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Erschienen in: Journal of Neurology 6/2015

01.06.2015 | Original Communication

Functional connectome assessed using graph theory in drug-naive Parkinson’s disease

verfasst von: Chun Yan Luo, Xiao Yan Guo, Wei Song, Qin Chen, Bei Cao, Jing Yang, Qi Yong Gong, Hui-Fang Shang

Erschienen in: Journal of Neurology | Ausgabe 6/2015

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Abstract

The purpose of this study is to investigate whether the topological organization of whole-brain functional network is disrupted in patients with Parkinson’s disease (PD). We employed resting-state functional MRI (R-fMRI) and graph theory to investigate the topological organization of the functional connectome in 47 early-stage drug-naïve PD patients and 47 healthy control subjects. Correlations between network properties and clinical variables were tested. Both the PD and control groups showed small-world architecture in brain functional networks. However, the PD patients had lower clustering coefficient and local efficiency relative to control subjects, indicating disrupted topologic organization and a shift toward randomization in their functional brain network. At node and connection level, reduced node centralities and connectivity strength were found mainly in temporal-occipital regions and also in sensorimotor regions of PD patients. In PD patients, altered global network properties correlated with cognitive function, while motor impairment was correlated with local connection changes. This study demonstrates a disruption of whole-brain topological organization of the functional brain networks in early-stage drug-naïve PD patients and this disruption might contribute to preclinical changes in cognitive process in these patients.
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Literatur
1.
Zurück zum Zitat Achard S, Bullmore ET (2007) Efficiency and cost of economical brain functional networks. PLoS Comput Biol 3:174–183CrossRef Achard S, Bullmore ET (2007) Efficiency and cost of economical brain functional networks. PLoS Comput Biol 3:174–183CrossRef
2.
Zurück zum Zitat Agosta F, Canu E, Valsasina P, Riva N, Prelle A, Comi G, Filippi M (2013) Divergent brain network connectivity in amyotrophic lateral sclerosis. Neurobiol Aging 34:419–427CrossRefPubMed Agosta F, Canu E, Valsasina P, Riva N, Prelle A, Comi G, Filippi M (2013) Divergent brain network connectivity in amyotrophic lateral sclerosis. Neurobiol Aging 34:419–427CrossRefPubMed
3.
Zurück zum Zitat Baggio HC, Sala-Llonch R, Segura B, Marti MJ, Valldeoriola F, Compta Y, Tolosa E, Junque C (2014) functional brain networks and cognitive deficits in Parkinson’s disease. Hum Brain Mapp 35:4620–4634CrossRefPubMed Baggio HC, Sala-Llonch R, Segura B, Marti MJ, Valldeoriola F, Compta Y, Tolosa E, Junque C (2014) functional brain networks and cognitive deficits in Parkinson’s disease. Hum Brain Mapp 35:4620–4634CrossRefPubMed
4.
5.
Zurück zum Zitat Baumer T, Pramstaller PP, Siebner HR, Schippling S, Hagenah J, Peller M, Gerloff C, Klein C, Munchau A (2007) Sensorimotor integration is abnormal in asymptomatic Parkin mutation carriers: a TMS study. Neurology 69:1976–1981CrossRefPubMed Baumer T, Pramstaller PP, Siebner HR, Schippling S, Hagenah J, Peller M, Gerloff C, Klein C, Munchau A (2007) Sensorimotor integration is abnormal in asymptomatic Parkin mutation carriers: a TMS study. Neurology 69:1976–1981CrossRefPubMed
6.
Zurück zum Zitat Blondel VD, Guillaume J-L, Lambiotte R, Lefebvre E (2008) Fast unfolding of communities in large networks. J Stat Mech: Theory Exp 2008:P10008CrossRef Blondel VD, Guillaume J-L, Lambiotte R, Lefebvre E (2008) Fast unfolding of communities in large networks. J Stat Mech: Theory Exp 2008:P10008CrossRef
7.
Zurück zum Zitat Braak H, Del Tredici K, Rub U, de Vos RA, Jansen Steur EN, Braak E (2003) Staging of brain pathology related to sporadic Parkinson’s disease. Neurobiol Aging 24:197–211CrossRefPubMed Braak H, Del Tredici K, Rub U, de Vos RA, Jansen Steur EN, Braak E (2003) Staging of brain pathology related to sporadic Parkinson’s disease. Neurobiol Aging 24:197–211CrossRefPubMed
8.
Zurück zum Zitat Bullmore E, Sporns O (2009) Complex brain networks: graph theoretical analysis of structural and functional systems. Nat Rev Neurosci 10:186–198CrossRefPubMed Bullmore E, Sporns O (2009) Complex brain networks: graph theoretical analysis of structural and functional systems. Nat Rev Neurosci 10:186–198CrossRefPubMed
9.
Zurück zum Zitat Cao Q, Shu N, An L, Wang P, Sun L, Xia MR, Wang JH, Gong GL, Zang YF, Wang YF, He Y (2013) Probabilistic diffusion tractography and graph theory analysis reveal abnormal white matter structural connectivity networks in drug-naive boys with attention deficit/hyperactivity disorder. J Neurosci 33:10676–10687CrossRefPubMed Cao Q, Shu N, An L, Wang P, Sun L, Xia MR, Wang JH, Gong GL, Zang YF, Wang YF, He Y (2013) Probabilistic diffusion tractography and graph theory analysis reveal abnormal white matter structural connectivity networks in drug-naive boys with attention deficit/hyperactivity disorder. J Neurosci 33:10676–10687CrossRefPubMed
10.
Zurück zum Zitat Cardoso EF, Fregni F, Maia FM, Melo LM, Sato JR, Cruz AC Jr, Bianchi ET, Fernandes DB, Monteiro ML, Barbosa ER, Amaro E Jr (2010) Abnormal visual activation in Parkinson’s disease patients. Mov Disord 25:1590–1596CrossRefPubMed Cardoso EF, Fregni F, Maia FM, Melo LM, Sato JR, Cruz AC Jr, Bianchi ET, Fernandes DB, Monteiro ML, Barbosa ER, Amaro E Jr (2010) Abnormal visual activation in Parkinson’s disease patients. Mov Disord 25:1590–1596CrossRefPubMed
11.
Zurück zum Zitat Craddock RC, James GA, Holtzheimer PE 3rd, Hu XP, Mayberg HS (2012) A whole brain fMRI atlas generated via spatially constrained spectral clustering. Hum Brain Mapp 33:1914–1928CrossRefPubMed Craddock RC, James GA, Holtzheimer PE 3rd, Hu XP, Mayberg HS (2012) A whole brain fMRI atlas generated via spatially constrained spectral clustering. Hum Brain Mapp 33:1914–1928CrossRefPubMed
12.
Zurück zum Zitat Delaveau P, Salgado-Pineda P, Fossati P, Witjas T, Azulay JP, Blin O (2010) Dopaminergic modulation of the default mode network in Parkinson’s disease. Eur Neuropsychopharmacol 20:784–792CrossRefPubMed Delaveau P, Salgado-Pineda P, Fossati P, Witjas T, Azulay JP, Blin O (2010) Dopaminergic modulation of the default mode network in Parkinson’s disease. Eur Neuropsychopharmacol 20:784–792CrossRefPubMed
13.
Zurück zum Zitat Eberling JL, Richardson BC, Reed BR, Wolfe N, Jagust WJ (1994) Cortical glucose metabolism in Parkinson’s disease without dementia. Neurobiol Aging 15:329–335CrossRefPubMed Eberling JL, Richardson BC, Reed BR, Wolfe N, Jagust WJ (1994) Cortical glucose metabolism in Parkinson’s disease without dementia. Neurobiol Aging 15:329–335CrossRefPubMed
14.
Zurück zum Zitat Esposito F, Tessitore A, Giordano A, De Micco R, Paccone A, Conforti R, Pignataro G, Annunziato L, Tedeschi G (2013) Rhythm-specific modulation of the sensorimotor network in drug-naive patients with Parkinson’s disease by levodopa. Brain 136:710–725CrossRefPubMed Esposito F, Tessitore A, Giordano A, De Micco R, Paccone A, Conforti R, Pignataro G, Annunziato L, Tedeschi G (2013) Rhythm-specific modulation of the sensorimotor network in drug-naive patients with Parkinson’s disease by levodopa. Brain 136:710–725CrossRefPubMed
15.
Zurück zum Zitat Georgiou N, Iansek R, Bradshaw JL, Phillips JG, Mattingley JB, Bradshaw JA (1993) An evaluation of the role of internal cues in the pathogenesis of parkinsonian hypokinesia. Brain 116(Pt 6):1575–1587CrossRefPubMed Georgiou N, Iansek R, Bradshaw JL, Phillips JG, Mattingley JB, Bradshaw JA (1993) An evaluation of the role of internal cues in the pathogenesis of parkinsonian hypokinesia. Brain 116(Pt 6):1575–1587CrossRefPubMed
16.
Zurück zum Zitat Gottlich M, Munte TF, Heldmann M, Kasten M, Hagenah J, Kramer UM (2013) Altered resting state brain networks in Parkinson’s disease. PLoS One 8:e77336PubMedCentralCrossRefPubMed Gottlich M, Munte TF, Heldmann M, Kasten M, Hagenah J, Kramer UM (2013) Altered resting state brain networks in Parkinson’s disease. PLoS One 8:e77336PubMedCentralCrossRefPubMed
17.
Zurück zum Zitat Hacker CD, Perlmutter JS, Criswell SR, Ances BM, Snyder AZ (2012) Resting state functional connectivity of the striatum in Parkinson’s disease. Brain 135:3699–3711PubMedCentralCrossRefPubMed Hacker CD, Perlmutter JS, Criswell SR, Ances BM, Snyder AZ (2012) Resting state functional connectivity of the striatum in Parkinson’s disease. Brain 135:3699–3711PubMedCentralCrossRefPubMed
18.
Zurück zum Zitat He Y, Dagher A, Chen Z, Charil A, Zijdenbos A, Worsley K, Evans A (2009) Impaired small-world efficiency in structural cortical networks in multiple sclerosis associated with white matter lesion load. Brain 132:3366–3379PubMedCentralCrossRefPubMed He Y, Dagher A, Chen Z, Charil A, Zijdenbos A, Worsley K, Evans A (2009) Impaired small-world efficiency in structural cortical networks in multiple sclerosis associated with white matter lesion load. Brain 132:3366–3379PubMedCentralCrossRefPubMed
19.
Zurück zum Zitat He Y, Evans A (2010) Graph theoretical modeling of brain connectivity. Curr Opin Neurol 23:341–350PubMed He Y, Evans A (2010) Graph theoretical modeling of brain connectivity. Curr Opin Neurol 23:341–350PubMed
20.
Zurück zum Zitat Helmich RC, Derikx LC, Bakker M, Scheeringa R, Bloem BR, Toni I (2010) Spatial remapping of cortico-striatal connectivity in Parkinson’s disease. Cereb Cortex 20:1175–1186CrossRefPubMed Helmich RC, Derikx LC, Bakker M, Scheeringa R, Bloem BR, Toni I (2010) Spatial remapping of cortico-striatal connectivity in Parkinson’s disease. Cereb Cortex 20:1175–1186CrossRefPubMed
21.
Zurück zum Zitat Kandiah N, Narasimhalu K, Lau PN, Seah SH, Au WL, Tan LC (2009) Cognitive decline in early Parkinson’s disease. Mov Disord 24:605–608CrossRefPubMed Kandiah N, Narasimhalu K, Lau PN, Seah SH, Au WL, Tan LC (2009) Cognitive decline in early Parkinson’s disease. Mov Disord 24:605–608CrossRefPubMed
22.
Zurück zum Zitat Kelly AM, Uddin LQ, Biswal BB, Castellanos FX, Milham MP (2008) Competition between functional brain networks mediates behavioral variability. Neuroimage 39:527–537CrossRefPubMed Kelly AM, Uddin LQ, Biswal BB, Castellanos FX, Milham MP (2008) Competition between functional brain networks mediates behavioral variability. Neuroimage 39:527–537CrossRefPubMed
23.
Zurück zum Zitat Latora V, Marchiori M (2001) Efficient behavior of small-world networks. Phys Rev Lett 87:198701CrossRefPubMed Latora V, Marchiori M (2001) Efficient behavior of small-world networks. Phys Rev Lett 87:198701CrossRefPubMed
24.
Zurück zum Zitat Luo C, Song W, Chen Q, Zheng Z, Chen K, Cao B, Yang J, Li J, Huang X, Gong Q, Shang HF (2014) Reduced functional connectivity in early-stage drug-naive Parkinson’s disease: a resting-state fMRI study. Neurobiol Aging 35(2):431–441CrossRefPubMed Luo C, Song W, Chen Q, Zheng Z, Chen K, Cao B, Yang J, Li J, Huang X, Gong Q, Shang HF (2014) Reduced functional connectivity in early-stage drug-naive Parkinson’s disease: a resting-state fMRI study. Neurobiol Aging 35(2):431–441CrossRefPubMed
25.
Zurück zum Zitat Luo C, Song W, Chen Q, Zheng Z, Chen K, Cao B, Yang J, Li J, Huang X, Gong Q, Shang HF (2014) Reduced functional connectivity in early-stage drug-naive Parkinson’s disease: a resting-state fMRI study. Neurobiol Aging 35:431–441CrossRefPubMed Luo C, Song W, Chen Q, Zheng Z, Chen K, Cao B, Yang J, Li J, Huang X, Gong Q, Shang HF (2014) Reduced functional connectivity in early-stage drug-naive Parkinson’s disease: a resting-state fMRI study. Neurobiol Aging 35:431–441CrossRefPubMed
26.
Zurück zum Zitat Melzer TR, Watts R, MacAskill MR, Pitcher TL, Livingston L, Keenan RJ, Dalrymple-Alford JC, Anderson TJ (2013) White matter microstructure deteriorates across cognitive stages in Parkinson disease. Neurology 80:1841–1849CrossRefPubMed Melzer TR, Watts R, MacAskill MR, Pitcher TL, Livingston L, Keenan RJ, Dalrymple-Alford JC, Anderson TJ (2013) White matter microstructure deteriorates across cognitive stages in Parkinson disease. Neurology 80:1841–1849CrossRefPubMed
27.
Zurück zum Zitat Meppelink AM, de Jong BM, Renken R, Leenders KL, Cornelissen FW, van Laar T (2009) Impaired visual processing preceding image recognition in Parkinson’s disease patients with visual hallucinations. Brain 132:2980–2993CrossRefPubMed Meppelink AM, de Jong BM, Renken R, Leenders KL, Cornelissen FW, van Laar T (2009) Impaired visual processing preceding image recognition in Parkinson’s disease patients with visual hallucinations. Brain 132:2980–2993CrossRefPubMed
28.
Zurück zum Zitat Olde Dubbelink KT, Hillebrand A, Stoffers D, Deijen JB, Twisk JW, Stam CJ, Berendse HW (2014) Disrupted brain network topology in Parkinson’s disease: a longitudinal magnetoencephalography study. Brain 137:197–207CrossRefPubMed Olde Dubbelink KT, Hillebrand A, Stoffers D, Deijen JB, Twisk JW, Stam CJ, Berendse HW (2014) Disrupted brain network topology in Parkinson’s disease: a longitudinal magnetoencephalography study. Brain 137:197–207CrossRefPubMed
29.
Zurück zum Zitat Palmer SJ, Li J, Wang ZJ, McKeown MJ (2010) Joint amplitude and connectivity compensatory mechanisms in Parkinson’s disease. Neuroscience 166:1110–1118CrossRefPubMed Palmer SJ, Li J, Wang ZJ, McKeown MJ (2010) Joint amplitude and connectivity compensatory mechanisms in Parkinson’s disease. Neuroscience 166:1110–1118CrossRefPubMed
30.
Zurück zum Zitat Peppard RF, Martin WR, Carr GD, Grochowski E, Schulzer M, Guttman M, McGeer PL, Phillips AG, Tsui JK, Calne DB (1992) Cerebral glucose metabolism in Parkinson’s disease with and without dementia. Arch Neurol 49:1262–1268CrossRefPubMed Peppard RF, Martin WR, Carr GD, Grochowski E, Schulzer M, Guttman M, McGeer PL, Phillips AG, Tsui JK, Calne DB (1992) Cerebral glucose metabolism in Parkinson’s disease with and without dementia. Arch Neurol 49:1262–1268CrossRefPubMed
31.
Zurück zum Zitat Rubinov M, Sporns O (2010) Complex network measures of brain connectivity: uses and interpretations. Neuroimage 52:1059–1069CrossRefPubMed Rubinov M, Sporns O (2010) Complex network measures of brain connectivity: uses and interpretations. Neuroimage 52:1059–1069CrossRefPubMed
32.
Zurück zum Zitat Schwartzman RJ, Alexander GM, Ferraro TN, Grothusen JR, Stahl SM (1988) Cerebral metabolism of parkinsonian primates 21 days after MPTP. Exp Neurol 102:307–313CrossRefPubMed Schwartzman RJ, Alexander GM, Ferraro TN, Grothusen JR, Stahl SM (1988) Cerebral metabolism of parkinsonian primates 21 days after MPTP. Exp Neurol 102:307–313CrossRefPubMed
33.
Zurück zum Zitat Skidmore F, Korenkevych D, Liu Y, He G, Bullmore E, Pardalos PM (2011) Connectivity brain networks based on wavelet correlation analysis in Parkinson fMRI data. Neurosci Lett 499:47–51CrossRefPubMed Skidmore F, Korenkevych D, Liu Y, He G, Bullmore E, Pardalos PM (2011) Connectivity brain networks based on wavelet correlation analysis in Parkinson fMRI data. Neurosci Lett 499:47–51CrossRefPubMed
34.
35.
36.
Zurück zum Zitat Tessitore A, Esposito F, Vitale C, Santangelo G, Amboni M, Russo A, Corbo D, Cirillo G, Barone P, Tedeschi G (2012) Default-mode network connectivity in cognitively unimpaired patients with Parkinson disease. Neurology 79:2226–2232CrossRefPubMed Tessitore A, Esposito F, Vitale C, Santangelo G, Amboni M, Russo A, Corbo D, Cirillo G, Barone P, Tedeschi G (2012) Default-mode network connectivity in cognitively unimpaired patients with Parkinson disease. Neurology 79:2226–2232CrossRefPubMed
37.
Zurück zum Zitat Tononi G, Sporns O, Edelman GM (1994) A measure for brain complexity: relating functional segregation and integration in the nervous system. Proc Natl Acad Sci USA 91:5033–5037PubMedCentralCrossRefPubMed Tononi G, Sporns O, Edelman GM (1994) A measure for brain complexity: relating functional segregation and integration in the nervous system. Proc Natl Acad Sci USA 91:5033–5037PubMedCentralCrossRefPubMed
38.
Zurück zum Zitat Uc EY, Rizzo M, Anderson SW, Qian S, Rodnitzky RL, Dawson JD (2005) Visual dysfunction in Parkinson disease without dementia. Neurology 65:1907–1913CrossRefPubMed Uc EY, Rizzo M, Anderson SW, Qian S, Rodnitzky RL, Dawson JD (2005) Visual dysfunction in Parkinson disease without dementia. Neurology 65:1907–1913CrossRefPubMed
39.
Zurück zum Zitat Wang J, Zuo X, Dai Z, Xia M, Zhao Z, Zhao X, Jia J, Han Y, He Y (2013) Disrupted functional brain connectome in individuals at risk for Alzheimer’s disease. Biol Psychiatry 73:472–481CrossRefPubMed Wang J, Zuo X, Dai Z, Xia M, Zhao Z, Zhao X, Jia J, Han Y, He Y (2013) Disrupted functional brain connectome in individuals at risk for Alzheimer’s disease. Biol Psychiatry 73:472–481CrossRefPubMed
40.
Zurück zum Zitat Watts DJ, Strogatz SH (1998) Collective dynamics of ‘small-world’ networks. Nature 393:440–442CrossRefPubMed Watts DJ, Strogatz SH (1998) Collective dynamics of ‘small-world’ networks. Nature 393:440–442CrossRefPubMed
41.
Zurück zum Zitat Wu T, Long X, Wang L, Hallett M, Zang Y, Li K, Chan P (2011) Functional connectivity of cortical motor areas in the resting state in Parkinson’s disease. Hum Brain Mapp 32:1443–1457CrossRefPubMed Wu T, Long X, Wang L, Hallett M, Zang Y, Li K, Chan P (2011) Functional connectivity of cortical motor areas in the resting state in Parkinson’s disease. Hum Brain Mapp 32:1443–1457CrossRefPubMed
42.
Zurück zum Zitat Zalesky A, Fornito A, Bullmore ET (2010) Network-based statistic: identifying differences in brain networks. Neuroimage 53:1197–1207CrossRefPubMed Zalesky A, Fornito A, Bullmore ET (2010) Network-based statistic: identifying differences in brain networks. Neuroimage 53:1197–1207CrossRefPubMed
43.
Zurück zum Zitat Zhang J, Wang J, Wu Q, Kuang W, Huang X, He Y, Gong Q (2011) Disrupted brain connectivity networks in drug-naive, first-episode major depressive disorder. Biol Psychiatry 70:334–342CrossRefPubMed Zhang J, Wang J, Wu Q, Kuang W, Huang X, He Y, Gong Q (2011) Disrupted brain connectivity networks in drug-naive, first-episode major depressive disorder. Biol Psychiatry 70:334–342CrossRefPubMed
44.
Zurück zum Zitat Zheng Z, Shemmassian S, Wijekoon C, Kim W, Bookheimer SY, Pouratian N (2014) DTI correlates of distinct cognitive impairments in Parkinson’s disease. Hum Brain Mapp 35(4):1325–1333PubMedCentralCrossRefPubMed Zheng Z, Shemmassian S, Wijekoon C, Kim W, Bookheimer SY, Pouratian N (2014) DTI correlates of distinct cognitive impairments in Parkinson’s disease. Hum Brain Mapp 35(4):1325–1333PubMedCentralCrossRefPubMed
Metadaten
Titel
Functional connectome assessed using graph theory in drug-naive Parkinson’s disease
verfasst von
Chun Yan Luo
Xiao Yan Guo
Wei Song
Qin Chen
Bei Cao
Jing Yang
Qi Yong Gong
Hui-Fang Shang
Publikationsdatum
01.06.2015
Verlag
Springer Berlin Heidelberg
Erschienen in
Journal of Neurology / Ausgabe 6/2015
Print ISSN: 0340-5354
Elektronische ISSN: 1432-1459
DOI
https://doi.org/10.1007/s00415-015-7750-3

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