Moheb Costandi blogs about molecules, minds, and everything in between at Neurophilosophy. See Azeen Ghorayshi’s article on the debate over how best to map an organ with infinite levels of complexity.
Several weeks ago, the National Institutes of Health announced the Human Connectome Project, an ambitious $30 million five-year initiative, which aims to map the connectivity of the human brain.
Is this feasible? In short, the answer is no. The idea that a complete connectivity map of the whole brain can be achieved within 5 years is unrealistic, and producing a microscale map at the level of single neurons and synapses within that time frame is impossible.
Firstly, the numbers involved are just too vast. The human brain is an incredibly complex structure, consisting of hundreds of billions of cells, which between them form something in the order of one quadrillion connections (synapses).
Secondly, it is technically impossible, at least at the moment. Brainbow, for example, the ingenious fluorescent protein-based method for visualizing neuronal connectivity developed in the labs of Jeff Lichtman and Josh Sanes, involves creating genetically engineered animals, and so is not applicable to humans.
A macroscale map of the connections between brain regions also poses problems. There is, for example, no universally accepted scheme for delineating the functional subdivisions of the human cerebral cortex. There is still much debate about exactly how—or if—tractography data from recently developed neuroimaging techniques such as diffusion tensor imaging are correlated to anatomy.
What might be possible is a connectivity map at a scale somewhere between these two levels of organization. Even so, drawing up such a map for the entire brain is still an enormous task. When the Human Connectome Project comes to an end in five years’ time, we may have a comprehensive map of the connections within a few of the brain’s subnetworks, such as the thalamocortical system, which alone comprises several hundred discrete brain regions and thousands of fiber tracts.
Thus, the connectome project is likely to lead to a rudimentary first draft, which, like that of the human genome, will undergo numerous subsequent revisions. The initiative to map the connectivity of the entire brain should be thought of as an open-ended one, which will be added to and refined for decades to come.
Undoubtedly, a whole-brain connectivity map will be useful to researchers once it is eventually completed. But what such a map can tell us about how the brain actually works is likely to be limited. This is because the connectome apparently ignores the phenomenon of neuroplasticity.
Plasticity refers to the brain’s ability to physically alter its structure in response to experience. Far from being immalleable, as was once thought, the brain is a highly dynamic organ. Neurons can sprout new connections within minutes of a given stimulus, and entire neural pathways can be rerouted so that function is recovered after a brain injury.
The connectome also disregards the functional importance of neuroglial cells, another class of cells which are found in the nervous system and which outnumber neurons by at least 10 to 1. Once thought to merely provide structural and nutritional support for neurons, glia have, in recent years, come into their own as key players in the brain. As well as performing the roles initially ascribed to them, glia carry out a whole host of other vital functions, including monitoring neuronal health, identifying damaged neurons, and regulating synaptic plasticity. They are also known to be capable of communicating not only with one another, but also with neurons. A map of brain connectivity cannot therefore be complete without taking glia into account.
Finally, although the large-scale connections are very similar among individuals, there are significant variations at smaller scales. And the fact that the large-scale connections change over time—from infancy, to adolescence, through to adulthood—complicates matters even more. A detailed, definitive description of brain connectivity will, therefore, remain out of our grasp for a long time yet.
