Abstract
Although mild cognitive impairment is a common non-motor symptom experienced by individuals with Parkinson’s Disease, the changes in intrinsic resting-state networks associated with its onset in Parkinson’s remain underexamined. To address the issue, our study sought to examine resting-state network alterations and their association with total performance in the Montreal Cognitive Assessment and its cognitive domains in Parkinson’s by means of functional magnetic resonance imaging of 29 Parkinson’s patients with normal cognition, 25 Parkinson’s patients with mild cognitive impairment, and 13 healthy controls. To contrast the Parkinson’s groups with each other and the controls, the images were used to estimate the Z-score coefficient between the regions of interest from the default mode network, the salience network and the central executive network. Our first finding was that default mode and salience network connectivity decreased significantly in Parkinson’s patients regardless of their cognitive status. Additionally, default mode network nodes had a negative and salience network nodes a positive correlation with the global assessment in Parkinson’s with normal cognition; this inverse relationship of both networks to total score was not found in the group with cognitive impairment. Finally, a positive correlation was found between executive scores and anterior and posterior cortical network connectivity and, in the group with cognitive impairment, between language scores and salience network connectivity. Our results suggest that specific resting-state networks of Parkinson’s patients with cognitive impairment differ from those of Parkinson’s patients with normal cognition, supporting the evidence that cognitive impairment in Parkinson’s Disease displays a differentiated neurodegenerative pattern.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
Data availability
The data supporting this article can be found in https://figshare.com/articles/dataset/Data_of_PD_and_Data_of_resting_state_networks_/23819142.
References
Alexander, G. E., & Crutcher, M. D. (1990). Functional architecture of basal ganglia circuits: Neural substrates of parallel processing. Trends in Neurosciences, 13(7), 266–271. https://doi.org/10.1016/0166-2236(90)90107-L.
Aracil-Bolaños, I., Sampedro, F., Marín-Lahoz, J., Horta-Barba, A., Martínez-Horta, S., Botí, M., Pérez-Pérez, J., Bejr-Kasem, H., Pascual-Sedano, B., Campolongo, A., Izquierdo, C., Gironell, A., Gómez-Ansón, B., Kulisevsky, J., & Pagonabarraga, J. (2019). A divergent breakdown of neurocognitive networks in Parkinson’s Disease mild cognitive impairment. Human Brain Mapping, 40(11), 3233–3242. https://doi.org/10.1002/hbm.24593.
Baggio, H. C., Segura, B., Sala-Llonch, R., Marti, M. J., Valldeoriola, F., Compta, Y., Tolosa, E., & Junqué, C. (2015). Cognitive impairment and resting-state network connectivity in Parkinson’s disease. Human Brain Mapping, 36(1), 199–212. https://doi.org/10.1002/hbm.22622.
Calderon-Villalon, J., Ramirez-Garcia, G., Fernandez-Ruiz, J., Sangri-Gil, F., Campos-Romo, A., & Galvez, V. (2021). Planning deficits in Huntington’s disease: A brain structural correlation by Voxel-based morphometry. PloS One, 16(3), e0249144. https://doi.org/10.1371/journal.pone.0249144.
Caminiti, S. P., Siri, C., Guidi, L., Antonini, A., & Perani, D. (2015). The neural correlates of spatial and object working memory in elderly and Parkinson’s disease subjects. Behavioural Neurology, 2015(123636). https://doi.org/10.1155/2015/123636.
Chen, B., Fan, G. G., Liu, H., & Wang, S. (2015). Changes in anatomical and functional connectivity of Parkinson’s disease patients according to cognitive status. European Journal of Radiology, 84(7), 1318–1324. https://doi.org/10.1016/j.ejrad.2015.04.014.
Chikama, M., McFarland, N. R., Amaral, D. G., & Haber, S. N. (1997). Insular cortical projections to functional regions of the striatum correlate with cortical cytoarchitectonic organization in the primate. J Neurosci off J Soc Neurosci, 17(24), 9686–9705. https://doi.org/10.1523/JNEUROSCI.17-24-09686.1997.
Christopher, L., Marras, C., Duff-Canning, S., Koshimori, Y., Chen, R., Boileau, I., Segura, B., Monchi, O., Lang, A. E., Rusjan, P., Houle, S., & Strafella, A. P. (2014). Combined insular and striatal dopamine dysfunction are associated with executive deficits in Parkinson’s disease with mild cognitive impairment. Brain J Neurol, 137(Pt 2), 565–575. https://doi.org/10.1093/brain/awt337.
Dalrymple-Alford, J. C., MacAskill, M. R., Nakas, C. T., Livingston, L., Graham, C., Crucian, G. P., Melzer, T. R., Kirwan, J., Keenan, R., Wells, S., Porter, R. J., Watts, R., & Anderson, T. J. (2010). The MoCA: Well-suited screen for cognitive impairment in Parkinson disease. Neurology, 75(19), 1717–1725. https://doi.org/10.1212/WNL.0b013e3181fc29c9.
Delgado-Alvarado, M., Gago, B., Navalpotro-Gomez, I., Jiménez-Urbieta, H., & Rodriguez-Oroz, M. C. (2016). Biomarkers for dementia and mild cognitive impairment in Parkinson’s disease. Mov Disord off J Mov Disord Soc, 31(6), 861–881. https://doi.org/10.1002/mds.26662.
Disbrow, E. A., Carmichael, O., He, J., Lanni, K. E., Dressler, E. M., Zhang, L., Malhado-Chang, N., & Sigvardt, K. A. (2014). Resting state functional connectivity is associated with cognitive dysfunction in non-demented people with Parkinson’s disease. J Park Dis, 4(3), 453–465. https://doi.org/10.3233/JPD-130341.
Droby, A., Pelosin, E., Putzolu, M., Bommarito, G., Marchese, R., Mazzella, L., Avanzino, L., & Inglese, M. (2021). A Multimodal Imaging Approach demonstrates reduced Midbrain Functional Network Connectivity is Associated with freezing of Gait in Parkinson’s Disease. Frontiers in Neurology, 12, 583593. https://doi.org/10.3389/fneur.2021.583593.
Fox, M. D., Snyder, A. Z., Vincent, J. L., Corbetta, M., Van Essen, D. C., & Raichle, M. E. (2005). The human brain is intrinsically organized into dynamic, anticorrelated functional networks. Proc Natl Acad Sci U S A, 102(27), 9673–9678. https://doi.org/10.1073/pnas.0504136102.
Fudge, J. L., Breitbart, M. A., Danish, M., & Pannoni, V. (2005). Insular and gustatory inputs to the caudal ventral striatum in primates. The Journal of Comparative Neurology, 490(2), 101–118. https://doi.org/10.1002/cne.20660.
Gluhm, S., Goldstein, J., Brown, D., Van Liew, C., Gilbert, P. E., & Corey-Bloom, J. (2013). Usefulness of the Montreal Cognitive Assessment (MoCA) in Huntington’s disease. Mov Disord off J Mov Disord Soc, 28(12), 1744–1747. https://doi.org/10.1002/mds.25578.
Goetz, C. G., Tilley, B. C., Shaftman, S. R., Stebbins, G. T., Fahn, S., Martinez-Martin, P., Poewe, W., Sampaio, C., Stern, M. B., Dodel, R., Dubois, B., Holloway, R., Jankovic, J., Kulisevsky, J., Lang, A. E., Lees, A., Leurgans, S., LeWitt, P. A., Nyenhuis, D., Olanow, C. W., Rascol, O., Schrag, A., Teresi, J. A., van Hilten, J. J., LaPelle, N., & Movement Disorder Society UPDRS Revision Task Force. (2008). Movement Disorder Society-sponsored revision of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS): Scale presentation and clinimetric testing results. Mov Disord off J Mov Disord Soc, 23(15), 2129–2170. https://doi.org/10.1002/mds.22340.
Greicius, M. D., Krasnow, B., Reiss, A. L., & Menon, V. (2003). Functional connectivity in the resting brain: A network analysis of the default mode hypothesis. Proc Natl Acad Sci U S A, 100(1), 253–258. https://doi.org/10.1073/pnas.0135058100.
Hohenfeld, C., Werner, C. J., & Reetz, K. (2018). Resting-state connectivity in neurodegenerative disorders: Is there potential for an imaging biomarker? NeuroImage Clin, 18, 849–870. https://doi.org/10.1016/j.nicl.2018.03.013.
Hoogland, J., Boel, J. A., de Bie, R. M. A., Geskus, R. B., Schmand, B. A., Dalrymple-Alford, J. C., Marras, C., Adler, C. H., Goldman, J. G., Tröster, A. I., Burn, D. J., Litvan, I., Geurtsen, G. J., & MDS Study Group. (2017). Mild cognitive impairment as a risk factor for Parkinson’s disease dementia. Mov Disord off J Mov Disord Soc, 32(7), 1056–1065. https://doi.org/10.1002/mds.27002.
Hoops, S., Nazem, S., Siderowf, A. D., Duda, J. E., Xie, S. X., Stern, M. B., & Weintraub, D. (2009). Validity of the MoCA and MMSE in the detection of MCI and dementia in Parkinson disease. Neurology, 73(21), 1738–1745. https://doi.org/10.1212/WNL.0b013e3181c34b47.
Karunanayaka, P. R., Lee, E. Y., Lewis, M. M., Sen, S., Eslinger, P. J., Yang, Q. X., & Huang, X. (2016). Default mode network differences between rigidity- and tremor-predominant Parkinson’s disease. Cortex J Devoted Study Nerv Syst Behav, 81, 239–250. https://doi.org/10.1016/j.cortex.2016.04.021.
Kehagia, A. A., Barker, R. A., & Robbins, T. W. (2013). Cognitive impairment in Parkinson’s disease: The dual syndrome hypothesis. Neurodegener Dis, 11(2), 79–92. https://doi.org/10.1159/000341998.
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. J Neural Transm Vienna Austria 1996, 119(4), 443–454. https://doi.org/10.1007/s00702-011-0723-5.
Lebedev, A. V., Westman, E., Simmons, A., Lebedeva, A., Siepel, F. J., Pereira, J. B., & Aarsland, D. (2014). Large-scale resting state network correlates of cognitive impairment in Parkinson’s disease and related dopaminergic deficits. Frontiers in Systems Neuroscience, 8, 45. https://doi.org/10.3389/fnsys.2014.00045.
Leh, S. E., Chakravarty, M. M., & Ptito, A. (2008). The connectivity of the human pulvinar: A diffusion tensor imaging tractography study. International Journal of Biomedical Imaging, 2008, 789539. https://doi.org/10.1155/2008/789539.
Lewis, S. J. G., Dove, A., Robbins, T. W., Barker, R. A., & Owen, A. M. (2003). Cognitive impairments in early Parkinson’s disease are accompanied by reductions in activity in frontostriatal neural circuitry. J Neurosci off J Soc Neurosci, 23(15), 6351–6356. https://doi.org/10.1523/JNEUROSCI.23-15-06351.2003.
Li, M. G., Bian, X. B., Zhang, J., Wang, Z. F., & Ma, L. (2021). Aberrant voxel-based degree centrality in Parkinson’s disease patients with mild cognitive impairment. Neuroscience Letters, 741, 135507. https://doi.org/10.1016/j.neulet.2020.135507.
Litvan, I., Goldman, J. G., Tröster, A. I., Schmand, B. A., Weintraub, D., Petersen, R. C., ... & Emre, M. (2012). Diagnostic criteria for mild cognitive impairment in Parkinson’s disease: Movement disorder society task force guidelines. Movement disorders, 27(3), 349–356. https://doi.org/10.1002/mds.24893.
Liu, A., Lin, S. J., Mi, T., Chen, X., Chan, P., Wang, Z. J., & McKeown, M. J. (2018). Decreased subregional specificity of the putamen in Parkinson’s Disease revealed by dynamic connectivity-derived parcellation. NeuroImage Clin, 20, 1163–1175. https://doi.org/10.1016/j.nicl.2018.10.022.
Lopes, R., Delmaire, C., Defebvre, L., Moonen, A. J., Duits, A. A., Hofman, P., Leentjens, A. F. G., & Dujardin, K. (2017). Cognitive phenotypes in parkinson’s disease differ in terms of brain-network organization and connectivity. Human Brain Mapping, 38(3), 1604–1621. https://doi.org/10.1002/hbm.23474.
Lucas-Jiménez, O., Ojeda, N., Peña, J., Díez-Cirarda, M., Cabrera-Zubizarreta, A., Gómez-Esteban, J. C., Gómez-Beldarrain, M., & Ibarretxe-Bilbao, N. (2016). Altered functional connectivity in the default mode network is associated with cognitive impairment and brain anatomical changes in Parkinson’s disease. Parkinsonism & Related Disorders, 33, 58–64. https://doi.org/10.1016/j.parkreldis.2016.09.012.
Meara, J., Mitchelmore, E., & Hobson, P. (1999). Use of the GDS-15 geriatric depression scale as a screening instrument for depressive symptomatology in patients with Parkinson’s disease and their carers in the community. Age and Ageing, 28(1), 35–38. https://doi.org/10.1093/ageing/28.1.35.
Menon, V., & Uddin, L. Q. (2010). Saliency, switching, attention and control: A network model of insula function. Brain Struct Funct, 214(5–6), 655–667. https://doi.org/10.1007/s00429-010-0262-0.
Monchi, O., Petrides, M., Mejia-Constain, B., & Strafella, A. P. (2007). Cortical activity in Parkinson’s disease during executive processing depends on striatal involvement. Brain J Neurol, 130(Pt 1), 233–244. https://doi.org/10.1093/brain/awl326.
Nasreddine, Z. S., Phillips, N. A., Bédirian, V., Charbonneau, S., Whitehead, V., Collin, I., Cummings, J. L., & Chertkow, H. (2005). The Montreal Cognitive Assessment, MoCA: A brief screening tool for mild cognitive impairment. Journal of the American Geriatrics Society, 53(4), 695–699. https://doi.org/10.1111/j.1532-5415.2005.53221.x.
Nasreddine, Z. S., Phillips, N. A., Bédirian, V., Charbonneau, S., Whitehead, V., Collin, I., Cummings, J. L., & Chertkow, H. (2019). The Montreal Cognitive Assessment, MoCA: A brief screening tool for mild cognitive impairment: Corrigendum. Journal of the American Geriatrics Society, 67(9), 1991–1991. https://doi.org/10.1111/jgs.15925.
Parkinson Progression Marker Initiative. (2011). The Parkinson progression marker Initiative (PPMI). Progress in Neurobiology, 95(4), 629–635. https://doi.org/10.1016/j.pneurobio.2011.09.005.
Putcha, D., Ross, R. S., Cronin-Golomb, A., Janes, A. C., & Stern, C. E. (2015). Altered intrinsic functional coupling between core neurocognitive networks in Parkinson’s disease. NeuroImage Clin, 7, 449–455. https://doi.org/10.1016/j.nicl.2015.01.012.
Raichle, M. E., MacLeod, A. M., Snyder, A. Z., Powers, W. J., Gusnard, D. A., & Shulman, G. L. (2001). A default mode of brain function. Proc Natl Acad Sci U S A, 98(2), 676–682. https://doi.org/10.1073/pnas.98.2.676.
Ravina, B., Marek, K., Eberly, S., Oakes, D., Kurlan, R., Ascherio, A., Beal, F., Beck, J., Flagg, E., Galpern, W. R., Harman, J., Lang, A. E., Schwarzschild, M., Tanner, C., & Shoulson, I. (2012). Dopamine transporter imaging is associated with long-term outcomes in Parkinson’s disease. Mov Disord off J Mov Disord Soc, 27(11), 1392–1397. https://doi.org/10.1002/mds.25157.
Rektorova, I., Krajcovicova, L., Marecek, R., & Mikl, M. (2012). Default mode network and extrastriate visual resting state network in patients with Parkinson’s disease dementia. Neurodegener Dis, 10(1–4), 232–237. https://doi.org/10.1159/000334765.
Ruppert, M. C., Greuel, A., Freigang, J., Tahmasian, M., Maier, F., Hammes, J., van Eimeren, T., Timmermann, L., Tittgemeyer, M., Drzezga, A., & Eggers, C. (2021). The default mode network and cognition in Parkinson’s disease: A multimodal resting-state network approach. Human Brain Mapping, 42(8), 2623–2641. https://doi.org/10.1002/hbm.25393.
Seeley, W. W., Menon, V., Schatzberg, A. F., Keller, J., Glover, G. H., Kenna, H., Reiss, A. L., & Greicius, M. D. (2007). Dissociable intrinsic connectivity networks for salience processing and executive control. J Neurosci off J Soc Neurosci, 27(9), 2349–2356. https://doi.org/10.1523/JNEUROSCI.5587-06.2007.
Shine, J. M., Matar, E., Ward, P. B., Frank, M. J., Moustafa, A. A., Pearson, M., Naismith, S. L., & Lewis, S. J. G. (2013). Freezing of gait in Parkinson’s disease is associated with functional decoupling between the cognitive control network and the basal ganglia. Brain J Neurol, 136(Pt 12), 3671–3681. https://doi.org/10.1093/brain/awt272.
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(23), 2226–2232. https://doi.org/10.1212/WNL.0b013e31827689d6.
Tessitore, A., Cirillo, M., & De Micco, R. (2019). Functional connectivity signatures of Parkinson’s Disease. J Park Dis, 9(4), 637–652. https://doi.org/10.3233/JPD-191592.
van de Wolters, A. F., Leentjens, A. F. G., Duits, A. A., Jacobs, H. I. L., & Kuijf, M. L. (2019). Resting-state fMRI in Parkinson’s disease patients with cognitive impairment: A meta-analysis. Parkinsonism & Related Disorders, 62, 16–27. https://doi.org/10.1016/j.parkreldis.2018.12.016.
van Eimeren, T., Monchi, O., Ballanger, B., & Strafella, A. P. (2009). Dysfunction of the default mode network in Parkinson disease: A functional magnetic resonance imaging study. Archives of Neurology, 66(7), 877–883. https://doi.org/10.1001/archneurol.2009.97.
Whitfield-Gabrieli, S., & Nieto-Castanon, A. (2012). Conn: A functional connectivity toolbox for correlated and anticorrelated brain networks. Brain Connectivity, 2(3), 125–141. https://doi.org/10.1089/brain.2012.0073.
Williams-Gray, C. H., Foltynie, T., Brayne, C. E. G., Robbins, T. W., & Barker, R. A. (2007). Evolution of cognitive dysfunction in an incident Parkinson’s disease cohort. Brain J Neurol, 130(Pt 7), 1787–1798. https://doi.org/10.1093/brain/awm111.
World Medical Association. (2013). World Medical Association Declaration of Helsinki: Ethical principles for Medical Research Involving human subjects. Journal of the American Medical Association, 310(20), 2191–2194. https://doi.org/10.1001/jama.2013.281053.
Yao, N., Shek-Kwan Chang, R., Cheung, C., Pang, S., Lau, K. K., Suckling, J., Rowe, J. B., Yu, K., Ka-Fung Mak, H., Chua, S. E., Ho, S. L., & McAlonan, G. M. (2014). The default mode network is disrupted in Parkinson’s disease with visual hallucinations. Human Brain Mapping, 35(11), 5658–5666. https://doi.org/10.1002/hbm.22577.
Zhan, Z. W., Lin, L. Z., Yu, E. H., Xin, J. W., Lin, L., Lin, H. L., Ye, Q. Y., Chen, X. C., & Pan, X. D. (2018). Abnormal resting-state functional connectivity in posterior cingulate cortex of Parkinson’s disease with mild cognitive impairment and dementia. Cns Neuroscience & Therapeutics, 24(10), 897–905. https://doi.org/10.1111/cns.12838.
Zhong, J., Guan, X., Zhong, X., Cao, F., Gu, Q., Guo, T., Zhou, C., Zeng, Q., Wang, J., Gao, T., & Zhang, M. (2019). Levodopa imparts a normalizing effect on default-mode network connectivity in non-demented Parkinson’s disease. Neuroscience Letters, 705, 159–166. https://doi.org/10.1016/j.neulet.2019.04.042.
Acknowledgements
We want to thank Santiago Fernandez-Ballina for his editorial help.
Funding
This study was supported by the “Fondo semilla 2019” grant to V. Galvez from FCS-Universidad Panamericana.
Author information
Authors and Affiliations
Contributions
VG: Methodology, Investigation, Data Curation, Writing - original draft, Writing – review editing, Visualization, Supervision, Project administration. CRR: Methodology, Investigation, Data Curation, Formal analysis, Writing – review editing, Visualization. MAEG: Methodology, Investigation, Writing – review editing, Visualization. JFR: Methodology, Investigation, Writing – review editing, Visualization.
Corresponding author
Ethics declarations
Ethics approval
The PPMI global study was approved by the Research Subjects Review Board at the University of Rochester. All patients provided written informed consent. All the procedures were performed according to the Declaration of Helsinki (World Medical Association, 2013) and approved by health and ethics committees of the Instituto Nacional de Neurología y Neurocirugía “MVS” and the Universidad Nacional Autónoma de México.
Consent to participate
All patients provided written informed consent to participate in this study.
Consent for publication
All patients provided written informed consent for the publication of this study.
Conflicts of interest/Competing interests
None of the authors have a conflict of interest to declare.
Additional information
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Electronic supplementary material
Below is the link to the electronic supplementary material.
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Galvez, V., Romero-Rebollar, C., Estudillo-Guerra, M.A. et al. Resting-state networks and their relationship with MoCA performance in PD patients. Brain Imaging and Behavior (2024). https://doi.org/10.1007/s11682-024-00860-3
Accepted:
Published:
DOI: https://doi.org/10.1007/s11682-024-00860-3