Brain research has come a long way since Vernon Mountcastle began his pioneering work during the 1950s.
Advances in diagnostic imaging techniques alone have brought vast improvements to clinical medicine, says Mountcastle, who will be honored next week by the National Academy of Sciences for his lifetime of work in the neurosciences.
"You can see the brain, in three dimensions," Mountcastle says. "It's so dramatic. You can follow the blood flow and you can determine whether there are lesions in vessels or lesions in the brain. It's a whole new world."
Yet, the brain still harbors a huge reservoir of mysteries, a gulf of unknown and exciting territories that may take another century to fully traverse, he says.
For example, scientists are far from understanding how the brain accomplishes the higher functions, such as consciousness and advanced analytical thinking, says Mountcastle, who influenced the creation of the Krieger Mind/Brain Institute at Johns Hopkins in 1990.
More than 30 years ago, Mountcastle discovered a fundamental truth about brain physiology: that cells performing like functions are connected in intricate "modules" arranged in vertical columns. The finding was controversial at the time because scientists had thought that brain cells, or neurons, were arranged only in horizontal layers.
Although his work pertained specifically to the portion of the brain that handles the sense of touch, other scientists have since discovered the same modular design throughout the cerebral cortex--sometimes commonly referred to as gray matter--the center of intelligence, perception and motor skills.
His later work, during the 1970s, shed light on populations of neurons responsible for higher functions, such as how the brain is able to locate and focus attention on an object in space, directing the motor commands necessary to reach out and touch or grasp something.
"He's been sort of like a Daniel Boone, who came back and said, 'There's a big river,' and that kind of thing," says Kenneth Johnson, scientific director of Mind/Brain. "Then a legion of people came along behind him. And now there are very detailed pictures of those areas. And there are people now using the kinds of methods that he pioneered in the '70s."
Mountcastle's groundbreaking work has earned him a rare honor. On April 27 he will receive the National Academy of Sciences' Award in the Neurosciences, which is given only once every three years for extraordinary achievement in the field. The award, which carries a $15,000 cash prize, recognizes Mountcastle for a lifetime of research, a career spent exclusively at Johns Hopkins that began with his admission to medical school here in 1938.
"I had the most fantastic experience," says Mountcastle, 79, professor emeritus of neuroscience. "I felt that I was welcomed into a society of scholars. For example, we never got any grades. I learned later that there was a very detailed grading of everything. But you were never told. And that produced a fantastic atmosphere. You never felt that you were competing with another student; you were competing with the subject."
After interning in surgery, he spent three years as a surgeon for the U.S. Naval Amphibious Forces during World War II. Mountcastle returned to Hopkins as a postdoctoral fellow in 1946 and never left.
His work in brain physiology led him into a new kind of research: By training monkeys to perform certain tasks and then using electrodes to pinpoint the specific neurons carrying out those tasks, he and other scientists were able to identify specific groups of brain cells directly involved in sensory perception.
Moreover, because monkey and human brains are so similar, scientists were able to match up the corresponding neural circuits in people, making major strides in human brain research.
"He pioneered a new type of science," says Michael Steinmetz, an associate professor of neuroscience who studied under Mountcastle, taking over his lab when he retired in 1992.
The strategy is to first analyze how people perceive or respond by giving them a series of non-invasive tests and recording the results. For example, the human visual system might be studied by testing how people perceive changing patterns or images on a computer screen. Then the actual neural mechanisms involved in the perception can be learned by having monkeys perform the same tests while electrodes are used to probe their brains.
"He was a major force in the development and refinement of methodologies that have made it a standard technique for studying the brain," Steinmetz says.
It was an important step beyond the more conventional method of brain research, in which only broad geographic regions of the brain are mapped and linked to certain functions.
"Just through the volume of neurons that he studied, he established a whole new standard by which critical areas of the brain would have to be studied," Johnson says.
To really understand how the brain works, scientists need to identify and study specialized pockets of neurons, each containing several million brain cells, compared to the brain's total circuitry of about 100 billion neurons.
Even today's advanced imaging techniques can't bring those smaller units into focus. Methods such as nuclear magnetic resonance, functional magnetic resonance imaging and positron emission tomography scanning measure changes in blood flow, oxygen consumption and other basic activities in brain regions. They reveal important information about which parts of the brain are active while it performs certain functions, such as remembering, perceiving or commanding motor movements.
"They sort of tell you that this area lights up, or that that area lights up, but that's kind of like saying that a football crowd all shouts 'hurrah' at the same time," Johnson says.
The imaging devices don't tell scientists anything about the precise details of neuronal performance, which are central to brain function.
"Most descriptions you see about the brain are metaphorical statements: 'The motor cortex controls movement. ...' Well, that doesn't tell you much, except for the geography," Mountcastle says.
He was among the first scientists to directly probe the neural mechanisms involved in the senses, the perception of objects in space and how the brain is able to focus visual attention on specific objects. Mountcastle was director of the Department of Physiology at the School of Medicine from 1964 to 1980, when he founded the Philip Bard Laboratories of Neurophysiology, which were incorporated into the Department of Neuroscience.
Scientists in the labs concentrated on research dealing with vision, the sense of touch and the brain mechanisms involved in sensation and perception in those fields. Then, about a decade ago, then Johns Hopkins President Steven Muller held a university-wide meeting to discuss plans for the future.
"A lot of suggestions were made, and then I said, 'You ought to strike big, establish an independent brain institute,'" Mountcastle says.
"He called me into his office on Monday morning, and he said: 'I think that's a grand idea, but it has to be at Homewood.'"
When the institute was formed at Krieger Hall, it was built around the Bard Labs, which were moved from the School of Medicine to the Homewood campus. Consequently, Mind/Brain scientists are faculty members of the Department of Neuroscience, and they teach in the School of Medicine.
They also are involved in the undergraduate program in neuroscience, a growing field that is attracting experts from many disciplines. Because of this, an arrangement was approved in February through which Mind/Brain now reports to the dean of Arts and Sciences. Appointments will be made through both Arts and Sciences and the School of Medicine.
"There is virtually no science that's not relevant to the study of the brain," Mountcastle says. "In this brain research institute there are two physicists, others trained in physiology, others in biomedical engineering."
The multidisciplinary nature of the research underscores the importance of establishing an independent institute; many of the researchers would not fit into a standard science department, but their services mesh perfectly in brain research.
"Brain science is extremely important, independently from its importance in medicine," Mountcastle says. "It provides the opportunity to understand ourselves, to understand how our brain functions, how we remember, how we generate emotions, etc."
By continuing brain research, he says, "we will come to understand ourselves a great deal better than we do now. Many people in neuroscience feel very strongly about that."