What's in Brian's Brain?
Despite the progress of neuroscience, I still don’t know my own mind
Dream the Impossible Dream
Frances Crick, who took up neuroscience after conquering molecular biology, wrote in 1979 about the prospects for understanding the brain: “It is no use asking for the impossible, such as, say, the exact wiring diagram for a cubic millimeter of brain tissue and the way all its neurons are firing.” Current brain-mapping projects do exactly what Crick believed impossible.
A goal of the Connectome Project at Harvard is to image the microanatomy of a cubic millimeter of mouse brain in sufficient detail to resolve individual synapses and create a full connectivity map. The first step is to slice the tiny block of tissue into 20,000 sections, each 50 nanometers thick. Each slice is imaged by an electron microscope with a resolution of 5 nanometers. The resulting data set will be about 800 terabytes. The second phase of the project is more difficult: Identifying features of cells in the individual images and correctly aligning the features in successive slices to reconstruct the full three-dimensional geometry. For these tasks to be completed at reasonable speed and cost, both phases of the operation must be automated. A group led by Jeff W. Lichtman and Hanspeter Pfister of Harvard has recently reported on a pilot project with a cube of tissue 30 micrometers on a side.
As for the second part of Crick’s impossible request, a manifesto for the Brain Activity Map declares: “We propose to record every action potential from every neuron within a circuit—a task we believe is feasible.” Admittedly, the task is not feasible with present instruments, which either average the activity of large ensembles of cells or isolate small numbers of single cells. One approach to bridging the gap would rely on arrays of nanoelectrodes to record simultaneously from many cells. The alternatives are optical techniques, in which molecules or nanoparticles implanted in neurons emit light in response to ion flows or voltage changes.
The new European project, led by Henry Markram of the Swiss Federal Institute of Technology in Lausanne, seems to go well beyond Crick’s impossible dream. Within a decade, Markram proposes to build a computer simulation of the entire human brain at a level of detail fine enough to include structural and physiological features of individual cells. Then he envisions linking the model brain to a virtual body in a virtual environment. He even mentions looking for cognitive abilities like those of a human infant.
Such a model can be built without first having a full wiring diagram of the brain, Markram says; its assembly will be guided by the same genetic and developmental rules that operate in the embryo. And it can be built without first ascertaining the nature of memory or the neural encoding of information; as a matter of fact, the simulation should help resolve those enigmas, according to Markram. Europe is now making a €1 billion bet that these grandiose plans will succeed.
Markram’s Human Brain Project is not the first program with that name; the U.S. National Academy of Sciences launched an identically named research effort more than 20 years ago, when President George H. W. Bush declared that the 1990s would be “the decade of the brain.” It’s a little discouraging to be starting down the same path again, with the big questions still unanswered. But, as the owner of a brain that’s still curious about itself, I believe the quest must go on.
- Alivisatos, A., et al. 2012. The Brain Activity Map project and the challenge of functional connectomics. Neuron 74:970–974.
- Braitenberg, V., and A. Schüz. 1998. Cortex: Statistics and Geometry of Neuronal Connectivity. Berlin: Springer.
- Crick, F. H. C. 1979. Thinking about the brain. Scientific American 241(3):219–232.
- Kaynig, V., et al. 2013 (preprint). Large-scale automatic reconstruction of neuronal processes from electron microscopy images. http://arxiv.org/abs/1303.7186.
- Lichtman, J. W., and W. Denk. 2011. The big and the small: Challenges of imaging the brain’s circuits. Science 334:618–623.
- Markram, H., et al. 2012. The Human Brain Project: A Report to the European Commission. Lausanne, Switzerland: HBP-PS Consortium.
- McCulloch, W. S., and W. H. Pitts. 1943. A logical calculus of the ideas immanent in nervous activity. Bulletin of Mathematical Biophysics 5:115–133.
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