Site detectives: Cabeza, left, and LaBar Photo: Jim Wallace

Take a journey back into the most vivid memories of your life. For me, there's the terrifying childhood attack by a deranged rooster; the gut-roiling public embarrassment of a forgotten speech; and, ah yes, the sweet, transporting taste of my first kiss. Such memories don't just benignly percolate up in our minds, like the mundane recall that we need to buy bread at the market. Rather, they envelop our consciousness in a nerve-tingling fog of sensory remembrance.

It's no surprise, then, that memories packing an emotional punch are not imprinted on the brain using routine memory circuits. Rather, our terrifying traumas and our delicious delights spark activity in a small but potent almond-shaped structure called the amygdala, buried deep in our neural gelatin. This little neural nugget abets our very survival--charging memories with an emotional force that compels us to avoid lunatic fowl, practice our speeches, and look for love in all the right places.

But this little clump of brain tissue also can smother our lives in the torment of post-traumatic stress disorder (PTSD), the corrosive dread of phobias, or the black dog of depression. The medical impact of traumatic disorders is immense. One in six soldiers in Iraq reports that his or her experience has produced major depression, anxiety, or PTSD, according to a study by the U.S. Army. Some mental-health experts estimate that at least 100,000 veterans of that war will need mental-health treatment. Here at home, our efforts to escape the anxiety provoked by the stresses of daily life have been prodigious, as evidenced by the 142-million prescriptions written in this country in 2003 for Prozac, Paxil, Zoloft, and other antidepressants.

First "Sad Gene"

The profound importance of emotional memory has impelled Duke neuroscientists Kevin LaBar and Roberto Cabeza to make it their scientific mission to understand the complexities of its neural machinery. In a wide variety of experiments, they expose volunteer subjects to stimuli designed to provoke an emotional response--tear-jerking scenes from movies, for example, or mild shocks to the wrist. Then, using magnetic resonance imaging (MRI), they examine how and, more important, where the brain responds when the subjects are asked to recall what happened. Their efforts will not only contribute to better treatments for anxiety disorders, but also could yield a deeper understanding of how emotional memories influence, and sometimes rule, our lives.

Routine memories are stored in the brain with the aid of the wishbone-shaped hippocampus, which filters the stream of sensory data flooding into our brains and helps imprint that data as lingering memories. But a jolt of danger--and the accompanying blast of adrenalin into our bloodstream--activates both of the amygdalae attached to the tips of the hippocampus. These structures somehow stamp the indelible imprint of emotion on the resulting memories. The scientific mystery being tackled by LaBar and Cabeza is how the amygdalae blaze such permanent and vivid memory pathways in the brain's circuitry.

Getting into people's heads, particularly into the brain's depths where the amygdalae nestle, has been among the biggest challenges for researchers like LaBar and Cabeza, both of whom are on the faculties of Duke's Center for Cognitive Neuroscience and the department of psychological and brain sciences.

Neuroscientists first explored emotional memory by studying patients with specific damage to the amygdalae or surrounding structures from accident or disease. "But studies of such patients are very difficult, given that the locations of the lesions are not always clear; and finding patients with lesions in particular brain areas is a matter of chance," says Cabeza. Even if neuroscientists did find the right patients, he says, "the brain undergoes adaptive changes to such lesions. So it's difficult to know whether any changes we measure are due to the lesion itself or adaptation of the brain to the lesion."

Finally, he says, brain lesions might not directly affect a structure such as the amygdala that is critical to a particular function. Instead, they might only block a neural pathway serving that structure--just as blocking a highway might not directly affect the operation of a roadside hamburger stand, but only block the pathway by which hungry customers can reach it. So, scientists studying the effects of such a lesion--or diners looking for a hamburger--could be misled by a lack of activity in the structure to think it's closed for business.

The real revolution in exploring brain function came with the development of functional magnetic resonance imaging (fMRI), which allows researchers to direct harmless magnetic fields and radio waves into the brain to produce detailed scans of brain activity while the subject is performing a specified mental task. These scans can reveal differences in magnetic properties between oxygenated blood and deoxygenated blood. Because regions of the brain that are in heavy use during mental tasks trigger influxes of oxygenated blood into the region, they can be readily distinguished on fMRI scans.

Thus, researchers can get an invaluable, albeit indirect, measure of brain activity in specific regions such as the amygdalae. "Some people compare the impact of brain imaging on cognitive neuroscience to the impact of the telescope on astronomy," says Cabeza. "In both cases, a new instrument has allowed scientists to see things they couldn't see before."