title: Functional consequences of neurite orientation dispersion and density in humans across the adult lifespan.
abstract: As humans age, a characteristic pattern of widespread neocortical dendritic disruption coupled with compensatory effects in hippocampus and other subcortical structures is shown in postmortem investigations. It is now possible to address age-related effects on gray matter (GM) neuritic organization and density in humans using multishell diffusion-weighted MRI and the neurite-orientation dispersion and density imaging (NODDI) model. In 45 healthy individuals across the adult lifespan (21-84 years), we used a multishell diffusion imaging and the NODDI model to assess the intraneurite volume fraction and neurite orientation-dispersion index (ODI) in GM tissues. We also determined the functional correlates of variations in GM microstructure by obtaining resting-state fMRI and behavioral data. We found a significant age-related deficit in neocortical ODI (most prominently in frontoparietal regions), whereas increased ODI was observed in hippocampus and cerebellum with advancing age. Neocortical ODI outperformed cortical thickness and white matter fractional anisotropy for the prediction of chronological age in the same individuals. Higher GM ODI sampled from resting-state networks with known age-related susceptibility (default mode and visual association networks) was associated with increased functional connectivity of these networks, whereas the task-positive networks tended to show no association or even decreased connectivity. Frontal pole ODI mediated the negative relationship of age with executive function, whereas hippocampal ODI mediated the positive relationship of age with executive function. Our in vivo findings align very closely with the postmortem data and provide evidence for vulnerability and compensatory neural mechanisms of aging in GM microstructure that have functional and cognitive impact in vivo.
authors: Kimel Family Translational Imaging-Genetics Laboratory, Research Imaging Centre, Campbell Family Mental Health Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada M5T 1R8, Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada M5T 1R8.
authors: Arash
authors: http://orcid.org/0000-0001-6983-0641
authors: A
authors: Nazeri
authors: Kimel Family Translational Imaging-Genetics Laboratory, Research Imaging Centre, Campbell Family Mental Health Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada M5T 1R8, Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada M5T 1R8, Cerebral Imaging Centre, Douglas Institute, Verdun, Quebec, Canada H4H 1R3, Departments of Psychiatry and Biomedical Engineering, McGill University, Montreal, Quebec, Canada H3A 2B4.
authors: M Mallar
authors: MM
authors: Chakravarty
authors: Kimel Family Translational Imaging-Genetics Laboratory, Research Imaging Centre, Campbell Family Mental Health Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada M5T 1R8.
authors: David J
authors: DJ
authors: Rotenberg
authors: Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada M5T 1R8, Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada M5S 1A8, Geriatric Mental Health Service, Centre for Addiction and Mental Health, Toronto, Ontario, Canada M6J 1H4.
authors: Tarek K
authors: TK
authors: Rajji
authors: Laboratory of Mathematics in Imaging, Psychiatry Neuroimaging Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02215, and.
authors: Yogesh
authors: http://orcid.org/0000-0002-9946-2314
authors: Y
authors: Rathi
authors: Department of Electrical and Computer Engineering, University of Waterloo, Waterloo, Ontario, Canada N2L 3G1.
authors: Oleg V
authors: OV
authors: Michailovich
authors: Kimel Family Translational Imaging-Genetics Laboratory, Research Imaging Centre, Campbell Family Mental Health Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada M5T 1R8, Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada M5T 1R8, Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada M5S 1A8, Geriatric Mental Health Service, Centre for Addiction and Mental Health, Toronto, Ontario, Canada M6J 1H4, Aristotle.Voineskos@camh.ca.
authors: Aristotle N
authors: AN
authors: Voineskos
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging; D016880:Anisotropy; D001921:Brain / Q000033:anatomy & histology* / Q000098:blood supply; D001931:Brain Mapping; D002452:Cell Count; D056324:Diffusion Tensor Imaging; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008297:Male; D008875:Middle Aged; D016501:Neurites / Q000502:physiology*; D009474:Neurons / Q000166:cytology*; D010100:Oxygen / Q000097:blood; D012146:Rest; D018709:Statistics, Nonparametric; D055815:Young Adult
chemical_list: D010100:Oxygen
keywords: GBSS; cognitive aging; diffusion-weighted MRI; gray matter; neurite orientation dispersion; structure–function relationship
references: Neuroimage. 2009 Jan 1;44(1):83-98
references: 18501637
references: Med Phys. 2010 Apr;37(4):1482-90
references: 20443469
references: Neuroimage. 2012 Aug 15;62(2):782-90
references: 21979382
references: Acta Neuropathol. 1985;65(3-4):281-4
references: 3976364
references: Neuroimage. 2014 Jul 1;94:65-78
references: 24650605
references: Neuroimage. 2012 Nov 15;63(3):1364-73
references: 22992492
references: Eur Arch Psychiatry Clin Neurosci. 1999;249 Suppl 3:28-36
references: 10654097
references: J Comp Neurol. 1993 Jan 1;327(1):83-96
references: 8432909
references: Brain. 1996 Dec;119 ( Pt 6):1983-90
references: 9010002
references: Nat Neurosci. 2007 Oct;10(10):1308-12
references: 17828254
references: Neuroimage. 2014 Apr 15;90:449-68
references: 24389422
references: Front Neuroanat. 2011 May 23;5:30
references: 21647397
references: Neuroimage. 2009 Jan 1;44(1):136-44
references: 18775785
references: Neuroimage. 2003 Aug;19(4):1273-302
references: 12948688
references: Psychiatry Res. 1992 Mar;41(3):237-48
references: 1594710
references: Eur J Neurosci. 1998 Apr;10(4):1261-9
references: 9749780
references: Neuroimage. 2007 Feb 15;34(4):1473-86
references: 17188901
references: Behav Res Methods. 2008 Aug;40(3):879-91
references: 18697684
references: Epilepsy Res. 2014 Feb;108(2):336-9
references: 24315018
references: Neuroscience. 2013 Oct 22;251:21-32
references: 23069756
references: Brain Res. 1984 Jan 30;292(1):23-32
references: 6199084
references: Nat Rev Neurosci. 2008 Mar;9(3):206-21
references: 18270515
references: Trends Cogn Sci. 2013 Dec;17(12):596-9
references: 24210964
references: Neuroscience. 2014 Aug 22;274:33-43
references: 24853052
references: J Neurosci. 2013 Nov 20;33(47):18618-30
references: 24259583
references: Neuroimage. 2012 Aug 15;62(2):774-81
references: 22248573
references: IEEE Trans Med Imaging. 2004 Feb;23(2):137-52
references: 14964560
references: Neuroinformatics. 2011 Dec;9(4):381-400
references: 21373993
references: Neuropsychologia. 1971 Mar;9(1):97-113
references: 5146491
references: J Neurocytol. 1999 Mar;28(3):187-96
references: 10617901
references: Nat Neurosci. 2011 Mar;14(3):285-93
references: 21346746
references: Neurol Clin. 2014 Nov;32(4):859-69
references: 25439284
references: Neuroimage. 2006 Jul 15;31(4):1487-505
references: 16624579
references: Brain Res. 1985 Oct 21;345(2):366-8
references: 4041896
references: Proc Natl Acad Sci U S A. 2010 Dec 28;107(52):22682-6
references: 21156826
references: Cereb Cortex. 2005 Nov;15(11):1676-89
references: 15703252
references: Hum Brain Mapp. 2002 Jan;15(1):1-25
references: 11747097
references: Neuroimage. 2012 Apr 2;60(2):1412-25
references: 22270351
references: J Comp Neurol. 1997 Oct 6;386(4):661-80
references: 9378859
references: Proc Natl Acad Sci U S A. 2009 Aug 4;106(31):13040-5
references: 19620724
references: Neuroimage. 2011 Feb 1;54(3):2033-44
references: 20851191
references: Int Rev Neurobiol. 1997;41:31-60
references: 9378595
references: Neuroimage. 2013 Oct 15;80:125-43
references: 23702418
references: Hum Brain Mapp. 2014 Aug;35(8):3841-56
references: 24382651
references: Proc Natl Acad Sci U S A. 2013 Jun 4;110(23):9541-6
references: 23696665
references: Neurobiol Aging. 1996 Jul-Aug;17(4):601-11
references: 8832635
references: Hippocampus. 2014 Apr;24(4):403-14
references: 24339261
references: Neurosci Biobehav Rev. 2013 Mar;37(3):384-400
references: 23333262
references: Trends Cogn Sci. 2013 Dec;17(12):666-82
references: 24238796
references: Cereb Cortex. 2003 Sep;13(9):950-61
references: 12902394
references: Neuroimage. 2007 Oct 15;38(1):114-23
references: 17804258
references: J Neurosci. 2011 Aug 10;31(32):11597-616
references: 21832190
references: Hum Brain Mapp. 2002 Nov;17(3):143-55
references: 12391568
references: Proc Natl Acad Sci U S A. 2009 Apr 28;106(17):7209-14
references: 19357304
references: Annu Rev Clin Psychol. 2011;7:113-40
references: 21128784
references: Proc Natl Acad Sci U S A. 2000 Sep 26;97(20):11050-5
references: 10984517
references: Neuroimage. 2014 Jul 15;95:232-47
references: 24657355
references: J Neurosci. 2012 Nov 28;32(48):17365-72
references: 23197727
references: Neuroimage. 1999 Feb;9(2):179-94
references: 9931268
references: Neuroimage. 2012 Jul 16;61(4):1000-16
references: 22484410
references: Brain. 2012 Aug;135(Pt 8):2350-7
references: 22669081
references: Science. 1979 Nov 16;206(4420):854-6
references: 493989
references: Philos Trans R Soc Lond B Biol Sci. 2005 May 29;360(1457):1001-13
references: 16087444
references: Neuroimage. 2013 Oct 15;80:273-82
references: 23727318
references: Magn Reson Med. 2009 Sep;62(3):717-30
references: 19623619