The Rich Club of theC. elegansNeuronal Connectome

Abstract

There is increasing interest in topological analysis of brain networks as complex systems, with researchers often using neuroimaging to represent the large-scale organization of nervous systems without precise cellular resolution. Here we used graph theory to investigate the neuronal connectome of the nematode worm Caenorhabditis elegans, which is defined anatomically at a cellular scale as 2287 synaptic connections between 279 neurons. We identified a small number of highly connected neurons as a rich club (N ϭ 11) interconnected with high efficiency and high connection distance. Rich club neurons comprise almost exclusively the interneurons of the locomotor circuits, with known functional importance for coordinated movement. The rich club neurons are connector hubs, with high betweenness centrality, and many intermodular connections to nodes in different modules. On identifying the shortest topological paths (motifs) between pairs of peripheral neurons, the motifs that are found most frequently traverse the rich club. The rich club neurons are born early in development, before visible movement of the animal and before the main phase of developmental elongation of its body. We conclude that the high wiring cost of the globally integrative rich club of neurons in the C. elegans connectome is justified by the adaptive value of coordinated movement of the animal. The economical trade-off between physical cost and behavioral value of rich club organization in a cellular connectome confirms theoretical expectations and recapitulates comparable results from human neuroimaging on much larger scale networks, suggesting that this may be a general and scale-invariant principle of brain network organization.

Cognitive relevance of the community structure of the human brain functional coactivation network

“…The rich club has a cognitively valuable (executive) role, but it is also costly as demonstrated by the longer distance connections between richclub nodes, and between rich and peripheral nodes, than between a pair of peripheral nodes. This combination of high functional capacity and high cost echoes analogous results on the rich club of the human brain anatomical network measured using diffusion tensor imaging (32) and on the rich club of the nervous system of the nematode worm Caenorhabditis elegans described at a cellular level by electron microscopy (33).…”

Rich Club Organization and Cognitive Performance in Healthy Older Participants

“…The overlap between rich club regions identified through neuroimaging techniques and those described through tract tracing in other mammals further supports this notion (Scholtens, Schmidt, de Reus, & van den Heuvel, 2014;De Reus & van den Heuvel, 2013b;Harriger et al, 2012). Importantly, the rich club organization described in our study is consistent with these and other ( Van den Heuvel, Scholtens, & de Reus, 2015;Towlson et al, 2013;Zamora-López, Zhou, & Kurths, 2009) animal tracing studies. A number of these tract tracing and MRI studies also report on rich club edges displaying high levels of connection strength ( Van den Heuvel et al, 2015;Collin et al, 2014), supporting the overall biological validity of rich club formation in the mammalian cortex.…”

“…These putative "neural hubs" are hypothesized to play a central role in overall network communication and intermodular information transfer (van den Heuvel & Sporns, 2013b;Sporns, Honey, & Kötter, 2007). Moreover, this set of hubs appears to be more highly connected to other highdegree nodes than predicted by chance, forming a group of highly interconnected regions (i.e., the "rich club") that may act as a backbone for global network integration (De Reus, Saenger, Kahn, & van den Heuvel, 2014;Mišić, Sporns, & McIntosh, 2014;Towlson, Vértes, Ahnert, Schafer, & Bullmore, 2013;Van den Heuvel, Kahn, Goñi, & Sporns, 2012). Functionally, the anatomical rich club is also hypothesized to act as a gatekeeper, modulating the dynamical interactions between lower-degree regions and the emergence of distinct functional network configurations (Senden, Deco, de Reus, Goebel, & van den Heuvel, 2014;Crossley et al, 2013).…”

The Budapest Reference Connectome Server v2.0

“…The difficulties come from the number of the neurons to be mapped, and also from the lack of the high-throughput methods for mapping their connections. The neuron-scale graphs were constructed only for very simple organisms with a very small number of neurons [4,5,6] or for just small cortical areas of more complex organisms [7,8].…”