title: A BOLD Perspective on Age-Related Neurometabolic-Flow Coupling and Neural Efficiency Changes in Human Visual Cortex.
abstract: Age-related performance declines in visual tasks have been attributed to reductions in processing efficiency. The neural basis of these declines has been explored by comparing the blood-oxygen-level-dependent (BOLD) index of neural activity in older and younger adults during visual task performance. However, neural activity is one of many factors that change with age and lead to BOLD signal differences. We investigated the origin of age-related BOLD changes by comparing blood flow and oxygen metabolic constituents of BOLD signal. Subjects periodically viewed flickering annuli and pressed a button when detecting luminance changes in a central fixation cross. Using magnetic resonance dual-echo arterial spin labeling and CO2 ingestion, we observed age-equivalent (i.e., similar in older and younger groups) fractional cerebral blood flow (ΔCBF) in the presence of age-related increases in fractional cerebral metabolic rate of oxygen (ΔCMRO2). Reductions in ΔCBF responsiveness to increased ΔCMRO2 in elderly led to paradoxical age-related BOLD decreases. Age-related ΔCBF/ΔCMRO2 ratio decreases were associated with reaction times, suggesting that age-related slowing resulted from less efficient neural activity. We hypothesized that reduced vascular responsiveness to neural metabolic demand would lead to a reduction in ΔCBF/ΔCMRO2. A simulation of BOLD relative to ΔCMRO2 for lower and higher neurometabolic-flow coupling ratios (approximating those for old and young, respectively) indicated less BOLD signal change in old than young in relatively lower CMRO2 ranges, as well as greater BOLD signal change in young compared to old in relatively higher CMRO2 ranges. These results suggest that age-comparative studies relying on BOLD signal might be misinterpreted, as age-related BOLD changes do not merely reflect neural activity changes. Age-related declines in neurometabolic-flow coupling might lead to neural efficiency reductions that can adversely affect visual task performance.
authors: School of Behavioral and Brain Sciences, University of Texas at Dallas Richardson, TX, USA ; Department of Psychiatry, University of Texas Southwestern Medical Center Dallas, TX, USA.
authors: Joanna Lynn
authors: JL
authors: Hutchison
authors: Ehsan
authors: E
authors: Shokri-Kojori
authors: Hanzhang
authors: H
authors: Lu
authors: Bart
authors: B
authors: Rypma
keywords: BOLD; CBF; CMRO2; aging; fMRI; hypercapnia; neural efficiency; neurometabolic-flow coupling
references: Neuroimage. 2004;23 Suppl 1:S220-33
references: 15501093
references: J Cell Biol. 1963 Mar;16:521-5
references: 13952284
references: J Neurosurg. 2010 May;112(5):1080-94
references: 19852540
references: Can J Exp Psychol. 2002 Sep;56(3):208-20
references: 12271751
references: Magn Reson Med. 1990 Oct;16(1):9-18
references: 2255240
references: Cereb Cortex. 2011 Jun;21(6):1426-34
references: 21051551
references: J Comput Assist Tomogr. 1998 Jul-Aug;22(4):514-7
references: 9676437
references: Proc Natl Acad Sci U S A. 1998 Feb 17;95(4):1834-9
references: 9465103
references: Proc Natl Acad Sci U S A. 1999 Aug 3;96(16):9403-8
references: 10430955
references: Nat Neurosci. 2000 May;3(5):509-15
references: 10769393
references: J Psychiatr Res. 1975 Nov;12(3):189-98
references: 1202204
references: Neuroimage. 2012 Aug 15;62(2):930-7
references: 22369993
references: Hum Brain Mapp. 2006 May;27(5):351-9
references: 16583364
references: Neuroimage. 2004 Jun;22(2):771-8
references: 15193606
references: Neuroimage. 2010 Nov 1;53(2):383-91
references: 20624474
references: NMR Biomed. 2009 Dec;22(10):1054-62
references: 19598180
references: Magn Reson Med. 2005 Apr;53(4):808-16
references: 15799063
references: Neurobiol Aging. 2012 Feb;33(2):433.e21-31
references: 21402431
references: Cereb Cortex. 2013 Oct;23(10):2337-46
references: 22879349
references: Magn Reson Imaging. 2000 Apr;18(3):227-35
references: 10745130
references: Neuroimage. 2007 Jun;36(2):277-81
references: 17223362
references: J Hirnforsch. 1984;25(4):353-74
references: 6481152
references: Neuroimage. 2007 Jul 15;36(4):1110-22
references: 17524665
references: Magn Reson Med. 2010 Mar;63(3):765-71
references: 20187183
references: Proc Natl Acad Sci U S A. 1992 Jul 1;89(13):5951-5
references: 1631079
references: Psychol Aging. 2001 Jun;16(2):281-92
references: 11405316
references: Stroke. 2007 May;38(5):1578-84
references: 17413048
references: Neuroimage. 2007 Jun;36(2):269-76
references: 17113313
references: J Cereb Blood Flow Metab. 2012 Oct;32(10):1909-18
references: 22739621
references: Psychol Aging. 2009 Dec;24(4):792-808
references: 20025396
references: Neuroimage. 2011 Mar 15;55(2):468-78
references: 21167947
references: Neuroimage. 2008 Feb 15;39(4):1510-21
references: 18164629
references: Nat Rev Neurosci. 2004 May;5(5):347-60
references: 15100718
references: J Comp Neurol. 1993 Aug 22;334(4):631-43
references: 8408770
references: Anat Rec. 1989 Mar;223(3):329-41
references: 2923284
references: J Neurophysiol. 1994 Jul;72(1):402-20
references: 7965023
references: Neuroimage. 2001 Jul;14(1 Pt 1):140-8
references: 11525323
references: Br J Ophthalmol. 1987 Oct;71(10):791-6
references: 3676151
references: J Vis. 2012 Aug 17;12(8):11
references: 22904356
references: Brain Res. 2010 Feb 22;1315:119-27
references: 20026320
references: Front Neuroenergetics. 2010 Jun 23;2:9
references: 20616884
references: J Cereb Blood Flow Metab. 1996 May;16(3):385-98
references: 8621743
references: Brain. 2005 Sep;128(Pt 9):1964-83
references: 16049041
references: Front Syst Neurosci. 2012 Nov 30;6:77
references: 23226117
references: J Cereb Blood Flow Metab. 2000 Apr;20(4):747-54
references: 10779019
references: J Appl Physiol (1985). 1995 Jul;79(1):136-40
references: 7559210
references: Invest Ophthalmol Vis Sci. 2012 May 31;53(6):3226-33
references: 22531695
references: Cogn Neurosci. 2011 Jan 1;2(1):1-10
references: 22792129
references: J Am Med Inform Assoc. 2001 Sep-Oct;8(5):443-59
references: 11522765
references: Magn Reson Med. 2008 Dec;60(6):1488-97
references: 19025913
references: J Neurosci. 2011 Mar 23;31(12):4496-503
references: 21430150
references: J Cereb Blood Flow Metab. 2006 Feb;26(2):263-73
references: 16079793
references: Hum Brain Mapp. 2013 May;34(5):1053-69
references: 23015481
references: J Neurosci. 1994 Mar;14(3 Pt 2):1450-62
references: 8126548
references: Vision Res. 2013 Jan 25;77:32-40
references: 23206550
references: Neuroimage. 2006 Nov 15;33(3):969-79
references: 17010646
references: Comput Biomed Res. 1996 Jun;29(3):162-73
references: 8812068
references: Nat Rev Neurosci. 2003 Nov;4(11):863-72
references: 14595398
references: Neuroimage. 2006 Mar;30(1):102-9
references: 16243545
references: Neuropsychol Rev. 2007 Jun;17(2):107-25
references: 17468956
references: Neuroimage. 1999 Jul;10(1):6-14
references: 10385577
references: Psychol Med. 2003 Aug;33(6):1039-50
references: 12946088
references: J Cereb Blood Flow Metab. 2007 Apr;27(4):690-6
references: 17033688
references: Cortex. 2005 Aug;41(4):582-94
references: 16042034
references: Neurobiol Aging. 2013 May;34(5):1469-85
references: 23218565
references: J Cereb Blood Flow Metab. 2004 Jul;24(7):764-70
references: 15241184
references: Neurology. 1997 Jan;48(1):173-6
references: 9008514
references: Neuroimage. 2012 Apr 2;60(2):1212-25
references: 22227047
references: Neuroimage. 2012 Jan 16;59(2):1143-51
references: 21843646
references: Neuroimage. 2007 Aug 15;37(2):430-9
references: 17590353
references: Hum Brain Mapp. 2009 Apr;30(4):1120-32
references: 18465743
references: Magn Reson Med. 1999 Nov;42(5):849-63
references: 10542343
references: Nat Rev Neurosci. 2004 Feb;5(2):87-96
references: 14735112
references: Magn Reson Med. 2000 Oct;44(4):511-5
references: 11025504
references: Stroke. 1974 Sep-Oct;5(5):630-9
references: 4472361
references: J Cereb Blood Flow Metab. 2000 May;20(5):847-60
references: 10826536
references: J Gerontol B Psychol Sci Soc Sci. 2013 Jul;68(4):522-8
references: 23009956
references: Radiology. 1992 Mar;182(3):769-75
references: 1535892
references: Intelligence. 2009 Mar 1;37(2):207-222
references: 20161012
references: Stroke. 2004 Nov;35(11 Suppl 1):2635-41
references: 15388903
references: Psychol Aging. 1989 Mar;4(1):98-105
references: 2803617
references: Dev Psychol. 2004 Jul;40(4):545-58
references: 15238042
references: Neuroimage. 2001 Jan;13(1):161-75
references: 11133319
references: Neuroimage. 2004 Feb;21(2):507-15
references: 14980553
references: Hum Factors. 1981 Feb;23(1):97-109
references: 7228049
references: Ann N Y Acad Sci. 1996 Jan 17;777:14-21
references: 8624077
references: J Cogn Neurosci. 2000;12 Suppl 2:24-34
references: 11506645
references: J Neurosci. 2010 Apr 7;30(14):4914-21
references: 20371811
references: Neuroimage. 2007 Jan 1;34(1):35-43
references: 17029987
references: Neuroimage. 2007 Mar;35(1):175-84
references: 17208013
references: Neuroimage. 2007 Sep 1;37(3):808-20
references: 17632016
references: Proc Natl Acad Sci U S A. 2001 Jun 5;98(12):6859-64
references: 11381119
references: Brain. 1990 Feb;113 ( Pt 1):27-47
references: 2302536