A parsimonious statistical method to detect groupwise differentially expressed functional connectivity networks

Group‐level functional connectivity analyses often aim to detect the altered connectivity patterns between subgroups with different clinical or psychological experimental conditions, for example, comparing cases and healthy controls. We present a new statistical method to detect differentially expressed connectivity networks with significantly improved power and lower false‐positive rates. The goal of our method was to capture most differentially expressed connections within networks of constrained numbers of brain regions (by the rule of parsimony). By virtue of parsimony, the false‐positive individual connectivity edges within a network are effectively reduced, whereas the informative (differentially expressed) edges are allowed to borrow strength from each other to increase the overall power of the network. We develop a test statistic for each network in light of combinatorics graph theory, and provide p‐values for the networks (in the weak sense) by using permutation test with multiple‐testing adjustment. We validate and compare this new approach with existing methods, including false discovery rate and network‐based statistic, via simulation studies and a resting‐state functional magnetic resonance imaging case–control study. The results indicate that our method can identify differentially expressed connectivity networks, whereas existing methods are limited. Hum Brain Mapp 36:5196–5206, 2015. © 2015 Wiley Periodicals, Inc.

[1]  Bryon A. Mueller,et al.  Altered resting state complexity in schizophrenia , 2012, NeuroImage.

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

[3]  Wei Pan,et al.  Comparison of statistical tests for group differences in brain functional networks , 2014, NeuroImage.

[4]  R Cameron Craddock,et al.  Disease state prediction from resting state functional connectivity , 2009, Magnetic resonance in medicine.

[5]  Edward T. Bullmore,et al.  Schizophrenia, neuroimaging and connectomics , 2012, NeuroImage.

[6]  Habib Benali,et al.  Regions, systems, and the brain: Hierarchical measures of functional integration in fMRI , 2008, Medical Image Anal..

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

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

[9]  Paul J. Laurienti,et al.  A two-part mixed-effects modeling framework for analyzing whole-brain network data , 2014, NeuroImage.

[10]  Ulrike von Luxburg,et al.  A tutorial on spectral clustering , 2007, Stat. Comput..

[11]  Edward T. Bullmore,et al.  Network-based statistic: Identifying differences in brain networks , 2010, NeuroImage.

[12]  M. Just,et al.  Functional connectivity in a baseline resting-state network in autism , 2006, Neuroreport.

[13]  R. Kahn,et al.  Aberrant Frontal and Temporal Complex Network Structure in Schizophrenia: A Graph Theoretical Analysis , 2010, The Journal of Neuroscience.

[14]  Katie L. McMahon,et al.  A multivariate distance-based analytic framework for connectome-wide association studies , 2014, NeuroImage.

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

[16]  Yong He,et al.  BrainNet Viewer: A Network Visualization Tool for Human Brain Connectomics , 2013, PloS one.

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

[18]  Andrew B. Kahng,et al.  New spectral methods for ratio cut partitioning and clustering , 1991, IEEE Trans. Comput. Aided Des. Integr. Circuits Syst..

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

[20]  Cedric E. Ginestet,et al.  Statistical network analysis for functional MRI: summary networks and group comparisons , 2013, Front. Comput. Neurosci..

[21]  N. Tzourio-Mazoyer,et al.  Automated Anatomical Labeling of Activations in SPM Using a Macroscopic Anatomical Parcellation of the MNI MRI Single-Subject Brain , 2002, NeuroImage.

[22]  O. Sporns,et al.  Dynamical consequences of lesions in cortical networks , 2008, Human brain mapping.

[23]  Olaf Sporns,et al.  THE HUMAN CONNECTOME: A COMPLEX NETWORK , 2011, Schizophrenia Research.

[24]  Moors Pieter,et al.  Test-retest reliability. , 2014 .

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

[26]  Daniel P. Kennedy,et al.  Largely typical patterns of resting-state functional connectivity in high-functioning adults with autism. , 2014, Cerebral cortex.

[27]  Paul J. Laurienti,et al.  A permutation testing framework to compare groups of brain networks , 2013, Front. Comput. Neurosci..

[28]  Edward T. Bullmore,et al.  On the use of correlation as a measure of network connectivity , 2012, NeuroImage.

[29]  Jianqing Fan,et al.  Journal of the American Statistical Association Estimating False Discovery Proportion under Arbitrary Covariance Dependence Estimating False Discovery Proportion under Arbitrary Covariance Dependence , 2022 .

[30]  Jitendra Malik,et al.  Normalized cuts and image segmentation , 1997, Proceedings of IEEE Computer Society Conference on Computer Vision and Pattern Recognition.

[31]  R. Buckner,et al.  Efficacy of Transcranial Magnetic Stimulation Targets for Depression Is Related to Intrinsic Functional Connectivity with the Subgenual Cingulate , 2012, Biological Psychiatry.

[32]  Daniel P. Kennedy,et al.  The Autism Brain Imaging Data Exchange: Towards Large-Scale Evaluation of the Intrinsic Brain Architecture in Autism , 2013, Molecular Psychiatry.

[33]  Thomas E. Nichols,et al.  Combining voxel intensity and cluster extent with permutation test framework , 2004, NeuroImage.

[34]  Paul J. Laurienti,et al.  An exponential random graph modeling approach to creating group-based representative whole-brain connectivity networks , 2011, NeuroImage.

[35]  Paul J. Laurienti,et al.  Exponential Random Graph Modeling for Complex Brain Networks , 2010, PloS one.

[36]  Rongjun Yu,et al.  Key functional circuitry altered in schizophrenia involves parietal regions associated with sense of self , 2014, Human brain mapping.

[37]  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.

[38]  Olaf Sporns,et al.  From simple graphs to the connectome: Networks in neuroimaging , 2012, NeuroImage.

[39]  Olaf Sporns,et al.  Weight-conserving characterization of complex functional brain networks , 2011, NeuroImage.

[40]  Paul J Laurienti,et al.  Analyzing complex functional brain networks: Fusing statistics and network science to understand the brain*† , 2013, Statistics surveys.

[41]  Cornelis J. Stam,et al.  Small-world and scale-free organization of voxel-based resting-state functional connectivity in the human brain , 2008, NeuroImage.

[42]  Andreas Heinz,et al.  Test–retest reliability of resting-state connectivity network characteristics using fMRI and graph theoretical measures , 2012, NeuroImage.

[43]  R. Kahn,et al.  Efficiency of Functional Brain Networks and Intellectual Performance , 2009, The Journal of Neuroscience.