Age-related changes in activation during tip-of-the-tongue: An event-related fMRI study.M.A. Shafto1, E.A. Stamatakis1, P.P. Tam1, D.M. Burke3, & L. K. Tyler1,2

1Department of Experimental Psychology , Cambridge, UK 2Wolfson Brain Imaging Center, Cambridge, UK 3Department of Psychology, Pomona College, Claremont, CA

BackgrounBackgroundd

Acknowledgements:Acknowledgements: We acknowledge The University of Cambridge Behavioural and Clinical Neuroscience Institute, supported by a joint award from the Medical Research Council and the Wellcome Trust; We also thank the radiographers at the Wolfson Brain Imaging Unit, Cambridge for their help with the study. This research was supported by NIA grant AG 08835 and a Sontag grant from Pomona College to Deborah Burke, and an MRC programme grant and grant from the Newton Trust to L. K. Tyler.

Methods & Methods & Analyses Analyses

Results & ConclusionsResults & Conclusions

http://csl.psychol.cam.ac.uk/ ; http://psych.pomona.edu/cogaging/

Phonological Retrieval Deficit Hypothesis:Phonological Retrieval Deficit Hypothesis:

ParticipantsParticipants

Behavioural performanceBehavioural performance

fMRI TOT taskfMRI TOT taskMaterialsMaterials

1. Younger and Older adults activate similar networks during TOTs including bilateral insula, ACC, R DLPFC, and R IFC.

2. Older adults show evidence of increased bilateral activation of insula, which may reflect recruitment following atrophy of areas relevant to phonological retrieval (i.e., left insula).

3. Older adults show reduced ACC and RIFC activity during TOTs, which may reflect age-related decreases in the availability of partial information and use of TOT resolution strategies.

Tip-of-the-tongueTip-of-the-tongue States (TOTs) States (TOTs)

•Temporary inability to produce a well-known word or name

•Most frequently involves proper names

•Phonological form of name inaccessible while semantic information about person available

•Sometimes partial phonological information about word available (e.g., initial phoneme or number of syllables)

TOT increase caused by Phonological Retrieval Deficit

ConclusionsConclusions

•TOTs less frequent than Know or Don’t Know responsesTOTs less frequent than Know or Don’t Know responses•TOTs slower than Know or Don’t Know responsesTOTs slower than Know or Don’t Know responses•No age effect or interactions for proportions or response times. No age effect or interactions for proportions or response times.

UNIVERSITY OF

CAMBRIDGEUNIVERSITY OFCAMBRIDGEUNIVERSITY OFCAMBRIDGE

TOT rates increase in old age

•Older adults produce more TOTs than young adults but less partial phonological information

•TOTs reduced by priming words phonologically related to target

•Semantic access spared in old age

•TOTs are the number one memory problem reported by older adults

•TOTs particularly increase for proper names

Phonological Retrieval Deficit and insula: Phonological Retrieval Deficit and insula: Structural imaging (Structural imaging (Burke et al., 2005Burke et al., 2005))

•Structural analysis correlating grey matter integrity with number of TOTs for each participant.

•Left insula associated with phonological production

•Age-related atrophy in left insula correlated with increasing TOTs

•Age-related atrophy in L insula not correlated with decreasing Ravens matrices performance

Increasing numbers of TOTs for famous faces Increasing numbers of TOTs for famous faces correlate with grey matter intensity in correlate with grey matter intensity in left insula left insula (Burke et al., 2005)(Burke et al., 2005)

TOT Resolution and ACC-PFC network: TOT Resolution and ACC-PFC network: Functional imaging (Functional imaging (Maril et al., 2001Maril et al., 2001))

1.1. Phonological Retrieval Deficit: Phonological Retrieval Deficit: • Will fMRI support structural Will fMRI support structural

findings that the insula is relevant findings that the insula is relevant for TOTs?for TOTs?

• Will fMRI performance in older Will fMRI performance in older adults reflect age-related atrophy adults reflect age-related atrophy in the insula?in the insula?

Bilateral InsulaBilateral Insula

ACC, R DLPFC, R IFCACC, R DLPFC, R IFC

Response proportionsResponse proportions Response timesResponse times

•200 famous faces•Pretested to include faces susceptible to TOTs for younger adults, and faces susceptible to TOTs for older adults

ProcedureProcedure•Each face presented for 3 sec•1 sec pause between pictures•Know, Don’t Know, or TOT response made with button press

3 sec picture

presentation

1 sec pause Etc.

Participant responds with button press

Etc.

•29 participants•15 younger aged 20 -37 (M=24.6, SD=4.45)•14 older aged 66 -88 (M= 74.5, SD=6.57)

•Activity examined for two areas:1. Bilateral insula; affiliated with phonological production 2. ACC, RIFC, RDLPFC; affiliated with conflict monitoring and strategic retrieval during TOT resolution

•Activity shown is unique to TOTs: TOT – [Know + Don’t Know]

2. ACC-PFC during Resolution: 2. ACC-PFC during Resolution: • Will current task replicate the Will current task replicate the

role of ACC-PFC network in role of ACC-PFC network in TOTs?TOTs?

• Will older adults make less use Will older adults make less use of the ACC-PFC network of the ACC-PFC network during TOTs?during TOTs?

•Based on structural findings, insula should be more active during TOTs for both young and older adults

•Based on the affiliation of left insula atrophy with age-related increases in TOTs, older adults may differentially recruit contralateral areas during TOTs

•Major language exclusion criteria

•Dyslexia self report or diagnosed•Non Native British English / bilingual•Left handed

•Major health exclusion criteria

•Neurological or hormonal disorder•Recent treatment for psychiatric disorder•Major head trauma•Stroke

Young and Older separatelyYoung and Older separately

Young versus OlderYoung versus Older

...

...

Current research: Current research: fMRI study of TOTs in younger and older adultsfMRI study of TOTs in younger and older adults

•Based on Maril et al., (2001), ACC-PFC network should be differentially active during TOTs

•Based on behavioural data that older adults report less partial information and fewer resolution strategies, older adults should show less ACC-PFC activity during TOTs

Bilateral InsulaBilateral Insula

Old> YoungOld> YoungYoung>OldYoung>Old

ACC, R DLPFC, R IFCACC, R DLPFC, R IFC

Both younger and older adults activate insula bilaterally

during TOTs, with left lateralized maxima

Both younger and older adults activate ACC, R DLPFC, and

R IFC during TOTs

Regions in right insula active for older > younger, supporting age-

related increase in activation during phonological production, and recruitment of contralateral

areas

Regions in ACC and R IFC active for younger > older, in

keeping with age-related decrease in reported TOT-

resolution strategies

•Scanning details: 3 Tesla Bruker Medspec Avance S300 system, gradient-echo EPI sequence, TR = 1102 ms, 21 oblique slices, 101 kHz bandwidth and spin echo guided reconstruction•Data analyses: SPM2 software (Wellcome Institute of cognitive Neurology, www. fil.ion.ucl.ac.uk). Contrast images from each subject combined into a group random effects analysis (RFX).

During TOTs, younger adults activated ACC,

RIFC, R DLPFC

•Cognitive model of TOT resolution which emphasizes conflict monitoring and strategic use of partial information to resolve TOTs

•Neural model of TOTs proposed implicating ACC-PFC network in conflict monitoring and strategic retrieval processes

Older adults report fewer strategies when resolving

TOTs

•Age-related decrease in reported partial information and resolution strategies (Burke et al., 1991)

•Age-related changes should be reflected in decreased use of ACC-PFC network

Behaviour-activity correlationsBehaviour-activity correlations•Maxima identified for unique TOT activity in L insula, R insula, ACC, RIFC•Activity at maxima correlated with behaviour for young and older separately*p<.05

OldOld YoungYoungLeft insulaLeft insula

Young and older TOT rates correlate with L insula activity

(young marginal p=.075)

YoungYoung

OlderOlder

YoungYoung

OlderOlder

0

0.1

0.2

0.3

0.4

0.5

Know TOT Don't Know

young

older

0

500

1000

1500

2000

2500

3000

Know TOT Don't Know

young

older

-5

0

5

10

15

20

0 0.1 0.2 0.3 0.4

TOT rate

Act

ivity

at L

insu

la m

axi

mu

m

r= -.66*

r= -.47

Right insulaRight insulaolder TOT rates correlate with R insula activity

-5

0

5

10

15

20

25

0 0.1 0.2 0.3 0.4

TOT rate

Act

ivity

at

R in

sula

ma

xim

um

r= -.65*

r= -.22

RIFCRIFCACCACCyounger TOT rates correlate with ACC

activity

-2

0

2

4

6

8

10

12

14

16

0 0.1 0.2 0.3 0.4TOT rate

Act

ivity

at

AC

C m

axi

mu

m

r= -.51*

r= -.44

-5

0

5

10

15

20

0 0.1 0.2 0.3 0.4

TOT rate

Act

ivity

at

RIF

C m

axi

mu

m

younger TOT rates correlate with RIFC activity (marginal

p=.083)r= -.46

r= -.29