An MRI

Seeing things they couldn't see before has led Cabeza and LaBar to ingenious new ways of exploring and monitoring brain activity. Their latest experiments, reported in the June 2004 issue of the journal Neuron, revealed for the first time that the brain's emotional centers affect or "modulate" the function of the memory centers as memories of emotion-laden events are being formed.

In the experiments, they slid volunteers into MRI machines and scanned their brains while showing them pictures that evoked both positive (romantic scenes, sports victories) and negative (aggressive acts, injured people) emotions. They also showed neutral pictures of buildings or scenes of routine shopping. After the scanning sessions, the researchers measured the emotional impact of the images by testing how well the participants remembered them. In their subsequent analysis of the brain scans, Cabeza and LaBar found that the emotional and memory regions interacted more during the formation of emotional than of neutral memories. The findings provide firm evidence that the amygdala modulates the function of the hippocampus and other memory regions, Cabeza said in the report. "Other studies have focused on the general enhancing effects of emotion on memory," he wrote. "But this study provides the first direct evidence for the modulation hypothesis in humans."

In an earlier discovery, published in the Proceedings of the National Academy of Sciences in 2002, LaBar and other colleagues used fMRI studies to show that fear-producing stimuli travel along separate brain pathways from tasks, such as driving, that require concentration. The two streams join in the prefrontal cortex--the higher processing area of the brain--and at that point can interfere with each other. "These findings are important because diseases that involve distractability, from Alzheimer's to attention-deficit disorder, always seem to involve the prefrontal cortex," says Gregory McCarthy, director of the Duke-UNC Brain Imaging and Analysis Center (BIAC). "Understanding the biology of this will speed efforts to develop drugs or therapies that may influence these systems."

In ongoing experiments, the researchers are studying the effects of "fear-conditioning." In one study, LaBar and his colleagues teach subjects to associate the image of a particular type of square with a mild shock to the wrist. Then the scientists add some type of social stress, such as asking the subjects to deliver a public speech. The following day, they bring the subjects back into the laboratory and test their physiological response to the square--increased perspiration caused by stress--to determine how well they have retained the fear response. "In psychiatry, it's known that stress can impair learning and memory," says LaBar. "This experimental approach gives us a way to study the role that the amygdala plays in mediating stress responses and how stress can aid or impair learning and memory."

Phobias constitute a far more general fear of specific situations, and LaBar has invented a way to mimic in the laboratory the development of these fears, which are what researchers call "context-dependent." In this case, the researchers use a specific setting to create the context. They place subjects in a small room where they teach them to associate the image of a square of a certain size and color with a mild shock. Keeping the subjects in that same room, the researchers proceed to "extinguish" the association by showing the square without administering the shock.

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The researchers then remove the subjects from the "shock" room and, after a short period, either return them to it or place them in an entirely different room. They then test how quickly the subjects recover the unpleasant association of the square with the shock--a measure of their created "phobia" of the room.

"We've found that the person only recovers this 'phobia' if the shock happens in the same room," says LaBar. If the shock happens in a different room, he says, the subject is no longer fearful. "This context-specific recovery of fear is thought to be important for phobias."

As anyone knows who has ever tried to get through a workday while in a blue funk, mood can also affect mental functioning. So, LaBar and his colleagues have also devised experiments to test how mood affects emotional, as well as cognitive, processing. First, the researchers establish a mood by showing subjects scenes from a happy or a sad movie--Bambi, Titanic, Shadowlands, and Death of a Salesman, among others. Then, while scanning the subjects' brains, the researchers give them a counting task, at the same time presenting them with emotional "distractors"--glimpses of sad clips that elicit an emotion, or neutral clips as a control. "We know little about how longer-lasting mood states can modulate the fast response to emotional stimuli in the amygdala," says LaBar. "In this study, we're looking at amygdala activation, as well as at how people perform cognitively in such situations." Studies like this can give important insights into how mood can affect cognitive function, and thus how people might be expected to perform tasks when they are under the added burden of sadness, he says.

Within his broader studies of memory's intricate machinery, Cabeza is also zeroing in on the processing of emotion, studying, for example, its function in depressed people. "There is some evidence that, while depressed people don't have a general memory deficit, they have difficulty remembering pleasant events and a better memory for negative events," says Cabeza. This tendency could help feed their depression, he adds. Cabeza is collaborating with Duke psychologist Timothy Strauman and his colleagues to investigate how well people who are depressed remember pictures depicting sad events, in comparison with people who are not depressed.

The researchers show their subjects pictures depicting sad events, while at the same time scanning their brains to measure differences in activity in the amygdala and connected memory structures. "A particularly exciting possibility is that we'll be able to combine drug treatments with such studies, to measure how effectively they change brain activity associated with depression," says Cabeza. "We might even be able to detect changes in the brain before they show up in behavior."

Aging also alters the processing of emotion, says Cabeza, and so he and his colleagues are planning fMRI studies of brains of elderly people to explore the activity of their emotional circuitry. "There is some evidence that regions critical to emotional processing might be affected in forms of pathological aging such as Alzheimer's disease," he says. "So, it may be possible to analyze activity in these regions using fMRI to detect early signs of Alzheimer's."