Inferring neural signalling directionality from undirected structural connectomes

Neural information flow is inherently directional. To date, investigation of directional communication in the human structural connectome has been precluded by the inability of non-invasive neuroimaging methods to resolve axonal directionality. Here, we demonstrate that decentralized measures of network communication, applied to the undirected topology and geometry of brain networks, can infer putative directions of large-scale neural signalling. We propose the concept of send-receive communication asymmetry to characterize cortical regions as senders, receivers or neutral, based on differences between their incoming and outgoing communication efficiencies. Our results reveal a send-receive cortical hierarchy that recapitulates established organizational gradients differentiating sensory-motor and multimodal areas. We find that send-receive asymmetries are significantly associated with the directionality of effective connectivity derived from spectral dynamic causal modeling. Finally, using fruit fly, mouse and macaque connectomes, we provide further evidence suggesting that directionality of neural signalling is significantly encoded in the undirected architecture of nervous systems. Neural signalling is directional, but non-invasive neuroimaging methods are unable to map directed connections between brain regions. Here, the authors show how network communication measures can be used to infer signalling directionality from the undirected topology of brain structural connectomes.

[1]  K. Sneppen,et al.  Searchability of networks. , 2005, Physical review. E, Statistical, nonlinear, and soft matter physics.

[2]  Karl J. Friston,et al.  Large-scale DCMs for resting-state fMRI , 2017, Network Neuroscience.

[3]  Keith A. Johnson,et al.  Stepwise Connectivity of the Modal Cortex Reveals the Multimodal Organization of the Human Brain , 2012, The Journal of Neuroscience.

[4]  Henry Kennedy,et al.  Cortical High-Density Counterstream Architectures , 2013, Science.

[5]  Olaf Sporns,et al.  Communication Efficiency and Congestion of Signal Traffic in Large-Scale Brain Networks , 2014, PLoS Comput. Biol..

[6]  Alan Connelly,et al.  MRtrix: Diffusion tractography in crossing fiber regions , 2012, Int. J. Imaging Syst. Technol..

[7]  O. Sporns,et al.  The economy of brain network organization , 2012, Nature Reviews Neuroscience.

[8]  H. Kennedy,et al.  A Large-Scale Circuit Mechanism for Hierarchical Dynamical Processing in the Primate Cortex , 2015, Neuron.

[9]  D. J. Felleman,et al.  Distributed hierarchical processing in the primate cerebral cortex. , 1991, Cerebral cortex.

[10]  Matthieu Gilson,et al.  Estimation of Directed Effective Connectivity from fMRI Functional Connectivity Hints at Asymmetries of Cortical Connectome , 2016, PLoS Comput. Biol..

[11]  Terrence J Sejnowski,et al.  Communication in Neuronal Networks , 2003, Science.

[12]  Mason A. Porter,et al.  Random walks and diffusion on networks , 2016, ArXiv.

[13]  Guan-Yu Chen,et al.  Three-Dimensional Reconstruction of Brain-wide Wiring Networks in Drosophila at Single-Cell Resolution , 2011, Current Biology.

[14]  Olaf Sporns,et al.  Path ensembles and a tradeoff between communication efficiency and resilience in the human connectome , 2016, Brain Structure and Function.

[15]  Michael Erb,et al.  Linking structural and effective brain connectivity: structurally informed Parametric Empirical Bayes (si-PEB) , 2018, Brain Structure and Function.

[16]  Allan R. Jones,et al.  A mesoscale connectome of the mouse brain , 2014, Nature.

[17]  A. Bernacchia,et al.  Hierarchy of transcriptomic specialization across human cortex captured by structural neuroimaging topography , 2018, Nature Neuroscience.

[18]  Morten L. Kringelbach,et al.  Hierarchy of Information Processing in the Brain: A Novel ‘Intrinsic Ignition’ Framework , 2017, Neuron.

[19]  Evan M. Gordon,et al.  Three Distinct Sets of Connector Hubs Integrate Human Brain Function. , 2018, Cell reports.

[20]  Nikola T. Markov,et al.  A Weighted and Directed Interareal Connectivity Matrix for Macaque Cerebral Cortex , 2012, Cerebral cortex.

[21]  Essa Yacoub,et al.  The WU-Minn Human Connectome Project: An overview , 2013, NeuroImage.

[22]  Andrew Zalesky,et al.  Navigation of brain networks , 2018, Proceedings of the National Academy of Sciences.

[23]  Olaf Sporns,et al.  Comparative Connectomics , 2016, Trends in Cognitive Sciences.

[24]  Richard F. Betzel,et al.  Resting-brain functional connectivity predicted by analytic measures of network communication , 2013, Proceedings of the National Academy of Sciences.

[25]  Karl J. Friston Functional and Effective Connectivity: A Review , 2011, Brain Connect..

[26]  O Sporns,et al.  Predicting human resting-state functional connectivity from structural connectivity , 2009, Proceedings of the National Academy of Sciences.

[27]  Elizabeth Jefferies,et al.  Situating the default-mode network along a principal gradient of macroscale cortical organization , 2016, Proceedings of the National Academy of Sciences.

[28]  Jesper Andersson,et al.  A multi-modal parcellation of human cerebral cortex , 2016, Nature.

[29]  Enrico Amico,et al.  Modeling Communication Processes in the Human Connectome through Cooperative Learning , 2018, IEEE Transactions on Network Science and Engineering.

[30]  Leonardo L. Gollo,et al.  Mapping how local perturbations influence systems-level brain dynamics , 2016, NeuroImage.

[31]  Haijun Zhou Network landscape from a Brownian particle's perspective. , 2003, Physical review. E, Statistical, nonlinear, and soft matter physics.

[32]  Jon M. Kleinberg,et al.  Navigation in a small world , 2000, Nature.

[33]  K. Sneppen,et al.  Specificity and Stability in Topology of Protein Networks , 2002, Science.

[34]  John D. Murray,et al.  Hierarchical Heterogeneity across Human Cortex Shapes Large-Scale Neural Dynamics , 2019, Neuron.

[35]  O. Sporns,et al.  Mapping the Structural Core of Human Cerebral Cortex , 2008, PLoS biology.

[36]  Richard F. Betzel,et al.  Exploring the Morphospace of Communication Efficiency in Complex Networks , 2013, PloS one.

[37]  Olaf Sporns,et al.  Optimized connectome architecture for sensory-motor integration , 2017, Network Neuroscience.

[38]  Olaf Sporns,et al.  Network-Level Structure-Function Relationships in Human Neocortex , 2016, Cerebral cortex.

[39]  Antoine Allard,et al.  Navigable maps of structural brain networks across species , 2018, PLoS Comput. Biol..

[40]  Leonardo L. Gollo,et al.  Estimating the impact of structural directionality: How reliable are undirected connectomes? , 2018, Network Neuroscience.

[41]  J. Mattingley,et al.  A hierarchy of timescales explains distinct effects of local inhibition of primary visual cortex and frontal eye fields , 2016, eLife.

[42]  Steen Moeller,et al.  Advances in diffusion MRI acquisition and processing in the Human Connectome Project , 2013, NeuroImage.

[43]  O. Sporns,et al.  Connectomics-Based Analysis of Information Flow in the Drosophila Brain , 2015, Current Biology.

[44]  Adeel Razi,et al.  Construct validation of a DCM for resting state fMRI , 2015, NeuroImage.

[45]  Adeel Razi,et al.  Variability and reliability of effective connectivity within the core default mode network: A multi-site longitudinal spectral DCM study , 2018, NeuroImage.

[46]  Edward T. Bullmore,et al.  Whole-brain anatomical networks: Does the choice of nodes matter? , 2010, NeuroImage.

[47]  Enrico Amico,et al.  Mapping hybrid functional-structural connectivity traits in the human connectome , 2017, Network Neuroscience.

[48]  Joaquín Goñi,et al.  Changes in structural and functional connectivity among resting-state networks across the human lifespan , 2014, NeuroImage.

[49]  Mark Jenkinson,et al.  The minimal preprocessing pipelines for the Human Connectome Project , 2013, NeuroImage.

[50]  Andrew J. Weitz,et al.  Studying Brain Circuit Function with Dynamic Causal Modeling for Optogenetic fMRI , 2017, Neuron.

[51]  Julia M. Huntenburg,et al.  Large-Scale Gradients in Human Cortical Organization , 2018, Trends in Cognitive Sciences.

[52]  Gorka Zamora-López,et al.  Cortical Hubs Form a Module for Multisensory Integration on Top of the Hierarchy of Cortical Networks , 2009, Front. Neuroinform..

[53]  Michael W. Cole,et al.  Cognitive task information is transferred between brain regions via resting-state network topology , 2017, Nature Communications.

[54]  Kotagiri Ramamohanarao,et al.  Mapping connectomes with diffusion MRI: deterministic or probabilistic tractography? , 2018, Magnetic resonance in medicine.

[55]  E. Bullmore,et al.  Wiring cost and topological participation of the mouse brain connectome , 2015, Proceedings of the National Academy of Sciences.

[56]  Olaf Sporns,et al.  The Human Connectome: A Structural Description of the Human Brain , 2005, PLoS Comput. Biol..

[57]  Olaf Sporns,et al.  Complex network measures of brain connectivity: Uses and interpretations , 2010, NeuroImage.

[58]  Peter F. Neher,et al.  The challenge of mapping the human connectome based on diffusion tractography , 2017, Nature Communications.

[59]  O. Sporns,et al.  Complex brain networks: graph theoretical analysis of structural and functional systems , 2009, Nature Reviews Neuroscience.

[60]  Marián Boguñá,et al.  Navigability of Complex Networks , 2007, ArXiv.

[61]  Zoltán Toroczkai,et al.  The role of long-range connections on the specificity of the macaque interareal cortical network , 2013, Proceedings of the National Academy of Sciences.

[62]  Richard F. Betzel,et al.  Cooperative and Competitive Spreading Dynamics on the Human Connectome , 2015, Neuron.

[63]  Ernesto Estrada,et al.  Communicability in complex networks. , 2007, Physical review. E, Statistical, nonlinear, and soft matter physics.

[64]  Adeel Razi,et al.  A DCM for resting state fMRI , 2014, NeuroImage.

[65]  Jonathan D. Power,et al.  Intrinsic and Task-Evoked Network Architectures of the Human Brain , 2014, Neuron.

[66]  Ad Aertsen,et al.  Portraits of communication in neuronal networks , 2018, Nature Reviews Neuroscience.

[67]  Edward T. Bullmore,et al.  Fundamentals of Brain Network Analysis , 2016 .

[68]  Marisa O. Hollinshead,et al.  The organization of the human cerebral cortex estimated by intrinsic functional connectivity. , 2011, Journal of neurophysiology.

[69]  Olaf Sporns,et al.  A spectrum of routing strategies for brain networks , 2018, PLoS Comput. Biol..

[70]  Michael Cole,et al.  Cognitive task information is transferred between brain regions via resting-state network topology , 2017 .

[71]  Olaf Sporns,et al.  Communication dynamics in complex brain networks , 2017, Nature Reviews Neuroscience.

[72]  Leonardo L. Gollo,et al.  Connectome sensitivity or specificity: which is more important? , 2016, NeuroImage.

[73]  H. Voss,et al.  Network diffusion accurately models the relationship between structural and functional brain connectivity networks , 2014, NeuroImage.