title: An age-related shift of resting-state functional connectivity of the subthalamic nucleus: a potential mechanism for compensating motor performance decline in older adults.
abstract: Healthy aging is associated with decline in basic motor functioning and higher motor control. Here, we investigated age-related differences in the brain-wide functional connectivity (FC) pattern of the subthalamic nucleus (STN), which plays an important role in motor response control. As earlier studies revealed functional coupling between STN and basal ganglia, which both are known to influence the conservativeness of motor responses on a superordinate level, we tested the hypothesis that STN FC with the striatum becomes dysbalanced with age. To this end, we performed a seed-based resting-state analysis of fMRI data from 361 healthy adults (mean age: 41.8, age range: 18-85) using bilateral STN as the seed region of interest. Age was included as a covariate to identify regions showing age-related changes of FC with the STN seed. The analysis revealed positive FC of the STN with several previously described subcortical and cortical regions like the anterior cingulate and sensorimotor cortex, as well as not-yet reported regions including central and posterior insula. With increasing age, we observed reduced positive FC with caudate nucleus, thalamus, and insula as well as increased positive FC with sensorimotor cortex and putamen. Furthermore, an age-related reduction of negative FC was found with precuneus and posterior cingulate cortex. We suggest that this reduced de-coupling of brain areas involved in self-relevant but motor-unrelated cognitive processing (i.e. precuneus and posterior cingulate cortex) from the STN motor network may represent a potential mechanism behind the age-dependent decline in motor performance. At the same time, older adults appear to compensate for this decline by releasing superordinate motor control areas, in particular caudate nucleus and insula, from STN interference while increasing STN-mediated response control over lower level motor areas like sensorimotor cortex and putamen.
authors.affiliation: Department of Diagnostic and Interventional Radiology, Medical Faculty, Heinrich Heine University Düsseldorf Düsseldorf, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Mathys
authors.affiliation: Institute of Clinical Neuroscience and Medical Psychology, Medical Faculty, Heinrich Heine University Düsseldorf Düsseldorf, Germany ; Institute of Neuroscience and Medicine (INM-1, INM-3), Research Centre Jülich Jülich, Germany.
authors.forename: Felix
authors.initials: F
authors.lastname: Hoffstaedter
authors.affiliation: Department of Diagnostic and Interventional Radiology, Medical Faculty, Heinrich Heine University Düsseldorf Düsseldorf, Germany ; Institute of Neuroscience and Medicine (INM-1, INM-3), Research Centre Jülich Jülich, Germany.
authors.forename: Julian
authors.initials: J
authors.lastname: Caspers
authors.affiliation: Institute of Neuroscience and Medicine (INM-1, INM-3), Research Centre Jülich Jülich, Germany.
authors.forename: Svenja
authors.initials: S
authors.lastname: Caspers
authors.affiliation: Institute of Clinical Neuroscience and Medical Psychology, Medical Faculty, Heinrich Heine University Düsseldorf Düsseldorf, Germany ; Center for Movement Disorders and Neuromodulation, Department of Neurology, Medical Faculty, Heinrich Heine University Düsseldorf Düsseldorf, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Südmeyer
authors.affiliation: Institute of Neuroscience and Medicine (INM-1, INM-3), Research Centre Jülich Jülich, Germany ; Neuromodulation and Neurorehabilitation Group, Max Planck Institute for Neurological Research Cologne, Germany ; Department of Neurology, University of Cologne Cologne, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Grefkes
authors.affiliation: Institute of Clinical Neuroscience and Medical Psychology, Medical Faculty, Heinrich Heine University Düsseldorf Düsseldorf, Germany ; Institute of Neuroscience and Medicine (INM-1, INM-3), Research Centre Jülich Jülich, Germany.
authors.forename: Simon B
authors.initials: SB
authors.lastname: Eickhoff
authors.affiliation: Institute of Clinical Neuroscience and Medical Psychology, Medical Faculty, Heinrich Heine University Düsseldorf Düsseldorf, Germany ; Institute of Neuroscience and Medicine (INM-1, INM-3), Research Centre Jülich Jülich, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Langner
keywords: age-related changes; functional connectivity; healthy aging; resting-state fMRI; subthalamic nucleus
references.citation: Neuroimage. 2013 Dec;83:45-57
references.pmid: 23792981
references.citation: J Neurol. 2012 Sep;259(9):1944-50
references.pmid: 22349870
references.citation: Neuroimage. 2009 May 15;46(1):39-46
references.pmid: 19457380
references.citation: PLoS One. 2012;7(2):e30920
references.pmid: 22319593
references.citation: Neuroimage. 2012 May 1;60(4):2389-98
references.pmid: 22387170
references.citation: Nature. 1996 Aug 29;382(6594):805-7
references.pmid: 8752272
references.citation: Brain Res. 2006 Mar 3;1076(1):171-6
references.pmid: 16476418
references.citation: Exp Brain Res. 2009 Mar;193(3):445-54
references.pmid: 19030850
references.citation: Lancet Neurol. 2006 Jun;5(6):525-35
references.pmid: 16713924
references.citation: Cereb Cortex. 2006 Feb;16(2):254-67
references.pmid: 15888607
references.citation: J Neurosci. 2005 Jul 20;25(29):6787-96
references.pmid: 16033888
references.citation: Brain Struct Funct. 2008 Aug;212(6):481-95
references.pmid: 18651173
references.citation: Neuroimage. 2007 Aug 15;37(2):579-88
references.pmid: 17604651
references.citation: Brain Struct Funct. 2015;220(3):1739-57
references.pmid: 24718622
references.citation: J Neurosci. 2013 Mar 13;33(11):4896-900
references.pmid: 23486960
references.citation: Science. 2007 Nov 23;318(5854):1309-12
references.pmid: 17962524
references.citation: Exp Neurol. 2013 Sep;247:178-81
references.pmid: 23664959
references.citation: Rev Neurosci. 2013;24(2):125-38
references.pmid: 23327862
references.citation: Am J Psychiatry. 1999 Jun;156(6):891-6
references.pmid: 10360128
references.citation: Prog Neurobiol. 2005 Aug;76(6):393-413
references.pmid: 16249050
references.citation: Neurobiol Aging. 2008 Sep;29(9):1434-46
references.pmid: 17566608
references.citation: PLoS One. 2012;7(6):e39061
references.pmid: 22768059
references.citation: Neuroimage. 2013 Feb 15;67:283-97
references.pmid: 23194819
references.citation: Nat Neurosci. 2003 Jul;6(7):750-7
references.pmid: 12808459
references.citation: J Neurosci. 2011 Oct 12;31(41):14688-92
references.pmid: 21994385
references.citation: Neuroimage. 2012 Jul 16;61(4):1129-42
references.pmid: 22440648
references.citation: Adv Anat Embryol Cell Biol. 2004;174:I-VIII, 1-89
references.pmid: 14750415
references.citation: Proc Natl Acad Sci U S A. 2010 Mar 9;107(10):4734-9
references.pmid: 20176931
references.citation: Anat Embryol (Berl). 2005 Dec;210(5-6):343-52
references.pmid: 16208455
references.citation: Neuroimage. 1999 Jul;10(1):63-83
references.pmid: 10385582
references.citation: Neuroimage. 2007 Sep 1;37(3):694-705
references.pmid: 17644361
references.citation: Neurosci Res. 2002 Jun;43(2):111-7
references.pmid: 12067746
references.citation: Neuroimage. 2001 Sep;14(3):617-31
references.pmid: 11506535
references.citation: Annu Rev Neurosci. 2002;25:563-93
references.pmid: 12052921
references.citation: Cereb Cortex. 2008 Apr;18(4):846-67
references.pmid: 17644831
references.citation: J Comp Neurol. 1999 Sep 20;412(2):319-41
references.pmid: 10441759
references.citation: Brain Struct Funct. 2010 Jun;214(5-6):519-34
references.pmid: 20512376
references.citation: Neuroimage. 2006 Nov 1;33(2):430-48
references.pmid: 16949304
references.citation: Exp Neurol. 2009 Feb;215(2):380-7
references.pmid: 19070616
references.citation: Hum Brain Mapp. 2012 Feb;33(2):398-418
references.pmid: 21438078
references.citation: Hum Brain Mapp. 2014 Jun;35(6):2741-53
references.pmid: 24115159
references.citation: J Neurophysiol. 1997 Mar;77(3):1313-24
references.pmid: 9084599
references.citation: Psychol Aging. 2009 Jun;24(2):438-449
references.pmid: 19485660
references.citation: Brain. 2006 Mar;129(Pt 3):564-83
references.pmid: 16399806
references.citation: J Neurophysiol. 2008 Oct;100(4):1800-12
references.pmid: 18684903
references.citation: Cereb Cortex. 2009 Mar;19(3):640-57
references.pmid: 18653667
references.citation: Hum Brain Mapp. 2014 Jul;35(7):3499-516
references.pmid: 25050431
references.citation: Prog Neurobiol. 2008 Nov;86(3):141-55
references.pmid: 18824075
references.citation: Neuroimage. 2011 Apr 15;55(4):1728-38
references.pmid: 21255661
references.citation: Brain. 2004 Jan;127(Pt 1):4-20
references.pmid: 14607789
references.citation: Hum Brain Mapp. 2007 Oct;28(10):1045-59
references.pmid: 17266106
references.citation: Cereb Cortex. 2013 Mar;23(3):520-30
references.pmid: 22414772
references.citation: Brain Res. 2007 Jun 2;1151:62-73
references.pmid: 17448452
references.citation: Trends Neurosci. 1990 Jul;13(7):266-71
references.pmid: 1695401
references.citation: Brain Struct Funct. 2015 Mar;220(2):999-1012
references.pmid: 24399178
references.citation: Neuroimage. 2007 Jul 1;36(3):511-21
references.pmid: 17499520
references.citation: Magn Reson Med. 1995 Oct;34(4):537-41
references.pmid: 8524021
references.citation: J Neurosci. 2012 Sep 26;32(39):13396-401
references.pmid: 23015430
references.citation: Hum Brain Mapp. 2012 Nov;33(11):2627-37
references.pmid: 21932264
references.citation: Behav Brain Res. 2012 Feb 1;227(1):241-51
references.pmid: 22074898
references.citation: Curr Opin Neurobiol. 2005 Dec;15(6):638-44
references.pmid: 16271465
references.citation: Nat Rev Neurosci. 2009 Jan;10(1):59-70
references.pmid: 19096369
references.citation: Cereb Cortex. 2006 Feb;16(2):268-79
references.pmid: 15888606
references.citation: Pharmacol Res. 2014 Sep;87:8-17
references.pmid: 24928737
references.citation: Neuroimage. 2011 Aug 1;57(3):1221-33
references.pmid: 21609772
references.citation: Neuroimage. 2000 Jun;11(6 Pt 1):684-96
references.pmid: 10860796
references.citation: Brain. 2005 Oct;128(Pt 10):2372-82
references.pmid: 16123144
references.citation: Neuroimage. 2006 May 15;31(1):440-57
references.pmid: 16466680
references.citation: Eur J Nucl Med Mol Imaging. 2010 Aug;37(8):1512-20
references.pmid: 20349231
references.citation: Neuroimage. 2010 Aug 15;52(2):643-57
references.pmid: 20434565
references.citation: Exp Gerontol. 2011 Jun;46(6):453-61
references.pmid: 21296649
references.citation: Nat Neurosci. 2006 Apr;9(4):562-8
references.pmid: 16501567
references.citation: J Neurosci. 2009 Jan 28;29(4):1175-90
references.pmid: 19176826
references.citation: Brain Res Bull. 2006 Oct 16;70(4-6):337-46
references.pmid: 17027769
references.citation: Hum Brain Mapp. 2012 Dec;33(12):2831-42
references.pmid: 21932259
references.citation: Brain Res. 2000 Oct 6;879(1-2):204-15
references.pmid: 11011024
references.citation: Hum Brain Mapp. 2012 Apr;33(4):895-908
references.pmid: 21432946
references.citation: Brain. 1995 Feb;118 ( Pt 1):279-306
references.pmid: 7895011
references.citation: Neuroimage. 2013 Jan 1;64:240-56
references.pmid: 22926292
references.citation: Nat Rev Neurosci. 2010 Feb;11(2):139-45
references.pmid: 20046193
references.citation: Neuroimage. 2004 May;22(1):42-56
references.pmid: 15109996
references.citation: Lancet. 1998 Jun 13;351(9118):1801-4
references.pmid: 9635969
references.citation: Cereb Cortex. 2010 Jun;20(6):1448-61
references.pmid: 19822572
references.citation: Cereb Cortex. 2008 Sep;18(9):2141-57
references.pmid: 18245042
references.citation: Neurosci Biobehav Rev. 2010 Apr;34(5):721-33
references.pmid: 19850077
references.citation: Behav Neurol. 2000;12(4):191-200
references.pmid: 11568431
references.citation: Parkinsonism Relat Disord. 2014 Jan;20(1):99-105
references.pmid: 24183678
references.citation: Cereb Cortex. 2011 Dec;21(12):2850-62
references.pmid: 21527785
references.citation: Neuroimage. 2005 Jul 1;26(3):839-51
references.pmid: 15955494
references.citation: Nat Rev Neurosci. 2007 Sep;8(9):700-11
references.pmid: 17704812
references.citation: J Neurosci. 2007 Apr 4;27(14):3743-52
references.pmid: 17409238
references.citation: Proc Natl Acad Sci U S A. 2003 Jan 7;100(1):253-8
references.pmid: 12506194
references.citation: J Neural Transm (Vienna). 2015 Aug;122 Suppl 1:S47-54
references.pmid: 24337666
references.citation: Neural Netw. 2006 Oct;19(8):1120-36
references.pmid: 16945502
references.citation: Brain. 2014 Jan;137(Pt 1):12-32
references.pmid: 23869106
references.citation: Lancet. 1995 Jan 14;345(8942):91-5
references.pmid: 7815888
references.citation: Neuroimage. 2012 Mar;60(1):83-94
references.pmid: 22173294
references.citation: Neuroimage. 2000 Jan;11(1):66-84
references.pmid: 10686118
references.citation: Cereb Cortex. 2013 Nov;23(11):2677-89
references.pmid: 22918987