As the prism of our senses, the human brain has ways of refracting sensory input in defiance of reality.

This is seen, for example, in the placebo effect, when simple sugar pills or inert salves taken by unwitting subjects are seen to ease pain or have some other beneficial physiological effect. How the brain processes this faked input and prompts the body to respond is largely a mystery of neuroscience.

Now, however, scientists have begun to peel back some of the neurological secrets of this remarkable phenomenon and show how the brain can be rewired in anticipation of sensory input to respond in prescribed ways. Writing in the current issue (March 1, 2006) of the journal Brain, Behavior, and Immunity, a team of University of Wisconsin-Madison scientists reports the results of experiments that portray the brain in action as it is duped.

The new work, conducted by a team led by UW-Madison assistant professor of psychology and psychiatry Jack B. Nitschke, tested the ability of the human brain to mitigate foul taste through a ruse of anticipation. The work, conducted at the UW-Madison Waisman Center using state-of-the-art brain imaging techniques and distasteful concoctions of quinine on a cohort of college students, reveals in detail how the brain responds to a manipulation intended to mitigate an unpleasant experience.

“There is a potent impact to expectancy,” says Nitschke, who, with his colleagues, exposed 43 undergraduate subjects to potions of quinine, sugar water or distilled water while undergoing magnetic resonance imaging (MRI).

The subjects, Nitschke explains, were asked beforehand to associate a prescribed set of cues with a taste. A “minus sign” flashed through fiber optic goggles to subjects undergoing MRI, for instance, was to be an anticipatory signal that a liquid subsequently dripped into the mouth would have a very bitter taste. A “zero “cue corresponded with a neutral taste, and a “plus sign” with a pleasant, sugary taste.

The cues, according to Nitschke, were flashed to subjects just prior to the administration of a few drops of liquid. But in the study, the cues would not always match the taste they were said to presage.

His group observed that when subjects were given a cue that suggested the taste they were about to experience would be less bitter, the taste was perceived as such, and the regions of the brain that code tastes were activated less.

“When the subject sees the warning signal, portions of the brain activated by the misleading cue predict the decreased brain response to the awful taste,” Nitschke says. What’s more, “the (brain’s) response to the misleading cue will predict the subject’s perception of what the taste is going to be. The subject anticipates that the taste won’t be that bad, and indeed that’s what they report.”

In short, the new study shows how expectancy affects how humans perceive sensory input, and how events in the brain are directly related to those perceptions.

Importantly, by mapping how the brain anticipates an event and kicks in a placebo effect, Nitschke argues, scientists can begin to think about ways that knowledge could be used in clinical settings.

For Nitschke, who also practices as a clinical psychologist specializing in the treatment of depression and anxiety disorders, the new detailed insights into the power of anticipation could lead to better treatments for such conditions.

“The placebo operates through expectancy. In this study, we’ve taken the pill out of the picture. We’re just manipulating expectancies,” he says. “The results beg the question of what can we do to target anticipatory processes in our patients that might lead to better outcomes.”

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