Rethinking Thought

The pathways that send signals darting across our brains could hold the key to understanding psychiatric conditions, according to Helen Barbas. Photo by Paula Lerner

As we go about our daily lives, our brains are flooded with information. Our eyes take in everything around us. We are bombarded by sounds and smells. We feel the temperature of the air, the clothes against our skin, minor aches and pains. And the outside world isn’t the only source of data: the limbic system, a network of relatively primitive structures deep within the brain, provides emotional and experiential context for this sensory input.

Processing all of this information is the prefrontal cortex, the foremost area of the cerebral cortex. Like an air-traffic controller, the prefrontal cortex sorts and synthesizes huge amounts of input, separating the essential from the nonessential to determine what actions need to be taken. In BU Sargent College’s Neural Systems Laboratory, Professor Helen Barbas and her colleagues are studying the communication system that enables this filtering to take place. They are mapping the circuitry of the brain from the level of neurons and neurotransmitters to the system of pathways that link the many discrete areas of the prefrontal cortex to one another and to other brain areas. “These areas act in concert to help us solve the problems of everyday life, from small to large,” Barbas says. “Each receives input from other areas in a system of pathways. We are trying to understand how these pathways are organized—and how they may be disrupted in disease.”

The proper functioning of these pathways allows us to stay focused enough to follow the thread of a conversation or even a train of thought, for example, by tuning out the chatter in a noisy coffee shop so we can focus on the person we’re conversing with. These pathways also aid in decision-making, enabling us to formulate a quick and appropriate response to a stimulus—an ability which is particularly important when we must identify and respond to some kind of danger. Barbas offers an example: You are walking down a poorly lit street at night and see something moving up ahead. How do you react?

In determining what action to take, your brain must figure out what the movement means. To do so, your prefrontal cortex needs to resolve the emotional danger signal of a potential threat lurking in the bushes with the rational knowledge that what you are seeing is most likely only some shrubbery blowing in the wind. “It used to be thought that thinking and emotions were separate, but we know from the pathway studies that they are not. They are very intricately synthesized in the prefrontal cortex,” Barbas says.

Her research is illuminating how the brain carries out this kind of decision-making via the intricate network of pathways connecting highly specialized brain areas. For example, the orbitofrontal cortex is a heavily connected region of the prefrontal cortex that synthesizes data from the brain’s sensory centers with contextual information from the amygdala, the brain’s emotional center. Also linked to this pathway is another prefrontal area, the anterior cingulate cortex, a part of the limbic system that is richly connected with prefrontal areas known to be involved in determining where our attention should be focused at a given moment. Should you continue to daydream about your weekend plans, or should you be concentrating on that shadow in the dark?

“We’re beginning to see how the brain can direct our attention to something that becomes important and then, if that changes, to shift attention to something else,” Barbas explains. That flexibility is key: Once the brain determines that the shadowy figure is likely just a bush blown by the wind, healthy people with this circuitry intact can relax and continue with their walk.

But when something goes wrong with these neural pathways, even ordinary decision-making can become a difficult task. “You have activation in these brain areas in anxiety disorders—in people who have phobias, panic disorders, PTSD,” Barbas says. “If those pathways are partially disconnected, the activity of the amygdala, which has to do with emotion, might be unchecked. So you have a disconnect about the significance of the stimulus, and you’re anxious all the time.”

Her laboratory’s study of this and other neural pathways holds the promise of offering insight into a number of psychiatric conditions, from anxiety disorders to autism and schizophrenia. New information about how the neurons communicate—what neurotransmitters they use, whether the neurons are inhibitory or excitatory—can be used in the development of pharmacological or other treatments targeting specific systems affected in psychiatric disorders such as depression or obsessive-compulsive disorder. The research can also help clinicians rethink established treatments. For example, older people who have trouble following conversations amid background noise, as in a crowded restaurant, are often given hearing aids. But Barbas’s research suggests that the problem may not be in their ears at all. Rather, prefrontal cortex dysfunction accompanied by the mild cognitive decline associated with aging can cause people to have difficulty filtering the signal from the background noise.

“Every time we design an experiment, we have the big picture in mind,” says Basilis Zikopoulos, a research assistant professor in the Neural Systems Laboratory. “So we’re thinking, ‘How does a specific function affect the brains of schizophrenics? How are repetitive behaviors manifested in autistic people?’”

It is becoming clear that our higher brain functions are not based in isolated locations of the cerebral cortex but instead require the coordinated activity of many areas processing information simultaneously. The research of Barbas and her colleagues is providing fundamental insight into how this cooperation works and how clinicians might respond to the many diseases in which the brain’s communication system is disrupted.

Take a video tour of the brain’s highways, and BU’s Neural Systems Lab, with Helen Barbas here.

Additional reporting contributed by Paula Lerner.

A version of this article was published in the fall 2010 issue of Inside Sargent.