Studying actions and emotions through research on brain wiring

Deanna Barch and her colleagues are trying to map connections in the human brain

Deanna Barch talks fast, as if she doesn’t want to waste any time getting to the task at hand, which is substantial. She is one of the researchers at St Louis, Washington University working on the first interactive wiring diagram of the living, working human brain.

To build this diagram she and her colleagues are doing brain scans and cognitive, psychological, physical and genetic assessments of 1,200 volunteers. They are more than a third of the way through collecting information. Then comes the processing of data, incorporating it into a three-dimensional, interactive map of the healthy human brain showing structure and function, with detail to one and a half cubic millimeters, or less than 0.0001 cubic inches.

Dr Barch is explaining the dimensions of the task, and the reasons for undertaking it, as she stands in a small room, where multiple monitors are set in front of a window that looks onto an adjoining room with an MRI machine, in the psychology building. She asks a research assistant to bring up an image. “It’s all there,” she says, reassuring a reporter who has just emerged from the machine, and whose brain is on display.

And so it is, as far as the parts are concerned: cortex, amygdala, hippocampus and all the other regions and subregions, where memories, fear, speech and calculation occur. But this is just a first go-round. It is a static image, in black and white. There are hours of scans and tests yet to do, though the reporter is doing only a demonstration and not completing the full routine.

Each of the 1, 200 subjects whose brain data will form the final database will spend a good 10 hours over two days being scanned and doing other tests. The scientists and technicians will then spend at least another 10 hours analysing and storing each person’s data to build something that neuroscience does not yet have: a baseline database for structure and activity in a healthy brain that can be cross-referenced with personality traits, cognitive skills and genetics. And it will be online, in an interactive map available to all.

Helen Mayberg, a doctor and researcher at the Emory University School of Medicine, who has used MRI research to guide her development of a treatment for depression with deep brain stimulation, a technique that involves surgery to implant a pacemaker-like device in the brain, is one of the many scientists who could use this sort of database to guide her research. With it, she said, she can ask, “how is this really critical node connected” to other parts of the brain, information that will inform future research and surgery.

The database and brain map are a part of the Human Connectome Project, a roughly $ 40 million five-year effort supported by the National Institutes of Health. It consists of two consortiums: a collaboration among Harvard, Massachusetts General Hospital and UCLA to improve MRI technology and the $30 million project Dr Barch is part of, involving Washington University, the University of Minnesota and the University of Oxford.

Barch is a psychologist by training and inclination who has concentrated on neuroscience because of the desire to understand severe mental illness. Her role in the project has been in putting together the battery of cognitive and psychological tests that go along with the scans, and overseeing their administration. This is the information that will give depth and significance to the images. She said the central question the data might help answer was, “How do differences between you and me, and how our brains are wired up, relate to differences in our behaviors, our thoughts, our emotions, our feelings, our experiences?” 

The Human Connectome Project is one of a growing number of large, collaborative information-gathering efforts that signal a new level of excitement in neuroscience, as rapid technological advances seem to be bringing the dream of figuring out the human brain into the realm of reality. 

New techniques

Optogenetics is one new technique that has been transformative. It uses light to turn on different parts of the brain in laboratory animals to open and shut modified genes. Powerful developments in microscopy made possible movies of brain activity in living animals. A modified rabies virus can target one brain cell and mark every other cell that is connected to it.

“There is an explosion of new techniques,” said R Clay Reid, a senior investigator at the Allen Institute, who recently moved there from Harvard Medical School. “And the end isn’t really in sight,” said Reid, who is taking advantage of just about every new technology imaginable in his quest to decipher the part of the mouse brain devoted to vision.

Of the many metaphors used for exploring and understanding the brain, mapping is probably the most durable, perhaps because maps are so familiar and understandable. “A century ago, brain maps were like 16th-century maps of the Earth’s surface,” said David Van Essen, who is in charge of the Connectome effort at Washington University, where Barch works. Much was unknown or mislabeled. “Now our characterizations are more like an 18th-century map.”

The continents, mountain ranges and rivers are getting more clearly defined. His hope, he said, is that the Human Connectome Project will be a step toward vaulting through the 19th and 20th centuries and reaching something more like Google Maps, which is interactive and has many layers.

Researchers may not be looking for the best sushi restaurants or how to get from one side of Los Angeles to the other while avoiding traffic, but they will eventually be looking for traffic flow, particularly popular routes for information, and matching traffic patterns to the tasks the brain is doing. They will also be asking how differences in the construction of the pathways that make up the brain’s roads relate to differences in behavior, intelligence, emotion and genetics.

The power of computers and mathematical tools devised for analysing vast amounts of data made such maps possible. The gathering tool of choice at Washington University is an MRI machine customised at the University of Minnesota.

There are a variety of ways to gather and interpret information in an MRI machine. And different types of scans can show both basic structure and activity. When a volunteer is trying to solve a memory problem, the hippocampus, the amygdala and the prefrontal cortex are all going to be involved. An MRI machine can detect the direction of information flow, in a technique called diffusion imaging. In that kind of scan, the movement of water molecules shows not only activity, but which way the traffic is headed.

For Barch, 48, another kind of interest in the human brain put her on the path to Washington University. “I always knew I wanted to be a psychologist,” she said — specifically, a school psychologist. But as an undergraduate at Northwestern, she excelled in an abnormal psychology class, and the professor recruited her to do research.As a professor at Washington University and a leader of one of five teams there working on the Human Connectome Project, Dr. Barch focuses her research on the way individual differences in the brains of healthy people are related to differences in personality or thinking.

For instance she said, people doing memory tasks in the MRI machine may differ in competitiveness and commitment to doing well. That ought to show up in activity in the parts of the brain that involve emotion, like the amygdala. However, she points out that the object of the Connectome Project is not to find the answers to these questions, but to provide the database for others to try to do so.