Understanding Structural-Functional Relationships in the Human Brain

Relating the brain’s structural connectivity (SC) to its functional connectivity (FC) is a fundamental goal in neuroscience because it is capable of aiding our understanding of how the relatively fixed SC architecture underlies human cognition and diverse behaviors. With the aid of current noninvasive imaging technologies (e.g., structural MRI, diffusion MRI, and functional MRI) and graph theory methods, researchers have modeled the human brain as a complex network of interacting neuronal elements and characterized the underlying structural and functional connectivity patterns that support diverse cognitive functions. Specifically, research has demonstrated a tight SC-FC coupling, not only in interregional connectivity strength but also in network topologic organizations, such as community, rich-club, and motifs. Moreover, this SC-FC coupling exhibits significant changes in normal development and neuropsychiatric disorders, such as schizophrenia and epilepsy. This review summarizes recent progress regarding the SC-FC relationship of the human brain and emphasizes the important role of large-scale brain networks in the understanding of structural-functional associations. Future research directions related to this topic are also proposed.

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

[2]  A. Mansour,et al.  Linking human brain local activity fluctuations to structural and functional network architectures , 2013, NeuroImage.

[3]  S. Bressler.  Understanding Cognition Through Large-Scale Cortical Networks , 2002 .

[4]  J. Gore,et al.  The Relationship of Anatomical and Functional Connectivity to Resting-State Connectivity in Primate Somatosensory Cortex , 2013, Neuron.

[5]  Alan C. Evans,et al.  Mapping anatomical correlations across cerebral cortex (MACACC) using cortical thickness from MRI , 2006, NeuroImage.

[6]  B. Biswal,et al.  Characterizing variation in the functional connectome: promise and pitfalls , 2012, Trends in Cognitive Sciences.

[7]  John C. Gore,et al.  Integrating Functional and Diffusion Magnetic Resonance Imaging for Analysis of Structure-Function Relationship in the Human Language Network , 2009, PloS one.

[8]  Vinod Menon,et al.  Functional connectivity in the resting brain: A network analysis of the default mode hypothesis , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[9]  Damiaan Denys,et al.  Relation Between Structural and Functional Connectivity in Major Depressive Disorder , 2013, Biological Psychiatry.

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

[11]  S. Bressler,et al.  Large-scale brain networks in cognition: emerging methods and principles , 2010, Trends in Cognitive Sciences.

[12]  Dietmar Cordes,et al.  Role of the corpus callosum in functional connectivity. , 2003, AJNR. American journal of neuroradiology.

[13]  Yong He,et al.  Assessment of system dysfunction in the brain through MRI-based connectomics , 2013, The Lancet Neurology.

[14]  G. Cecchi,et al.  Scale-free brain functional networks. , 2003, Physical review letters.

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

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

[17]  Kaustubh Supekar,et al.  Dynamic Reconfiguration of Structural and Functional Connectivity Across Core Neurocognitive Brain Networks with Development , 2011, The Journal of Neuroscience.

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

[19]  Edward T. Bullmore,et al.  Neuroinformatics Original Research Article , 2022 .

[20]  Richard F. Betzel,et al.  Multi-scale community organization of the human structural connectome and its relationship with resting-state functional connectivity , 2013, Network Science.

[21]  Vince D. Calhoun,et al.  Function–structure associations of the brain: Evidence from multimodal connectivity and covariance studies , 2014, NeuroImage.

[22]  M. Raichle,et al.  Resting-state activity in development and maintenance of normal brain function , 2011, Proceedings of the National Academy of Sciences.

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

[24]  P. Skudlarski,et al.  Detection of functional connectivity using temporal correlations in MR images , 2002, Human brain mapping.

[25]  Karl J. Friston.  Functional and effective connectivity in neuroimaging: A synthesis , 1994 .

[26]  V. Calhoun,et al.  Disrupted correlation between low frequency power and connectivity strength of resting state brain networks in schizophrenia , 2013, Schizophrenia Research.

[27]  O. Sporns,et al.  Motifs in Brain Networks , 2004, PLoS biology.

[28]  Olaf Sporns,et al.  Modeling the Impact of Lesions in the Human Brain , 2009, PLoS Comput. Biol..

[29]  Derek K. Jones,et al.  Virtual in Vivo Interactive Dissection of White Matter Fasciculi in the Human Brain , 2002, NeuroImage.

[30]  Maximilian Reiser,et al.  White matter microstructure underlying default mode network connectivity in the human brain , 2010, NeuroImage.

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

[32]  M M Mesulam,et al.  Large‐scale neurocognitive networks and distributed processing for attention, language, and memory , 1990, Annals of neurology.

[33]  Heidi Johansen-Berg,et al.  Using diffusion imaging to study human connectional anatomy. , 2009, Annual review of neuroscience.

[34]  E. Bullmore,et al.  A Resilient, Low-Frequency, Small-World Human Brain Functional Network with Highly Connected Association Cortical Hubs , 2006, The Journal of Neuroscience.

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

[36]  Yufeng Zang,et al.  Relationship Between Large-Scale Functional and Structural Covariance Networks in Idiopathic Generalized Epilepsy , 2013, Brain Connect..

[37]  O. Sporns,et al.  Structural and Functional Aspects Relating to Cost and Benefit of Rich Club Organization in the Human Cerebral Cortex , 2013, Cerebral cortex.

[38]  Susumu Mori,et al.  Fiber tracking: principles and strategies – a technical review , 2002, NMR in biomedicine.

[39]  Justin L. Vincent,et al.  Intrinsic functional architecture in the anaesthetized monkey brain , 2007, Nature.

[40]  Michael D. Greicius,et al.  Development of functional and structural connectivity within the default mode network in young children , 2010, NeuroImage.

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

[42]  E. S. B. van Oort,et al.  An investigation into the functional and structural connectivity of the Default Mode Network , 2014, NeuroImage.

[43]  Huafu Chen,et al.  Altered functional-structural coupling of large-scale brain networks in idiopathic generalized epilepsy. , 2011, Brain : a journal of neurology.

[44]  Yong He,et al.  Graph theoretical modeling of brain connectivity. , 2010, Current opinion in neurology.

[45]  Andreas Horn,et al.  The structural–functional connectome and the default mode network of the human brain , 2014, NeuroImage.

[46]  M. P. van den Heuvel,et al.  The Ontogeny of the Human Connectome , 2013, The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry.

[47]  Scott T. Grafton,et al.  Dynamic reconfiguration of human brain networks during learning , 2010, Proceedings of the National Academy of Sciences.

[48]  Karl J. Friston,et al.  Structural and Functional Brain Networks: From Connections to Cognition , 2013, Science.

[49]  G L Shulman,et al.  INAUGURAL ARTICLE by a Recently Elected Academy Member:A default mode of brain function , 2001 .

[50]  Rex E. Jung,et al.  Neuroinformatics Original Research Article Correspondence between Structure and Function in the Human Brain at Rest , 2022 .

[51]  M. Fox,et al.  Spontaneous fluctuations in brain activity observed with functional magnetic resonance imaging , 2007, Nature Reviews Neuroscience.

[52]  Daniel C Alexander,et al.  Probabilistic anatomical connectivity derived from the microscopic persistent angular structure of cerebral tissue , 2005, Philosophical Transactions of the Royal Society B: Biological Sciences.

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

[54]  M. Greicius,et al.  Greater than the sum of its parts: a review of studies combining structural connectivity and resting-state functional connectivity , 2009, Brain Structure and Function.

[55]  Edward T. Bullmore,et al.  Modular and Hierarchically Modular Organization of Brain Networks , 2010, Front. Neurosci..

[56]  B. Biswal,et al.  Functional connectivity in the motor cortex of resting human brain using echo‐planar mri , 1995, Magnetic resonance in medicine.

[57]  O. Sporns,et al.  An Anatomical Substrate for Integration among Functional Networks in Human Cortex , 2013, The Journal of Neuroscience.

[58]  Kevin Murphy,et al.  The impact of global signal regression on resting state correlations: Are anti-correlated networks introduced? , 2009, NeuroImage.

[59]  Philip G. F. Browning,et al.  Causal effect of disconnection lesions on interhemispheric functional connectivity in rhesus monkeys , 2013, Proceedings of the National Academy of Sciences.

[60]  Bill Seeley,et al.  Neurodegenerative diseases target large-scale human brain networks , 2010, Alzheimer's & Dementia.

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

[62]  S. Wakana,et al.  Fiber tract-based atlas of human white matter anatomy. , 2004, Radiology.

[63]  J. Kurths,et al.  Structure–function relationship in complex brain networks expressed by hierarchical synchronization , 2007 .

[64]  Guangming Lu,et al.  Generalized tonic-clonic seizures: aberrant interhemispheric functional and anatomical connectivity. , 2014, Radiology.

[65]  O. Sporns,et al.  High-cost, high-capacity backbone for global brain communication , 2012, Proceedings of the National Academy of Sciences.

[66]  Alan C. Evans,et al.  Small-world anatomical networks in the human brain revealed by cortical thickness from MRI. , 2007, Cerebral cortex.

[67]  Michael Breakspear,et al.  Graph analysis of the human connectome: Promise, progress, and pitfalls , 2013, NeuroImage.

[68]  J. Lurito,et al.  Correlations in Low-Frequency BOLD Fluctuations Reflect Cortico-Cortical Connections , 2000, NeuroImage.

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

[70]  Karl J. Friston,et al.  Structural Covariance in the Human Cortex , 2005, The Journal of Neuroscience.

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

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

[73]  Denis Le Bihan,et al.  Looking into the functional architecture of the brain with diffusion MRI , 2003, Nature Reviews Neuroscience.

[74]  Maurizio Corbetta,et al.  The human brain is intrinsically organized into dynamic, anticorrelated functional networks. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[75]  Eswar Damaraju,et al.  Tracking whole-brain connectivity dynamics in the resting state. , 2014, Cerebral cortex.

[76]  E. Bullmore,et al.  The Convergence of Maturational Change and Structural Covariance in Human Cortical Networks , 2013, The Journal of Neuroscience.

[77]  O. Sporns,et al.  Rich-Club Organization of the Human Connectome , 2011, The Journal of Neuroscience.

[78]  Maurizio Corbetta,et al.  Resting-State Functional Connectivity Emerges from Structurally and Dynamically Shaped Slow Linear Fluctuations , 2013, The Journal of Neuroscience.

[79]  Alan C. Evans,et al.  Uncovering Intrinsic Modular Organization of Spontaneous Brain Activity in Humans , 2009, PloS one.

[80]  Stephen D. Mayhew,et al.  The structural and functional connectivity of the posterior cingulate cortex: Comparison between deterministic and probabilistic tractography for the investigation of structure–function relationships , 2014, NeuroImage.

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

[82]  M. P. van den Heuvel,et al.  Microstructural Organization of the Cingulum Tract and the Level of Default Mode Functional Connectivity , 2008, The Journal of Neuroscience.

[83]  Kyungsik Kim,et al.  Comparison of the small-world topology between anatomical and functional connectivity in the human brain , 2008 .

[84]  Liang Wang,et al.  Parcellation‐dependent small‐world brain functional networks: A resting‐state fMRI study , 2009, Human brain mapping.

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

[86]  Erik B. Erhardt,et al.  Modular Organization of Functional Network Connectivity in Healthy Controls and Patients with Schizophrenia during the Resting State , 2011, Front. Syst. Neurosci..

[87]  Joaquín Goñi,et al.  Abnormal rich club organization and functional brain dynamics in schizophrenia. , 2013, JAMA psychiatry.

[88]  Xiangyu Long,et al.  Functional segmentation of the brain cortex using high model order group PICA , 2009, Human brain mapping.

[89]  P. Skudlarski,et al.  Brain Connectivity Is Not Only Lower but Different in Schizophrenia: A Combined Anatomical and Functional Approach , 2010, Biological Psychiatry.

[90]  Efstathios D. Gennatas,et al.  Network-level structural covariance in the developing brain , 2010, Proceedings of the National Academy of Sciences.

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

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

[93]  Anders M. Dale,et al.  An automated labeling system for subdividing the human cerebral cortex on MRI scans into gyral based regions of interest , 2006, NeuroImage.

[94]  Lester Melie-García,et al.  Studying the human brain anatomical network via diffusion-weighted MRI and Graph Theory , 2008, NeuroImage.

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

[96]  E. Bullmore,et al.  Neurophysiological architecture of functional magnetic resonance images of human brain. , 2005, Cerebral cortex.

[97]  Mark W. Woolrich,et al.  Probabilistic diffusion tractography with multiple fibre orientations: What can we gain? , 2007, NeuroImage.

[98]  Changsong Zhou,et al.  Hierarchical organization unveiled by functional connectivity in complex brain networks. , 2006, Physical review letters.

[99]  Samuel D. Carpenter,et al.  Structural and Functional Rich Club Organization of the Brain in Children and Adults , 2014, PloS one.

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

[101]  Wei Liao,et al.  Altered Functional and Structural Connectivity Networks in Psychogenic Non-Epileptic Seizures , 2013, PloS one.

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

[103]  Bharat B. Biswal,et al.  Functional Covariance Networks: Obtaining Resting-State Networks from Intersubject Variability , 2012, Brain Connect..

[104]  H. Nusbaum,et al.  Task-dependent organization of brain regions active during rest , 2009, Proceedings of the National Academy of Sciences.

[105]  Thomas E. Nichols,et al.  Functional connectomics from resting-state fMRI , 2013, Trends in Cognitive Sciences.

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

[107]  Scott T. Grafton,et al.  Structural foundations of resting-state and task-based functional connectivity in the human brain , 2013, Proceedings of the National Academy of Sciences.

[108]  Alan C. Evans,et al.  Mapping anatomical connectivity patterns of human cerebral cortex using in vivo diffusion tensor imaging tractography. , 2009, Cerebral cortex.

[109]  Huafu Chen,et al.  Resting-State Brain Organization Revealed by Functional Covariance Networks , 2011, PloS one.

[110]  Edwin M. Robertson,et al.  The Resting Human Brain and Motor Learning , 2009, Current Biology.

[111]  David G. Norris,et al.  An Investigation of Functional and Anatomical Connectivity Using Magnetic Resonance Imaging , 2002, NeuroImage.

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

[113]  Jordi García-Ojalvo,et al.  Relating structural and functional anomalous connectivity in the aging brain via neural mass modeling , 2010, NeuroImage.

[114]  David A. Leopold,et al.  Dynamic functional connectivity: Promise, issues, and interpretations , 2013, NeuroImage.

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

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

[117]  Jonathan S. Adelstein,et al.  Residual functional connectivity in the split-brain revealed with resting-state functional MRI , 2008, Neuroreport.

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

[119]  Keith Heberlein,et al.  Imaging human connectomes at the macroscale , 2013, Nature Methods.

[120]  Alan Connelly,et al.  Track-weighted functional connectivity (TW-FC): A tool for characterizing the structural–functional connections in the brain , 2013, NeuroImage.

[121]  Yong He,et al.  Topological organization of the human brain functional connectome across the lifespan , 2013, Developmental Cognitive Neuroscience.

[122]  M. Filippi,et al.  Assessing Brain System Dysfunction In Amnesic Mild Cognitve Impairment Through MRI-Based Connectomics (P4.012) , 2014 .

[123]  Huafu Chen,et al.  Default mode network abnormalities in mesial temporal lobe epilepsy: A study combining fMRI and DTI , 2011, Human brain mapping.

[124]  M. Raichle,et al.  Tracking neuronal fiber pathways in the living human brain. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[125]  G. Edelman,et al.  Large-scale model of mammalian thalamocortical systems , 2008, Proceedings of the National Academy of Sciences.

[126]  P. Thiran,et al.  Mapping Human Whole-Brain Structural Networks with Diffusion MRI , 2007, PloS one.

[127]  Ning Yang,et al.  Fusing DTI and fMRI data: A survey of methods and applications , 2014, NeuroImage.

[128]  R Cameron Craddock,et al.  A whole brain fMRI atlas generated via spatially constrained spectral clustering , 2012, Human brain mapping.

[129]  Vince D. Calhoun,et al.  Altered Topological Properties of Functional Network Connectivity in Schizophrenia during Resting State: A Small-World Brain Network Study , 2011, PloS one.

[130]  Daniel P. Kennedy,et al.  Intact Bilateral Resting-State Networks in the Absence of the Corpus Callosum , 2011, The Journal of Neuroscience.

[131]  Ning Zhong,et al.  Changes in the brain intrinsic organization in both on-task state and post-task resting state , 2012, NeuroImage.

[132]  M. P. van den Heuvel,et al.  The parcellation-based connectome: limitations and extensions. , 2013, NeuroImage.

[133]  Ravi S. Menon,et al.  Information Processing Architecture of Functionally Defined Clusters in the Macaque Cortex , 2012, The Journal of Neuroscience.

[134]  Lijun Zhang,et al.  Determining functional connectivity using fMRI data with diffusion-based anatomical weighting , 2009, NeuroImage.