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An Overview of the Brain Activity Map Project
Brandon Mentley
The Brain Activity Map (BAM) Project, a multi-billion dollar “big science” initiative
proposed by the Obama administration is set to take the stage as this generation’s equivalent to
the Human Genome Project. In fact, the goals set for the project may even be far loftier than
those of the Human Genome Project. The project’s stated goal, to record every voltage spike
from every neuron in the brain, seems simple in principle, but it comes with a massive number of
technical hurdles that will need to be overcome if the project is to be successful. The hope is that
the project’s findings will lead to a much better understanding of how the brain works, which in
addition to being interesting information, could possibly lead to better treatments for mental
illnesses, such as schizophrenia and autism.1
The team is nowhere near having the capabilities necessary to image a human brain at the
neuronal level. In fact, the only connectome (the neuronal equivalent of a genome) that has been
completely reconstructed is that of C. elegans, a small, transparent roundworm possessing only
302 neurons that form just 7,000 synapses.1 Obviously, this is a far cry from a human brain,
which is estimated to have somewhere on the order of 100 billion neurons forming 100 trillion
synapses.2 In the short term, the team plans to focus on imaging the brains of other relatively
simple organisms, such as Drosophila, of which the connectome is already 20% complete and
could be completed within three years. Within ten years, the team hopes to move on to imaging
the brains of small animals, and they hope to move on to primates within fifteen years. While
they do hope to eventually be able to image a human brain, the ability to do so is still many years
away.1
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In the past, most research on the function of neurons has been limited to recording signals
from a small number of neurons at a time. Through previous efforts, scientists have gained some
understanding of the functions of different parts of the brain, but this understanding is
incomplete, and not all theories on brain function are universally accepted within the scientific
community. The scientists behind the project claim that studying small groups of neurons is
insufficient and that there are emergent properties of neuronal circuits that can only be revealed
by measuring activity in large regions of the brain at once, ideally imaging the entire brain.
Neurons often synapse with thousands of other neurons and can even undergo dynamic
rearrangements, making the task of determining how they function within the brain very
difficult.1
fMRI and MEG have allowed scientists to image the entire brain in the past, giving some
idea of the function of different regions of the brain, but these techniques lack single-neuron
resolution.1 The reason that this level of resolution is necessary is that any given piece of the
brain has different cell types with dendrites in the same cortical layer but that receive functional
input from different sources. Therefore, one area of the brain may show activity in response to a
given stimulus, but not all of the neurons within that region will necessarily show activity. In
addition, neighboring neurons of the same cell type can be connected differently and embedded
in different subunits.3 Finally, imaging of the brains of less complex organisms has provided
evidence that the brain contains broadly distributed functional circuits that might not be apparent
without sufficient resolution.4 For these reasons, the BAM team feels that it is important to
differentiate between cell types and even between single neurons. One technique that has been
used for brain imaging and that does provide single-neuron resolution is calcium imaging.
Because calcium is involved in signal transduction, fluorescent calcium indicators can be used to
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measure spiking activity in several thousand neurons at a time. Unfortunately, calcium imaging
is far too slow to truly capture the rapid firing of neurons in the brain. For this reason, the team
plans to use voltage imaging, a term that refers to a number of techniques for directly measuring
voltage changes within the brain.1
While several techniques for voltage imaging exist, there are a number of issues that
complicate the task of measuring voltage changes within the brain. One issue is that the electric
field produced by an action potential is only detectable at very small distances from the
membrane of a neuron, meaning that any voltage indicator needs to be inside the membrane or
directly contacting it. Other challenges include fitting a sufficient number of voltage sensors in
the relatively thin membrane of the neuron; avoiding the use of sensors that will bind
indiscriminately to any membrane, including internal membranes; and not damaging the
membrane of the neurons. A promising technology for voltage imaging is the use of
nanoparticles, which are very small, inorganic particles that are often sensitive to electric fields.
These could be used as the sole voltage indicators, or they could be used to amplify the
fluorescence of other chromophores.5 No matter what indicator is chosen, advances in
technology that will allow more neurons to be imaged at once and that can image deeper into the
brain are necessary. In addition, current methods involve opening the skull, which makes
experimentation on humans impossible. An additional and fairly interesting method of detecting
voltage changes being considered by the group is the use of DNA polymerase, which has an
error rate that is dependent on cation concentration.1
If the Brain Activity Map Project is approved by Congress, it will likely receive
somewhere in the area of $3 billion in funding.6 The plan is intended to be “in the public
domain” due to the massive scale of the project and the number of participants it will require.
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Any member of the public will have full access to any data produced by the project. Potential
benefits that could result from the project include new diagnostic tool, treatments from mental
diseases, and technological advances in the areas of imaging and analyzing large data sets.1 It is
also hoped that the project will stimulate the economy in much the same way that the Human
Genome Project did.1 In his State of the Union address, President Obama emphasized the fact
that every dollar that was invested in the Human Genome Project returned approximately $140 to
the U.S. economy.6 Potential negative consequences foreseen include issues of mind control,
discrimination, health disparities, unintended short- and long-term toxicities, among other
things.1 While the potential for mind control may seem somewhat unlikely, it is definitely within
the realm of possibilities. Many experiments on the function of neural circuits involve
stimulating or inhibiting certain neurons in an animal’s brain and observing the results. Given
sufficiently advanced technology, human mind control could be possible in the same manner.7
The Brain Activity Map Project has drawn criticism from a number of members of the
scientific community. Much of the criticism is focused on the fact that mapping the human brain
is a far more challenging undertaking than sequencing the human genome, and the task may
simply be unrealistically difficult. The Human Genome Project was already technically feasible
at the time of its inception, but the technology required to complete the Brain Activity Map
Project does not exist and may not exist for many years.8 Another issue is that the U.S.
government only devotes so much money to scientific research, and such an expensive project
would draw funds away from other scientists struggling to receive any government funding. Still
others question the value of the data that the project is attempting to produce. They believe that
activity of individual neurons is not the most important information required in order to
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understand the brain and that the money would be better spent on research that does not
necessarily have single-neuron resolution but instead images groups of neurons.9
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Works Cited
1
Alivisatos, A. P.; Chun, M.; Church, G. M.; Greenspan, R. J.; Roukes, M. L.; & Yuste, R.
(2012). The brain activity map project and the challenge of functional connectomics.
Neuron, 74(6), 970-974.
2
Williams, R. W.; Herrup, K. (1988). The Control of Neuron Number. Annual Review of
Neuroscience, 11, 423-453.
3
Callaway, Edward. Neural Circuits in Action (Webinar). Cell Press. March 27, 2013.
4
Ahrens, Misha B.; Keller, Philipp J. (2013). Whole-brain Functional Imaging at Cellular
Resolution Using Light-Sheet Microscopy. Nature Methods. doi:10.1038/nmeth.2434
5
Peterka, Darcy S.; Takahashi, Hiroto; Yuste, Rafael. Imaging Voltage in Neurons. Neuron,
69(1), 9-21.
6
Markoff, John (2013). Obama Seeking to Boost Study of Human Brain. The New York Times.
Retrieved from http://www.nytimes.com/2013/02/18/science/
project-seeks-to-build-map-of-human-brain.html?pagewanted=all&_r=0
7
Sternson, Scott. Neural Circuits in Action (Webinar). Cell Press. March 27, 2013.
8
Markoff, John (2013). Connecting the Neural Dots. The New York Times. Retrieved from
http://www.nytimes.com/2013/02/26/science/
proposed-brain-mapping-project-faces-significant-hurdles.html?pagewanted=all
9
Mitra, Partha (2013). What’s Wrong with the Brain Activity Map Proposal. Scientific
American. Retrieved from http://www.scientificamerican.com/
article.cfm?id=whats-wrong-with-the-brain-activity-map-proposal