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AVAILABLE TOOLS FOR WHOLE BRAIN EMULATION

DIANA DECA
IMPRS-LS, Am Klopferspitz 18, Munich, Germany
dianadeca@yahoo.com
Whole brain emulation (WBE) has been, for a long time, the subject of interest for many science
ction productions and a subject for debate for many philosophers. This is one of the reasons
why many mainstream scientists have remained skeptical about a scientically sound approach
to it. Whole brain emulation might be considered more complex than it actually is because of all
the philosophical and methodological issues that people have been pointing out in the last
decade. However, not everything that every brain and computer scientist had ever said needs to
be taken into account when designing a realistic brain emulation system. In this paper I would
like to give a brief overview of the relevant research for WBE coming from the neurosciences and
how it can be combined with other disciplines in order to achieve the goals of WBE.
Keywords: Whole brain emulation; neurobiology; data acquisition tools.
1. What is Whole Brain Emulation?
Whole brain emulation (WBE) has been, for a long time, the subject of interest for
many science ction productions and a subject for debate for many philosophers.
This is one of the reasons why many mainstream scientists have remained skeptical
about a scientically sound approach to it. Whole brain emulation might be con-
sidered more complex than it actually is because of all the philosophical and meth-
odological issues that people have been pointing out in the last decade. This might
have appeared so because the concept of brain emulation is currently treated as a
philosophical issue or at most a futuristic idea which needs to refer to an undened
number of scientic advancements, and the amount of information that all the rel-
evant scientic papers include just cannot be ltered by a few writers with a philo-
sophical inclination. For example, a number of philosophical critiques to brain
emulation refer to the term \qualia" and the impossibility of an articial brain to
produce such an eect [BDGP, 2011]. Assuming that a brain emulation would need
to reproduce qualia, there is already a lot of available information about the
neurobiological substrate of qualia and how it is produced in dierent organisms
[Flybrain, 2000] [Virtual Fly Brain] [Newland]. For example, Nagel's famous critique
[Nagel, 1974; NCBI] on the impossibility of scientists to understand bat vision (and
therefore qualia), there are recent neuroscientic papers showing precisely how the
International Journal of Machine Consciousness
Vol. 4, No. 1 (2012) 6786
#.
c World Scientic Publishing Company
DOI: 10.1142/S1793843012400045
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bat visual system works [Shishido et al., 1998; Brenman et al., 2001; Henrich et al.,
2001]. The only limitation in this sense is that the information is very vast, and the
extent to which it satises this critique can only be decided after one computes all the
available information. I will argue that it is time for brain emulation to be treated as a
scientic project, rather than a philosophical issue by the entire scientic community
who is doing relevant research in dierent elds. Besides the two books mentioned in
the previous reference, some general knowledge about the state of research in
neuroscience and biochemistry would be necessary to assess the importance of these
ndings for Nagel's arguments. Although some arguments against the qualia critique
have been formulated by philosophers of mind [Collins and DiAntonio, 2007; Collins
et al., 2006], they include very few details about the neurobiological substrate on
either side of the argument, and therefore the debate remains in a vague area where it
is hard to decide which arguments hold and, if so, on what basis. In this sense, I would
like to propose a theory of WBE that runs parallel to these debates, and is based on
simpler assumptions. The question of whether the resulting emulations will satisfy
the philosophical criteria for qualia and consciousness will be decided at the time
when the underlying high level functions will be suciently understood and modeled.
The main idea behind WBE is getting very detailed information about a par-
ticular brain or an average of some type of brains, scan and analyze its structure in
detail, and then make a reimplementation that is similar enough to the original data
that it would behave essentially like the original [Wu et al., 2007]. There are three
important components to this denition, namely how much neurobiological infor-
mation we would need, how similar must the reimplementation be, and what criteria
we would need to formulate in order to decide whether this reimplementation
behaves like the original or not. Sandberg and Bostrom [2008] argue that we do not
need to know everything about the brain in order to emulate it. They argued in
2008 that while WBE would not yet be achieved just by giving complete scans,
parts list and brain databases, these would however be important milestones towards
that end, according to them. Section 3 will give a brief overview of the current
databases and how they correspond to what was mentioned in the emulation road-
map. Before that, however, I would like to give three possible denitions of the term
hwhole braini.
(a) Whole brain one brain that emulates all the features of all the brains in the
world. But in order to combine all the features of approximately six billion
brains, one would need to emulate all the dierent external factors that interact
with the brain, which are related to particular events in each individual's life. A
lot of these structural features which are the direct result of particular events in
one's life would overlap, so an average of all of these cannot be the basis of a
proper emulation.
(b) Whole brain universal neurobiological substrate which is common to all the
brains in the world. If this is so, then there are in fact not so many features which
need to be taken into account. Brains are extremely plastic and their particular
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physiology will therefore depend to a very large extent on genetic heritage,
environmental conditions and the rest of the body (from the type of climate the
individual encountered to the kindergarten teacher's personality and to the type
of car one drives a GPS can have a huge impact on the brain for example, and
so can prescription glasses or playing sports). An average brain that abstracts
from all of these structural dierences would be based on some well-known
fundamental neuroscientic principles. The question is how much of the brain
would remain if all particular features are ignored. This brings us to the third,
working denition.
(c) Whole brain a reimplementation with a set of features which are considered
sucient and necessary for a brain reimplementation to be able to perform all
the function of a biological brain if put in the right environment, and this is a
concept that any scientist would need to dene before embarking on a brain
emulation project. This concept need not satisfy all the scientists/philosophers
in the world, in fact it might be more useful if more brain emulation projects
appear in parallel, depending on particular goals.
I will only be using hwhole braini in its third sense here, namely as a model which
satises the scientic community's criteria for a brain.
2. Brain Models
Current neuroscientic research is carried out on a number of organisms, ranging
from ies, rodents, lower-level mammals, primates to humans. There are some
techniques which are somewhat specic to some species, while other techniques are
used on a wide range of organisms. The easiest way to list these techniques according
to dierent types of animal models.
2.1. The y brain (insects)
The humble Drosophila has given some of the most important information science
has ever provided, in particular genetic information [BDGP, 2011]. The simplicity of
its behavior allowed for the accurate analysis of the inuence of dierent genes at
dierent levels, which can then be abstracted from and used to answer important
questions about how the brain works. Given the amount of information genetics has
already provided by using this organism, it is then easier to understand and model
important functions of the brain and the responsible genes for this [BDGP, 2001].
Other similarly simple organisms which helped neuroscientists understand the most
fundamental aspects of the brain are locusts, cockroaches and ants [Newland] which
have helped in understanding the biological basis of taste or smell.
Genetic research on the Drosophila allowed for targeting the genes responsible for
the development of the visual system (aecting synapse targeting, axonal path-
nding and guidance) [Shishido et al., 1998; Brenman et al., 2001]. Furthermore, the
genes regulating synaptic growth and brain plasticity during development have been
Available Tools for Whole Brain Emulation 69
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found [Collins and DiAntonio, 2007; Collins et al., 2006; Wu et al., 2007]. The elegant
and simple olfactory system of the Drosophila led to some important results for
understanding how odor discrimination works [Bhandawat et al., 2007; Fishilevich
et al., 2005]. These molecular genetic studies opened up the horizon for combining
electrophysiological and genetic techniques in order to understand functional chan-
ges in the brain during development and in response to the environment. Behavioral
genetic research has proven useful in seeing the role of dierent genes in under-
standing feeding behaviors, reproduction and social behavior in the y models [Ha
and Smith, 2006]. Furthermore, the simple knock-out genetic procedure allows for
understanding memory and learning eects. More biochemical research has pointed
out which genes and neurons are crucial in regulating the circadian rhythm
[Fernandez et al., 2007; Huang et al., 2007]. The impact of genes on the neural
architecture is relevant for WBE in that it provides a model for how plasticity can be
controlled and coded for.
Importantly, the discovery of the role of Channelrhodopsin-2 and the purinor-
eceptor P2X2 in making neurons responsive to optical stimulation has been suc-
cessfully used on ies [Lima and Miesenbock, 2005; Schroll et al., 2006]. Through
optical stimulation of neurons in specic brain areas (light stimulation directly on
specic neurons), the behavior of these ies was shown to be manipulable in a remote-
control fashion. Its applicability goes through all the ranges of organisms mentioned
above, including humans. This particular technique is particularly interesting for
WBE as it allows, by manipulating the brain's functional connections, to view how a
particular neural system works (such as the dopaminergic system) and therefore how
it can be emulated starting from imitating a function without needing to understand
the entire structure.
As previously mentioned, since the visual system in the Drosophila is quite well
documented at this point, projects analyzing the way visual information is translated
into navigation directions in the y brain are now possible. The Borst lab [Borst,
2012a] has produced some interesting models of the integration of visual information
in the Drosophila Melanogaster (fruit y) and the Calliphora vicina (blow y).
Importantly, the membrane properties and pharmacology of individual neurons of
these species during ight is currently being digitally reconstructed [Borst, 2012b]
and its robotic version is currently being implemented based on the y visual
and navigation system [Borst, 2012c], which will be further discussed in the future
sections about computational models of the brain.
2.2. The mouse brain (rodents and lower-level mammals)
The mouse model (as well as a few others lower-level mammals, such as the ferret or
the cat) have allowed for in vivo imaging at single cell (even dendritic spine) resol-
ution with the aid of electron and two photon microscope. The invention of the two
photon microscope [Denk et al., 1990; Goeppert-Mayer, 1931] has allowed the ima-
ging of neuronal networks in the living animal, and therefore the possibility to look at
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activity dependent functional changes in these networks. The modules mentioned in
the y brain analyses (vision, sound, smell, reproduction, social behavior, etc.) have
thus been explored in much more depth in these animal models, which are also closer
to the primate and human brain modules. Furthermore, structure and function in the
brain can now be correlated by combining in vivo and in vitro imaging. After in vivo
imaging, the brains of these animal models can then be sliced (the machinery for this
will be further documented in the following chapters) and 3D models showing the
correlation between the structural and functional changes in dierent types of cells in
dierent brain areas in response to particular environmental stimuli have been made
[Bock et al., 2011]. The data obtained in this way can then be stored and combined in
repositories [Allen Institute for Brain Science, 2012; Open Connectome Project,
2011a] thereby making the complete model of the mouse adult, as well as the
developing brain with all of the genes involved, with connectivity in response to
dierent stimuli, only a matter of time. In the future chapter I will further explain
how the data from dierent animal models can be correlated, and how the structural
and functional dierences and similarities of the dierent types of brains can be
explored and used for dierent types of brain emulation.
What is obtained through the electron or the two photon microscope is a change
in uorescence of particular neurons (which have been injected with a specic dye
before the experiment). The dierence is that the two photon microscope allows for
imaging at greater depths with little photodamage and phototoxicity. What is
approximated by the change in uorescence in these neurons is their electrical
charge. A higher uorescence rate is correlated with a higher electrical charge. This
can be veried by electrophysiological techniques. An electrode can be inserted
directly into the neuron and the membrane potential can be measured quite accu-
rately. This potential can also be modied by changing the charge on the other
electrode [Margrie et al., 2002].
Optical stimulation on dierent brain areas has also been used successfully, in
order to manipulate the behavior of these animals and thereby allowing to precisely
locate the neural systems involved in these behaviors [Miesenbock, 2011; Bernstein
and Boyden, 2011; Stuber et al., 2011; Tye et al., 2011]. Importantly, the ability to
control these behaviors by altering the electrical neurocircuitry has provided neu-
roscientists with important evidence that the brain works in a manner which can be
explained in terms of electrical engineering. This information should be extracted and
popularized for computer scientists and philosophers interested in the project of
whole brain emulation.
2.3. The primate brain (human and non-human primates)
The neuroscientic explorations into the human and non-human primate brains are
probably the most relevant ones for WBE. The structure and function of these brains
is very dierent than that of mice or insects. For example, while the visual cortex of
cats and primates is organized into columns [Crair et al., 2001], the visual cortex of
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mice has a salt-and-pepper-like organization [Sirotin and Das, 2010] given the less
developed visual system of mice. However, the hippocampus of mice, corresponding
to navigation and memory, is much more delevoped compared to that of humans
[Harvey et al., 2009], suggesting how a brain emulation could be made that combines
the advantages of the brain of dierent animals, while avoiding the limitations of
each of them. However, because of the fact that primates have such developed brains,
the kind of research that can be performed on these animals is essentially the same as
the neuroscientic research that can be done on humans, for obvious ethical reasons. I
will briey mention them here, and say how the dierent techniques work on the
primate brain and how the monkey and human brain can be correlated. First,
positron emission tomography (PET) and functional magnetic resonance imaging
(fMRI) can be used in order to assess high-level mental processes and their corre-
sponding brain areas and electric activity [Cross et al., 2000]. While these methods
can provide us with important information about the corresponding brain areas of
high-level functions and how they dier in monkeys and humans, the data obtained
in this manner is based on the level of O
2
in the blood (its magnetic properties in
combination with the MRI scanner give the very esthetic, yet mathematically
speculative images) or electrical signals averaged over large brain areas and therefore
not much spatial resolution (PET). One way of verifying the validity of this kind of
data is by performing the same experiment on the same task, but with optical
stimulation in mice [Logothetis, 2002]. One of the main limitations in these studies is
the fact that the skull also masks a lot of the observed changes; however both pro-
cedures are not invasive and are much less stressful for the animal. Importantly, these
correlations between the human and monkey brain can tell the scientic community a
lot about what features might have evolved in the human brain, how they came
about, and also a glimpse of how the human brain might evolve in the future (and
therefore a WBE that could incorporate the upgraded model).
Scientists have tried to overcome the poor temporal resolution of fMRI and poor
spatial resolution of PET with the aid of electroencefalography (EEG) and magne-
toencefalography (MEG). However, because of the skull, again the information
provided by these methods is not very exact compared to the data obtained with
microscopes from the mouse or y brains.
Transcranial magnetic stimulation works on a very simple principle: an exper-
iment using the technique asks if temporarily disrupting brain activity in a specic
area will interfere with the behavioral performance during a task. It then becomes
apparent that such tasks would need to be quite simple in order to obtain clear
information about the exact role of that particular area. However, there are ingenious
projects exploring the concept of consciousness with this technique [van Gaal and
Lamme, 2011].
One way of matching neuroanatomy with the functional data obtained with this
method is to do a post-mortem anatomical analysis of these brains, which is not
very dierent to the one done with mouse brains with electron microscopy
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[Schleicher et al., 1999; Zilles et al., 2002]. Also, to study the causal connections
between two specic areas in the monkey brain, lesion studies can be performed
[Chafee and Goldman-Rakic, 2000]. As it was previously mentioned, techniques like
TMS, lesion studies and optical stimulation allow us to see if the brain has some
particular switches and to analyze the brain as if it were one big circuit, and
therefore connecting only structure to function, without the need to understand all
other processes. The only limitation with this kind of study is, however, that we
cannot know whether these binary, unidirectional correlations oer us just enough
information to eciently emulate the brain. What could help in that sense is of
course a clear system for deciding whether a particular WBE is satisfactory or not,
and continuously update the model with more detailed information according to its
requirements.
A more invasive procedure done both in monkeys as well as in human patients
with Parkinson's disease is the single cell recording. This is done with a surgery in
order to remove the skull and therefore more noise-free data can be obtained in order
to understand the role of particular neurons or populations of neurons in response to
dierent stimuli, as well as in more high-level tasks [Riehle and Requin, 1989; Liebe
et al., 2011; Buschman et al., 2011]. Interestingly, these techniques can be correlated
at the analysis level, and models can be made on the dierence between monkey and
man high-level functions, by combining, for example, single cell recordings in mon-
keys and fMRI in humans [Kriegeskorte et al., 2008].
Finally, some studies on the dierences in human brains can provide WBE with an
outline of the answer to the initial question of how much neurobiological information
on stimulus-dependent plasticity of the brain must be included in the emulation.
For example, studies on autism suggest how increased connectivity in some brain
areas might account for mathematical talent [Rinaldi et al., 2008; Markram and
Markram, 2010].
3. Brain Databases
3.1. The Allen brain atlas
These atlases [Allen Institute for Brain Science, 2012] cover the mouse, human and
non-human primate brains, along with their gene expression and complete (although
growing) 3D neuroanatomical data. The dierent averaged brains include atlases for
brain development, sleep, glioblastoma etc. These ropositories are very important
because they can embed more such data and are free to use for any type of scientist.
Furthermore, the data can be analyzed with dierent types of software and func-
tional data can also be embedded within in (for example, the human neuronanato-
mical data can then include neuroanatomical data in response to dierent stimuli and
therefore changes in the brain). These databases oer enough information for
building dierent goal-oriented brain emulations.
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3.2. The connectome
The Open Connectome [Open Connectome Project, 2011a] has as its main goal to
completely reverse-engineer the brain. It already includes an impressive connectome
data, including both anatomical (mouse) and functional (fMRI) data [Open Con-
nectome Project, 2011b]. The Open Connectome is also free to use for anyone, and
open source, therefore any type of code used for analyzing the data can be down-
loaded and modied. Furthermore, since the goal of the project is receiving and
combining as much neural data as possible, ranging from micro (cellular) data to
macro data (fMRI) data, as well as the types of analysis that can be performed on the
data, anyone can contribute to the project [Open Connectome Project, 2011c].
This and the human connectome [NIH Human Connectome Project, 2010] are the
most important recent advances in the emerging eld of connectomics, which is
similar to the project of the human genome, except it attempts to give a complete
map of the brain ranging from neurons and synapses to functional connectivity
between dierent brain areas. These databases represent important milestones in the
WBE project and provide vital information ready to be analyzed and combined with
the tools mentioned below.
Based on Sec. 6, we should be able to estimate how much information from the
genome [NCBI] and the physiome [NSR, 2011] we need to incorporate in a brain
emulation in the nal discussion.
4. Data Acquisition Tools
There are a number of tools which I would like to briey describe in order to
understand what kind of information about the brain can be currently obtained. In
the next chapter I will mention the dierent repositories or databases that store and
combine the information obtained with these dierent methods. The subsequent
chapter will explain the computational means to reproduce the eects observed in the
meta-analysis of the brain data obtained and how it can be emulated. The dierent
tools are used for dierent types of brain data.
4.1. fMRI, EEG, PET, MEG, TMS
All these techniques were briey mentioned in 2.3 as they are relevant in under-
standing the connections between the human and non-human primate brain struc-
ture and function. As previously mentioned, they are the only available non-invasive
tools for the analysis of brain function in higher mammals (except for the single cell
recordings, which will be discussed in Sec. 4.5). They all depend on the electrical
properties of the brain, but are of course limited spatially and temporally by the
presence of the skull, blood ow and the interpretation of the role of the dierent
wavelengths in the presence of specic stimuli. However, more basic studies have
conrmed to some extent the coupling between some of these techniques and loca-
lized neural activity. Furthermore, the results obtained on more high level and
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complex brain functions (such as those required in memory processes, decision
making and socializing) can be interpreted and connected to the other ndings within
the scientic domains. This is one of the important advantages for WBE, in that
specic functions can be emulated and their evolution understood by combining data
from dierent techniques, with dierent types of acquisition and analysis tools.
Again, while fMRI is based on the BOLD (blood-oxygen-level-dependent) signal, the
images obtained will show activation bulbs based on this ratio, and the correlation
between this and neural activity is not completely established. EEG, MEG, and
PET will show dierent wavelengths which in time have led to correlations between
brain activity and particular values for them. TMS is a stimulation technique
and it allows for the temporary shutdown of a particular brain area and therefore its
relevance for a particular task can be speculated. However, as in the case of
optogenetics and other methods of direct manipulation of neural activity, it is
unclear whether these \switches" are responsible for a mental function all by
themselves or are part of a circuit that is itself necessary for carrying out a particular
function. The correlation between this type of data and other data will be mentioned
in Secs. 5 and 6.
4.2. Microscopy: electron, confocal, two-photon
The role of microscopy has changed in neuroscience in the past years, mostly due to
the technological advances that led to microscopes which allow for higher temporal
and spatial resolution, as well as for imaging at greater depths, while reducing the
damage that the light is doing to the tissue. In particular, two photon microscopy has
allowed for imaging in the living animal by optimizing these features. The main
dierence between these three types of microscopes comes from the way in which the
photons coming back from the scanned tissue are collected and analyzed. For
example, experiments made on slices of brain tissue (which therefore have a small
depth), electron microscopy will be sucient and also it allows for the large scale
reconstruction of neuronal networks. Confocal microscopes are useful in that they use
a pinhole which rejects all the light not coming directly from the point of focus of the
microscope. Two photon microscopes also allow for obtaining 3D models by changing
the depth of the focal point. Together with the structural 3D information provided by
the electron microscope and a common way of correlating the analysis for the two
types of data, computational models of dierent mental functions can be constructed.
Finally, two photon microscopes avoid this problem by focusing all the light in a laser
beam which will be focused only on the particular spot which is analyzed. Further-
more, two photon microscopes allow for the tracking of one or more neurons for a
timespan of weeks with the aid of a chronically implanted window in mice. Such
experiments are very important for understanding morphological as well as func-
tional changes in the brain as a result of repeated stimulation, and therefore
understanding the basis of learning and memory. Such experiments will prove very
useful for the project of WBE in that they allow for the reproduction of mental
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functions in the brain based on a thorough understanding of the contribution of the
most elementary parts (namely, neurons with their axons, dendrites and spines).
4.3. Staining techniques for microscopy
The images obtained by means of non-electron microscopes are based on the amount
of uorescence that the neurons and other cells have in comparison with the back-
ground. In order to make the cells uorescent, a number of dyes can be used
[Bolsoveri et al., 2001]. Some dyes are inserted via an electrode either directly into a
particular neuron [Zalvidea and Claverol-Tinture, 2011] or in a specic brain area
where the dye penetrates a larger number of neurons through their membrane
[Garaschuk and Konnerth, 2010] just before starting an experiment. Other uor-
escent dyes are injected into an animal weeks before the experiment in combination
with a virus [Wallace et al., 2008]. The eciency of these uorescent dyes which are
usually indicators of the amount of Ca
2
there is in the cell is very important for an
accurate assessment of the neural activity. There are currently a number of projects
trying to analyze the connection between the uorescence ratio and the actual
electrical activity of a given neuron, as well as projects attempting to optimize the
SNR of the images obtained with these dyes. The limitations of using Ca
2
indicators
relate to the inability to capture and understand rapid signaling event in neurons, as
well as the precise underlying electronic events in neurons. These limitations can be
overcome by combining data obtained in this way with dierent electrophysiology
techniques, which have already been discussed in detail.
A very promising uorescent dye project is called the Brainbow project, which
allowed for the labeling of specic neurons with a large palette of colors, thereby
allowing an in depth and long term analysis of stimulus related plasticity [Weissman
et al., 2011]. Combined with advanced microscopy techniques such as two photon
microscopy, this method allows for the mapping of structural changes of a specic
neural network in time in response to dierent stimuli. One could look, for example,
at the long-term eects of learning in the appropriate brain areas, by repeated
imaging experiments on the same neuron and even dendrite. Furthermore, these two
techniques can be further combined in order to control the activity of specic
neurons.
4.4. Genetic tools in neuroscientic research
Genetic research is particularly important in neuroscience in that it oers infor-
mation about how the structure and function of the brain can be manipulated. Also,
it provides a direct tool in analyzing some functions. As previously mentioned, it can
help with making some neurons uorescent, and neuroscientists able to observe the
changes in uorescence for weeks. Furthermore, the number of some genes can be
diminished or amplied in order to understand the eect of those particular genes.
This is usually done in neuroscience with mutant (or knock-out KO) mice. Base
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on such experiments, impressive databases have been made explaining the eects of
dierent genes on brain physiology and thus behavior [MGI, 2012]. This type of
genetic manipulation is particularly interesting for WBE because it shows how a very
large number of factors (or switches) inuence the brain, and thereby oers infor-
mation about the number and type of switches necessary in order to control a whole
brain emulation. Another interesting genetic tools is optical stimulation. Optoge-
netics is the rst method which allows for the precise control of neurons, even in freely
moving animals, with a millisecond precision. Miesenboeck rst demonstrated the
eect of this technique by altering the behavior of fruit ies with light [Miesenbock,
2011]. Later on, Boyden and Deisseroth controlled the motor behavior of mammals
with Channelrhodopsin and coined the term optogenetics [Boyden et al., 2005]. As
previously mentioned, controlling neuronal activity and thus of behavior in vivo is an
extremely powerful tool for WBE and neuroscience in general since it provides the
possibility of nding the switches for dierent systems, such as the dopaminerginc
and motor ones. Once these systems may be controlled directly in the brain of ani-
mals, they can be more easily emulated once their key parts are distinguished.
Furthermore, optogenetic control could lead to better humanmachine fusions in
which the brain directly interacts with the machine and vice versa, by means of
changes in electric potential.
4.5. Electrophysiology
Electrophysiology is the branch of physiology that deals with understanding the
electrical properties of tissues. Classical electrophysiology usually requires the use of
electrodes. These electrodes vary in size (from smaller than a single cell, like the ones
used in patch clamp) to the electrodes used for deep brain stimulation in humans
and single cell recordings in monkeys. The patch clamp technique [Neher et al.,
1978] is important as it allows for an accurate measure of the electrical potential of
the membrane, and the contribution of dierent ions and ion channels to this
potential. As previously mentioned, the uorescence ratios in microscopy approxi-
mate the electrical charge by showing the Ca
2
concentration; however, there are
experiments combining the use of electrodes and microscopy, as well as single cell
recordings with electrodes and fMRI studies, thereby allowing neuroscientists to
understand a particular mental event at the electrical, chemical and physiological
level at the same time. Such correlations are particularly important for reproducing
the material substrate of a brain and knowing what the factors are in creating high-
level mental functions. Recent developments of the patch clamp even allow for
recording the electrical state of a single ion channel on the membrane of a neuron
[Hamill et al., 1981].
As the reader might have noticed already, each of these techniques can bring
something new, and some of them are quite impressive in their ability to provide
information about the neural substrate of mental events. However, within neuro-
science, the techniques and domains are still rather sparse and thus a direction for
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whole brain emulation is needed. One of the important goals of neuroscience was to
not view the brain as a black box when analyzing mental functions. However, an in
depth analysis of the brain shows that looking at dierent levels creates smaller black
boxes. As previously mentioned, the non-invasive techniques do not tell us very much
about the neurons, the microscopy techniques do not yet give a clear connection
between large-scale neural networks and their role in a specic mental event, and
genetics can only oer little information about the interaction between the brain and
the environment. One of the biggest challenges in neuroscience at the moment is to
nd a way to combine large-scale and high resolution data, in order to understand
functional changes in the brain. In order to achieve whole brain emulation, the
scientic community involved in the project must decide what kind of data and
models would be relevant for brain reimplementation.
4.6. Other tools
A neuronal circuit typically spans quite a large volume of brain tissue, namely tens of
cubic millimeters. At the same time, the axonal anddendritic processes comprising such
a circuit are so ne and interconnected that only electron microscopy of ultrathin
(50 nm) serial sections can resolve their connectivity. In order to map out the brain's
neuronal circuits, a team of neuroscientists has built the automatic tape-collecting
lathe ultramicrotome (ATLUM) [Hayworth et al., 2006; Lichtman Lab], which should
allow for nanoscale imaging over large tissue volumes [Hayworth et al., 2006]. Its
creators envision a conuence of techniques in the future, including the ATLUM, two-
photon microscopy, neuronal tracing algorithms, random-access nanoscale imaging,
and large scale simulations of neuronal circuits.
64
The hope is that combining all the
data acquired with these techniques will complete the Human Brain Connectome
Project suchas those inthe Blue BrainProject, whichwill be discussedlater onindetail.
Other tools for acquiring large-scale structural neural data with the scanning
electron microscope (SEM) are the Tape to SEM and Focused Ion Beam SEM. For
the acquisition of functional data through electron microscopy, electrical recordings
can be made, as well as two photon microscopy, and with the aid of the molecular
ticker tape [Shimizu, 2010].
5. WBE
5.1. Existing computational models of the brain
The Blue Brain Project [EPFL, 2011] is currently one of the most ambitious attempts
to model the whole brain [Markram, 2006]. One of the advantages with this project is
that it makes use of the Blue Gene supercomputer [IBM, a]. Since its establishment in
2002, some advancements have been made towards that goal, such as creating the
rst model of a cortical column of 10,000 neurons, followed by an auto-generated one.
This was followed by a paper on how to x the location and dimensions of a given
cortical column [Markram, 2008].
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Meanwhile, there have been some other projects attempting large-scale brain
inspired computer simulations. Some models attempt to mimic the ight of the
Drosophila based on the available information about its brain [Borst, 2012c] or to
reproduce a cortical column in silico, in order to understand the functional and
morphological changes needed for something to be able to learn [Sakmann, 2012].
The IBM cognitive computer [Dharmendra et al., 2011] is based on the cognitive
computing project called systems of neuromorphic adaptive plastic scalable elec-
tronics (SyNAPSE) and is a biologically-based large-scale computer simulation of the
brain. The main ideas behind it can be viewed on the website [IBM, b]. In its initial
phase, the program developed nanometer-scale electronic components which were
capable of adapting the connection strength between two nodes in a manner similar
to neural plasticity in biological brains (imitating Hebbian learning). Some of the
future directions of this ambitious project include developing increasingly capable
architecture and very large-scale computer simulations of the neuromorphic systems
already made, as well as the virtual environments needed to test these simulations.
One discussion that may easily arise is whether such a neuromorphic computer would
indeed be cognitive as its makers claim it to be. As mentioned in the beginning of the
paper, the term cognitive has a number of meanings in dierent contexts (for example
depending on the subdiscipline in philosophy, biology or cognitive science) and
therefore a lot of the critiques will be based on the fact that the denition of the word
\cognitive" employed by the researchers at IBM is completely dierent than that
used by other people. If one denes \cognitive" as something that is able to process,
store information and change its structure in order to adapt to the environment, then
a neuromorphic computer capable of satisfying these criteria would indeed be cog-
nitive. Obviously, the cognitive computer is still in project phase, but given the
resources involved in the project, WBE enthusiasts have good reasons to be opti-
mistic that it will contribute signicantly.
Neurogrid [Boahen, 2006] is a project similar to Blue Brain, but it diers in that it
uses one millionth of its power in order to run. The chip was made by the Brains in
Silicon group at Stanford University, ran by Kwabena Boahen [Boahen, 2006].
Neurogrid can model one million neurons and six billion synapses in real time. In
order to do that, it emulates ion channel activity by means of analog computation,
and it can be used for simulation experiments. Importantly it can abstract from and
model individual data and create large-scale simulations in order to verify localized
experimental observations and therefore see if a particular neurophysiological process
can sustain a particular cognitive task.
The complete connectomes that have been mentioned are of course not enough at
this point to give a complete in silico replica. Although there is a lot of existing
information about the contribution of dierent types of ion channels (along with how
their crystal structure allows for their morphological changes and which genes code
for this) within single neurons to the electrical potential which makes them connect in
dierent ways and produce the plasticity which underlies complex brain functions, all
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this information is still rather sparse and there is a strong need for goal-driven
interdisiplinarity, in this case the goal of WBE includes the goal of connecting
structure and function, as well as high resolution with large scale simulations.
5.2. Building an interface for facilitating information
exchange between neuroscientists and AI scientists
An important issue that I would like to point out in this paper is that there is an
obvious need for communication between neurobiologists, computer scientists and
engineers in order to be updated on the requirements for WBE. All three domains will
rapidly produce more knowledge in the eld and given the number of relevant papers
being published each year it seems almost impossible for a given scientist or even a
team of scientists to be fully updated on all the relevant information. That being said,
one of the aims of this paper is to suggest that it is imperative for the WBE project
that the scientists from the dierent domains nd a platform where they can com-
municate eciently and stay updated. One possibility for doing so would be to create
an internet platform which would facilitate collaboration [UniPHY] perhaps with
online means of voting on the most important features, in light of the existing sci-
entic information from all relevant elds. This could include philosophers, computer
scientists, neurobiologists, cognitive scientists etc. One interesting feature of the
WBE project is that the people interested in the topic seem to dynamically organize,
while coming from many dierent disciplines. Oering an ocial web platform for
doing so would greatly speed up the process. Another way of attaining this is by
creating specic events; some of them have already been organized [Future of
Humanity Institute, 2011] and websites have been made [Koene; Goertzel] towards
that goal, however a website that does not have a networking component will make it
hard for people to interact eciently and events which are biannual will spark
interest among scientists but will probably not be enough to keep all the scientists
involved very active on the topic. Adding a social networking feature to a particular
website is not very hard to do, as long as the rest of the website clearly exposes the
goals of WBE. For example, Facebook gives out its source code for adding a net-
working plugin online [github, 2012].
6. Conclusion
6.1. What we do not need
There are some things which, based on the current computational models, can be
excluded as irrelevant neurobiological information for whole brain emulation. For
example, the emulation roadmap mentions the role of understanding neuroglia in
order to achieve a computer model of the brain. It is true that glial cells (the brain's
antibodies) are an interesting topic of study for neurologists, and that the immune
system of the brain can be interesting in itself. There are even papers speculating
about the role of glial cells in cognitive functions, suggesting that they might remove
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dead neurons from networks and thereby speed up thinking processes. This is helpful
if we think about the neuronal network in the neural-Darwinistic sense originally
proposed by Edelman. For now, however, given the increased eciency of computers,
an immunitary system would be more or less equal to a debugging algorithm in the
emulation. Also, it is important to mention that in principle a computer chip would
not be sensitive to biological viruses and pathogens, making the debugging system
much easier to reproduce. Although the arguments for tossing out glia from the WBE
project are not yet sucient, it would be recommended at this stage to focus on other
issues already mentioned, since there is no clear proof at the moment that their role in
cognitive function is direct.
One idea that neurobiologists would almost unanimously toss out of the WBE
project would be the one supported by Penrose and others suggesting that one must
understand the underlying quantum phenomena in the neuron in order to fully
understand it. A very simple analogy with a computer would show that one does not
need to understand the quantum phenomena in order to understand the underlying
circuitry at an electronic level. There is no clear neuroscientic proof that there would
be any connection between consciousness and quantum processes.
Furthermore, we do not need to read all the papers on the ocial medical data-
base (pubmed), since this would take the average reader about 70,000 years. All the
detailed papers about specic neuroscientic ndings, whether they refer to the role
of genes in forming the brain or research on cognitive processes, do not need to be
understood by brain emulators. The information that the entire WBE scientic
community needs should be decided based on the proposals of neurobiologists by the
community itself.
6.2. What we need to take out of the neurosciences
A common question arising at conferences about the correlation between AI and
neuroscience is how much information about the underlying neurobiology computer
scientists and engineers need to extract before embarking on bold claims such as that
of building of cognitive computer. As mentioned in the beginning of the paper, we do
not need to know everything, as also Bostrom and Sandberg mentioned in their
collected data about an emulation roadmap.
The goal of this paper was to briey mention the neuroscientic techniques that
can be used for brain emulation, and how they can be applied and combined on
dierent types of brains. As we saw, the techniques used on higher level mammals can
tell us something about the most high-level functions of the brain, and answer
detailed questions posed by philosophers of mind, such as how categories are formed,
how memories are formed, how socializing works etc. One of the limitations of these
techniques is that while they are not invasive or stressful, they do not provide as
much detailed information about the neural substrate as other techniques used on
lower-level animals. In a sense, one could say that the black box in human and non-
human primate neuroscientic research is given by the individual neurons and the
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neuronal networks that form in response to these stimuli. On the other hand, the
research done on mice and insects tells us a lot about how individual neurons
rearrange in response to stimuli, and how neuronal networks are formed. However,
the black box here remains in the higher-level reorganization, and the construction of
mechanistic models of how the brain reacts. Some eorts are made towards this end,
and also towards understanding the correlation between low- and high-level brain
function, with the aid of the dierent databases such as the Allan Brain Atlas and the
Open Connectome. Furthermore, computational models of these brain processes are
now in progress, such as the Blue Brain and the IBM cognitive computer. All these
need to converge into a unitary whole, and also a more ecient web platform needs to
be constructed to assure the fast transfer of information between projects which are
relevant for WBE from neurobiology, computer science and engineering. As pre-
viously mentioned, quite a few of the projects that were mentioned in the emulation
roadmap as a big step towards the goal of WBE have already been made or are in
project and close to completion. The two databases already mentioned are relevant in
this sense, and so is the IBM cognitive computer. Another goal of this paper was to
show what kind of information the dierent neuroscientic elds can provide, and
how close to the biological reality of the brain these dierent ndings are (as the
reader might have guessed by now, there is no single technique that tells us exactly
how the brain works, and there are dierent approaches for dierent conceptual
levels at dierent physical levels, ranging from the physiological to the biochemical
and physic-chemical level of analysis).
There is no single way to decide what kind of neuroscientic research is relevant
for whole brain emulation, since that depends to a large extent on what kind of
emulation people have in mind (whether it is something that would satisfy the Turing
test, or that would be able to change its structure according to changes in the
environment thereby imitating brain plasticity, or something that is an upgraded
version of the human brain and therefore in line with the transhumanist ideals).
However, this is something that the various scientic communities can decide, as the
researchers interested in whole brain emulation also nd a way to communicate more
eciently and agree on dierent parameters. For now, localized projects made by
neuroscientists (Blue Brain) and engineers (IBM cognitive computer, the Neurogrid)
provide good examples of how WBE-related projects can start and be carried out. Of
course, the role of philosophers, such as that of the editors of the 2008 Oxford
emulation roadmap, cannot be ignored, provided that the people involved in the
WBE project are at all times updated on the same relevant information.
To conclude, the amount of information that needs to be taken out of the
neurosciences in order to achieve the WBE varies in quantity and quality with the
goals of WBE. This also depends on the background of the WBE enthusiast. Again,
the idea of this paper is that the information presented here, along with the relevant
links, is the minimum amount of information needed in order to have an overview of
the current state of relevant research.
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