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Tytuł:
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Differences in network controllability and regional gene expression underlie hallucinations in Parkinson's disease.
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Autorzy:
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Zarkali A; Dementia Research Centre, University College London, 8-11 Queen Square, London, WC1N 3AR, UK.
McColgan P; Huntington's Disease Centre, University College London, Russell Square House, London, WC1B 5EH, UK.
Ryten M; Department of Neurodegenerative Disease, UCL Institute of Neurology, 10-12 Russell Square House, London, UK.
Reynolds R; Department of Neurodegenerative Disease, UCL Institute of Neurology, 10-12 Russell Square House, London, UK.
Leyland LA; Dementia Research Centre, University College London, 8-11 Queen Square, London, WC1N 3AR, UK.
Lees AJ; Reta Lila Weston Institute of Neurological Studies, 1 Wakefield Street, London, WC1N 1PJ, UK.
Rees G; Institute of Cognitive Neuroscience, University College London, 17-19 Queen Square, London, WC1N 3AR, UK.; Wellcome Centre for Human Neuroimaging, University College London, 12 Queen Square, London, WC1N 3AR, UK.
Weil RS; Dementia Research Centre, University College London, 8-11 Queen Square, London, WC1N 3AR, UK.; Wellcome Centre for Human Neuroimaging, University College London, 12 Queen Square, London, WC1N 3AR, UK.; Movement Disorders Consortium, University College London, London WC1N 3BG, UK.
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Źródło:
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Brain : a journal of neurology [Brain] 2020 Dec 05; Vol. 143 (11), pp. 3435-3448.
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Typ publikacji:
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Journal Article; Research Support, Non-U.S. Gov't
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Język:
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English
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Imprint Name(s):
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Publication: Oxford : Oxford University Press
Original Publication: London.
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MeSH Terms:
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Gene Expression Regulation/*genetics
Hallucinations/*genetics
Hallucinations/*physiopathology
Nerve Net/*physiopathology
Parkinson Disease/*genetics
Parkinson Disease/*physiopathology
Aged ; Algorithms ; Chromosome Mapping ; Connectome ; Diffusion Magnetic Resonance Imaging ; Female ; Hallucinations/etiology ; Humans ; Image Processing, Computer-Assisted ; Male ; Middle Aged ; Nerve Net/diagnostic imaging ; Neuropsychological Tests ; Parkinson Disease/complications ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; Transcriptome
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References:
-
Front Cell Neurosci. 2018 Nov 16;12:399. (PMID: 30524235)
Neurobiol Dis. 2011 Jun;42(3):360-7. (PMID: 21303699)
Am J Ophthalmol. 1959 Dec;48:807-13. (PMID: 13831682)
Neuroimage. 2019 Apr 1;189:353-367. (PMID: 30648605)
Mov Disord. 2004 Sep;19(9):1043-9. (PMID: 15372593)
Neuroimage. 2012 Sep;62(3):1924-38. (PMID: 22705374)
Genome Biol. 2015 Jan 30;16:25. (PMID: 25633388)
Mov Disord. 2010;25 Suppl 1:S49-54. (PMID: 20187257)
Neurobiol Aging. 2013 Dec;34(12):2699-714. (PMID: 23855984)
Nat Rev Genet. 2009 May;10(5):295-304. (PMID: 19308066)
Nat Commun. 2015 Oct 01;6:8414. (PMID: 26423222)
Mov Disord. 2010 Nov 15;25(15):2649-53. (PMID: 21069833)
J Neural Transm Suppl. 1993;39:165-72. (PMID: 8360656)
Nat Rev Genet. 2012 Apr 03;13(5):343-57. (PMID: 22473383)
Mol Psychiatry. 2021 Apr;26(4):1299-1309. (PMID: 31659272)
Neuroimage. 2018 Apr 15;170:5-30. (PMID: 28412442)
PLoS Comput Biol. 2011 Jan 20;7(1):e1001057. (PMID: 21283776)
Neuroimage Clin. 2017 Feb 16;14:417-421. (PMID: 28275542)
Biol Psychiatry. 2018 Mar 1;83(5):456-465. (PMID: 29174593)
Neurology. 2011 Jul 19;77(3):276-80. (PMID: 21734182)
Nat Neurosci. 2008 Nov;11(11):1271-82. (PMID: 18849986)
JAMA Neurol. 2014 Jul 1;71(7):831-9. (PMID: 24862029)
Hum Brain Mapp. 2014 May;35(5):2206-19. (PMID: 23760982)
Mol Cell. 2013 Jan 24;49(2):359-367. (PMID: 23177740)
Nat Cell Biol. 2019 Feb;21(2):133-142. (PMID: 30602725)
Brain. 2019 Oct 1;142(10):3072-3085. (PMID: 31359041)
Hum Brain Mapp. 2014 Nov;35(11):5658-66. (PMID: 24985056)
Sci Rep. 2016 Jul 29;6:30770. (PMID: 27468904)
Neuroimage. 2010 Dec;53(4):1197-207. (PMID: 20600983)
Cell. 2008 Sep 5;134(5):769-81. (PMID: 18775310)
Brain Commun. 2019;1(1):fcz007. (PMID: 31886459)
Nucleic Acids Res. 2019 Jul 2;47(W1):W191-W198. (PMID: 31066453)
Nat Rev Genet. 2004 Jan;5(1):11-22. (PMID: 14708012)
Cochrane Database Syst Rev. 2016 Jan 13;(1):CD011145. (PMID: 26760674)
Magn Reson Med. 2016 Nov;76(5):1582-1593. (PMID: 26599599)
Brain. 2009 Jul;132(Pt 7):1783-94. (PMID: 19286695)
Am J Ophthalmol. 2000 Aug;130(2):261-2. (PMID: 11004314)
Nat Rev Neurosci. 2009 Mar;10(3):186-98. (PMID: 19190637)
Nat Rev Mol Cell Biol. 2019 Oct;20(10):573-589. (PMID: 31270442)
PLoS One. 2013 Jul 04;8(7):e68910. (PMID: 23861951)
Sci Signal. 2019 Jul 02;12(588):. (PMID: 31266852)
Acta Psychiatr Scand. 1983 Jun;67(6):361-70. (PMID: 6880820)
CNS Neurosci Ther. 2015 Oct;21(10):793-801. (PMID: 26224057)
Sci Rep. 2016 Aug 19;6:31380. (PMID: 27539639)
Neuroimage Clin. 2018 Jan 31;18:456-466. (PMID: 29868450)
Neurology. 2006 Nov 14;67(9):1605-11. (PMID: 17101891)
Mov Disord. 2008 Nov 15;23(15):2129-70. (PMID: 19025984)
BMC Syst Biol. 2017 Apr 12;11(1):47. (PMID: 28403906)
PLoS One. 2011;6(7):e21800. (PMID: 21789182)
J Am Geriatr Soc. 2000 Aug;48(8):938-42. (PMID: 10968298)
Cell Rep. 2016 May 31;15(9):1866-75. (PMID: 27210754)
Chem Senses. 1997 Feb;22(1):39-52. (PMID: 9056084)
Proc Biol Sci. 2015 Jan 7;282(1798):20142047. (PMID: 25429016)
Neuropsychiatr Dis Treat. 2017 May 16;13:1313-1330. (PMID: 28553118)
BMC Neurol. 2008 Jun 20;8:21. (PMID: 18570642)
Radiology. 2017 Dec;285(3):896-903. (PMID: 28952907)
Brain. 2008 Aug;131(Pt 8):1969-78. (PMID: 18187492)
Nat Methods. 2017 Oct;14(10):955-958. (PMID: 28846088)
IEEE Trans Med Imaging. 2010 Jun;29(6):1310-20. (PMID: 20378467)
Neurology. 2010 Nov 9;75(19):1717-25. (PMID: 21060094)
Biol Psychiatry. 2017 Mar 15;81(6):495-502. (PMID: 27720199)
Neurology. 2020 Apr 7;94(14):e1525-e1538. (PMID: 32094242)
Neuroimage. 2015 Oct 1;119:338-51. (PMID: 26163802)
Neuroimage. 2009 Oct 15;48(1):63-72. (PMID: 19573611)
Conscious Cogn. 2017 Jan;47:63-74. (PMID: 27222169)
Stat Appl Genet Mol Biol. 2005;4:Article17. (PMID: 16646834)
Netw Neurosci. 2019 Mar 01;3(2):521-538. (PMID: 30984905)
Cell Rep. 2018 Nov 27;25(9):2447-2456.e4. (PMID: 30485811)
Mov Disord. 2007 Dec;22(16):2386-93. (PMID: 17894337)
Parkinsonism Relat Disord. 2008;14(1):37-42. (PMID: 17627863)
Brain Commun. 2019;1(1):fcz006. (PMID: 31608325)
Mov Disord. 2014 Nov;29(13):1591-8. (PMID: 25154807)
BMC Bioinformatics. 2008 Dec 29;9:559. (PMID: 19114008)
J Cell Mol Med. 2011 Oct;15(10):2025-39. (PMID: 21722302)
Brain. 2014 Mar;137(Pt 3):834-48. (PMID: 24477431)
Genome Med. 2013 May 25;5(5):48. (PMID: 23705665)
Neuroimage. 2007 May 1;35(4):1459-72. (PMID: 17379540)
Neurology. 1995 Apr;45(4):669-71. (PMID: 7723953)
PLoS One. 2015 Oct 01;10(10):e0139516. (PMID: 26426330)
Magn Reson Med. 2016 Nov;76(5):1574-1581. (PMID: 26745823)
Neuron. 2002 Jan 31;33(3):341-55. (PMID: 11832223)
Neuron. 2013 Mar 6;77(5):873-85. (PMID: 23473318)
Mov Disord. 2008 Apr 30;23(6):837-44. (PMID: 18307261)
Mov Disord. 2019 Aug;34(8):1100-1111. (PMID: 31307115)
Brain. 2016 Nov 1;139(11):2827-2843. (PMID: 27412389)
Front Neurosci. 2016 Jan 27;10:16. (PMID: 26858593)
Curr Neurol Neurosci Rep. 2010 May;10(3):190-8. (PMID: 20425034)
Nature. 2016 Aug 11;536(7615):171-178. (PMID: 27437579)
Nat Genet. 2020 May;52(5):482-493. (PMID: 32341526)
Neurology. 2019 May 7;92(19):e2209-e2220. (PMID: 31004070)
Nat Neurosci. 2015 Dec;18(12):1832-44. (PMID: 26571460)
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Grant Information:
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United Kingdom WT_ Wellcome Trust; 205167/Z/16/Z United Kingdom WT_ Wellcome Trust; MR/N008324/1 United Kingdom MRC_ Medical Research Council; 201567/Z/16/Z United Kingdom WT_ Wellcome Trust
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Contributed Indexing:
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Keywords: Parkinson’s disease; controllability; diffusion weighted imaging; regional gene expression; visual hallucinations
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Substance Nomenclature:
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0 (RNA, Messenger)
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Entry Date(s):
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Date Created: 20201029 Date Completed: 20210301 Latest Revision: 20240331
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Update Code:
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20240331
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PubMed Central ID:
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PMC7719028
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DOI:
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10.1093/brain/awaa270
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PMID:
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33118028
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Visual hallucinations are common in Parkinson's disease and are associated with poorer prognosis. Imaging studies show white matter loss and functional connectivity changes with Parkinson's visual hallucinations, but the biological factors underlying selective vulnerability of affected parts of the brain network are unknown. Recent models for Parkinson's disease hallucinations suggest they arise due to a shift in the relative effects of different networks. Understanding how structural connectivity affects the interplay between networks will provide important mechanistic insights. To address this, we investigated the structural connectivity changes that accompany visual hallucinations in Parkinson's disease and the organizational and gene expression characteristics of the preferentially affected areas of the network. We performed diffusion-weighted imaging in 100 patients with Parkinson's disease (81 without hallucinations, 19 with visual hallucinations) and 34 healthy age-matched controls. We used network-based statistics to identify changes in structural connectivity in Parkinson's disease patients with hallucinations and performed an analysis of controllability, an emerging technique that allows quantification of the influence a brain region has across the rest of the network. Using these techniques, we identified a subnetwork of reduced connectivity in Parkinson's disease hallucinations. We then used the Allen Institute for Brain Sciences human transcriptome atlas to identify regional gene expression patterns associated with affected areas of the network. Within this network, Parkinson's disease patients with hallucinations showed reduced controllability (less influence over other brain regions), than Parkinson's disease patients without hallucinations and controls. This subnetwork appears to be critical for overall brain integration, as even in controls, nodes with high controllability were more likely to be within the subnetwork. Gene expression analysis of gene modules related to the affected subnetwork revealed that down-weighted genes were most significantly enriched in genes related to mRNA and chromosome metabolic processes (with enrichment in oligodendrocytes) and upweighted genes to protein localization (with enrichment in neuronal cells). Our findings provide insights into how hallucinations are generated, with breakdown of a key structural subnetwork that exerts control across distributed brain regions. Expression of genes related to mRNA metabolism and membrane localization may be implicated, providing potential therapeutic targets.
(© The Author(s) (2020). Published by Oxford University Press on behalf of the Guarantors of Brain.)