title: Brainstem stimulation increases functional connectivity of basal forebrain-paralimbic network in isoflurane-anesthetized rats.
abstract: Brain states and cognitive-behavioral functions are precisely controlled by subcortical neuromodulatory networks. Manipulating key components of the ascending arousal system (AAS), via deep-brain stimulation, may help facilitate global arousal in anesthetized animals. Here we test the hypothesis that electrical stimulation of the oral part of the pontine reticular nucleus (PnO) under light isoflurane anesthesia, associated with loss of consciousness, leads to cortical desynchronization and specific changes in blood-oxygenation-level-dependent (BOLD) functional connectivity (FC) of the brain. BOLD signals were acquired simultaneously with frontal epidural electroencephalogram before and after PnO stimulation. Whole-brain FC was mapped using correlation analysis with seeds in major centers of the AAS. PnO stimulation produced cortical desynchronization, a decrease in δ- and θ-band power, and an increase in approximate entropy. Significant increases in FC after PnO stimulation occurred between the left nucleus Basalis of Meynert (NBM) as seed and numerous regions of the paralimbic network. Smaller increases in FC were present between the central medial thalamic nucleus and retrosplenium seeds and the left caudate putamen and NBM. The results suggest that, during light anesthesia, PnO stimulation preferentially modulates basal forebrain-paralimbic networks. We speculate that this may be a reflection of disconnected awareness.
authors.affiliation: 1 Department of Anesthesiology, Medical College of Wisconsin , Milwaukee, Wisconsin.
authors.forename: Siveshigan
authors.initials: S
authors.lastname: Pillay
authors.forename: Xiping
authors.initials: X
authors.lastname: Liu
authors.forename: Péter
authors.initials: P
authors.lastname: Baracskay
authors.forename: Anthony G
authors.initials: AG
authors.lastname: Hudetz
mesh_terms: D018685:Anesthetics, Inhalation / Q000494:pharmacology; D000818:Animals; D001143:Arousal / Q000502:physiology*; D066187:Basal Forebrain / Q000502:physiology*; D001921:Brain / Q000502:physiology*; D001931:Brain Mapping; D058256:Brain Waves; D004558:Electric Stimulation; D004569:Electroencephalography; D007530:Isoflurane / Q000494:pharmacology; D008279:Magnetic Resonance Imaging; D008297:Male; D009415:Nerve Net / Q000502:physiology*; D065821:Pontine Tegmentum / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D018685:Anesthetics, Inhalation; D007530:Isoflurane
keywords: anesthesia; ascending arousal system; consciousness; functional connectivity magnetic resonance imaging (fcMRI)
references.citation: Anesthesiology. 2009 Apr;110(4):766-73
references.pmid: 19322942
references.citation: Biol Psychiatry. 2010 Dec 1;68(11):1016-22
references.pmid: 20951978
references.citation: Neuron. 2001 Jan;29(1):145-56
references.pmid: 11182087
references.citation: Dent Mater. 2012 Sep;28(9):1024-31
references.pmid: 22770675
references.citation: Nature. 2007 Aug 2;448(7153):600-3
references.pmid: 17671503
references.citation: Neuroscience. 1991;44(3):521-35
references.pmid: 1754050
references.citation: Trends Cogn Sci. 2005 Dec;9(12):556-9
references.pmid: 16271507
references.citation: Front Hum Neurosci. 2009 Sep 02;3:22
references.pmid: 19750197
references.citation: Lancet Neurol. 2012 May;11(5):429-42
references.pmid: 22516078
references.citation: Sleep. 2005 May;28(5):551-9
references.pmid: 16171268
references.citation: Neuroscience. 1994 Jun;60(3):665-77
references.pmid: 7936193
references.citation: Ann N Y Acad Sci. 2012 Aug;1265:56-68
references.pmid: 22834729
references.citation: Neuroimage. 2005 Nov 15;28(3):720-37
references.pmid: 16150610
references.citation: Anesthesiology. 2005 Feb;102(2):447-71
references.pmid: 15681963
references.citation: N Engl J Med. 2010 Dec 30;363(27):2638-50
references.pmid: 21190458
references.citation: J Biomed Mater Res B Appl Biomater. 2008 Feb;84(2):468-77
references.pmid: 17668860
references.citation: Life Sci. 1991;48(25):2469-74
references.pmid: 2046472
references.citation: Trends Neurosci. 1999 Jun;22(6):273-80
references.pmid: 10354606
references.citation: J Neurosci Methods. 2006 Jul 15;155(1):72-6
references.pmid: 16466802
references.citation: Neuropsychologia. 1999 Jan;37(1):103-18
references.pmid: 9920476
references.citation: J Neurosci. 2004 Nov 24;24(47):10670-8
references.pmid: 15564583
references.citation: Memory. 1999 Sep-Nov;7(5-6):661-78
references.pmid: 10659091
references.citation: J Neurosci. 2014 Jan 15;34(3):839-45
references.pmid: 24431442
references.citation: Sleep. 2011 Mar 01;34(3):283-91A
references.pmid: 21358845
references.citation: Nat Neurosci. 2013 Apr;16(4):386-7
references.pmid: 23434914
references.citation: Electroencephalogr Clin Neurophysiol. 1949 Nov;1(4):455-73
references.pmid: 18421835
references.citation: Neuron. 2012 Oct 4;76(1):209-22
references.pmid: 23040816
references.citation: Clin Neurophysiol. 2005 Apr;116(4):799-806
references.pmid: 15792889
references.citation: Trends Cogn Sci. 2010 Jun;14(6):277-90
references.pmid: 20493761
references.citation: Neuropharmacology. 2014 Sep;84:79-89
references.pmid: 24012656
references.citation: Eur J Neurosci. 2002 Feb;15(4):744-52
references.pmid: 11886439
references.citation: Hum Brain Mapp. 2010 Feb;31(2):185-92
references.pmid: 19621368
references.citation: Biomaterials. 2007 Sep;28(26):3757-85
references.pmid: 17543382
references.citation: Lancet Neurol. 2013 Jan;12(1):37-44
references.pmid: 23168021
references.citation: J Neurosci. 2002 Jul 1;22(13):5597-605
references.pmid: 12097511
references.citation: Annu Rev Psychol. 2002;53:1-25
references.pmid: 11752477
references.citation: Science. 2008 Nov 7;322(5903):876-80
references.pmid: 18988836
references.citation: Brain. 2014 Apr;137(Pt 4):1130-44
references.pmid: 24566670
references.citation: Sleep. 1995 Jul;18(6):478-500
references.pmid: 7481420
references.citation: Anesthesiology. 2005 Dec;103(6):1268-95
references.pmid: 16306742
references.citation: Nat Rev Neurosci. 2008 May;9(5):370-86
references.pmid: 18425091
references.citation: Neuroimage. 2014 Jan 1;84:11-8
references.pmid: 23988274
references.citation: Nat Neurosci. 2000 Aug;3(8):831-6
references.pmid: 10903578
references.citation: Proc Natl Acad Sci U S A. 2001 Jan 16;98(2):676-82
references.pmid: 11209064
references.citation: Neuron. 2005 Mar 3;45(5):651-60
references.pmid: 15748841
references.citation: PLoS One. 2014 Jan 22;9(1):e86496
references.pmid: 24466120
references.citation: Adv Anat Embryol Cell Biol. 2011;208:1-128
references.pmid: 21166301
references.citation: Nat Rev Neurosci. 2009 Nov;10(11):803-13
references.pmid: 19794431
references.citation: Anesthesiology. 2012 Apr;116(4):946-59
references.pmid: 22314293
references.citation: Adv Exp Med Biol. 1991;295:43-100
references.pmid: 1776580
references.citation: Psychopharmacology (Berl). 2008 Aug;199(3):457-80
references.pmid: 18311558
references.citation: Science. 1971 May 7;172(3983):601-2
references.pmid: 4324472
references.citation: Sleep. 2008 Apr;31(4):453-64
references.pmid: 18457232
references.citation: Magn Reson Imaging. 2008 Sep;26(7):978-86
references.pmid: 18479870
references.citation: Magn Reson Med. 2009 Jan;61(1):222-8
references.pmid: 19097225
references.citation: Philos Trans R Soc Lond B Biol Sci. 2001 Sep 29;356(1413):1351-61
references.pmid: 11571027
references.citation: Psychophysiology. 1997 May;34(3):377-81
references.pmid: 9175452
references.citation: Best Pract Res Clin Anaesthesiol. 2005 Sep;19(3):349-64
references.pmid: 16013686
references.citation: Front Biosci. 2003 May 01;8:s438-51
references.pmid: 12700104
references.citation: Anesthesiology. 2014 Aug;121(2):311-9
references.pmid: 24398816
references.citation: Anesthesiology. 2007 Aug;107(2):264-72
references.pmid: 17667571
references.citation: Crit Rev Neurobiol. 2005;17(3-4):161-217
references.pmid: 17341198
references.citation: Proc Natl Acad Sci U S A. 1991 Mar 15;88(6):2297-301
references.pmid: 11607165
references.citation: Trends Neurosci. 2010 Jan;33(1):1-9
references.pmid: 19954851
references.citation: Curr Opin Neurol. 2005 Dec;18(6):726-33
references.pmid: 16280686
references.citation: J Neurosci. 2010 Sep 15;30(37):12301-9
references.pmid: 20844126
references.citation: J Neurosci. 1992 Dec;12(12):4701-11
references.pmid: 1361197
references.citation: Curr Biol. 2011 Dec 6;21(23):1988-93
references.pmid: 22100063
references.citation: Magn Reson Imaging. 2006 May;24(4):335-42
references.pmid: 16677938
references.citation: Acta Anaesthesiol Scand. 1997 Nov;41(10):1335-40
references.pmid: 9422302
references.citation: Biomed Microdevices. 2006 Mar;8(1):81-5
references.pmid: 16491335
references.citation: Neuroreport. 1994 Jan 31;5(5):577-80
references.pmid: 8025247
references.citation: Brain. 2002 Oct;125(Pt 10):2308-19
references.pmid: 12244087
references.citation: Proc Natl Acad Sci U S A. 2012 Dec 4;109(49):E3377-86
references.pmid: 23129622
references.citation: J Neurophysiol. 2008 Dec;100(6):3328-42
references.pmid: 18799601
references.citation: Front Psychol. 2011 Dec 16;2:366
references.pmid: 22203808
references.citation: Anesthesiology. 2003 Nov;99(5):1125-31
references.pmid: 14576549
references.citation: Exp Brain Res. 2009 Feb;192(4):657-67
references.pmid: 18830586
references.citation: Anesthesiology. 2005 May;102(5):937-47
references.pmid: 15851880
references.citation: Nature. 2001 Jul 12;412(6843):150-7
references.pmid: 11449264
references.citation: Nature. 2002 Jun 20;417(6891):854-8
references.pmid: 12075353
references.citation: Annu Rev Psychol. 1997;48:649-84
references.pmid: 9046571
references.citation: Front Integr Neurosci. 2011 May 02;5:8
references.pmid: 21577250
references.citation: Anesth Analg. 2006 Jun;102(6):1709-14
references.pmid: 16717314
references.citation: Proc Natl Acad Sci U S A. 2013 Mar 19;110(12):E1142-51
references.pmid: 23487781
references.citation: Annu Rev Neurosci. 2011;34:601-28
references.pmid: 21513454
references.citation: J Neurosci. 2002 Jan 15;22(2):RC200
references.pmid: 11784812
references.citation: Nat Neurosci. 2014 May;17(5):652-60
references.pmid: 24686784
references.citation: Neuroimage. 2006 Dec;33(4):1082-92
references.pmid: 17035045
references.citation: J Neuropathol Exp Neurol. 2012 Jun;71(6):531-46
references.pmid: 22592840
references.citation: Neuroscience. 1987 Dec;23(3):809-21
references.pmid: 2893995
references.citation: J Neurosci. 2012 Apr 4;32(14):4935-43
references.pmid: 22492049
references.citation: Prog Brain Res. 2002;136:359-72
references.pmid: 12143394
references.citation: J Cogn Neurosci. 2000 Jan;12(1):1-47
references.pmid: 10769304
references.citation: J Neurophysiol. 1999 Oct;82(4):2015-9
references.pmid: 10515993
references.citation: Anesthesiology. 2012 May;116(5):998-1005
references.pmid: 22446983
references.citation: Nature. 2000 Nov 16;408(6810):357-61
references.pmid: 11099042
references.citation: Brain. 1978 Mar;101(1):83-117
references.pmid: 638728
references.citation: Anesthesiology. 2000 Mar;92(3):715-26
references.pmid: 10719951
references.citation: Prog Brain Res. 2004;145:157-69
references.pmid: 14650914
references.citation: Anesthesiology. 2011 Oct;115(4):733-42
references.pmid: 21804378
references.citation: Anesthesiology. 1978 Jan;48(1):4-10
references.pmid: 619706
references.citation: Brain Connect. 2014 Feb;4(1):1-14
references.pmid: 24147633
references.citation: J Comp Neurol. 1985 Dec 1;242(1):56-92
references.pmid: 2416786