Experts have long known that we have a virtually unlimited capacity to store new long-term memories. Yet there’s a limit on how much information we can cram into our working memory.
In studying the prefrontal cortex’s functions, Miller and others are coming closer to finally explaining this contradiction. And by solving this riddle, we may find ways to get beyond those limits.
Someday, Miller believes, he’ll be able to make us all smarter.
Building the Picture
Much of what we know about how neurons allow animals to make sense of their surroundings began with experiments performed on the visual cortex of animals by David Hubel and Torsten Wiesel. As postdoctoral students at Baltimore’s Johns Hopkins University in the 1960s, they set out to solve a long-standing mystery: What happens in the brain when we see objects and shapes?
Every one of us has about 100 billion neurons, separated by gaps called synapses. Neurons talk to each other by passing signals across these spaces. When one neuron’s signal is strong enough, it causes the neuron on the other side of the synapse to fire an electrical spike. When that second neuron fires, it passes messages to all the other neurons it’s connected to, which can cause those neurons to fire. This sequential firing of neurons allows us to think, to move — and to see.
Hubel and Wiesel inserted tiny, pin-shaped microelectrodes directly into a cat’s visual cortex to measure the activity there. By projecting angled lines onto the surface of the animal’s retina, they demonstrated that each neuron in this thin sheet at the back of the head has a distinct function.
It was as if the brain was on autopilot, primed to notice repetition without any active effort to do so, even when that repetition had no meaning.
Some fired with the greatest intensity in response to lines at specific angles, while others fired at angled lines moving in a specific direction. It is the consecutive firing of these individual, specialized neurons, each responsible for a specific detail in a picture or pattern, they argued, that helps us build complex images in our mind’s eye.
Their work was so impressive within the field that it earned them the Nobel Prize in Physiology or Medicine in 1981.
As it happened, Miller entered college at Kent State University the same year — though back then, Miller dreamed of becoming a doctor.
That quickly changed when he started working in a neuroscience lab.
“The moment I first dropped an electrode into a slice of brain and heard all these neurons firing away like a thunderstorm, I was hooked,” Miller recalls.
As a Princeton University graduate student, Miller studied the inferior temporal cortex, a patch of neurons slightly forward of the visual cortex. Scientists had demonstrated this was the region that knits together a unified image from all the complex individual components Hubel and Wiesel identified. Then it starts the “higher level” processing of the outside world.
By the time Miller earned his Ph.D. in 1990, he was asking the questions that would later define his career: What happens in the inferior temporal cortex after a unified picture emerges? How do our brains tell us what it means?
Miller tried to answer those questions while working in the lab of National Institute of Mental Health neuroscientist Bob Desimone. Miller was looking for neurons that fired only when an animal spotted an item it was storing in short-term memory. Miller and Desimone trained animals to hold a single image in mind — such as an apple — and release a lever when that picture reappeared on a screen.
If the animal remembered the first picture it saw and released the lever, a drop of delicious juice would roll down a tube and into its cage.
The pair noticed that certain parts of the animal brain were inherently sensitive to repetition — regardless of whether it translated into a valued juice reward. Some neurons fired when animals saw a second banana or second image of trees. It was as if the brain was on automatic pilot, primed to notice repetition without any active effort to do so, even when that repetition had no meaning.
But the pair also discovered a second type of firing pattern. When the animal spotted a picture it was actively holding in his memory — hoping for a juice reward — not only did different neurons fire, those neurons fired far more intensely.
“Something was switching the volume to make these neurons fire, more or less, depending on the nature of the memory,” Miller says. “That got me wondering. Who’s turning up or down the volume?”
Turn It Up
Scientists have suspected that the prefrontal cortex plays a key role in high-level cognition since the case of Phineas Gage. On Sept. 13, 1848, Gage, who worked in railroad construction, was setting an explosive charge with a tamping iron when the gunpowder detonated, rocketing a metal rod up through the roof of his mouth, into his left frontal lobe and through the top of his skull. The rod landed 75 feet away, coated in pieces of Gage’s brain.