Dr. Rafael Yuste, a neuroscientist at Columbia University, has pioneered the use of lasers to measure the activity of neurons in the cortex of mice.

Michael Nagle • New York Times ,


Goal to map the human brain holds challenges for scientists

  • Article by: JOHN MARKOFF
  • New York Times
  • March 2, 2013 - 5:31 PM


In setting the nation on a course to map the active human brain, President Obama may have picked a challenge even more daunting than ending the war in Afghanistan or finding common ground with his Republican opponents.

In more than a century of scientific inquiry into the interwoven cells known as neurons that make up the brain, researchers acknowledge they are only beginning to scratch the surface of a scientific challenge that is certain to prove vastly more complicated than sequencing the human genome.

The Obama administration is hoping to announce as soon as next month its intention to assemble the pieces — and, even more challenging, the financing — for a decade-long research project that will have the goal of building a comprehensive map of the brain’s activity. Scientists are currently a long way from doing so. Before they can even begin the process, they have to develop the tools to examine the brain. And before they develop tools that will work on humans, they must succeed in doing so in a number of simpler species — assuming that what they learn can even be applied to humans.

Besides the technological and scientific challenges, there are a host of issues involving storing the information researchers gather, and ethical concerns about what can be done with the data. Also highly uncertain is whether the science will advance quickly enough to meet the time frames being considered for what is being called the Brain Activity Map project. Many neuroscientists are skeptical that a multiyear, multibillion dollar effort to unlock the brain’s mysteries will succeed. Donald G. Stein, a neurologist at the Emory University School of Medicine in Atlanta, said, “The search for a road map of stable, neural pathways that can represent brain functions is futile.”

‘The million neuron march’

The state of the art in animal research is to sample from roughly a thousand neurons simultaneously. The human brain has 85 billion to 100 billion neurons. “For a human we must develop new techniques, and some of them from scratch,” said Dr. Rafael Yuste, a neuroscientist at Columbia who has pioneered the use of lasers to measure the activity of neurons in the cortex of mice. An article last year in the journal Neuron described a possible path toward mapping the active human brain. The article, signed by six scientists, proposes that the project begin with species that have brains with very small numbers of neurons and then work toward complex animals.

The scientists cited the worm C. elegans, which to date is the only animal for which there is a complete static map, or “connectome.” That worm has just 302 neurons with 7,000 connections. The authors propose moving on to the Drosophila fly, which has 135,000 neurons; the zebra-fish; the mouse; and then the Etruscan shrew, the smallest known mammal, whose cortex is composed of about 1 million neurons.

But the leap to the human brain is so enormous that one of the scientists who has participated in planning sessions, neuroscientist Terry Sejnowski from the Salk Institute, has called the challenge “the million neuron march.”

While the researchers have proposed a wide range of technologies that might be applied to the problems, many of them are still prototypes or speculative.

Moreover, many technologies now used to sample human brain activity at high resolution require opening the skull, dramatically restricting what is possible. Progress is being made, but only at a basic level.

Still, last week in the journal Nature a group of neurosurgeons at the University of California, San Francisco, reported new insights into mechanisms of the language function of the human brain. That research, which was conducted with permission from three people who had severe epileptic seizures, involved installing a dense sensor mesh of electrodes on the surface of their brains. The 264 electrodes each sampled from an area that might encompass as many as millions of neurons, said Dr. Edward F. Chang, a neurosurgeon who led the team.

‘Incremental advances’

Although the sensor’s resolution was crude, it was four times more powerful than what has been used until now. It revealed how the speech centers in the human cortex control the larynx, tongue, jaw, lips and face, all of which are involved in making the sounds that constitute human speech. Chang said, “It demonstrates the power of even incremental advances.”

The goal of the University of California group is to gain enough understanding of the speech mechanism in the brain to be able develop sophisticated prosthetics, making it possible for victims of paralysis or stroke to speak. It is that potential — and more — that has excited scientists, and generated pressure for a multibillion dollar effort to develop a human brain activity map, backed by the U.S. government, in partnership with research foundations and institutions.

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