Synaptic tail-chasing: Will we ever have a human connectome?
By John Hewitt on November 13, 2012 at 11:46 am
The field of artificial intelligence has been set abuzz by a recent plan to create a connectome for a human brain. To borrow a term from circuit board design, a connectome can be described as a netlist for the brain. Basically, a netlist is a file that contains a description of all the wired connections between components on the board. The actual structure of a netlist is similar to that found in object-oriented programming in that it defines electronic component in terms of "objects" instantiated from classes. Components can then be individually described by overriding values in the class definitions. For a brain, the components are the different kinds of neurons, and the wire connections are the synapses between neurons.
The first connectome was created in 1986 for a worm known as C. Elegans, by slicing its brain into thin sections and magnifying them with an electron microscope. The 302 neurons and 7,000 synaptic connections of the worm were then reconstructed in 3D on a computer (pictured below). Researchers have been using the connectome to guide experiments which link behaviors to the underlying circuitry. This is done by deactivating select parts of the neural circuit with laser micro-dissection, just as one would trace a short to ground in an electrical circuit by serially removing components or wire connections to see the result. A much more crude approach is taken to preserve important speech areas in humans during neurosurgery to treat otherwise intractable epilepsy. In this case, the surgeon stimulates the exposed cortex of an awake, talking patient to see if the stimulation interferes with their speech. If it does, the tissue is not removed.
If we can capture a human connectome, what would it look like and what could we do with it?
What does a connectome look like?
For the worm, the connectome is completely specified by the genome. Provided no drastic changes are made to its genome, the connectome of every worm is for all practical purposes, identical. Furthermore, it is largely invariant through the span of the worm's life. In more complex animals however, only the rough plan for the connectome is defined by the genes; the details emerge and change through feedback with the environment. A consequence of this situation, wherein the mechanisms of developmental construction of the brain are left at idle, is that there can be no such thing as a connectome for an animal like a human.
Fortunately, there are some constraints on the way the brain evolves over time that may allow in a some respects, a satisfactory, "living connectome" to be achieved. Periodicity in synaptic connections that are as evident as the annual antler growth on a deer can be readily resolved under the microscope. Cycles of fertility, wakefulness, and illumination (daylight) result in predictable changes in structure. For example, in adaption to the dark, the pupil constricts by a factor of 25 in seconds, the photoreceptors regenerate extra pigment within 10 minutes, and the whole functional synaptic structure of retinal "horizontal" cells grows in parallel with the pigment change to average more photoreceptors together for greater detection power at the expense of resolution.
What this means is that the static, object-oriented netlist of the worm will not be sufficient. To draw from physics, the description needs to be more like a vector field, representing instantaneous directions of growth, divergence, and curl for the synaptic space. Any would-be connectomist should take ample notice of the fact that they will be embarking on a fantastic but never-ending journey, a Sisyphean task where the mountain's landscape changes anew each day.
While most of the information stored in your genome is in the sequence of the data itself, it also exists within a 3D regulatory structure. Just as a knowledge of the genome has little value without an understanding of the functions and interactions of the genes, a connectome will need some additional input to be useful. In many respects however, structure of the brain is itself the function. From a distance, the brain might appear as inert as the red spot of Jupiter, but when it is approached on it's own scale its malevolent glory can be seen. The connectome is just the starting point, but for those inclined to follow, the rewards will be worth the effort.
What could we do with a human connectome?
A connectome would make a lot of things we try to do today in the operating room a whole lot easier. The epilepsy surgery mentioned above could be pre-programmed and carried out by robot while the patient remained anesthetized. Implants to greatly extend sensory abilities and memory could be optimally integrated. Devices which currently perform sub-vocal recording of the larynx for patients that cannot speak will evolve pure thought-to-text capability by retracing the laryngeal nerve pathways back to the premotor areas of the brain.
Comparisons of connectomes between twins, parents, and friends would fuel and affirm private intuitions, leading to greater understanding of links between structure and function. Multidisciplinary courses like "Intro to Connectomics" now offered at MIT will completely subsume traditional instruction, reinvigorating students to drive their own education with the zeal of the gamer.
The method known as BOINC (Bar-Coding of Individual Neuronal Connections) has been proposed for creating a human connectome without destroying it. It is fiendishly complex and requires the brain to be, in essence, immunized by viruses that have been engineered to generate and process DNA bar codes as they migrate from one neuron to the next across synapses. The data generated by the process would dwarf that of the genome and raises the question as to whose connectome do we build?
Expectant mothers have long enjoyed benefit of ultrasounds, and the newborn's birthright provides for a hearing test and perhaps soon DNA analysis. Pursuit of a connectome will need to be evaluated in terms of an "at what cost" approach to ensure that other technologies are not excluded by funding bodies. Projects like, for example, the National Ignition Facility have been criticized for excluding other valid but smaller approaches which sought to investigate the possibility of fusion power.
Crowd funding and private funding ventures are now combining to create a vibrant community which aims to make the connectome a reality. The Brain Preservation Foundation has recently announced that its prize for the first human connectome, albeit destructively obtained, is now more than $100,000. The International Journal of Machine Consciousness is currently running a special issue on mind uploading, which even in its most primitive form would require a high-resolution connectome.
With some luck, young readers may be able to access the first non-destructive connectome within their lifetimes, but in the meantime, as one famous neuroscientist chided on twitter, "let me know when you see one."
Now read: First map of the human brain reveals a simple, grid-like structure between neurons