Apr 12 2011

Connectomics

There are approximately 100 billion neurons in the adult human brain. Each neuron makes thousands of connections to other neurons, resulting in an approximate 150 trillion connections in the human brain. The pattern of those connections is largely responsible for the functionality of the brain – everything we sense, feel, think, and do. Neuroscientists are attempting to map those connections – in an effort known as connectomics. (Just as genomics is the effort to map the genome, and proteomics is mapping all the proteins that make up an organism.)

This is no small task. No matter how you look at it, 150 trillion is a lot of connections. One research group working on this project is a team led by Thomas Mrsic-Flogel at the University College London. They recently published a paper in Nature in which they map some of the connections in the mouse visual cortex.

What they did was to first determine the function of specific areas and neurons in the mouse visual cortex in living mice. For example, they determined which orientation they are sensitive to. In the visual cortex different neurons respond to different orientations (vertical vs horizontal, for example). Once they mapped the directional function of the neurons they then mapped the connections between those neurons in vitro (after removing the brain). They found that neurons made more connections to other neurons with the same directional response, rather than neurons with sensitivity to different (orthogonal) directions.

The techniques used allowed them to make a map of connections in part of the mouse visual cortex and correlate the pattern of those connections to the functionality of that cortex. The resulting connectomics map is still partial and crude, but it is a step in the direction of reproducing the connections in the brain.

One way to think about these kinds of techniques is that they promise to take us a level deeper in our understanding of brain anatomy. At present we have mapped the mammalian, and specifically human, brain to the point that we can identify specific regions of the brain and link them to some specific function. For the more complex areas of the brain we are still refining our map of these brain modules and the networks they form.

To give an example of where we are with this, clinical neurologists are often able to predict where a stroke is located simply by the neurological exam. We can correlate specific deficits with known brain structures, and the availability of MRI scanning means that we get rapid and precise feedback on our accuracy. We are very good at localizing deficits of strength, sensation, vision, and also many higher cortical functions like language, calculations, visuo-spatial reasoning, performing learned motor tasks, and others.

But we are still a long way from being able to reproduce the connections in the brain in fine detail – say, with sufficient accuracy to produce a virtual brain in a computer simulation (even putting aside the question of computing power). And that is exactly the goal of connectomics.

Along the way these research efforts will increase our knowledge of brain anatomy and function, as we learn exactly how different brain regions connect to each other and correlate them with specific functions. Neuroscientists are still picking the low-hanging fruit, such as mapping the visual cortex, which has some straightforward organization that correlates with concepts that are easy to identify and understand – like mapping to an actual layout of the visual field, and to specific features of vision such as contrast and orientation.

For more abstract areas of the brain, like those that are involved with planning, making decision, directing our attention, feeling as if we are inside our own bodies, etc. connectomics is likely to be more challenging. Right now we are mainly using fMRI scans for these kinds of studies, which has been very successful, but does not produce a fine map of connections (more of a brain region map). Also, the more abstract the function the more difficult it will be to use mice or other animals as subjects, and when using humans you cannot use certain techniques, like removing the brain and slicing it up (at least not on living subjects).

The utility of this kind of research is a better understanding of brain function, and all that flows from that. We cannot anticipate all the potential benefits, and the most fruitful outcome may derive from knowledge we are not even aware we are missing.

This also plays into the research efforts to create a virtual representation of the human brain, complete with all the connections. This is one pathway to artificial intelligence. Estimates vary, but it seems like we will have the computer power sometime this century to create a virtual human brain that can function in real time, and then, of course, become progressively faster.

I should note that the connections among neurons in the brain are not the only feature that contributes to brain function. The astrocytes and other “support” cells also contribute to brain function. There is also a biochemical level to brain function – the availability of specific neurotransmitters, for example. So even if we could completely reproduce the neuronal connections in the brain, there are other layers of complexity superimposed upon this.

 

In any case, this is fascinating research and it will be nice to see how it progresses over the next few decades.

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