A Review of Functional Brain Imaging Correlates of SuccessfulCognitive Aging

Lisa T. Eyler, Ph.D.1,2, Abdullah Sherzai, M.D., MAS3, and Dilip V. Jeste, M.D.11Sam and Rose Stein Institute for Research on Aging, and Department of Psychiatry, Universityof California, San Diego2Mental Illness Research, Education, and Clinical Center, VA San Diego Healthcare System3Department of Neurology, Loma Linda University

AbstractPreserved cognitive performance is a key feature of successful aging. Several theoretical models(compensation, hemispheric asymmetry reduction, and posterior-anterior shift) have beenproposed to explain the putative underlying relationship between brain function and performance.We aimed to review imaging studies of the association between brain functional response andcognitive performance among healthy younger and older adults in order to understand the neuralcorrelates of successful cognitive aging. MEDLINE-indexed articles published between January1989 and May 2008, and bibliographies of these articles and related reviews were searched.Studies that measured brain function using fMRI or PET, evaluated cognitive performance,analyzed how cognitive performance related to brain response, and studied healthy olderindividuals were included. Forty-seven of 276 articles met these criteria. Eighty-one percent of thestudies reported some brain regions in which greater activation related to better cognitiveperformance among older participants. This association was not universal, however, and was seenmainly in frontal cortex brain response and seemed to be more common among older compared toyounger individuals. This review supports the notion of compensatory increases in brain activityin old age resulting in better cognitive performance, as suggested by hemispheric asymmetryreduction and posterior-anterior shift models of functional brain aging. However, a simple modelof bigger structure → greater brain response → better cognitive performance may not be accurate.Suggestions for future research are discussed.

KeywordsAging; fMRI; PET; cognition; brain imaging; frontal cortex

IntroductionA great challenge for future society will be to better understand the aging process. As theproportion of individuals over age 65 grows, it is of utmost socioeconomic importance topromote functional independence and quality of life in this group. Cognitive health hasconsistently been cited by seniors as important for quality of life (1) and is widelyrecognized by researchers as an important contributor to late life functioning (2–4). Thus, a

Send reprint requests to: Lisa T. Eyler, Ph.D., lteyler@ucsd.edu, Mail Code 9151B, 9500 Gilman Drive, La Jolla, CA 92093.

Financial DisclosuresThe authors have no specific financial interests, relationships, or additional affiliations relevant to the subject of this manuscript.

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Published in final edited form as:Biol Psychiatry. 2011 July 15; 70(2): 115–122. doi:10.1016/j.biopsych.2010.12.032.

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key element in dealing with the “graying of the world” must be to discover ways to optimizecognitive performance in old age.

Cognitive performance in most domains declines with age, particularly processes such aspsychomotor speed; however, some abilities may remain stable or even improve up to acertain age, such as vocabulary (5). Importantly, there is large heterogeneity in cognitivechanges that occur with aging (6). Some seniors are exceptional in their cognitiveperformance, and understanding this aspect of cognitive aging (as opposed to focusing onpathological change or normal declines) is likely to guide the search for ways to enhancecognitive functioning in aging (3).

Brain health is an important determinant of cognitive health, so a fuller understanding ofneural aging, especially those aspects that most influence cognition, is necessary. Much isalready known about structural brain changes due to age and age-related diseases (7) andhow these relate to cognitive performance (8). We observed, in a comprehensive review ofthe literature focusing on structural correlates of cognitive performance in healthy elders,that most studies find a positive relationship between regional brain size and cognitiveperformance (9).

Brain structural integrity, however, is only one neural factor influencing individualdifferences in cognitive function among older people. Studies of brain function usingtechniques such as positron emission tomography (PET) and functional magnetic resonanceimaging (fMRI) have revealed reliable changes in the level and pattern of brain activity withage. Older age has been associated with lower blood flow and metabolism at rest,particularly in frontal cortex (10). Reduced regional brain response to challenge tasks amongolder compared to younger participants has also been seen (11). Notably, however, greaterregional brain response in older participants also is commonly observed (11). In someinstances, pattern of brain response is qualitatively different, for example, when“overactivation” occurs in a homologous region in the opposite hemisphere from the regiontypically responsive in the young group and is less lateralized (12), referred to as HAROLD:Hemispheric Asymmetry Reduction in OLDer adults (13). In other cases, brain response inposterior regions has been found to be lower in older adults whereas anterior regions showgreater response than in younger individuals (14). This relative shift from posterior toanterior involvement has been termed the Posterior-Anterior Shift with Aging (PASA (11)).

An unresolved issue is how these age-related changes in brain responsiveness and alteredpatterns (e.g., HAROLD or PASA) are associated with cognitive differences between olderindividuals and with rates of cognitive decline with aging. Age-related alterations in brainfunction may be associated with poorer cognitive performance, as is seen most dramaticallyin the case of decreased regional metabolism associated with steep cognitive declines inAlzheimer’s dementia (15). Interestingly, however, there is also evidence that the degree towhich older individuals manifest some age-related patterns of brain activity may beassociated with better cognitive performance (i.e., compensation (16)). Such findings are incontrast to the idea that alterations of neural function reflect inefficient processing (i.e., de-differentiation (17)).

The purpose of this review was to comprehensively review studies of the associationbetween cognitive performance and brain function among healthy older individuals in orderto weigh evidence in support of age-related compensatory versus de-differentiated brainresponses, examine factors related to these findings, and evaluate their specificity to old age.Previous reviews of functional imaging changes with age (11, 18) have summarized a subsetof findings covered in the present review, but none has focused specifically on correlationsbetween brain function and cognitive performance.

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MethodsTo retrieve studies for this review, MEDLINE citations (January, 1989 – May, 2008) weresurveyed using the National Library of Medicine’s PubMed online search engine using thefollowing search string: ("functional MRI" OR "fMRI" OR "PET" OR "positron emissiontomography" OR "cerebral blood flow") AND (brain OR cognition OR cognitive ORcerebral) NOT (dementia OR Alzheimer's OR psychiatric OR disorder OR disease ORimpair*) AND (age[Title] OR aging[Title] OR ageing[Title] OR old[Title] ORelderly[Title]). This search revealed 256 articles of potential interest. All references cited inthese articles were also reviewed, and we found 20 additional relevant publications.

Inclusion criteriaWe applied several selection criteria. To be included in the review, studies had to 1) usefMRI or PET methodology to examine neural functioning, 2) evaluate cognitiveperformance either on a task given during imaging or on a measure administered on aseparate occasion, 3) report results of an analysis examining how differences in cognitiveperformance related to differences in brain response, and 4) include at least one group ofhealthy elderly individuals (mean age > 60 years of age).

Review processWe found 47 reports that met review criteria. Flow of information through different stagesof the systematic review is shown in Figure 1.

Each study was examined by two authors (LTE, AS) and the following information wasextracted: numbers and characteristics of participants, definition of “healthy” used,neuroimaging method and scanning paradigm employed, and brain regions examined. Wealso noted whether participants overlapped between samples in the review. Based on studyresults, we summarized the relationship of age to functional brain imaging measures toprovide a context for understanding brain-cognition relationships. We then extracted themeasures of cognitive performance used and summarized associations between cognitiveperformance level and measures of brain functioning. We noted the direction of associationand whether this reflected greater response among those with successful versus normalcognitive performance (e.g., positive correlations for accuracy and negative correlations forreaction time both imply that better cognitive performers have greater brain response). Whenpossible, we summarized correlations separately for younger and older groups and notedwhether a direct statistical comparison had been made.

ResultsCharacteristics of Reviewed Studies

Study characteristics and results for the 47 reviewed papers are presented chronologically inTable 1. There was one longitudinal study (19), one study in which cognitive change wasexamined longitudinally but brain response was measured once (20), and all otherinvestigations were cross-sectional. Among cross-sectional studies, two (21, 22) includedonly older participants, one examined a large cohort ranging in age from 20 to 87 (23), andthe rest (n=41) compared younger adults to at least one group of older individuals. Onestudy (24) reported partial overlap in participants with another study (25).

Summary statistics for the reviewed studies are given in Table 2. The review included morestudies using fMRI than PET, and sample sizes were typical of many functionalneuroimaging investigations. A large majority of reports employed medical, neurological,and psychiatric screening criteria to assure a healthy sample, most also employed cognitive

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screening (e.g., Mini-Mental State Examination (26)), about half also excluded subjectsbased on current medication usage, and a smaller number had an additional criterion that thestructural MRI be normal (21, 22, 27–40). Education level, when reported, was generallyhigh (median four years of college) and comparable between younger and older groups. Allstudies had both male and female participants except for two that enrolled only men (41, 42)and one that included only women (43). Gender ratio was comparable between old andyoung groups in most reports. Participants’ ethnicity was not reported in any reviewedstudies and so, could not be summarized.

The reviewed studies employed a variety of cognitive paradigms: episodic learning andmemory tasks were most frequently used, followed by working memory tasks, and thoseassessing inhibitory processing. Less commonly examined domains included motorfunction, language, nondeclarative memory, visual search, and visual attention.

In terms of analysis strategies, age effects were often examined in a voxel-wise fashionacross the entire brain. In many other studies, mean response in a priori regions of interestdetermined either by previous studies or by significant within-group differences were usedin the age analysis. In many studies, brain-behavior correlations were only examined in thesubset of regions in which an age difference in mean brain response was observed.

The cognitive performance variable examined differed among studies, but was most oftenaccuracy of task performance, followed by mean reaction time. Most investigations usedtask performance during imaging as the measure of cognitive performance.

Correlation of Brain Function and Cognitive PerformanceGreater brain response generally was associated with better cognitive performance in thereviewed studies: there was at least one finding of such an association in all but 6 of the 47studies (25, 44–48)(See Table 3). In 19 studies, only positive associations betweenmagnitude of brain response in the older group and cognitive performance were found; 19others found both positive and negative associations. Thus, across many different types oftasks, more cognitively successful seniors had greater brain response in at least one brainregion compared to their lower-performing peers. Positive correlations, when observed,were frequently found in frontal lobe regions and negative correlations were rare in thisregion: 19 studies reporting correlations within the frontal lobes found positive associations,6 found negative correlations, and 9 found some evidence for both positive and negativeassociations. Findings within parietal and temporal cortex were similarly skewed in favor ofpositive associations. In occipital cortex and in hippocampal / medial temporal cortex, anequal number of studies reported each direction of correlation with performance. Among the22 studies in which the analysis could have revealed brain-behavior correlations in anyregion (i.e., analysis was not restricted to particular areas), there were 9 studies that foundpositive associations in frontal cortex (one negative); for all other regions, positivecorrelations were observed in 5 studies or fewer. Thus, positive associations were morecommonly found in frontal cortex than in other regions even among studies in which therewas a chance of finding such correlations in any brain region.

Six investigations found only negative correlations (i.e., greater brain response in poorerperforming elders); these involved reaction time to incongruent vs. congruent visualdistracters (44), go/no-go task accuracy evaluated across the whole brain (25) and in thebasal ganglia (45) (participants overlapped between these studies), relationship of cognitivereserve to age-differential networks during learning and recognition of difficult versus easyword lists (46), reaction time during a facial emotion matching task (47), and relationship ofreaction time slope and discriminability to load-dependent and load-independent brain

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response in spatial networks responsive during different phases of a working memory task(48).

Given known differences in cognitive and brain aging patterns between men and women(49, 50), we examined whether gender ratio in the older study group appeared to be relatedto the direction of associations between brain function and cognitive performance. Wedivided studies into three categories based on whether the older sample was predominantlymale (>67% men; n=10), predominantly female (>67% women; n=10), or gender-balanced(≤67% men or women; n=26). Studies with greater or equal numbers of women in the oldersample were slightly more likely to observe positive compared to negative correlations(predominantly female: 70% positive vs. 30% negative, gender-balanced: 73% positive vs.50% negative), whereas those with more men had mixed findings (100% positive vs. 70%negative).

Two studies had a longitudinal component, permitting inferences about the temporalrelationship between changes in cognitive performance and changes in brain function. In astudy with repeated assessment of both cognition and brain function (19), older adults wereassessed at baseline and after 8 years with PET imaging during a recognition memory test.Overall cognitive performance did not change significantly in this sample, but longitudinalincreases and decreases of brain activity were observed. Positive relationships between brainresponse changes and performance changes were seen in temporal and parietal regions; andnegative associations were found in temporal and frontal regions. The findings suggest somedegree of reorganization of cortical networks of older individuals in the context of preservedcognitive performance, with both beneficial and detrimental regional changes observed. In aretrospective design in which cognition, but not brain response, was measuredlongitudinally, Persson et al (20), compared measures of brain response between two groupsof individuals – those who had stable memory performance over the previous decade andthose who had declined (although none had declined out of the normal range). Brainresponse during verbal encoding was measured with fMRI, and analyses of brain-behaviorrelationships were conducted within frontal regions activated by both groups. Greaterresponse was found in right ventral prefrontal cortex among individuals whose memoryperformance had declined compared to those whose performance had remained stable.

Uniqueness of Brain-Behavior Correlation Pattern in Older IndividualsThirty-three studies included a young comparison group in which the relationship betweenbrain response and cognitive performance was also examined. Many studies found strongcorrelations in both younger and older groups. Most identified some brain regions in whichsimilar brain-behavior correlations were observed in both age groups, but many alsoreported regions in which correlations were significant only in one group. An interestingcategory of finding was the observation of brain regions in which the relationship betweenperformance and brain response was opposite in direction in the two age groups. In 13studies (40%), the correlation with performance was much more strongly positive in the oldthan in the young group, and in many cases the relationship was negative in youngerindividuals (30, 31, 51–60). In contrast, positive correlations among the young group andnegative associations among the old also were observed in some studies; this was somewhatmore likely to be the case in posterior and medial temporal brain regions (30, 31, 35, 46, 48,54, 55, 57, 59, 60). In a small number of studies (32, 41, 61, 62), brain-behavior correlationswere much more pronounced in the old group than the young, but the opposite pattern (nocorrelations in old and multiple significant correlations in young) was not seen in any study.

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Relationship of Brain-Behavior Correlations to Nature of Age-Related ChangesAn aim of this review was to understand whether older individuals who display qualitativelydifferent patterns of brain response perform better than those with a more youthful pattern.Although few studies examined this directly (48, 58), we were able to classify age effectsinto those that were broadly supportive of HAROLD and PASA and then examine thedirection of brain-behavior associations in these studies. We found 14 studies in whichgroup aging results were broadly consistent with either HAROLD (n=7) or PASA (n=6) orboth (n=1). Of these, 10 studies reported positive correlations between brain function andcognitive performance in some region and 7 reported negative correlations in some region.Six studies found positive correlations in frontal cortex (4 found negative correlations) andno other region had more than 3 reports of significant function-cognition relationships,either positive or negative. Thus, studies that demonstrated altered brain patterns in olderindividuals consistent with HAROLD and PASA models were slightly more likely to findthese changes to be beneficial rather than detrimental, but findings of negative relationshipswere also prevalent.

DiscussionIn our review of studies addressing how brain function relates to cognitive performanceamong older individuals, we found frequent support for the notion that increased brainresponsiveness is associated with better cognitive performance. Positive correlationsbetween frontal cortex brain response and performance were much more frequently reportedthan negative correlations, and positive associations were more often observed in frontalcortex than in other regions. Positive correlations also outnumbered negative ones in parietaland temporal cortices, whereas findings were more mixed for both occipital cortex andmedial temporal lobe. The predominance of positive correlations in frontal cortex isconsistent with findings of our review of the relationship between brain structure andcognitive performance in late-life, in which frontal findings were also the most numerousand consistent (9). Interestingly, although greater size of medial temporal lobe was alsofairly consistently linked to greater cognitive success (9), the directionality of relationshipsbetween brain function in this region and cognitive performance was mixed. This suggeststhat a simple model of: bigger structure → greater brain response → better cognitiveperformance may not be accurate, and points out the necessity to measure both brainstructure and function in the same study in order to test more complete models.

Positive correlations with performance, particularly in frontal cortex, have previously beeninterpreted as compensatory in nature (13). Specifically, it has been theorized that frontalcortex must become more active in order to support good performance in the face ofdeficient responses elsewhere (63). Although many studies observed positive correlationswith performance, most did not directly test how this might be related to deficient brainresponse in other regions. It was also not always clear how performance of the highestperforming seniors compared to that of high performing younger adults. Thus, it wasdifficult to know whether brain response in regions of positive correlation with cognitiveperformance was truly compensatory or, instead, represented an attempt at compensationthat was only partially successful. It was also difficult to evaluate whether there was abenefit to qualitatively different patterns of activation as opposed to quantitative differencesin response in the same brain regions (48). Among studies that demonstrated a group effectof age consistent with HAROLD or PASA, positive associations between brain response inthese regions were more frequently observed than negative ones. Mixed results were foundin two studies examining this question more directly using working memory tasks; Reuter-Lorenz et al (58) found that older adults with a more bilateral activation pattern performedmore quickly, but Zarahn et al (48) found only one qualitatively different pattern of brainresponse among older adults, which was associated with worse performance. Clearly, further

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work is needed to develop techniques to classify the pattern of brain activity amongindividual participants and examine cognitive consequences of those patterns.

The exceptions to findings of positive correlations between brain response level andcognitive performance, perhaps suggestive of de-differentiated responses, are potentiallyilluminating. Most notable is a quasi-longitudinal study in which individuals with thegreatest cognitive decline had the most subsequent frontal overactivity (20). If excess frontalresponse is compensatory, one might expect to observe it most in individuals who maintaingood cognitive performance. However, as the authors point out, it could be that extra brainresponse in frontal cortex is only recruited when other systems begin to fail and thatdecliners’ brains were attempting a reorganization (in response to hippocampal and whitematter deficits observed in this group) while those who were stable did not require it (yet).Of the six cross-sectional studies that found only negative associations between brainresponse and cognitive performance, three involved inhibitory processing and/orovercoming prepotent responses. Frontal overactivity may be detrimental for this particulartype of cognitive activity. Another pattern that emerged was one of negative correlationswith performance in posterior regions but positive correlations in anterior regions. Thisappears to be consistent with the concept that individuals who show the PASA pattern havethe best cognitive performance. Still, if one postulates that anterior shift occurs in responseto loss of posterior function, it is perhaps surprising that those with the most residualposterior function would have the worst cognitive performance. Perhaps earlier sensoryprocesses require a more focal response that, once weakened in the course of aging, cannotbe compensated for by greater posterior activation. This might suggest that only thoseindividuals who can strengthen and broaden their anterior response and reciprocally quiettheir posterior response can continue to perform at a high level.

The above discussion highlights the largest gap in our knowledge regarding the link betweenbrain function and cognition in old age – i.e., how it may change along the course ofdevelopment. Many theories posit a dynamic process (e.g., (63, 64)), in which functionalincreases occur in response to structural changes that decrease focal responses elsewhere.Direct evidence addressing this dynamic process is extremely limited. Only one studymeasured both brain function and cognitive performance longitudinally (19). Results of thisstudy were mixed and cognitive changes were minimal, so we do not yet know how thebrain may reorganize itself in people who maintain cognitive performance levels versusthose that decline. The reviewed studies comparing brain-behavior associations amongyounger versus older samples generally supported the notion that the association strengthensand becomes more positive with age. Although this may sometimes have resulted fromrestricted variability in the younger sample leading to lower correlations, in some reportsthere were significant negative correlations in the young group and significant positivecorrelations in the old group. This suggests that a switch may occur at some point inadulthood so that more brain response is better instead of worse. This could perhaps beconsistent with antagonistic pleiotropy in which effects of certain genes are detrimental atone point in life but beneficial at another (65). When and how such a switch may happen iscurrently unknown. Longitudinal functional neuroimaging, in combination with geneticstudies, may be a particularly powerful combination for better understanding individualtrajectories of neural aging (66).

The finding that additional brain response is generally positively associated with cognitivesuccess in old age emphasizes the existence of continued functional plasticity which shouldlead to optimism about improving cognitive function in old age. Cognitive training is onetype of intervention that is gaining in popularity and evidence for efficacy (67). Changes inbrain function after cognitive training may result in a more youthful, unilateral pattern ofbrain response rather than a strengthening of the HAROLD-like response of untrained

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seniors (68), however. This raises the possibility that some interventions might berestorative for brain functioning, while others may result in patterns that more closelyresemble the brain’s naturalistic compensatory changes.

There are several limitations to this review, including that, in spite of our best efforts, wemight have missed some relevant papers on this topic. Also, as with any review, there mayhave been publication biases that influenced the type of results available to include. Inaddition, our review only focused on functional correlates of successful cognitiveperformance and did not address other aspects that may contribute to quality of life in oldage, such as emotional well-being (69). Although functional neuroimaging has been appliedto understanding emotional disorders in late life (70, 71), few studies have addressed braincorrelates of individual differences in emotional outlook among healthy seniors (72).

The conclusions we drew could also be influenced by limitations of the reviewed papers.The studies’ sample sizes, although typical for neuroimaging investigations, were relativelysmall for examining correlations. Study participants were highly educated, which could limitgeneralizability of results. Also, studies varied greatly in terms of their selection criteria,cognitive tests administered, imaging techniques used, and analysis methods employed,making it difficult to summarize findings across studies. As discussed above, very fewstudies examined cognitive correlates of coordinated brain networks and many did notstatistically compare correlations between young and old groups. Finally, few studiesdirectly addressed the concern that observed brain response-behavior correlations may beaccounted for partially or wholly by associations between cerebrovascular function andcognition (73). Future studies that measure blood flow, metabolic rate of oxygen, and bloodoxygenation dependent response in both younger and older participants may help determinethe relative contribution of vascular versus neuronal components to individual differences incognitive performance, and how these may change with age.

In summary, results of this review offer support for the view that augmented brain response,particularly in frontal cortex, serves a compensatory role in older adults. In some cases,however, extraneous activation might be detrimental, such as when it occurs in posteriorregions or during tasks that require inhibitory processes. The existing literature does notfully address the important question of how such relationships are built up or may changeacross adulthood, although there is some suggestion that positive brain function-cognitionrelationships strengthen with age. Whether there is eventually a point at which compensationfails and how the timing of such changes might relate to other genetic or environmentalfactors will be a productive area for further exploration.

AcknowledgmentsThis work was supported, in part, by the Sam and Rose Stein Institute for Research on Aging, by grants from theNational Institute of Mental Health (P30-MH080002), and by the Department of Veterans Affairs.

AstraZeneca, Bristol-Myers Squibb, Eli Lilly, and Janssen donate medication for an NIMH funded research grantawarded to Dr. Jeste entitled “Metabolic Effects of Newer Antipsychotics in Older Patients.”

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Figure 1.PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) flow ofinformation through the different phases of the systematic review

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Eyler et al. Page 14

Tabl

e 1

Chr

onol

ogic

al R

epor

t of

Stud

y C

hara

cter

istic

s an

d R

esul

ts R

elev

ant t

o A

ssoc

iatio

n of

Bra

in R

espo

nse

and

Cog

nitiv

e Pe

rfor

man

ce in

47

Rev

iew

ed S

tudi

es.

Cit

atio

nN

umbe

r of

Par

tici

pant

sC

hara

cter

isti

cs o

fpa

rtic

ipan

tsD

efin

itio

n of

"Hea

lthy

"T

ype

ofIm

agin

gP

arad

igm

tes

ted

Bra

inR

egio

n(s)

Exa

min

ed

Age

Dif

fere

nce(

s) in

Bra

inF

unct

ion

Succ

ess/

Per

form

ance

Det

erm

inat

ion

Succ

ess/

Per

form

ance

Cor

rela

tion

or

Eff

ect(

s)

Cab

eza

et a

l., 1

997,

Age

-re

late

d di

ffer

ence

s in

neur

al a

ctiv

ity d

urin

gm

emor

y en

codi

ng a

ndre

trie

val:

A p

ositr

onem

issi

on to

mog

raph

yst

udy

Y:

12, O

: 12

Y:

mea

n ag

e =

26,

age

ran

ge=

19–

31, 6

M:6

F, m

ean

year

sed

ucat

ion

= 1

7.8;

O:

mea

nag

e =

70,

age

ran

ge =

67–

75,

5M:7

F, m

ean

year

s ed

ucat

ion

= 1

6.0

No

hist

ory

of n

euro

logi

cal

or p

sych

iatr

ic il

lnes

s or

use

of m

edic

atio

n or

cond

ition

that

cou

ld a

ffec

tC

BF.

PET

Epi

sodi

c en

codi

ng a

nd r

etri

eval

(bot

h re

cogn

ition

and

ret

riev

al)

ofw

ord

pair

s. C

ontr

ast(

s): p

artia

lle

ast s

quar

es a

naly

sis

of a

gegr

oup

diff

eren

ces

rela

tive

toen

codi

ng v

s. re

trie

val a

ndre

cogn

ition

vs.

reca

ll

Who

le b

rain

ana

lysi

sE

ncod

ing

vs. r

etri

eval

: Y >

O:

supe

rior

ant

erio

r ci

ngul

ate,

Lte

mpo

ral c

orte

x (Y

: E

NC

> R

ET

,O

: RE

T >

EN

C),

infe

rior

ant

erio

rci

ngul

ate,

RE

T m

edia

l fro

ntal

pole

(Y

: R

ET

> E

NC

, O: E

NC

≥R

ET

); O

> Y

: B in

sula

, RE

Toc

cipi

tal c

orte

x (O

: EN

C >

RE

T,

Y:

EN

C ≤

RE

T),

cun

eus/

prec

uneu

s, L

pre

fron

tal c

orte

x(O

: R

ET

> E

NC

, Y: E

NC

≥R

ET

).

Del

ayed

rec

all a

ccur

acy

Mos

tly n

on-s

ignf

ican

t cor

rela

tions

, but

in Y

and

O c

ombi

ned:

NE

G c

orre

latio

n(

) w

ith r

ecal

l in

R in

sula

.

Mad

den

et a

l., 1

997,

Sele

ctiv

e an

d di

vide

dvi

sual

atte

ntio

n: A

ge-

rela

ted

chan

ges

inre

gion

al c

ereb

ral b

lood

flow

mea

sure

d by

PE

T

Y:

12, O

: 12

Y:

mea

n ag

e =

24.

33, a

gera

nge

= 2

1–28

, 12M

:0F;

O:

mea

n ag

e =

65.

5, a

ge r

ange

=60

–77,

12M

:12F

; all

had

com

plet

ed s

ome

post

-se

cond

ary

educ

atio

n

No

maj

or h

ealth

pro

blem

son

scr

eeni

ngqu

estio

nnai

re. n

egat

ive

neur

olog

ic s

cree

ning

exam

. MM

SE o

f >

28 a

nd<

5 o

n B

eck

depr

essi

onin

vent

ory.

MR

I fr

ee o

fan

y at

roph

y or

str

uctu

ral

abno

rmal

ities

.

PET

Vis

ual a

ttent

ion

task

s: P

assi

ve(l

ook

at le

tter

arra

y an

d al

tern

ate

butto

n pr

ess)

, Cen

tral

(lo

ok f

oron

e of

2 ta

rget

lette

rs in

cen

ter

ofar

ray)

, Div

ided

(lo

ok f

or o

ne o

ftw

o ta

rget

lette

rs a

nyw

here

in 9

lette

r ar

ray)

. Con

tras

t(s)

: Cen

tral

vs. P

assi

ve, D

ivid

ed v

s. P

assi

ve,

Div

ided

vs

Cen

tral

Who

le b

rain

ana

lysi

sC

entr

al v

s Pa

ssiv

e: a

ctiv

atio

ns: Y

> O

for

ant

erio

r ci

ngul

ate,

deac

tivat

ions

: Y >

O f

or R

mid

dle

fron

tal g

yrus

; Div

ided

vs

Pass

ive:

act

ivat

ions

: Y >

O f

or B

fusi

form

gyr

us, O

> Y

for

Lm

iddl

e fr

onta

l gyr

us,

deac

tivat

ions

: Y =

O; D

ivid

ed v

sC

entr

al: a

ctiv

atio

ns: Y

> O

inB

A 1

8, O

> Y

in a

nter

ior

cing

ulat

e, L

sup

erio

r fr

onta

lgy

rus,

R m

iddl

e fr

onta

l gyr

us,

deac

tivat

ions

: Y >

O in

L m

iddl

efr

onta

l gyr

us, O

> Y

in L

insu

la.

Mea

n re

actio

n tim

e on

cor

rect

tria

lsY

: C

entr

al v

s. P

assi

ve: N

EG

cor

rela

tion

with

RT

in R

sup

erio

r te

mpo

ral a

nd m

iddl

e fr

onta

lgy

rus;

Div

ided

vs.

Pas

sive

: PO

S co

rrel

atio

nw

ith R

T in

L s

uper

ior

pari

etal

, ant

erio

rci

ngul

ate,

and

infe

rior

occ

ipita

l gyr

us, N

EG

corr

elat

ion

in R

fro

ntal

and

B in

feri

or te

mpo

ral;

Div

ided

vs.

Cen

tral

: PO

S co

rrel

atio

n in

Lsu

peri

or p

arie

tal a

nd L

occ

ipito

tem

pora

l, N

EG

corr

elat

ion

in R

sup

erio

r fr

onta

l gyr

us. O

:D

ivid

ed v

s. P

assi

ve: P

OS

corr

elat

ion

with

RT

()

L f

ront

al, R

sup

erio

r pa

riet

al,

L c

ereb

ellu

m, L

infe

rior

tem

pora

l cor

tex,

NE

Gco

rrel

atio

n w

ith R

T (

) in

Bm

edia

l tem

pora

l gyr

us, R

sup

erio

r te

mpo

ral,

mid

line

supe

rior

fro

ntal

gyr

us; D

ivid

ed v

s.C

entr

al: P

OS

corr

elat

ion

with

RT

()

in B

sup

erio

r pa

riet

al lo

bean

d L

BA

6, N

EG

cor

rela

tion

with

RT

()

in B

med

ial t

empo

ral g

yrus

,L

insu

la, a

nter

ior

cing

ulat

e, s

uper

ior

tem

pora

lgy

rus.

Gra

dy e

t al.,

199

8, A

ge-

rela

ted

chan

ges

inre

gion

al c

ereb

ral b

lood

flow

dur

ing

wor

king

mem

ory

for

face

s

Y:

13, O

: 16

Y:

mea

n ag

e =

25,

mea

nye

ars

of e

duca

tion

= 1

6,10

M:3

F; O

: mea

n ag

e =

66,

mea

n ye

ars

of e

duca

tion

=16

, 11M

:5F

Exc

lude

d th

ose

with

dise

ases

or

med

icat

ions

that

mig

ht a

ffec

t bra

infu

nctio

n.

PET

Wor

king

mem

ory

task

for

fac

es(d

elay

ed m

atch

-to-

sam

ple)

.C

ontr

ast:

wor

king

mem

ory

vs.

sens

orim

otor

con

trol

; par

tial l

east

squa

res

anal

ysis

use

d to

exa

min

eef

fect

of

diff

erin

g de

lays

.

Who

le b

rain

ana

lysi

sO

vera

ll ef

fect

s: O

> Y

in L

dors

olat

eral

pre

fron

tal a

ctiv

atio

nan

d R

ext

rast

riat

e (b

oth

activ

atio

n an

d de

activ

atio

n); Y

>O

in B

infe

rior

pre

fron

tal

activ

atio

n an

d R

pre

fron

tal,

Lpr

emot

or, R

per

isyl

vian

and

mid

line

cing

ulat

e de

activ

atio

n.

Rea

ctio

n tim

eY

and

O: P

OS

corr

elat

ions

in R

orb

itofr

onta

lan

d ex

tras

tria

te, N

EG

cor

rela

tions

inpe

risy

lvia

n, d

orso

med

ial p

refr

onta

l, an

dpo

ster

ior

cing

ulat

e (

); Y

mor

ePO

S sl

ope

than

O: R

mid

dle

tem

pora

l and

med

ial p

rest

riat

e; O

mor

e PO

S sl

ope

than

Y: B

dors

olat

eral

PFC

, L h

ippo

cam

pus,

and

Bfu

sifo

rm (

).

Haz

lett

EA

, Buc

hsba

umet

al.,

199

8, A

ge-r

elat

edsh

ift i

n br

ain

regi

onac

tivity

dur

ing

succ

essf

ulm

emor

y pe

rfor

man

ce

N=

70 (

10 p

erde

cade

of

age)

;A

lso

subs

et o

fY

: 16

, O:

16

over

all a

ge r

ange

= 2

0–87

,35

M:3

5F, S

ubsa

mpl

e: Y

:m

ean

age

= 3

3.4,

age

ran

ge =

20–4

9; O

: m

ean

age

= 7

3.5,

age

rang

e =

60–

87, m

ean

year

s of

edu

catio

n =

16.

1

Med

ical

and

psy

chia

tric

exam

inat

ion.

Exc

lusi

ons;

psyc

hoac

tive

med

icat

ion

use,

sub

stan

ce a

buse

/de

pend

ence

, psy

chia

tric

illne

ss, p

ositi

ve u

rine

drug

scr

een.

Cog

nitiv

ely

norm

al.

PET

Seri

al V

erba

l Lea

rnin

g te

st(S

VL

T)

with

5 li

sts

of 1

6 w

ords

(fro

m 4

sem

antic

cat

egor

ies)

eac

hpr

esen

ted

visu

ally

, rea

d al

oud

byth

e pa

rtic

ipan

t, an

d re

calle

d 5

times

. Con

tras

t(s)

: N/A

.

15 c

ortic

al R

OIs

. Als

o,vo

xel-

wis

e st

atis

tical

para

met

ric

map

ping

.

NE

G a

ssoc

iatio

n w

ith m

etab

olic

rate

in s

uper

ior,

mid

dle,

and

infe

rior

fro

ntal

gyr

us; P

OS

asso

ciat

ion

in o

ccip

ital l

obe.

On

voxe

l-w

ise,

reg

ions

of

grea

test

NE

G c

orre

latio

n w

ere

med

ial

fron

tal/c

ingu

late

gyr

us a

ndan

teri

or ti

p of

tem

pora

l lob

e.

With

in Y

and

O g

roup

s,cr

eate

d su

bgro

up w

ithG

oodR

ecal

l (>

13.3

wor

ds)

and

Poor

Rec

all (

<12

.2w

ords

). W

ithin

Goo

dRec

all

and

Poor

Rec

all s

ubgr

oups

, Y=

O f

or n

umbe

r of

wor

dsre

calle

d.

Y:

Goo

dRec

all >

Poo

rRec

all i

n fr

onta

l; O

:G

oodR

ecal

l > P

oorR

ecal

l ()

inoc

cipi

tal.

Fron

tal/o

ccip

ital r

atio

fav

ored

fro

ntal

in Y

Goo

dRec

all v

s. P

oorR

ecal

l, fa

vore

doc

cipi

tal i

n O

Goo

dRec

all v

s. P

oorR

ecal

l(

) ; G

oodR

ecal

l > P

oorR

ecal

lin

L f

ront

al/o

ccip

ital r

atio

reg

ardl

ess

of a

ge.

Mad

den,

Got

tlob

et a

l.,19

99, A

ging

and

reco

gniti

on m

emor

y:

Y:

12, O

: 12

(sam

e as

Mad

den,

Y: m

ean

age

= 2

3.17

, 6F:

6M,

age

rang

e =

20-

2; O

: mea

nag

e =

71.

0, 7

F:5M

, age

ran

ge

No

maj

or h

ealth

pro

blem

son

scr

eeni

ngqu

estio

nnai

re. N

egat

ive

PET

Thr

ee ta

sk c

ondi

tions

for

wor

dle

arni

ng a

nd r

ecog

nitio

n:E

ncod

ing

(int

entio

nal;

livin

g/

RO

IS in

whi

ch a

sign

ific

ant c

orre

latio

nw

ith m

ean

reac

tion

time

Non

e re

port

edE

x-G

auss

ian

curv

e fi

tted

tore

actio

n tim

e di

stri

butio

nyi

elde

d m

easu

res

of m

u

Y:

Ret

riev

al v

s. B

asel

ine:

PO

S co

rrel

atio

n w

ithm

u (b

ut n

ot ta

u) in

R m

iddl

e fr

onta

l gyr

us. O

:E

ncod

ing

vs. B

asel

ine:

PO

S co

rrel

atio

n w

ith

Biol Psychiatry. Author manuscript; available in PMC 2013 May 02.

NIH

-PA Author Manuscript

NIH

-PA Author Manuscript

NIH

-PA Author Manuscript

Eyler et al. Page 15

Cit

atio

nN

umbe

r of

Par

tici

pant

sC

hara

cter

isti

cs o

fpa

rtic

ipan

tsD

efin

itio

n of

"Hea

lthy

"T

ype

ofIm

agin

gP

arad

igm

tes

ted

Bra

inR

egio

n(s)

Exa

min

ed

Age

Dif

fere

nce(

s) in

Bra

inF

unct

ion

Succ

ess/

Per

form

ance

Det

erm

inat

ion

Succ

ess/

Per

form

ance

Cor

rela

tion

or

Eff

ect(

s)

Cha

nges

in r

egio

nal

cere

bral

blo

od f

low

asso

ciat

ed w

ithco

mpo

nent

s of

rea

ctio

ntim

e di

stri

butio

ns

Tur

king

ton,

et

al.,

1999

)=

62–

79, m

ean

age

= 7

1.0;

All

part

icip

ants

had

fin

ishe

dhi

gh s

choo

l.

neur

olog

ic s

cree

ning

exam

. MM

SE o

f ≥2

8 an

d≤

6 on

Bec

k de

pres

sion

inve

ntor

y. M

RI

free

of

abno

rmal

ities

.

nonl

ivin

g ju

dgm

ent)

, Bas

elin

e(t

old

that

wor

ds w

ill n

ot b

e te

sted

;ca

pita

lizat

ion

judg

men

t), a

ndR

etri

eval

(ye

s/no

rec

ogni

tion

judg

men

t); C

ontr

ast(

s): E

ncod

ing

vs. B

asel

ine

and

Ret

riev

al v

s.B

asel

ine.

had

been

obs

erve

d in

Mad

den,

Tur

king

ton,

et

al.,

1999

.

(mea

n of

the

Gau

ssia

nco

mpo

nent

; lea

ding

edg

e) a

ndta

u (m

ean

of th

e ex

pone

ntia

lco

mpo

nent

; tai

l).

tau

in R

mid

dle

fron

tal g

yrus

and

Lpa

rahi

ppoc

ampa

l gyr

us; R

etri

eval

vs.

Bas

elin

e:PO

S co

rrel

atio

n w

ith m

u in

R m

iddl

e fr

onta

lgy

rus

and

with

tau

in R

BA

10,

NE

Gco

rrel

atio

ns w

ith m

u in

R in

feri

or p

arie

tal

lobu

le, w

ith ta

u in

R c

uneu

s, a

nd w

ith b

oth

mu

and

tau

in L

tran

sver

se te

mpo

ral g

yrus

Mad

den,

Tur

king

ton

etal

., 19

99, A

dult

age

diff

eren

ces

in th

efu

nctio

nal n

euro

anat

omy

of v

erba

l rec

ogni

tion

mem

ory

Y:

12, O

: 12

Y: m

ean

age

= 2

3.17

, 6F:

6M,

age

rang

e =

20–

29; O

: mea

nag

e =

71.

0, 7

F:5M

, age

ran

ge=

62–

79, a

ll pa

rtic

ipan

ts h

adfi

nish

ed h

igh

scho

ol.

No

maj

or h

ealth

pro

blem

son

scr

eeni

ngqu

estio

nnai

re. N

egat

ive

neur

olog

ic s

cree

ning

exam

. MM

SE o

f ≥2

8 an

d≤

6 on

Bec

k de

pres

sion

inve

ntor

y. M

RI

free

of

abno

rmal

ities

.

PET

Thr

ee ta

sk c

ondi

tions

for

wor

dle

arni

ng a

nd r

ecog

nitio

n:E

ncod

ing

(int

entio

nal;

livin

g/no

nliv

ing

judg

men

t), B

asel

ine

(tol

d th

at w

ords

will

not

be

test

ed;

capi

taliz

atio

n ju

dgm

ent)

, and

Ret

riev

al (

yes/

no r

ecog

nitio

nju

dgm

ent)

; con

tras

t(s)

: Enc

odin

gvs

. Bas

elin

e an

d R

etri

eval

vs.

Bas

elin

e

Who

le b

rain

ana

lysi

s;su

cces

s an

alys

is o

nly

for

valu

es a

t loc

al m

axim

aof

reg

ions

of

sign

ific

ant

rCB

F.

Enc

odin

g m

inus

Bas

elin

e: O

> Y

in th

alam

us; R

etri

eval

min

usB

asel

ine:

Y >

O in

thal

amus

, O>

Y in

B p

refr

onta

l cor

tex.

Rea

ctio

n tim

e di

ffer

ence

betw

een

expe

rim

enta

l and

base

line

cond

ition

s.

Bas

elin

e an

d E

ncod

ing

cond

ition

: O:

POS

corr

elat

ion

of R

T d

iffe

renc

e w

ith r

CB

Fdi

ffer

ence

in le

ft p

arah

ippo

cam

pal g

yrus

and

Rm

iddl

e fr

onta

l gyr

us (

);B

asel

ine

and

Ret

riev

al c

ondi

tion:

Y:

POS

corr

elat

ion

in R

mid

dle

fron

tal g

yrus

; O:

POS

corr

elat

ion

in R

mid

dle

fron

tal g

yrus

(),

NE

G c

orre

latio

ns in

sev

eral

post

erio

r re

gion

s (

)

McI

ntos

h et

al.,

199

9,R

ecru

itmen

t of

uniq

uene

ural

sys

tem

s to

sup

port

visu

al m

emor

y in

nor

mal

agin

g

Y:

10, O

: 9

Y:

mea

n ag

e =

23,

age

ran

ge=

20–

30; O

: m

ean

age

= 6

5,ag

e ra

nge

= 6

0–79

In g

ood

heal

th a

nd in

norm

al r

ange

on

MM

SEan

d a

voca

bula

ry te

st.

PET

Dis

crim

inat

ion

of s

patia

lfr

eque

ncy

betw

een

two

sine

wav

egr

atin

gs p

rese

nted

eith

er 5

00m

sec

(sho

rt I

SI)

or 4

000

mse

c(l

ong

ISI)

apa

rt (

pret

estin

g to

mat

ch d

iffi

culty

/acc

urac

ybe

twee

n gr

oups

). C

ontr

ast(

s):

part

ial l

east

squ

are

of b

rain

-be

havi

or c

orre

latio

ns th

at w

ere

com

mon

to o

r di

stin

guis

hed

ISI

cond

ition

s an

d gr

oup

( old

vs.

youn

g)

Who

le b

rain

ana

lysi

sN

one

repo

rted

(on

ly b

rain

-be

havi

or p

atte

rns

exam

ined

)D

iscr

imin

atio

n th

resh

old

(low

er is

bet

ter)

Y a

nd O

: Sho

rt I

SI: N

EG

cor

rela

tion

with

disc

rim

inat

ion

thre

shol

d (

) in

occi

pita

l, PO

S co

rrel

atio

n (

) in

stri

atum

, inf

erio

r pr

efro

ntal

and

infe

rote

mpo

ral.

Lon

g IS

I: r

ever

se p

atte

rn c

ompa

red

to a

bove

. Oon

ly: S

hort

ISI

: NE

G c

orre

latio

n w

ithdi

scri

min

atio

n th

resh

old

()

inte

mpo

ral a

nd d

orsa

l occ

ipita

l, PO

S co

rrel

atio

n(

) in

pos

teri

or th

alam

us a

nddo

rsom

edia

l pre

fron

tal c

orte

x. L

ong

ISI:

reve

rse

patte

rn c

ompa

red

to a

bove

. Y:

oppo

site

and

atte

ntua

ted

diff

eren

ce b

etw

een

ISI

cond

ition

s.

Reu

ter-

Lor

enz

et a

l.,20

00, A

ge d

iffe

renc

es in

the

fron

tal l

ater

aliz

atio

nof

ver

bal a

nd s

patia

lw

orki

ng m

emor

yre

veal

ed b

y PE

T

Ver

bal t

ask:

Y:

8, O

: 16

; Spa

tial

task

: Y:

10, O

:10

Y:

verb

al: m

ean

age

= 2

3.3,

age

rang

e =

21–

30, m

ean

year

s ed

ucat

ion

= 1

5, 8

F:0M

;Sp

atia

l: m

ean

age

= 2

1.2,

age

rang

e =

18–

25, m

ean

year

sed

ucat

ion

= 1

5; O

: ver

bal:

mea

n ag

e =

69.

9, a

ge r

ange

=62

–75,

mea

n ye

ars

educ

atio

n=

16;

Spa

tial:

mea

n ag

e =

67.4

, age

ran

ge =

62–

73,

mea

n ye

ars

educ

atio

n =

16

Rig

ht h

ande

d, n

egat

ive

neur

olog

ical

his

tori

es,

norm

al o

r co

rrec

ted

tono

rmal

vis

ion.

Opa

rtic

ipan

ts e

xclu

ded

from

ana

lysi

s if

had

spat

ial p

erfo

rman

ce >

1SD

bel

ow Y

gro

up.

PET

Ver

bal a

nd s

patia

l del

ayed

mat

chto

sam

ple

task

s; C

ontr

ast(

s):

Del

ayed

ver

bal m

atch

vs.

imm

edia

te v

erba

l mat

ch; D

elay

edsp

atia

l mat

ch v

s. im

med

iate

spat

ial m

atch

.

85 (

verb

al)

and

98(s

patia

l) b

ilate

ral R

OIs

from

lite

ratu

re, d

ivid

edin

to a

nter

ior

and

post

erio

r R

OIs

. For

corr

elat

ions

, lat

eral

itydi

ffer

ence

sco

reca

lcul

ated

for

ant

erio

r,po

ster

ior,

and

all

RO

Is.

Ver

bal:

Y >

O:

diff

eren

cebe

twee

n L

and

R a

cros

s al

lan

teri

or R

OIs

(L

> R

in Y

, L =

Rin

O, a

lthou

gh th

is e

xact

pat

tern

only

see

n in

one

sub

regi

on -

Bro

ca's

are

a); S

patia

l: Y

> O

:di

ffer

ence

bet

wee

n L

and

Rac

ross

all

ante

rior

RO

Is (

R >

L in

Y, R

= L

in O

, alth

ough

this

exac

t pat

tern

onl

y se

en in

one

subr

egio

n -

R s

uppl

emen

tary

mot

or a

rea)

.

Com

posi

te m

easu

re o

f Z

-sc

ore

for

aver

age

reac

tion

time

subt

ract

ed f

rom

the

z-sc

ore

for

perc

ent c

orre

ct, a

sw

ell a

s ea

ch o

f th

ese

sepa

rate

ly. A

dditi

onal

anal

ysis

usi

ng a

med

ian

split

base

d on

rea

ctio

n tim

e.

Ver

bal:

RT

med

ian

split

: in

L-

R la

tera

lity

of d

orso

late

ral p

refr

onta

l cor

tex

(SC

A =

bila

tera

l, N

CA

= R

onl

y); S

CA

= N

CA

in B

roca

's a

rea

late

ralit

y (b

oth

bila

tera

l).

Spat

ial:

SCA

= N

CA

. Who

le g

roup

: Ver

bal:

O:

POS

corr

elat

ion

of z

sco

re c

ompo

site

with

all

LR

OIs

, L p

oste

rior

RO

Is (

),N

EG

cor

rela

tion

of R

T w

ith L

Bro

ca's

();

Y:

no s

igni

fica

ntco

rrel

atio

ns w

ith c

ompo

site

, NE

G c

orre

latio

nle

ft la

tera

l sup

plem

enta

ry m

otor

are

a; S

patia

l:N

o si

gnif

ican

t cor

rela

tions

.

Ryp

ma

and

D'E

spos

ito,

2000

, Iso

latin

g th

e ne

ural

mec

hani

sms

age-

rela

ted

chan

ges

in h

uman

wor

king

mem

ory

3 ex

peri

men

t s:

Exp

. 1: Y

: 6,

O:

6; E

xp. 2

: Y:

7,O

: 6;

Exp

. 3: Y

:6,

O:

6

Exp

. 1-

Y: a

ge r

ange

= 2

1–30

, 3M

:3F,

mea

n ye

ars

educ

atio

n =

15.

4; O

; age

rang

e= 6

1–82

, 3M

:3F,

mea

nye

ars

educ

atio

n =

17.

6; E

xp.

2- Y

: ag

e ra

nge

= 1

9–26

,4M

:3F,

mea

n ye

ars

educ

atio

n=

16

year

s; O

: ag

e ra

nge

=55

–83,

2M

:4F,

mea

n ye

ars

educ

atio

n =

14.

5; E

xp. 3

- Y

:ag

e ra

nge

= 2

0–29

, 4M

:2F,

mea

n ye

ars

educ

atio

n =

15.

5;O

: ag

e ra

nge

= 6

6–71

, 3M

:3F

, mea

n ye

ars

educ

atio

n =

16.8

No

med

ical

, neu

rolo

gica

l,or

psy

chia

tric

illn

ess

oran

y pr

escr

iptio

nm

edic

atio

n. O

had

no

evid

ence

of

dem

entia

and

MM

SE >

26

and

Bec

kde

pres

sion

inve

ntor

y <

10.

fMR

IE

vent

-rel

ated

ver

bal d

elay

edre

spon

se ta

sk w

ith a

sm

all (

2le

tters

) or

larg

e (6

lette

rs)

mem

ory

load

(E

xp 1

and

2);

eve

nt-r

elat

edob

ject

or

spat

ial o

r ob

ject

+sp

atia

lm

atch

to s

ampl

e ta

sk (

Exp

3);

Con

tras

t(s)

: enc

odin

g pe

riod

vs.

base

line,

mai

nten

ance

per

iod

vs.

base

line,

retr

ieva

l per

iod

vs.

base

line.

Dor

sola

tera

l(B

rodm

ann’

s ar

eas

9 an

d46

) an

d ve

ntro

late

ral

(Bro

dman

n’s

area

s 44

,45

and

47)

pre

fron

tal

cort

ex; a

vera

ged

acro

ssL

and

R h

emis

pher

es.

Y >

O in

dor

sola

tera

l pre

fron

tal

cort

ex d

urin

g re

spon

se p

erio

d in

high

load

con

ditio

n in

all

thre

eex

peri

men

ts.

Mea

n re

actio

n tim

e.A

ll 3

Exp

ts: O

: N

EG

cor

rela

tion

of R

T a

nddo

rsol

ater

al p

refr

onta

l act

ivat

ion

duri

ng th

ere

spon

se p

erio

d (

); Y

: PO

Sco

rrel

atio

n of

RT

and

dor

sola

tera

l pre

fron

tal

activ

atio

n du

ring

the

resp

onse

per

iod.

Biol Psychiatry. Author manuscript; available in PMC 2013 May 02.

NIH

-PA Author Manuscript

NIH

-PA Author Manuscript

NIH

-PA Author Manuscript

Eyler et al. Page 16

Cit

atio

nN

umbe

r of

Par

tici

pant

sC

hara

cter

isti

cs o

fpa

rtic

ipan

tsD

efin

itio

n of

"Hea

lthy

"T

ype

ofIm

agin

gP

arad

igm

tes

ted

Bra

inR

egio

n(s)

Exa

min

ed

Age

Dif

fere

nce(

s) in

Bra

inF

unct

ion

Succ

ess/

Per

form

ance

Det

erm

inat

ion

Succ

ess/

Per

form

ance

Cor

rela

tion

or

Eff

ect(

s)

Reu

ter-

Lor

enz

et a

l.,20

01 (

42),

Neu

roco

gniti

ve a

gein

g of

stor

age

and

exec

utiv

epr

oces

ses

Y:

12, O

: 12

(com

bine

d w

ithsu

bjec

ts f

rom

Reu

ter-

Lor

enz

etal

., 20

00 f

orsu

cces

s an

alys

is)

Y:

age

rang

e =

19–

30, 1

2M:

0F; O

: ag

e ra

nge

= 6

1–72

,12

M:0

F

Rig

ht h

ande

d, n

egat

ive

neur

olog

ical

his

tori

es,

norm

al o

r co

rrec

ted

visi

on. O

par

ticip

ants

excl

uded

if s

patia

lpe

rfor

man

ce >

1SD

bel

owY

gro

up.

PET

Ver

bal d

elay

ed m

atch

to s

ampl

eta

sk; C

ontr

ast(

s): D

elay

ed v

erba

lm

atch

vs.

imm

edia

te v

erba

lm

atch

.

RO

Is b

ased

on

resu

lts o

fR

eute

r-L

oren

z et

al,

2000

.

O >

Y:

R d

orso

late

ral p

refr

onta

lco

rtex

, R a

rea

44, R

par

ieta

lar

eas

40 a

nd 7

; Y >

O: L

are

a 44

.

Rea

ctio

n tim

eO

: N

EG

cor

rela

tion

with

RT

()

in R

dor

sola

tera

l pre

fron

tal c

orte

x.

Cab

eza

R e

t al.,

200

2,A

ging

gra

cefu

lly:

Com

pens

ator

y br

ain

activ

ity in

hig

h-pe

rfor

min

g n

olde

r ad

ults

Y:

12, O

: 16

(SC

A: 8

, NC

A:

8)

Y: m

ean

age

= 2

5.3,

age

rang

e =

20–

35, 7

M:5

F; S

CA

:m

ean

age

= 6

8, a

ge r

ange

=64

–78,

4M

:4F;

NC

A: m

ean

age

= 6

9.9,

age

ran

ge =

63–

74, 4

M:4

F

No

neur

olog

ic o

rps

ychi

atri

c hi

stor

y. N

one

on m

edic

atio

n or

with

med

ical

con

ditio

naf

fect

ing

cere

bral

blo

odfl

ow.

PET

Epi

sodi

c m

emor

y fo

r re

cent

lyst

udie

d w

ords

. Con

tras

t(s)

: Rec

all

vs. s

ourc

e m

emor

y an

d so

urce

mem

ory

vs. r

ecal

l.

Pref

ront

al r

egio

nsac

tivat

ed b

y en

tire

grou

p.

Non

e re

port

edD

ivid

ed in

to S

CA

vs.

NC

Aba

sed

on c

ompo

site

mem

ory

scor

e of

sub

test

s fr

omW

echs

ler

Mem

ory

Scal

e an

dC

alif

orni

a V

erba

l Lea

rnin

gT

est.

Rec

all-

sour

ce c

ontr

ast:

Y >

SC

A =

NC

A in

Ldo

rsol

ater

al p

refr

onta

l, Y

=

inle

ft v

entr

olat

eral

; Sou

rce-

reca

ll co

ntra

st: Y

>SC

A =

NC

A in

R d

orso

late

ral p

refr

onta

l, Y

<N

CA

= S

CA

in r

ight

ant

erio

r pr

efro

ntal

, SC

A >

Y =

NC

A in

left

ant

erio

r pr

efro

ntal

.

Gra

dy e

t al.,

200

2, T

heef

fect

s of

enc

odin

g ta

skon

age

-rel

ated

diff

eren

ces

in th

efu

nctio

nal n

euro

anat

omy

of f

ace

mem

ory

Y:

12, O

: 11

Y:

mea

n ag

e =

23.

2, a

gera

nge

= 2

0–28

, 6M

:6F,

mea

nye

ars

educ

atio

n =

17;

O:

mea

n ag

e 70

, age

ran

ge =

62–7

9, 6

M:5

F, m

ean

year

sed

ucat

ion

= 1

5.7

No

dise

ases

or

med

icat

ions

that

aff

ect

brai

n fu

nctio

n; n

oab

norm

aliti

es o

n M

RI;

MM

SE a

nd v

ocab

ular

y in

norm

al r

ange

.

PET

Epi

sodi

c en

codi

ng a

nd r

etri

eval

for

face

s. L

evel

s of

pro

cess

ing

man

ipul

atio

n du

ring

enc

odin

g (3

leve

ls: i

nten

tiona

l, in

cide

ntal

with

orie

ntat

ion

judg

men

t, in

cide

ntal

with

ple

asan

tnes

s ju

dgm

ent)

.R

etri

eval

pha

se in

volv

ed f

orce

d-ch

oice

rec

ogni

tion

task

s.C

ontr

ast(

s): p

artia

l lea

st s

quar

esan

alys

is o

f pa

ttern

s as

soci

ated

with

enc

odin

g vs

. con

trol

,re

trie

val v

s. c

ontr

ol, e

ncod

ing

vs.

retr

ieva

l.

Who

le b

rain

ana

lysi

sB

rain

reg

ions

that

dis

tingu

ish

all

enco

ding

vs.

con

trol

(in

feri

orpr

efro

ntal

and

L a

myg

dala

) an

dal

l rec

ogni

tion

vs. c

ontr

ol (

Bpr

efro

ntal

, L p

rem

otor

, cin

gula

tegy

rus)

in Y

onl

y di

stin

guis

hin

tent

iona

l and

dee

p vs

. con

trol

in O

. Thu

s, Y

> O

in th

ese

regi

ons

duri

ng s

hallo

w e

ncod

ing

and

reco

gniti

on o

f sh

allo

wly

enco

ded

wor

ds (

conf

irm

ed in

cont

rast

of

enco

ding

vs.

reco

gniti

on).

Rec

ogni

tion:

O >

Yin

L a

nter

ior

tem

pora

l and

prem

otor

cor

tex;

Y >

O in

Rdo

rsol

ater

al p

refr

onta

l. E

ncod

ing

vs. r

ecog

nitio

n: Y

> O

in L

pref

ront

al a

nd a

nter

ior

cing

ulat

e(Y

: E >

R, O

: R >

E).

Part

ial l

east

squ

are

anal

ysis

of

reco

gniti

on a

ccur

acy.

Enc

odin

g an

d R

ecog

nitio

n: Y

: PO

S co

rrel

atio

nw

ith a

ccur

acy

in B

hip

poca

mpu

s, o

rbito

fron

tal

cort

ex, L

tem

pora

l pol

e, O

: PO

S co

rrel

atio

nw

ith a

ccur

acy

()

in B

pos

teri

orte

mpo

ral a

nd o

ccip

ital a

nd R

pre

fron

tal c

orte

x,B

oth

Y a

nd O

: D

eep

inci

dent

al e

ncod

ing:

PO

Sco

rrel

atio

n (

) w

ith L

pre

fron

tal

(2 r

egio

ns),

L p

oste

rior

tem

pora

l; Sh

allo

win

cide

ntal

enc

odin

g: P

OS

corr

elat

ion

()

with

ext

rast

riat

e re

gion

s.

Iida

ka, O

kada

et a

l.,20

02, A

ge-r

elat

eddi

ffer

ence

s in

the

med

ial

tem

pora

l lob

e re

spon

ses

to e

mot

iona

l fac

es a

sre

veal

ed b

y fM

RI

Y:

12, O

: 12

Y:

mea

n ag

e =

25.

1, a

gera

nge

= 1

9–36

, 6M

:6F,

mea

nye

ars

educ

atio

n =

15.

8; O

:m

ean

age

= 6

5.2,

6M

:6F,

age

rang

e =

62–

72, m

ean

year

sed

ucat

ion

= 1

6.0

No

hist

ory

of n

euro

logi

cal

dise

ases

, psy

chia

tric

dise

ases

, or

drug

or

alco

hol a

buse

bas

ed o

nin

terv

iew

. No

med

icat

ions

that

cou

ld a

ffec

t CB

F. T

2M

RI

free

of

inci

dent

alin

farc

tions

.

fMR

IE

mot

iona

l fac

e pe

rcep

tion:

judg

ing

the

gend

er o

f fa

ces

with

nega

tive

(ang

ry o

r di

sgus

ting)

,po

sitiv

e (h

appy

), o

r ne

utra

lem

otio

nal v

alen

ce; C

ontr

ast(

s):

nega

tive

vs. b

asel

ine

(jud

ging

rela

tive

size

of

rect

angl

es),

posi

tive

vs. b

asel

ine,

neu

tral

vs.

base

line;

neg

ativ

e vs

. neu

tral

,po

sitiv

e vs

. neu

tral

, and

neg

ativ

evs

. pos

itive

als

o as

sess

ed f

or a

gean

alys

is.

Who

le b

rain

ana

lysi

s:si

ngle

gro

up r

esul

ts u

sed

as m

asks

for

com

pari

son

of a

ge g

roup

s; s

ucce

ssan

alys

es c

ondu

cted

inam

ygda

la, h

ippo

-cam

pus

and

para

hipp

o-ca

mpa

lgy

rus.

Neg

ativ

e co

nditi

on: Y

> O

: L

amyg

dala

; Pos

itive

con

ditio

n: Y

> O

: R

par

ahip

poca

mpa

l gyr

us,

R li

ngua

l gyr

us, R

ang

ular

gyr

us;

Neu

tral

con

ditio

n: Y

> O

: B

mid

brai

n, L

ling

ual g

yrus

; tas

k-in

depe

nden

t act

ivity

of

Rhi

ppoc

ampu

s P

OS

corr

elat

edw

ith a

ge in

O g

roup

onl

y.

Scor

e on

the

firs

t pri

ncip

alco

mpo

nent

of

four

neur

opsy

chol

ogic

al te

sts

(dig

it sy

mbo

l, tr

ail-

mak

ing,

wor

d re

call,

and

fig

ure

reca

ll).

O:

POS

corr

elat

ion

betw

een

glob

al n

euro

psyc

han

d ov

eral

l act

ivat

ion

of R

par

ahip

poca

mpu

s(o

nly

wor

d re

call

indi

vidu

ally

sig

nifi

cant

)(

); Y

: no

sig

nifi

cant

corr

elat

ions

.

Mad

den,

Lan

gley

et a

l.,20

02, A

dult

age

diff

eren

ces

in v

isua

lw

ord

iden

tific

atio

n:Fu

nctio

nal

Neu

roan

atom

y by

PE

T

Y: 1

2, O

: 12

Y: m

ean

age

= 2

3.58

, age

rang

e =

20–

29, 6

M:6

F,ed

ucat

ion

= 1

5.67

; O: m

ean

age

= 6

5.0,

age

ran

ge =

62–

70, 6

M:6

F, e

duca

tion

=16

.75

No

curr

ent h

ealth

prob

lem

s or

pre

viou

ssi

gnif

ican

t med

ical

eve

nts

(e.g

., he

ad in

jury

with

loss

of

cons

ciou

snes

s >

5m

in.,

stro

ke, T

IA, M

I, a

ndhe

art s

urge

ry),

det

erm

ined

by q

uest

ionn

aire

. MM

SE≥

27. M

RI

revi

ewed

toru

le o

ut s

igni

fica

ntab

norm

ality

.

PET

Lex

ical

dec

isio

n ta

sk (

wor

d/no

nwor

d di

scri

min

atio

n) w

ith 3

cond

ition

s of

dif

fere

nt d

urat

ion

and

pres

enta

tion

rate

s.C

ontr

ast(

s): L

exic

al d

ecis

ion

cond

ition

vs.

non

sem

antic

(si

mpl

evi

sual

sea

rch)

con

ditio

n, lo

ngdu

ratio

n le

xica

l dec

isio

n vs

. sho

rtdu

ratio

n, s

hort

pre

sent

atio

n ra

tele

xica

l dec

isio

n vs

. lon

gpr

esen

tatio

n ra

te.

Who

le b

rain

ana

lysi

s:si

ngle

gro

up r

esul

ts u

sed

as m

asks

for

com

pari

son

of a

ge g

roup

s; s

ucce

ssan

alys

es o

nly

cond

ucte

din

loca

l max

ima

of a

geef

fect

s.

Lex

ical

dec

isio

n m

inus

Bas

elin

e:Y

> O

in a

ctiv

atio

n of

L s

tria

teco

rtex

(B

A 1

7) a

nd d

eact

ivat

ion

of p

arie

tal c

orte

x, O

> Y

in L

infe

rior

tem

pora

l cor

tex

(BA

37)

.N

o ag

e di

ffer

ence

s in

eff

ect o

fdu

ratio

n or

pre

sent

atio

n ra

te.

Pear

son

corr

elat

ions

bet

wee

nst

anda

rdiz

ed R

Ts

and

norm

aliz

ed c

ount

val

ues

for

the

left

str

iate

and

left

infe

rior

tem

pora

l vox

els.

Y:

POS

corr

elat

ion

of R

T w

ith r

CB

F in

Lst

riat

e; O

: sm

all,

non-

sign

ific

ant P

OS

corr

elat

ion

in th

is r

egio

n, th

at w

as n

otsi

gnif

ican

tly d

iffe

rent

fro

m Y

().

Biol Psychiatry. Author manuscript; available in PMC 2013 May 02.

NIH

-PA Author Manuscript

NIH

-PA Author Manuscript

NIH

-PA Author Manuscript

Eyler et al. Page 17

Cit

atio

nN

umbe

r of

Par

tici

pant

sC

hara

cter

isti

cs o

fpa

rtic

ipan

tsD

efin

itio

n of

"Hea

lthy

"T

ype

ofIm

agin

gP

arad

igm

tes

ted

Bra

inR

egio

n(s)

Exa

min

ed

Age

Dif

fere

nce(

s) in

Bra

inF

unct

ion

Succ

ess/

Per

form

ance

Det

erm

inat

ion

Succ

ess/

Per

form

ance

Cor

rela

tion

or

Eff

ect(

s)

Mad

den,

Tur

king

ton

etal

., 20

02, A

ging

and

atte

ntio

nal g

uida

nce

duri

ng v

isua

l sea

rch

func

tiona

l neu

roan

atom

yby

PE

T

Y:

12, O

: 12

Y:

mea

n ag

e =

23.

0, 5

M:7

F,ag

e ra

nge

= 2

0–27

; O:

mea

nag

e =

63.

5, 5

M:7

F, a

ge r

ange

= 6

0–77

, all

subj

ects

had

at

leas

t hig

h sc

hool

edu

catio

n

No

curr

ent h

ealth

prob

lem

s or

pre

viou

ssi

gnif

ican

t med

ical

even

ts, a

s de

term

ined

by

asc

reen

ing

ques

tionn

aire

.M

MSE

> 2

7. N

osi

gnif

ican

t atr

ophy

or

stru

ctur

al a

bnor

mal

ity o

nM

RI.

PET

Vis

ual s

earc

h ta

sk w

ith 3

cond

ition

s: F

eatu

re (

targ

etdi

stin

guis

hed

by c

olor

fro

m a

ll 17

dist

ract

ors)

, Gui

ded

(tar

get +

2di

stra

ctor

s in

sam

e co

lor)

, and

Con

junc

tion

(tar

get +

8 d

istr

acto

rsin

sam

e co

lor)

; Con

tras

t(s)

:co

njun

ctio

n vs

. fea

ture

, gui

ded

vs.

feat

ure,

con

junc

tion

vs. g

uide

d.

Who

le b

rain

ana

lysi

sw

ith a

ge a

naly

sis

only

inar

eas

of s

igni

fica

nt r

CB

Fta

sk r

espo

nse.

Con

junc

tion

min

us f

eatu

re: Y

>O

in R

str

iate

and

ext

rast

riat

eco

rtex

; O >

Y d

eact

ivat

ion

of R

mid

dle

tem

pora

l gyr

us;

Con

junc

tion

min

us g

uide

d: Y

>O

in R

str

iate

cor

tex

and

Bve

ntra

l ext

rast

riat

e co

rtex

;G

uide

d m

inus

fea

ture

: O >

Yde

activ

atio

n in

R m

iddl

ete

mpo

ral g

yrus

and

B a

nter

ior

cing

ulat

e.

Acc

urac

y of

vis

ual s

earc

h.Y

> O

: m

ore

POS

corr

elat

ion

in Y

in v

entr

alpr

oces

sing

str

eam

and

R m

iddl

e fr

onta

l gyr

us,

mor

e N

EG

cor

rela

tion

in Y

in R

mid

dle

tem

pora

l gyr

us; O

: man

y ot

her

regi

ons

of P

OS

corr

elat

ion

().

Mat

tay,

Tes

sito

re e

t al.,

2002

,N

euro

phys

iolo

gica

lco

rrel

ates

of

age-

rela

ted

chan

ges

in h

uman

mot

orfu

nctio

n

Y:

10, O

: 12

Y: m

ean

age

= 3

0, a

ge r

ange

= 2

4–34

, 9M

:1F;

O: a

gera

nge

= 5

0–74

, mea

n ag

e =

59, 7

M:5

F

No

hist

ory

of n

euro

logi

c,ps

ychi

atri

c, o

r m

edic

alpr

oble

ms;

no

curr

ent

med

icat

ions

. No

sign

ific

ant c

hang

es a

bove

norm

al a

ge-r

elat

ed o

n T

1an

d T

2 M

RI.

fMR

IV

isua

lly p

aced

"Pu

sh b

utto

n"m

otor

task

with

dom

inan

t han

dal

tern

atin

g w

ith a

res

t sta

te.

Con

tras

t(s)

: mot

or ta

sk v

s. re

st.

Who

le b

rain

ana

lysi

s.O

> Y

: B

pri

mar

y m

otor

, Rpr

imar

y se

nsor

y, R

late

ral

prem

otor

are

a, B

sup

plem

enta

rym

otor

, L p

utam

en, B

par

ieta

lco

rtex

, B c

ereb

ellu

m.

Mea

n re

actio

n tim

eO

: N

EG

cor

rela

tions

with

res

pect

to R

T(

) in

B p

rim

ary

mot

or c

orte

x,B

late

ral p

rem

otor

are

a, m

idlin

e su

pple

men

tary

mot

or a

rea,

L p

arie

tal c

orte

x, L

occ

ipita

l cor

tex,

R c

ereb

ellu

m.

Nie

lson

et a

l., 2

002,

Dif

fere

nces

in th

efu

nctio

nal n

euro

anat

omy

of in

hibi

tory

con

trol

acro

ss th

e ad

ult l

ife

dpan

Par

t 1:

Y:

10,

MA

: 7,

YE

: 9,

O:

8; P

art

2:Y

oung

Old

Goo

d (Y

O/G

):4,

You

ng O

ldPo

or (

YO

/P)

6;O

ld O

ld G

ood

(OO

/G)

6, O

ldO

ld P

oor

(OO

/P

) 4.

Par

t 1:

Y: m

ean

age

= 2

5.5,

age

rang

e =

18–

31, m

ean

year

s ed

ucat

ion

= 1

5.5,

6M

:4F

; MA

: mea

n ag

e =

43.

3,ag

e ra

nge

= 3

3–55

, mea

nye

ars

educ

atio

n =

17.

1, 3

M:

4F; Y

E:

mea

n ag

e =

68.

9,ag

e ra

nge

= 6

2–72

, mea

nye

ars

educ

atio

n =

16.

9, 1

M:

8F; O

: mea

n ag

e =

75.

1, a

gera

nge

= 7

3–78

, mea

n ye

ars

educ

atio

n =

19.

3, 4

M:4

F.P

art

2: Y

O/G

: m

ean

age

=64

.3, m

ean

year

s ed

ucat

ion

=18

.3; Y

O/P

: m

ean

age

=62

.5, m

ean

year

s ed

ucat

ion

=17

.2; O

O/G

: mea

n ag

e =

73.5

, mea

n ye

ars

educ

atio

n =

17.7

; OO

/P:

mea

n ag

e =

76.0

, mea

n ye

ars

educ

atio

n =

19.8

No

med

icat

ions

,su

bsta

nces

or

dise

ases

affe

ctin

g pe

rfor

man

ce o

rim

agin

g; n

o hi

stor

y of

or

curr

ent p

sych

olog

ical

or

neur

olog

ical

con

ditio

ns;

O >

50

had

to h

ave

MM

SE o

f >

26

and

Ger

iatr

ic D

epre

ssio

nSc

ale

< 1

0.

fMR

IG

o/N

o G

o ta

sk in

whi

ch r

espo

nse

is m

ade

to a

ltern

atin

g st

imul

i (X

or Y

) th

us r

equi

ring

inhi

bitio

n of

resp

onse

to p

revi

ousl

y co

rrec

tst

imul

us. C

ontr

ast:

corr

ect t

arge

tsvs

. bas

elin

e an

d co

rrec

t lur

es v

s.ba

selin

e.

Par

t 1:

43

clus

ters

, Par

t2:

27

clus

ters

, all

thos

eth

at m

et c

rite

ria

for

sign

ific

ant a

ctiv

atio

n in

at le

ast o

ne g

roup

.

Par

t 1:

Inh

ibiti

on (

NoG

o): Y

>M

A, Y

E, a

nd O

in R

mid

dle

fron

tal a

nd f

usif

orm

gyr

i; M

A <

Y, Y

E, a

nd O

in s

tria

tal-

thal

amic

clus

ters

; O >

Y, M

A, Y

E in

RB

A 6

, mul

tiple

L p

refr

onta

lcl

uste

rs. T

arge

ts (

Go)

: Y >

MA

,Y

E, a

nd O

in b

asal

gan

glia

,th

alam

us, R

cin

gula

te, L

fusi

form

; Par

t 2:

OO

> Y

O in

2of

17

R h

emis

pher

e cl

uste

rs(m

iddl

e fr

onta

l gyr

us a

nd in

feri

orpa

riet

al lo

bule

) an

d 7

of 1

0 L

hem

isph

ere

clus

ters

(pa

riet

al,

pref

ront

al, a

nd th

alam

ic).

Med

ian

split

of

over

all

inhi

bitio

n pe

rfor

man

ce in

subg

roup

of

20 o

lder

part

icip

ants

: goo

dpe

rfor

mer

s ≤

5 er

rors

of

com

mis

sion

(>

78%

corr

ect)

, poo

r pe

rfor

mer

s >

6er

rors

(<

78%

cor

rect

).

in B

pre

supp

lem

enta

ry m

otor

area

and

L th

alam

us; p

erfo

rman

ce e

ffec

t in

Rpr

esup

plem

enta

ry m

otor

mos

t pro

noun

ced

inO

O g

roup

. Acr

oss

entir

e sa

mpl

e: P

OS

asso

ciat

ion

betw

een

R p

arie

tal a

ctiv

atio

n an

dbe

tter

inhi

bitio

n pe

rfor

man

ce, t

arge

tpe

rfor

man

ce, a

nd f

aste

r ta

rget

RT

().

NE

G c

orre

latio

n in

Lm

iddl

e fr

onta

l gyr

us: i

ncre

ased

act

ivat

ion

asso

ciat

ed w

ith s

low

ed R

T to

targ

ets

().

Ros

en e

t al

., 20

02 (

74),

Var

iabl

e ef

fect

s of

agi

ngon

fro

ntal

lobe

cont

ribu

tions

to m

emor

y

Y:

8, O

: 14

(SC

A: 7

, NC

A:

7)

Y: m

ean

age

= 2

4, a

ge r

ange

= 1

9–33

, 5M

:3F,

mea

n ye

ars

educ

atio

n =

17.

3; O

: mea

nag

e =

71,

age

ran

ge =

61–

81,

3M:1

1, m

ean

year

s of

educ

atio

n: 1

6.3

Scre

en f

or n

euro

logi

c,ps

ychi

atri

c, v

ascu

lar

risk

fact

ors,

or

med

icat

ion

know

n to

aff

ect v

ascu

lar

reac

tivity

or

cogn

ition

.

fMR

IV

erba

l enc

odin

g ta

sk (

bloc

kde

sign

). C

ontr

ast(

s): S

eman

tic v

s.no

n-se

man

tic e

ncod

ing

(lev

el o

fpr

oces

sing

eff

ect)

.

L a

nd R

infe

rior

PFC

,an

teri

or /

med

ial f

ront

al(b

ased

on

area

s of

activ

ity in

com

bine

dgr

oup)

.

SCA

= Y

in le

ft in

feri

or a

ndan

teri

or /

med

ial P

FC; S

CA

> Y

in r

ight

infe

rior

PFC

. NC

A =

Yin

all

3 re

gion

s.

Mem

ory

scre

enin

g (2

yea

rspr

ior)

: hig

h an

d lo

w m

emor

ygr

oups

sig

. dif

fere

nt o

npr

opor

tion

corr

ect o

n fo

urm

emor

y te

sts

Ran

ges

not

repo

rted

.

in th

e an

teri

or /

med

ial f

ront

al,

L in

feri

or f

ront

al, a

nd R

infe

rior

fro

ntal

.

Steb

bins

et a

l., 2

002,

Agi

ng e

ffec

ts o

n m

emor

yen

codi

ng in

the

fron

tal

lobe

s

Y:

15, O

: 15

Y:

mea

n ag

e 25

.3, a

ge r

ange

= 2

2–32

, 3M

:12F

, mea

nye

ars

educ

atio

n =

16.

7; O

:m

ean

age

= 7

6.5,

age

ran

ge =

65–8

7, 2

M:1

3F, m

ean

year

sed

ucat

ion

= 1

7.8

No

hist

ory

of n

euro

logi

cal

illne

ss; O

wer

e fr

om th

eR

elig

ious

Ord

ers

stud

yan

d ha

d m

edic

al a

ndne

urol

ogic

al e

xam

inat

ion

and

none

urop

sych

olog

ical

abno

rmal

ities

.

fMR

IIn

cide

ntal

wor

d en

codi

ng d

urin

gei

ther

sem

antic

(ab

stra

ct v

s.co

ncre

te)

or n

on-s

eman

tic(u

pper

case

vs.

low

erca

se)

deci

sion

s. C

ontr

ast(

s): s

eman

ticvs

. non

-sem

antic

enc

odin

g.

Who

le b

rain

ana

lysi

s in

each

gro

up m

aske

d by

RO

Is tr

aced

on

4 sl

ices

from

eac

h in

divi

dual

: Bsu

peri

or, m

iddl

e, in

feri

orfr

onta

l and

cin

gula

tegy

ri

Y >

O:

L s

uper

ior

and

mid

dle

fron

tal a

ctiv

atio

n (o

vera

ll: L

> R

in Y

, L =

R in

O).

Neu

rops

ycho

logi

cal m

easu

res

of: g

ener

al m

enta

l sta

tus,

imm

edia

te a

nd d

elay

ed s

tory

reca

ll, p

roce

ssin

g sp

eed,

wor

king

mem

ory,

rea

soni

ng;

educ

atio

n, w

ord

know

ledg

e.

Y:

POS

corr

elat

ion

with

wor

king

mem

ory

in L

cing

ulat

e; O

: PO

S co

rrel

atio

n(

) w

ith w

orki

ng m

emor

y in

Lin

feri

or a

nd m

iddl

e fr

onta

l gyr

i, an

d w

ithim

med

iate

rec

all m

emor

y in

R in

feri

or f

ront

algy

rus

and

L m

iddl

e gy

rus.

Das

elaa

r SM

et a

l., 2

003,

Neu

roan

atom

ical

corr

elat

es o

f ep

isod

icen

codi

ng a

nd r

etri

eval

in

Y:

17, O

: 40

(Nor

mal

Mem

ory

O:

19,

Y:

mea

n ag

e =

32.

7, a

gera

nge

= 3

0–35

, 17M

:0F,

educ

atio

n sc

ore

(7 p

oint

scal

e) =

5.9

; O:

age

rang

e

Non

e ta

king

psy

choa

ctiv

em

edic

atio

ns, n

one

urol

ogic

and

/or

psyc

holo

gica

l im

pair

men

t

fMR

IIn

cide

ntal

epi

sodi

c en

codi

ng f

orw

ords

(pl

easa

ntne

ss ju

dgm

ents

),in

term

ixed

with

bas

elin

e ta

sk(l

eft/r

ight

but

ton

pres

s);

Who

le b

rain

ana

lysi

sN

one

repo

rted

Div

ided

O p

artic

ipan

ts in

toR

educ

ed M

emor

y O

ver

sus

Nor

mal

Mem

ory

O b

ased

on

whe

ther

per

form

ance

on

Enc

odin

g: Y

= N

orm

al M

emor

y O

> R

educ

edM

emor

y O

()

in p

erir

hina

l/pa

rahi

ppoc

ampa

l clu

ster

. Slig

htly

less

left

late

raliz

atio

n in

Nor

mal

Mem

ory

O. R

etri

eval

Biol Psychiatry. Author manuscript; available in PMC 2013 May 02.

NIH

-PA Author Manuscript

NIH

-PA Author Manuscript

NIH

-PA Author Manuscript

Eyler et al. Page 18

Cit

atio

nN

umbe

r of

Par

tici

pant

sC

hara

cter

isti

cs o

fpa

rtic

ipan

tsD

efin

itio

n of

"Hea

lthy

"T

ype

ofIm

agin

gP

arad

igm

tes

ted

Bra

inR

egio

n(s)

Exa

min

ed

Age

Dif

fere

nce(

s) in

Bra

inF

unct

ion

Succ

ess/

Per

form

ance

Det

erm

inat

ion

Succ

ess/

Per

form

ance

Cor

rela

tion

or

Eff

ect(

s)

youn

g an

d el

derl

ysu

bjec

tsR

educ

edM

emor

y O

: 21)

63–7

1, 4

0M:0

F; N

orm

alM

emor

y O

: mea

n ag

e =

66.

4,m

ean

educ

atio

n sc

ore=

5.6

;R

educ

ed M

emor

y O

: m

ean

age

= 6

6.2,

mea

n ed

ucat

ion

scor

e =

5.3

repo

rted

on

gene

ral h

ealth

ques

tionn

aire

. O >

25

onM

MSE

. No

anat

omic

abno

rmal

ities

aty

pica

l for

age

on s

truc

tura

l MR

I.

Con

tras

t(s)

: suc

cess

fully

enc

oded

vs. b

asel

ine;

cor

rect

ly re

ject

ed v

s.ba

selin

e (r

etri

eval

atte

mpt

);co

rrec

tly re

cogn

ized

vs.

cor

rect

lyre

ject

ed (

retr

ieva

l suc

cess

);co

rrec

tly re

ject

ed v

s. c

orre

ctly

reco

gniz

ed.

scan

ner

task

was

less

than

or

grea

ter

than

the

mea

n of

the

Y g

roup

.

Atte

mpt

: Red

uced

Mem

ory

O >

Nor

mal

Mem

ory

O (

) =

Y in

L I

nsul

a,R

Mid

dle

Tem

pora

l, L

Sup

ram

argi

nal,

Cer

ebel

lum

, and

Occ

ipita

l cor

tex;

Nor

mal

Mem

ory

O >

Y =

Red

uced

Mem

ory

O(

) in

L I

nf F

ront

al G

yrus

.R

etri

eval

Suc

cess

: Red

uced

Mem

ory

O >

Y in

L I

nf F

ront

al G

yrus

.

Gra

dy, M

cInt

osh,

&C

raik

, 200

3, A

ge-r

elat

eddi

ffer

ence

s in

the

func

tiona

l con

nect

ivity

of th

e hi

ppoc

ampu

sdu

ring

mem

ory

enco

ding

Y:

11, O

: 12

Y:

mea

n ag

e =

23,

age

ran

ge=

19–

28, 6

M:6

F, m

ean

year

sed

ucat

ion

= 1

6; O

: m

ean

age

= 6

6, a

ge r

ange

= 5

8–73

, 6M

:6F

, mea

n ye

ars

educ

atio

n =

15

No

dise

ases

or

med

icat

ions

that

aff

ect

brai

n fu

nctio

n; n

oab

norm

aliti

es o

n M

RI;

MM

SE a

nd v

ocab

ular

y in

norm

al r

ange

PET

Inte

ntio

nal e

ncod

ing

of w

ords

and

line

draw

ings

dur

ing

a se

man

ticta

sk (

livin

g/no

n-liv

ing)

;C

ontr

ast(

s): p

artia

l lea

st s

quar

esan

alys

is o

f re

latio

nshi

p of

obj

ect

enco

ding

or w

ord

enco

ding

activ

ity to

reco

gniti

on a

ccur

acy

Reg

ions

of

sign

ific

ant

corr

elat

ion

with

rig

hthi

ppoc

ampa

l see

dre

gion

s (c

hose

n be

caus

eof

rel

atio

nshi

p to

perf

orm

ance

in b

oth

grou

ps)

Non

e re

port

edR

ecog

nitio

n ac

cura

cy(p

ropo

rtio

n hi

ts m

inus

prop

ortio

n fa

lse

alar

ms)

Y o

nly:

Obj

ect e

ncod

ing:

PO

S co

rrel

atio

ns w

ithac

cura

cy (

and

R h

ippo

cam

pus

activ

ity)

in L

hipp

ocam

pus,

ven

trol

ater

al p

refr

onta

l, in

feri

orte

mpo

ral,

vent

ral e

xtra

stri

ate,

R d

orso

late

ral

pref

ront

al, L

par

ieta

l, N

EG

cor

rela

tions

with

accu

racy

in d

orso

med

ial e

xtra

stri

ate,

sup

erio

rte

mpo

ral g

yrus

, pos

teri

or c

ingu

late

; O o

nly:

Obj

ect e

ncod

ing:

PO

S co

rrel

atio

ns(

) in

pre

fron

tal,

supe

rior

tem

pora

l, an

d in

feri

or p

arie

tal,

NE

Gco

rrel

atio

ns (

) in

ven

tral

extr

astr

iate

. Y >

O (

posi

tive

in Y

, NE

G in

O[

]): O

bjec

t enc

odin

g: R

thal

amus

, L s

enso

rim

otor

, and

R s

uper

ior

tem

pora

l. W

ord

enco

ding

: ven

tral

fro

ntal

,ve

ntra

l ext

rast

riat

e, in

feri

or te

mpo

ral.

O >

Y(P

OS

in O

[],

NE

G in

Y):

Wor

d en

codi

ng: d

orso

late

ral p

refr

onta

l, do

rsal

occi

pita

l, an

d su

peri

or te

mpo

ral.

Y =

O: O

bjec

ten

codi

ng: P

OS

corr

elat

ions

in R

ven

trol

ater

alpr

efro

ntal

; Wor

d en

codi

ng: P

OS

corr

elat

ions

inB

mid

dle

fron

tal g

yri,

R in

sula

, NE

Gco

rrel

atio

ns in

orb

itofr

onta

l cor

tex,

pre

cune

us,

and

dors

al a

nter

ior

cing

ulat

e.

Gro

n et

al.,

200

3,V

aria

bilit

y in

mem

ory

perf

orm

ance

in a

ged

heal

thy

indi

vidu

als:

An

fMR

I st

udy

O:

24O

: m

ean

age

= 6

4.4,

age

rang

e =

56–

76, 1

3M:1

1FN

o pa

thol

ogy

on m

edic

alhi

stor

y, r

adio

logi

cal,

neur

olog

ical

, and

neur

opsy

chol

ogic

alte

stin

g an

d no

sub

ject

ive

mem

ory

com

plai

nts.

fMR

IIn

tent

iona

l enc

odin

g of

abs

trac

tpa

ttern

s an

d re

call

of th

e pa

ttern

.C

ontr

ast(

s): I

nitia

l lea

rnin

g vs

.la

te le

arni

ng; m

axim

um re

call

bloc

k vs

. ini

tial r

ecal

l blo

ck.

Who

le b

rain

ana

lysi

sIn

itial

lear

ning

: PO

S co

rrel

atio

nw

ith a

ge (

OO

> Y

O)

in a

nter

ior

cing

ulat

e; M

axim

um r

ecal

l: N

EG

corr

elat

ion

with

age

(Y

O >

OO

)in

R p

ulvi

nar

and

R p

recu

neus

,PO

S co

rrel

atio

n (O

O >

YO

) in

med

ial f

ront

al g

yrus

.

Are

a un

der

the

curv

e of

num

ber

corr

ect o

ver

repe

ated

reca

ll bl

ocks

.

O: I

nitia

l lea

rnin

g: P

OS

corr

elat

ion

with

perf

orm

ance

()

in o

ccip

ital

regi

ons

(inc

ludi

ng m

iddl

e oc

cipi

tal g

yrus

tom

edia

l occ

ipito

-tem

pora

l inc

ludi

ng li

ngua

l,fu

sifo

rm, a

nd p

arah

ippo

cam

pal g

yri,

Rhi

ppoc

ampu

s, L

infe

rior

and

mid

dle

fron

tal

gyru

s, a

nter

ior

cing

ulat

e, a

nd L

ant

erio

rth

alam

us. M

axim

um r

ecal

l: PO

S co

rrel

atio

nw

ith p

erfo

rman

ce (

) in

Bdo

rsol

ater

al a

nd a

nter

ior

pref

ront

al, R

infe

rior

fron

tal g

yrus

, R la

tera

l mid

dle

tem

pora

l gyr

us,

R h

ippo

cam

pus,

med

ial s

uper

ior

tem

pora

lgy

rus,

R la

tera

l am

ygda

la.

Lan

gene

cker

and

Nie

lson

, 200

3, F

ront

alre

crui

tmen

t dur

ing

resp

onse

inhi

bitio

n in

olde

r ad

ults

Y:

11, O

: 11

(O

wer

e su

bsam

ple

from

Lan

gene

cker

et

al.,

2002

test

ed a

seco

nd ti

me)

Y: m

ean

age

= 2

8.1,

mea

nye

ars

educ

atio

n =

17,

4M

:7F;

O: m

ean

age

= 7

2.8,

mea

nye

ars

educ

atio

n =

18,

3M

:8F

Nor

mal

cog

nitiv

e an

dem

otio

nal s

tatu

s (M

MSE

> 2

6, G

DS

< 1

0), p

lus

ane

urop

sych

olog

ical

batte

ry f

or o

lder

part

icip

ants

onl

y.

fMR

IG

o/N

o G

o ta

sk in

whi

ch r

espo

nse

is m

ade

to a

ltern

atin

g st

imul

i (X

or Y

) th

us r

equi

ring

inhi

bitio

n of

resp

onse

to p

revi

ousl

y co

rrec

tst

imul

us. C

ontr

ast(

s): c

orre

ctta

rget

s vs

. bas

elin

e an

d co

rrec

tlu

res

vs. b

asel

ine.

26 c

lust

ers

that

met

sign

ific

ance

cri

teri

a in

at

leas

t one

gro

up.

O >

Y:

L in

feri

or f

ront

al g

yrus

,L

infe

rior

par

ieta

l lob

ule,

Lcl

aust

rum

, and

L p

utam

en, R

med

ial a

nd m

iddl

e fr

onta

l gyr

i.19

out

of

26 c

lust

ers

not

sign

ific

antly

dif

fere

nt u

pon

rete

stin

old

er p

artic

ipan

ts.

Perc

ent c

orre

ct in

hibi

tion.

Wea

k PO

S co

rrel

atio

ns in

R m

edia

l fro

ntal

gyru

s an

d R

sup

ram

argi

nal g

yrus

in O

(),

but

sam

ple

was

too

smal

l to

adeq

uate

ly in

vest

igat

e th

is id

ea.

Scar

mea

s et

al.,

200

3,C

ogni

tive

rese

rve

mod

ulat

es f

unct

iona

lbr

ain

resp

onse

s du

ring

mem

ory

task

s: a

PE

T

Y:

19, O

: 17

Y: m

ean

age

= 2

3, a

ge r

ange

= 1

9–28

, 7M

:12F

, mea

nye

ars

educ

atio

n =

16.

7; O

:m

ean

age

= 7

1, a

ge r

ange

=

Scre

en f

or m

edic

al,

neur

olog

ic (

espe

cial

lyde

men

tia),

psy

chia

tric

,an

d ne

urop

sych

olog

ical

diso

rder

s, a

nd

PET

Seri

al r

ecog

nitio

n m

emor

y ta

sk:

enco

ding

and

rec

ogni

tion

of li

st o

fun

ique

sha

pes

(lis

t len

gth

indi

vidu

ally

titr

ated

to 7

5%ac

cura

cy)

vs. n

onm

emor

y co

ntro

l

Who

le b

rain

ana

lysi

sN

one

repo

rted

Firs

t pri

ncip

al c

ompo

nent

of

New

Adu

lt R

eadi

ng T

est-

Nor

th A

mer

ican

Ver

sion

,W

AIS

-R v

ocab

ular

y su

btes

t,an

d ye

ars

of e

duca

tion

used

Y: P

OS

corr

elat

ion

with

CR

in R

Pos

tcen

tral

Gyr

us, a

nd R

Inf

erio

r T

empo

ral G

yrus

, O:

POS

corr

elat

ion

with

CR

in R

Cun

eus,

Pos

teri

orC

ingu

late

, and

R C

uneu

s (

);an

d N

EG

cor

rela

tion

with

CR

in R

Sup

erio

r

Biol Psychiatry. Author manuscript; available in PMC 2013 May 02.

NIH

-PA Author Manuscript

NIH

-PA Author Manuscript

NIH

-PA Author Manuscript

Eyler et al. Page 19

Cit

atio

nN

umbe

r of

Par

tici

pant

sC

hara

cter

isti

cs o

fpa

rtic

ipan

tsD

efin

itio

n of

"Hea

lthy

"T

ype

ofIm

agin

gP

arad

igm

tes

ted

Bra

inR

egio

n(s)

Exa

min

ed

Age

Dif

fere

nce(

s) in

Bra

inF

unct

ion

Succ

ess/

Per

form

ance

Det

erm

inat

ion

Succ

ess/

Per

form

ance

Cor

rela

tion

or

Eff

ect(

s)

stud

y in

hea

lthy

youn

gan

d el

derl

y su

bjec

ts59

–81,

8M

:9F,

mea

n ye

ars

ofed

ucat

ion

= 1

5m

edic

atio

ns w

ith v

ascu

lar

or c

ogni

tive

effe

cts.

Scre

enin

g M

RI

of th

ebr

ain.

(sam

e sh

ape

pres

ente

d on

eac

htr

ial)

. Con

tras

t(s)

: sha

pe le

arni

ng /

reco

gniti

on v

s. n

on-m

emor

yre

peat

ed o

bjec

t lea

rnin

g /

reco

gniti

on.

as a

mea

sure

of

cogn

itive

rese

rve

(CR

).T

empo

ral G

yrus

, L C

laus

trum

-Ins

ula,

RSu

peri

or T

empo

ral G

yrus

, L I

nf P

arie

tal

Lob

ule,

Cin

gula

te G

yrus

, Inf

Fro

ntal

Gyr

us,

and

L P

arah

ippo

cam

pal G

yrus

();

O m

ore

NE

G s

lope

than

Y:

R I

nf T

empo

ral,

Post

cent

ral;

O m

ore

POS

slop

eth

an Y

: L C

uneu

s

Lus

tig

& B

uckn

er, 2

004

(75)

, Pre

serv

ed n

eura

lC

orre

late

s of

pri

min

g in

old

age

and

dem

entia

Y:

34, O

: 33

Y:

mea

n ag

e =

22.

3, a

gera

nge

= 1

8–34

, 18M

:16F

; O:

mea

n ag

e =

78.

3, a

ge r

ange

=61

–93,

12M

:21F

, mea

n ye

ars

educ

atio

n =

13.

7

Clin

ical

dem

entia

rat

ing

scal

e =

0fM

RI

Rep

etiti

on p

rim

ing

for

wor

dsdu

ring

a s

eman

tic c

lass

ific

atio

nta

sk. C

ontr

ast(

s): r

epea

ted

vs. n

eww

ords

.

Tw

o re

gion

s of

Lin

feri

or f

ront

al g

yrus

(BA

45/

47 a

nd 4

4/6)

.

No

diff

eren

ces

in b

rain

res

pons

ein

eith

er R

OI t

o re

peat

ed v

s. n

eww

ords

(bo

th g

roup

s sh

owed

redu

ctio

ns),

nor

on

who

le b

rain

anal

ysis

, nor

in h

omol

ogou

s R

hem

isph

ere

RO

Is.

Mag

nitu

de o

f re

petit

ion-

indu

ced

redu

ctio

n in

rea

ctio

ntim

e

Y =

O: P

OS

corr

elat

ions

bet

wee

n re

duce

dac

tivity

and

red

uced

RT

()

inB

A 4

5/47

RO

I

Col

com

be, K

ram

er e

t al.,

2005

, The

impl

icat

ions

of c

ortic

al r

ecru

itmen

tan

d br

ain

mor

phol

ogy

for

indi

vidu

al d

iffe

renc

esin

inhi

bito

ry f

unct

ion

inag

ing

hum

ans

Y:

20, O

: 40

(SC

A: 2

0, N

CA

:20

)

Y:

mea

n ag

e =

23.

5, a

gera

nge

= 1

9–28

, 11M

:9F;

O:

mea

n ag

e =

67.

5, a

ge r

ange

=52

–87,

22M

:18F

; SC

A: m

ean

age

= 6

7.6,

mea

n ed

ucat

ion

=16

.3, 1

0M:1

0F; N

CA

: mea

nag

e =

67.

4, m

ean

educ

atio

n =

16.5

, 12M

:8F

Scre

en f

or n

euro

logi

cdi

seas

e, a

nd a

bilit

y to

be

test

ed in

MR

I. O

with

MM

SE <

27

excl

uded

.V

isio

n te

st <

20/

30 w

ere

corr

ecte

d.

fMR

IFl

anke

r te

st (

iden

tify

dire

ctio

n of

cent

ral a

rrow

sur

roun

ded

byco

ngru

ent o

r in

cong

ruen

tdi

stra

cter

arr

ows)

eve

nt-r

elat

edw

ith lo

ng in

tert

rial

inte

rval

.C

ontr

ast:

inco

ngru

ent v

s.ba

selin

e.

Reg

ions

of

sign

ific

ant

activ

atio

n ac

ross

gro

ups

in in

cong

ruen

t tri

als

vs.

base

line.

O >

Y: B

mid

dle

fron

tal g

yrus

,an

teri

or c

ingu

late

/su

pple

men

tary

mot

or a

rea.

Med

ian

split

of

perc

ent

incr

ease

in r

eact

ion

time

for

inco

ngru

ent o

ver

cong

ruen

ttr

ials

.

: L m

iddl

e fr

onta

l gyr

us.

Fer

a F

. et

al.,

2005

(76

),N

eura

l mec

hani

sms

unde

rlyi

ng p

roba

bilis

ticca

tego

ry le

arni

ng in

norm

al a

ging

Y:

18, O

: 15

Y:

mea

n ag

e =

25.

5, m

ean

year

s ed

ucat

ion

= 1

6.7,

9M

:9F

; O:

mea

n ag

e =

67.

1,m

ean

year

s ed

ucat

ion

= 1

6.8,

9M:6

F

No

hist

ory

or c

urre

ntne

urol

ogic

al, m

edic

al o

rps

ychi

atri

c co

nditi

ons,

no

curr

ent m

edic

atio

ns.

fMR

IPr

obab

ilist

ic c

ateg

ory

lear

ning

:“w

eath

er p

redi

ctio

n” te

st;

Con

tras

t: w

eath

er p

redi

ctio

n vs

.pe

rcep

tual

mot

or c

ontr

ol a

cros

sfo

ur e

poch

s.

Who

le b

rain

ana

lysi

sY

> O

: C

auda

te, a

nter

ior

and

post

erio

r ci

ngul

ate,

B p

refr

onta

l;O

> Y

: B

par

ieta

l.

Perc

enta

ge c

orre

ct a

ndre

actio

n tim

e in

eac

h of

4ep

ochs

.

Who

le b

rain

cor

rela

tiona

l ana

lysi

s an

d on

lyPO

S co

rrel

atio

ns a

re s

how

n. Y

: PO

Sco

rrel

atio

ns w

ith R

T in

pre

fron

tal,

prem

otor

,m

edia

l fro

ntal

, cin

gula

te, c

auda

te, o

ccip

ital,

pari

etal

, and

thal

amus

; pos

itive

cor

rela

tion

with

accu

racy

in d

orso

late

ral a

nd in

feri

or p

refr

onta

l,ca

udat

e, p

arie

tal,

Bro

ca's

are

a, a

nd th

alam

us;

O:

POS

corr

elat

ion

with

RT

in p

refr

onta

l,pa

riet

al, t

hala

mus

and

occ

ipita

l(

); P

OS

corr

elat

ion

with

accu

racy

in p

refr

onta

l, ca

udat

e,pr

esup

plem

enta

ry m

otor

and

par

ieta

l(

).

Gra

dy, M

cInt

osh,

&C

raik

, 200

5, T

ask-

rela

ted

activ

ity in

pre

fron

tal

cort

ex a

nd it

s re

latio

n to

reco

gniti

on m

emor

ype

rfor

man

ce in

you

ngan

d ol

d ad

ults

Y:

12, O

: 12

Y:

mea

n ag

e =

25.

6, a

gera

nge

= 2

1–29

, 6M

:6F,

mea

nye

ars

educ

atio

n =

16.

6; O

:m

ean

age

= 7

0.4,

age

ran

ge =

58–8

5, 7

M:5

F, m

ean

year

sed

ucat

ion

= 1

4.3

No

dise

ases

or

med

icat

ions

that

aff

ect

brai

n fu

nctio

n; n

oab

norm

aliti

es o

n M

RI;

MM

SE a

nd v

ocab

ular

y in

norm

al r

ange

.

PET

Rec

ogni

tion

mem

ory

for

wor

ds o

rlin

e dr

awin

gs e

ncod

ed d

urin

g a

sem

antic

(liv

ing/

nonl

ivin

g) o

rpe

rcep

tual

(ca

se o

f w

ords

or

size

of p

ictu

re)

task

. Con

tras

t(s)

:re

cogn

ition

of

sem

antic

ally

-en

code

d ite

ms

vs. s

ilent

read

ing/

nam

ing

cont

rol;

reco

gniti

on o

fpe

rcep

tual

ly-e

ncod

ed it

ems

vs.

sile

nt re

adin

g/na

min

g co

ntro

l.

Who

le b

rain

ana

lysi

s(p

artia

l lea

st q

uare

sco

vari

ance

ana

lysi

s).

Y >

O:

L m

iddl

e te

mpo

ral g

yrus

,hi

ppoc

ampu

s, a

nd R

infe

rior

pari

etal

(Y

act

ivat

ions

, O n

ore

spon

se),

L s

uper

ior

tem

pora

l, R

infe

rior

tem

pora

l (Y

no

resp

onse

,O

dea

ctiv

atio

n); O

> Y

: ro

stra

lan

teri

or c

ingu

late

, Lpa

rahi

ppoc

ampu

s, R

infe

rior

fron

tal g

yrus

(O

act

ivat

ions

, Yno

res

pons

e or

dea

ctiv

atio

n).

Mea

n nu

mbe

r of

hits

Y =

O:

POS

corr

elat

ion

with

per

form

ance

()

in a

nter

ior

and

post

erio

rci

ngul

ate

gyru

s, R

cau

date

nuc

leus

, NE

Gco

rrel

atio

ns (

) in

pos

teri

orfr

onta

l, L

tem

pora

l, ad

R o

ccip

ital a

nd p

arie

tal

area

s; O

> Y

(PO

S in

O [

] an

dN

EG

or

smal

l in

Y)

in B

ant

erio

r an

d in

feri

orpr

efro

ntal

cor

tex,

L d

orso

med

ial p

refo

rnta

l, B

mid

dle

tem

pora

l, an

d L

vis

ual c

orte

x; Y

> O

(PO

S or

sm

all i

n Y

and

NE

G in

O[

]) in

R m

otor

cor

tex,

Rpa

rahi

ppoc

ampa

l gyr

us, i

nfer

ior

pari

etal

.

Ros

ano

C, A

izen

stei

nH

. et

al.,

2005

(77

),Fu

nctio

nal n

euro

imag

ing

indi

cato

rs o

f su

cces

sful

exec

utiv

e co

ntro

l in

the

olde

st o

ld

Y:

20, O

: 8

Y:

mea

n ag

e =

23.

0, 9

M:1

1F,

mea

n ye

ars

educ

atio

n =

14.5

;O

: mea

n ag

e =

81.

5, 5

M:3

F,m

ean

year

s ed

ucat

ion

= 1

3.7

Nor

mal

ran

ge o

n a

cogn

itive

bat

tery

;E

xclu

ded

for

psyc

holo

gica

l and

CN

Sm

edic

al p

robl

ems,

old

erw

ere

excl

uded

for

sign

ific

ant n

euro

logi

cal o

rne

urod

egen

erat

ive

dise

ases

.

fMR

IPO

P (P

repa

ring

to O

verc

ome

Prep

oten

cy)

task

: pre

-cue

fixa

tion,

cue

to e

xpec

t to

mak

eei

ther

a c

ongr

uent

but

ton

pres

s(s

ame

dire

ctio

n as

arr

ow; l

owlo

ad)

or a

n in

cong

ruen

t but

ton

pres

s (o

ppos

ite d

irec

tion

from

arro

w; h

igh

load

); C

ontr

ast(

s):

aver

age

sign

al c

hang

e in

hig

h-lo

ad v

s. lo

w-l

oad

tria

ls fo

r

Dor

sola

tera

l pre

fron

tal

cort

ex: B

A 9

, 45,

46

(pre

para

tion)

, ant

erio

rci

ngul

ate

cort

ex(d

ecis

ion)

, and

pos

teri

orpa

riet

al c

orte

x: B

A 7

, 40

(pre

para

tion)

Y >

O in

BA

7, 9

, and

46,

but

no

age

× lo

ad in

tera

ctio

ns.

Hig

h lo

ad m

inus

low

load

accu

racy

and

rea

ctio

n tim

e.Y

and

O: P

OS

corr

elat

ion

of lo

ad-r

elat

edin

crea

ses

of a

ctiv

atio

n w

ith s

tabi

lity

ofpe

rfor

man

ce a

ccur

acy

acro

ss lo

ad in

R B

A 7

,40

, and

with

sta

bilit

y of

RT

acr

oss

load

in R

46;

O, b

ut n

ot Y

, sho

wed

PO

S re

latio

nshi

p be

twee

nin

crea

sed

activ

atio

n an

d R

T s

tabi

lity

acro

sslo

ad in

BA

40

().

Biol Psychiatry. Author manuscript; available in PMC 2013 May 02.

NIH

-PA Author Manuscript

NIH

-PA Author Manuscript

NIH

-PA Author Manuscript

Eyler et al. Page 20

Cit

atio

nN

umbe

r of

Par

tici

pant

sC

hara

cter

isti

cs o

fpa

rtic

ipan

tsD

efin

itio

n of

"Hea

lthy

"T

ype

ofIm

agin

gP

arad

igm

tes

ted

Bra

inR

egio

n(s)

Exa

min

ed

Age

Dif

fere

nce(

s) in

Bra

inF

unct

ion

Succ

ess/

Per

form

ance

Det

erm

inat

ion

Succ

ess/

Per

form

ance

Cor

rela

tion

or

Eff

ect(

s)

prep

arat

ion

(fir

st 9

s of

tria

l) o

rde

cisi

on (l

ast 9

s of

tria

l) p

hase

.

Ryp

ma

et a

l., 2

005,

Dis

soci

atin

g ag

e-re

late

dch

ange

s in

cog

nitiv

est

rate

gy a

nd n

eura

lef

fici

ency

usi

ng e

vent

-re

late

d fM

RI

Y:

8, O

: 6

Y: m

ean

age

= 1

9.5,

age

rang

e =

19–

26, 4

M: 4

F,m

ean

year

s of

edu

catio

n =

16.0

; O: m

ean

age

= 7

0.2,

age

rang

e =

55–

83, 3

M:4

F,m

ean

year

s of

edu

catio

n =

14.5

Scre

en f

or h

yper

tens

ion,

othe

r m

edic

al,

neur

olog

ical

, or

psyc

hiat

ric

diso

rder

and

use

of p

resc

ript

ion

med

icat

ion;

MM

SE >

26,

BD

I <

10.

fMR

IIt

em-r

ecog

nitio

n ta

sk w

ith s

et s

ize

1–8

lette

rs (

slow

eve

nt-r

elat

edde

sign

). C

ontr

ast(

s): m

ean

activ

ity v

s. b

asel

ine

duri

ngE

ncod

ing,

Del

ay, a

nd R

espo

nse

peri

ods

for

each

mem

ory

load

.

Dor

sal (

BA

9 &

46)

and

vent

ral (

BA

44,

45,

&47

) pr

efro

ntal

cor

tex

(ana

tom

ical

ly d

efin

ed)

O =

Y in

rel

atio

nshi

p w

ith lo

addu

ring

all

peri

ods

in d

orsa

l and

vent

ral P

FC (

Dor

sal:

incr

ease

with

load

in b

oth

grou

ps in

Del

aype

riod

onl

y; V

entr

al: d

ecre

ase

with

load

dur

ing

Enc

odin

g in

both

gro

ups,

incr

ease

with

load

duri

ng D

elay

and

Res

pons

e in

both

gro

ups)

Com

posi

te p

erfo

rman

ce s

core

of a

ccur

acy

and

reac

tion

time

(bot

h Y

and

O)

usin

g z-

scor

es; Y

: ran

ge =

1.5

8 to

−1.

46; O

: ran

ge =

2.4

9 to

−2.

94

Y:

NE

G c

orre

latio

n w

ith p

erfo

rman

ce, O

: PO

Sco

rrel

atio

n w

ith p

erfo

rman

ce d

urin

g E

ncod

ing

and

Res

pons

e fo

r do

rsal

PFC

; dur

ing

Enc

odin

gan

d la

te-D

elay

for

ven

tral

PFC

().

Enc

odin

g di

ffer

ence

sm

ainl

y du

e to

acc

urac

y; R

espo

nse

diff

eren

ces

mai

nly

due

to R

T.

Ster

n et

al.,

200

5, B

rain

netw

orks

ass

ocia

ted

with

cogn

itive

res

erve

inhe

alth

y yo

ung

and

old

adul

ts

Y:

20, O

: 17

Y:

mea

n ag

e =

23.

4 8M

:12F

,m

ean

year

s ed

ucat

ion

= 1

5.7;

O:

mea

n ag

e =

70.

9, 7

M:

10M

, mea

n ye

ars

educ

atio

n =

15

No

med

ical

, neu

rolo

gica

l,or

psy

chia

tric

con

ditio

ns.

No

cogn

itive

impa

irm

ent

or d

emen

tia.

PET

Con

tinuo

us r

ecog

nitio

n ta

sk f

orno

nver

bal s

hape

s w

ith li

st le

ngth

of o

ne (

easy

con

ditio

n) o

r tit

rate

dle

ngth

so

that

per

form

ance

was

at

75%

acc

urac

y (h

ard

cond

ition

);C

ontr

ast(

s): c

hang

e in

net

wor

kac

tivat

ion

from

the

easy

enco

ding

/rec

ogni

tion

to th

e ha

rden

codi

ng/r

ecog

nitio

n co

nditi

ons.

Who

le b

rain

cov

aria

tion

anal

ysis

.O

> Y

: R h

ippo

cam

pus,

pos

teri

orin

sula

, tha

lam

us, a

nd B

oper

culu

m (

O s

how

incr

ease

sw

ith ta

sk d

iffi

culty

and

Y s

how

decr

ease

s); Y

> O

: R li

ngua

lgy

rus,

infe

rior

par

ieta

l lob

e, L

post

erio

r ci

ngul

ate,

B c

alca

rine

cort

ex (

Y s

how

incr

ease

s w

ithta

sk d

iffi

culty

and

O s

how

decr

ease

s.)

Cog

nitiv

e re

serv

e fa

ctor

sco

refr

om y

ears

of

educ

atio

n an

dpe

rfor

man

ce o

n th

e N

ewA

dult

Rea

ding

Tes

t and

Voc

abul

ary

subt

est o

f th

eW

AIS

-R.

Y:

POS

corr

elat

ion

of c

ogni

tive

rese

rve

with

brai

n re

spon

se w

ithin

the

regi

ons

that

dif

fere

dby

age

; O:

NE

G c

orre

latio

n (

)

Tes

sito

re e

t al,

2005

,Fu

nctio

nal c

hang

es in

the

activ

ity o

f br

ain

regi

ons

unde

rlyi

ng e

mot

ion

proc

essi

ng in

the

elde

rly

Y:

12, O

: 15

Y:

mea

n ag

e =

25,

6M

:6F,

age

rang

e =

20–

29; O

: m

ean

age

= 6

7, 8

M:7

F, a

ge r

ange

=60

–80

No

hist

ory

ofne

urol

ogic

al, p

sych

iatr

ic,

or m

edic

al p

robl

ems.

No

curr

ent m

edic

atio

n ex

cept

birt

h co

ntro

l and

hor

mon

ere

plac

emen

t.

fMR

IE

mot

iona

l fac

ial e

xpre

ssio

nm

atch

ing

(ang

ry o

r af

raid

).C

ontr

ast(

s): E

mot

ion

mat

chin

g vs

.sh

ape

mat

chin

g

Who

le b

rain

ana

lysi

sY

> O

: R

am

ygda

la, B

pos

teri

orfu

sifo

rm; O

> Y

: B

ven

tral

and

Lm

edia

l pre

fron

tal

Rea

ctio

n tim

e an

d ac

cura

cyY

: PO

S co

rrel

atio

ns o

f R

T w

ith L

dor

sal

pref

ront

al, B

pos

teri

or f

usif

orm

; O:

POS

corr

elat

ions

of

RT

with

L d

orsa

l and

med

ial

pref

ront

al a

nd R

infe

rior

occ

ipita

l(

)

Pers

son

et a

l., 2

006,

Stru

ctur

e-fu

nctio

nco

rrel

ates

of

cogn

itive

decl

ine

in a

ging

O:

40(D

eclin

ing:

20,

Stab

le:

20

Dec

linin

g: m

ean

age

= 6

5.3,

7M:1

3F, m

ean

year

sed

ucat

ion

= 1

0.4;

Sta

ble:

mea

n ag

e =

66.

0, 7

M:1

3F,

mea

n ye

ars

educ

atio

n =

10.

0

No

repo

rted

neu

rolo

gica

lpr

oble

ms;

MM

SE ≥

25;

no g

roup

dif

fere

nces

inva

scul

ar r

isk

fact

ors

fMR

IIn

cide

ntal

enc

odin

g of

wor

dsdu

ring

a c

ateg

oriz

atio

n ta

sk(a

bstr

act v

s. c

oncr

ete)

.C

ontr

ast(

s): e

ncod

ing

vs. f

ixat

ion

Reg

ions

of

inte

rest

bas

edon

act

ivat

ion

in b

oth

grou

ps: L

dor

sal f

ront

al,

L in

feri

or f

ront

al, R

dors

al f

ront

al, R

ven

tral

fron

tal

Non

e re

port

edSt

able

: un

chan

ging

perf

orm

ance

on

3 m

emor

yta

sks

over

10

year

per

iod

(3ev

alua

tions

), D

eclin

ing:

sig

.de

clin

e at

bot

h ev

alua

tions

,en

ding

at a

sig

. low

erm

emor

y pe

rfor

man

ce (

norm

alra

nge)

Dec

linin

g >

Stab

le (

): R

vent

ral p

refr

onta

l

Rab

bitt

et a

l, 20

06,

Los

ses

in g

ross

bra

invo

lum

e an

d ce

rebr

albl

ood

flow

acc

ount

for

age

rela

ted

diff

eren

ce in

spee

d bu

t not

in f

luid

inte

llige

nce

N =

69

O:

29M

:40F

, mal

e m

ean

age

= 7

2.7,

fem

ale

mea

n ag

e =

73.1

Abs

ence

of

diab

etes

,hy

pert

ensi

on, o

rne

urol

ogic

al c

ondi

tions

,ab

senc

e of

MR

Iab

norm

aliti

es

MR

I m

easu

re o

far

teri

al b

lood

flow

Res

tT

otal

blo

od f

low

into

the

brai

n, n

ot r

egio

nal

Not

giv

enPe

rfor

man

ce o

n 10

neur

opsy

chol

ogic

al te

sts

POS

corr

elat

ion

of C

BF

to p

erfo

rman

ce o

n 8

out o

f 10

test

s. (

) A

fter

cont

rolli

ng f

or a

ge w

ithin

this

eld

erly

gro

up,

only

3 ta

sks

(tw

o sp

eed

and

one

exec

utiv

e)w

ere

still

rel

ated

Van

der

Vee

n, F

rouk

e et

al.,

2006

, Eff

ects

of

agin

g on

rec

ogni

tion

ofin

tent

iona

lly a

ndin

cide

ntal

ly s

tore

dw

ords

: An

fMR

I st

udy

Y: 1

2, O

: 12

Y: m

ean

age

= 2

5.1,

12M

:0F,

age

rang

e =

23–

27; O

: m

ean

age

= 6

4.7,

12M

:0F,

age

rang

e =

63–

67, s

ubje

cts

mat

ched

for

leve

l of

educ

atio

n

No

hist

ory

of m

edic

al,

neur

olog

ical

or

psyc

hiat

ric

illne

ss, c

urre

ntus

e of

psy

choa

ctiv

em

edic

atio

n, d

iast

olic

BP>

95, u

se o

f re

crea

tiona

ldr

ugs

or e

xces

sive

alco

hol,

no h

isto

ry o

fcl

aust

roph

obia

.

fMR

IV

erba

l epi

sodi

c re

trie

val f

orin

tent

iona

lly-e

ncod

ed,

inci

dent

ally

-enc

oded

, and

nov

elw

ords

. Con

tras

t(s)

: eve

nt-r

elat

edan

alys

is o

f cor

rect

ly re

cogn

ized

vs. c

orre

ctly

reje

cted

(su

cces

ful

retr

ieva

l); c

orre

ctly

reco

gniz

edin

tent

iona

lly- v

s. in

cide

ntal

ly-

enco

ded

wor

ds.

Who

le b

rain

ana

lysi

san

d R

OIs

bas

ed o

npr

evio

us s

tudi

es.

Cor

rect

ly r

ecog

nize

d vs

.co

rrec

tly r

ejec

ted:

O >

Y:

Who

lebr

ain

anal

ysis

: B m

edia

lpr

efro

ntal

gyr

us; R

OI

anal

ysis

: 2cl

uste

rs R

par

ahip

poca

mpa

lgy

rus;

Inc

iden

tal v

s In

tent

iona

l:Y

> O

: Who

le b

rain

ana

lysi

s:m

iddl

e oc

cipi

tal g

yrus

(Y

:in

cide

ntal

> in

tent

iona

l, O

:in

tent

iona

l > in

cide

ntal

Perc

enta

ge c

orre

ctly

reco

gniz

ed it

ems

O:

POS

corr

elat

ions

with

acc

urac

y(

) in

L p

arah

ippo

cam

pal g

yrus

and

L li

ngua

l gyr

us (

from

who

le b

rain

ana

lysi

s)an

d B

par

ahip

poca

mpa

l gyr

us (

from

RO

Ian

alys

is).

NE

G c

orre

latio

ns w

ith a

ccur

acy

()

in B

pos

teri

or c

ingu

late

gyru

s an

d B

infe

rior

par

ieta

l gyr

us. Y

: no

sign

ific

ant c

orre

latio

ns.

Ber

nard

et a

l., 2

007,

Neu

ral c

orre

late

s of

age

-re

late

d ve

rbal

epi

sodi

cm

emor

y de

clin

e: A

PE

T

Y:

12, O

: 12

Y:

mea

n ag

e =

22.

5, 6

M:6

F;O

: m

ean

age

= 5

9, a

ge r

ange

= 5

5–63

, 6M

:6F

(O <

Y f

orye

ars

of e

duca

tion)

No

med

ical

, psy

chia

tric

,or

neu

rolo

gica

l dis

orde

rs;

unm

edic

ated

; no

mem

ory

com

plai

nt, n

o

PET

Inte

ntio

nal v

erba

l enc

odin

g an

dre

adin

g ta

sk, b

oth

with

livi

ng/

nonl

ivin

g ju

dgm

ent;

Stem

-cue

dre

call

task

for

the

inte

ntio

nally

-

Who

le b

rain

ana

lysi

sE

ncod

ing:

no

sign

ific

ant

diff

eren

ces;

Rec

all:

nosi

gnif

ican

t dif

fere

nces

Cue

d re

call

accu

racy

Y:

POS

corr

elat

ion

with

acc

urac

y in

left

para

hipp

ocam

pal g

yrus

; O:

POS

corr

elat

ions

with

acc

urac

y (

) in

R in

feri

or

Biol Psychiatry. Author manuscript; available in PMC 2013 May 02.

NIH

-PA Author Manuscript

NIH

-PA Author Manuscript

NIH

-PA Author Manuscript

Eyler et al. Page 21

Cit

atio

nN

umbe

r of

Par

tici

pant

sC

hara

cter

isti

cs o

fpa

rtic

ipan

tsD

efin

itio

n of

"Hea

lthy

"T

ype

ofIm

agin

gP

arad

igm

tes

ted

Bra

inR

egio

n(s)

Exa

min

ed

Age

Dif

fere

nce(

s) in

Bra

inF

unct

ion

Succ

ess/

Per

form

ance

Det

erm

inat

ion

Succ

ess/

Per

form

ance

Cor

rela

tion

or

Eff

ect(

s)

stud

y w

ith c

ombi

ned

subt

ract

ion/

corr

elat

ion

anal

ysis

abno

rmal

ities

on

MR

Iim

agin

g.en

code

d w

ords

and

ste

m-

com

plet

ion

task

. Con

tras

t(s)

:en

codi

ng v

s. re

adin

g; c

ued-

reca

llvs

ste

m-c

ompl

etio

n

fron

tal g

yrus

, L h

ippo

cam

pus;

O >

Y:

Rin

feri

or f

ront

al g

yrus

Bra

ssen

et a

l., 2

007,

Stru

ctur

e–fu

nctio

nin

tera

ctio

ns o

f co

rrec

tre

trie

val i

n he

alth

yel

derl

y w

omen

Y:

14, O

: 14

Y:

mea

n ag

e =

25.

6, a

gera

nge

= 2

1–33

, 0M

:14F

; O:

mea

n ag

e =

64.

9, a

ge r

ange

=60

–71,

0M

:14F

No

hist

ory

of n

euro

logi

cal

or p

sych

iatr

ic il

lnes

s;no

rmal

blo

od p

ress

ure;

no

med

icat

ions

or

cond

ition

sth

at c

ould

aff

ect C

BF;

norm

al v

alue

s (n

o le

ssth

an 1

SD b

elow

mea

n) o

nne

urop

sych

olog

ical

batte

ry a

nd n

orm

alM

MSE

.

fMR

IE

piso

dic

enco

ding

and

ret

riev

al o

fem

otio

nally

-val

ence

d an

d ne

utra

lw

ords

. Con

tras

t(s)

: cor

rect

reco

gniti

on v

s. in

corr

ect

reco

gniti

on o

f neu

tral

wor

ds.

Who

le b

rain

ana

lysi

s.G

roup

dif

fere

nce

anal

ysis

mas

ked

byw

ithin

gro

up r

esul

ts.

Succ

ess

anal

ysis

onl

y in

regi

ons

of g

roup

eff

ect.

Y >

O:

R s

uper

ior

fron

tal g

yrus

;O

> Y

: B

mid

dle

tem

pora

l gyr

us.

Am

ount

of

corr

ectly

reco

gniz

ed/r

ejec

ted

wor

dsO

: PO

S co

rrel

atio

n w

ith a

ccur

acy

()

in L

mid

dle

tem

pora

l gyr

us(t

rend

tow

ard

R m

iddl

e te

mpo

ral g

yrus

), Y

:PO

S co

rrel

atio

n w

ith a

ccur

acy

in R

pre

fron

tal

cort

ex.

Gut

ches

s et

al,

2007

,C

onte

xtua

l int

erfe

renc

ein

rec

ogni

tion

mem

ory

with

age

Y:

20, O

: 20

Y:

mea

n ag

e =

21.

05, 1

0M:

10F,

age

ran

ge =

18–

28,

mea

n ye

ars

of e

duca

tion

=14

.88;

O:

mea

n ag

e =

68.

10,

6M:1

4F, a

ge r

ange

= 6

0–84

,m

ean

educ

atio

n =

14.

97

In g

ood

neur

olog

ical

,ph

ysic

al, a

ndps

ycho

logi

cal h

ealth

, fre

eof

med

icat

ions

or

cond

ition

s af

fect

ing

cere

bral

blo

od f

low

, at

leas

t 27

out o

f 30

on

MM

SE

fMR

IR

ecog

nitio

n m

emor

y fo

rin

tent

iona

lly-e

ncod

ed o

bjec

tsw

ith f

amili

ar o

r un

fam

iliar

back

grou

nds.

Con

tras

t(s)

:re

ject

ion

of n

ovel

obj

ects

infa

mili

ar c

onte

xts:

new

obj

ect /

old

back

grou

nd m

inus

new

obj

ect /

new

bac

kgro

und

for c

orre

ctre

ject

ions

Who

le b

rain

and

RO

Is in

pref

ront

al c

orte

x; f

orpe

rfor

man

ceas

soci

atio

ns, m

edia

lsu

peri

or p

refr

onta

l and

Rm

iddl

e fr

onta

l RO

Is

Y >

O: B

dor

sola

tera

l pre

fron

tal,

L a

nter

ior

mid

dle

fron

tal,

ante

rior

cin

gula

te, p

oste

rior

cing

ulat

e, L

cal

cari

ne/li

ngua

lgy

rus,

L a

ngul

ar/m

iddl

e te

mpo

ral

gyru

s

Rec

ogni

tion

disc

rim

inat

ion

scor

es (

A';

both

con

tinuo

usan

d m

edia

n sp

lit)

Poor

Rec

ogni

tion

O <

Goo

d R

ecog

nitio

n O

<Y

in R

dor

sola

tera

l pre

fron

tal;

Poor

Rec

ogni

tion

O <

Goo

d R

ecog

nitio

n O

= Y

inm

edia

l and

rig

ht m

iddl

e fr

onta

l gyr

us(

); C

orre

latio

ns: Y

: N

ore

latio

nshi

p; O

: po

sitiv

e co

rrel

atio

n in

Bdo

rsol

ater

al p

refr

onta

l ()

Lan

gene

cker

et a

l., 2

007,

An

eval

uatio

n of

dis

tinct

volu

met

ric

and

func

tiona

l MR

Ico

ntri

butio

ns to

war

dun

ders

tand

ing

age

and

task

per

form

ance

: Ast

udy

in th

e ba

sal g

angl

ia

Y:

11, O

: 11

(sam

e as

Lan

gene

cker

et

al.,

2003

)

Y:

mea

n ag

e =

28.

1, a

gera

nge

= 2

5–32

, 4M

:7F,

mea

nye

ars

educ

atio

n =

17;

O:

mea

n ag

e =

72.

8, a

ge r

ange

=67

–77,

3M

:8F,

mea

n ye

ars

educ

atio

n =

18

No

hist

ory

of p

sych

iatr

ic,

neur

olog

ical

or

othe

rm

edic

al f

acto

rsin

flue

ncin

g co

gniti

on;

MM

SE >

27,

Ger

iatr

icD

epre

ssio

n Sc

ale

< 9

, Oha

d no

rmal

per

form

ance

for

age

on a

neur

opsy

chol

ogic

alba

ttery

.

fMR

IG

o/N

o G

o ta

sk in

whi

ch r

espo

nse

is m

ade

to a

ltern

atin

g st

imul

i (X

or Y

) th

us r

equi

ring

inhi

bitio

n of

resp

onse

to p

revi

ousl

y co

rrec

tst

imul

us. C

ontr

ast:

corr

ect t

arge

tsvs

. all

othe

rs.

Cau

date

and

put

amen

/gl

obus

pal

lidus

.Y

> O

: ca

udat

e, O

> Y

:pu

tam

en/g

lobu

s pa

llidu

s.Y

and

O s

plit

into

2 g

roup

sba

sed

on m

edia

n pe

rcen

tco

rrec

t tar

get t

rial

s.

O:

poor

per

form

ers

> g

ood

perf

orm

ers

()

in B

put

amen

/glo

bus

palli

dus;

Y:

poor

per

form

ers

> g

ood

perf

orm

ers

in L

put

amen

/glo

bus

palli

dus

and

R c

auda

te.

Mad

den,

Spa

niol

et a

l.,20

07, A

dult

age

diff

eren

ces

in th

efu

nctio

nal n

euro

anat

omy

of v

isua

l atte

ntio

n: A

com

bine

d fM

RI

and

DT

Ist

udy

Y:

16, O

: 16

Y: m

ean

age

= 2

3.4,

8F:

8M,

age

rang

e =

19–

28, m

ean

year

s ed

ucat

ion:

16.

7; O

:m

ean

age

= 6

7.0,

8F:

8M, a

gera

nge

= 6

0–82

, mea

n ye

ars

educ

atio

n =

17.

5

No

sign

ific

ant h

ealth

prob

lem

s or

med

icat

ion

know

n to

aff

ect c

ogni

tive

func

tioni

ng o

r ce

rebr

albl

ood

flow

rep

orte

d on

scre

enin

g qu

estio

nnai

re.

MM

SE ≥

27,

and

Bec

kD

epre

ssio

n In

vent

ory

≤ 9.

T2

MR

I im

ages

judg

ed to

be f

ree

of s

igni

fica

ntab

norm

aliti

es.

fMR

I (a

nd D

TI)

Vis

ual s

earc

h ta

sk w

ith tw

oco

nditi

ons:

Gui

ded

(tar

get h

ad 3

/4ch

ance

of

bein

g un

ique

ly c

olor

edco

mpa

red

to 3

dis

trac

tors

) or

Neu

tral

(ta

rget

had

1/4

cha

nce

ofbe

ing

uniq

uely

col

ored

); d

urat

ion

of d

ispl

ay g

reat

er f

or O

than

Y;

Con

tras

t(s)

: are

a un

der

curv

e of

perc

enta

ge s

igna

l cha

nge

(for

12s

afte

r tr

ial o

nset

com

pare

d to

the

6s b

efor

e tr

ial o

nset

) fo

r ea

chco

nditi

on (

Gui

ded

or N

eutr

al)

and

tria

l typ

e (t

arge

t uni

quel

y co

lore

dor

not

).

13 b

ilate

ral c

ortic

al a

ndsu

bcor

tical

reg

ions

of

inte

rest

:

O >

Y in

fro

ntal

(fr

onta

l eye

fiel

ds, m

iddl

e fr

onta

l gyr

us)

and

pari

etal

(an

gula

r an

dsu

pram

argi

nal g

yri a

nd s

uper

ior

pari

etal

lobu

le)

RO

Is r

egar

dles

sof

con

ditio

n or

tria

l typ

e.

Tar

get t

ype

effe

ct o

n re

actio

ntim

e (p

erce

ntag

e di

ffer

ence

inR

T b

etw

een

targ

ets

that

wer

eun

ique

ly c

olor

ed v

s. n

ot).

Gui

ded

cond

ition

: O >

Y:

mor

e PO

Sco

rrel

atio

n in

in f

ront

al e

ye f

ield

s an

d su

peri

orpa

riet

al lo

bule

();

Y >

O:

mor

ePO

S co

rrel

atio

n in

fus

ifor

m g

yrus

(SC

A =

NC

A).

Ryp

ma,

Eld

reth

et a

l.,20

07, A

ge-r

elat

eddi

ffer

ence

s in

act

ivat

ion-

perf

orm

ance

rel

atio

ns in

dela

yed-

resp

onse

task

s:A

mul

tiple

-com

pone

ntan

alys

is

Y:

8, O

: 6

Y: m

ean

age

= 1

9.5,

4M

:4F,

age

rang

e =

19–

26, m

ean

year

s ed

ucat

ion

= 1

6.0;

O:

mea

n ag

e =

70.

2, 3

M:3

F, a

gera

nge

= 5

5–83

, mea

n ye

ars

educ

atio

n =

14.

5

No

age-

rela

ted

diso

rder

ssu

ch a

s hy

pert

ensi

on, o

ran

y ot

her

med

ical

,ne

urol

ogic

al, o

rps

ychi

atri

c di

sord

er b

ased

on n

euro

logi

st s

cree

ning

of h

isto

ries

; no

use

ofpr

escr

iptio

n m

edic

atio

n,M

MSE

>26

, and

BD

I <

10.

fMR

ID

elay

ed r

espo

nse

task

: enc

odin

g,m

aint

enan

ce, a

nd r

etri

eval

of

sets

of le

tters

that

var

ied

in s

ize

betw

een

1 an

d 8

lette

rs.

Con

tras

t(s)

: Enc

odin

g vs

.B

asel

ine,

Del

ay v

s. B

asel

ine,

Res

pons

e vs

. Bas

elin

e.

Dor

sal p

refr

onta

l cor

tex:

mid

dle

and

supe

rior

fron

tal g

yri (

BA

9 &

46)

and

Ven

tral

pre

fron

tal

cort

ex: i

nfer

ior

fron

tal

gyru

s (B

A 4

4,45

, & 4

7).

Non

e re

port

ed.

Rea

ctio

n tim

e (R

T)

and

accu

racy

acr

oss

mem

ory

load

s.

Dor

sal P

FC: E

ncod

ing:

Y =

non

-sig

nifi

cant

NE

G c

orre

latio

n w

ith a

ccur

acy;

O =

PO

Sco

rrel

atio

n (

) w

ith a

ccur

acy;

Ret

riev

al: Y

= P

OS

corr

elat

ion

with

RT

; O =

POS

corr

elat

ion

with

acc

urac

y(

), n

on-s

igni

fica

nt N

EG

corr

elat

ion

with

RT

().

Ven

tral

PFC

: Enc

odin

g: O

= P

OS

corr

elat

ion

()

with

acc

urac

y; D

elay

: Y =

Biol Psychiatry. Author manuscript; available in PMC 2013 May 02.

NIH

-PA Author Manuscript

NIH

-PA Author Manuscript

NIH

-PA Author Manuscript

Eyler et al. Page 22

Cit

atio

nN

umbe

r of

Par

tici

pant

sC

hara

cter

isti

cs o

fpa

rtic

ipan

tsD

efin

itio

n of

"Hea

lthy

"T

ype

ofIm

agin

gP

arad

igm

tes

ted

Bra

inR

egio

n(s)

Exa

min

ed

Age

Dif

fere

nce(

s) in

Bra

inF

unct

ion

Succ

ess/

Per

form

ance

Det

erm

inat

ion

Succ

ess/

Per

form

ance

Cor

rela

tion

or

Eff

ect(

s)

NE

G c

orre

latio

n w

ith a

ccur

acy;

Ret

riev

al: O

=PO

S co

rrel

atio

n w

ith R

T (

).

Zar

ahn

et a

l., 2

007,

Age

-re

late

d ch

ange

s in

bra

inac

tivat

ion

duri

ng a

dela

yed

item

rec

ogni

tion

task

Y:

40, O

: 18

Y:

mea

n ag

e =

25.

1, 3

1M:9

F,m

ean

year

s ed

ucat

ion

= 1

5.7;

O:

mea

n ag

e =

74.

4, 7

M:

11F,

mea

n ye

ars

educ

atio

n =

15.3

No

psyc

hiat

ric

orne

urol

ogic

al il

lnes

s, n

on-

dem

ente

d

fMR

ID

elay

ed r

espo

nse

task

: enc

odin

g,m

aint

enan

ce, a

nd r

etri

eval

of

sets

of le

tters

that

var

ied

in s

ize

(1,3

,6le

tters

). C

ontr

ast(

s): L

oad-

depe

nden

t and

load

-ind

epen

dent

chan

ges

duri

ng e

ncod

ing,

del

ay,

and

resp

onse

Who

le b

rain

cov

aria

tion

anal

ysis

.A

ge e

ffec

ts o

nly

for

load

-de

pend

ent c

hang

es in

bra

inre

spon

se d

urin

g th

e de

lay

peri

od:

O >

Y f

or tw

o sp

atia

l net

wor

ks,

one

incl

udin

g le

ft p

rem

otor

cort

ex a

nd o

ne in

clud

ing

righ

tpa

rahi

ppoc

ampa

l gyr

us

Dis

crim

inab

ility

at s

et s

ize

6;1/

RT

slo

pe, a

nd 1

/RT

inte

rcep

t

O:

NE

G c

orre

latio

n be

twee

n R

T s

lope

and

expr

essi

on o

f el

derl

y-sp

ecif

ic la

tent

fac

tor

that

incl

uded

par

ahip

poca

mpu

s (

);O

> Y

: M

ore

NE

G c

orre

latio

n of

load

-de

pend

ent e

ncod

ing

resp

onse

and

bot

hdi

scri

min

abili

ty a

nd R

T s

lope

, mor

e N

EG

corr

elat

ion

of lo

ad-i

ndep

ende

nt d

elay

res

pons

ean

d bo

th R

T s

lope

and

RT

inte

rcep

t(

)

Bea

son-

Hel

d et

al.,

200

8,I.

Lon

gitu

dina

l cha

nges

in a

ging

bra

in f

unct

ion

O:

25 (

8 ye

arlo

ngitu

dina

lst

udy)

O:

mea

n ag

e at

bas

elin

e =

67.8

, 15M

: 10F

, mea

n ye

ars

educ

atio

n =

17.

3

No

hist

ory

of c

entr

alne

rvou

s sy

stem

, maj

orps

ychi

atri

c, o

r se

vere

card

iova

scul

ar d

isor

der;

deem

ed c

ogni

tivel

yno

rmal

at 9

yea

r fo

llow

-up

.

PET

Rec

ogni

tion

mem

ory

for

inte

ntio

nally

-enc

oded

wor

ds o

rfi

gure

s an

d a

rest

con

ditio

n.C

ontr

ast(

s): Y

ear9

vs.

Yea

r1 f

orea

ch c

ondi

tion

sepa

rate

ly;

conj

unct

ion

of s

imila

r Y

ear 9

vs.

Yea

r 1 e

ffec

ts f

or a

ll ta

sks;

Yea

r 9vs

. Yea

r 1 e

ffec

t for

eac

hco

nditi

on v

s. b

oth

othe

rs.

Who

le b

rain

ana

lysi

sC

omm

on t

o al

l con

diti

ons:

long

itudi

nal d

ecre

ases

in R

supe

rior

and

med

ial f

ront

al,

supe

rior

and

insu

lar

tem

pora

l,an

teri

or a

nd m

iddl

e ci

ngul

ate,

thal

amus

, and

cau

date

; inc

reas

esin

B s

uper

ior

and

R p

refr

onta

lw

hite

mat

ter,

pos

teri

or L

hipp

ocam

pus,

infe

rior

par

ieta

l,m

iddl

e oc

cipi

tal g

yrus

, and

puta

men

.

Cha

nge

in a

ccur

acy

(sen

sitiv

ity)

over

8 y

ears

.O

: V

erba

l mem

ory:

PO

S co

rrel

atio

n of

accu

racy

cha

nge

with

blo

od f

low

cha

nge

()

in in

feri

or te

mpo

ral a

ndin

feri

or p

arie

tal (

grea

ter

decr

ease

in f

low

rela

ted

to g

reat

er d

ecre

ase

in p

erfo

rman

ce),

pre

/po

stce

ntra

l gyr

us (

incr

ease

d pe

rfor

man

cere

late

d to

incr

ease

d fl

ow),

NE

G c

orre

latio

n of

accu

racy

cha

nge

with

blo

od f

low

cha

nge

()

in s

uper

ior

tem

pora

l gyr

us(i

ncre

ased

per

form

ance

rel

ated

to d

ecre

ased

flow

), N

EG

cor

rela

tion

with

RT

cha

nge

()

in p

arah

ippo

cam

pal g

yrus

.Fi

gura

l mem

ory:

NE

G c

orre

latio

n w

ithac

cura

cy (

) in

pre

cent

ral g

yrus

,N

EG

cor

rela

tion

with

RT

cha

nge

()

in in

sula

, and

sup

erio

r an

dm

iddl

e te

mpo

ral g

yri,

POS

corr

elat

ion

with

RT

()

in m

iddl

e fr

onta

l gyr

us.

Heu

ninc

kx e

t al.,

200

8,Sy

stem

s ne

urop

last

icity

in th

e ag

ing

brai

n:re

crui

ting

addi

tiona

lne

ural

res

ourc

es f

orsu

cces

sful

mot

orpe

rfor

man

ce in

eld

erly

pers

ons

Y:

12, O

: 26

Y:

mea

n ag

e =

22.

4, 6

M:6

F,ag

e ra

nge

= 2

0–25

; O:

mea

nag

e =

65.

7, 1

4M:1

2F, a

gera

nge

= 6

2–72

No

hist

ory

of n

euro

logi

cal

dise

ase

or u

se o

fps

ycho

activ

e or

vaso

activ

e m

edic

atio

n.M

MSE

≥ 2

6.

fMR

IPa

ced

(slo

wer

for

O),

cyc

lical

hand

and

foo

t mov

emen

ts th

atw

ere

in s

ame

dire

ctio

n(i

sodi

rect

iona

l: bo

th f

lexe

d to

both

ext

ende

d) o

r op

posi

tedi

rect

ions

(no

niso

dire

ctio

nal:h

and

flex

ed/f

oot e

xten

ded

to h

and

exte

nded

/foo

t fle

xed)

and

res

t.C

ontr

ast(

s): i

sodi

rect

iona

l vs.

rest

;no

niso

dire

ctio

nal v

s. re

st.

Who

le b

rain

ana

lysi

sIs

odir

ectio

nal:

O >

Y in

Lan

teri

or in

sula

r co

rtex

;N

onis

odir

ectio

nal:

O >

Y in

Lan

teri

or in

sula

, fro

ntal

gyr

us p

ars

oper

cula

ris,

infe

rior

fro

ntal

gyr

uspa

rs tr

iang

ular

is, m

iddl

e fr

onta

lgy

rus,

sup

erio

r fr

onta

l sul

cus

and

gyru

s, s

uper

ior

tem

pora

l gyr

us,

angu

lar

gyru

s, s

uper

ior

pari

etal

gyru

s, f

usif

orm

gyr

us, a

ndin

feri

or p

ost c

entr

al g

yrus

, Rpa

race

ntra

l lob

ule,

para

hipp

ocam

pal g

yrus

, pos

teri

orce

rebe

llum

, B li

ngua

l gyr

us,

ante

rior

cer

ebel

lum

.

Coo

rdin

atio

n ac

cura

cy(i

nver

se o

f ph

ase

erro

rbe

twee

n ha

nd a

nd f

oot)

.

Isod

irec

tiona

l: O

: PO

S co

rrel

atio

ns(

) w

ith c

oord

inat

ion

in r

egio

nsw

here

Y =

O in

act

ivat

ion:

L p

rece

ntra

l and

post

cent

ral g

yri,

tren

d in

R a

nter

ior

cere

bellu

m,

Y:

no c

orre

latio

ns. N

onis

odir

ectio

nal:

O:

POS

corr

elat

ions

()

in r

egio

ns w

here

Y =

O in

act

ivat

ion:

L s

uper

ior

post

cent

ral

gyru

s/su

lcus

, inf

erio

r po

stce

ntra

l gyr

us, R

supp

lem

enta

ry m

otor

are

a an

d L

SM

A, L

cing

ulat

e m

otor

are

a, a

nd in

reg

ions

whe

re Y

>O

in a

ctiv

atio

n: L

infe

rior

fro

ntal

gyr

us p

ars

oper

cula

ris

and

pars

tria

ngul

aris

, ant

erio

rin

sula

, sup

erio

r pa

riet

al g

yrus

, sup

erio

r fr

onta

lsu

lcus

and

gyr

us, m

iddl

e fr

onta

l gyr

us, a

nter

ior

cere

bellu

m a

nd R

pos

teri

or c

ereb

ellu

m; Y

: no

corr

elat

ions

.

Raj

ah &

McI

ntos

h, 2

008,

Age

-rel

ated

dif

fere

nces

in b

rain

act

ivity

dur

ing

verb

al r

ecen

cy m

emor

y

Y:

8, O

: 8

Y:

mea

n ag

e =

25.

6, 1

M:7

F,ag

e ra

nge

= 2

1–35

; O:

mea

nag

e =

72.

7, 6

M:2

F, a

ge r

ange

= 6

2–80

No

med

ical

, neu

rolo

gica

l,or

psy

chia

tric

dis

orde

rs,

all M

MSE

sco

res

grea

ter

than

27

out o

f 30

fMR

IR

ecog

nitio

n or

rec

ency

judg

men

tsfo

r in

tent

iona

lly e

ncod

ed li

sts

ofw

ords

with

or

with

out s

eman

ticas

soci

atio

ns to

eac

h ot

her

com

pare

d to

a b

asel

ine

alph

abet

izin

g ta

sk. C

ontr

ast(

s):

Part

ial L

east

Squ

ares

ana

lysi

s of

Ret

riev

al v

s. A

lpha

betiz

ing,

Rec

ency

vs.

Rec

ogni

tion,

Rec

ency

and

Alp

habe

tizin

g vs

Rec

ogni

tion,

and

Dif

ficu

lt vs

.E

asy

Who

le b

rain

; suc

cess

anal

ysis

onl

y in

reg

ions

of s

igni

fica

nt a

ge e

ffec

ts

O >

Y: R

par

ahip

poca

mpu

s, R

pari

etal

, L p

recu

neus

, Rpr

efro

ntal

for

Rec

ency

and

Rec

ogni

tion

Acc

urac

y an

d re

actio

n tim

ese

para

tely

for

rec

ogni

tion

and

rece

ncy

judg

men

ts

Rec

ogni

tion:

O:

POS

corr

elat

ion

with

acc

urac

yan

d N

EG

with

RT

in R

pre

fron

tal r

egio

ns(

); N

EG

cor

rela

tion

with

accu

racy

and

PO

S co

rrel

atio

n w

ith R

T in

Rpa

rahi

ppoc

ampu

s (

); Y

: N

EG

corr

elat

ion

with

acc

urac

y an

d PO

S co

rrel

atio

nw

ith R

T in

R p

refr

onta

l; N

EG

cor

rela

tion

with

accu

racy

and

NE

G c

orre

latio

n w

ith R

T in

Rpa

rahi

ppoc

ampu

s. R

ecen

cy: O

: no

cor

rela

tion

with

acc

urac

y (S

CA

=N

CA

) an

d N

EG

corr

elat

ion

with

RT

in R

pre

fron

tal r

egio

ns

Biol Psychiatry. Author manuscript; available in PMC 2013 May 02.

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Eyler et al. Page 23

Cit

atio

nN

umbe

r of

Par

tici

pant

sC

hara

cter

isti

cs o

fpa

rtic

ipan

tsD

efin

itio

n of

"Hea

lthy

"T

ype

ofIm

agin

gP

arad

igm

tes

ted

Bra

inR

egio

n(s)

Exa

min

ed

Age

Dif

fere

nce(

s) in

Bra

inF

unct

ion

Succ

ess/

Per

form

ance

Det

erm

inat

ion

Succ

ess/

Per

form

ance

Cor

rela

tion

or

Eff

ect(

s)

();

NE

G c

orre

latio

n w

ithac

cura

cy a

nd P

OS

corr

elat

ion

with

RT

in R

para

hipp

ocam

pal (

); Y

: PO

Sco

rrel

atio

n w

ith a

ccur

acy

and

NE

G w

ith R

T in

R p

arah

ippo

cam

pal;

NE

G c

orre

latio

n w

ithac

cura

cy a

nd P

OS

corr

elat

ion

with

RT

in R

pref

ront

al (

in B

A 9

)

Ster

n et

al.,

200

8, A

com

mon

neu

ral n

etw

ork

for

cogn

itive

res

erve

inve

rbal

and

obj

ect

wor

kiin

g m

emor

y in

youn

g bu

t not

old

.

Let

ter

task

: Y:

40, O

: 18

; Sha

peta

sk: Y

: 24

, O:

21

Let

ter

task

: Y:

mea

n ag

e =

25.1

, 30M

:10F

, mea

n ye

ars

educ

atio

n: 1

5.7;

O:

mea

n ag

e=

74.

4, 7

M:1

1F, m

ean

year

sed

ucat

ion

= 1

5.3.

Sha

pe ta

sk:

Y:

mea

n ag

e =

24.

0; 1

2M:

12F;

mea

n ye

ars

educ

atio

n =

14.7

; O:

mea

n ag

e =

75.

8,11

M:1

0F, m

ean

year

sed

ucat

ion

= 1

5.8

No

neur

olog

ic o

rps

ychi

atri

c ill

ness

; no

dem

entia

fMR

ID

elay

ed r

espo

nse

task

: enc

odin

g,m

aint

enan

ce, a

nd r

etri

eval

of

sets

of le

tters

or

shap

es th

at v

arie

d in

size

(1,

3,6

lette

rs; 1

,2,3

sha

pes)

.C

ontr

ast(

s): L

oad-

rela

ted

chan

ges

duri

ng e

ncod

ing,

del

ay, a

ndre

spon

se

Who

le b

rain

cov

aria

tion

anal

ysis

.N

ot g

iven

Cog

nitiv

e re

serv

e: e

qual

wei

ghtin

g of

WA

IS-R

Voc

abul

ary

and

Nat

iona

lA

dult

Rea

ding

Tes

t

Y:

Let

ter

and

shap

e ta

sks

duri

ng e

ncod

ing,

PO

San

d N

EG

cor

rela

tions

of

cogn

itive

res

erve

with

activ

ity in

a n

etw

ork

incl

udin

g su

peri

or a

ndm

edia

l fro

ntal

; in

lette

r en

codi

ng o

nly,

NE

Gco

rrel

atio

n of

res

erve

with

act

ivity

in a

net

wor

kin

clud

ing

fron

tal,

pari

etal

, tem

pora

l, an

d ba

sal

gang

lia; O

: Fo

r le

tter

enco

ding

, PO

Sco

rrel

atio

n of

cog

nitiv

e re

serv

e w

ith a

ctiv

ity in

a ne

twor

k in

clud

ing

fron

tal,

pari

etal

, tem

pora

l,an

d ba

sal g

angl

ia (

); f

or le

tter

rete

ntio

n, P

OS

corr

elat

ion

with

act

ivity

in a

netw

ork

incl

udin

g fr

onta

l, ci

ngul

ate,

and

pari

etal

; for

lette

r re

trie

val (

),m

ix o

f N

EG

and

PO

S co

rrel

atio

ns w

ith r

egio

nal

activ

ity in

net

wor

k in

clud

ing

fron

tal a

ndth

alam

us (

and

); N

o si

gnif

ican

t cor

rela

tions

with

the

task

-ind

epen

dent

net

wor

k se

en in

Y,

but t

ende

ncy

tow

ards

opp

osite

cor

rela

tions

of

cogn

itive

res

erve

dur

ing

shap

e ta

sk e

ncod

ing

phas

e.

Wie

reng

a et

al.,

200

8,A

ge-r

elat

ed c

hang

es in

wor

d re

trie

val:

Rol

e of

bila

tera

l fro

ntal

and

subc

ortic

al n

etw

orks

Y:

20, O

: 20

Y:

mea

n ag

e =

25.

1, a

gera

nge

= 2

0–34

, 10M

:10F

,m

ean

year

s ed

ucat

ion

=15

.85;

O:

mea

n ag

e =

74.

9,ag

e ra

nge

= 6

8–84

, 10M

:10F

,m

ean

year

s ed

ucat

ion

=15

.65

No

hist

ory

of n

euro

logi

cal

dise

ase,

dem

entia

, mild

cogn

itive

impa

irm

ent-

amne

stic

type

,ca

rdio

vasc

ular

dis

ease

,un

cont

rolle

dhy

pert

ensi

on, p

sych

iatr

icdi

agno

sis;

no

psyc

hoac

tive

med

icat

ions

.

fMR

IO

vert

pic

ture

nam

ing

for

anim

als,

tool

s an

d ve

hicl

es a

nd a

pas

sive

view

ing

cond

ition

. Con

tras

t(s)

:E

vent

-rel

ated

ana

lysi

s of

nam

ing

vs. p

assi

ve v

iew

ing.

Who

le b

rain

ana

lysi

s;su

cces

s an

alys

is o

nly

infr

onta

l and

sub

cort

ical

regi

ons.

O >

Y:

B r

ostr

al c

ingu

late

, Ran

teri

or c

ingu

late

, B p

oste

rior

supp

lem

enta

ry m

otor

are

a, B

mot

or c

orte

x, R

Bro

ca's

hom

olog

ue, R

infe

rior

fro

ntal

gyru

s, R

sen

sori

mot

or c

orte

x, B

peri

sylv

ian

cort

ex, a

nd L

ling

ual

gyru

s.

Nam

ing

accu

racy

and

resp

onse

late

ncy;

als

osu

bdiv

ided

into

hig

h ac

cura

cy(>

90%

) an

d lo

w a

ccur

acy

(<87

%)

due

to a

bim

odal

dist

ribu

tion.

Y:

POS

corr

elat

ions

with

acc

urac

y in

Lsu

peri

or f

ront

al g

yrus

, L m

iddl

e fr

onta

l gyr

us,

L a

nter

ior

cing

ulat

e, R

neo

stri

atum

, NE

Gco

rrel

atio

ns in

R in

feri

or f

ront

al a

nd s

uper

ior

fron

tal g

yrus

; O:

POS

corr

elat

ions

with

accu

racy

()

in R

thal

amus

, Lle

ntif

orm

nuc

leus

, R in

feri

or f

ront

al g

yrus

,N

EG

cor

rela

tions

with

acc

urac

y(

) in

R p

rece

ntra

l gyr

us a

nd L

mid

dle

fron

tal g

yrus

, NE

G c

orre

latio

ns w

ithre

spon

se la

tenc

y (

) in

Lne

ostr

iatu

m, L

thal

amus

, B a

nter

ior

supe

rior

fron

tal g

yrus

; Hig

h O

: PO

S co

rrel

atio

ns w

ithac

cura

cy (

VSC

A >

SC

A)

in B

infe

rior

fro

ntal

gyru

s, R

BA

45,

B m

edia

l fro

ntal

gyr

us, L

supe

rior

fro

ntal

gyr

us, B

thal

amus

, L le

ntif

orm

nucl

eus,

NE

G c

orre

latio

ns (

SCA

> V

SCA

) in

Rsu

peri

or f

ront

al g

yrus

and

R p

rece

ntra

l gyr

us;

Low

O: P

OS

corr

elat

ions

()

inL

infe

rior

fro

ntal

, R th

alam

us, a

nd le

ntif

orm

nucl

eus,

NE

G c

orre

latio

ns (

) in

L in

sula

, R in

feri

or f

ront

al

NO

TE

: B=

bila

tera

l, B

A=

Bro

dman

n’s

area

, BD

I=B

eck

Dep

ress

ion

Inve

ntor

y, C

NS=

cent

ral n

ervo

us s

yste

m, D

TI=

diff

usio

n te

nsor

imag

ing,

EN

C=

enco

ding

, F=

fem

ale,

fM

RI=

func

tiona

l mag

netic

res

onan

ce im

agin

g, G

DS=

Ger

iatr

ic D

epre

ssio

n Sc

ale,

ISI

=in

ter-

stim

ulus

inte

rval

,L

=le

ft, M

=m

ale,

MI=

myo

card

ial i

nfar

ctio

n, M

MSE

=M

ini-

Men

tal S

tatu

s E

xam

, NC

A=

norm

al c

ogni

tive

agin

g, N

EG

=ne

gativ

e, O

=ol

d, P

ET

=po

sitr

on e

mis

sion

tom

ogra

phy,

PO

S=po

sitiv

e, R

=ri

ght,

rCB

F=re

gion

al c

ereb

ral b

lood

flo

w, R

ET

=re

trie

val,

RO

I=re

gion

of

inte

rest

,R

T=

reac

tion

time,

SC

A=

succ

essf

ul c

ogni

tive

agin

g, S

D=

stan

dard

dev

iatio

n, T

IA=

tran

sien

t isc

hem

ic a

ttack

, WA

IS-R

=W

echs

ler

Adu

lt In

telli

genc

e Sc

ale-

Rev

ised

, Y =

youn

g.

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Table 2

Summary of Study Characteristics for Reports in the Review

Study Characteristic Summary

Sample Characteristic Young Sample Old Sample

Median Range Median Range

Number of Participants 12 0–40 14 6–69

Gender Ratio (Men/Women) 1 (mean: 1.3) 0–9 1 (mean: 0.97) 0–3

Mean Age (years) 24 19.5–33.4 69.9 59–81.5

Minimum Age (years) 20 18–30 61 50–73

Maximum Age (years) 29 25–49 78 63–93

Mean Education (years) 16 14.5–17.8 16 10.2–19.3

Image Modality (no. of studies) 28 fMRI, 19 PET

Exclusion Criteria (no. of

studies)*45 neurological, 37 psychiatric, 36 medical, 35 cognitive, 25 medications, 16 radiological abnormalities

Challenge Task (no. of studies)* 1 rest, 21 episodic memory (phase: 13 encoding, 15 retrieval [method: 4 recall, 10 recognition]; stimuli: 13verbal, 3 figural, 2 faces, 2 abstract), 8 working memory (stimuli: 7 verbal, 1 spatial, 1 facial), 5inhibitory, 2 motor, 2 language, 2 visual search, 2 nondeclarative memory, 1 visual attention

Brain Regions Examined (no. of

studies) *1 whole brain (single value), 28 voxel-wise with whole brain coverage, 24 region of interest

Measure of Cognitive

Performance (no. of studies) *35 accuracy, 20 reaction time, 4 composite of accuracy and reaction time; 38 based on scanner taskperformance, 9 based on tasks given outside of scanner

*Note that the number of studies does not always add up to 47 across the categories because a study could be counted in more than one category.

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Eyler et al. Page 25

Table 3

Summary of Brain-Behavior Relationships in the Reviewed Studies

Brain Response

SuccessfulPerformers> Normal

Performers

NormalPerformers> SuccessfulPerformers

MixedFindings

Any region 38 25 19

All examined regions* 19 6 19

Frontal cortex 19 6 9

Temporal cortex 7 3 5

Parietal cortex 10 4 2

Occipital cortex 6 6 2

Hippocampal / Medial Temporal 5 5 0

Basal ganglia 4 2 0

Thalamus 2 4 1

Posterior cingulate 3 1 0

Cerebellum 3 1 0

*Note that for 2 studies there were no significant regions that were related to task performance (12, 35), and for 1 study the measure of

performance was not readily classified into “successful vs. unsuccessful” (34)

Biol Psychiatry. Author manuscript; available in PMC 2013 May 02.