Neuroscientist William Newsome is captivated by how the "three pounds of goo" inside our craniums is able to respond appropriately to the world around it, creating as it does a rich mental life.
To understand the brain, Newsome pokes inside it. He does this, remarkably, in awake monkeys, by placing tiny electrodes inside their brains and mapping the brain's painless responses to visual stimuli.
"We were the first people to train monkeys to 'tell' us what they were seeing, and then to manipulate what they were seeing by altering the activity of specific circuits within the visual cortex," Newsome says. Monkey and human brains are similar enough that the neural mechanisms he finds are likely at play in human perception and action as well.
Newsome became interested in the burgeoning research on the brain's visual system as a graduate student. He had read about the work of David Hubel and Torsten Weisel, at Harvard, who had identified part of the visual system, called the primary visual cortex, that allowed monkeys to perceive edges or the forms of objects.
Hubel and Weisel, who won the 1981 Nobel Prize in Physiology or Medicine for their work, projected lights onto a screen in front of anesthetized monkeys [whose eyes were propped open and protected with contact lenses] and listened [with electrodes] to the activity of single brain cells. The ability to study the electrical activity of brain cells in response to visual stimuli controlled by the experimenter was radical and exciting to Newsome.
Newsome's excitement led him to also work with anesthetized monkeys, and in his doctoral work he found that regions outside the primary visual cortex are also involved in processing visual information. His interest grew when he became aware of the pioneering work of Edward Evarts, at the National Institute of Mental Health, who was using electrodes in awake animals to study the brain's motor system. By recording the electrical activity of motor cortex neurons while trained animals used their arms in specific ways, Evarts was able to understand in unprecedented detail how the brain plans and executes movements.
"Once you could train an awake monkey to perform simple cognitive tasks, it became possible to map in the brain where information relevant to task execution was being processed; this opened up the study of memory, attention, decision making, planning, and other types of cognitive activities," Newsome explains.
Newsome moved to the National Eye Institute for a postdoctoral fellowship to learn how to do brain research with awake monkeys, a method he has continually adapted. At first, he trained a monkey to move his eyes to report the direction of dots moving on a computer screen. If the monkey moved his eyes correctly, he received a reward. Electrodes implanted in the brain recorded the activity of cells responding to the different directions of motion.
Using that method, Newsome showed that cells in the middle temporal visual area of the cerebral cortex respond to different directions of moving dots. Distinct populations of cells respond to upward, downward, leftward, and rightward motions.
Later, after his move to Stanford University, Newsome designed a different type of experiment: Instead of using an electrode to "listen" to the traffic of electrical activity among nerve cells, he used it to stimulate specific cells in the middle temporal area that respond to one direction of motion—upward, for example. At the same time, he showed a monkey dots moving in the downward direction and "asked" him what he saw. The monkey reported seeing upward motion by moving his eyes up. Artificial activation of the "up" cells had actually changed the monkey's judgment of the motion in the visual stimulus!
Although the results showed that certain middle temporal cells provide the signals that monkeys use to judge direction, Newsome acknowledges it is impossible to know what the monkey subjectively thinks. Does he see upward motion (even though it is downward)? Does he think he sees downward motion but reports upward motion, without knowing why? Newsome is so curious about these perceptions that he sometimes wishes he could replicate the experiment with electrodes in his own brain.
Newsome's interest in how the brain detects motion has expanded into an interest in how perception is translated into a decision. "In the mid 1990s, I realized we were poised for the first time in the history of neuroscience and neurophysiology to start looking at decision-making mechanisms in the brain in a rigorous scientific way," he says.
By the late 1990s, Newsome had found cells in the parietal region that could predict how the monkey would move its eyes before the animal did so. "It was the first example of crossing the brain's sensory circuitry to the decision-making circuitry to the motor behavior circuitry," Newsome says. Additional research from his laboratory revealed that the superior colliculus, another region in the brain stem, also acts in decision making to move the eyes.
"Multiple parts of the brain apparently are involved in creating behavior, in this case, decisions to move the eyes," Newsome says.
Although visual cues help us make decisions about how to act, other factors also determine our behavior, Newsome explains. Fishermen, he points out, decide where to fish based on past success in catching a fish at a particular point in a stream. "Our brains have evolved to estimate probabilities," Newsome says, "Our decisions are influenced by our judgments of value relative to the risk."
More recently, Newsome has been studying the neurophysiological basis behind these value-based decisions. These "neuroeconomic" studies, Newsome says, involve the brain's estimation of a return on an investment. If scientists rig an experiment so that monkeys are more likely to receive a reward if they move their eyes in one direction, in time, monkeys learn to respond to these probabilities by moving their eyes in that direction. The estimation of mathematical probabilities underlying this behavior is quite sophisticated.
Newsome has recently found that the same parietal cells that integrate visual motion information for making decisions are also used when monkeys base their decision on reward probabilities. But his research group does not believe that the reward probabilities are actually calculated in the parietal cortex. Rather, other parts of the brain tell the parietal cells what to do, and Newsome is trying to identify those regions and the mechanism that is used to calculate the probabilities. He also is beginning to explore altruistic behavior. Economic and altruistic behaviors probably follow different circuitry in the brain, Newsome suggests. They all, however, must converge on the motor pathways in the brain for an action to occur.
"[Albert] Einstein can do math in his head, but unless he writes down an equation, by moving the muscles in his hand, it doesn't amount to much," Newsome says.
While Newsome's research shows that neuroscientists are now beginning to illuminate the brain mechanisms that underlie sophisticated cognitive behaviors, he believes that the surface has been barely scratched in understanding higher brain function. Newsome remains dedicated to this "grand enterprise"—to understand how our brains enable the mental functions that make us uniquely ourselves.