William T. Newsome, an HHMI investigator at Stanford University School of Medicine and one of the acknowledged leaders in the field of visual neurosciences during the past few decades, has expanded on leads uncovered by Hubel and Wiesel—such as their discoveries of different types of brain cells specialized to respond to specific kinds of visual signals transmitted from the retina. Newsome credits recent progress to the field's move away from anesthetized laboratory animals to the more flexible and realistic system of humanely using alert, unsedated monkeys, whose brain activity can be recorded while they respond to visual cues and perform carefully designed tasks.

When he explains his work to engineers, Newsome says, "I tell them we have monkeys looking at visual displays and 'telling' us what they see. Our goal, in turn, is to go into the brain with tiny microelectrodes and attempt to understand how the brain 'sees' by studying the electrical activity of single neurons one by one. It seems outrageous in principle—somewhat like taking the back off a Cray supercomputer and understanding how it works by measuring the activity of single resistors and capacitors one by one—but the amazing thing is that we can really make progress this way."

The "single most exhilarating moment" of his research career, says Newsome, came in 1989 when he and Daniel Salzmann, a Stanford medical student at the time, showed that they could do more than just locate the neurons responsive to incoming visual signals—they also could artificially stimulate them. The neurons in question were cells that respond exclusively to motion in a particular direction. When Newsome stimulated cells that respond to upward motion while the animal was watching a downward-moving target, the monkey's reaction indicated that it "saw" the target moving in the opposite direction.

"This was proof of principle," says Van Essen, "that you can go into a collection of neurons and with these moderately sized jolts of electricity actually produce subtle and precisely measurable changes in what the animal perceives."

		Stephen Lisberger has discovered that visual pursuit—tracking an object in motion—is not a reflexive action, but is actually a "complex voluntary behavior that comprises many components." The eye and brain must choose which moving object to track, estimate the direction and speed of the target with respect to the moving eye, and command the eyeball to rotate along the object's path at the correct speed. Photo: Paul Fetters

More recently, Newsome has been interested in the processes that transform perceptual information into decisions for action. "Exactly where and how the sensory signals are evaluated to reach a categorical decision about an appropriate behavioral response is still quite mysterious," he says.

Moving from perception to decision is something like electing a nation's president: Millions of voters have many different views of the candidates, but, when the votes are in, one bloc carries the day. Similarly, millions of neurons represent visual inputs in various parts of the brain, but only one or a limited number of actions can be taken.

For example, if a monkey is presented with visual targets moving in random directions but overall in a downward direction, how does the animal's brain "pool," or process, the cavalcade of information coming from different motion-detecting cells? "We realized there has to be some decision mechanism that takes the sensory evidence and reaches a judgment about whether the overall direction is up or down," says Newsome. "The monkey has to put all of his eggs in one basket."

Some of Newsome's newest work incorporates research on the brain's reward system—a field of study called "neuroeconomics." This name reflects the fact that the expectation of a reward influences an individual's decision about taking action—a fisherman, for example, throws a line into a part of the river that has produced catches before. "The question," says Newsome, "is whether we can measure emotional arousal, manipulate those responses, show that they have effects on choice and behavior, and track the underlying neural signals."

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