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Effects of levodopa therapy on voxel-based degree centrality in Parkinson’s disease

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Abstract

Levodopa therapy is widely recognized as an effective treatment for PD patients, however, it is rare of the study looking at effects of levodopa therapy on the whole-brain network. This study was to evaluate the effects of levodopa on whole-brain degree centrality (DC) and seed-based functional connectivity (FC) in PD patients. We recruited 26 PD patients and acquired their resting-state fMRI data before (‘OFF’ state) and after (‘ON’ state) taking a dose of 400 mg levodopa. Through constructing the voxel-based brain functional network, we calculated distant and local DC and seed-based FC. We found that compared to the healthy controls, the PD patients at ‘OFF’ state showed significantly decreased distant DC in several occipital regions and left postcentral gyrus, but increased distant DC in the right precentral gyrus, supplementary motor area, and several frontal regions. Meanwhile, we detected decreased local DC in the left cuneus and bilateral insula but increased local DC in several temporal regions in the PD patients at ‘OFF’ state compared to the controls. Using paired-sample t-tests, we found that levodopa effectively normalized the distant DC abnormalities in the PD patients particularly in the occipital regions and postcentral gyrus. Additionally, compared to ‘OFF’ state, the PD patients at ‘ON’ state showed decreased FC of the left median cingulate gyrus to brain regions in default mode network. The decreased FC of the left median cingulate gyrus to right temporal pole was associated with improved UPDRS-III score. This study provided new evidence for understanding the neural effects of levodopa therapy on the whole-brain network in PD patients.

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Abbreviations

ALFF:

amplitude of low-frequency oscillations

ANG:

angular gyrus

CUN:

cuneus

DC:

degree centrality

DMN:

default mode network

FWHM:

Full-Width at Half Maximum

FC:

functional connectivity

H-Y:

Hoehn and Yahr stage

ICA:

independent component analysis

INS:

insula

IFGoperc:

opercular part of inferior frontal gyrus

IFGtriang:

triangular part of inferior frontal gyrus

IOG:

inferior occipital gyrus

LING:

lingual gyrus

MMSE:

Mini-Mental State Examination

MFG:

middle frontal gyrus

MTG:

middle temporal gyrus

MCG:

median cingulate gyrus

MOG:

middle occipital gyrus

MCI:

mild cognitive impairment

ORBinf:

orbital part of inferior frontal gyrus

PMC:

premotor cortex

PoCG:

postcentral gyrus

PreCG:

precentral gyrus

PHG:

parahippocampal gyrus

PCUN:

precuneus

ReHo:

regional homogeneity

ROI:

region of interest

SMA:

supplementary motor area

STG:

superior temporal gyrus

SFGmed:

medial superior frontal gyrus

SOG:

superior occipital gyrus

TPOmid:

temporal pole of middle temporal gyrus

THA:

thalamus

UPDRS-III:

Unified Parkinson’s Disease Rating Scale-motor

‘OFF’ state:

before levodopa therapy

‘ON’ state:

after levodopa therapy

DCi :

degree centrality for a given voxel i

dij :

connection or edge weight from voxel i to voxel j

\( \overline{DC} \) :

mean degree across all voxels in the whole brain degree centrality map

σDC :

standard deviation of degree centrality

zDC:

z-score of degree centrality

szDC:

smoothed z-score of degree centrality

zFC:

z-score of functional connectivity

ΔDC:

difference in degree centrality between ‘ON’ and ‘OFF’ state

ΔFC:

difference in functional connectivity between ‘ON’ and ‘OFF’ state

ΔUPDRS-III:

difference in UPDRS-III score between ‘ON’ and ‘OFF’ state

ΔMMSE :

difference in MMSE score between ‘ON’ and ‘OFF’ state

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. Journal of Neuroscience, 26(1), 63–72.

    Article  CAS  PubMed  Google Scholar 

  • Anderson, J. S., Druzgal, T. J., Lopez-Larson, M., Jeong, E. K., Desai, K., & Yurgelun-Todd, D. (2011). Network anticorrelations, global regression, and phase-shifted soft tissue correction. Human Brain Mapping, 32(6), 919–934.

    Article  PubMed  Google Scholar 

  • Bell, P. T., Gilat, M., O'Callaghan, C., Copland, D. A., Frank, M. J., Lewis, S. J., et al. (2015). Dopaminergic basis for impairments in functional connectivity across subdivisions of the striatum in Parkinson's disease. Human Brain Mapping, 36(4), 1278–1291.

    Article  PubMed  Google Scholar 

  • Beucke, J. C., Sepulcre, J., Talukdar, T., Linnman, C., Zschenderlein, K., Endrass, T., et al. (2013). Abnormally high degree connectivity of the orbitofrontal cortex in obsessive-compulsive disorder. JAMA Psychiatry, 70(6), 619–629.

    Article  PubMed  Google Scholar 

  • Birn, R. M., Diamond, J. B., Smith, M. A., & Bandettini, P. A. (2006). Separating respiratory-variation-related fluctuations from neuronal-activity-related fluctuations in fMRI. Neuroimage, 31(4), 1536–1548.

    Article  PubMed  Google Scholar 

  • Braak, H., Del Tredici, K., Rüb, U., De Vos, R. A., Steur, E. N. J., & Braak, E. (2003). Staging of brain pathology related to sporadic Parkinson’s disease. Neurobiology of Aging, 24(2), 197–211.

    Article  PubMed  Google Scholar 

  • Braak, H., Bohl, J. R., Müller, C. M., Rüb, U., de Vos, R. A., & Del Tredici, K. (2006). Stanley Fahn Lecture 2005: The staging procedure for the inclusion body pathology associated with sporadic Parkinson's disease reconsidered. Movement Disorders, 21(12), 2042–2051.

    Article  PubMed  Google Scholar 

  • Bressler, S. L., & Menon, V. (2010). Large-scale brain networks in cognition: emerging methods and principles. Trends in Cognitive Sciences, 14(6), 277–290.

    Article  PubMed  Google Scholar 

  • Buccino, G., Vogt, S., Ritzl, A., Fink, G. R., Zilles, K., Freund, H.-J., et al. (2004). Neural circuits underlying imitation learning of hand actions: an event-related fMRI study. Neuron, 42(2), 323–334.

    Article  CAS  PubMed  Google Scholar 

  • Buckner, R. L., Sepulcre, J., Talukdar, T., Krienen, F. M., Liu, H., Hedden, T., et al. (2009). Cortical hubs revealed by intrinsic functional connectivity: mapping, assessment of stability, and relation to Alzheimer's disease. Journal of Neuroscience, 29(6), 1860–1873.

    Article  CAS  PubMed  Google Scholar 

  • Bullmore, E., & Sporns, O. (2009). Complex brain networks: graph theoretical analysis of structural and functional systems. Nature Reviews. Neuroscience, 10(3), 186–198.

    Article  CAS  PubMed  Google Scholar 

  • Cardoso, E. F., Maia, F. M., Fregni, F., Myczkowski, M. L., Melo, L. M., Sato, J. R., et al. (2009). Depression in Parkinson's disease: convergence from voxel-based morphometry and functional magnetic resonance imaging in the limbic thalamus. Neuroimage, 47(2), 467–472.

    Article  PubMed  Google Scholar 

  • Cha, J., Ide, J. S., Bowman, F. D., Simpson, H. B., Posner, J., & Steinglass, J. E. (2016). Abnormal reward circuitry in anorexia nervosa: A longitudinal, multimodal MRI study. Human Brain Mapping, 37(11), 3835–3846.

    Article  PubMed  PubMed Central  Google Scholar 

  • Chang, C., & Glover, G. H. (2009). Effects of model-based physiological noise correction on default mode network anti-correlations and correlations. Neuroimage, 47(4), 1448–1459.

    Article  PubMed  PubMed Central  Google Scholar 

  • Chen, Y., Pressman, P., Simuni, T., Parrish, T. B., & Gitelman, D. R. (2015). Effects of acute levodopa challenge on resting cerebral blood flow in Parkinson’s Disease patients assessed using pseudo-continuous arterial spin labeling. PeerJ, 3, e1381.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chéron, G., Dan, B., & Borenstein, S. (2000). Sensory and motor interfering influences on somatosensory evoked potentials. Journal of Clinical Neurophysiology, 17(3), 280–294.

    Article  PubMed  Google Scholar 

  • Christopher, L., Koshimori, Y., Lang, A. E., Criaud, M., & Strafella, A. P. (2014a). Uncovering the role of the insula in non-motor symptoms of Parkinson’s disease. Brain, 137(8), 2143–2154.

    Article  PubMed  PubMed Central  Google Scholar 

  • Christopher, L., Marras, C., Duff-Canning, S., Koshimori, Y., Chen, R., Boileau, I., et al. (2014b). Combined insular and striatal dopamine dysfunction are associated with executive deficits in Parkinson’s disease with mild cognitive impairment. Brain, 137(2), 565–575.

    Article  PubMed  Google Scholar 

  • Cohen, J. (1992). A power primer. Psychological Bulletin, 112(1), 155.

    Article  CAS  Google Scholar 

  • Contin, M., & Martinelli, P. (2010). Pharmacokinetics of levodopa. Journal of Neurology, 257(2), 253–261.

    Article  CAS  Google Scholar 

  • Di Martino, A., Zuo, X.-N., Kelly, C., Grzadzinski, R., Mennes, M., Schvarcz, A., et al. (2013). Shared and distinct intrinsic functional network centrality in autism and attention-deficit/hyperactivity disorder. Biological Psychiatry, 74(8), 623–632.

    Article  PubMed  PubMed Central  Google Scholar 

  • Diederich, N. J., Stebbins, G., Schiltz, C., & Goetz, C. G. (2014). Are patients with Parkinson’s disease blind to blindsight? Brain, 137(6), 1838–1849.

    Article  PubMed  PubMed Central  Google Scholar 

  • Dubbelink, K. T. O., Hillebrand, A., Stoffers, D., Deijen, J. B., Twisk, J. W., Stam, C. J., et al. (2013). Disrupted brain network topology in Parkinson’s disease: a longitudinal magnetoencephalography study. Brain, 137(1), 197–207.

    Article  Google Scholar 

  • Dubbelink, K. T. O., Schoonheim, M. M., Deijen, J. B., Twisk, J. W., Barkhof, F., & Berendse, H. W. (2014). Functional connectivity and cognitive decline over 3 years in Parkinson disease. Neurology, 83(22), 2046–2053.

    Article  CAS  Google Scholar 

  • Esposito, F., Tessitore, A., Giordano, A., De Micco, R., Paccone, A., Conforti, R., et al. (2013). Rhythm-specific modulation of the sensorimotor network in drug-naive patients with Parkinson’s disease by levodopa. Brain, 136(3), 710–725.

    Article  PubMed  Google Scholar 

  • Fahn, S. (1999). Parkinson disease, the effect of levodopa, and the ELLDOPA trial. Archives of Neurology, 56(5), 529–535.

    Article  CAS  PubMed  Google Scholar 

  • Fahn, S., & Elton, R. (1987). Unified rating scale for Parkinson’s disease. (pp. 153–163): Macmillan, Florham Park, New York.

  • Fang, J., Chen, H., Cao, Z., Jiang, Y., Ma, L., Ma, H., et al. (2017). Impaired brain network architecture in newly diagnosed Parkinson’s disease based on graph theoretical analysis. Neuroscience Letters, 657, 151–158.

    Article  CAS  PubMed  Google Scholar 

  • Felger, J. C., Li, Z., Haroon, E., Woolwine, B. J., Jung, M. Y., Hu, X., et al. (2016). Inflammation is associated with decreased functional connectivity within corticostriatal reward circuitry in depression. Molecular Psychiatry, 21(10), 1358.

    Article  CAS  PubMed  Google Scholar 

  • Folstein, M. F., Folstein, S. E., & McHugh, P. R. (1975). “Mini-mental state”: a practical method for grading the cognitive state of patients for the clinician. Journal of Psychiatric Research, 12(3), 189–198.

    Article  CAS  PubMed  Google Scholar 

  • Forno, L. S. (1981). Pathology of Parkinson's disease. In Movement Disorders (pp. 25–40): Elsevier.

  • Fox, M. D., Zhang, D., Snyder, A. Z., & Raichle, M. E. (2009). The global signal and observed anticorrelated resting state brain networks. Journal of Neurophysiology, 101(6), 3270–3283.

    Article  PubMed  PubMed Central  Google Scholar 

  • Gallagher, D. A., Parkkinen, L., O'sullivan, S. S., Spratt, A., Shah, A., Davey, C. C., et al. (2011). Testing an aetiological model of visual hallucinations in Parkinson's disease. Brain, 134(11), 3299–3309.

    Article  PubMed  Google Scholar 

  • Gao, L. L., Zhang, J. R., Chan, P., & Wu, T. (2017). Levodopa Effect on Basal Ganglia Motor Circuit in Parkinson's Disease. CNS Neuroscience & Therapeutics, 23(1), 76–86.

    Article  CAS  Google Scholar 

  • Gibb, W., & Lees, A. (1988). The relevance of the Lewy body to the pathogenesis of idiopathic Parkinson's disease. Journal of Neurology, Neurosurgery and Psychiatry, 51(6), 745–752.

    Article  CAS  PubMed  Google Scholar 

  • Göttlich, M., Münte, T. F., Heldmann, M., Kasten, M., Hagenah, J., & Krämer, U. M. (2013). Altered resting state brain networks in Parkinson’s disease. PLoS One, 8(10), e77336.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Group, P. S. (2004). Levodopa and the progression of Parkinson's disease. New England Journal of Medicine, 351(24), 2498–2508.

    Article  Google Scholar 

  • Hagmann, P., Cammoun, L., Gigandet, X., Meuli, R., Honey, C. J., Wedeen, V. J., et al. (2008). Mapping the structural core of human cerebral cortex. PLoS Biology, 6(7), e159.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Harding, A., Broe, G., & Halliday, G. (2002). Visual hallucinations in Lewy body disease relate to Lewy bodies in the temporal lobe. Brain, 125(2), 391–403.

    Article  CAS  PubMed  Google Scholar 

  • Hayasaka, S. (2013). Functional connectivity networks with and without global signal correction. Frontiers in Human Neuroscience, 7, 880.

    Article  PubMed  PubMed Central  Google Scholar 

  • Helmich, R. C., Derikx, L. C., Bakker, M., Scheeringa, R., Bloem, B. R., & Toni, I. (2010). Spatial remapping of cortico-striatal connectivity in Parkinson's disease. Cerebral Cortex, 20(5), 1175–1186.

    Article  PubMed  Google Scholar 

  • Hoehn, M. M., & Yahr, M. D. (1998). Parkinsonism: onset, progression, and mortality. Neurology, 50(2), 318–318.

    Article  PubMed  Google Scholar 

  • Hou, Y., Wu, X., Hallett, M., Chan, P., & Wu, T. (2014). Frequency-dependent neural activity in Parkinson's disease. Human Brain Mapping, 35(12), 5815–5833.

    Article  Google Scholar 

  • Hu, X., Song, X., Li, E., Liu, J., Yuan, Y., Liu, W., et al. (2015). Altered resting-state brain activity and connectivity in depressed Parkinson’s disease. PLoS One, 10(7), e0131133.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jankovic, J. (2008). Parkinson’s disease: clinical features and diagnosis. Journal of Neurology, Neurosurgery and Psychiatry, 79(4), 368–376.

    Article  CAS  PubMed  Google Scholar 

  • Jenkins, I. H., Jahanshahi, M., Jueptner, M., Passingham, R. E., & Brooks, D. J. (2000). Self-initiated versus externally triggered movements: II. The effect of movement predictability on regional cerebral blood flow. Brain, 123(6), 1216–1228.

    Article  PubMed  Google Scholar 

  • Jubault, T., Gagnon, J.-F., Karama, S., Ptito, A., Lafontaine, A.-L., Evans, A. C., et al. (2011). Patterns of cortical thickness and surface area in early Parkinson's disease. Neuroimage, 55(2), 462–467.

    Article  PubMed  Google Scholar 

  • Kelly, C., de Zubicaray, G., Di Martino, A., Copland, D. A., Reiss, P. T., Klein, D. F., et al. (2009). L-dopa modulates functional connectivity in striatal cognitive and motor networks: a double-blind placebo-controlled study. Journal of Neuroscience, 29(22), 7364–7378.

    Article  CAS  PubMed  Google Scholar 

  • Kempster, P. A., O’Sullivan, S. S., Holton, J. L., Revesz, T., & Lees, A. J. (2010). Relationships between age and late progression of Parkinson’s disease: a clinico-pathological study. Brain, 133(6), 1755–1762.

    Article  PubMed  Google Scholar 

  • Kish, S. J., Shannak, K., & Hornykiewicz, O. (1988). Uneven pattern of dopamine loss in the striatum of patients with idiopathic Parkinson's disease. New England Journal of Medicine, 318(14), 876–880.

    Article  CAS  PubMed  Google Scholar 

  • Krajcovicova, L., Mikl, M., Marecek, R., & Rektorova, I. (2012). The default mode network integrity in patients with Parkinson’s disease is levodopa equivalent dose-dependent. Journal of Neural Transmission, 119(4), 443–454.

    Article  CAS  PubMed  Google Scholar 

  • Kurani, A. S., Seidler, R. D., Burciu, R. G., Comella, C. L., Corcos, D. M., Okun, M. S., et al. (2014). Subthalamic nucleus-sensorimotor cortex functional connectivity in de novo and moderate Parkinson's disease. Neurobiology of Aging, 36(1), 462–469.

    Article  PubMed  PubMed Central  Google Scholar 

  • Kwak, Y., Peltier, S., Bohnen, N., Müller, M., Dayalu, P., & Seidler, R. D. (2010). Altered resting state cortico-striatal connectivity in mild to moderate stage Parkinson's disease. Frontiers in Systems Neuroscience, 4, 143.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kwak, Y., Peltier, S., Bohnen, N., Müller, M., Dayalu, P., & Seidler, R. D. (2012). L-DOPA changes spontaneous low-frequency BOLD signal oscillations in Parkinson's disease: a resting state fMRI study. Frontiers in Systems Neuroscience, 6, 52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ledberg, A., Åkerman, S., & Roland, P. E. (1998). Estimation of the probabilities of 3D clusters in functional brain images. Neuroimage, 8(2), 113–128.

    Article  CAS  PubMed  Google Scholar 

  • Liu, W., Wei, D., Sun, J., Yang, J., Meng, J., Wang, L., et al. (2015). Abnormal Degree Centrality of Functional Hubs Associated with Negative Coping in Older Chinese Adults Who Lost Their Only Child. Biological Psychology, 112, 46–55.

    Article  PubMed  Google Scholar 

  • Luo, C., Guo, X., Song, W., Chen, Q., Yang, J., Gong, Q., et al. (2015). The trajectory of disturbed resting-state cerebral function in Parkinson's disease at different Hoehn and Yahr stages. Human Brain Mapping, 36(8), 3104–3116.

    Article  PubMed  Google Scholar 

  • Melzer, T. R., Watts, R., MacAskill, M. R., Pitcher, T. L., Livingston, L., Keenan, R. J., et al. (2012). Grey matter atrophy in cognitively impaired Parkinson's disease. Journal of Neurology, Neurosurgery and Psychiatry, 83(2), 188–194.

    Article  PubMed  Google Scholar 

  • Meppelink, A. M., de Jong, B. M., Renken, R., Leenders, K. L., Cornelissen, F. W., & van Laar, T. (2009). Impaired visual processing preceding image recognition in Parkinson's disease patients with visual hallucinations. Brain, 132(11), 2980–2993.

    Article  PubMed  Google Scholar 

  • Miller, E. K., & Cohen, J. D. (2001). An integrative theory of prefrontal cortex function. Annual Review of Neuroscience, 24(1), 167–202.

    Article  CAS  PubMed  Google Scholar 

  • Murphy, K., Birn, R. M., Handwerker, D. A., Jones, T. B., & Bandettini, P. A. (2009). The impact of global signal regression on resting state correlations: are anti-correlated networks introduced? Neuroimage, 44(3), 893–905.

    Article  PubMed  Google Scholar 

  • Oldfield, R. C. (1971). The assessment and analysis of handedness: the Edinburgh inventory. Neuropsychologia, 9(1), 97–113.

    Article  CAS  Google Scholar 

  • Pereira, J. B., Aarsland, D., Ginestet, C. E., Lebedev, A. V., Wahlund, L. O., Simmons, A., et al. (2015). Aberrant cerebral network topology and mild cognitive impairment in early Parkinson's disease. Human Brain Mapping, 36(8), 2980–2995.

    Article  PubMed  Google Scholar 

  • Qing, Z., Dong, Z., Li, S., Zang, Y., & Liu, D. (2015). Global signal regression has complex effects on regional homogeneity of resting state fMRI signal. Magnetic Resonance Imaging, 33(10), 1306–1313.

    Article  PubMed  Google Scholar 

  • Rice, K., Moraczewski, D., & Redcay, E. (2016). Perceived live interaction modulates the developing social brain. Social Cognitive and Affective Neuroscience, 11(9), 1354–1362.

    Article  PubMed  PubMed Central  Google Scholar 

  • Roland, P. E., Larsen, B., Lassen, N. A., & Skinhoj, E. (1980). Supplementary motor area and other cortical areas in organization of voluntary movements in man. Journal of Neurophysiology, 43(1), 118–136.

    Article  CAS  PubMed  Google Scholar 

  • Rubinov, M., & Sporns, O. (2010). Complex network measures of brain connectivity: uses and interpretations. Neuroimage, 52(3), 1059–1069.

    Article  Google Scholar 

  • Saad, Z. S., Gotts, S. J., Murphy, K., Chen, G., Jo, H. J., Martin, A., et al. (2012). Trouble at rest: how correlation patterns and group differences become distorted after global signal regression. Brain Connectivity, 2(1), 25–32.

    Article  PubMed  PubMed Central  Google Scholar 

  • Salat, D., & Tolosa, E. (2013). Levodopa in the treatment of Parkinson's disease: current status and new developments. Journal of Parkinson's Disease, 3(3), 255–269.

    CAS  PubMed  Google Scholar 

  • Schölvinck, M. L., Maier, A., Frank, Q. Y., Duyn, J. H., & Leopold, D. A. (2010). Neural basis of global resting-state fMRI activity. Proceedings of the National Academy of Sciences of the United States of America, 107(22), 10238–10243.

    Article  PubMed  PubMed Central  Google Scholar 

  • Sepulcre, J., Liu, H., Talukdar, T., Martincorena, I., Yeo, B. T., & Buckner, R. L. (2010). The organization of local and distant functional connectivity in the human brain. PLoS Computational Biology, 6(6), e1000808.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shine, J. M., Halliday, G. M., Gilat, M., Matar, E., Bolitho, S. J., Carlos, M., et al. (2014). The role of dysfunctional attentional control networks in visual misperceptions in Parkinson's disease. Human Brain Mapping, 35(5), 2206–2219.

    Article  PubMed  Google Scholar 

  • Skidmore, F., Yang, M., Baxter, L., Von Deneen, K., Collingwood, J., He, G., et al. (2013). Reliability analysis of the resting state can sensitively and specifically identify the presence of Parkinson disease. Neuroimage, 75, 249–261.

    Article  CAS  PubMed  Google Scholar 

  • Takeuchi, H., Taki, Y., Nouchi, R., Sekiguchi, A., Hashizume, H., Sassa, Y., et al. (2015). Degree centrality and fractional amplitude of low-frequency oscillations associated with Stroop interference. Neuroimage, 119, 197–209.

    Article  PubMed  Google Scholar 

  • Tanji, J., & Hoshi, E. (2001). Behavioral planning in the prefrontal cortex. Current Opinion in Neurobiology, 11(2), 164–170.

    Article  CAS  PubMed  Google Scholar 

  • Tessitore, A., Amboni, M., Esposito, F., Russo, A., Picillo, M., Marcuccio, L., et al. (2012a). Resting-state brain connectivity in patients with Parkinson's disease and freezing of gait. Parkinsonism & Related Disorders, 18(6), 781–787.

    Article  Google Scholar 

  • Tessitore, A., Esposito, F., Vitale, C., Santangelo, G., Amboni, M., Russo, A., et al. (2012b). Default-mode network connectivity in cognitively unimpaired patients with Parkinson disease. Neurology, 79(23), 2226–2232.

    Article  PubMed  Google Scholar 

  • Tomasi, D., & Volkow, N. D. (2010). Functional connectivity density mapping. Proceedings of the National Academy of Sciences of the United States of America, 107(21), 9885–9890.

    Article  PubMed  PubMed Central  Google Scholar 

  • Tuovinen, N., Seppi, K., de Pasquale, F., Müller, C., Nocker, M., Schocke, M., et al. (2018). The reorganization of functional architecture in the early-stages of Parkinson's disease. Parkinsonism & Related Disorders.

  • Uc, E., Rizzo, M., Anderson, S., Qian, S., Rodnitzky, R., & Dawson, J. (2005). Visual dysfunction in Parkinson disease without dementia. Neurology, 65(12), 1907–1913.

    Article  CAS  PubMed  Google Scholar 

  • Vogt, B. A., Berger, G. R., & Derbyshire, S. W. (2003). Structural and functional dichotomy of human midcingulate cortex. European Journal of Neuroscience, 18(11), 3134–3144.

    Article  PubMed  Google Scholar 

  • Wang, J. H., Zuo, X. N., Gohel, S., Milham, M. P., Biswal, B. B., & He, Y. (2011). Graph theoretical analysis of functional brain networks: test-retest evaluation on short-and long-term resting-state functional MRI data. PLoS One, 6(7), e21976.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang, L. F., Dai, Z. J., Peng, H. J., Tan, L. W., Ding, Y. Q., He, Z., et al. (2014). Overlapping and segregated resting-state functional connectivity in patients with major depressive disorder with and without childhood neglect. Human Brain Mapping, 35(4), 1154–1166.

    Article  PubMed  Google Scholar 

  • Wang, L., Xia, M., Li, K., Zeng, Y., Su, Y., Dai, W., et al. (2015). The effects of antidepressant treatment on resting-state functional brain networks in patients with major depressive disorder. Human Brain Mapping, 36(2), 768–778.

    Article  PubMed  Google Scholar 

  • Weissenbacher, A., Kasess, C., Gerstl, F., Lanzenberger, R., Moser, E., & Windischberger, C. (2009). Correlations and anticorrelations in resting-state functional connectivity MRI: a quantitative comparison of preprocessing strategies. Neuroimage, 47(4), 1408–1416.

    Article  PubMed  Google Scholar 

  • Wu, T., & Hallett, M. (2005). A functional MRI study of automatic movements in patients with Parkinson's disease. Brain, 128(10), 2250–2259.

    Article  PubMed  Google Scholar 

  • Wu, T., Long, X., Zang, Y., Wang, L., Hallett, M., Li, K., et al. (2009a). Regional homogeneity changes in patients with Parkinson's disease. Human Brain Mapping, 30(5), 1502–1510.

    Article  PubMed  Google Scholar 

  • Wu, T., Wang, L., Chen, Y., Zhao, C., Li, K., & Chan, P. (2009b). Changes of functional connectivity of the motor network in the resting state in Parkinson's disease. Neuroscience Letters, 460(1), 6–10.

    Article  CAS  PubMed  Google Scholar 

  • Wu, T., Long, X., Wang, L., Hallett, M., Zang, Y., Li, K., et al. (2011). Functional connectivity of cortical motor areas in the resting state in Parkinson's disease. Human Brain Mapping, 32(9), 1443–1457.

    Article  PubMed  Google Scholar 

  • Wu, X., Zou, Q., Hu, J., Tang, W., Mao, Y., Gao, L., et al. (2015). Intrinsic functional connectivity patterns predict consciousness level and recovery outcome in acquired brain injury. Journal of Neuroscience, 35(37), 12932–12946.

    Article  CAS  PubMed  Google Scholar 

  • Xie, C. l., Zhang, Y. Y., Wang, X. D., Chen, J., Chen, Y. H., Pa, J. L., et al. (2015). Levodopa alone compared with levodopa-sparing therapy as initial treatment for Parkinson’s disease: a meta-analysis. Neurological Sciences, 36(8), 1319–1329.

    Article  PubMed  Google Scholar 

  • Yan, C. G., & Zang, Y. F. (2010). DPARSF: a MATLAB toolbox for “pipeline” data analysis of resting-state fMRI. Frontiers in Systems Neuroscience, 4, 13.

    Google Scholar 

  • Yan, C. G., Wang, X. D., Zuo, X. N., & Zang, Y. F. (2016). DPABI: Data Processing & Analysis for (Resting-State) Brain Imaging. Neuroinformatics, 14(3), 339.

    Article  PubMed  Google Scholar 

  • Young, D. E., Wagenaar, R. C., Lin, C.-C., Chou, Y.-H., Davidsdottir, S., Saltzman, E., et al. (2010). Visuospatial perception and navigation in Parkinson’s disease. Vision Research, 50(23), 2495–2504.

    Article  PubMed  PubMed Central  Google Scholar 

  • Zarei, M., Ibarretxe-Bilbao, N., Compta, Y., Hough, M., Junque, C., Bargallo, N., et al. (2013). Cortical thinning is associated with disease stages and dementia in Parkinson's disease. Journal of Neurology, Neurosurgery and Psychiatry, 84(8), 875–882.

    Article  PubMed  Google Scholar 

  • Zhang, J., Wei, L., Hu, X., Zhang, Y., Zhou, D., Li, C., et al. (2013). Specific frequency band of amplitude low-frequency fluctuation predicts Parkinson's disease. Behavioural Brain Research, 252, 18–23.

    Article  PubMed  Google Scholar 

  • Zhang, J., Bi, W., Zhang, Y., Zhu, M., Zhang, Y., Feng, H., et al. (2015). Abnormal functional connectivity density in Parkinson's disease. Behavioural Brain Research, 280, 113–118.

    Article  PubMed  Google Scholar 

  • Zuo, X. N., Ehmke, R., Mennes, M., Imperati, D., Castellanos, F. X., Sporns, O., et al. (2012). Network centrality in the human functional connectome. Cerebral Cortex, 22(8), 1862–1875.

    Article  PubMed  Google Scholar 

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Acknowledgements

The authors are grateful to the two anonymous reviewers for constructive and insightful comments on a previous version of this article.

Funding

This work was supported by the funding from the Natural Science Foundation of China (Grant numbers: 81271548, 81271560, 81371535, 81428013, and 81471654) and Planned Science and Technology Project of Guangzhou, China (Grant numbers: 20160402007).

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Author notes

  1. Miao Zhong and Wanqun Yang contributed equally to this work.

Authors and Affiliations

  1. School of Psychology, Institute of Brain Science and Rehabilitation, Key Laboratory of Mental Health and Cognitive Science of Guangdong Province, South China Normal University, Guangzhou, 510631, People’s Republic of China

    Miao Zhong, Wenjie Jiang, Xiaojin Liu, Junjing Wang, Ling Zhao, Jiabao Lin & Ruiwang Huang

  2. Department of Radiology, Guangdong Academy of Medical Sciences, Guangdong General Hospital, Guangzhou, People’s Republic of China

    Wanqun Yang & Biao Huang

  3. Department of Neurology, Guangdong Academy of Medical Sciences, Guangdong General Hospital, Guangzhou, People’s Republic of China

    Xiong Zhang, Lijuan Wang & Yuhu Zhang

  4. School of Biomedical Engineering, Southern Medical University, Guangzhou, People’s Republic of China

    Yingjun Liu

  5. Department of Applied Psychology, Guangdong University of Foreign Studies, Guangzhou, People’s Republic of China

    Junjing Wang

Authors
  1. Miao Zhong
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  2. Wanqun Yang
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  3. Biao Huang
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  4. Wenjie Jiang
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  7. Lijuan Wang
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  8. Junjing Wang
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  9. Ling Zhao
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  10. Yuhu Zhang
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  12. Jiabao Lin
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  13. Ruiwang Huang
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Corresponding authors

Correspondence to Biao Huang or Ruiwang Huang.

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Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Conflict of interest

All of the authors declare no conflicts of interest.

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Informed consent was obtained from all individual participants included in the study.

Additional information

Highlights

1. The PD patients at ‘OFF’ state showed altered distant DC mainly in several occipital, frontal and motor areas compared to the healthy controls.

2. Levodopa therapy can normalize the abnormal distant DC in the PD patients in the occipital areas and left PoCG.

3. Levodopa therapy decreased FC of the left MCG to brain regions in DMN in the PD patients. The decreased FC of the left MCG to right TPOmid was associated with improved UPDRS-III score.

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Zhong, M., Yang, W., Huang, B. et al. Effects of levodopa therapy on voxel-based degree centrality in Parkinson’s disease. Brain Imaging and Behavior 13, 1202–1219 (2019). https://doi.org/10.1007/s11682-018-9936-7

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  • DOI: https://doi.org/10.1007/s11682-018-9936-7

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