title: Frontostriatal and mediotemporal lobe contributions to implicit higher-order spatial sequence learning declines in aging and Parkinson's disease.
abstract: Sequence learning depends on the striatal system, but recent findings also implicate the mediotemporal lobe (MTL) system. Schendan, Searl, Melrose, and Stern (2003) found higher-order associative, learning-related activation in the striatum, dorsolateral prefrontal cortex, and the MTL during the early acquisition phase of both implicit and explicit variants of a serial response time task. This functional MRI (fMRI) study capitalized on this task to determine how changes in MTL function observed in aging and compromised frontostriatal function characteristic of patients with Parkinson's disease (PD) impacts sequence learning and memory under implicit instructions. Brain activity was compared between "sequence" and "random" conditions in 12 nondemented patients with PD and education- and gender-matched healthy control participants of whom 12 were age matched (MC) and 14 were younger (YC). Behaviorally, sequence-specific learning of higher-order associations was reduced with aging and changed further with PD and resulted primarily in implicit knowledge in the older participants. fMRI revealed reduced intensity and extent of sequence learning-related activation in older relative to younger people in frontostriatal circuits and the MTL. This was because signal was greater for the sequence than random condition in younger people, whereas older people, especially those with PD, showed the opposite pattern. Both older groups also showed increased activation to the task itself relative to baseline fixation. In addition, right MTL showed hypoactivation and left MTL hyperactivation in PD relative to the MC group. The results suggest changes in frontostriatal and MTL activity occur during aging that affect task-related activity and the initial acquisition phase of implicit higher-order sequence learning. In addition, the results suggest that Parkinson's disease adversely affects processes in the MTL including sequence learning and memory.
authors.affiliation: School of Psychology, Centre for Brain, Cognition and Behaviour, Cognition Institute, Plymouth University, Drake Circus, Portland Square A208, Plymouth, Devon PL4 8AA, United Kingdom. Haline.Schendan@plymouth.ac.uk
authors.forename: Haline E
authors.initials: HE
authors.lastname: Schendan
authors.forename: Sule
authors.initials: S
authors.lastname: Tinaz
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Maher
authors.forename: Chantal E
authors.initials: CE
authors.lastname: Stern
mesh_terms: D000328:Adult; D000368:Aged; D000375:Aging / Q000502:physiology* / Q000523:psychology; D003342:Corpus Striatum / Q000503:physiopathology*; D005260:Female; D005625:Frontal Lobe / Q000503:physiopathology*; D006801:Humans; D007858:Learning / Q000502:physiology*; D008279:Magnetic Resonance Imaging; D008297:Male; D008568:Memory / Q000502:physiology; D008875:Middle Aged; D009434:Neural Pathways / Q000503:physiopathology; D009483:Neuropsychological Tests; D010300:Parkinson Disease / Q000503:physiopathology* / Q000523:psychology; D011930:Reaction Time / Q000502:physiology; D013702:Temporal Lobe / Q000503:physiopathology*
references.citation: Behav Brain Res. 2009 Apr 12;199(1):53-60
references.pmid: 19059285
references.citation: Neuron. 2012 Jun 7;74(5):936-46
references.pmid: 22681696
references.citation: Proc Natl Acad Sci U S A. 2008 Feb 12;105(6):2181-6
references.pmid: 18238903
references.citation: Brain Res. 2007 May 25;1147:265-71
references.pmid: 17368575
references.citation: Hum Brain Mapp. 1997;5(2):124-32
references.pmid: 10096417
references.citation: Brain. 1997 Jan;120 ( Pt 1):123-40
references.pmid: 9055803
references.citation: Psychol Sci. 2010 Mar;21(3):399-405
references.pmid: 20424077
references.citation: Nat Rev Neurosci. 2002 Mar;3(3):243-9
references.pmid: 11994756
references.citation: Psychol Aging. 1997 Dec;12(4):634-56
references.pmid: 9416632
references.citation: J Cogn Neurosci. 1997 Jul;9(4):522-33
references.pmid: 23968215
references.citation: J Psychiatr Res. 1975 Nov;12(3):189-98
references.pmid: 1202204
references.citation: Cognition. 2012 Jun;123(3):380-91
references.pmid: 22425486
references.citation: Neuropsychologia. 1995 May;33(5):577-93
references.pmid: 7637854
references.citation: Eur J Neurosci. 1996 Apr;8(4):637-48
references.pmid: 9081615
references.citation: J Cogn Neurosci. 2002 Nov 15;14(8):1200-14
references.pmid: 12495526
references.citation: Behav Neurosci. 2004 Apr;118(2):438-42
references.pmid: 15113271
references.citation: Brain Cogn. 2001 Apr;45(3):378-91
references.pmid: 11305880
references.citation: Neurology. 1967 May;17(5):427-42
references.pmid: 6067254
references.citation: Psychol Aging. 2010 Dec;25(4):940-8
references.pmid: 20822256
references.citation: Neuroimage. 2010 Apr 15;50(3):1303-12
references.pmid: 20079855
references.citation: Arch Sex Behav. 2002 Feb;31(1):145-52
references.pmid: 11910787
references.citation: Behav Neurosci. 2009 Feb;123(1):125-36
references.pmid: 19170437
references.citation: Cereb Cortex. 2009 Mar;19(3):733-44
references.pmid: 18653664
references.citation: Hum Brain Mapp. 2000 Aug;10(4):179-94
references.pmid: 10949055
references.citation: Annu Rev Neurosci. 2002;25:563-93
references.pmid: 12052921
references.citation: Proc Natl Acad Sci U S A. 1998 Jan 20;95(2):747-50
references.pmid: 9435264
references.citation: Psychol Aging. 2000 Sep;15(3):527-41
references.pmid: 11014715
references.citation: J Neurol. 1997 Jan;244(1):2-8
references.pmid: 9007738
references.citation: Nature. 2001 Nov 29;414(6863):546-50
references.pmid: 11734855
references.citation: J Cogn Neurosci. 2000 Jan;12(1):197-206
references.pmid: 10769316
references.citation: J Clin Exp Neuropsychol. 1998 Jun;20(3):413-8
references.pmid: 9845167
references.citation: Neuropsychologia. 1989;27(3):341-52
references.pmid: 2710324
references.citation: Learn Mem. 1994 Nov-Dec;1(4):217-29
references.pmid: 10467599
references.citation: Neurobiol Aging. 2008 Mar;29(3):397-407
references.pmid: 17157417
references.citation: Behav Neurosci. 1996 Oct;110(5):861-71
references.pmid: 8918990
references.citation: Exp Brain Res. 2006 Oct;175(1):153-64
references.pmid: 16788812
references.citation: J Neurosci. 2007 Sep 19;27(38):10073-5
references.pmid: 17881512
references.citation: Brain Res Cogn Brain Res. 2000 Sep;10(1-2):197-206
references.pmid: 10978709
references.citation: J Clin Exp Neuropsychol. 1991 Nov;13(6):933-49
references.pmid: 1779032
references.citation: Brain Cogn. 2000 Mar;42(2):183-200
references.pmid: 10744919
references.citation: Neurobiol Aging. 2003 Nov;24(7):1013-9
references.pmid: 12928061
references.citation: Brain Res Cogn Brain Res. 2003 Apr;16(2):273-84
references.pmid: 12668237
references.citation: Neuropsychology. 2004 Oct;18(4):679-91
references.pmid: 15506836
references.citation: Psychol Aging. 2005 Mar;20(1):33-46
references.pmid: 15769212
references.citation: Psychiatr Clin North Am. 1997 Dec;20(4):741-68
references.pmid: 9443348
references.citation: Brain Cogn. 2008 Nov;68(2):134-43
references.pmid: 18456379
references.citation: Psychol Rev. 1996 Jul;103(3):403-28
references.pmid: 8759042
references.citation: Neurology. 1987 May;37(5):789-94
references.pmid: 3574678
references.citation: Psychol Aging. 2002 Jun;17(2):351-5
references.pmid: 12061417
references.citation: Psychon Bull Rev. 2004 Dec;11(6):1067-73
references.pmid: 15875977
references.citation: Science. 1997 May 23;276(5316):1272-5
references.pmid: 9157889
references.citation: Neurobiol Aging. 2011 Dec;32(12):2318.e17-30
references.pmid: 20471139
references.citation: Annu Rev Neurosci. 2007;30:99-122
references.pmid: 17417938
references.citation: Neural Netw. 2005 Nov;18(9):1172-90
references.pmid: 16263240
references.citation: J Exp Psychol Gen. 2001 Dec;130(4):746-63
references.pmid: 11757878
references.citation: Brain. 2001 May;124(Pt 5):1020-32
references.pmid: 11335704
references.citation: Neuropsychologia. 2006;44(3):339-49
references.pmid: 16061263
references.citation: J Cogn Neurosci. 1998 Mar;10(2):248-63
references.pmid: 9555110
references.citation: J Neurophysiol. 2009 Oct;102(4):2462-76
references.pmid: 19692514
references.citation: Neurology. 1987 May;37(5):784-8
references.pmid: 3574677
references.citation: J Neurophysiol. 2002 Sep;88(3):1451-60
references.pmid: 12205165
references.citation: J Exp Psychol Learn Mem Cogn. 1999 Nov;25(6):1435-51
references.pmid: 10605830
references.citation: J Exp Psychol Learn Mem Cogn. 1989 Nov;15(6):1070-82
references.pmid: 2530307
references.citation: Neuron. 2003 Mar 27;37(6):1013-25
references.pmid: 12670429
references.citation: Mem Cognit. 1996 Jul;24(4):403-16
references.pmid: 8757490
references.citation: Cereb Cortex. 2011 Sep;21(9):2166-76
references.pmid: 21282317
references.citation: Brain. 2008 Nov;131(Pt 11):2882-93
references.pmid: 18957454
references.citation: J Cogn Neurosci. 1995 Fall;7(4):497-510
references.pmid: 23961907
references.citation: Neuron. 2008 Apr 24;58(2):261-72
references.pmid: 18439410