The human connectome: Origins and challenges

The human connectome refers to a map of the brain's structural connections, rendered as a connection matrix or network. This article attempts to trace some of the historical origins of the connectome, in the process clarifying its definition and scope, as well as its putative role in illuminating brain function. Current efforts to map the connectome face a number of significant challenges, including the issue of capturing network connectivity across multiple spatial scales, accounting for individual variability and structural plasticity, as well as clarifying the role of the connectome in shaping brain dynamics. Throughout, the article argues that these challenges require the development of new approaches for the statistical analysis and computational modeling of brain network data, and greater collaboration across disciplinary boundaries, especially with researchers in complex systems and network science.

[1]  Timothy E. J. Behrens,et al.  The topographic connectome , 2013, Current Opinion in Neurobiology.

[2]  E. Marder Variability, compensation, and modulation in neurons and circuits , 2011, Proceedings of the National Academy of Sciences.

[3]  Biyu J. He,et al.  Loss of Resting Interhemispheric Functional Connectivity after Complete Section of the Corpus Callosum , 2008, The Journal of Neuroscience.

[4]  Karl J. Friston,et al.  The Dynamic Brain: From Spiking Neurons to Neural Masses and Cortical Fields , 2008, PLoS Comput. Biol..

[5]  Heidi Johansen-Berg,et al.  Diffusion MRI at 25: Exploring brain tissue structure and function , 2012, NeuroImage.

[6]  G. Deco,et al.  Emerging concepts for the dynamical organization of resting-state activity in the brain , 2010, Nature Reviews Neuroscience.

[7]  Yaniv Assaf,et al.  Learning in the Fast Lane: New Insights into Neuroplasticity , 2012, Neuron.

[8]  Katrin Amunts,et al.  White matter fiber tracts of the human brain: Three-dimensional mapping at microscopic resolution, topography and intersubject variability , 2006, NeuroImage.

[9]  A. Barabasi,et al.  Interactome Networks and Human Disease , 2011, Cell.

[10]  M. Corbetta,et al.  Individual variability in functional connectivity predicts performance of a perceptual task , 2012, Proceedings of the National Academy of Sciences.

[11]  F. Crick,et al.  Backwardness of human neuroanatomy , 1993, Nature.

[12]  M. Young The organization of neural systems in the primate cerebral cortex , 1993, Proceedings of the Royal Society of London. Series B: Biological Sciences.

[13]  O. Sporns,et al.  Functional connectivity between anatomically unconnected areas is shaped by collective network-level effects in the macaque cortex. , 2012, Cerebral cortex.

[14]  O. Sporns Discovering the Human Connectome , 2012 .

[15]  Ravi S. Menon,et al.  Resting‐state networks show dynamic functional connectivity in awake humans and anesthetized macaques , 2013, Human brain mapping.

[16]  G. Edelman,et al.  Reentrant signaling among simulated neuronal groups leads to coherency in their oscillatory activity. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[17]  Zeynep M. Saygin,et al.  Anatomical connectivity patterns predict face-selectivity in the fusiform gyrus , 2011, Nature Neuroscience.

[18]  Lav R. Varshney,et al.  Structural Properties of the Caenorhabditis elegans Neuronal Network , 2009, PLoS Comput. Biol..

[19]  Archana Venkataraman,et al.  Intrinsic functional connectivity as a tool for human connectomics: theory, properties, and optimization. , 2010, Journal of neurophysiology.

[20]  D. Pandya,et al.  Cerebral White Matter — Historical Evolution of Facts and Notions Concerning the Organization of the Fiber Pathways of the Brain , 2007, Journal of the history of the neurosciences.

[21]  Marcus Kaiser,et al.  Clustered organization of cortical connectivity , 2007, Neuroinformatics.

[22]  S. Brenner,et al.  The structure of the nervous system of the nematode Caenorhabditis elegans. , 1986, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[23]  Stefan Rotter,et al.  How Structure Determines Correlations in Neuronal Networks , 2011, PLoS Comput. Biol..

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

[25]  E. Marder Neuromodulation of Neuronal Circuits: Back to the Future , 2012, Neuron.

[26]  HERBERT A. SIMON,et al.  The Architecture of Complexity , 1991 .

[27]  Olaf Sporns,et al.  Synchronization dynamics and evidence for a repertoire of network states in resting EEG , 2012, Front. Comput. Neurosci..

[28]  Heidi Johansen-Berg,et al.  Tractography: Where Do We Go from Here? , 2011, Brain Connect..

[29]  M. Greicius,et al.  Resting-state functional connectivity reflects structural connectivity in the default mode network. , 2009, Cerebral cortex.

[30]  Elly Nedivi,et al.  Clustered Dynamics of Inhibitory Synapses and Dendritic Spines in the Adult Neocortex , 2012, Neuron.

[31]  S. Petersen,et al.  Concepts and principles in the analysis of brain networks , 2011, Annals of the New York Academy of Sciences.

[32]  M P Young,et al.  Anatomical connectivity defines the organization of clusters of cortical areas in the macaque monkey and the cat. , 2000, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[33]  Karl J. Friston,et al.  Tractography-based priors for dynamic causal models , 2009, NeuroImage.

[34]  Annchen R. Knodt,et al.  Impulsivity and the modular organization of resting-state neural networks. , 2013, Cerebral cortex.

[35]  C. Gilbert,et al.  Axons and Synaptic Boutons Are Highly Dynamic in Adult Visual Cortex , 2006, Neuron.

[36]  Steen Moeller,et al.  The Human Connectome Project: A data acquisition perspective , 2012, NeuroImage.

[37]  David Parker,et al.  Neuronal network analyses: premises, promises and uncertainties , 2010, Philosophical Transactions of the Royal Society B: Biological Sciences.

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

[39]  G. Deco,et al.  Ongoing Cortical Activity at Rest: Criticality, Multistability, and Ghost Attractors , 2012, The Journal of Neuroscience.

[40]  O. Sporns,et al.  Key role of coupling, delay, and noise in resting brain fluctuations , 2009, Proceedings of the National Academy of Sciences.

[41]  R. Kahn,et al.  Functionally linked resting‐state networks reflect the underlying structural connectivity architecture of the human brain , 2009, Human brain mapping.

[42]  G Tononi,et al.  Measures of degeneracy and redundancy in biological networks. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[43]  Changsong Zhou,et al.  Sustained Activity in Hierarchical Modular Neural Networks: Self-Organized Criticality and Oscillations , 2010, Front. Comput. Neurosci..

[44]  Danielle S. Bassett,et al.  Conserved and variable architecture of human white matter connectivity , 2011, NeuroImage.

[45]  Thomas R. Knösche,et al.  White matter integrity, fiber count, and other fallacies: The do's and don'ts of diffusion MRI , 2013, NeuroImage.

[46]  B. Biswal,et al.  The resting brain: unconstrained yet reliable. , 2009, Cerebral cortex.

[47]  Susan Lindquist,et al.  Prions as adaptive conduits of memory and inheritance , 2005, Nature Reviews Genetics.

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

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

[50]  Vince D. Calhoun,et al.  Measuring brain connectivity: Diffusion tensor imaging validates resting state temporal correlations , 2008, NeuroImage.

[51]  G. Edelman,et al.  A measure for brain complexity: relating functional segregation and integration in the nervous system. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[52]  O. Sporns,et al.  White matter maturation reshapes structural connectivity in the late developing human brain , 2010, Proceedings of the National Academy of Sciences.

[53]  David C. Van Essen,et al.  The future of the human connectome , 2012, NeuroImage.

[54]  Olaf Sporns,et al.  Network attributes for segregation and integration in the human brain , 2013, Current Opinion in Neurobiology.

[55]  D. Pandya,et al.  Association fibre pathways of the brain: parallel observations from diffusion spectrum imaging and autoradiography. , 2007, Brain : a journal of neurology.

[56]  C. Koch,et al.  What is the function of the claustrum? , 2005, Philosophical Transactions of the Royal Society B: Biological Sciences.

[57]  R. Traub,et al.  Model of the origin of rhythmic population oscillations in the hippocampal slice. , 1989, Science.

[58]  P. Hagmann,et al.  Mapping complex tissue architecture with diffusion spectrum magnetic resonance imaging , 2005, Magnetic resonance in medicine.

[59]  David T. Jones,et al.  Non-Stationarity in the “Resting Brain’s” Modular Architecture , 2012, PloS one.

[60]  V. Brezina Beyond the wiring diagram: signalling through complex neuromodulator networks , 2010, Philosophical Transactions of the Royal Society B: Biological Sciences.

[61]  G. Edelman,et al.  Reentry and the problem of integrating multiple cortical areas: simulation of dynamic integration in the visual system. , 1992, Cerebral cortex.

[62]  Eric Shea-Brown,et al.  Impact of Network Structure and Cellular Response on Spike Time Correlations , 2011, PLoS Comput. Biol..

[63]  Jonathan D. Power,et al.  A Parcellation Scheme for Human Left Lateral Parietal Cortex , 2010, Neuron.

[64]  T. Bonhoeffer,et al.  Experience leaves a lasting structural trace in cortical circuits , 2008, Nature.

[65]  Olaf Sporns,et al.  Network structure of cerebral cortex shapes functional connectivity on multiple time scales , 2007, Proceedings of the National Academy of Sciences.

[66]  Yong-Yeol Ahn,et al.  Topological Cluster Analysis Reveals the Systemic Organization of the Caenorhabditis elegans Connectome , 2011, PLoS Comput. Biol..

[67]  Geraint Rees,et al.  Anatomy of Human Sensory Cortices Reflects Inter-Individual Variability in Time Estimation , 2011, Front. Integr. Neurosci..

[68]  Arthur W. Wetzel,et al.  Network anatomy and in vivo physiology of visual cortical neurons , 2011, Nature.

[69]  Gustavo Deco,et al.  Role of local network oscillations in resting-state functional connectivity , 2011, NeuroImage.

[70]  G. Rees,et al.  The structural basis of inter-individual differences in human behaviour and cognition , 2011, Nature Reviews Neuroscience.

[71]  W. Gan,et al.  Stably maintained dendritic spines are associated with lifelong memories , 2009, Nature.

[72]  E. Marder,et al.  Multiple models to capture the variability in biological neurons and networks , 2011, Nature Neuroscience.

[73]  D. Long Networks of the Brain , 2011 .

[74]  Gustavo Deco,et al.  Structural connectivity allows for multi-threading during rest: The structure of the cortex leads to efficient alternation between resting state exploratory behavior and default mode processing , 2012, NeuroImage.

[75]  Malcolm P. Young,et al.  Objective analysis of the topological organization of the primate cortical visual system , 1992, Nature.

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

[77]  M. Corbetta,et al.  Temporal dynamics of spontaneous MEG activity in brain networks , 2010, Proceedings of the National Academy of Sciences.

[78]  P. Skudlarski,et al.  Brain Connectivity Related to Working Memory Performance , 2006, The Journal of Neuroscience.

[79]  Travis A. Jarrell,et al.  The Connectome of a Decision-Making Neural Network , 2012, Science.

[80]  Eve Marder,et al.  Functional consequences of animal-to-animal variation in circuit parameters , 2009, Nature Neuroscience.

[81]  S. Shipp,et al.  The functional logic of cortical connections , 1988, Nature.

[82]  J G Kiernan,et al.  Psychiatry: A Clinical Treatise on Diseases of the Fore- Brain, based upon a study of its structure, functions, and nutrition , 1886 .

[83]  R. Deriche,et al.  From Diffusion MRI to Brain Connectomics , 2013 .

[84]  Kevin L. Briggman,et al.  Towards neural circuit reconstruction with volume electron microscopy techniques , 2006, Current Opinion in Neurobiology.

[85]  Timothy Edward John Behrens,et al.  Training induces changes in white matter architecture , 2009, Nature Neuroscience.

[86]  Kevin L. Briggman,et al.  Structural neurobiology: missing link to a mechanistic understanding of neural computation , 2012, Nature Reviews Neuroscience.

[87]  Xi-Nian Zuo,et al.  Resting-State Functional Connectivity Indexes Reading Competence in Children and Adults , 2011, The Journal of Neuroscience.

[88]  Randolph Blake,et al.  Callosal Connections of Primary Visual Cortex Predict the Spatial Spreading of Binocular Rivalry Across the Visual Hemifields , 2011, Front. Hum. Neurosci..

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

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

[91]  Stephen M. Smith,et al.  Temporally-independent functional modes of spontaneous brain activity , 2012, Proceedings of the National Academy of Sciences.

[92]  O. Sporns,et al.  Organization, development and function of complex brain networks , 2004, Trends in Cognitive Sciences.

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

[94]  Flavio Dell'Acqua,et al.  Structural human brain networks: hot topics in diffusion tractography. , 2012, Current opinion in neurology.

[95]  K. Svoboda,et al.  Experience-dependent structural synaptic plasticity in the mammalian brain , 2009, Nature Reviews Neuroscience.

[96]  Arvind Kumar,et al.  Beyond Statistical Significance: Implications of Network Structure on Neuronal Activity , 2012, PLoS Comput. Biol..

[97]  A. Toga,et al.  Three-Dimensional Statistical Analysis of Sulcal Variability in the Human Brain , 1996, The Journal of Neuroscience.

[98]  B. Fischer,et al.  Visual field representations and locations of visual areas V1/2/3 in human visual cortex. , 2003, Journal of vision.

[99]  Timothy Edward John Behrens,et al.  Changes in connectivity profiles define functionally distinct regions in human medial frontal cortex. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[100]  M. Cohen,et al.  Measuring and interpreting neuronal correlations , 2011, Nature Neuroscience.

[101]  G. Glover,et al.  Dissociable Intrinsic Connectivity Networks for Salience Processing and Executive Control , 2007, The Journal of Neuroscience.

[102]  Viktor K. Jirsa,et al.  Noise during Rest Enables the Exploration of the Brain's Dynamic Repertoire , 2008, PLoS Comput. Biol..

[103]  A. Anwander,et al.  Connectivity-Based Parcellation of Broca's Area. , 2006, Cerebral cortex.

[104]  Klaas E. Stephan,et al.  The anatomical basis of functional localization in the cortex , 2002, Nature Reviews Neuroscience.

[105]  R. W. Draft,et al.  Transgenic strategies for combinatorial expression of fluorescent proteins in the nervous system , 2007, Nature.

[106]  R. Yuste,et al.  The Brain Activity Map Project and the Challenge of Functional Connectomics , 2012, Neuron.

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

[108]  Hernando Ombao,et al.  Quantifying temporal correlations: A test–retest evaluation of functional connectivity in resting-state fMRI , 2013, NeuroImage.

[109]  Catie Chang,et al.  Time–frequency dynamics of resting-state brain connectivity measured with fMRI , 2010, NeuroImage.

[110]  Rosa Cossart,et al.  Dissecting functional connectivity of neuronal microcircuits: experimental and theoretical insights , 2011, Trends in Neurosciences.

[111]  G Tononi,et al.  Theoretical neuroanatomy: relating anatomical and functional connectivity in graphs and cortical connection matrices. , 2000, Cerebral cortex.

[112]  Christian Windischberger,et al.  Toward discovery science of human brain function , 2010, Proceedings of the National Academy of Sciences.

[113]  M. Corbetta,et al.  Learning sculpts the spontaneous activity of the resting human brain , 2009, Proceedings of the National Academy of Sciences.

[114]  Olaf Sporns,et al.  Can structure predict function in the human brain? , 2010, NeuroImage.

[115]  Kevin L. Briggman,et al.  Wiring specificity in the direction-selectivity circuit of the retina , 2011, Nature.

[116]  Cori Bargmann Beyond the connectome: How neuromodulators shape neural circuits , 2012, BioEssays : news and reviews in molecular, cellular and developmental biology.