Connectome - The Connectome at Multiple Scales

The Connectome At Multiple Scales

Brain networks can be defined at different levels of scale, corresponding to levels of spatial resolution in brain imaging (Kötter, 2007, Sporns, 2010). These scales can be roughly categorized as microscale, mesoscale and macroscale. Ultimately, it may be possible to join connectomic maps obtained at different scales into a single hierarchical map of the neural organization of a given species that ranges from single neurons to populations of neurons to larger systems like cortical areas. Given the methodological uncertainties involved in inferring connectivity from the primary experimental data, and given that there are likely to be large differences in the connectomes of different individuals, any unified map will likely rely on probabilistic representations of connectivity data (Sporns et al., 2005).

Mapping the connectome at the "microscale" (micrometer resolution) means building a complete map of the neural systems, neuron-by-neuron. The challenge of doing this becomes obvious: the number of neurons comprising the brain easily ranges into the billions in more highly evolved organisms. According to various estimates, the human cerebral cortex alone contains at least 1010 neurons linked by 1014 synaptic connections. By comparison, the number of base-pairs in a human genome is 3×109. A few of the main challenges of building a human connectome at the microscale today include: (1) data collection would take years given current technology; (2) machine vision tools to annotate the data remain in their infancy, and are inadequate; and (3) neither theory nor algorithms are readily available for the analysis of the resulting brain-graphs. To address the data collection issues, several groups are building high-throughput serial electron microscopes (Kasthuri et al., 2009; Bock et al. 2011). To address the machine-vision and image-processing issues, the Open Connectome Project is alg-sourcing (algorithm outsourcing) this hurdle. Finally, statistical graph theory is an emerging discipline which is developing sophisticated pattern recognition and inference tools to parse these brain-graphs (Goldenberg et al., 2009).

A "mesoscale" connectome corresponds to a spatial resolution of hundreds of micrometers. Rather than attempt to map each individual neuron, a connectome at the mesoscale would attempt to capture anatomically and/or functionally distinct neuronal populations, formed by local circuits (e.g. cortical columns) that link hundreds or thousands of individual neurons. This scale still presents a very ambitious technical challenge at this time and can only be probed on a small scale with invasive techniques or very high field MRI on a local scale.

A connectome at the macroscale (millimeter resolution) attempts to capture large brain systems that can be parcellated into anatomically distinct modules (areas, parcels or nodes), each having a distinct pattern of connectivity. Connectomic databases at the mesoscale and macroscale may be significantly more compact than those at cellular resolution, but they require effective strategies for accurate anatomical or functional parcellation of the neural volume into network nodes (for complexities see, e.g., Wallace et al., 2004).