The result is the most-detailed digital map, or “connectome,” of the human brain ever created.
On Thursday, Lichtman and his partners unveiled the results of their efforts in the prestigious journal Science, and also posted to the internet renderings of the human brain unlike any ever seen. They came complete with a program that allows viewers to move through a microscopic alien landscape so detailed Lichtman can’t resist waxing poetic when he talks about it.
“It’s an alien world inside your own head,” he said. “Neurons themselves are truly awe inspiringly beautiful. There’s no two ways about it.”
True, the insights gleaned from the tiny sample have not yet unraveled the mysteries of autism, schizophrenia, or depression. They can’t yet explain the mechanics of human learning, memory, and personality on the cellular level. But they represent an important first step in that direction, and provide a tantalizing preview of the kind of insights we might see in the decades ahead.
In this intricate landscape are strange structures never before seen, and not contained in any textbook, including, in Lichtman’s words, “fantastically weird” nerve cells that point in one of only two directions, exactly opposite from one another. Axons, the long-distance fiber optic cables of the brain, that detour from straight lines into strange “whirls” that look like turbans — then unravel and resolve back into straight lines. The purpose of many of these strange anomalies remains a topic for future study.
Some are already generating potentially paradigm-shifting theories and may reveal fundamental new insights into how the brain works. Most notable, said Lichtman, is the discovery of what appears to be a new, extremely rare kind of “super connection” that links individual neurons to the information-carrying axon fibers that crisscross the brain. Each super connection contains a jumble of some 50 or so protrusions where normally there is only one. These structures, Lichtman hypothesizes, may help explain how learned habits, such as stopping at a red light without thinking, are etched into the physical architecture of the brain.
“Maybe 99 percent of the connections between axons and individual brain cells are these super weak connections,” Lichtman says. But, “those strong connections are so strong that information can flow very efficiently. And this may be a way to explain the fact that, after you’ve learned something, there is this automatic ability to do it.”
The new paper is part of a far larger series of projects funded by the BRAIN initiative, a massive scientific effort launched by the Obama Administration in 2013 to reveal fundamental insights about the human brain.
“It’s a pretty big deal,” said Ed Lein, a neuroscientist at the Allen Institute for Brain Science in Seattle who was not involved in the study. The mapping is “really the first of its kind in a human.”
Lein, who helps lead another component of the BRAIN initiative, said Lichtman’s work could help transform our understanding of the human brain and vastly improve our ability to cure disease.
“We have just a terribly poor understanding of that circuitry,” he said. “Imagine that your cell phone broke and you didn’t know anything about the components of the cell phone or how they’re connected to one another, and you’re trying to fix it. If we don’t understand how the thing is wired together at all, we have little chance of being able to fix it.”
Originally funded with part of a $7 million five-year grant from the National Institutes of Health, Lichtman’s project recently received an additional $30 million over five years from a related NIH program. The federal agency’s goal is to improve our understanding of diseases that affect cognition and emotion.
The money, which is also funding other related projects, is supplemented by the free collaborative efforts of Google, which provided the computational muscle and engineering labor needed to power the project.
After the human brain sample was stained, sliced and imaged in Lichtman’s lab, Google’s engineers applied machine learning to stitch those slices back together and apply colors to render the wiring visible to the naked eye.
The scope of the challenge to simply recreate that 1-cubic-millimeter sample of human brain in digital form was so great that the effort to go on and image an entire human brain will have to wait. An accurate image of the entire human brain at scale would roughly equal the amount of data produced in the entire world in a single year, Lichtman says.
Which is why the next effort will be more modest: Over the next five years, Lichtman and his collaborators aim to image the first 10-cubic-millimeter section of a mouse brain. The project is a proof-of-concept for the ultimate goal: an entire mouse brain, 50 times larger.
“The human brain would be another factor of a thousand bigger than a mouse brain,” Lichtman says. “We don’t have the capacity to store that information.”
The payoff from all these efforts could eventually prove huge. Google and others expect to use the findings to improve their ability to invent artificial intelligence algorithms modeled on the human brain.
Lichtman, for his part, hopes to answer fundamental questions about the human mind: How is it that a representation of the world gets imprinted inside our heads? What are the physical underpinning of knowledge?
The project has already taken him into intellectual territory he never expected to enter. He describes the experience of sitting down in his office with the new “neuroglancer” tool that allowed him to maneuver through the visual landscape of the neural connectome as “wondrous,” “magical,” and “like a fantasy.” He wanted to click on every single cell.
Invoking the names of Magellan, Amerigo Vespucci, and other famous explorers, Lichtman extolled the thrill of discovery.
“This is a lot like using the Hubble telescope or the James Webb telescope,” Lichtman says. “But it’s not a telescope, it’s a microscope that allows us to look inside. And sure enough, there’s all sorts of things there that we’ve never seen before. We’re exploring a terra incognita.”
This story originally appeared in STAT’s sister publication, the Boston Globe.