2015: OUT OF SIGHT: NEUROPLASTICITY AND VISION

AWARDEES: Torsten Wiesel & David Hubel

SCIENCE: Neuroplasticity

FEDERAL FUNDING AGENCIES: National Institutes of Health, Air Force Office of Scientific Research

Research can be unpredictable. Sometimes a small mistake during already odd-sounding research can lead to major scientific advances. There are few better examples than when two neurophysiologists, Drs. David Hubel and Torsten Wiesel, were studying how cats’ brains responded as they were shown a moving dot or a spot of light on a screen, and accidentally pushed a glass slide a bit too far across their projector. That small error kicked off a wave of discoveries that have led to extraordinary progress in our understanding of how mammals’ brains process the world around them—progress that has opened entirely new avenues in brain research, helped untold numbers of children grow up with better vision, and is now influencing the development of machine vision technology.

In the 1950s and ‘60s, the National Institutes of Health and the Air Force Office of Scientific Research supported the work of Drs. Hubel and Wiesel, who were studying how the visual centers in cats and monkeys process simple stimuli. Across a 20-year collaboration, beginning at The Johns Hopkins University School of Medicine and continuing at Harvard Medical School, the pair would go on to make extraordinary discoveries that eventually earned them a Nobel Prize.

But their breakthroughs began with a simple, fortuitous accident during their earliest experiments with cats —a glass slide pushed too far across an overhead projector.

The researchers had begun with what was known: light stimulates light-sensing receptor cells in the retina of the eye, and different receptor cells respond to stimuli in different parts of the retina’s visual field. But Hubel and Weisel were studying nerve cells, or neurons, in higher-functioning areas of the brain not previously studied, which they found frustratingly unresponsive to their simple stimuli—small spots of light or a black dot on a clear glass slide projected onto a screen. Then, as the cats watched, one of the researchers accidentally moved the glass slide a little too far, bringing its faint edge into view. And suddenly those same neurons began firing like mad!

Over the course of the next several months, Hubel and Wiesel made the first crucial steps forward in our understanding of visual processing. They found that particular neurons in the visual cortexes of cats and monkeys—the areas in their brains responsible for processing visual information—didn’t respond to simple points of light, but rather to lines, and in particular, lines and contours with specific orientations. Some neurons responded to horizontal lines, others to vertical, and still others to orientations in between. In addition, they found neurons responding to signals from both eyes, but usually one or the other would dominate.

Dr. David Hubel

Over subsequent years, Hubel and Wiesel refined their understanding, mapping the visual centers of their feline and primate subjects with increasing precision. They found the visual cortex consisted of narrow columns of cells organized by eye preference and response to orientation—which they termed “ocular dominance columns” and “orientation columns.” Combined they formed an elegantly organized functional map of neurons that could process the complex input arriving from both of the animal’s eyes.

Soon after moving from Johns Hopkins to Harvard, with their newfound understanding of the brain’s organizational structure in hand, Hubel and Wiesel sought to address a perennial question in biology: nature or nurture?

Dr. Torsten Wiesel

Hubel and Wiesel began by studying the brains of newborn animals with no visual experience. They found that their feline and primate subjects were born with that elegant functional map already in place in their visual cortices. They found neurons that would respond only to oriented stimuli and that responded to stimulation of both eyes. They concluded that nature provides the neural connections necessary for these two basic response properties.

What then is the role of nurture for the normal development of the brain? It was known from medical clinics that children born with cataracts suffer from severe visual deficits even after their opaque lens is removed a few years after birth. With the physical blockage gone why would this be the case? Hubel and Wiesel had shown that the necessary neural connections should be present at birth.

The researchers addressed this question by studying the impact of raising kittens and monkeys from birth with one eye covered and the other left open. They found that the animal behaved as if it was blind in the previously covered eye, just like in a child after cataract surgery. The cause of this loss of vision turned out to be that neurons in the visual cortex no longer responded to stimulation of the deprived eye but only vigorously to the normal eye. The elegant patterns of ocular dominance the researchers had seen in healthy animals disappeared, with the one dominant eye taking over almost the entire visual cortex. Over a series of experiments, they demonstrated that the brain could literally wire or rewire itself in response to external input (or lack thereof)—a phenomenon known as neuroplasticity—and that this ability seemed to fade with age.

Almost immediately, this realization of the importance of early stimulation to the wiring of the visual cortex translated from the lab to the clinic, where doctors were working to treat children born with cataracts and other eye impairments. With Hubel and Wiesel’s new understanding, doctors began treating children as early as possible, with much better outcomes.

Drs. Wiesel and Hubel in 1981.

Hubel and Wiesel were pioneers of the visual system, exploring the physiology behind visual perception in animals, thereby teaching us much about how our own minds work. This is critical for today’s computing technology. For some tasks, like computing and factoring large numbers, silicon has our “wetware” beat handily, but for the complex tasks like visual processing, machines are only beginning to catch up to the human brain. This is no small matter; teaching computers how our minds work is big business. The “machine vision” market is projected to grow to tens of billions of dollars in the next few years. Hubel and Wiesel’s work is extremely important to this burgeoning field.

From a slip of the hand while cats watched images on a screen have come better treatments for childhood vision disorders and teaching computers how to process images—this is a powerful example of how science can advance society in the most unexpected ways.

 

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