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March 15, 2012
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By:
Dave Deriso
The Brain As A Network
References:
The brain is an enormously complicated system of interconnected cells. To give a rough estimate, Johnson and Wu suggest that the human brain has 1012 neurons with 1015 synapses1. To wrap your head around the magnitude of 1015 synapses, consider that it's about 222 times greater than the distance from Earth to Pluto in meters2. How do you begin to understand all the madness compressed into the three pound ball of flesh? I have no idea, and I don't trust anyone who claims to know either. However, there are some clever approaches to chipping away at the problem.
At the systems-level, the brain distributes computation over multiple regions. A good analogy is a peer-to-peer network that distributes number crunching across multiple computers, where each computer is specialized to perform some specific aspect of the computation. Abstract this by simply calling the computers "nodes" (which can represent anything, for example, brain regions) and the connections "edges," and viola! you have reached the entry point of network theory, which is a quantitative and visual approach to understanding how nodes relate to one another and how networks function as a whole.
Figure: Network Graphs, (Left) Undirected cyclic graph, (Right) Undirected acyclic graph viewed as a tree. Generated using NetworkX, a Python package developed by Los Alamos National Laboratory. Notice how in this particular case there are no arrows; these graphs do not depict the effective (causal) relationship between nodes. Such a graph can be called a "structural connectivity" graph.
Olaf Sporns is a professor of Psychological and Brain Sciences at Indiana University who wrote a book entitled Networks of the Brain, where he outlines the case for using network theory to better understand the how the brain works.
Why should we take advantage of modern network approaches to study the brain? Primarily, because these approaches can provide fundamental insights into the means by which simple elements organize into dynamic patterns, thus greatly adding to the insights that can be gained by considering the individual elements in isolation. Virtually all complex systems form networks of interacting components. [...] The brain is a complex system par excellence where complex components continually create complex patterns. The collective actions of individual nerve cells linked by a dense web of intricate connectivity guide behavior, shape, thoughts, form and retrieve memories, and create consciousness. No single nerve cell can carry out any of these functions, but when large numbers are linked together in networks and organized into a nervous system, behavior, thought, memory , and consciousness become possible. Understanding these integrative functions of the brain requires an understanding of brain networks and complex and irreducible dynamic patterns they create.3
Studying the brain as a network is an advancement of the older view of brain function as a series of modular parts. This added dimension provides additinal insight to the analysis of neurological dysfunction. The 19th century Harvard neurosurgeon Henery Jacob Bigelow carefully observed Phineas Gage, the famous lesion patient who lost part of his frontal lobe when an explosion rammed a railroad spike through his skull. Bigelow writes of post-recovery Phineas:
He is fitful, irreverent, indulging at times in the grossest profanity (which was not previously his custom), manifesting but little deference for his fellows, impatient of restraint or advice when it conflicts with his desires, at times pertinaciously obstinate, yet capricious and vacillating, devising many plans of future operations, which are no sooner arranged than they are abandoned in turn for others appearing more feasible.4
Should one conclude that the region through which the spike penetrated possessed the sole responsibility for making an individual polite and disciplined? Such a view would argue that the region is necessary and sufficient for producing the computation underlying that specific genre of thought and behavior. However, the brain is highly interconnected and plasticity occurs following damage. Furthermore, that region would have to get information from the eyes and ears to know how to compute an appropriate response, and such information would travel through a cascade of layers where information is further processed and abstracted. At what point does the abstracted representation of information become necessary and sufficient for computing an appropriate response? To answer this question, you cannot study the process as a series of regions with fluctuating activity, but rather one must study the system as a dynamic network that processes the information in a highly parallel and distributed fashion. Professor Sporns writes:
Interestingly, science is concerned with the structure, behavior, and evolution of complex systems such as cells, brains, ecosystems, societies, or the global economy. To understand these systems, we require not only knowledge of elementary system components but also knowledge of the ways in which these components interact and the emergent properties of their interactions. [...] In all cases, the quantitative analysis of connectivity requires sophisticated mathematical and statistical techniques.3
Network Graph Method Overview: (L to R) (1) Acquire diffusion weighted image from MRI, (2) segment the MRI into labeled anatomical regions, (3) compute the magnitude of flow from each region to each region into a connectivity matrix, (4) average this matrix across individuals, (5) plot the x,y,z location of the center of each region, the number of connections as the node size (red sphere diameter), and strength of each connection as line thickness. From Heuvel & Sporns (2011)5
So how does one get a network graph of the brain? While the simple graph above belies the prodigious amount of physics and neuroscience behind its construction, the basic idea is to measure water molecules as they bounce from place to place and find the direction that they tend to flow most often (the fractional anisotropy). The more water molecules that flow along one tract and the more coherent the flow, the "stronger" that tract is said to be. With functional data, one can compute the functional connectivity between each region (the extent to which two areas communicate). Integrate causal estimates, such as Granger causalities, and the model begins to explore the direction through which the information flows. SiFT, written by my friend and fellow network enthusiast, Tim Mullen, is a great toolkit for exploring dynamic causal relationships.
Hopefully this brief overview hasn't been too vague or misleading-–this approach certainly does not explain how the brain works. But the application of network theory to neuroscience is a great example of how the convergence of scientific disciplines results in a deeper understanding of complex phenomena. I recommend picking up a copy of Networks of the Brain by Olaf Sporns, if not just to marvel at all of the beautiful figures, but to really soak in the complexity of it all and ask yourself just how in the heck are we going to make sense of this complex machine?
References:
1. Johnston, D. (1995). Foundations of Cellular Neurophysiology. MIT Press.
2. Wolfram Alpha: http://www.wolframalpha.com/input/?i=distance+from+Earth+to+Pluto
3. Sporns, O. (2010). Networks of the Brain. MIT Press.
4. Harlow J. M. (1868). Recovery from the passage of an iron bar through the head. Public Massachusetts Medical Society 2, 327–347.
5. Heuvel, M. P. & Sporns, O. (2011). Rich-club organization of the human connectome. The Journal of neuroscience, 31(44), 15775-15786.
Note: 3/15/2012 The intoductory estimate was adjusted to reflect figures that acually made sense. Credit belongs to the folks on Google Plus who kindly pointed this out, without burning me to a stake. Cheers!
November 18, 2011
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By:
Dave Deriso
The Cause of Zombie Attacks: Genes or Cosmic Twinkies?
Extremely important to science, yet too often overlooked, is the element of simplicity. Good science writing should be as accessible to the general public as possible because it is the public who will fund or forbid the progress of science. Though simplicity sounds easy to adopt, it is quite difficult as it requires one to organize their thoughts before writing them down. Believe it or not, some people have trouble doing this, much to the detriment of their work. A science talk is no fun if half of your audience has no idea what you are talking about, and grant funding is difficult to obtain when the government is clueless on what researchers "do with the money." Making information accessible not only allows more people to understand, adapt, and implement your ideas, but it also rouses support from others outside the field.
It's always a great watch a non-scientist smile and say, "Ahhhh, I get it," after you explain your research in easy-to-understand terms. That wonderful feeling of epiphany also makes people feel smarter because they feel closer to understanding a field that is traditionally elitist, and often taught in a way that demands the memorization of endless facts and formulae and discourages the masses from following its path. Although difficulty gives science a charming mystique, it is also a fatal flaw. The masses fear what they do not understand, and consequently, and largely due to the poor communication ability of scientists, a lot of great ideas are misconstrued as threats to society.
Scientists, and especially those who write about science, need to be acutely aware of this double-edged sword. Although the mystery of genetics could lead to cures beyond the imagination of modern medicine, how many zombie films start out with a science experiment gone wrong?
Equally plausible to causing zombie-syndrome is an intergalactic cosmic twinkie that explodes on impact, spreading its nefarious alien marshmallow filling into the atmosphere, instantly causing the uprising of a blood-sucking army of undead zombies. But the public doesn't think of stale cosmic twinkies as a potential cause of zombie-syndrome; instead, they think of stem-cells, gene therapy, and pharmaceuticals. Why? Because they understand the limits of twinkies, but they have no idea what limits are on science.
Science is unknown, and is therefore a scary, and dangerous thing. What is unknown is often distorted into sacrilege, cruelty, greed, and worse --zombies. The misguided public response is often based on these assumptions, and is appropriate considering their line of reasoning and their perceived threats. After all, who wouldn't try to stop gene science to prevent zombie attacks?
When under public scrutiny, scientists finally realize how important simplicity is, and try to calm the situation by explaining the science in simpler terms. Usually, this response is too late as the rift between the scientists and non-scientists has already grown too large to bridge. Consequently, science pays for it dearly by being excluded from schools, funding, and, worst of all, patient access. Stem cell research is still suffering from this kind of punishment.
Until the importance of simplicity is realized and more readily adopted, science may continue to suffer from public resistance, governmental red-tape, and tight funding. Until then, geneticists might as well put anti-zombie medication in the "future directions" slide of their presentations.
October 28, 2011
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By:
Dave Deriso
Mind Over Matter
The second, and perhaps the most compelling assumption, is that such births represent an "inhumane cruelty." Clearly, Dr. Walker has never interacted with such individuals. Despite their striking disability, craniopagus twins have normal intelligent minds. The Bijani sisters, who studied law in Iran -an impressive achievement for anyone --conjoined or not-- were described as "a single unit albeit with diverse personalities." (Khan, 2005) The fact that the condition places a burden on society is not enough of a reason to terminate birth. Would you terminate a blind child's life? Or one with down syndrome? Stephen Hawkings is far more disabled than Dr. Walker, but I wonder who has accomplished more?
The interesting clinical condition of craniopagus affords a though-provoking debate over medical ethics. Here, we take a step back and decide whether it is ethical to for the physician to decide if the birth of such debilitated individuals should be allowed.
Ken Walker is a Canadian physician who claims that most doctors lack the "intestinal fortitude" to say that the birth of craniphagus twins "should never have happened." He goes on to say that that allowing such a birth is a "cruel experiment and will cost taxpayers millions of dollars in medical and social costs." He attempts to substantiate his utilitarian arguments by asserting that the Canadian "health care system cannot afford reckless expenditures of this kind." Finally, he claims that "Like it or not, we have reached a point where some medical decisions have to be based on financial realities" (Walker, 2007).
There are several assumptions underlying this argument. The first is that providing for these cases is a "reckless expenditure." Recent cases of craniopagus twins, such as Tatiana and Kristen Hogan, belie the veracity of his bold assertion. Despite the nature of their conjoined brains, the twins are not a massive financial burden to society and require only a modest regimen of anti-seizure medication --tantamount to the anyone else who may be prescribed medication. While, the courage of those who dare to be the Devil's advocate is admirable in some cases, regardless of the frugal motives behind his utilitarian argument- he has clearly assigned too low of a value to human life.
The second, and perhaps the most compelling assumption, is that such births represent an "inhumane cruelty." Clearly, Dr. Walker has never interacted with such individuals. Despite their striking disability, craniopagus twins have normal intelligent minds. The Bijani sisters, who studied law in Iran -an impressive achievement for anyone --conjoined or not-- were described as "a single unit albeit with diverse personalities." (Khan, 2005) The fact that the condition places a burden on society is not enough of a reason to terminate birth. Would you terminate a blind child's life? Or one with down syndrome? Stephen Hawkings is far more disabled than Dr. Walker, but I wonder who has accomplished more?Allowing a physician, who may have the best of intentions, from taking the life of a child from its mother is an "inhumane cruelty" intolerable above all others. For this reason, the decision to terminate birth should be left to the mother --not to a physician-- as it may have been in Spartan times.
Rather than termination, such dramatic cases are strong impetus for the development of advanced surgical techniques. Indeed, there have been recent reports of successful separation operations, most under the hands of the talented John Hopkins neurosurgeon, Ben Carson. Dr. Carson, who's personal story is only matched by his phenomenal clinical feats, pioneered the use of cardiovascular surgery techniques, such as inducing cardiac arrest to prevent craniopagus patients from exsanguinating (bleeding to death) while undergoing separation surgery. To understand why exsanguination is so common, look at these images from Goh (2004).
From L-R: MR venogram image of the shared superior sagittal sinus, 3D CT of the twins’ cranium, Sagittal MRI of the twins’ brains. (Goh, 2004)
The venous architecture of craniopagus twins is extremely complex and highly intertwined, and the work of pumping all that blood is shared -sometimes unequally- between the two hearts. A detailed account of the separation procedure is documented in Goh (2004). In deciding if the twins could be separated, the multidisciplinary team of "neurosurgeons, plastic surgeons, anaesthetists, paediatricians, neurologists, a geneticist, dietician and physical, speech and occupational therapists" considered three main points: "(1) Were the brains separate? (2) Were the arterial and venous systems separate? (3) Could the resulting defect be closed?" Despite the daunting task of separating all of the vessels, the surgery is possible and the case presented below ended successfully for both twins.
I'll leave you with the conclusion written in Goh (2004): "Separation of craniopagus twins is technically possible, but demands extraordinary efforts from a large team of experienced and skilled personnel in the preoperative, operative and postoperative stages. Despite the advanced state of technology and knowledge available today, the complexity and rarity of this congenital malformation precludes a good outcome in all cases and will continue to present a formidable challenge to the medical field."
References:
Walker, K. (2007). The tragedy that should never have happened. Canadian Medical Association Journal, 177(3), 312. doi:10.1503/cmaj.070878
Khan, Z. H. (2005) Separated but oceans apart and fathoms deep: the conjoined twins’legacy. Singapore Medical Journal, 7(46), 363.
Goh, K. Y. C. (2004). Separation surgery for total vertical craniopagus twins. Child's Nervous System, 8(20), 567-575, doi:10.1007/s00381-004-0978-3
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