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February 11, 2013 / neurograce

The Right Tool for the Job: How the nature of the brain explains why computational neuroscience is done

Recently, I was charged with giving a presentation to a group of high schoolers preparing for the Brain Bee on the topic of computational approaches to neuroscience. Of course, in order to reach my goal of informing and exciting these kids about the subject, I had to start with the very basic questions of ‘what’ and ‘why.’ It seems like this task should be simple enough for someone in the field. But what I’ve discovered–in the course of doing computational work and in trying to explain my work to others–is that neither answer is entirely straightforward. There is the general notion that computational neuroscience is an approach to studying the brain that uses mathematics and computational modeling. But as far what exactly falls under that umbrella and why it’s done, we are far from having a consensus. Ask anyone off the street and they’re probably unaware that computational neuroscience exists. Scientists and even other neuroscientists are more likely to have encountered it but don’t necessarily understand the motivation for it or see the benefits. And even the people doing computational work will come up with different definitions and claim different end goals.

So to add to that occasionally disharmonious chorus of voices, I’d like to present my own explanation of what computational neuroscience is and why we do it. And while the topic itself may be complicated and convoluted, my description, I hope, will not be. Basically, I want to stress that computational neuroscience is merely a continuation of the normal observation- and model-based approach to research that explains what so many other scientists do. It needn’t be more difficult to justify or explain than any other methodology.  Its potential to be viewed as something qualitatively different comes from the complex and relatively abstract nature of the tools it uses. But the choice of those tools is necessitated simply by the complex and relatively abstract nature of what they’re being applied to, the brain. At its core, however, computational neuroscience follows the same basic steps common to any scientific practice: making observations, combining observations into a conceptual framework, and using that framework to explain or predict further observations.

That was, after all, the process used by two of the founding members of computational neuroscience, Hodgkin and Huxley. They used a large set of data about membrane voltage, ion concentrations, conductances, and currents associated with the squid giant axon (much of which they impressively collected themselves). They integrated the patterns that they found in this data into a model of a neural membrane, which they laid out as a set of coupled mathematical equations each representing different aspects of the membrane. Given the right parameters, the solutions to these equations matched what was seen experimentally. If a given amount of current injection made the squid giant axon spike, then you could put in the same amount of current as a parameter in the equations and you would see the value of the membrane potential respond the same way. Thus, this set of equations served (and still does serve) as framework for understanding and predicting a neuron’s response under different conditions. With some understanding of what each of the parameters in the equations is meant to represent physically, this model has great explanatory power (as defined here) and provides some intuition about what is really happening at the membrane. By providing a unified explanation for a set of observations, the Hodgkin-Huxley model does exactly what any good scientific theory should do.

It may seem, perhaps, that the the actual mathematical model is superfluous. If Hodgkin and Huxley knew enough to know how to build the model, and if knowledge of the what the model means has to be applied in order to understand its results, then what is the mathematical model contributing? Two things that math is great for: precision and the ability to handle complexity. If we wanted to, say, predict what happens when we throw a ball up in the air, we could use a very simple conceptual model that says the force of gravity will counteract the throwing force, causing the ball to go up, pause at its peak height, and come back down. So we could use this to predict that more force would allow the ball to evade gravity’s pull for longer. But how much longer? Without using previous experiments to quantify the force of gravity and formalize its effect in the form of an equation, we can’t know. So, building mathematical models allows for more precise predictions. Furthermore, what if we wanted to perform this experiment on a windy day, or put a jetpack on the ball, or see what happens in the presence of second planet’s gravitational pull, or all of the above? The more complicated a system is, and the more its component parts counteract each other, the less likely it is that simply “thinking through” a conceptual model will provide the correct results. This is especially true in the nervous system, where all the moving parts can interact with each other in frequently nonlinear ways, providing some unintuitive results. For example, the Hodgkin-Huxley model demonstrates a peculiar ability of some neurons: the post-inhibitory rebound spike. This is when a cell fires (counterintuitively) after the application of an inhibitory input. It occurs due to the reliance of the sodium channels on two different mechanisms for opening, and the fact that these mechanisms respond to voltage changes on a different timescale. This phenomenon would not be understandable without a model that had the appropriate complexity (multiple sodium channel gates) and precision (exact timescales for each). So, building models is not a fundamentally different approach to science; we do it every time we infer some kind of functional explanation for a process. However, formalizing our models in terms of mathematics allows us to see and understand more minute and complex processes.

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A Hodgkin-Huxley simulation showing post-inhibitory rebound spiking.

Additionally, the act of building explicit models requires that we investigate which properties are worth modeling and in what level of detail. In this way, we discover what is crucial for a given phenomenon to a occur and what is not. In many regards, this can be considered a main goal of computational modeling. The Human Brain Project seeks to use its 1 billion Euro prize to model the human brain in the highest level of detail and complexity possible. But, as many detractors point out, having a complete model of the brain in equation form does little to decrease the mystery of it. The value of this simulation, I would say, then comes in seeing what parameters can be fudged, tweaked, or removed entirely and still allow the proper behavior to occur. Basically, we want to build it to learn how to break it. Furthermore, as with any hypothesis testing, the real opportunity comes when the predictions from this large-scale model don’t line up with reality. This lets us hunt for the crucial aspect that’s missing.

Computational neuroscience, however, is more than just modeling of neurons. But, in the same way that computational models are just an extension of the normal scientific practice of modeling, the rest of computational neuroscience is just an extension of other regular scientific practices as well. It is the nature of what we’re studying, however, that makes this not entirely obvious. Say you want to investigate the function of the liver. Knowing it has some role in the processing of toxins, it makes sense to measure toxin levels in the blood, presence of enzymes in the liver, etc when trying to understand how it works. But the brain is known to have a role in processing information. So we have to try, as best we can, to quantify and measure that. This leads to some abstract concepts about how much information the activity of a population of cells contains and how that information is being transferred between populations. The fact that we don’t even know exactly what feature of the neural activity contains this information does not make the process any simpler. But the basic notion of desiring to quantify an important aspect of your system of interest is in no way novel. And much of computational neuroscience is simply trying to do that.

So, the honest answer to the question of what computational neuroscience is is that it is the study of the brain. We do it because we want to know how the brain works, or doesn’t work. But, as a hugely complex system with a myriad of functions (some of which are ill- or undefined), the brain is not an easy study. If we want to make progress we need to choose our tools accordingly. So we end up with a variety of approaches that rely heavily on computations as a means of managing the complexity and measuring the function. But this does not necessarily mean that computational neuroscientists belong to a separate school of thought. The fact that we can use computers and computations to understand the brain does not mean that the brain works like a computer. We merely recognize the limitations inherent in studying the brain, and we are willing to take help wherever we can get it in order to work around them. In this way, computational approaches to neuroscience simply emerge as potential solutions to the very complicated problem of understanding the brain.

ResearchBlogging.org Kaplan, D. (2011). Explanation and description in computational neuroscience Synthese, 183 (3), 339-373 DOI: 10.1007/s11229-011-9970-0

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2 Comments

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  1. gw / Jul 17 2013 8:08 am

    very interesting post thanks !

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