News and Views: The Brain Activity Mapping Project – What’s the plan?

“If the human brain were so simple that we could understand it, we would be so simple that we couldn’t” – Dr. Emerson Pugh

Isabelle Abbey:

An ambitious project intended to unlock the inscrutable mysteries of nerve cell interactions in the brain is on its way. Labelled America’s ‘next big thing’ in neuroscience research, the ‘BRAIN’ (Brain Research through Advancing Innovative Neurotechnologies) initiative will use highly advanced technologies in an attempt to map the wiring of the human brain.

Cajal drew some of the billions of neurons in the human has come a long way since 1899

Also referred to as the ‘Brain Activity Map’ Project (BAM), the BRAIN initiative aims to decode the tens of thousands of connections between each of the ~86 billion neurones that form the basis of human brain. Scientists believe completing the map will be an invaluable step that may have huge implications for therapeutically tackling neurological pathology.

Moving forward in this manner does seem particularly appropriate. For the past 10 years, we have been reaping the benefits of technologies like fMRI and PET scanning, which have allowed us to visualize the brain in a way that has never been done before. From measuring behaviours to diagnosing abnormalities, the contribution of neuroimaging to our understanding of brain physiology and pathology is undeniable.

Paul Alivastos, the lead author of the paper detailing the BAM proposal, aims to develop novel toolkits that can simultaneously record the activities of billions of the cells in the live brain, rather than from macroscopic slices. Eventually, these technologies will allow for the accurate depiction of the flow of information in the human brain, and how this may differ in pathological states such as in Alzheimer’s or autism.

Despite the daunting nature of the task at hand, this proposal has been met with much political enthusiasm. On 2nd April Barack Obama announced the American Government would be backing the project by approving a $100m funding budget for its first year of operation.

The humble nematode worm, 1mm long

But might this project need some grounding? After all, Alivastos and his co-authors are yet to establish the basis for which such tools can be developed or the extent to which these technologies could be used. The years of extensive research that has concentrated on mapping the wiring of a simple nematode worm, consisting of only several hundred nervous system cells, is yet to allow us to accurately predict the worm’s behaviour. So, some scepticism does seem reasonable.

While we must be cautious in predicting ambitious benefits from such a project, the map Alivastos and his colleagues have envisaged gives reason enough to be hopeful for the next decade in our neuroscientific appreciation of human cognition.

Natasha Bray:

As a neuroscience researcher, I can’t help but take an interest in the BRAIN initiative proposed by President Obama earlier this month. It’s a massive pot of cash designed not only to further the neuroscientific knowledge base, but also to create jobs and technologies that can’t even be described yet. As Izzy mentions above, the project is an ambitious and important undertaking that merits the now fashionable label of ‘big science’.

The BRAIN initiative is funded by a big pot of money from different resources including DARPA (the Defence Advanced Research Projects Agency), the National Science Foundation, the National Institute for Health, Google and various other institutes and charities.

So far, even defining the project and choosing suitable methods has been a challenge. The research leaders have proposed “to record every action potential from every neuron within a circuit”. Bear in mind action potentials (nerve impulses) happen in a matter of a couple of thousandths of a second, while a single circuit may encompass many millions of cells. At the moment, neuroscientists can record action potentials from up to about 100 cells simultaneously. We can work out anatomical circuits. We just can’t record from every cell within them; there is not one single tool in neuroscience’s toolbox that is currently capable of gathering that kind of data (yet).

There are, however, candidate techniques that could be improved or perhaps combined. Imaging techniques, including optical, calcium or voltage imaging, or magnetic imaging such as fMRI and MEG can scan on different scales in both time and space. Neurons’ electrical activity can be recorded using silicon-based nanoprobes or very tightly-spaced electrodes. Researchers have even suggested synthesising DNA that records action potentials as errors in the DNA strand like a ticker tape. Advances in all these technologies are still being made, making them the most likely candidates.

Added to the difficult choice of method is the serious task of storing and analysing quadrillions of bytes of data, plus the fact that it’ll take about ten years just to complete an activity map of the fly brain. It’s clear there are significant hurdles to jump. Then again, no one said big science would be easy…or cheap. But the potential benefits of big science are huge. The Human Genome Project had a projected cost of $3 billion, but was completed within its budget and has already proved a huge investment both intellectually and financially. It’s famously estimated that for every dollar originally invested in the Human Genome Project, an economic return of $140 has already been made.

I see the BRAIN initiative as a very worthy cause, a good example of aspirational ‘big science’ and a great endorsement for future neuroscience. One gripe I have with it, however, is that it seems a little like Obama’s catch-up effort in response to Europe’s Human Brain Project (HBP). The HBP involves 80 institutions striving towards creating a complex computer infrastructure powerful enough to mimic the human brain, right down to the molecular level. Which begs the question: surely in order to build an artificial brain you need to understand how it’s put together in the first place? I really hope that the BRAIN initiative and Human Brain Project put their ‘heads together’ to help each other in untangling the complex workings of the brain.

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