Michigan Neural Distinctiveness (MiND) study protocol: investigating the scope, causes, and consequences of age-related neural dedifferentiation.
Aging
Cognition
Dedifferentiation
Functional MRI
GABA
Individual differences
Lorazepam
MR spectroscopy
Journal
BMC neurology
ISSN: 1471-2377
Titre abrégé: BMC Neurol
Pays: England
ID NLM: 100968555
Informations de publication
Date de publication:
12 Apr 2019
12 Apr 2019
Historique:
received:
14
11
2018
accepted:
31
03
2019
entrez:
14
4
2019
pubmed:
14
4
2019
medline:
22
5
2019
Statut:
epublish
Résumé
Aging is often associated with behavioral impairments, but some people age more gracefully than others. Why? One factor that may play a role is individual differences in the distinctiveness of neural representations. Previous research has found that neural activation patterns in visual cortex in response to different visual stimuli are often more similar (i.e., less distinctive) in older vs. young participants, a phenomenon referred to as age-related neural dedifferentiation. Furthermore, older people whose neural representations are less distinctive tend to perform worse on a wide range of behavioral tasks. The Michigan Neural Distinctiveness (MiND) project aims to investigate the scope of neural dedifferentiation (e.g., does it also occur in auditory, motor, and somatosensory cortex?), one potential cause (age-related reductions in the inhibitory neurotransmitter gamma-aminobutyric acid (GABA)), and the behavioral consequences of neural dedifferentiation. This protocol paper describes the study rationale and methods being used in complete detail, but not the results (data collection is currently underway). The MiND project consists of two studies: the main study and a drug study. In the main study, we are recruiting 60 young and 100 older adults to perform behavioral tasks that measure sensory and cognitive function. They also participate in functional MRI (fMRI), MR spectroscopy, and diffusion weighted imaging sessions, providing data on neural distinctiveness and GABA concentrations. In the drug study, we are recruiting 25 young and 25 older adults to compare neural distinctiveness, measured with fMRI, after participants take a placebo or a benzodiazepine (lorazepam) that should increase GABA activity. By collecting multimodal imaging measures along with extensive behavioral measures from the same subjects, we are linking individual differences in neurochemistry, neural representation, and behavioral performance, rather than focusing solely on group differences between young and old participants. Our findings have the potential to inform new interventions for age-related declines. This study was retrospectively registered with the ISRCTN registry on March 4, 2019. The registration number is ISRCTN17266136 .
Sections du résumé
BACKGROUND
BACKGROUND
Aging is often associated with behavioral impairments, but some people age more gracefully than others. Why? One factor that may play a role is individual differences in the distinctiveness of neural representations. Previous research has found that neural activation patterns in visual cortex in response to different visual stimuli are often more similar (i.e., less distinctive) in older vs. young participants, a phenomenon referred to as age-related neural dedifferentiation. Furthermore, older people whose neural representations are less distinctive tend to perform worse on a wide range of behavioral tasks. The Michigan Neural Distinctiveness (MiND) project aims to investigate the scope of neural dedifferentiation (e.g., does it also occur in auditory, motor, and somatosensory cortex?), one potential cause (age-related reductions in the inhibitory neurotransmitter gamma-aminobutyric acid (GABA)), and the behavioral consequences of neural dedifferentiation. This protocol paper describes the study rationale and methods being used in complete detail, but not the results (data collection is currently underway).
METHODS
METHODS
The MiND project consists of two studies: the main study and a drug study. In the main study, we are recruiting 60 young and 100 older adults to perform behavioral tasks that measure sensory and cognitive function. They also participate in functional MRI (fMRI), MR spectroscopy, and diffusion weighted imaging sessions, providing data on neural distinctiveness and GABA concentrations. In the drug study, we are recruiting 25 young and 25 older adults to compare neural distinctiveness, measured with fMRI, after participants take a placebo or a benzodiazepine (lorazepam) that should increase GABA activity.
DISCUSSION
CONCLUSIONS
By collecting multimodal imaging measures along with extensive behavioral measures from the same subjects, we are linking individual differences in neurochemistry, neural representation, and behavioral performance, rather than focusing solely on group differences between young and old participants. Our findings have the potential to inform new interventions for age-related declines.
TRIAL REGISTRATION
BACKGROUND
This study was retrospectively registered with the ISRCTN registry on March 4, 2019. The registration number is ISRCTN17266136 .
Identifiants
pubmed: 30979359
doi: 10.1186/s12883-019-1294-6
pii: 10.1186/s12883-019-1294-6
pmc: PMC6460537
doi:
Types de publication
Clinical Trial
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
61Subventions
Organisme : NIA NIH HHS
ID : R01 AG050523
Pays : United States
Organisme : National Institutes of Health
ID : R01AG050523
Références
Nature. 1999 Nov 11;402(6758):176-8
pubmed: 10647007
Science. 2001 Sep 28;293(5539):2425-30
pubmed: 11577229
Psychol Aging. 2002 Jun;17(2):299-320
pubmed: 12061414
JAMA. 2002 Nov 13;288(18):2271-81
pubmed: 12425704
Psychol Sci. 2003 Mar;14(2):125-30
pubmed: 12661673
Science. 2003 May 2;300(5620):812-5
pubmed: 12730605
Neuroimage. 2003 Aug;19(4):1578-88
pubmed: 12948713
Int J Audiol. 2004 Jan;43(1):15-28
pubmed: 14974624
Proc Natl Acad Sci U S A. 2004 Aug 31;101(35):13091-5
pubmed: 15322270
J Am Geriatr Soc. 2005 Apr;53(4):695-9
pubmed: 15817019
Neuroreport. 2006 Apr 3;17(5):487-91
pubmed: 16543812
Nat Rev Neurosci. 2006 Jul;7(7):523-34
pubmed: 16791142
Trends Cogn Sci. 2006 Sep;10(9):424-30
pubmed: 16899397
Dement Geriatr Cogn Disord. 2006;22(5-6):486-99
pubmed: 17050952
Arch Gen Psychiatry. 2007 Feb;64(2):156-67
pubmed: 17283283
JAMA. 2008 Sep 3;300(9):1027-37
pubmed: 18768414
Proc Natl Acad Sci U S A. 2008 Sep 23;105(38):14325-9
pubmed: 18787113
PLoS One. 2008;3(10):e3399
pubmed: 18852896
Assessment. 2009 Jun;16(2):145-58
pubmed: 19066391
Neuroimage. 2011 May 15;56(2):736-43
pubmed: 20451629
J Neurosci. 2010 Jul 7;30(27):9253-9
pubmed: 20610760
Proc Natl Acad Sci U S A. 2010 Aug 3;107(31):13900-5
pubmed: 20643928
Neuroimage. 2012 Feb 15;59(4):3976-94
pubmed: 22036682
J Neurosci Methods. 2012 Mar 15;204(2):215-20
pubmed: 22155443
Front Aging Neurosci. 2011 Dec 08;3:18
pubmed: 22163221
PLoS One. 2011;6(12):e29411
pubmed: 22216274
Neuroimage. 2014 Feb 1;86:43-52
pubmed: 23246994
Neurology. 2013 Mar 12;80(11 Suppl 3):S2-6
pubmed: 23479538
NMR Biomed. 2013 Dec;26(12):1775-86
pubmed: 24038308
Exp Brain Res. 2014 Nov;232(11):3601-12
pubmed: 25080130
Magn Reson Med. 2015 Dec;74(6):1523-9
pubmed: 25521836
Neuroimage. 2015 Aug 15;117:40-55
pubmed: 26004503
Schizophr Res. 2015 Oct;168(1-2):338-44
pubmed: 26363970
Neuroimage. 2017 Jan 1;144(Pt A):58-73
pubmed: 27639350
IEEE Trans Pattern Anal Mach Intell. 2018 Jun;40(6):1452-1464
pubmed: 28692961
Br J Clin Psychol. 1982 Feb;21 (Pt 1):1-16
pubmed: 7126941
Neuroreport. 1995 Feb 15;6(3):469-73
pubmed: 7766845
Spat Vis. 1997;10(4):433-6
pubmed: 9176952