Monday, January 27, 2014

Carl Zimmer - Secrets of the Brain

The human brain is a three-pound wad of flesh able to explore the universe, imagine a better world, and ponder its own nature. Armed with far more sophisticated imaging techniques, scientists today are reaching toward an ultimate understanding of what makes us us.

Here is a very cool article from Carl Zimmer at National Geographic - the developments in brain imaging that are helping us gain better understanding of how the brain functions.

Secrets of the Brain

New technologies are shedding light on biology’s greatest unsolved mystery: how the brain really works.

Text by Carl Zimmer | February 2014
Photographs by Robert Clark

Brain Terrain The human brain is a three-pound wad of flesh able to explore the universe, imagine a better world, and ponder its own nature. Armed with far more sophisticated imaging techniques, scientists today are reaching toward an ultimate understanding of what makes us us. U.S. National Library of Medicine, Visible Human Project

Van Wedeen strokes his half-gray beard and leans toward his computer screen, scrolling through a cascade of files. We’re sitting in a windowless library, surrounded by speckled boxes of old letters, curling issues of scientific journals, and an old slide projector that no one has gotten around to throwing out.

“It’ll take me a moment to locate your brain,” he says.

On a hard drive Wedeen has stored hundreds of brains—exquisitely detailed 3-D images from monkeys, rats, and humans, including me. Wedeen has offered to take me on a journey through my own head.

“We’ll hit all the tourist spots,” he promises, smiling.

This is my second trip to the Martinos Center for Biomedical Imaging, located in a former ship-rope factory on Boston Harbor. The first time, a few weeks ago, I offered myself as a neuroscientific guinea pig to Wedeen and his colleagues. In a scanning room I lay down on a slab, the back of my head resting in an open plastic box. A radiologist lowered a white plastic helmet over my face. I looked up at him through two eyeholes as he screwed the helmet tight, so that the 96 miniature antennas it contained would be close enough to my brain to pick up the radio waves it was about to emit. As the slab glided into the cylindrical maw of the scanner, I thought of The Man in the Iron Mask.

Mind Machine An engineer wears a helmet of sensors at the Martinos Center for Biomedical Imaging—part of a brain scanner requiring almost as much power as a nuclear submarine. Antennas pick up signals produced when the scanner’s magnetic field excites water molecules in the brain. Computers convert this data into brain maps like the one below.

The magnets that now surrounded me began to rumble and beep. For an hour I lay still, eyes closed, and tried to keep myself calm with my own thoughts. It wasn’t easy. To squeeze as much resolution as possible out of the scanner, Wedeen and his colleagues had designed the device with barely enough room for a person of my build to fit inside. To tamp down the panic, I breathed smoothly and transported myself to places in my memory, at one point recalling how I had once walked my nine-year-old daughter to school through piles of blizzard snow.

As I lay there, I reflected on the fact that all of these thoughts and emotions were the creation of the three-pound loaf of flesh that was under scrutiny: my fear, carried by electrical impulses converging in an almond-shaped chunk of tissue in my brain called the amygdala, and the calming response to it, marshaled in regions of my frontal cortex. My memory of my walk with my daughter was coordinated by a seahorse-shaped fold of neurons called the hippocampus, which reactivated a vast web of links throughout my brain that had first fired when I had clambered over the snowbanks and formed those memories.

I was submitting to this procedure as part of my cross-country reporting to chronicle one of the great scientific revolutions of our times: the stunning advances in understanding the workings of the human brain. Some neuroscientists are zooming in on the fine structure of individual nerve cells, or neurons. Others are charting the biochemistry of the brain, surveying how our billions of neurons produce and employ thousands of different kinds of proteins. Still others, Wedeen among them, are creating in unprecedented detail representations of the brain’s wiring: the network of some 100,000 miles of nerve fibers, called white matter, that connects the various components of the mind, giving rise to everything we think, feel, and perceive. The U.S. government is throwing its weight behind this research through the Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative. In an announcement last spring President Barack Obama said that the large-scale project aimed to speed up the mapping of our neural circuitry, “giving scientists the tools they need to get a dynamic picture of the brain in action.”

Centuries of study have provided increasingly detailed understanding of human brain anatomy. Now scientists are turning their attention to the complex circuits that connect the brain’s many regions—some 100,000 miles of fibers called white matter, enough to circle the Earth four times. In this image taken at the Martinos Center, pink and orange bundles transmit signals critical for language. VAN WEEDEN AND L. L. WALD, MARTINOS CENTER FOR BIOMEDICAL IMAGING, HUMAN CONNECTOME PROJECT; BRAIN PREPARATION PERFORMED AT ALLEN INSTITUTE FOR BRAIN SCIENCE

As they see the brain in action, neuroscientists can also see its flaws. They are starting to identify differences in the structure of ordinary brains and brains of people with disorders such as schizophrenia, autism, and Alzheimer’s disease. As they map the brain in greater detail, they may learn how to diagnose disorders by their effect on anatomy, and perhaps even understand how those disorders arise.

On my return trip to his lab Wedeen finally locates the image from my session in the scanner. My brain appears on his screen. His technique, called diffusion spectrum imaging, translates radio signals given off by the white matter into a high-resolution atlas of that neurological Internet. His scanner maps bundles of nerve fibers that form hundreds of thousands of pathways carrying information from one part of my brain to another. Wedeen paints each path a rainbow of colors, so that my brain appears as an explosion of colorful fur, like a psychedelic Persian cat.

Wedeen focuses in on particular pathways, showing me some of the circuitry important to language and other kinds of thought. Then he pares away most of the pathways in my brain, so that I can more easily see how they’re organized. As he increases the magnification, something astonishing takes shape before me. In spite of the dizzying complexity of the circuits, they all intersect at right angles, like the lines on a sheet of graph paper.

“It’s all grids,” says Wedeen.

Anatomy of a Mystery New technologies let scientists peer deep into the hidden structure of the brain. A high-resolution view of the image above reveals white matter fibers arranged in a mysterious grid structure, like longitude and latitude lines on a map. Van Wedeen and L. L. Wald, Martinos Center for Biomedical Imaging, Human Connectome Project

When Wedeen first unveiled the grid structure of the brain, in 2012, some scientists were skeptical, wondering if he’d uncovered only part of a much more tangled anatomy. But Wedeen is more convinced than ever that the pattern is meaningful. Wherever he looks—in the brains of humans, monkeys, rats—he finds the grid. He notes that the earliest nervous systems in Cambrian worms were simple grids—just a pair of nerve cords running from head to tail, with runglike links between them. In our own lineage the nerves at the head end exploded into billions but still retained that gridlike structure. It’s possible that our thoughts run like streetcars along these white matter tracks as signals travel from one region of the brain to another.

“There’s zero chance that there are not principles lurking in this,” says Wedeen, peering intently at the image of my brain. “We’re just not yet in a position to see the simplicity.”

Scientists are learning so much about the brain now that it’s easy to forget that for much of history we had no idea at all how it worked or even what it was. In the ancient world physicians believed that the brain was made of phlegm. Aristotle looked on it as a refrigerator, cooling off the fiery heart. From his time through the Renaissance, anatomists declared with great authority that our perceptions, emotions, reasoning, and actions were all the result of “animal spirits”—mysterious, unknowable vapors that swirled through cavities in our head and traveled through our bodies.

The scientific revolution in the 17th century began to change that. The British physician Thomas Willis recognized that the custardlike tissue of the brain was where our mental world existed. To understand how it worked, he dissected brains of sheep, dogs, and expired patients, producing the first accurate maps of the organ.

It would take another century for researchers to grasp that the brain is an electric organ. Instead of animal spirits, voltage spikes travel through it and out into the body’s nervous system. Still, even in the 19th century scientists knew little about the paths those spikes followed. The Italian physician Camillo Golgi argued that the brain was a seamless connected web. Building on Golgi’s research, the Spanish scientist Santiago Ramón y Cajal tested new ways of staining individual neurons to trace their tangled branches. Cajal recognized what Golgi did not: that each neuron is a distinct cell, separate from every other one. A neuron sends signals down tendrils known as axons. A tiny gap separates the ends of axons from the receiving ends of neurons, called dendrites. Scientists would later discover that axons dump a cocktail of chemicals into the gap to trigger a signal in the neighboring neuron.

Intimate View Two hundred sections of a piece of mouse brain, each less than 1/1,000 the thickness of a human hair, are readied to be imaged by an electron microscope. Arranged in stacks, 10,000 such photomicrographs form a 3-D model no larger than a grain of salt (in tweezers). A human brain visualized at this level of detail would require an amount of data equal to all the written material in all the libraries of the world.

Jeff Lichtman, a neuroscientist, is the current Ramón y Cajal Professor of Arts and Sciences at Harvard, carrying Cajal’s project into the 21st century. Instead of making pen-and-ink drawings of neurons stained by hand, he and his colleagues are creating extremely detailed three-dimensional images of neurons, revealing every bump and stalk branching from them. By burrowing down to the fine structure of individual nerve cells, they may finally get answers to some of the most basic questions about the nature of the brain. Each neuron has on average 10,000 synapses. Is there some order to their connections to other neurons, or are they random? Do they prefer linking to one type of neuron over others?

To produce the images, Lichtman and his colleagues load pieces of preserved mouse brain into a neuroanatomical version of a deli meat slicer, which pares off layers of tissue, each less than a thousandth the thickness of a strand of human hair. The scientists use an electron microscope to take a picture of each cross section, then use a computer to order them into a stack. Slowly a three-dimensional image takes shape—one that the scientists can explore as if they were in a submarine traveling through an underwater kelp forest.

“Everything is revealed,” says Lichtman.

The only problem is the sheer enormity of “everything.” So far the largest volume of a mouse’s brain that Lichtman and his colleagues have managed to re-create is about the size of a grain of salt. Its data alone total a hundred terabytes, the amount of data in about 25,000 high-definition movies.

A Voyage Into the Brain Thought, feeling, sense, action—all derive from unimaginably complex interactions among billions of nerve cells. A section of mouse brain no larger than a grain of salt serves as a window into this hidden world.

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