Basal Ganglia Contribute to Learning, but Also Certain Disorders


by Kayt Sukel

January, 2007

Move over, hippocampus. The basal ganglia, a group of interconnected brain areas located deep in the cerebral cortex, have proved to be at work in learning, the formation of good and bad habits, and some psychiatric and addictive disorders.

Scientists have found that the neurotransmitter dopamine, already linked to the basal ganglia in movement disorders, also is important in learning via reward and punishment, as well as in disorders including schizophrenia and attention-deficit/hyperactivity disorder. This new understanding of how the basal ganglia work has revealed possible avenues for treatment of these and other disorders.

Moving Beyond Movement

Historically, the basal ganglia were thought to be mainly involved with aspects of motor control. “Patients with damage to the basal ganglia often have deficits in movement,” says Michael Frank, a neuroscientist at the University of Arizona. “The most obvious are tremors in patients with Parkinson’s disease.”

Earlier studies of Parkinson’s disease showed that, in patients with the disorder, dopamine-producing neurons in the basal ganglia area die, resulting in less dopamine transmission.

Thanks in part to more sophisticated neuroimaging techniques, researchers have found that the basal ganglia are active in far more than movement. “Although no one found gross physical lesions in people with obsessive-compulsive disorder or schizophrenia, often the basal ganglia were implicated by abnormal metabolic activity in the region,” says Ann Graybiel, a leading researcher in the function of basal ganglia at the Massachusetts Institute of Technology. “And now we’re finding that there’s razzle-dazzle plasticity in the basal ganglia during learning.”

Reward, Punishment, and Focus

Recent studies by numerous researchers show that the basal ganglia facilitate learning, with the neurotransmitter dopamine important to the process. One way that these behavioral routines are encoded is by the processing of reward information.

Wolfram Schultz, a principal research fellow at the University of Cambridge in England, studies how the brain processes such information. “When something is really good, you go back for it again,” he says. “One of the definitions of reward is that it is a learning function, that it can increase a particular behavior.”

Several studies have now confirmed that when an animal makes a decision that results in an unexpected reward, the dopamine neurons in the striatum—formed by the caudate nucleus and putamen—increase their rate of fire. Conversely, when a decision or action is met with a punishment, dopamine transmission decreases. More recent neuroimaging studies have provided indirect evidence that this phenomenon also occurs in humans.

But recent studies have shown that this dopamine-related learning function is not quite so simple. Humans seem to learn from both reward and punishment. Randall C. O’Reilly of the University of Colorado at Boulder, says that a subset of neurons in the basal ganglia actually become more active with the depleted dopamine transmission produced by punishment.

“We showed that Parkinson’s patients learned better than age-matched controls from negative feedback because this type of learning depends on a subset of neurons that become more active with less dopamine,” O’Reilly says. “Interestingly, this pattern reversed when these patients were given their medication, causing them to learn better from positive feedback.”

Given the complex circuitry of the basal ganglia, research has suggested that they also are a coordination system. Patients with Parkinson’s disease have difficulty coordinating not only movements but more complex cognitive tasks.

“The basal ganglia help you focus,” Frank says. “Think of multiplying 42 times 17. It’s the kind of information you can manipulate in your head but you have to break the problem into parts.”

It is likely that the dopamine released in the basal ganglia system communicates with the brain areas in the prefrontal cortex to allow people to pay attention to critical tasks, ignore distracting information, and update only the most relevant task information in working memory during problem-solving tasks.

The Force of Habit

Neurotransmitters released in the striatum communicate with the learning centers in prefrontal cortex. These neurotransmitters can encourage repeat performances of behaviors and lead to the creation of habits.

Graybiel’s group trains rats on maze tasks and records the firings of groups of neurons in the striatum as the rats learn, forget, and then relearn the task. “Nerve cells are interested in everything,” says Graybiel. “But as rats get good at running the maze, lots of cells in motor striatum tend to fire at the beginning and the end of the run instead of the whole thing. This network in the basal ganglia has ‘chunked’ the behavior.”

Chunking, at its simplest, is the organization of information into specific associated groupings. Graybiel hypothesizes that the basal ganglia system helps the cortex to chunk learning into habits and routines to help the brain more quickly access stored information.

Graybiel and colleagues also found a group of nerve cells in the striatum that are not firing in the same way as the others. “These nerve cells don’t care about the [maze] task at all,” she says. “And yet, there is some electrical activity in those cells that shuts down when the animal learns the task.”

She hypothesizes that these cells work in an attenuating manner by helping the brain tune out information that is not critical to the task at hand: “Perhaps these neurons turn down the noise so you get this beautiful set of expert neurons that know exactly what to do. After all, when you get in the car and press the accelerator, your whole body knows what to do without thinking. It’s a well-oiled procedure that effortlessly comes out of your behavioral repertoire.”

Psychiatric Disorders and Addiction

The basal ganglia are involved not only with Parkinson’s disease but also an array of psychiatric and addiction disorders. Neuroimaging studies have shown abnormal activation of the striatum and other areas of the basal ganglia in patients with schizophrenia, attention-deficit/hyperactivity disorder (ADHD), Tourette’s syndrome, obsessive-compulsive disorder (OCD), and anorexia nervosa, as well as drug addiction.

O’Reilly and Frank have recently started looking at the basal ganglia in learning in patients with ADHD and OCD. Their research has shown that patients with ADHD, who generally show an overall decrease of dopamine in the basal ganglia, show not only impaired learning with positive feedback but also coordination deficits.

“More relevant to the classic ADHD symptoms, reduced dopamine also leads to distractibility by impairing the activation of the prefrontal areas that are important for staying on task,” O’Reilly says.

The common symptoms of OCD, however, may be caused by inappropriately processed reward information, a loop in which certain thoughts and actions are reinforced in an unhealthy way. “One idea about OCD is that it is triggered by a runaway positive feedback loop in the basal ganglia, which drives the dopaminergic reinforcement of obsessive thoughts and actions,” O’Reilly suggests.

Anorexia nervosa is another disorder that may be affected by this faulty positive feedback loop. “Disturbances involving the neural circuits between the cortex and basal ganglia, similar to those found in patients with OCD, may also be present in anorexic patients,” says Dr. Paolo Cavedini, a psychiatrist at the San Raffaele Scientific Institute in Milan.

A recent positron emission tomography (PET) study by Drs. Walter Kaye and Guido Frank of the University of Pittsburgh Medical School showed overactive dopamine receptors in the basal ganglia of anorexic patients. They hypothesize that this overactivity may underlie anorexic patients’ obsessive feelings about food as well as provide rewardlike dopamine releases when they engage in starving behaviors, potentially perpetuating those behaviors into habit.

Research also has implicated the basal ganglia in drug addiction. “Dopamine release is overactive in drug addiction,” Schultz says. “It’s nothing but a reward process spinning out of control.” This increased reward-based dopamine release reinforces addiction with increased use.

Promising Avenues of Treatment

This deeper understanding of how the basal ganglia operate provides researchers with several promising avenues for treatment for psychiatric disorders and disease. “If we can understand how dopamine neurons code reward information and know where they project, then we have a solid basis of knowledge to create better treatments,” Schultz says.

Tailored pharmacological treatments targeted specifically to neurons and receptors in the basal ganglia would likely have more benefit than those currently on the market. “As we move towards really understanding how the brain works, to understanding better the underlying basis of why these problems occur, we can then target a very specific medication,” Frank says, adding that the research also could lead to behavioral therapies and new learning strategies.

“Kids with ADHD learn more from rewards when they are on their medication,” Frank says. “So it follows that if you have a kid with this disorder and he’s frustrated with a problem-solving task, it’s better to ask him to do things that are rewarding. Otherwise, he might not learn.”