Connectomics, Neuroscience, and Computational Models of the Brain

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When an idea in science is stamped a theory most scientists just shrug. Unlike the public they know that theory or not, an idea can’t be taken as ground truth until it has been thoroughly vetted through extensive and redundant experimentation. In 2012 Dr. Sebastion Seung published a book advocating a theory neither new, old, nor entirely his own. The science of some aspects of his idea is, however, becoming quite acceptable to the neuroscience community. His scientific idea is that, aside from our DNA, it is the uniqueness of the pattern and characteristics of connections between the neurons in our brains that makes us who we are. In all fairness, Dr. Seung is not the first to propose this idea, nor is he the only proponent of what has become known as Connectomics—but he has found ample resistance to the idea that our “connectome” could have a role in establishing identity that rivals the uniqueness of our individual genetic code. Many question that the mere architecture of the connections in a brain could yield the rich functionality that we all enjoy. Another established expert in the field, Dr. Cristof Koch said,”Even though we have known the connectome of the nematode worm for 25 years we are far from reading its mind. We don’t yet understand how its nerve cells work.” As Dr. Koch and others have intimated, the more likely whole theory of the brain is a hybrid one taking into account not only connections but also the chemical-laden soupy milieu that neurons sit in.

Connectomics As A Theory Is Great But Incomplete

Imagine yourself as a competitor in a wrestling match. Pretend that before the match you get to choose between two competitions—one option is to wrestle a thoroughly muscled man twice your size, the second is to wrestle 25 small, but very angry, eight year old children. It is likely that you will be overpowered in either case but it is a useful analogy to help you see the differences between connections of neurons. These connections determine how similar, or coupled, the behavior of two neurons are and they are not all the same strength; Some connections are weak, and others are strong. It would take many more weak connections to achieve a similar response from a neuron as you might expect from a few very strong connections. Connections between cells are called synapses, and synapses are essentially a gap across which neurons send chemicals. The upstream neurons typically do most of the sending, and the downstream neuron pays attention to how much the signaling neurons sends.

It is possible, however, for this process to be interrupted. Foreign chemicals, not usually found at the synapse can block or replace those that belong…the results could be dramatic. The body releases specific chemicals on a regular basis— dopamine, serotonin, glutamate, calcium, and many others that are routinely synthesised in the body and play an important role in the way your neurons function. The role that these extra-neural chemicals play is an example of a crucial non-Connectome feature of your brain which contributes to what makes you who you are. While the connectome forms the primary architectural framework on which these processes are possible, it cannot tell the whole story alone.

How To Measure the Importance of Connectomics?

The concept of experimental control is central to what makes scientific results at all verifiable. If you wanted to determine if lavender oil cures cancer you would need to isolate cancerous cells by controlling for all other potentially cancer killing compounds or mechanisms that might also be nearby…otherwise how could you prove that exposure to the lavender was what did the deed? How do you control for the contribution of connectomics to identity when the connectome is never the only variable that changes from person to person? To put it in other words…how do you know that the differences between my connectome and yours is what makes me walk, talk, and think differently than you? How do we know that factors such as environment, genetics, diet, and habits are also coming into play?

We obviously need some kind of experimental control…where we can observe the changes in behavior in a single connectome when exposed to different environments or perhaps the differences in behavior between two connectomes exposed to the exact same environment. It turns out that the easiest, most practical, and ethical method of doing this is to build what is called a computational model…this is essentially a version of the system in question reproduced via mathematical equivalents inside of a computer. If you are a bit mystified as to how this could be done…take the example of a pitcher throwing a baseball. If you knew the trajectory and initial velocity of the baseball, as well as a few essential details about the ball itself, you could predict the path with near perfect precision. Similarly, if you know a few of the rules by which neurons behave, you can predict their behavior with very high accuracy. When you add to that a model of the behavior of connections between cells you have all of the functional components of a connectome. Simulations of connectomes, real and hypothetical, have the power to yield incredibly valuable insights.

Connectomics, A Piece Of The Puzzle And A Clue For Further Investigation

While it is unlikely that a connectome holds all of the information necessary to reconstruct your cerebral identity, it is undoubtedly a crucial component. But how do we test the idea and gauge just how important it is? Computational models can shed some light into the black box of the brain by building toy versions, simple and complex, to explore how variations of the connectome impacts the behavior of a network of neurons. Combined with models of extracellular features of neural systems, we may be able to learn the balance of influence each structural component of our brains hold over our behavior. Like behavior, connectomics is very difficult to study via reductionist methods…it may very well be the completeness of the brain that makes us so special.

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Clayton S. Bingham is a Biomedical Engineer working at the Center for Neural Engineering at University of Southern California. Under the direction of Drs. Theodore Berger and Dong Song, Clayton builds large-scale computational models of neurological systems. Currently, the emphasis is on the modeling of hippocampal tissue in response to electrical stimulation with the goal of optimizing the placement of stimulating electrodes in regions of the brain that are dysfunctional. These therapies can be used for a broad range of pathologies including Alzheimer’s, various motor disorders, depression, and Epilepsy.

If you would like to hear more about the work done by Clayton, and his colleagues, in the USC Center for Neural Engineering he can be reached at: csbingha-at-usc-dot-edu.

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