Abstract
The human brain has been documented to be spatially organized in a finite set of specific coherent patterns, namely resting state networks (RSNs). The interactions among RSNs, being potentially dynamic and directional, may not be adequately captured by simple correlation or anticorrelation. In order to evaluate the possible effective connectivity within those RSNs, we applied a conditional Granger causality analysis (CGCA) to the RSNs retrieved by independent component analysis (ICA) from resting state functional magnetic resonance imaging (fMRI) data. Our analysis provided evidence for specific causal influences among the detected RSNs: default-mode, dorsal attention, core, central-executive, self-referential, somatosensory, visual, and auditory networks. In particular, we identified that self-referential and default-mode networks (DMNs) play distinct and crucial roles in the human brain functional architecture. Specifically, the former RSN exerted the strongest causal influence over the other RSNs, revealing a top-down modulation of self-referential mental activity (SRN) over sensory and cognitive processing. In quite contrast, the latter RSN was profoundly affected by the other RSNs, which may underlie an integration of information from primary function and higher level cognition networks, consistent with previous task-related studies. Overall, our results revealed the causal influences among these RSNs at different processing levels, and supplied information for a deeper understanding of the brain network dynamics.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Achard S, Salvador R, Whitcher B, Suckling J, Bullmore E (2006) A resilient, low-frequency, small-world human brain functional network with highly connected association cortical hubs. J Neurosci 26: 63–72
Amodio DM, Frith CD (2006) Meeting of minds: the medial frontal cortex and social cognition. Nat Rev Neurosci 7: 268–277
Bartels A, Zeki S (2005) Brain dynamics during natural viewing conditions—a new guide for mapping connectivity in vivo. Neuroimage 24: 339–349
Beckmann CF, DeLuca M, Devlin JT, Smith SM (2005) Investigations into resting-state connectivity using independent component analysis. Philos Trans R Soc Lond B 360: 1001–1013
Biswal B, Yetkin FZ, Haughton VM, Hyde JS (1995) Functional connectivity in the motor cortex of resting human brain using echo-planar MRI. Magn Reson Med 34: 537–541
Biswal BB, Van Kylen J, Hyde JS (1997) Simultaneous assessment of flow and BOLD signals in resting-state functional connectivity maps. NMR Biomed 10: 165–170
Brovelli A, Ding M, Ledberg A, Chen Y, Nakamura R, Bressler SL (2004) Beta oscillations in a large-scale sensorimotor cortical network: directional influences revealed by Granger causality. Proc Natl Acad Sci USA 101: 9849–9854
Buckner RL, Carroll DC (2007) Self-projection and the brain. Trends Cogn Sci 11: 49–57
Buckner RL, Andrews-Hanna JR, Schacter DL (2008) The brain’s default network: anatomy, function, and relevance to disease. Ann NY Acad Sci 1124: 1–38
Calhoun VD, Adali T, Pearlson GD, Pekar JJ (2001) A method for making group inferences from functional MRI data using independent component analysis. Hum Brain Mapp 14: 140–151
Chen Y, Bressler SL, Ding M (2006) Frequency decomposition of conditional Granger causality and application to multivariate neural field potential data. J Neurosci Methods 150: 228–237
Chen S, Ross TJ, Zhan W, Myers CS, Chuang KS, Heishman SJ, Stein EA, Yang Y (2008) Group independent component analysis reveals consistent resting-state networks across multiple sessions. Brain Res 1239: 141–151
Chen H, Yang Q, Liao W, Gong Q, Shen S (2009) Evaluation of the effective connectivity of supplementary motor areas during motor imagery using Granger causality mapping. Neuroimage 47: 1844–1853
Corbetta M, Shulman GL (2002) Control of goal-directed and stimulus-driven attention in the brain. Nat Rev Neurosci 3: 201–215
Cordes D, Haughton VM, Arfanakis K, Wendt GJ, Turski PA, Moritz CH, Quigley MA, Meyerand ME (2000) Mapping functionally related regions of brain with functional connectivity MR imaging. AJNR Am J Neuroradiol 21: 1636–1644
Cordes D, Haughton VM, Arfanakis K, Carew JD, Turski PA, Moritz CH, Quigley MA, Meyerand ME (2001) Frequencies contributing to functional connectivity in the cerebral cortex in “resting-state” data. AJNR Am J Neuroradiol 22: 1326–1333
Damoiseaux JS, Rombouts SA, Barkhof F, Scheltens P, Stam CJ, Smith SM, Beckmann CF (2006) Consistent resting-state networks across healthy subjects. Proc Natl Acad Sci USA 103: 13848–13853
D’Argembeau A, Collette F, Vander Linden M, Laureys S, Del Fiore G, Degueldre C, Luxen A, Salmon E (2005) Self-referential reflective activity and its relationship with rest: a PET study. Neuroimage 25: 616–624
De Luca M, Beckmann CF, De Stefano N, Matthews PM, Smith SM (2006) fMRI resting state networks define distinct modes of long-distance interactions in the human brain. Neuroimage 29: 1359–1367
Dosenbach NU, Visscher KM, Palmer ED, Miezin FM, Wenger KK, Kang HC, Burgund ED, Grimes AL, Schlaggar BL, Petersen SE (2006) A core system for the implementation of task sets. Neuron 50: 799–812
Dosenbach NU, Fair DA, Miezin FM, Cohen AL, Wenger KK, Dosenbach RA, Fox MD, Snyder AZ, Vincent JL, Raichle ME, Schlaggar BL, Petersen SE (2007) Distinct brain networks for adaptive and stable task control in humans. Proc Natl Acad Sci USA 104: 11073–11078
Eckert MA, Kamdar NV, Chang CE, Beckmann CF, Greicius MD, Menon V (2008) A cross-modal system linking primary auditory and visual cortices: evidence from intrinsic fMRI connectivity analysis. Hum Brain Mapp 29: 848–857
Fox MD, Snyder AZ, Vincent JL, Corbetta M, Van Essen DC, Raichle ME (2005) The human brain is intrinsically organized into dynamic, anticorrelated functional networks. Proc Natl Acad Sci USA 102: 9673–9678
Fox MD, Snyder AZ, Zacks JM, Raichle ME (2006) Coherent spontaneous activity accounts for trial-to-trial variability in human evoked brain responses. Nat Neurosci 9: 23–25
Fox MD, Zhang D, Snyder AZ, Raichle ME (2009) The global signal and observed anticorrelated resting state brain networks. J Neurophysiol 101: 3270–3283
Fransson P (2005) Spontaneous low-frequency BOLD signal fluctuations: an fMRI investigation of the resting-state default mode of brain function hypothesis. Hum Brain Mapp 26: 15–29
Friston KJ (1994) Functional and effective connectivity in neuroimaging: a synthesis. Hum Brain Mapp 2: 56–78
Friston K (2009a) Dynamic causal modeling and Granger causality Comments on: the identification of interacting networks in the brain using fMRI: model selection, causality and deconvolution. Neuroimage
Friston KJ (2009b) Causal modelling and brain connectivity in functional magnetic resonance imaging. PLoS Biol 7: e33
Friston KJ, Frith CD, Frackowiak RSJ (1993) Time-dependent changes in effective connectivity measured with PET. Hum Brain Mapp 1: 69–80
Friston KJ, Frith CD, Fletcher P, Liddle PF, Frackowiak RS (1996) Functional topography: multidimensional scaling and functional connectivity in the brain. Cereb Cortex 6: 156–164
Gao Q, Chen H, Gong Q (2008) Evaluation of the effective connectivity of the dominant primary motor cortex during bimanual movement using Granger causality. Neurosci Lett 443: 1–6
Geweke JF (1984) Measures of conditional linear dependence and feedback between time series. J Am Stat Assoc 79: 709–715
Goebel R, Roebroeck A, Kim DS, Formisano E (2003) Investigating directed cortical interactions in time-resolved fMRI data using vector autoregressive modeling and Granger causality mapping. Magn Reson Imaging 21: 1251–1261
Granger CWJ (1969) Investigating causal relations by econometric models and cross-spectral methods. Econometrica 37: 424–438
Greicius MD, Krasnow B, Reiss AL, Menon V (2003) Functional connectivity in the resting brain: a network analysis of the default mode hypothesis. Proc Natl Acad Sci USA 100: 253–258
Greicius MD, Srivastava G, Reiss AL, Menon V (2004) Default-mode network activity distinguishes Alzheimer’s disease from healthy aging: evidence from functional MRI. Proc Natl Acad Sci USA 101: 4637–4642
Gusnard DA, Raichle ME (2001) Searching for a baseline: functional imaging and the resting human brain. Nat Rev Neurosci 2: 685–694
Gusnard DA, Akbudak E, Shulman GL, Raichle ME (2001) Medial prefrontal cortex and self-referential mental activity: relation to a default mode of brain function. Proc Natl Acad Sci USA 98: 4259–4264
Hampson M, Peterson BS, Skudlarski P, Gatenby JC, Gore JC (2002) Detection of functional connectivity using temporal correlations in MR images. Hum Brain Mapp 15: 247–262
Harrison L, Penny WD, Friston K (2003) Multivariate autoregressive modeling of fMRI time series. Neuroimage 19: 1477–1491
Hyvarinen A (1999) Fast and robust fixed-point algorithms for independent component analysis. IEEE Trans Neural Netw 10: 626–634
Jafri MJ, Pearlson GD, Stevens M, Calhoun VD (2008) A method for functional network connectivity among spatially independent resting-state components in schizophrenia. Neuroimage 39: 1666–1681
Kelly AM, Uddin LQ, Biswal BB, Castellanos FX, Milham MP (2008) Competition between functional brain networks mediates behavioral variability. Neuroimage 39: 527–537
Koechlin E, Summerfield C (2007) An information theoretical approach to prefrontal executive function. Trends Cogn Sci 11: 229–235
Kwong KK, Belliveau JW, Chesler DA, Goldberg IE, Weisskoff RM, Poncelet BP, Kennedy DN, Hoppel BE, Cohen MS, Turner R et al (1992) Dynamic magnetic resonance imaging of human brain activity during primary sensory stimulation. Proc Natl Acad Sci USA 89: 5675–5679
Li YO, Adali T, Calhoun VD (2007) Estimating the number of independent components for functional magnetic resonance imaging data. Hum Brain Mapp 28: 1251–1266
Liao W, Marinazzo D, Pan Z, Gong Q, Chen H (2009) Kernel Granger causality mapping effective connectivity on fMRI data. IEEE Trans Med Imaging 28: 1825–1835
Londei A, D’Ausilio A, Basso D, Sestieri C, Del Gratta C, Romani GL, Olivetti Belardinelli M (2007) Brain network for passive word listening as evaluated with ICA and Granger causality. Brain Res Bull 72: 284–292
Lowe MJ, Mock BJ, Sorenson JA (1998) Functional connectivity in single and multislice echoplanar imaging using resting-state fluctuations. Neuroimage 7: 119–132
Macrae CN, Moran JM, Heatherton TF, Banfield JF, Kelley WM (2004) Medial prefrontal activity predicts memory for self. Cereb Cortex 14: 647–654
Mantini D, Perrucci MG, Del Gratta C, Romani GL, Corbetta M (2007) Electrophysiological signatures of resting state networks in the human brain. Proc Natl Acad Sci USA 104: 13170–13175
Mantini D, Corbetta M, Perrucci MG, Romani GL, Del Gratta C (2009) Large-scale brain networks account for sustained and transient activity during target detection. Neuroimage 44: 265–274
McKeown MJ, Jung TP, Makeig S, Brown G, Kindermann SS, Lee TW, Sejnowski TJ (1998) Spatially independent activity patterns in functional MRI data during the stroop color-naming task. Proc Natl Acad Sci USA 95: 803–810
McKiernan KA, Kaufman JN, Kucera-Thompson J, Binder JR (2003) A parametric manipulation of factors affecting task-induced deactivation in functional neuroimaging. J Cogn Neurosci 15: 394–408
Murphy K, Birn RM, Handwerker DA, Jones TB, Bandettini PA (2009) The impact of global signal regression on resting state correlations: are anti-correlated networks introduced? Neuroimage 44: 893–905
Northoff G, Bermpohl F (2004) Cortical midline structures and the self. Trends Cogn Sci 8: 102–107
Northoff G, Heinzel A, de Greck M, Bermpohl F, Dobrowolny H, Panksepp J (2006) Self-referential processing in our brain—a meta-analysis of imaging studies on the self. Neuroimage 31: 440–457
Ongur D, Price JL (2000) The organization of networks within the orbital and medial prefrontal cortex of rats, monkeys and humans. Cereb Cortex 10: 206–219
Raichle ME, MacLeod AM, Snyder AZ, Powers WJ, Gusnard DA, Shulman GL (2001) A default mode of brain function. Proc Natl Acad Sci USA 98: 676–682
Roebroeck A, Formisano E, Goebel R (2005) Mapping directed influence over the brain using Granger causality and fMRI. Neuroimage 25: 230–242
Roebroeck A, Formisano E, Goebel R (2009) The identification of interacting networks in the brain using fMRI: model selection, causality and deconvolution. Neuroimage
Salvador R, Suckling J, Coleman MR, Pickard JD, Menon D, Bullmore E (2005) Neurophysiological architecture of functional magnetic resonance images of human brain. Cereb Cortex 15: 1332–1342
Seifritz E, Esposito F, Hennel F, Mustovic H, Neuhoff JG, Bilecen D, Tedeschi G, Scheffler K, Di Salle F (2002) Spatiotemporal pattern of neural processing in the human auditory cortex. Science 297: 1706–1708
Seth AK (2005) Causal connectivity of evolved neural networks during behavior. Network 16: 35–54
Sridharan D, Levitin DJ, Menon V (2008) A critical role for the right fronto-insular cortex in switching between central-executive and default-mode networks. Proc Natl Acad Sci USA 105: 12569–12574
Stam CJ, Reijneveld JC (2007) Graph theoretical analysis of complex networks in the brain. Nonlinear Biomed Phys 1: 3
Stark DE, Margulies DS, Shehzad ZE, Reiss P, Kelly AM, Uddin LQ, Gee DG, Roy AK, Banich MT, Castellanos FX, Milham MP (2008) Regional variation in interhemispheric coordination of intrinsic hemodynamic fluctuations. J Neurosci 28: 13754–13764
Stevens MC, Kiehl KA, Pearlson G, Calhoun VD (2007) Functional neural circuits for mental timekeeping. Hum Brain Mapp 28: 394–408
Stevens MC, Pearlson GD, Calhoun VD (2009) Changes in the interaction of resting-state neural networks from adolescence to adulthood. Hum Brain Mapp 30: 2356–2366
Tian L, Jiang T, Liang M, Li X, He Y, Wang K, Cao B, Jiang T (2007) Stabilities of negative correlations between blood oxygen level-dependent signals associated with sensory and motor cortices. Hum Brain Mapp 28: 681–690
Uddin LQ, Clare Kelly AM, Biswal BB, Xavier Castellanos F, Milham MP (2009) Functional connectivity of default mode network components: correlation, anticorrelation, and causality. Hum Brain Mapp 30: 625–637
Upadhyay J, Silver A, Knaus TA, Lindgren KA, Ducros M, Kim DS, Tager-Flusberg H (2008) Effective and structural connectivity in the human auditory cortex. J Neurosci 28: 3341–3349
van de Ven V, Formisano E, Prvulovic D, Roeder CH, Linden DE (2004) Functional connectivity as revealed by spatial independent component analysis of fMRI measurements during rest. Hum Brain Mapp 22: 165–178
van de Ven V, Bledowski C, Prvulovic D, Goebel R, Formisano E, Di Salle F, Linden DE, Esposito F (2008) Visual target modulation of functional connectivity networks revealed by self-organizing group ICA. Hum Brain Mapp 29: 1450–1461
van den Heuvel M, Mandl R, Hulshoff Pol H (2008) Normalized cut group clustering of resting-state FMRI data. PLoS ONE 3: e2001
Vincent JL, Snyder AZ, Fox MD, Shannon BJ, Andrews JR, Raichle ME, Buckner RL (2006) Coherent spontaneous activity identifies a hippocampal-parietal memory network. J Neurophysiol 96: 3517–3531
Wilke M, Lidzba K, Krageloh-Mann I (2009) Combined functional and causal connectivity analyses of language networks in children: a feasibility study. Brain Lang 108: 22–29
Wu CW, Gu H, Lu H, Stein EA, Chen JH, Yang Y (2008) Frequency specificity of functional connectivity in brain networks. Neuroimage 42: 1047–1055
Zhou Z, Chen Y, Ding M, Wright P, Lu Z, Liu Y (2009) Analyzing brain networks with PCA and conditional Granger causality. Hum Brain Mapp 30: 2197–2206
Author information
Authors and Affiliations
Corresponding author
Additional information
Wei Liao and Dante Mantini contribute equally to this work.
Electronic Supplementary Material
The Below is the Electronic Supplementary Material.
Rights and permissions
About this article
Cite this article
Liao, W., Mantini, D., Zhang, Z. et al. Evaluating the effective connectivity of resting state networks using conditional Granger causality. Biol Cybern 102, 57–69 (2010). https://doi.org/10.1007/s00422-009-0350-5
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00422-009-0350-5