Connectivity; Entropy; Fractional anisotropy; Graph-theory; Negative symptoms; Schizophrenia; Adult; Anisotropy; Diffusion Tensor Imaging; Electroencephalography; Female; Humans; Image Processing, Computer-Assisted; Male; Neural Pathways/diagnostic imaging; Predictive Value of Tests; Principal Component Analysis; Schizophrenia/diagnostic imaging; Schizophrenia/physiopathology; Theta Rhythm/physiology; Young Adult; Neural Pathways; Theta Rhythm; Radiology, Nuclear Medicine and Imaging; Neurology; Neurology (clinical); Cognitive Neuroscience
Abstract :
[en] Spectral entropy (SE) allows comparing task-related modulation of electroencephalogram (EEG) between patients and controls, i.e. spectral changes of the EEG associated to task performance. A SE modulation deficit has been replicated in different schizophrenia samples. To investigate the underpinnings of SE modulation deficits in schizophrenia, we applied graph-theory to EEG recordings during a P300 task and fractional anisotropy (FA) data from diffusion tensor imaging in 48 patients (23 first episodes) and 87 healthy controls. Functional connectivity was assessed from phase-locking values among sensors in the theta band, and structural connectivity was based on FA values for the tracts connecting pairs of regions. From those data, averaged clustering coefficient (CLC), characteristic path-length (PL) and connectivity strength (CS, also known as density) were calculated for both functional and structural networks. The corresponding functional modulation values were calculated as the difference in SE and CLC, PL and CS between the pre-stimulus and response windows during the task. The results revealed a higher functional CS in the pre-stimulus window in patients, predictive of smaller modulation of SE in this group. The amount of increase in theta CS from pre-stimulus to response related to SE modulation in patients and controls. Structural CLC was associated with SE modulation in the patients. SE modulation was predictive of negative symptoms, whereas CLC and PL modulation was associated with cognitive performance in the patients. These results support that a hyperactive functional connectivity and/or structural connective deficits in the patients hamper the dynamical modulation of connectivity underlying cognition.
Disciplines :
Neurology
Author, co-author :
Gomez-Pilar, Javier; Biomedical Engineering Group, University of Valladolid, Paseo de Belén, 15, 47011 Valladolid, Spain
de Luis-García, Rodrigo; Imaging Processing Laboratory, University of Valladolid, Paseo de Belén, 15, 47011 Valladolid, Spain
Lubeiro, Alba; Psychiatry Department, School of Medicine, University of Valladolid, Av. Ramón y Cajal, 7, 47005 Valladolid, Spain
de Uribe, Nieves; Psychiatry Service, Clinical Hospital of Valladolid, Ramón y Cajal, 3, 47003 Valladolid, Spain
Poza, Jesús; Biomedical Engineering Group, University of Valladolid, Paseo de Belén, 15, 47011 Valladolid, Spain, Neurosciences Institute of Castilla y León (INCYL), Pintor Fernando Gallego, 1, 37007, University of Salamanca, Spain, IMUVA, Mathematics Research Institute, University of Valladolid, Valladolid, Spain
Nunez Novo, Pablo ; University of Valladolid > Biomedical Engineering Group
Ayuso, Marta; Neurophysiology Service, Clinical Hospital of Valladolid, Ramón y Cajal, 3, 47003 Valladolid, Spain
Hornero, Roberto; Biomedical Engineering Group, University of Valladolid, Paseo de Belén, 15, 47011 Valladolid, Spain, Neurosciences Institute of Castilla y León (INCYL), Pintor Fernando Gallego, 1, 37007, University of Salamanca, Spain, IMUVA, Mathematics Research Institute, University of Valladolid, Valladolid, Spain
Molina, Vicente ; Psychiatry Department, School of Medicine, University of Valladolid, Av. Ramón y Cajal, 7, 47005 Valladolid, Spain, Psychiatry Service, Clinical Hospital of Valladolid, Ramón y Cajal, 3, 47003 Valladolid, Spain., Neurosciences Institute of Castilla y León (INCYL), Pintor Fernando Gallego, 1, 37007, University of Salamanca, Spain. Electronic address: vicente.molina@uva.es
Language :
English
Title :
Deficits of entropy modulation in schizophrenia are predicted by functional connectivity strength in the theta band and structural clustering.
ISCIII - Instituto de Salud Carlos III JCYL - Junta de Castilla y León MINECO - Gobierno de Espana. Ministerio de Economia y Competitividad FEDER - Fonds Européen de Développement Régional UVA - University of Valladolid
Funding text :
This research project was supported in part by grants from Instituto de Salud Carlos III under project PI15/00299, Consejería de Educacion de Castilla y Leon project VA057P17, “Gerencia Regional de Salud de Castilla y León” under projects GRS 1263/A/16 and GRS 1485/A/17, and “Ministerio de Economía y Competitividad” and FEDER under grants TEC2014-53196-R and TEC2013-44194-P; by ‘European Commission’ and FEDER under project ‘Análisis y correlación entre el genoma completo y la actividad cerebral para la ayuda en el diagnóstico de la enfermedad de Alzheimer’ (’Cooperation Programme Interreg V-A Spain-Portugal POCTEP 2014-2020’). J. Gomez-Pilar was in receipt of a grant from University of Valladolid and A. Lubeiro was in receipt of a grant from Consejería de Educación de la Junta de Castilla y León.This research project was supported in part by grants from Instituto de Salud Carlos III under project PI15/00299 , Consejería de Educacion de Castilla y Leon project VA057P17 , “ Gerencia Regional de Salud de Castilla y León ” under projects GRS 1263/A/16 and GRS 1485/A/17 , and “ Ministerio de Economía y Competitividad ” and FEDER under grants TEC2014-53196-R and TEC2013-44194-P ; by ‘European Commission’ and FEDER under project 'Análisis y correlación entre el genoma completo y la actividad cerebral para la ayuda en el diagnóstico de la enfermedad de Alzheimer' ('Cooperation Programme Interreg V-A Spain-Portugal POCTEP 2014-2020'). J. Gomez-Pilar was in receipt of a grant from University of Valladolid and A. Lubeiro was in receipt of a grant from Consejería de Educación de la Junta de Castilla y León .
Bachiller, A., Diez, A., Suazo, V., Dominguez, C., Ayuso, M., Hornero, R. et al., Decreased spectral entropy modulation in patients with schizophrenia during a P300 task. Eur Arch Psychiatry Clin Neurosci. 264:6 (2014), 533–543 (Sep, PubMed PMID: 24496581. Epub 2014/02/06. eng).
Bachiller, A., Poza, J., Gomez, C., Molina, V., Suazo, V., Hornero, R., A comparative study of event-related coupling patterns during an auditory oddball task in schizophrenia. J Neural Eng., 12(1), 2015, 016007 (Feb, PubMed PMID: 25474418. Epub 2014/12/05. eng).
Bachiller, A., Romero, S., Molina, V., Alonso, J.F., Mananas, M.A., Poza, J. et al., Auditory P3a and P3b neural generators in schizophrenia: an adaptive sLORETA P300 localization approach. Schizophr Res. 169:1-3 (2015), 318–325 (Dec, PubMed PMID: 26481687. Epub 2015/10/21. eng).
Bledowski, C., Prvulovic, D., Hoechstetter, K., Scherg, M., Wibral, M., Goebel, R. et al., Localizing P300 generators in visual target and distractor processing: a combined event-related potential and functional magnetic resonance imaging study. J Neurosci., 24(42), 2004, 9353-60 (Oct 20, PubMed PMID: 15496671. eng).
Bob, P., Palus, M., Susta, M., Glaslova, K., EEG phase synchronization in patients with paranoid schizophrenia. Neurosci Lett. 447:1 (2008), 73–77 (Dec 05, PubMed PMID: 18835328. Epub 2008/10/07. eng).
Bressler, S.L., Tognoli, E., Operational principles of neurocognitive networks. Int J Psychophysiol. 60:2 (2006), 139–148 (May, PubMed PMID: 16490271. Epub 2006/02/24. eng).
Buzsáki, G., Diversity of Cortical Functions: Inhibition. Rythms of the Brain. 2006, Oxford University Press, New York, 61–79.
Desikan, R.S., Segonne, F., Fischl, B., Quinn, B.T., Dickerson, B.C., Blacker, D. et al., An automated labeling system for subdividing the human cerebral cortex on MRI scans into gyral based regions of interest. Neuroimage. 31:3 (2006), 968–980 (Jul 01, PubMed PMID: 16530430. Epub 2006/03/15. eng).
Dhollaner T, Connelly A. Unsupervised 3-tissue response function estimation from single-shell or multi-shell diffusion mr data without a co-registered t1 image. ISMRM Workshop on Breaking the Barriers of Diffusion MRI2016.
Di Biase, M.A., Cropley, V.L., Baune, B.T., Olver, J., Amminger, G.P., Phassouliotis, C. et al., White matter connectivity disruptions in early and chronic schizophrenia. Psychol Med. 22 (2017), 1–14 (May, PubMed PMID: 28528586. Epub 2017/05/23. eng).
van Diessen, E., Numan, T., van Dellen, E., van der Kooi, A.W., Boersma, M., Hofman, D. et al., Opportunities and methodological challenges in EEG and MEG resting state functional brain network research. Clin. Neurophysiol. 126 (2015), 1468–1481.
Diez, A., Suazo, V., Casado, P., Martin-Loeches, M., Molina, V., Spatial distribution and cognitive correlates of gamma noise power in schizophrenia. Psychol Med. 43:6 (2013), 1175–1186 (Sep 11, PubMed PMID: 22963867. Epub 2012/09/12. Eng).
Duff, B.J., Macritchie, K.A., Moorhead, T.W., Lawrie, S.M., Blackwood, D.H., Human brain imaging studies of DISC1 in schizophrenia, bipolar disorder and depression: a systematic review. Schizophr Res. 147:1 (2013), 1–13 (Jun, PubMed PMID: 23602339. Epub 2013/04/23. eng).
Ellison-Wright, I., Bullmore, E., Meta-analysis of diffusion tensor imaging studies in schizophrenia. Schizophr Res. 108:1–3 (2009), 3–10 (Mar, PubMed PMID: 19128945. Epub 2009/01/09. eng).
Fischl, B., van der Kouwe, A., Destrieux, C., Halgren, E., Segonne, F., Salat, D.H. et al., Automatically parcellating the human cerebral cortex. Cereb Cortex. 14:1 (2004), 11–22 (Jan, PubMed PMID: 14654453. Epub 2003/12/05. eng).
Gomez-Pilar, J., Poza, J., Bachiller, A., Gómez, C., Molina, V., Hornero, R., Neural network reorganization analysis during an auditory oddball task in schizophrenia using wavelet entropy. Entropy. 17 (2015), 5241–5256.
Gomez-Pilar, J., Lubeiro, A., Poza, J., Hornero, R., Ayuso, M., Valcarcel, C. et al., Functional EEG network analysis in schizophrenia: evidence of larger segregation and deficit of modulation. Prog Neuropsychopharmacol Biol Psychiatry., 20, 2017 (Mar, PubMed PMID: 28336496. Epub 2017/03/25. eng).
Gomez-Pilar, J., Poza, J., Bachiller, A., Gomez, C., Nuñez, P., Lubeiro, A. et al., Quantification of graph complexity based on the edge weight distribution balance: application to brain networks. Int. J. Neural Syst., 28(1), 2018, 1750032.
Honey, C.J., Sporns, O., Cammoun, L., Gigandet, X., Thiran, J.P., Meuli, R. et al., Predicting human resting-state functional connectivity from structural connectivity. Proc Natl Acad Sci U S A. 106:6 (2009), 2035–2040 (Feb 10, PubMed PMID: 19188601. Pubmed Central PMCID: 2634800. Epub 2009/02/04. eng).
Jones, J.T., DiFrancesco, M., Zaal, A.I., Klein-Gitelman, M.S., Gitelman, D., Ying, J. et al., Childhood-onset lupus with clinical neurocognitive dysfunction shows lower streamline density and pairwise connectivity on diffusion tensor imaging. Lupus. 24:10 (2015), 1081–1086 (Sep, PubMed PMID: 25701565. Pubmed Central PMCID: Pmc4529818. Epub 2015/02/24. eng).
Kay, S.R., Fiszbein, A., Opler, L.A., The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophr Bull. 13:2 (1987), 261–276 (PubMed PMID: 3616518).
Manoach, D.S., Prefrontal cortex dysfunction during working memory performance in schizophrenia: reconciling discrepant findings. Schizophr Res. 60:2-3 (2003), 285–298 (Apr 1, PubMed PMID: 12591590).
Mazaheri, A., Picton, T.W., EEG spectral dynamics during discrimination of auditory and visual targets. Brain Res Cogn Brain Res. 24:1 (2005), 81–96 (Jun, PubMed PMID: 15922161. Epub 2005/06/01. eng).
Molina, V., Bachiller, A., Suazo, V., Lubeiro, A., Poza, J., Hornero, R., Noise power associated with decreased task-induced variability of brain electrical activity in schizophrenia. Eur Arch Psychiatry Clin Neurosci. 266:1 (2016), 55–61 (Feb, PubMed PMID: 25547316. Epub 2014/12/31. eng).
Molina, V., Bachiller, A., Gomez-Pilar, J., Lubeiro, A., Hornero, R., Cea-Canas, B. et al., Deficit of entropy modulation of the EEG in schizophrenia associated to cognitive performance and symptoms. A replication study. Schizophr. Res., 2017, 10.1016/j.schres.2017.08.057 (in press, Sep 5. pii: S0920-9964(17)30533-9, Epub ahead of print).
Molina, V., Lubeiro, A., Soto, O., Rodriguez, M., Alvarez, A., Hernandez, R. et al., Alterations in prefrontal connectivity in schizophrenia assessed using diffusion magnetic resonance imaging. Prog Neuropsychopharmacol Biol Psychiatry. 76 (2017), 107–115 (Mar 10, PubMed PMID: 28288855. Epub 2017/03/16. eng).
Nunez, P., Poza, J., Bachiller, A., Gomez-Pilar, J., Lubeiro, A., Molina, V. et al., Exploring non-stationarity patterns in schizophrenia: neural reorganization abnormalities in the alpha band. J Neural Eng., 14(4), 2017, 046001 (Aug., PubMed PMID: 28424430. Epub 2017/04/21. eng).
Patenaude, B., Smith, S.M., Kennedy, D.N., Jenkinson, M., A Bayesian model of shape and appearance for subcortical brain segmentation. Neuroimage. 56:3 (2011), 907–922 (Jun 01, PubMed PMID: 21352927. Pubmed Central PMCID: 3417233. Epub 2011/03/01. eng).
Roach, B.J., Mathalon, D.H., Event-related EEG time-frequency analysis: an overview of measures and an analysis of early gamma band phase locking in schizophrenia. Schizophr Bull. 34:5 (2008), 907–926 (Sep, PubMed PMID: 18684772. Pubmed Central PMCID: 2632478. Epub 2008/08/08. eng).
Rubinov, M., Sporns, O., Complex network measures of brain connectivity: uses and interpretations. Neuroimage. 52:3 (2010), 1059–1069 (Sep, PubMed PMID: 19819337. Epub 2009/10/13. eng).
Salvador, R., Pena, A., Menon, D.K., Carpenter, T.A., Pickard, J.D., Bullmore, E.T., Formal characterization and extension of the linearized diffusion tensor model. Hum Brain Mapp. 24:2 (2005), 144–155 (Feb, PubMed PMID: 15468122. Epub 2004/10/07. eng).
Segarra, N., Bernardo, M., Gutierrez, F., Justicia, A., Fernadez-Egea, E., Allas, M. et al., Spanish validation of the brief assessment in cognition in schizophrenia (BACS) in patients with schizophrenia and healthy controls. Eur Psychiatry. 26:2 (2011), 69–73 (Mar, PubMed PMID: 20435446. Epub 2010/05/04. eng).
Sporns, O., Networks for Cognition. Networks of the Brain. 2011, MIT Press, Cambridge, Massachussets, 182.
Stam, C.J., de Haan, W., Daffertshofer, A., Jones, B.F., Manshanden, I., van Cappellen van Walsum, A.M. et al., Graph theoretical analysis of magnetoencephalographic functional connectivity in Alzheimer's disease. Brain. 132:Pt 1 (2009), 213–224 (Jan, PubMed PMID: 18952674. Epub 2008/10/28. eng).
Tanaka, K., Inferotemporal cortex and object vision. Annu Rev Neurosci. 19 (1996), 109–139 (PubMed PMID: 8833438. Epub 1996/01/01. eng).
Tournier, J.D., Calamante, F., Connelly, A., Robust determination of the fibre orientation distribution in diffusion MRI: non-negativity constrained super-resolved spherical deconvolution. Neuroimage. 35:4 (2007), 1459–1472 (May 01, PubMed PMID: 17379540. Epub 2007/03/24. eng).
Varela, F., Lachaux, J.P., Rodriguez, E., Martinerie, J., The brainweb: phase synchronization and large-scale integration. Nat Rev Neurosci. 2:4 (2001), 229–239 (Apr, PubMed PMID: 11283746. Epub 2001/04/03. eng).
Winterer, G., Coppola, R., Goldberg, T.E., Egan, M.F., Jones, D.W., Sanchez, C.E. et al., Prefrontal broadband noise, working memory, and genetic risk for schizophrenia. Am J Psychiatry. 161:3 (2004), 490–500 (Mar, PubMed PMID: 14992975).
Zhang, Y., Brady, M., Smith, S., Segmentation of brain MR images through a hidden Markov random field model and the expectation-maximization algorithm. IEEE Trans Med Imaging. 20:1 (2001), 45–57 (Jan, PubMed PMID: 11293691. Epub 2001/04/11. eng).
