Fundamental Differences: A Basis Set for Characterizing Inter-Individual Variation in Resting State Connectomes

Resting state functional connectomics holds the promise of illuminating and predicting individual differences in behavioral and clinical phenotypes. To realize this goal, however, it is critical to gain greater understanding of the nature, kind, and extent of population-wide interindividual connectomic variation. We examined whole-brain resting state functional connectomes from healthy young adults from the Human Connectome Project 1200 release. We found clear evidence of low rank structure in which a modest number of connectomic components, around 50-150, account for a sizable portion of cross-individual connectomic variation. This number was convergently arrived at with multiple methods including estimation of intrinsic dimensionality and assessment of reconstruction of out-of-sample data. In addition, we show that these connectomic components enable prediction of a broad array of neurocognitive and clinical symptom variables at levels comparable to a leading method that is trained on the whole connectome. Qualitative observation reveals that these connectomic components exhibit extensive community structure reflecting interrelationships between intrinsic connectivity networks. We provide quantitative validation of this observation using novel stochastic block model-based methods. We propose that the fundamental connectivity units identified in this study form an effective basis set for quantifying and interpreting inter-individual connectomic differences, and for predicting behavioral and clinical phenotypes.

[1]  Timothy O. Laumann,et al.  Data Quality Influences Observed Links Between Functional Connectivity and Behavior , 2017, Cerebral cortex.

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

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

[4]  Timothy O. Laumann,et al.  Methods to detect, characterize, and remove motion artifact in resting state fMRI , 2014, NeuroImage.

[5]  M. Chun,et al.  A neuromarker of sustained attention from whole-brain functional connectivity , 2015, Nature Neuroscience.

[6]  S. Petersen,et al.  Development of distinct control networks through segregation and integration , 2007, Proceedings of the National Academy of Sciences.

[7]  R. Tibshirani,et al.  Selecting the number of principal components: estimation of the true rank of a noisy matrix , 2014, 1410.8260.

[8]  M. Chun,et al.  Functional connectome fingerprinting: Identifying individuals based on patterns of brain connectivity , 2015, Nature Neuroscience.

[9]  Moriah E. Thomason,et al.  Functional Connectivity of the Human Brain in Utero , 2016, Trends in Cognitive Sciences.

[10]  M. Fox,et al.  Individual Variability in Functional Connectivity Architecture of the Human Brain , 2013, Neuron.

[11]  Timothy O. Laumann,et al.  Functional Network Organization of the Human Brain , 2011, Neuron.

[12]  Thomas T. Liu,et al.  A component based noise correction method (CompCor) for BOLD and perfusion based fMRI , 2007, NeuroImage.

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

[14]  E. Formisano,et al.  Functional connectivity as revealed by spatial independent component analysis of fMRI measurements during rest , 2004, Human brain mapping.

[15]  R. Adolphs,et al.  Building a Science of Individual Differences from fMRI , 2016, Trends in Cognitive Sciences.

[16]  Joaquín Goñi,et al.  The quest for identifiability in human functional connectomes , 2017, Scientific Reports.

[17]  Kathryn B. Laskey,et al.  Stochastic blockmodels: First steps , 1983 .

[18]  Edward T. Bullmore,et al.  Connectivity differences in brain networks , 2012, NeuroImage.

[19]  Marcus Kaiser,et al.  The potential of the human connectome as a biomarker of brain disease , 2013, Front. Hum. Neurosci..

[20]  Linda B. Smith,et al.  Developmental process emerges from extended brain–body–behavior networks , 2014, Trends in Cognitive Sciences.

[21]  Patric Hagmann,et al.  Comparing connectomes across subjects and populations at different scales , 2013, NeuroImage.

[22]  R. Cameron Craddock,et al.  Clinical applications of the functional connectome , 2013, NeuroImage.

[23]  Dustin Scheinost,et al.  Connectome-based predictive modeling of attention: Comparing different functional connectivity features and prediction methods across datasets , 2018, NeuroImage.

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

[25]  D. Tulsky,et al.  The NIH Toolbox Pattern Comparison Processing Speed Test: Normative Data. , 2015, Archives of clinical neuropsychology : the official journal of the National Academy of Neuropsychologists.

[26]  Dustin Scheinost,et al.  Using connectome-based predictive modeling to predict individual behavior from brain connectivity , 2017, Nature Protocols.

[27]  Deanna M. Barch,et al.  Brain network interactions in health and disease , 2013, Trends in Cognitive Sciences.

[28]  Stephen M. Smith,et al.  Investigations into resting-state connectivity using independent component analysis , 2005, Philosophical Transactions of the Royal Society B: Biological Sciences.

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

[30]  Evan M. Gordon,et al.  Individual-specific features of brain systems identified with resting state functional correlations , 2017, NeuroImage.

[31]  Luke J. Chang,et al.  Building better biomarkers: brain models in translational neuroimaging , 2017, Nature Neuroscience.

[32]  C. Sripada,et al.  Modality-Spanning Deficits in Attention-Deficit/Hyperactivity Disorder in Functional Networks, Gray Matter, and White Matter , 2014, The Journal of Neuroscience.

[33]  Peter J. Bickel,et al.  Maximum Likelihood Estimation of Intrinsic Dimension , 2004, NIPS.

[34]  Sharon L. Thompson-Schill,et al.  A Functional Cartography of Cognitive Systems , 2015, PLoS Comput. Biol..

[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]  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.

[37]  M Deanna,et al.  Brain network interactions in health and disease , 2013, Trends in Cognitive Sciences.

[38]  Chandra Sripada,et al.  Growth Charting of Brain Connectivity Networks and the Identification of Attention Impairment in Youth. , 2016, JAMA psychiatry.

[39]  Yoed N. Kenett,et al.  Robust prediction of individual creative ability from brain functional connectivity , 2018, Proceedings of the National Academy of Sciences.

[40]  J. Fleiss,et al.  Intraclass correlations: uses in assessing rater reliability. , 1979, Psychological bulletin.

[41]  Fenna M. Krienen,et al.  Opportunities and limitations of intrinsic functional connectivity MRI , 2013, Nature Neuroscience.

[42]  Danielle S. Bassett,et al.  Personalized Neuroscience: Common and Individual-Specific Features in Functional Brain Networks , 2018, Neuron.

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

[44]  Dustin Scheinost,et al.  The functional brain organization of an individual predicts measures of social abilities in autism spectrum disorder:Predicting symptoms in autism with brain imaging , 2018, bioRxiv.

[45]  Gaël Varoquaux,et al.  Learning and comparing functional connectomes across subjects , 2013, NeuroImage.

[46]  Christos Davatzikos,et al.  Functional Maturation of the Executive System during Adolescence , 2013, The Journal of Neuroscience.

[47]  V. Menon Large-scale brain networks and psychopathology: a unifying triple network model , 2011, Trends in Cognitive Sciences.

[48]  M. Greicius,et al.  Default-mode network activity distinguishes Alzheimer's disease from healthy aging: Evidence from functional MRI , 2004, Proc. Natl. Acad. Sci. USA.

[49]  P. Costa,et al.  A contemplated revision of the NEO Five-Factor Inventory , 2004 .

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

[51]  S. Petersen,et al.  The maturing architecture of the brain's default network , 2008, Proceedings of the National Academy of Sciences.

[52]  Jessica A. Turner,et al.  Behavioral Interpretations of Intrinsic Connectivity Networks , 2011, Journal of Cognitive Neuroscience.

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

[54]  J. Shimony,et al.  Resting-State fMRI: A Review of Methods and Clinical Applications , 2013, American Journal of Neuroradiology.

[55]  Jonathan D. Power,et al.  Functional Brain Networks Develop from a “Local to Distributed” Organization , 2009, PLoS Comput. Biol..

[56]  Mary E. Meyerand,et al.  The effect of scan length on the reliability of resting-state fMRI connectivity estimates , 2013, NeuroImage.

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

[58]  Jeffrey S. Anderson,et al.  Connectivity Gradients Between the Default Mode and Attention Control Networks , 2011, Brain Connect..

[59]  Joshua R. Loftus,et al.  Inference in adaptive regression via the Kac–Rice formula , 2016 .

[60]  Danielle S Bassett,et al.  Understanding the Emergence of Neuropsychiatric Disorders With Network Neuroscience. , 2018, Biological psychiatry. Cognitive neuroscience and neuroimaging.

[61]  P. Matthews,et al.  Clinical Concepts Emerging from fMRI Functional Connectomics , 2016, Neuron.

[62]  Serena J Counsell,et al.  The emergence of functional architecture during early brain development , 2017, NeuroImage.

[63]  Damien A. Fair,et al.  Development of large-scale functional networks from birth to adulthood: A guide to the neuroimaging literature , 2017, NeuroImage.

[64]  Dustin Scheinost,et al.  Influences on the Test–Retest Reliability of Functional Connectivity MRI and its Relationship with Behavioral Utility , 2017, Cerebral cortex.

[65]  M. Chun,et al.  Functional connectome fingerprinting: Identifying individuals based on patterns of brain connectivity , 2015, Nature Neuroscience.

[66]  L. Rescorla,et al.  The Achenbach System of Empirically Based Assessment. , 2016 .

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

[68]  Ludovica Griffanti,et al.  Automatic denoising of functional MRI data: Combining independent component analysis and hierarchical fusion of classifiers , 2014, NeuroImage.

[69]  Joaquín Goñi,et al.  Mapping the functional connectome traits of levels of consciousness , 2016, NeuroImage.

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

[71]  Jonathan D. Power,et al.  Multi-task connectivity reveals flexible hubs for adaptive task control , 2013, Nature Neuroscience.