Seinfeld, The Simpsons spark same nerve circuits. (The Brain's Funny Bone).

Neuroscientists--normally a reserved group--were laughing at William M. Kelley's presentation. He wasn't upset, however. The researcher had just shown the scientists a clip from the sitcom Seinfeld to illustrate how his group investigates the brain's response to humor.

With the aid of Jerry Seinfeld and his friends, as well as the animated characters of the cartoon The Simpsons, Kelley and his colleagues have found that different brain regions spark with activity when a person gets a joke versus when he or she reacts to it.

"Humor is a significant part of what makes us unique as human beings," says Kelley, a neuroscientist at Dartmouth College in Hanover, N.H. He presented his group's brain-imaging data last week at the Society for Neuroscience meeting in Orlando, Fla.

Despite humor's appeal, few researchers have studied its neural basis. Last year, a British group described the brain activity of people listening to real jokes and puns and to nonsense versions.

Seeking a more natural study of humor, Kelley's group initially had a dozen or so self-professed fans of Seinfeld watch an episode--the one in which George seeks a baldness remedy from China. Meanwhile, a magnetic resonance imaging machine continuously scanned their brains for nerve-cell activity. Ultimately, the scientists analyzed the data for the few seconds before and after each joke, as indicated by the show's laugh track.

As a participant viewed something funny, regions of the brain's left hemisphere--the posterior temporal cortex and inferior frontal cortex--initially crackled with activity. Neuroscientists have previously associated these regions with resolving ambiguities, says Kelley.

A few seconds later, presumably as the person responded to the humor, brain regions called the insula and amygdala became active across both hemispheres of the brain. The insula plays a role in emotional sensations, while researchers usually link the amygdala to memory processing. "You tend to recall the funny bits" of a sitcom, notes Kelley.

Studying the brain's response to humor is a challenge, and Kelley's effort is innovative, says Ralph Adolphs of the University of Iowa College of Medicine in Iowa City. "It seems that actually watching a full-length episode [of a sitcom] is going to elicit humor in a more realistic, intense fashion than if you just read or hear a punch line in a lab," says Adolphs.

Concerned that the laugh track on Seinfeld influenced study volunteers' reactions, Kelley and his colleagues repeated their experiment with an episode of The Simpsons, which doesn't use recorded laughs. "We observed a near-identical pattern of [brain] activation," says Kelley.