute (PNI) used functional magnetic resonance imaging (fMRI) to scan subjects and find out where and how the human brain reprioritizes goals. Unsurprisingly, they found that the shifting of goals takes place in the prefrontal cortex, a region of the brain which is known to be associated with a variety of higher-level behaviors. They also observed that the powerful neurotransmitter dopamine – also known as the “pleasure chemical” – appears to play a critical role in this process.

Using a harmless magnetic pulse, the scientists interrupted activity in the prefrontal cortex of the participants while they were playing games and found they were unable to switch to a different task in the game.

“We have found a fundamental mechanism that contributes to the brain’s ability to concentrate on one task and then flexibly switch to another task,” explained Jonathan Cohen, co-director of PNI and the university’s Robert Bendheim and Lynn Bendheim Thoman Professor in Neuroscience.

“Impairments in this system are central to many critical disorders of cognitive function such as those observed in schizophrenia and obsessive-compulsive disorder.”

Previous research had already demonstrated that when the brain uses new information to modify its goals or behaviors, this information is temporarily filed away into the brain’s working memory, a type of short-term memory storage. Until now, however, scientists have not understood the mechanisms controlling how this information is updated.


Together with the study’s lead author Kimberlee D’Ardenne of Virginia Tech as well as fellow researchers Neir Eshel, Joseph Luka, Agatha Lenartowicz and Leight Nystrom, Cohen and his team devised a study that allowed them to scan the brains of their subjects while they played a game. The game required the participants to press specific buttons depending on different visual cues. If they were shown the letter A before the letter X, they were asked to press a button labeled “1”. However, if they saw the letter B before the X, then they had to press a button labeled “2”.

In an earlier version of the task, however, participants were first asked to press the 1 button when they saw X regardless of which letters preceded it. Thus the A and B rule that was introduced in the second round served as the ‘new information’ that the participant had to use in order to update their goal of deciding which button to press.

Examining the fMRI afterwards, the researchers found increased activity in the right prefrontal cortex when participants were completing the more complex task that involved making a decision between two buttons based on the visual cues A and B. This was not the case, however, for the simpler version of the task.

Cohen’s results corroborate the findings of his own previous research project from 2010 which used a different scanning method to measure the timing of brain activity.

In the current study, the research team also delivered short magnetic pulses to the prefrontal cortex in order to confirm that this is in fact the brain region involved in updating working memory. Basing the timing of the pulse on the previous study, the scientists delivered the magnetic pulse at the precise moment when they believed the right prefrontal cortex should be updating memory. They found that if they delivered the pulse exactly 0.15 seconds after the participants saw the letters A or B, they were unable to hit the correct button. They were thus able to use the magnetic pulse to disrupt the memory-updating process.

“We predicted that if the pulse was delivered to the part of the right prefrontal cortex observed using fMRI, and at the time when the brain is updating its information as revealed by EEG, then the subject would not retain the information about A and B, interfering with his or her performance on the button-pushing task,” explained Cohen.


In the last part of the experiment, Cohen’s team wanted to test their theory that the neurotransmitter dopamine is responsible for tagging new information and important for updating working memory and goals as it enters the prefrontal cortex. Dopamine is a naturally occurring chemical that is known to play key roles in a number of mental processes like the ones that involve motivation and reward.

To do this, the team again used the fMRI to scan a region called the midbrain that is densely populated with specialized nerve cells – known as dopaminergic nuclei – that are responsible for producing most of the brain’s dopamine signals. The researchers tracked the activity of these dopamine-emitting nerve cells while participants performed the tasks and found a significant correlation between brain activity in these areas and in the right prefrontal cortex.

“The remarkable part was that the dopamine signals correlated both with the behavior of our volunteers and their brain activity in the prefrontal cortex,” explained Cohen.

“This constellation of findings provides strong evidence that the dopaminergic nuclei are enabling the prefrontal cortex to hold on to information that is relevant for updating behavior, but not information that isn’t.”

Professor David Badre of Brown University, a specialist in cognitive, linguistic and psychological sciences, believes that the work of Cohen’s team represents a large step forward in science’s attempt to understand how our brain updates its working memory.

Though not directly involved with the study, Badre wrote a commentary on the study that was published online in early November by PNAS. In it he stated that: “The mechanisms by which the brain achieves an adaptive balance between flexibility and stability remain the basis of much current investigation in cognitive neuroscience. These results provide a basis for new investigations into the neural mechanisms of flexible, goal-directed behavior.”