Scientists Plan to Map the Brain

[General Mung Beans]

http://www.nytimes.com/2013/02/18/scien ... d=all&_r=0

Obama Seeking to Boost Study of Human Brain
By JOHN MARKOFF
Published: February 17, 2013


The Obama administration is planning a decade-long scientific effort to examine the workings of the human brain and build a comprehensive map of its activity, seeking to do for the brain what the Human Genome Project did for genetics.

George M. Church, a molecular biologist at Harvard, said he was helping to plan the project, the Brain Activity Map.

The project, which the administration has been looking to unveil as early as March, will include federal agencies, private foundations and teams of neuroscientists and nanoscientists in a concerted effort to advance the knowledge of the brain’s billions of neurons and gain greater insights into perception, actions and, ultimately, consciousness.

Scientists with the highest hopes for the project also see it as a way to develop the technology essential to understanding diseases like Alzheimer’s and Parkinson’s, as well as to find new therapies for a variety of mental illnesses.

Moreover, the project holds the potential of paving the way for advances in artificial intelligence.

The project, which could ultimately cost billions of dollars, is expected to be part of the president’s budget proposal next month. And, four scientists and representatives of research institutions said they had participated in planning for what is being called the Brain Activity Map project.

The details are not final, and it is not clear how much federal money would be proposed or approved for the project in a time of fiscal constraint or how far the research would be able to get without significant federal financing.

In his State of the Union address, President Obama cited brain research as an example of how the government should “invest in the best ideas.”

“Every dollar we invested to map the human genome returned $140 to our economy — every dollar,” he said. “Today our scientists are mapping the human brain to unlock the answers to Alzheimer’s. They’re developing drugs to regenerate damaged organs, devising new materials to make batteries 10 times more powerful. Now is not the time to gut these job-creating investments in science and innovation.”

Story C. Landis, the director of the National Institute of Neurological Disorders and Stroke, said that when she heard Mr. Obama’s speech, she thought he was referring to an existing National Institutes of Health project to map the static human brain. “But he wasn’t,” she said. “He was referring to a new project to map the active human brain that the N.I.H. hopes to fund next year.”

Indeed, after the speech, Francis S. Collins, the director of the National Institutes of Health, may have inadvertently confirmed the plan when he wrote in a Twitter message: “Obama mentions the #NIH Brain Activity Map in #SOTU.”

A spokesman for the White House Office of Science and Technology Policy declined to comment about the project.

The initiative, if successful, could provide a lift for the economy. “The Human Genome Project was on the order of about $300 million a year for a decade,” said George M. Church, a Harvard University molecular biologist who helped create that project and said he was helping to plan the Brain Activity Map project. “If you look at the total spending in neuroscience and nanoscience that might be relative to this today, we are already spending more than that. We probably won’t spend less money, but we will probably get a lot more bang for the buck.”

Scientists involved in the planning said they hoped that federal financing for the project would be more than $300 million a year, which if approved by Congress would amount to at least $3 billion over the 10 years.

The Human Genome Project cost $3.8 billion. It was begun in 1990 and its goal, the mapping of the complete human genome, or all the genes in human DNA, was achieved ahead of schedule, in April 2003. A federal government study of the impact of the project indicated that it returned $800 billion by 2010.

The advent of new technology that allows scientists to identify firing neurons in the brain has led to numerous brain research projects around the world. Yet the brain remains one of the greatest scientific mysteries.

Composed of roughly 100 billion neurons that each electrically “spike” in response to outside stimuli, as well as in vast ensembles based on conscious and unconscious activity, the human brain is so complex that scientists have not yet found a way to record the activity of more than a small number of neurons at once, and in most cases that is done invasively with physical probes.

But a group of nanotechnologists and neuroscientists say they believe that technologies are at hand to make it possible to observe and gain a more complete understanding of the brain, and to do it less intrusively.

In June in the journal Neuron, six leading scientists proposed pursuing a number of new approaches for mapping the brain.

One possibility is to build a complete model map of brain activity by creating fleets of molecule-size machines to noninvasively act as sensors to measure and store brain activity at the cellular level. The proposal envisions using synthetic DNA as a storage mechanism for brain activity.

“Not least, we might expect novel understanding and therapies for diseases such as schizophrenia and autism,” wrote the scientists, who include Dr. Church; Ralph J. Greenspan, the associate director of the Kavli Institute for Brain and Mind at the University of California, San Diego; A. Paul Alivisatos, the director of the Lawrence Berkeley National Laboratory; Miyoung Chun, a molecular geneticist who is the vice president for science programs at the Kavli Foundation; Michael L. Roukes, a physicist at the California Institute of Technology; and Rafael Yuste, a neuroscientist at Columbia University.

The Obama initiative is markedly different from a recently announced European project that will invest 1 billion euros in a Swiss-led effort to build a silicon-based “brain.” The project seeks to construct a supercomputer simulation using the best research about the inner workings of the brain.

Critics, however, say the simulation will be built on knowledge that is still theoretical, incomplete or inaccurate.

The Obama proposal seems to have evolved in a manner similar to the Human Genome Project, scientists said. “The genome project arguably began in 1984, where there were a dozen of us who were kind of independently moving in that direction but didn’t really realize there were other people who were as weird as we were,” Dr. Church said.

However, a number of scientists said that mapping and understanding the human brain presented a drastically more significant challenge than mapping the genome.

“It’s different in that the nature of the question is a much more intricate question,” said Dr. Greenspan, who said he is involved in the brain project. “It was very easy to define what the genome project’s goal was. In this case, we have a more difficult and fascinating question of what are brainwide activity patterns and ultimately how do they make things happen?”

The initiative will be organized by the Office of Science and Technology Policy, according to scientists who have participated in planning meetings.

The National Institutes of Health, the Defense Advanced Research Projects Agency and the National Science Foundation will also participate in the project, the scientists said, as will private foundations like the Howard Hughes Medical Institute in Chevy Chase, Md., and the Allen Institute for Brain Science in Seattle.

A meeting held on Jan. 17 at the California Institute of Technology was attended by the three government agencies, as well as neuroscientists, nanoscientists and representatives from Google, Microsoft and Qualcomm. According to a summary of the meeting, it was held to determine whether computing facilities existed to capture and analyze the vast amounts of data that would come from the project. The scientists and technologists concluded that they did.

They also said that a series of national brain “observatories” should be created as part of the project, like astronomical observatories.

Glad to see this occurring.

[Eternal_Freedom]

This is certainly exciting, but I have a feeling that because Obama is pushing for it the Republicans will come up with inventive ways and reasons to oppose it.

[Guardsman Bass]

Here's some skeptical commentary from a psychology professor:

Today's New York Times reports that the Obama administration is considering a massive, partly government-funded project to map the human brain, the Brain Activity Map (BAM!) Project, inspired by the success of the Human Genome Project.

Let me start by saying that I am all in favor of more research in neuroscience, because there is certainly a lot we don't know about how the brain works. While to outsiders like Ray Kurzweil it may look like progress is coming in leaps and bounds, and backing up the mind's hard drive is therefore a calculable number of years away, from the inside the effort to understand the brain often seems to zigzag from new idea to cool finding to neat technology without a clear forward trajectory. I am also a big fan of George Church, a genius and visionary of molecular biology who is one of the driving forces behind the new plan. (I even once co-taught a course on cognitive genetics at Harvard with George's wife, the geneticist Ting Wu.) But before we all jump on this bandwagon, let's discuss the pros and cons—based on what has been said publicly so far (mainly in the Times article, which was prefigured by a Neuron article by Church and several others published last June).

Per the Times, the project is expected to cost "billions of dollars" and last 10 years. Its goals are to "advance the knowledge of the brain's billions of neurons and gain greater insights into perception, actions, and, ultimately, consciousness." So far, so good—basic science. Some also hope that the project will "develop the technology essential to understanding diseases like Alzheimer's and Parkinson's, as well as to find new therapies for a variety of mental illnesses." That's certainly possible, though I cannot think of any treatments for mental illness or brain disease that have been derived from previous maps of the brain or knowledge of its activity patterns. Perhaps this is just an argument that we need better maps. Finally, "the project holds the potential of paving the way for advances in artificial intelligence." Certainly also possible, but I think AI has been doing pretty well lately by ignoring brain architecture and going with whatever algorithms work on computer hardware to produce intelligent-seeming behavior.

The Times account is short on details of what precisely is being proposed, which has led some people to think that the idea is to map every connection and the firing activity of every neuron in (at least) one human brain, or to make more maps of the functions of brain regions using neuroimaging techniques. But the Neuron article by the Brain Activity Map proponents makes it clear that, last June at least, the idea was to start with small circuits in very small organisms, where it may soon be possible to record from every participating neuron at once, and to work up to larger circuits and larger organisms. All these maps would record "the patterns and sequences of neuronal firing by all neurons" in the relevant circuit or brain, so they would be much more detailed, in both space and time, than any existing databases. A drosophila brain might be done in ten years, a mouse neocortex in fifteen. The entire human brain would be a more distant goal. And of course there would be ethical issues to be surfaced and solved along the way to that ultimate step.

There are a lot of things to like about this ambition. Although we already have lots of maps of the brain, none of them (but one—the structural connectome of the C. elegans worm) approach the spatial resolution of a neuron-by-neuron map. The main source of our knowledge about how neurons represent information, carry out computations, and communicate with other neurons is still the single-cell recording, a technique developed about half a century ago. Such methods are based on inserting tiny electrodes in or near living neurons, and have obvious limitations, not least their inability to scale to full circuits or brain regions. Recording entire circuits in action would be a fantastic achievement and probably would lead to all sorts of ancillary benefits for advancing brain research, some foreseeable and some not. And perhaps more neuroscientists would be able to find jobs along the way!

But there are some considerations on the other side of the ledger, too. One that should not be underestimated is the opportunity cost; always, but especially nowadays, it would be a mistake to imagine that the funding for a new, large project will appear out of thin air. If the BAM goes forward, other areas are likely to get less funding, and other neuroscience and behavioral science projects will likely be among the first to be reduced. Moreover, a single mega-project is likely to supplant many smaller projects. Is our neuroscience money best spent on one project costing, say, $5 billion, or instead a thousand projects of $5 million each, or ten thousand projects with $500K budgets? Which funding strategy is likely to result in more important discoveries, as viewed from the perspective of the next generation of scientists looking back? Maybe the BAM, but maybe not. The answer is hardly obvious to me. The big project is concrete and tangible, with milestones in the near future. The net effect of the tinkering of ten thousand labs with comparatively small budgets is harder to conceive of, but might turn out to be much larger.

One reason to be suspicious of the potential return-on-investment of a massive BAM project is that it's being sold by comparing it to the Human Genome Project (HGP), with a claim that the HGP produced $141 in economic activity for every $1 the government spent on it. President Obama cited this figure in his State of the Union Address. That's a return of fourteen thousand percent! Can that be right? If so, it would mean that about $800 billion in economic activity has been generated by that one government "investment." It turns out that this claim comes from a Batelle report (which is cited by the BAM advocates in their Neuron article) that was sponsored by a company that makes equipment used in life science research.

I find this figure hard to believe, not to say preposterous. Does it really represent net economic activity, or does it account for activity displaced from other spheres, and was all that economic activity the best activity that could have been done, or was it activity that pursuit of grant funding and other non-market incentives encouraged? To be clear: I think the genome project was a great scientific idea, I suspect that it has produced a lot of benefits, and I am personally happy it was done. I just don't think it should be oversold. As Richard Feynman pointed out in his famous "Cargo Cult" speech, public support for research will eventually erode if it is sold with outrageous-sounding claims or promises of early benefits.

But suppose it is true that the Human Genome Project was the single best thing the U.S. government ever spent its money on—sorry, "investment it ever made"—the government's version of buying Apple stock for $5 and selling at $700. Should we expect similar returns from the next big science project? Or should we expect to see the economic return and gains in knowledge achieved by the average of the big science projects that the government has funded over the past decades? The abandoned supercollider, the war on cancer, the cancelled breeder reactor, and I am sure many others fade from memory—and certainly never get mentioned—when we are told about the 141X ROI of the genome project (worthy as it was). An analysis that looked at all the comparable projects rather than just the all-time outlier might come to a different projection of the likely value of the BAM. We might still expect a positive return, but without the 141X (or whatever the true value is), it will have a tougher time competing with other priorities, or with other ways of parceling out neuroscience funding.

Europe has thrown its lot behind the single mega-project approach, with an effort to simulate an entire brain at a cost of over 1 billion Euros. Regardless of the (questionable) merit of this idea, perhaps the U.S. should play a different strategy in the competition for research glory by letting a thousand flowers bloom rather than planting one ginormous tree. Indeed, such a contrarian approach may have value precisely because of the limits of the mapmaking approach to understanding the brain.

Forty years ago, single-cell neurophysiologist Horace Barlow famously proposed that "a description of that activity of a single nerve cell which is transmitted to and influences other nerve cells and of a nerve cell's response to such influences from other cells, is a complete enough description for functional understanding of the nervous system." The BAM Project seems to be a plan to create exactly this sort of description, but at a much larger scale. But as David Marr explained in his 1982 book Vision, and as Hilary Putnam also suggested in his 1973 Cognition article "Reductionism and the Nature of Psychology," there are several other levels of explanation that are equally important in reaching a "functional understanding" of how the brain works. The representations, algorithms, and computational functions of the brain and its circuits, as well as the relationship of the brain to the organism and its environment and niche, are just as important as a map that shows how the neurons are wired up and how they send signals to one another.

Again, it is not that a BAM would have no value. I would personally be fascinated to see its results, and those results might well help us to crack the problem of how higher-level properties emerge out of agglomerations of lower-level events (which the psychologist Stephen Kosslyn, a founder of cognitive neuroscience, proposed as one of the hardest problems in social science). But the sheer size of a full BAM project might focus our attention and hopes on the BAM as the be-all and end-all of neuroscience, and distract the field from devoting energy to those other levels. Cognitive scientist Mark Changizi has eloquently argued, in fact, that the massive project we ought to be pursuing is a map of the "teleome," his coinage for the suite of functions and abilities that the nervous system was designed by evolution to perform. Without knowing more about function, it will be hard to understand the BAM's results, and perhaps even harder to build the EU's whole-brain computer simulation. As the proposal moves forward, I hope the decision-makers keep in mind that maps, while incredibly useful tools, don't give answers to every important question.

[K. A. Pital]

I think we are going to see major advances in the next 10 years or so with such projects like BAM and Blue Brain. Which is... exciting to say the least.

[Ziggy Stardust]

There are already dozens of brain "maps." MRI analysis is basically impossible without them. I use them on a weekly basis for some of my experiments. And while there is always room for new methods of mapping the brain, and new computational paradigms to go along with it, that isn't the major obstacle to a fuller understanding of how the brain works.

While this project will certainly be interesting, I am a bit skeptical that this will be as revolutionary a development as they claim. From what I can gather, the plan is to record every action potential from every neuron within a circuit (using a combination of calcium and voltage imaging). It's not that this is useless (quite the contrary), but that it in and of itself doesn't seem like it will be significantly more nuanced than a DTI analysis. It is basically just a more sophisticated analogue to EEG and MEG.

[Covenant]

Here's a question from the profoundly uneducated: what really stops us (aside from making a perfect recreation the old fashioned way) from building a brain?

There's the brain, there's brain activity, there's the squidgy concept of "The Mind" and there's... is that it, really?

Don't get me wrong, the brain is an insanely complex inter-related system that seems to operate in such an unusual manner that understanding at all seems to take a good bit of education. I'm somewhat comforted by the idea that we're not able to just build one out of silicon the way you build a computer, as I'm not a big fan of the idea of a brain upload, but my bias aside I'm wondering what makes it so complex and what are the roadblocks to us actually being able to create a primitive brain?

Without assuming there's some kind of unknown electrochemical process that is responsible for a lot more than we thought, what do people think is the deal? It'll be exciting to finally get some experimental data from the build-a-brain workshops.

Is it processing power? Storage? the way storage is interlinked? Or do we really have no idea how the genie gets in the bottle and are hoping to kinda fumble our way around in the dark by building an experimental model and then goofing with it?

[K. A. Pital]

I'm somewhat comforted by the idea that we're not able to just build one out of silicon the way you build a computer, as I'm not a big fan of the idea of a brain upload, but my bias aside I'm wondering what makes it so complex and what are the roadblocks to us actually being able to create a primitive brain?

Google the interviews of the Blue Brain project chief; he spends a great deal on explaining why the more primitive brain simulations do not really (a) help us get there (b) work in the same way as a real, even animal, brain.

[Formless]

Here's a question from the profoundly uneducated: what really stops us (aside from making a perfect recreation the old fashioned way) from building a brain?

There's the brain, there's brain activity, there's the squidgy concept of "The Mind" and there's... is that it, really?

There's brain development... you don't hear about that part very often, but unlike the computer sitting on your desktop, a brain isn't something you can just turn on, boot up, and install whatever software you please. Things need to grow and activate in a certain order to fine-tune the neural network on a case by case basis.

But the short of it is, our current models of how the brain works are very incomplete. To give an example, it wasn't until the last decade that we knew that neurons can and do get replaced over time by special stem cells (located at the base of the brain stem, IIRC); before that it was believed that you had as many as you were ever going to at birth. This is why Neuroscience exists in the first place, after all. Our best theories about electro-chemical signalling are paintings in such broad strokes that when you go about creating a simulation, it just doesn't capture even the nuanced thought of a mouse. We are at the stage where we can still discover new things about the role of dopamine and other major neurotransmitters, and on top of that our understanding of genetic regulation and activation are even more inadequate. So it shouldn't come as a surprise that things get omitted from simulations... but in the process you lose something significant.

[The Grim Squeaker]

Here's a question from the profoundly uneducated: what really stops us (aside from making a perfect recreation the old fashioned way) from building a brain?

There's the brain, there's brain activity, there's the squidgy concept of "The Mind" and there's... is that it, really?
..
Is it processing power? Storage? the way storage is interlinked? Or do we really have no idea how the genie gets in the bottle and are hoping to kinda fumble our way around in the dark by building an experimental model and then goofing with it?

Without getting too deeply into it (Also, YAY, My old seminar instructor, Idan Segev, is in charge of the Israeli branch of the Blue Brain project ),

The big thing we currently have no clue about is the "Connectome". AKA, the connections between neurons and how that all adds up.
We can build rather decent models of single neuron computational abilities (and they can do pretty impressive things!), but we lack the ability to effectively simulate the work of networks of neurons which can have completely different properties, affect each other at the same time, affect themselves at the same time, affect differently based on time, activity, long term activity or other effectors, and other networks ... And this is just the baseline background!
It's harder than it sounds .

Here's a question from the profoundly uneducated: what really stops us (aside from making a perfect recreation the old fashioned way) from building a brain?

There's the brain, there's brain activity, there's the squidgy concept of "The Mind" and there's... is that it, really?

There's brain development... you don't hear about that part very often, but unlike the computer sitting on your desktop, a brain isn't something you can just turn on, boot up, and install whatever software you please. Things need to grow and activate in a certain order to fine-tune the neural network on a case by case basis.

Also, as has been said - Connections during development. There is Literally not enough data in the entire human genome to contain mapping instructions for our 86 billion neurons. But they're all mapped up to each other, to areas, to modalities or functionalities, etc'.

[cosmicalstorm]

I wish them the best of luck. I don't expect much in the short term. But in the long term it's obvious that our current method of generating minds will be replaced by something much more efficient. I long ago gave up on my childhood dream that there would one day be a galaxy spanning empire of human brains being trucked around in giant human biology friendly cans.