Abstract
This study aims to characterize the connective profiles and the coupling relationship between dynamic and static functional connectivity (dFC and sFC) in large-scale brain networks in patients with generalized epilepsy (GE). Functional, structural and diffuse MRI data were collected from 83 patients with GE and 106 matched healthy controls (HC). Resting-state BOLD time course was deconvolved to neural time course using a blind hemodynamic deconvolution method. Then, five connective profiles, including the structural connectivity (SC) and BOLD/neural time course-derived sFC/dFC networks, were constructed based on the proposed whole brain atlas. Network-level weighted correlation probability (NWCP) were proposed to evaluate the association between dFC and sFC. Both the BOLD signal and neural time course showed highly concordant findings and the present study emphasized the consistent findings between two functional approaches. The patients with GE showed hypervariability and enhancement of FC, and notably decreased SC in the subcortical network. Besides, increased dFC, weaker anatomic links, and complex alterations of sFC were observed in the default mode network of GE. Moreover, significantly increased SC and predominantly increased sFC were found in the frontoparietal network. Remarkably, antagonism between dFC and sFC was observed in large-scale networks in HC, while patients with GE showed significantly decreased antagonism in core epileptic networks. In sum, our study revealed distinct connective profiles in different epileptic networks and provided new clues to the brain network mechanism of epilepsy from the perspective of antagonism between dynamic and static functional connectivity.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Abarrategui B, Parejo-Carbonell B, Garcia MEG, Di Capua D, Garcia-Morales I (2018) The cognitive phenotype of idiopathic generalized epilepsy. Epilepsy Behav 89:99–104. https://doi.org/10.1016/j.yebeh.2018.10.007
Allen EA, Damaraju E, Plis SM, Erhardt EB, Eichele T, Calhoun VD (2014) Tracking whole-brain connectivity dynamics in the resting state. Cereb Cortex 24(3):663–676. https://doi.org/10.1093/cercor/bhs352
Badawy RA, Curatolo JM, Newton M, Berkovic SF, Macdonell RA (2007) Changes in cortical excitability differentiate generalized and focal epilepsy. Ann Neurol 61(4):324–331. https://doi.org/10.1002/ana.21087
Bartolini E, Pesaresi I, Fabbri S, Cecchi P, Giorgi FS, Sartucci F, Bonuccelli U, Cosottini M (2014) Abnormal response to photic stimulation in Juvenile Myoclonic Epilepsy: An EEG-fMRI study. Epilepsia 55(7):1038–1047. https://doi.org/10.1111/epi.12634
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(4):537–541. https://doi.org/10.1002/mrm.1910340409
Brigo F, Bongiovanni LG, Nardone R, Trinka E, Tezzon F, Fiaschi A, Manganotti P (2013) Visual cortex hyperexcitability in idiopathic generalized epilepsies with photosensitivity: a TMS pilot study. Epilepsy Behav 27(2):301–306. https://doi.org/10.1016/j.yebeh.2013.02.010
Cao XZ, Qian ZY, Xu Q, Shen JS, Zhang ZQ, Lu GM (2014) Altered intrinsic connectivity networks in frontal lobe epilepsy: a Resting-State fMRI Study. Comput Math Methods Med. https://doi.org/10.1155/2014/864979
Carney PW, Masterton RA, Flanagan D, Berkovic SF, Jackson GD (2012) The frontal lobe in absence epilepsy: EEG-fMRI findings. Neurology 78(15):1157–1165. https://doi.org/10.1212/WNL.0b013e31824f801d
Cerliani L, Mennes M, Thomas RM, Di Martino A, Thioux M, Keysers C (2015) Increased functional connectivity between subcortical and cortical resting-state networks in autism spectrum disorder. Jama Psychiat 72(8):767–777. https://doi.org/10.1001/jamapsychiatry.2015.0101
Chang C, Glover GH (2010) Time-frequency dynamics of resting-state brain connectivity measured with fMRI. Neuroimage 50(1):81–98. https://doi.org/10.1016/j.neuroimage.2009.12.011
Chen MM, Guo DQ, Li M, Ma T, Wu SD, Ma JL, Cui Y, Xia Y, Xu P, Yao DZ (2015) Critical roles of the direct GABAergic pallido-cortical pathway in controlling absence seizures. PLoS Comp Biol 11(10):e1004539. https://doi.org/10.1371/journal.pcbi.1004539
Chowdhury FA, Elwes RDC, Koutroumanidis M, Morris RG, Nashef L, Richardson MP (2014) Impaired cognitive function in idiopathic generalized epilepsy and unaffected family members: an epilepsy endophenotype. Epilepsia 55(6):835–840. https://doi.org/10.1111/epi.12604
Deransart C, Vercueil L, Marescaux C, Depaulis A (1998) The role of basal ganglia in the control of generalized absence seizures. Epilepsy Res 32(1–2):213–223. https://doi.org/10.1016/S0920-1211(98)00053-9
DeSalvo MN, Douw L, Tanaka N, Reinsberger C, Stufflebeam SM (2014) Altered structural connectome in temporal lobe epilepsy. Radiology 270(3):842–848. https://doi.org/10.1148/radiol.13131044
Dong L, Luo C, Zhu Y, Hou C, Jiang S, Wang P, Biswal BB, Yao D (2016) Complex discharge-affecting networks in juvenile myoclonic epilepsy: a simultaneous EEG-fMRI study. Hum Brain Mapp 37(10):3515–3529. https://doi.org/10.1002/hbm.23256
Engel J, Jr., International League Against E (2001) A proposed diagnostic scheme for people with epileptic seizures and with epilepsy: report of the ILAE Task Force on Classification and Terminology. Epilepsia 42(6):796–803
Fan LZ, Li H, Zhuo JJ, Zhang Y, Wang JJ, Chen LF, Yang ZY, Chu CY, Xie SM, Laird AR, Fox PT, Eickhoff SB, Yu CS, Jiang TZ (2016) The human brainnetome atlas: a new brain atlas based on connectional architecture. Cereb Cortex 26(8):3508–3526. https://doi.org/10.1093/cercor/bhw157
Gotman J (2008a) Epileptic networks studied with EEG-fMRI. Epilepsia 49(Suppl 3):42–51. https://doi.org/10.1111/j.1528-1167.2008.01509.x
Gotman J (2008b) Epileptic networks studied with EEG-fMRI. Epilepsia 49:42–51. https://doi.org/10.1111/j.1528-1167.2008.01509.x
Gotman J, Grova C, Bagshaw A, Kobayashi E, Aghakhani Y, Dubeau F (2005) Generalized epileptic discharges show thalamocortical activation and suspension of the default state of the brain. Proc Natl Acad Sci USA 102(42):15236–15240. https://doi.org/10.1073/pnas.0504935102
Groppa S, Siebner HR, Kurth C, Stephani U, Siniatchkin M (2008) Abnormal response of motor cortex to photic stimulation in idiopathic generalized epilepsy. Epilepsia 49(12):2022–2029. https://doi.org/10.1111/j.1528-1167.2008.01709.x
He XS, Chaitanya G, Asma B, Caciagli L, Bassett DS, Tracy JI, Sperling MR (2020) Disrupted basal ganglia-thalamocortical loops in focal to bilateral tonic-clonic seizures. Brain 143:175–190. https://doi.org/10.1093/brain/awz361
Hutchison RM, Womelsdorf T, Allen EA, Bandettini PA, Calhoun VD, Corbetta M, Della Penna S, Duyn JH, Glover GH, Gonzalez-Castillo J, Handwerker DA, Keilholz S, Kiviniemi V, Leopold DA, de Pasquale F, Sporns O, Walter M, Chang C (2013a) Dynamic functional connectivity: promise, issues, and interpretations. Neuroimage 80:360–378. https://doi.org/10.1016/j.neuroimage.2013.05.079
Hutchison RM, Womelsdorf T, Allen EA, Bandettini PA, Calhoun VD, Corbetta M, Penna S, Duyn JH, Glover GH, Gonzalez-Castillo J, Handwerker DA, Keilholz S, Kiviniemi V, Leopold DA, Pasquale F, Sporns O, Walter M, Chang C (2013b) Dynamic functional connectivity: promise, issues, and interpretations. Neuroimage 80:360–378. https://doi.org/10.1016/j.neuroimage.2013.05.079
Hutchison RM, Womelsdorf T, Gati JS, Everling S, Menon RS (2013c) Resting-state networks show dynamic functional connectivity in awake humans and anesthetized macaques. Hum Brain Mapp 34(9):2154–2177. https://doi.org/10.1002/hbm.22058
Jiang S, Luo C, Gong J, Peng R, Ma S, Tan S, Ye G, Dong L, Yao D (2018) Aberrant thalamocortical connectivity in juvenile myoclonic epilepsy. IJNS 28(1):1750034. https://doi.org/10.1142/S0129065717500344
Kramer MA, Kolaczyk ED, Kirsch HE (2008) Emergent network topology at seizure onset in humans. Epilepsy Res 79(2–3):173–186. https://doi.org/10.1016/j.eplepsyres.2008.02.002
Laufs H (2012) Functional imaging of seizures and epilepsy: evolution from zones to networks. Curr Opin Neurol 25(2):194–200. https://doi.org/10.1097/WCO.0b013e3283515db9
Leonardi N, Van De Ville D (2015) On spurious and real fluctuations of dynamic functional connectivity during rest. Neuroimage 104:464–465. https://doi.org/10.1016/j.neuroimage.2014.10.045
Li YY, Wang JH, Jia LF, Zhao ZL, Lu J, Li KC, Jia JP, He Y, Jiang CL, Han Y (2012) Structural and functional Changes in subcortical vascular mild cognitive impairment: a combined voxel-based morphometry and Resting-State fMRI Study. PLoS ONE 7(9):e44758. https://doi.org/10.1371/journal.pone.0044758
Liu F, Wang YF, Li ML, Wang WQ, Li R, Zhang ZQ, Lu GM, Chen HF (2017) Dynamic functional network connectivity in idiopathic generalized epilepsy with generalized tonic-clonic seizure. Hum Brain Mapp 38(2):957–973. https://doi.org/10.1002/hbm.23430
Loddenkemper T, Pan A, Neme S, Baker KB, Rezai AR, Dinner DS, Montgomery EB Jr, Luders HO (2001) Deep brain stimulation in epilepsy. J Clin Neurophysiol 18(6):514–532
Lowe MJ, Dzemidzic M, Lurito JT, Mathews VP, Phillips MD (2000) Correlations in low-frequency BOLD fluctuations reflect cortico-cortical connections. Neuroimage 12(5):582–587. https://doi.org/10.1006/nimg.2000.0654
Luo C, Li QF, Lai YX, Xia Y, Qin Y, Liao W, Li SS, Zhou D, Yao DZ, Gong QY (2011) Altered functional connectivity in default mode network in absence epilepsy: a Resting-State fMRI Study. Hum Brain Mapp 32(3):438–449. https://doi.org/10.1002/hbm.21034
Luo C, Li QF, Xia Y, Lei X, Xue KQ, Yao ZP, Lai YX, Martinez-Montes E, Liao W, Zhou D, Valdes-Sosa PA, Gong QY, Yao DZ (2012) Resting state basal ganglia network in idiopathic generalized epilepsy. Hum Brain Mapp 33(6):1279–1294. https://doi.org/10.1002/hbm.21286
Mishra AM, Ellens DJ, Schridde U, Motelow JE, Purcaro MJ, DeSalvo MN, Enev M, Sanganahalli BG, Hyder F, Blumenfeld H (2011) Where fMRI and electrophysiology agree to disagree: corticothalamic and striatal activity patterns in the WAG/Rij rat. J Neurosci 31(42):15053–15064. https://doi.org/10.1523/JNEUROSCI.0101-11.2011
Miyamoto H, Tatsukawa T, Shimohata A, Yamagata T, Suzuki T, Amano K, Mazaki E, Raveau M, Ogiwara I, Oba-Asaka A, Hensch TK, Itohara S, Sakimura K, Kobayashi K, Kobayashi K, Yamakawa K (2019) Impaired cortico-striatal excitatory transmission triggers epilepsy. Nat Commun. 10:1917. https://doi.org/10.1038/S41467-019-09954-9
Mori S, van Zijl PCM (2002) Fiber tracking: principles and strategies-a technical review. NMR Biomed 15(7–8):468–480. https://doi.org/10.1002/nbm.781
Pawley AD, Chowdhury FA, Tangwiriyasakul C, Ceronie B, Elwes RDC, Nashef L, Richardson MP (2017) Cortical excitability correlates with seizure control and epilepsy duration in chronic epilepsy. Ann Clin Trans Neurol 4(2):87–97. https://doi.org/10.1002/acn3.383
Ponten SC, Bartolomei F, Stam CJ (2007) Small-world networks and epilepsy: graph theoretical analysis of intracerebrally recorded mesial temporal lobe seizures. Clin Neurophysiol 118(4):918–927. https://doi.org/10.1016/j.clinph.2006.12.002
Power JD, Barnes KA, Snyder AZ, Schlaggar BL, Petersen SE (2012) Spurious but systematic correlations in functional connectivity MRI networks arise from subject motion (vol 59, pg 2142, 2012). Neuroimage 63(2):999–999. https://doi.org/10.1016/j.neuroimage.2012.01.069
Preti MG, Bolton TAW, Van De Ville D (2017) The dynamic functional connectome: state-of-the-art and perspectives. Neuroimage 160:41–54. https://doi.org/10.1016/j.neuroimage.2016.12.061
Rangaprakash D, Deshpande G, Daniel TA, Goodman AM, Robinson JL, Salibi N, Katz JS, Denney TS, Dretsch MN (2017a) Compromised hippocampus-striatum pathway as a potential imaging biomarker of mild-traumatic brain injury and posttraumatic stress disorder. Hum Brain Mapp 38(6):2843–2864. https://doi.org/10.1002/hbm.23551
Rangaprakash D, Dretsch MN, Yan WJ, Katz JS, Denney TS, Deshpande G (2017b) Hemodynamic variability in soldiers with trauma: implications for functional MRI connectivity studies. Neuroimage-Clin 16:409–417. https://doi.org/10.1016/j.nicl.2017.07.016
Rangaprakash D, Dretsch MN, Venkataraman A, Katz JS, Denney TS, Deshpande G (2018a) Identifying disease foci from static and dynamic effective connectivity networks: illustration in soldiers with trauma. Hum Brain Mapp 39(1):264–287. https://doi.org/10.1002/hbm.23841
Rangaprakash D, Wu GR, Marinazzo D, Hu XP, Deshpande G (2018b) Hemodynamic response function (HRF) variability confounds resting-state fMRI functional connectivity. Magn Reson Med 80(4):1697–1713. https://doi.org/10.1002/mrm.27146
Richardson MP (2012) Large scale brain models of epilepsy: dynamics meets connectomics. J Neurol Neurosur Ps 83(12):1238–1248. https://doi.org/10.1136/jnnp-2011-301944
Rubinov M, Sporns O (2011) Weight-conserving characterization of complex functional brain networks. Neuroimage 56(4):2068–2079. https://doi.org/10.1016/j.neuroimage.2011.03.069
Sakoglu U, Pearlson GD, Kiehl KA, Wang YM, Michael AM, Calhoun VD (2010) A method for evaluating dynamic functional network connectivity and task-modulation: application to schizophrenia. MRMPB 23(5–6):351–366. https://doi.org/10.1007/s10334-010-0197-8
Schindler KA, Bialonski S, Horstmann MT, Elger CE, Lehnertz K (2008) Evolving functional network properties and synchronizability during human epileptic seizures. Chaos 18(3):033119. https://doi.org/10.1063/1.2966112
Shen K, Hutchison RM, Bezgin G, Everling S, McIntosh AR (2015) Network structure shapes spontaneous functional connectivity dynamics. J Neurosci 35(14):5579–5588. https://doi.org/10.1523/Jneurosci.4903-14.2015
Sporns O, Chialvo DR, Kaiser M, Hilgetag CC (2004) Organization, development and function of complex brain networks. Trends Cogn Sci 8(9):418–425. https://doi.org/10.1016/j.tics.2004.07.008
Strigaro G, Prandi P, Varrasi C, Monaco F, Cantello R (2012) Defective visual inhibition in photosensitive idiopathic generalized epilepsy. Epilepsia 53(4):695–704. https://doi.org/10.1111/j.1528-1167.2012.03411.x
Szaflarski JP, DiFrancesco M, Hirschauer T, Banks C, Privitera MD, Gotman J, Holland SK (2010) Cortical and subcortical contributions to absence seizure onset examined with EEG/fMRI. Epilepsy Behav 18(4):404–413. https://doi.org/10.1016/j.yebeh.2010.05.009
Tagliazucchi E, Balenzuela P, Fraiman D, Chialvo DR (2012) Criticality in large-scale brain fMRI dynamics unveiled by a novel point process analysis. Front Physiol 3:15. https://doi.org/10.3389/Fphys.2012.00015
Toth K, Hofer KT, Kandracs A, Entz L, Bago A, Eross L, Jordan Z, Nagy G, Solyom A, Fabo D, Ulbert I, Wittner L (2018) Hyperexcitability of the network contributes to synchronization processes in the human epileptic neocortex. J Physiol-London 596(2):317–342. https://doi.org/10.1113/JP275413
Vollmar C, O’Muircheartaigh J, Symms MR, Barker GJ, Thompson P, Kumari V, Stretton J, Duncan JS, Richardson MP, Koepp MJ (2012) Altered microstructural connectivity in juvenile myoclonic epilepsy: the missing link. Neurology 78(20):1555–1559. https://doi.org/10.1212/WNL.0b013e3182563b44
Vuong J, Devergnas A (2018) The role of the basal ganglia in the control of seizure. J Neural Transm 125(3):531–545. https://doi.org/10.1007/s00702-017-1768-x
Wang Z, Dai Z, Gong G, Zhou C, He Y (2015) Understanding structural-functional relationships in the human brain: a large-scale network perspective. Neuroscientist 21(3):290–305. https://doi.org/10.1177/1073858414537560
Wang Z, Lariviere S, Xu Q, Vos de Wael R, Hong SJ, Wang Z, Xu Y, Zhu B, Bernasconi N, Bernasconi A, Zhang B, Zhang Z, Bernhardt BC (2019) Community-informed connectomics of the thalamocortical system in generalized epilepsy. Neurology 93(11):e1112–e1122. https://doi.org/10.1212/WNL.0000000000008096
Wang ZG, Lu GM, Zhang ZQ, Zhong YA, Jiao Q, Zhang ZJ, Tan QF, Tian L, Chen GH, Liao W, Li K, Liu YJ (2011) Altered resting state networks in epileptic patients with generalized tonic-clonic seizures. Brain Res 1374:134–141. https://doi.org/10.1016/j.brainres.2010.12.034
Wei HL, An J, Zeng LL, Shen H, Qiu SJ, Hu DW (2015) Altered functional connectivity among default, attention, and control networks in idiopathic generalized epilepsy. Epilepsy Behav 46:118–125. https://doi.org/10.1016/j.yebeh.2015.03.031
Winkler AM, Ridgway GR, Webster MA, Smith SM, Nichols TE (2014) Permutation inference for the general linear model. Neuroimage 92:381–397. https://doi.org/10.1016/j.neuroimage.2014.01.060
Wu GR, Liao W, Stramaglia S, Ding JR, Chen HF, Marinazzo D (2013) A blind deconvolution approach to recover effective connectivity brain networks from resting state fMRI data. Med Image Anal 17(3):365–374. https://doi.org/10.1016/j.media.2013.01.003
Xue K, Luo C, Zhang D, Yang T, Li J, Gong D, Chen L, Medina YI, Gotman J, Zhou D, Yao D (2014) Diffusion tensor tractography reveals disrupted structural connectivity in childhood absence epilepsy. Epilepsy Res 108(1):125–138. https://doi.org/10.1016/j.eplepsyres.2013.10.002
Yeo BTT, Krienen FM, Sepulcre J, Sabuncu MR, Lashkari D, Hollinshead M, Roffman JL, Smoller JW, Zoller L, Polimeni JR, Fischl B, Liu HS, Buckner RL (2011) The organization of the human cerebral cortex estimated by intrinsic functional connectivity. J Neurophysiol 106(3):1125–1165. https://doi.org/10.1152/jn.00338.2011
Zalesky A, Breakspear M (2015) Towards a statistical test for functional connectivity dynamics. Neuroimage 114:466–470. https://doi.org/10.1016/j.neuroimage.2015.03.047
Zalesky A, Fornito A, Cocchi L, Gollo LL, Breakspear M (2014) Time-resolved resting-state brain networks. Proc Natl Acad Sci USA 111(28):10341–10346. https://doi.org/10.1073/pnas.1400181111
Zhang ZQ, Liao W, Chen HF, Mantini D, Ding JR, Xu Q, Wang ZG, Yuan CP, Chen GH, Jiao Q, Lu GM (2011) Altered functional-structural coupling of large-scale brain networks in idiopathic generalized epilepsy. Brain 134:2912–2928. https://doi.org/10.1093/brain/awr223
Acknowledgements
The authors thank Professor Xiaoming Wang in the Affiliated Hospital of North Sichuan Medical College for their clinical support in the present study.
Funding
This work was supported by the grant from National Key R&D Program of China (2018YFA0701400), the National Nature Science Foundation of China (U2033217, 61933003, 81960249 and 81771822), the PCSIRT project (IRT0910), and the CAMS Innovation Fund for Medical Sciences(CIFMS) (No. 2019-I2M-5–039).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Ethical approval
All procedures performed in studies involving human participants were approved by the ethical committee of the University of Electronic Science and Technology of China according to the standards of the Declaration of Helsinki.
Informed consent
All participants provided written consent.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary Information
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Jiang, S., Li, H., Pei, H. et al. Connective profiles and antagonism between dynamic and static connectivity underlying generalized epilepsy. Brain Struct Funct 226, 1423–1435 (2021). https://doi.org/10.1007/s00429-021-02248-1
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00429-021-02248-1