In Romo's experiments, a monkey receives a gentle stimulus to a finger and then another one a split-second later. The monkey's task is to compare them and press a button indicating which stimulus it perceives as stronger. To accomplish this, the monkey has to retain a sensation of the first poke in very short-term "working memory" while it takes note of the second stimulus and compares the two. So far, Romo has shown that the touch signals are initially received and encoded in electrical activity patterns in the primary somatosensory cortex. These patterns are sent on to the secondary somatosensory cortex, and then to the prefrontal cortex of the brain's frontal lobes. It's here that the second wave of touch signals are combined with memories of the initial stimulus (which came less than a half-second later).

"This comparison creates a decision signal that determines which stimulus the monkey is going to report as stronger," comments Romo. "We are seeing how neurons are interacting with each other to shape behavior." His next challenge is to determine whether the signals are processed by one brain area after another, or whether they somehow all work on the information simultaneously, controlled by some "master" controller.

Although monkeys do not approach the sophisticated brain function of humans, they can be trained in tasks that illuminate different aspects of human decision making. Other animal models have other advantages: they are inexpensive, reproduce quickly, and large numbers of them can be used in studies. Decision behavior has been identified, for example, in the roundworm Caenorhabditis elegans and the common fruit fly Drosophila, which also lend themselves to genetic manipulation as a means of singling out nerve circuits of interest.

Rockefeller University's Bargmann has devised minuscule mazes, coaxing C. elegans through them with food rewards (and deterrents). Because every single gene and nerve cell in this worm has been mapped—its nervous system, for example, contains just 302 neurons—Bargmann can trace decision-making functions, if any, to specific nerve cells.

She and her colleagues have looked for such behavior, asking whether the worms can learn to associate a particular choice with a pleasant or disagreeable sensation. The researchers designed their miniature mazes using technology from the microfluidics field, with small channels projecting out like the arms of a starfish: the end of each arm contained tasty bacteria to lure the worms in their direction.

Then came the switch: the scientists infected the worms with disease-causing bacteria that made them sick. As a result, their previously preferred maze channels were now associated with an unpleasant feeling and the worms avoided them. "So, signals from nerves that make serotonin [a chemical messenger that triggered the sick feeling] converged with signals from the olfactory neurons [which sensed the bacteria to which they were initially attracted]," says Bargmann, "and the worms associated one with the other."

If not a full-fledged decision, this avoidance was at least a choice, Bargmann notes. In new research, she is studying how changing conditions influence the foraging behavior of roundworms. In their hunt for food, the worms search a region more thoroughly when food is expected nearby than when they think food is unlikely; it's as if the roundworms are doing the numbers and playing the odds.

Rebecca Yang has been attempting to learn more about the decision-making capacities in fruit flies by using little more than some Drosophila food, a video camera, and her own ingenuity.

Yang, a postdoc in the laboratory of HHMI investigators Lily and Yuh Nung Jan at the University of California, San Francisco, studies the genetic basis of choice behaviors. While observing pregnant fruit flies in miniature plastic chambers she designed, Yang noticed that the females spent considerable time searching their environment for a suitable spot to lay their eggs.

She concluded that the Drosophila females considered both the consistency and taste of the medium on which they walked before committing their future offspring to a specific site. "After all, selecting an appropriate site to lay its eggs is presumably the ultimate decision a fly mother has to make, as the consequences of such decisions are likely to have a significant impact on the reproductive success of the species," says Yang.

In one experiment, she placed pregnant fruit flies in a small plastic chamber with a sweet substance on one half of the floor and a bitter compound on the other. Would the flies choose one side over the other for egg laying? Surprisingly, the mothers-to-be shunned the good-tasting medium and favored the bad-tasting side to deposit their eggs.

"Initially, I assumed that maybe I had accidentally switched the flavors," recalls Yang. "So I checked by licking them!"

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