!

!!!!!

COGNITIVE!FLEXIBILITY!AND!FRONTO2PARIETAL!CONTROL!DYNAMICS!IN!AGING!!!!!!!BY!!

PAULINE!BANIQUED!! !

!!!!!!!

DISSERTATION!!

Submitted!in!partial!fulfillment!of!the!requirements!!for!the!degree!of!Doctor!of!Philosophy!in!Psychology!

in!the!Graduate!College!of!the!University!of!Illinois!at!Urbana2Champaign,!2014!

!!!!

Urbana,!Illinois!!!

Doctoral!Committee:!!

Professor!Arthur!Kramer,!Chair!Professor!Monica!Fabiani,!Co2Director!of!Research!Professor!Gabriele!Gratton,!Co2Director!of!Research!Associate!Professor!Diane!Beck!Professor!Neal!Cohen!

! !

ii!

ABSTRACT''

How!do!we!prepare!for!complex!tasks?!Can!we!optimize!preparatory!control!

processes,!especially!as!they!decline!with!age?!The!research!program!detailed!here!sheds!

light!on!these!questions!by!employing!integrative!paradigms!to!investigate!brain!dynamics!

related!to!successful!performance!in!attention!or!control2demanding!situations.!These!

control2demanding!processes!are!broadly!referred!to!as!“executive!functions,”!known!to!

heavily!involve!the!frontal!cortex.!The!relationship!between!frontal!brain!activity!and!

behavioral!performance!however,!is!not!straightforward.!Some!studies!find!that!increased!

activation!in!this!region!relates!to!better!performance,!while!others,!particularly!studies!

that!involve!older!adults,!show!that!increased!activation!can!also!indicate!failure!to!engage!

appropriate!control!processes.!Given!these!mixed!observations,!as!well!as!the!myriad!of!

areas!involved!in!any!complex!task,!research!has!increasingly!shifted!towards!

understanding!how!brain!processes!are!implemented!via!activity!in!a!set!of!networked!

regions,!with!the!main!idea!that!correlation!of!activity!or!“connectivity”!between!regions!is!

more!informative!than!activity!from!a!single!region.!Moreover,!studies!have!shown!that!

factors!such!as!aging,!as!well!as!training!or!interventions!do!not!only!change!the!structure!

or!activity!of!specific!regions,!but!the!dynamics!of!the!brain!networks!these!regions!belong!

to.!!

This!dissertation!involves!two!main!goals:!1)!investigating!preparatory!control!

processes!by!evaluating!the!connectivity!of!brain!regions,!particularly!the!interaction!of!the!

prefrontal!cortex!and!task2relevant!regions,!and!2)!investigating!how!aging!may!modify!the!

dynamics!of!these!processes,!with!future!plans!to!use!these!findings!to!inform!training!or!

intervention!research.!!

iii!

! In!the!first!experiment!(Chapter!2),!I!investigate!preparatory!processes!in!middle2

to2older!aged!adults!using!a!cued!task2switching!paradigm.!Older!adults!show!a!specific!

decline!in!fronto2parietal!regions!and!in!executive!function!abilities,!particularly!in!tasks!

that!involve!flexibly!allocating!attention.!Here,!in!addition!to!age,!corpus!callosum!and!

modulation!over!left!frontal!cortex!predicted!switch!costs.!Using!cross2correlations!to!

examine!the!flow!of!activity!in!a!switching!task,!I!found!that!left!middle!frontal!gyrus!

activity!preceded!up2regulation!of!task2relevant!lateralized!processes!in!frontal!regions.!In!

addition!to!highlighting!the!flexible!dynamics!and!timing!of!these!processes,!this!

experiment!also!confirmed!the!importance!of!the!corpus!callosum!structural!connection!in!

supporting!the!task2dependent!interaction!between!frontal!regions.!

In!the!second!experiment!(Chapters!3!and!4),!I!examine!preparatory!control!by!

studying!whether!older!adults!modulate!frontal!control!processes!in!response!to!cues!that!

indicate!the!degree!of!control!needed!for!an!upcoming!target!stimulus.!Similar!to!young!

adults,!older!adults!showed!cue2related!behavioral!adjustments!and!up2regulated!frontal!

regions!for!cues!predicting!a!greater!need!for!attentional!control.!Lagged!cross2correlations!

showed!that!control2demanding!cues!led!to!greater!coupling!between!the!dorsal!anterior!

cingulate!cortex!and!the!left!middle!frontal!gyrus,!regions!important!for!evaluating!control!

and!implementing!control,!respectively.!Although!older!adults!showed!weaker!and!trends!

for!slower!up2regulation!of!frontal!regions!overall,!they!also!showed!greater!bilateral!

recruitment!of!dorsal!frontal!regions,!with!cross2correlations!pointing!to!a!left2to2right!

hemisphere!flow!of!activation!and!up2regulation!during!the!control2demanding!cues.!

Overall,!this!line!of!work!uses!converging!behavioral!and!imaging!methods!to!obtain!

a!more!comprehensive!view!of!the!brain!dynamics!that!are!important!for!complex!

iv!

performance.!Chapter!5!integrates!the!findings!from!the!two!experiments!to!identify!

common!mechanisms!of!preparatory!control!and!age2related!change.!Identifying!the!neural!

processes!that!are!important!for!executive!function!can!better!inform!research!that!seeks!

to!maintain!or!improve!this!ability!across!the!lifespan.!Potential!applications!include!

monitoring!brain!activity!and!providing!real2time!feedback!to!support!performance,!and!

identifying!tasks!or!interventions!that!promote!and!engage!the!neurocognitive!dynamics!

that!are!important!for!performance!in!real2world!tasks.!!

v!

ACKNOWLEDGEMENTS!

! I!am!lucky!to!have!learned!from!among!the!best:!from!my!parents!and!teachers!in!

the!Philippines,!to!my!mentors!at!Penn!and!Illinois.!To!my!doctoral!committee:!Diane,!Neal,!

Monica,!Gabriele!and!Art,!thank!you!for!the!wisdom,!resources!and!guidance!you!provided!

throughout!my!graduate!career.!To!my!IGERT!mentors!Todd!and!Doug,!thank!you!for!

helping!me!realize!I!can!do!more.!!!

! I!especially!thank!my!advisors!Monica,!Gabriele!and!Art,!for!all!the!knowledge,!wit,!

kindness!and!grit!you!have!taught!me!and!allowed!me!to!learn!over!the!last!five!and!a!half!

years!(and!counting).!Thank!you!for!trusting!me!with!all!this!work,!and!for!your!

unwavering!encouragement.!I!am!also!deeply!grateful!to!Kathy!Low,!for!her!mentorship,!

understanding!and!support!as!I!entered!unfamiliar!territory.!

! I!thank!the!members!of!the!Cognitive!Neuroimaging!Lab,!without!whom!none!of!this!

work!would!be!possible:!Maclin,!Low,!Stanley,!Burton,!DeJong,!Koury,!Weng,!Mathewson,!

Schneider2Garces,!Tse,!Gorden,!Fletcher,!Walker,!Zimmerman,!Chiarelli,!Tan!&!Kong.!

! I!thank!the!members!of!the!Lifelong!Brain!and!Cognition!lab!who!have!enriched!my!

academic!and!personal!life.!Special!thanks!to!the!graduate!students,!lab!managers!and!

undergraduate!research!assistants!who!have!allowed!me!carry!on!work!in!two!labs:!

Knecht,!Kranz,!Allen,!Lutz,!Weisshappel,!Johnson,!Kienzler,!Mourad,!King,!Changlani,!Henry,!

Lewis,!DeSouza,!Golshani,!O'Keefe,!Powers,!Tseng,!Steinberg,!Sipolins,!Banducci,!Nikolaidis,!

&!Ang.!I!am!also!indebted!to!all!the!guidance!and!encouragement!from!Voss,!Wong,!Lee,!

Chaddock2Heyman,!Cooke,!Burzynska,!Parks,!Batt,!Basak,!Medeiros2Ward,!Monti,!Gaspar,!

Yamani!&!Alves.!

vi!

For!their!work!and!efforts!to!make!life!better!for!me!and!many!others!everyday,!I!

thank!the!BIC!staff!especially!Nancy!and!Holly,!Beckman!ITS!especially!Tim!and!Mark,!the!

Beckman!cafeteria!staff!led!by!Chris,!and!the!delivery!personnel!who!keep!me!going!on!

many!late!nights.!

I!am!very!thankful!for!the!friends!who!keep!me!in!mental!and!physical!shape.!My!

deepest!gratitude!to!Ate!Carleen!and!Kuya!Edward!for!welcoming!me!into!the!Illinois!

barkada,!and!into!their!home!during!my!last!semester!in!Illinois.!Thank!you!to!my!

roommates!and!workout!buddies!Diana,!Aibee,!Tintin,!Jay,!and!Lito!for!the!countless!laughs!

and!raw!friendship.!Thank!you!to!the!colleagues!who!have!become!good!friends—I!am!

eternally!grateful!to!Anya,!from!whom!I!draw!strength!and!kindness.!!

! I!am!deeply!grateful!to!Mikhail,!whose!love!and!companionship!inspire!me!to!be!

better!everyday.!Thank!you!for!sharing!this!life!with!me.!

! I!am!very!grateful!to!my!family!for!their!unconditional!support:!to!my!sisters!who!

show!their!love!in!unique!ways,!to!my!lolols,!lolas,!titas,!titos,!and!cousins!back!home!who!I!

miss!very!much.!Thank!you!to!Carol!and!Richard!for!welcoming!me!into!your!home,!and!for!

bringing!Rachel!into!this!world.!!

! To!my!parents,!I!owe!you!everything.!!

!

! For!their!financial!support!during!my!time!as!a!graduate!student,!I!thank!the!

Neuroengineering!NSF!IGERT!Program,!the!Beckman!Institute!Graduate!Fellows!Program,!

and!the!National!Institutes!of!Health.!

vii!

TABLE'OF'CONTENTS'

'CHAPTER!1:!Introduction……………………………………………………………………………………….1!

!CHAPTER!2:!Fronto2parietal!task!switching!dynamics!in!middle2to2older!age…………..19! !!CHAPTER!3:!Control!adjustments!in!aging:!Behavioral!and!ERP!Findings………………....60! !

!CHAPTER!4:!Control!adjustments!in!aging:!EROS!Findings……………………………………….87!!CHAPTER!5:!Conclusions………………………………………………………………………………………..104!!REFERENCES…………………………………………………………………………………………………………107! !!

!

1!

CHAPTER'1'INTRODUCTION1'

Age9related'differences'in'executive'control'

The!earliest!theories!to!explain!age2related!decline!or!differences!in!cognition!

sought!to!account!for!a!single!mechanism!to!explain!aging’s!broad!effects.!Aging!is!

characterized!by!a!decline!in!a!wide!array!of!functions,!although!not!all!abilities!are!affected!

to!the!same!extent.!Processes!that!require!“online”!or!complex!operations!that!build!on!one!

another!show!unique!and!more!profound!changes,!while!more!“crystallized”!abilities!such!

as!verbal!knowledge!and!numerical!ability!stay!relatively!intact.!Reduced!processing!speed!

was!one!of!the!earliest!mechanisms!proposed!to!explain!age2related!differences!in!

cognition!(Salthouse,!1996),!with!path!analyses!and!hierarchical!regression!analyses!

showing!that!while!age!and!speed!ability!were!directly!related!(as!well!as!speed!with!other!

cognitive!variables),!there!was!no!direct!link!between!age!and!cognition.!The!processing!

speed!theory!revolved!around!2!main!principles:!1)!limited!time—that!performance!

decrements!observed!with!age!are!a!result!of!an!inability!to!properly!and!timely!execute!

operations!needed!for!cognitive!processing!and!that!such!delay!laid!to!a!failure!in!2)!

simultaneity,!where!information!from!previous!operations!were!no!longer!available!in!

usable!form!thereby!hurting!performance!in!complex!tasks!that!require!activation!or!use!of!

multiple!pieces!of!information,!as!in!measures!of!fluid!intelligence!or!tasks!of!executive!

control.!

1 Sections!of!this!chapter!(Task2switching!as!an!insight!into!preparatory!control,!Fronto2parietal!network!connectivity!in!young!adults)!include!text!from!a!published!article!on!which!the!student!was!the!lead!author:!Baniqued,!P.L.,!Low,!K.A.,!Fabiani,!M.!&!Gratton,!G.!(2013).!Frontoparietal!traffic!signals:!A!fast!optical!imaging!study!of!preparatory!dynamics!in!response!mode!switching.!Journal!of!Cognitive!Neuroscience,!25(6),!8872902.!doi:10.1162/jocn_a_00341.!Copyright!Journal!of!Cognitive!Neuroscience!http://www.mitpressjournals.org/loi/jocn'

!

2!

The!simultaneity!principle!overlaps!with!a!growing!framework!for!explaining!aging2

related!decline,!that!of!a!reduced!capacity!for!control2demanding!processes,!such!as!

working!memory!and!attention.!Craik!&!Byrd!(1982)!argued!that!it!is!the!performance!of!

controlled!operations,!or!those!that!require!“mental!energy”!as!opposed!to!“automatic”!

processes!that!are!selectively!compromised!in!aging.!Specifically,!working!memory!(WM)!

theories!of!aging!point!out!the!difficulty!older!adults!face!when!they!have!to!actively!

maintain!and!manipulate!information!in!mind.!Unlike!the!processing!speed!theory!that!

emphasized!timely!execution!of!operations,!this!theory!focused!more!on!the!simultaneity!

aspect!of!being!able!to!use!or!represent!multiple!pieces!of!information.!The!impaired!ability!

to!do!this!is!thought!to!stem!from!reduced!capacity!or!resources!that!comes!with!age,!in!

that!older!adults!have!less!“slots”!available!to!encode!and!consequently!maintain!

increasingly!huge!or!complex!amounts!of!information,!as!supported!by!magnified!age!

differences!in!complex!vs.!simple!span!tasks!(Reuter2Lorenz!&!Park,!2010).!

The!HAROLD!theory:!Hemispheric!Asymmetry!Reduction!in!OLDer!adults!(Cabeza,!

2002)!developed!out!of!the!observation!that!during!attention2demanding!tasks!such!as!

working!memory!paradigms,!older!adults!recruit!more!regions!across!various!tasks,!such!

as!bilateral!frontal!activation!in!contrast!to!the!unilateral!pattern!of!activity!typically!seen!

in!young.!The!theory!proposes!two!main!explanations!for!the!lateralization!findings:!1)!

dedifferentiation!and!2)!compensation.!Dedifferentiation!is!the!idea!that!age2related!

bilateral!recruitment!comes!from!a!difficulty!in!engaging!specialized!neural!mechanisms.!

Behavioral!evidence!comes!in!the!form!of!higher!correlations!between!various!cognitive!

abilities!with!increasing!age.!Neuroimaging!studies!have!found!such!reduced!functional!

specificity!in!sensory!or!association!areas,!although!more!work!needs!to!be!done!to!support!

!

3!

this!view—in!particular!to!explain!bilateral!recruitment!in!frontal!regions.!Compensation!is!

the!more!widely!studied!explanation!for!HAROLD,!and!it!stems!from!the!finding!that!

despite!equivalent!performance!in!old!and!young!adults,!differences!in!neural!activity!are!

found!with!older!subjects!showing!more!bilateral!activity.!The!theory!proposes!that!in!

older!adults!who!suffer!from!reduced!processing!resources!or!capacity,!increased!neural!

recruitment!is!needed!to!achieve!the!same!level!of!performance!as!younger!adults!(Cabeza,!

2002).!Moreover,!findings!by!Reuter2Lorenz!and!colleagues!(2000)!revealed!that!this!

bilateral!activation!was!most!evident!in!faster2responding!older!adults,!providing!further!

support!that!this!pattern!was!optimal!or!compensatory,!and!not!necessarily!a!marker!of!

cognitive!failure.!This!theory!was!formalized!by!Reuter2Lorenz!and!colleagues!(2008)!as!

the!CompensationBrelated!utilization!of!neural!circuits!hypothesis!(CRUNCH).!!

Strong!support!for!CRUNCH!is!found!in!transcranial!magnetic!stimulation!(TMS)!

studies!that!find!performance!decrements!when!older!adults!who!typically!show!bilateral!

activation!receive!TMS!to!either!hemisphere!(Rossi!et!al.,!2004).!TMS!as!typically!

administered!in!“deactivating”!mode!induces!noise!in!the!underlying!neural!signals!and!

thus!creates!a!temporary!“lesion”!in!the!area.!Meanwhile,!another!study!used!TMS!in!the!

“activating”!mode!to!promote!activity!in!the!underlying!tissue!and!found!results!as!

predicted!by!CRUNCH:!older!adults!who!initially!showed!poor!performance!now!improved!

and!also!now!showed!more!bilateral!activation!(Sole2Padulles,!et!al.,!2006).!An!interesting!

and!yet!unresolved!question!is!what!the!brain!is!compensating!for,!and!theories!range!from!

increased!noise!(as!in!the!dedifferentiation!hypothesis)!to!compensation!due!to!poorer!

input!from!other!areas.!This!latter!explanation!receives!some!support,!as!increasingly!more!

!

4!

studies!find!that!brain!regions!interact!as!a!network!to!support!optimal!performance.!Such!

network!findings!and!age2related!differences!will!be!discussed!in!a!later!section.!

Although!CRUNCH!findings!show!unequal!neural!recruitment!in!the!face!of!

equivalent!performance,!quantitative!support!for!the!theory!is!minimal!and!little!is!known!

about!the!neural2behavior!relationship!at!the!other!ends!of!the!performance!spectrum,!at!

extremely!low!and!high!task!loads.!The!theory!predicts!that!compensatory!activity!

increases!at!higher!task!loads,!and!that!older!adults!will!do!this!at!earlier/easier!task!loads!

than!young!adults.!Then!at!maximum!task!load,!older!adults!will!no!longer!be!able!to!

recruit!or!“deploy!additional!resources.”!To!better!test!this,!Schneider2Garces!and!

colleagues!!(2010)!used!a!Sternberg!working!memory!task!and!included!5!memory!set!

sizes!to!study!the!neural2behavior!relationship!parametrically!and!in!more!detail.!They!

replicated!previous!findings!showing!that!overall,!collapsed!across!set!sizes,!older!adults!

recruited!more!bilaterally!than!younger!adults.!At!low!set!sizes,!they!found!bilateral!

frontoparietal!activation!in!older!adults,!with!only!visual!cortex!activity!in!young!adults.!At!

higher!set!sizes!however,!young!adults!now!showed!increasingly!bilateral!activation!while!

old!adults!showed!no!increase!in!activation!with!increasing!levels!of!high!load.!This!latter!

result!was!interesting,!as!overactivation!or!bilateral!activation,!which!is!“typical”!of!older!

adults,!is!now!absent!and!instead!present!in!the!young.!Is!the!neural!phenomenon!then!not!

general!to!aging!but!a!manifestation!of!individual!differences!in!resources!or!memory!span?!!

To!probe!this,!each!subject’s!span!was!computed!and!fMRI!activation!was!

determined!for!spans!below!and!above!the!subject’s!limit.!Here!they!found!that!older!and!

young!adults!had!a!similar2shaped!sigmoid!function,!such!that!activity!increased!up!to!the!

individual’s!span,!then!leveled!off!at!above!capacity.!They!concluded!that!bilateral!

!

5!

activation!was!not!an!age!phenomenon!per!se,!but!one!that!comes!out!of!older!adults!

having!lower!spans!on!average.!CRUNCH!it!seems!is!not!solely!an!age2specific!theory,!but!

one!that!extends!to!relative!task!difficulty!(Schneider2Garces,!et!al.,!2010).!The!asymptotes!

found!in!performance!and!neural!activity!remains!to!be!explored,!but!primary!explanations!

include!limitations!in!cognitive!capacity!or!in!neurovascular!capacity.!Overall,!these!

findings!suggest!that!aging!is!characterized!by!more!of!a!shift!in!pre2existing!individual!

differences,!more!formally!described!in!terms!of!“GOLDEN!aging,”!or!growth!of!lifelong!

differences!explains!normal!aging!(Fabiani,!2012).!

Earlier!studies!on!age2related!working!memory!differences!hint!that!capacity!limits!

are!not!related!to!reduced!resources!or!slots!in!memory!per!se,!but!to!a!reduced!ability!to!

control!or!use!them!efficiently.!Hasher,!Lustig!and!Zacks!(2007)!proposed!the!inhibitory!or!

attentional!control!theory!of!aging,!which!was!consistent!at!the!time!with!findings!of!lack!of!

age2related!differences!at!WM!memory!encoding!or!simple!maintenance!(Rypma!&!

D’Esposito,!2000;!Gazzaley,!Cooney,!Rissman!&!D’Esposito,!2005).!That!is,!older!adults!

were!not!impaired!in!processing!huge!amounts!of!information,!but!in!processing!such!

information!in!the!face!of!distraction!or!task2irrelevant!or!competing!information.!

Propelled!by!findings!that!working!memory!age!differences!were!observed!only!at!retrieval!

stages!and!not!encoding!(Rypma!&!D’Esposito,!2000),!Gazzaley!and!colleagues!went!a!step!

further!and!this!time!manipulated!the!information!presented!during!the!delay!or!

maintenance!period!such!that!task2irrelevant!information!was!presented!together!with!the!

to2be2remembered!stimuli!(2005).!Consistent!with!the!inhibitory!hypothesis,!they!found!

that!older!adults!had!a!preserved!ability!to!enhance!task2relevant!representations!but!a!

relatively!impaired!ability!to!suppress!task2irrelevant!information,!as!evidenced!by!

!

6!

comparable!activity!in!a!scene2selective!ROI!during!remember2scenes!and!ignore2scenes!

trials.!While!younger!adults!showed!a!significant!down2regulation!during!the!ignore2scenes!

trials,!older!adults!did!not.!This!was!also!accompanied!by!behavioral!impairments!by!older!

adults!in!the!ignore!scenes!condition,!with!both!reduced!accuracy!and!longer!reaction!

times.!The!findings!of!longer!reaction!times!in!this!study!and!others!provide!support!for!the!

processing!speed!theory,!but!build!on!it!such!that!processes!that!require!control!of!

attention!are!selectively!impaired!with!age.!

A!review!by!Kramer,!Fabiani!and!Colcombe!(2006)!summarizes!research!consistent!

with!the!inhibitory!hypothesis.!Some!relatively!well2characterized!ERPs!can!index!the!

degree!to!which!certain!information!is!processed!and!can!highlight!where!the!bottlenecks!

in!age2related!processing!occur.!For!example,!older!adults,!compared!to!young,!have!been!

found!to!show!persistent!auditory!N100s,!despite!repetition!and!task2irrelevance!of!the!

tones,!as!well!as!despite!explicit!instruction!to!ignore!the!tones.!A!similar!pattern!has!been!

found!for!the!P3a!or!novelty!P3!that!is!typically!seen!in!response!to!unexpected!or!novel!

stimuli.!A!study!also!found!that!a!measure!of!attentional!control—the!operation!span!task!

(OSPAN)!is!predictive!of!the!parietally2distributed!P300!or!P3b,!which!unlike!the!P3a,!is!

more!sensitive!to!stimulus!sequence!and!maintenance!of!mental!representations,!with!a!

smaller!amplitude!corresponding!to!a!better!maintained!representation.!Brumback2Peltz,!

Gratton!and!Fabiani!(2011)!investigated!this!in!older!adults!and!found!that!participants!

with!high!attentional!control!displayed!smaller!P3bs,!indicating!that!they!were!better!able!

to!keep!track!of!information.!In!this!study,!aging!was!found!to!be!related!to!decreased!

recruitment!of!parietal!activity!and!an!increased!reliance!on!frontal!processes.!This!is!

reminiscent!of!the!HAROLD!and!CRUNCH!theories!where!increased!frontal!activity!is!

!

7!

thought!to!be!related!to!decreased!activity!in!other!regions.!Indeed,!aging!studies!are!

shifting!towards!understanding!trade2off!or!network!mechanisms!and!integrating!these!

with!individual!differences!in!cognitive!ability.!!

Task9switching'as'an'insight'into'preparatory'control'

Given!the!complexity!of!the!observations!discussed!previously,!an!ideal!paradigm!to!

study!executive!control!in!aging!is!task2switching,!with!its!demand!on!attention!control!and!

the!opportunity!to!study!switch2general!processes!and!task2related!activation,!deactivation!

and!any!interactions!between!regions.!Switching!between!tasks!typically!results!in!slower!

and!less!accurate!performance,!although!switch!costs!are!reduced!after!extended!practice!

and!when!when!people!are!given!time!to!prepare!(Jersild,!1927;!Monsell,!2003;!Allport,!

Styles!&!Hsieh,!1994;!Kramer,!Hahn!&!Gopher,!1999;!Wylie!&!Allport,!2000).!Decreased!

performance!such!as!longer!reaction!times!in!mixed!blocks!compared!to!single2task!blocks!

(global!costs)!are!often!found!in!older!adults,!although!more!recent!work!has!found!local!

switch!costs!(repeat!vs!switch!trials!in!a!mixed!task!block),!with!greater!age!differences!in!

paradigms!that!place!a!higher!memory!load,!such!as!in!requiring!subjects!to!keep!track!of!

when!to!switch!or!in!tasks!that!introduce!additional!elements!of!interference,!such!as!in!

response!selection!(Kramer!et!al.,!1999).!Nonetheless,!training!studies!have!shown!that!at!

least!for!some!paradigms,!switch!costs!can!be!ameliorated!to!a!certain!degree,!even!in!older!

adults!(Kramer,!Larish,!Weber!&!Bardell,!1999).!

Superior!performance!and!practice2related!improvements!in!switching!efficiency!

have!been!attributed!to!greater!recruitment!of!preparatory!control!processes!on!switch!

trials,!during!which!attention!is!thought!to!be!redirected!from!previously!relevant!tasks!to!

focus!on!new!demands!(Meiran!1996;!Sohn,!Ursu,!Anderson,!Stenger,!&!Carter,!2000;!

!

8!

Hopfinger,!Buonocore,!&!Mangun,!2000;!for!a!review,!see!Karayanidis!et!al.,!2010).!These!

effects!are!associated!with!increased!activity!in!prefrontal!and!parietal!brain!regions!(i.e.,!

the!“frontoparietal!network”!or!FPN;!Gilbert!&!Shallice,!2002;!Mesulam,!1990;!Posner!&!

Petersen,!1990),!but!they!also!typically!involve!differential!activation!of!task2specific!

regions!(see!Kim,!Cilles,!Johnson!&!Gold,!2012!for!a!meta2analysis).!Theories!of!switching!

efficiency!highlight!two!mechanisms:!general!cue2triggered!instantiation!or!directing!of!

attention,!and!a!succeeding!cascade!of!task2specific!preparatory!processes!that!may!involve!

discarding!or!inhibiting!irrelevant!task!rules,!retrieving!trial2appropriate!ones!and!

maintaining!the!relevant!task2set!(Monsell,!2003;!Corbetta!&!Shulman,!2002;!Dosenbach!et!

al.,!2006;!Rushworth,!Walton,!Kennerley!&!Bannerman,!2004;!Gilbert!&!Shallice,!2002;!

Perianez!et!al.,!2004).!Preparatory!control!theories!assert!that!prefrontal!regions!initiate!

coordination!of!attention!processes!and!bias!brain!states!towards!the!relevant!stimulus!or!

task!(Miller!&!Cohen,!2001;!Corbetta!&!Shulman,!2002;!Brass,!Ullsperger,!Knoesche,!von!

Cramon!&!Philips,!2005).!However,!general!knowledge!of!such!dynamics!across!switching!

paradigms!is!limited!(Monsell,!2003;!Kim,!Cilles,!Johnson!&!Gold,!2011).!

In!a!previous!study,!we!chose!response!domains!with!well2characterized!and!

anatomically!specific!functional!profiles:!manual!and!vocal!responses.!As!numerous!studies!

have!shown!increased!activity!within!sensory!cortices!due!to!attentional!shifts!related!to!

the!task!stimulus!or!modality!(Weissman,!Warner,!Woldorff,!2004;!Hopfinger,!Buonocore,!

&!Mangun,!2000),!we!predicted!modulation!of!the!motor!cortex!and!Broca’s!area!during!the!

delay!period!where!preparation!likely!involves!“pre2activation”!of!response!production!

areas!(Wylie,!Javitt!&!Foxe,!2006;!Dosenbach!et!al.,!2006).!Indeed,!we!found!activity!in!

!

9!

posterior!parietal!and!left2lateralized!perisylvian!areas!regions!during!the!preparatory!

interval,!with!activation!modulated!by!the!modality!of!the!current!trial.!!!

Task2specific!reconfiguration!may!also!involve!reciprocal!inhibition,!an!idea!

proposed!in!some!models!of!attention!control!(Miller!&!Cohen!2001;!Hasher,!Lustig,!&!

Zacks,!2007;!Herd!et!al.,!2006),!where!processes!required!for!a!particular!task!may!be!

suppressed!when!different!task!demands!are!imposed.!!For!example,!activity!in!middle2to2

inferior!frontal!gyrus!in!the!left!and!right!hemispheres!has!been!shown!to!be!differentially!

responsive!to!verbal!or!spatial!tasks!(Gratton,!Wee,!Rykhlevskaia,!Leaver!&!Fabiani,!2009;!

Smith,!Jonides!&!Koeppe,!1996;!Reuter2Lorenz!et!al.,!2000).!In!a!previous!EROS!study,!

switching!to!a!verbal!task!resulted!in!activation!of!left!prefrontal!cortex!while!switching!to!

a!spatial!task!involved!right!prefrontal!cortex!(Gratton!et!al.,!2009).!Such!effects!are!

accompanied!by!deactivation!in!the!task2irrelevant!region!(Rykhlevskaia!et!al.,!2006)!and!

are!modulated!by!the!strength!of!the!structural!or!functional!connections!between!

preparatory!control!areas.!Thus,!in!the!experiments!described!in!this!dissertation,!we!

expect!to!observe!both!down2!and!up2regulation!of!networks!in!preparation!for!response!

production!depending!on!which!aspects!of!response!activation!are!being!primed!or!

suppressed.!

Cognitive'flexibility'and'strategic'control'

' Task!switching!studies!shed!light!on!how!individuals!flexibly!control!their!attention,!

but!this!assumes!that!similar!strategies!are!engaged!to!prepare!for!different!tasks!or!stimuli!

that!may!vary!in!the!demand!for!control.!As!discussed!previously,!older!adults’!abilities!do!

not!uniformly!decline!with!age.!In!fact,!older!adults!demonstrate!relatively!preserved!

attentional!capture!(Kramer,!Hahn,!Irwin!&!Theeuwes,!1999;!Cashdollar!et!al.,!2012)!which!

!

10!

may!help!in!low2conflict!or!congruent!type!trials!where!processing!distractors!or!

“irrelevant”!information!can!facilitate!performance,!although!such!processing!may!also!

make!them!especially!susceptible!to!distracting!information.!In!many!paradigms,!it!takes!

longer!for!older!adults!to!recover!or!disengage!from!irrelevant!information,!and!this!has!

been!related!to!working!memory!capacity!(Fukuda!&!Vogel,!2011)!which!is!known!to!be!

negatively!affected!by!age.!One!popular!yet!controversial!idea!of!how!attention!is!

controlled!is!“conflict!adaptation,”!where!control!processes!are!thought!to!be!triggered!by!

the!experience!of!a!high2conflict!previous!trial,!such!that!control!is!engaged!and!helps!

performance!on!the!succeeding!high2conflict!trial,!with!little!modulation!of!low2conflict!

trials!(for!a!review,!see!Egner!2008).!This!phenomenon!was!first!described!by!Gratton,!

Coles!and!Donchin!(1992),!who!found!that!in!a!flanker!task,!subjects!performed!better!after!

high2conflict!“incongruent”!trials!(HHSHH)!than!after!low2conflict!“congruent”!trials!

(HHHHH).!Gratton!and!colleagues!suggested!a!strategic!or!expectancy!account!wherein!

subjective!expectations!as!to!the!nature!of!the!upcoming!trial!drove!them!to!regulate!

behavior,!with!a!greater!tendency!to!select!a!focused!strategy!after!a!high!conflict!trial!(and!

default!to!a!parallel!or!less!focused!strategy!after!low2conflict!trials).!In!a!series!of!

experiments!that!aimed!to!rule!out!stimulus!repetition!or!response!priming,!they!

confirmed!that!expectancy!did!relate!to!strategy!selection,!such!that!a!high!probability!of!

congruent!trials!led!to!a!“early!selection”!strategy!that!allowed!for!greater!processing!of!

flankers!to!facilitate!performance,!while!a!high!probability!of!incompatible!trials!led!to!a!

more!focused!selection!strategy.!Interestingly,!this!has!been!found!to!occur!without!

awareness!(Ghinescu,!Schachtman,!Stadler,!Fabiani!&!Gratton,!2010)!in!a!paradigm!that!

manipulated!whether!subjects!were!aware!of!the!predictive!utility!of!the!cues!that!

!

11!

preceded!stimulus!onset.!In!another!cued!preparation!paradigm!(AX2!continuous!

performance!test),!older!adults!have!also!been!shown!to!engage!more!“reactive”!than!

proactive!control!by!default,!but!that!task2strategy!training!can!shift!them!words!a!more!

proactive!mode!(Braver,!Paxton,!Locke!&!Barch,!2009)!associated!with!increased!lateral!

PFC!activity!and!improved!performance.!!

! In!the!conflict!adaptation!literature,!which!emphasizes!the!experience!of!conflict!

over!an!expectancy!account,!previous2trial!or!cue2triggered!reconfiguration!of!behavior!has!

been!linked!to!frontal!and!parietal!cortices.!In!a!review,!Egner!and!Hirsch!(2005)!

highlighted!the!role!of!the!anterior!cingulate!in!monitoring!performance!and!detecting!

conflict,!and!its!interaction!with!the!dorsolateral!prefrontal!cortex!to!adjust!performance!

on!the!next!trial!(Botvinick!et!al.,!2001;!Botvinick,!Cohen!&!Carter,!2004;!Kerns!et!al.,!2004;!

Hanslmayr!et!al.,!2008).!Indeed,!there!is!increasing!data!to!support!the!involvement!of!

oscillatory!processes!or!an!interplay!between!regions.!Pastötter,!Dreisbach!&!Bäuml!(2013)!

found!that!left!parietal!theta!and!mid2central!beta!frequencies!related!to!attentional!control!

were!higher!after!conflict2demanding!than!after!low2conflict!(incongruent)!trials!during!the!

inter2trial!interval.!Interestingly,!these!were!found!during!the!inter2trial!period,!and!were!

related!to!mid2frontal!theta!on!the!succeeding!trial!for!incongruent!trials,!with!mid2frontal!

theta!power!positively!correlated!with!reaction!time.!In!an!elegant!exploration!of!task2

switching!trial2to2trial!dynamics,!Mayr,!Kuhns!and!Rieter!(2012)!provide!complementary!

eye2tracking!evidence!for!adjustments!in!control,!finding!that!eye!movements!to!distractors!

in!trial!n21!predicted!more!target!eye!movements!in!trial!n.!Consistent!with!previous!

behavioral!findings,!King,!Korb!&!Egner!(2012)!also!found!that!control!processing!can!

occur!non2explicitly.!

!

12!

The!conflict!adaptation!and!expectancy!accounts!both!hinge!on!the!idea!that!

prefrontal!cortex!acts!to!bias!activity!in!other!regions.!However,!fMRI!and!EEG!parardigms!

are!limited!in!characterizing!shown!the!dynamics!between!the!two!regions,!with!the!

majority!of!analyses!limited!to!correlations!of!absolute!activity!or!correlations!at!the!zero2

lag!order.!In!the!next!section,!we!discuss!what!is!currently!known!about!the!functional!

interactions!of!regions!important!for!controlling!attention,!and!how!we!can!use!the!event2

related!optical!signal!to!better!characterize!the!dynamics!of!these!processes.!!

Fronto9parietal'network'connectivity'in'young'adults'

Attention2demanding!situations!heavily!involve!frontal!and!parietal!regions,!or!

“frontoparietal”!attention!networks,!so!called!due!to!their!frequently!observed!co2

activation!(Corbetta!&!Shulman,!2002).!In!young!adults,!interactions!between!FPN2

dependent!control!activity!and!sensory2motor!areas!have!been!shown!to!be!important!for!

performance,!particularly!for!resolving!conflict!or!promoting!task2relevant!processing!in!

the!presence!of!distraction!(Egner!&!Hirsch,!2005).!Functional!network!connectivity!is!

most!often!assessed!by!computing!correlations!between!patterns!of!activity!in!distinct!

areas!(for!a!review,!see!Rykhlevskaia,!Gratton!and!Fabiani,!2008).!These!analyses!are!

typically!carried!out!on!functional!magnetic!resonance!imaging!(fMRI)!data!(Fox!et!al.,!

2005;!Cohen!et!al.,!2008;!Smith!et!al.,!2009;!Bullmore!&!Sporns,!2009;!Gratton,!Nomura,!

Perèz,!&!D’Esposito,!2012)!using!multivariate!or!seed2based!approaches!that!reveal!

regional!patterns!of!synchronization.!Using!beta2series!correlation!analysis,!Rissman!and!

colleagues!(2004)!showed!that!the!right!fusiform!face!area!showed!robust!correlations!

with!prefrontal!and!parietal!regions!during!the!delay!period!of!encoding!face!stimuli,!albeit!

overall!activation!in!frontal!and!parietal!regions!was!not!found!in!a!univariate!analysis.!

!

13!

Disruption!of!the!prefrontal!cortex!via!transcranial!magnetic!stimulation!(TMS,!Zanto,!

Rubens,!Thangavel!&!Gazzaley,!2011)!confirmed!the!importance!of!prefrontal!cortical!

activity!in!such!a!delayed2recognition!or!memory!task,!as!disrupting!the!inferior!frontal!

junction!prior!to!the!task!reduced!modulation!of!posterior!visual!processing!areas!and!was!

related!to!impaired!performance!in!the!working!memory!task.!These!findings!underscore!

the!importance!of!studying!the!connectivity!between!regions,!and!stress!the!importance!of!

high!resolution!spatiotemporal!analyses!to!identify!the!component!preparatory!processes.!!

Although!very!useful!for!extracting!network!components,!the!slow2evolving!

hemodynamic!signals!associated!with!fMRI2based!connectivity!analyses!limit!our!ability!to!

identify!network!dynamics,!and!in!particular!the!order!of!activation!of!network!areas.!

Electroencephalography2based!(EEG!and!event2related!brain!potential,!or!ERP)!techniques!

can!better!characterize!the!millisecond2scale!unfolding!of!events!within!and!across!trials.!

Source!localization!techniques!can!in!some!cases!identify!distinct!signal!generators!in!the!

brain!and!thus!provide!a!way!to!examine!the!flow!of!information!between!areas,!such!as!

the!proposed!frontal!to!posterior!cascade!of!attentional!control!processes.!Nonetheless,!

some!details!about!the!areas!involved!are!likely!to!be!lost!due!to!EEG’s!limited!spatial!

resolution.!Increasingly!more!studies!are!conducted!with!magnetoencephalography!(MEG;!

de!Pasquale!et!al.,!2010),!which!possesses!a!temporal!resolution!similar!to!EEG,!but!a!better!

spatial!resolution.!!MEG!findings!and!studies!that!integrate!fMRI!with!ERP!results!show!that!

the!distribution!of!frontoparietal!activity!generally!proceeds!in!an!anterior!to!posterior!

direction!(Brass,!Ullsperger,!Knoesche,!von!Cramon,!&!Phillips,!2005;!Perianez!et!al.,!2003),!

but!other!studies!using!EEG!source!reconstruction!and!dynamic!causal!modeling!of!fMRI!

data!have!observed!the!opposite!flow!of!activity!(Green!&!McDonald,!2008;!Wang!et!al.,!

!

14!

2010).!Similarly!to!EEG,!MEG!has!difficulty!measuring!independently!the!time!course!of!

activity!in!adjacent!cortical!regions!(i.e.,!regions!located!less!than!a!few!cm!apart);!this,!as!

well!as!its!high!cost!and!limited!access!constrain!functional!connectivity!research!with!

MEG.!In!the!current!studies!we!employ!the!event2related!optical!signal!(EROS;!see!Gratton!

&!Fabiani,!2010!for!a!review),!a!technique!that!combines!high!spatial!and!temporal!

resolution,!to!identify!rapidly!oscillating!and!distinct!sources!of!cortical!activity.!!

EROS!uses!near2infrared!light!to!detect!variations!in!the!optical!properties!of!neural!

tissues!caused!by!neuronal!activity!(Foust!&!Rector,!2007;!Rector!et!al.,!1997,!2005)!and!is!

thus!capable!of!localizing!activity!to!the!sub2centimeter!scale!and!with!a!temporal!

resolution!of!less!than!50!milliseconds.!We!use!a!frequency2domain!method!as!this!

technique!allows!us!to!measure!both!the!amount!of!light!that!diffuses!through!a!brain!

region,!and!the!average!time!taken!by!photons!to!travel!between!sources!and!detectors.!

Despite!its!high!spatiotemporal!resolution,!the!limitations!of!EROS!include!its!inability!to!

detect!activity!from!deeper!sub2cortical!regions!and!its!relatively!low!signal2to2noise!ratio!

(SNR).!In!addition!to!increasing!the!amount!of!trials!and!subjects,!one!way!to!address!the!

SNR!issue!while!taking!advantage!of!the!spatiotemporal!properties!of!EROS!is!to!employ!

lagged!cross2correlation!analyses!(see!Rykhlevskaia!et!al.,!2006).!Computations!between!

time!series!are!conducted!separately!for!each!subject,!and!thus!increase!the!power!to!

detect!rapidly!evolving!patterns!of!activity!with!onsets!that!may!vary!across!individuals.!

This!approach!has!been!used!for!time!and!frequency!analyses!of!EEG!and!MEG!data!(Gevins!

et!al.,!1983;!Bressler!1995;!Gross!et!al.,!2001).!!The!rich!spatio2temporal!information!

provided!by!EROS!can!help!characterize!the!millisecond!progression!of!activity!across!

regions,!and!thus!assess!functional!connectivity!at!a!high!spatiotemporal!resolution.!We!use!

!

15!

timing!information!in!the!form!of!lags!to!model!how!activity!in!one!area!may!precede!or!

follow!activity!in!other!regions!(Rykhlevskaia,!Fabiani!&!Gratton,!2006).!To!test!the!

predictions!of!prefrontal2directed!disengagement!and!engagement!of!task2specific!

processes,!we!incorporated!the!seed2based!approach!from!fMRI!with!cross!correlations!

across!a!range!of!time!lags.!!From!the!resulting!positive!and!negative!correlations,!we!can!

infer!relative!increases!and!decreases!in!brain!activity.!!

In!a!previous!study!with!young!adults!(Baniqued!et!al.,!2013),!we!investigated!

switching!between!response!modalities,!where!cross2correlations!revealed!a!robust!

association!between!an!early!parietal!switch!effect!and!a!subsequent!frontal!switch!effect,!

confirming!the!functional!connectivity!of!these!two!regions.!More!interestingly,!our!results!

revealed!distinct!fronto2parietal!networks!based!on!correlation!and!propagation!of!activity!

from!the!frontal!seed,!with!network!topology!differing!according!to!switching!modality.!

The!remarkable!finding!was!the!dynamic!nature!of!these!connections:!when!preparing!for!a!

hand!response,!prefrontal!activity!became!negatively!coupled!with!verbal!regions!and!then!

positively!coupled!with!the!hand!areas.!Conversely,!when!preparing!for!a!verbal!response,!

prefrontal!regions!became!negatively!correlated!with!the!now!task2irrelevant!hand!motor!

regions,!then!positively!correlated!with!the!now!relevant!verbal!preparation!regions.!These!

results!underscore!that!flexible!network!dynamics!in!fronto2parietal!networks!are!critical!

to!switching2related!control!of!attention.!!

Fronto9parietal'network'connectivity'in'older'adults'

! In!this!work,!we!employ!lagged!cross2correlation!analyses!in!addition!to!univariate!

analyses!to!probe!preparatory!dynamics!in!older!adults.!Older!adults!show!selective!

decline!of!frontal!cortices!(among!other!regions),!so!in!Experiment!1,!we!use!a!switching!

!

16!

paradigm!that!primarily!recruits!frontal!cortex!of!both!hemispheres!and!is!known!to!show!

age2related!differences!both!in!behavioral!switch!costs!and!recruitment!of!frontal!regions!

(Gratton!et!al.,!2009).!In!the!previous!study,!Gratton!and!colleagues!did!not!examine!

functional!connectivity,!but!corpus!callosum!and!lateralization!effects!hinted!at!the!

importance!of!functional!connections!for!performance.!!

The!importance!of!connectivity!analyses!in!augmenting!univariate!analyses!is!

demonstrated!further!in!a!study!by!Madden!and!colleagues!(2010)!that!found!no!age!

differences!in!cue2related!switch!activation,!but!revealed!differences!in!connectivity!such!

that!younger!adults!showed!greater!connectivity!between!switch2related!regions,!with!

greater!connectivity!related!to!better!performance.!In!another!study,!Nagel!and!colleagues!

(2011)!found!that!regardless!of!age!(consistent!with!the!GOLDEN!Aging!view),!individuals!

who!displayed!greater!working!memory!performance!also!showed!greater!connectivity!

between!left!PFC!and!left!premotor!cortex!with!increasing!load.!!

The!importance!of!frontal!connectivity!is!unpacked!in!a!study!by!Rieckmann!et!al.!

(2010)!which!found!reduced!anterior2to2posterior!connectivity!in!older!adults,!but!

increased!fronto2frontal!connectivity!during!a!working!memory!task.!Moreover,!it!was!the!

latter!that!related!to!better!performance!in!older!adults,!suggesting!increased!reliance!on!

frontal!mechanisms!as!communication!with!parietal!cortex!declines!(Grady!et!al.,!2010).!

The!same!group!also!conducted!a!psychophysiological!interaction!analysis!(PPI,!to!test!for!

load2dependent!connectivity)!and!found!greater!within2PFC!connectivity!for!higher!than!

for!lower!load!trials,!although!this!effect!was!only!present!for!older!and!not!young!adults.!

Here!again!we!find!network!dynamics!that!only!differ!with!age,!but!vary!from!trial!to!trial!

according!to!the!demands!of!the!task.!

!

17!

Structural'connectivity'and'age9related'differences'

Function!is!necessarily!tied!to!the!structures!that!support!it,!so!it!is!to!be!expected!

that!the!main!connections!between!regions!that!carry!out!the!important!control!processes!

play!a!significant!role.!Many!studies!have!shown!that!white!matter,!particularly!those!that!

connect!prefrontal!and!parietal!regions,!account!for!a!significant!portion!of!the!variance!in!

the!relationship!between!brain!activity!and!performance!on!attention2demanding!tasks!

(Gratton!et!al.,!2009,!Burzynska,!et!al.,!2011).!Age!is!accompanied!by!changes!in!brain!

structure,!with!reductions!in!gray!matter!(Gordon!et!al.,!2008;!Davatzikos!&!Resnick,!2002;!

Raz,!Gunning2Dixon,!Head,!Dupuis,!&!Acker,!1998)!and!white!matter!such!as!changes!in!

diffusivity,!hyperintensities!and!reduction!in!volume!(Raz!et!al.,!2005).!We!have!also!seen!

evidence!that!cortical!“disconnection”!accompanies!age2related!cognitive!decline!(Sullivan!

et!al.,!2001),!although!not!all!studies!show!the!relationship!between!structural!and!

functional!interactions!(Madden!et!al.,!2010).!This!may!be!due!to!the!non2uniform!pattern!

of!degeneration!and!the!importance!of!particular!regions!for!the!task!being!studied.!An!

anterior2posterior!gradient!of!change!is!usually!observed,!with!greater!decline!in!frontal!

regions!(Burzynska!et!al.,!2010).!

In!a!study!that!aimed!to!examine!the!importance!of!white!matter!connectivity!to!the!

ability!to!efficiently!switch!tasks,!anterior!corpus!callosum!(CC)!volume!predicted!

switching!costs!in!an!attention2demanding!task!that!primarily!recruits!processes!in!

opposite!hemispheres!of!the!frontal!cortex!(Gratton!et!al.,!2009).!Smaller!CCs!predicted!

greater!switch!costs!and!reduced!lateralization!of!task2specific!switching!processes.!This!

was!evident!in!switching2to2spatial!condition,!where!older!adults!showed!specific!

impairments.!Task2general!and!meaning2specific!switching!activity!were!localized!to!the!

!

18!

left!middle!frontal!gyrus!(MFG),!while!spatial2specific!activity!to!right!MFG.!While!both!

young!and!old!adults!displayed!the!task2general!and!task2specific!activation!of!left!MFG,!

only!young!adults!displayed!right!MFG!for!the!switch2to2position!condition.!Older!adults,!

particularly!those!with!small!CC,!recruited!the!left!MFG!instead,!suggesting!that!the!control!

signal!in!left!MFG!may!not!have!been!able!to!adequately!communicate!to!the!position2

specialized!right!MFG.!

In!summary,!research!suggests!that!connectivity!between!brain!regions!is!important!

for!performance!on!control2demanding!tasks,!likely!by!enabling!communication!between!

regions!to!transfer!information!quickly!and!as!such!reduce!switch!costs!(consistent!with!

the!processing!speed!theory),!or!to!promote!synergistic!or!cross2inhibitory!processing.!This!

dissertation!aims!to!fill!in!some!of!these!gaps!in!our!understanding!of!aging!and!cognitive!

control!by!examining!connectivity!dynamics!using!the!high!spatial!and!temporal!resolution!

of!the!event2related!optical!signal!(EROS).!In!this!work,!EROS!recordings!are!supplemented!

by!acquisition!of!magnetic!resonance!imaging!(MRI)!and!event2related!potentials!(ERPs),!

which!all!together!enable!a!more!comprehensive!view!of!brain!dynamics.!

!

!

19!

CHAPTER'2'FRONTO9PARIETAL'TASK'SWITCHING'DYNAMICS'IN'MIDDLE9TO9OLDER'AGE'

!Abstract'

! Control2demanding!tasks!rely!on!communication!among!regions!of!the!

frontoparietal!network,!areas!that!undergo!significant!age2related!decline.!Here!we!

integrate!data!from!brain!structure,!event2related!potentials!(ERPs)!and!event2related!

optical!signals!(EROS)!to!better!characterize!preparatory!control!dynamics!in!middle!to!old!

age.!Older!adults!completed!a!task!that!required!switching!between!processes!that!

primarily!recruit!opposite!prefrontal!cortex!hemispheres!and!thus!involve!the!corpus!

callosum!(CC;!Gratton!et!al.,!JoCN,!2009).!Participants!were!split!into!young2old!(YO;!55267!

yrs)!and!old2old!(OO;!68285!yrs),!and!large2!and!small2CC!groups.!Larger!anterior!CCs!

significantly!predicted!smaller!switch!costs,!but!only!in!the!YO!group.!Switch!trials!resulted!

in!greater!negativity!over!F3!in!the!YO!group,!paralleling!their!smaller!behavioral!switch!

costs.!This!frontal!negativity!was!accompanied!by!switch2related!EROS!activation!in!left!

middle!frontal!gyrus!(MFG).!Importantly,!MFG2seeded!lagged!cross2correlations!revealed!

task2dependent!coupling:!MFG!activation!predicted!up2regulation!in!left!inferior!frontal!

and!parietal!areas!for!the!meaning!task,!and!in!right!dorsal!frontal!regions!for!the!position!

task.!In!the!right2hemisphere!dependent!position!task,!greater!coupling!of!left!MFG!to!right!

MFG!was!predicted!by!greater!CC!volume.!Together!these!results!suggest!that!a!strong!

structural!connection!is!critical!to!overcome!the!demands!of!shifting!processing!across!

hemispheres,!and!that!difficulties!engaging!such!control!dynamics!may!lead!to!sub2optimal!

preparation!strategies.!!

' '

!

20!

Introduction!

When!attention!must!be!flexibly!and!unpredictably!re2allocated!from!one!task!to!

another!such!as!in!switching!paradigms,!efficient!performance!as!reflected!in!smaller!

reaction!time!switch!costs!is!typically!accompanied!by!increased!activation!in!frontal!and!

parietal!cortices!(Meiran!1996;!Sohn,!Ursu,!Anderson,!Stenger,!&!Carter,!2000;!Hopfinger,!

Buonocore,!&!Mangun,!2000;!DiGirolamo!et!al.,!2000;!Wylie!et!al.,!2004;!Liston,!Matalon,!

Hare,!Davidson!&!Casey,!2006;!Karayanidis!et!al.,!2010;!Kim,!Cilles,!Johnson!&!Gold,!2011).!

These!regions,!coined!the!“fronto2parietal!network”!(FPN)!due!to!their!frequent!co2

activation,!are!consistently!involved!in!a!wide!array!of!tasks!that!demand!control!of!

attention!(Gilbert!&!Shallice,!2002;!Mesulam,!1990;!Posner!&!Petersen,!1990)!and!are!thus!

thought!to!direct!up2regulation!of!task2appropriate!processes!(Miller!&!Cohen,!2001;!

Corbetta!&!Shulman,!2002;!Brass,!Ullsperger,!Knoesche,!von!Cramon!&!Philips,!2005).!!

Cognitive!functions!such!as!attentional!control!(Greenwood!and!Parasuraman,!1997;!

Fabiani,!2002;!Kramer!et!al.,!2006;!Madden!et!al.,!2005;!Madden,!2007)!and!FPN!regions!

undergo!significant!age2related!decline,!with!reductions!in!gray!matter!(Gordon!et!al.,!

2008;!Davatzikos!&!Resnick,!2002;!Raz,!Gunning2Dixon,!Head,!Dupuis,!&!Acker,!1998)!and!

pronounced!changes!in!white!matter!(Gunning2Dixon!et!al.,!2009;!Guttman!et!al.,!2000;!

Courchesne!et!al.,!2000!and!Raz!et!al.,!2005).!Nonetheless,!while!normal!aging!is!

characterized!by!broad!changes!in!brain!function,!the!degree!to!which!an!individual!

manifests!behavioral!changes!is!strongly!associated!not!only!with!chronological!age!per!se,!

but!also!with!a!variety!of!factors!including!differences!in!educational!level,!lifestyle,!and!the!

health!of!brain!structures!(Stern,!2002;!Fabiani,!2012).!!

!

21!

Various!measures!of!white!matter!health,!particularly!those!of!tracts!that!connect!

prefrontal!and!parietal!regions,!are!significantly!associated!with!brain!activity!and!

performance!in!switching,!working!memory!and!other!attentional!control!paradigms!

(Gratton!et!al.,!2009;!Madden!et!al.,!2010;!Gold!et!al.,!2010;!Burzynska,!et!al.,!2011;!Jolly!et!

al.,!In!Preparation).!!Decline!in!these!functions!is!often!accompanied!by!age2related!cortical!

“disconnection”!as!manifested!in!reduced!white!matter!integrity!or!smaller!white!matter!

volume!(Gunning2Dixon!et!al.,!2008;!Sullivan!et!al.,!2001).!It!is!important!to!note,!however,!

that!not!all!studies!find!a!synergistic!relationship!between!structural!and!functional!

connections!(Madden!et!al.,!2010).!These!mixed!findings!may!in!part!be!due!to!the!non2

uniform!pattern!of!degeneration!across!the!brain!and!the!relative!importance!of!particular!

regions!for!chosen!task!paradigms.!An!anterior2posterior!gradient!of!change!is!commonly!

observed!when!examining!white!matter!integrity!in!aging,!with!greater!decline!in!frontal!

regions!(Head!et!al.,!2004;!Bennett!et!al.,!2010;!Burzynska!et!al.,!2010).!The!volume!of!the!

anterior!portion!of!the!corpus!callosum!(CC),!for!example,!predicted!switch!costs!in!a!

paradigm!that!primarily!recruited!opposite!frontal!hemispheres!(Gratton!et!al.,!2009),!with!

smaller!CCs!showing!greater!switch!costs!and!reduced!lateralization!of!task2specific!

processes.!In!young!adults,!early2onset!task2general!and!later2onset!meaning2specific!

switching!activity!were!localized!to!the!left!middle!frontal!gyrus!(MFG),!while!later2onset!

spatial2specific!activity!was!localized!to!the!right!MFG.!Older!adults,!particularly!those!with!

small!CC,!recruited!the!left!MFG!instead!for!the!position!task,!suggesting!that!the!general!

control!signal!in!left!MFG!may!not!been!adequately!relayed!to!the!position2specialized!right!

MFG.!The!functional!relationship!between!such!task2general!and!task2specific!processes,!

however,!was!not!analyzed!in!the!previous!study.!In!the!current!study,!we!examine!these!

!

22!

interactions!in!time!and!integrate!these!functional!connectivity!findings!with!CC!structural!

connectivity.!We!also!investigate!this!within!a!bigger!sample!of!older!adults,!and!with!

greater!coverage!of!brain!areas!including!parietal!regions!known!to!support!control!of!

attention.!

!To!analyze!the!functional!interaction!between!areas,!we!employ!the!event2related!

optical!signal!(EROS;!see!Gratton!&!Fabiani,!2010!for!a!review),!which!uses!near2infrared!

light!to!measure!neural2related!changes!in!the!light!scattering!properties!of!brain!tissue!

(Foust!&!Rector,!2007;!Rector!et!al.,!1997,!2005).!As!EROS!directly!measures!neural!

activity,!its!centimeter2scale!spatial!resolution!and!millisecond2scale!temporal!resolution!

allow!for!a!more!comprehensive!view!of!brain!dynamics!during!the!preparatory!period.!In!

addition,!we!used!lagged!cross2correlations!to!investigate!not!only!how!activity!in!

disparate!areas!are!synchronized!with!each!other,!but!also!how!activity!in!one!seed!region!

may!be!systematically!related!to!activity!in!another!area!at!a!later!interval.!Correlations!

between!time!series!are!conducted!on!an!individual!basis!and!thus!rely!less!on!activity!

occurring!within!similar!narrow!intervals!across!subjects.!Thus,!this!analysis!has!greater!

power!to!detect!patterns!of!activity!that!oscillate!rapidly!and!whose!onsets!may!differ!

across!participants.!Although!not!a!new!approach!for!analyzing!electrophysiological!data!

(Gevins!et!al.,!1983;!Bressler!1995;!Gross!et!al.,!2001),!this!approach!has!been!relatively!

underused!for!neuroimaging!methods!with!higher!spatial!resolution!such!as!magnetic!

resonance!imaging,!perhaps!due!to!the!challenges!posed!by!the!slower2evolving!

hemodynamic!response.!More!recent!analyses!using!event2related!optical!methods!have!

begun!to!incorporate!this!method!with!promising!results—such!as!in!confirming!the!

!

23!

coupling!of!frontal!and!parietal!regions!and!how!such!FPN!activity!predicts!specific!

cognitive!task!states!(Baniqued!et!al.,!2013;!Walker!et!al.,!2014;!Mathewson!et!al.,!2014).!!

In!a!previous!task2switching!experiment!with!young!adults!(Baniqued!et!al.,!2013),!

EROS!cross2correlations!showed!that!cue2locked!MFG!activity!first!predicted!down2

regulation!in!task2irrelevant!sensorimotor!areas!followed!by!up2regulation!in!task2relevant!

sensorimotor!areas.!These!results!not!only!mirrored!overall!activation!findings!of!early!

activation!in!MFG!and!then!later!activation!in!sensorimotor!regions—but!they!also!

demonstrated!their!sub2second2scale!functional!relationship!and!thus!provided!a!window!

into!the!rapid!dynamics!of!switching.!Due!to!the!easier!nature!of!the!task!however,!there!

was!inadequate!variance!to!examine!the!relationship!between!connectivity!and!

performance.!In!the!current!experiment,!we!capitalize!on!the!increased!variability!!in!both!

performance!and!brain!function!observed!in!an!aging!population!to!better!probe!brain2

behavior!relationships.!

The!relationship!between!brain!functional!connectivity!and!behavior!is!not!

straightforward,!especially!in!the!context!of!aging.!In!a!working!memory!task,!Rieckmann!et!

al.!(2010)!found!reduced!anterior2to2posterior!connectivity!in!older!adults,!but!increased!

fronto2frontal!connectivity.!The!latter!was!predictive!of!better!performance!in!older!adults,!

supporting!theories!about!increased!reliance!on!frontal!mechanisms!as!communication!

with!parietal!cortex!declines!with!age!(Grady!et!al.,!2010).!Moreover,!they!found!that!

within2PFC!connectivity!increased!for!high!compared!to!low!load!trials.!This!study!is!one!of!

many!(Fabiani!&!Friedman,!1995;!Hasher!&!Zacks,!1988;!Davis!et!al.,!2008;!Grady,!2008;!

Gratton!et!al.,!2009;!Nagel!et!al.,!2011;!for!a!review!see!Fabiani,!2012)!that!underscores!the!

continued!importance!of!frontal!regions,!and!more!importantly,!shows!that!frontal!network!

!

24!

dynamics!varies!with!task!demands.!The!current!study!aims!to!show!not!only!the!flexible!

nature!of!these!couplings,!but!also!the!timing!at!which!these!connections!occur.!

We!employ!electrophysiological!recording!(ERPs)!to!provide!converging!

information!regarding!the!timing!of!preparatory!processes!and!their!consequences!for!

behavior.!Cue2switch,!task2switch!and!target2related!processes!are!relatively!separable!in!

ERP!paradigms,!with!task!switching!components!dominating!at!longer!preparatory!

intervals!between!cue!and!target!stimulus!(Jost,!Mayr,!Rösler,!2008;!Travers!&!West,!2008;!

Karayanidis,!Coltheart,!Michie!&!Murphy,!2003;!Nicholson,!Karayanidis,!Bumak,!Poboka!&!

Michie,!2006;!Kieffaber!&!Hetrick,!2005;!Swainson!et!al.,!2003).!In!cued!task!paradigms,!

switching!effects!are!primarily!observed!around!3002500!ms!post2cue!in!frontal!and!

parietal!electrodes,!with!frontal!negativity!for!switch!trials!(Baniqued!et!al.,!2013;!Mueller,!

Swainson,!Jackson,!2007)!in!young!adults,!and!modulations!of!the!P3!component!related!to!

task!updating.!Specifically,!aging!studies!find!latency!differences!and!frontal!shifts!in!the!

topography!of!the!P3!(Adrover2Roig!&!Barcelo,!2010;!West!&!Travers,!2008;!West,!2004;!

Kray,!Eppinger,!Mecklinger,!2005;!Friedman!et!al.,!2007;!Hillman,!Kramer,!Belopolsky!&!

Smith,!2006),!as!well!as!modulations!of!slow!frontal!negative!potentials!(Kray,!Eppinger!&!

Mecklinger,!2005)!in!old!but!not!young!adults,!complementing!fMRI!findings!of!increased!

frontal!recruitment!in!older!age.!Spatial!stroop!ERP!data!from!Gratton!and!colleagues!

(2009,!unpublished!data)!find!the!greatest!switch!effects!in!frontal!electrodes,!with!young!

adults!showing!greater!negativity!for!switch!compared!to!repeat!trials,!and!older!adults!

showing!the!reverse!pattern.!In!the!current!experiment,!concurrently!recorded!ERPs!

provide!insight!into!when!brain!activity!significantly!diverges!across!conditions,!and!

further!confirmation!of!the!spatio2temporal!dynamics!observed!with!EROS.!

!

25!

In!summary,!there!is!strong!evidence!to!support!that!connectivity!between!brain!

regions!of!the!frontoparietal!network!is!important!to!performance!in!control2demanding!

situations,!likely!by!enabling!communication!between!regions!to!transfer!information!

quickly!and!as!such!reduce!switch!costs.!However,!no!studies!to!our!knowledge!have!

examined!the!timing!and!flexible!nature!of!these!functional!interactions!and!integrated!

these!dynamics!with!measures!of!structural!connectivity.!To!address!this!in!this!

experiment,!we!use!the!spatial!Stroop!paradigm!given!its!previously!documented!reliance!

on!frontal!activation!and!structure!(Gratton!et!al.,!2009;!Smith,!Jonides!&!Koeppe,!1996).!In!

addition!to!replicating!previous!findings!of!task2general!switch!activation!in!left!MFG!and!

lateralized!switch!activity!for!the!meaning!and!position!tasks,!the!current!experiment!will!

use!converging!methods!of!structural!MRI,!ERPs!and!EROS!to!shed!light!on!the!following!

questions:!1)!After!taking!age!into!account,!will!greater!anterior!corpus!callosum!volume!

predict!smaller!switch!costs?!2)!After!taking!age!into!account,!will!greater!switch2related!

modulation!of!frontal!cortex!predict!smaller!switch!costs?!3)!Does!frontal!activation!early!

in!the!preparatory!period!relate!to!later!task2specific!preparatory!up2regulation?!4)!Does!

greater!anterior!corpus!callosum!volume!translate!into!greater!functional!connectivity!

between!frontal!hemispheres,!and!5)!Does!greater!activation!and!connectivity!jointly!or!

uniquely!predict!smaller!switching!costs?!!

!

' '

!

26!

Methods'

Participants!

Forty2five!right2handed!adults!aged!55287!(23!female)!participated!in!a!multi2

session!study!and!received!compensation!of!$10/hr!(see!Zimmerman!et!al.,!2014!and!

Fabiani!et!al.,!2014!for!data!published!from!this!same!cohort).!Selection!criteria!consisted!

of!the!following:!1)!no!serious!or!chronic!medical!or!psychological!conditions,!2)!no!history!

of!drug!abuse,!3)!no!signs!of!dementia!as!reflected!in!a!score!of!at!least!51!on!the!modified!

Mini2Mental!Status!examination!(Mayeux!et!al.,!1981),!4)!no!signs!of!depression!as!indexed!

by!a!score!of!less!than!14!on!the!Beck!Depression!Inventory!(Beck!et!al.,!1996),!5)!no!

habitual!consumption!of!alcohol!or!cigarette,!or!at!least!of!no!more!than!2!alcoholic!drinks!

per!day!and/or!half!a!pack!of!cigarettes!per!day,!and!6)!normal!or!corrected2to2normal!

vision!and!7)!being!a!native!English!speaker.!!

In!all!analyses!related!to!the!spatial!Stroop!task,!participants!were!excluded!if!they!

missed!more!than!50!trials!overall!(n=3),!or!scored!less!than!66%!on!any!condition!(n=7,!2!

due!to!unrecorded!responses!from!one!hand).!Summary!demographics!from!remaining!

participants!are!presented!in!Table!2.1.!Due!to!technical!difficulties!in!data!acquisition,!two!

additional!subjects!were!excluded!from!EEG!analysis.!Participants!had!normal!or!corrected2

to2normal!vision!and!signed!informed!consent.!The!University!of!Illinois!Institutional!

Review!Board!approved!all!procedures!used!in!the!study.!

Spatial!Stroop!Task!

' While!undergoing!concurrent!EROS2ERP!recording,!participants!completed!the!

spatial!Stroop!paradigm!(Figure!2.1),!which!required!them!to!respond!to!either!the!

meaning!or!position!of!a!word.!Participants!were!positioned!81!cm!from!the!screen.!At!the!

!

27!

beginning!of!each!trial,!a!letter!cue!was!displayed!for!500!ms!on!either!side!of!fixation!and!

indicated!the!task!for!that!trial:!the!letter!M!for!the!meaning!task,!or!the!letter!P!for!the!

position!task.!Cues!subtended!a!visual!angle!of!0.71°!horizontally!and!0.85°!vertically,!while!

the!fixation!cross!subtended!a!visual!angle!of!0.71°.!After!a!15002ms!interval,!participants!

responded!to!the!reaction!stimulus,!which!was!the!word!“above”!or!“below”!positioned!

above!or!below!fixation!for!200!ms.!The!reaction!stimulus!was!either!congruent,!such!as!the!

word!“below”!positioned!below!the!fixation!cross,!or!incongruent,!such!as!the!word!“below”!

positioned!above!fixation.!The!reaction!stimulus!subtended!a!visual!angle!of!3.89°!

horizontally!and!1.27°!vertically.!Participants!responded!by!pressing!a!button!with!their!

left!or!right!hand,!with!one!button!representing!“above”!and!the!other!“below.”!They!were!

told!to!respond!as!quickly!and!as!accurately!as!possible.!Hand!assignment!was!

counterbalanced!across!subjects!and!consistent!within!subject.!The!eight!main!trial!types!

(combinations!of!task,!switch,!congruency!and!hand!to!be!used!to!respond)!occurred!

equiprobably!and!randomly!within!a!block,!with!switch!or!repeat!trials!determined!

randomly.!The!inter2trial!interval!was!1600!ms!and!participants!completed!20!blocks!of!40!

trials!each.!

! Prior!to!EROS2ERP!recording,!participants!completed!a!practice!session!that!

consisted!of!a!brief!introduction!to!the!spatial!Stroop!stimuli!and!responses,!eight!meaning2

only!trials,!eight!position2only!trials,!16!mixed!meaning!and!position!trials!with!a!response!

window!2002ms!longer!than!the!experimental!parameters,!and!another!16!mixed!trials!

with!the!experimental!parameters.!During!the!aforementioned!trials,!feedback!was!issued!

at!the!end!of!each!trial.!Participants!then!completed!a!402trial!practice!block!using!the!

!

28!

experimental!parameters!and!without!feedback!for!each!trial.!The!last!practice!block!was!

repeated!if!mean!accuracy!fell!below!80%.!!

Mean!accuracy!scores!(proportion!correct)!were!computed!and!median!reaction!

times!for!correct!trials!were!analyzed!to!reduce!the!influence!of!within2participant!outliers.!

To!integrate!accuracy!and!RT!measures,!we!also!computed!“inverse!efficiency!scores”!(IES)!

by!dividing!each!subject’s!median!RT!by!mean!accuracy!(Townsend!&!Ashby!1983;!Bruyer!

&!Brysbaert,!2011).!

Structural!MRI!Acquisition!

Corpus!callosum!volume!was!obtained!from!high2resolution!T12weighted!MPRAGE!

(Magnetization!Prepared!Rapid!Gradient!Echo)!images!acquired!on!a!3!Tesla!Siemens!Trio!

MR!Scanner!using!a!standard!body!coil!transmission!and!a!122channel!head!array!receive!

coil.!The!MPRAGE!was!acquired!with!the!following!parameters:!phase!encoding!direction!=!

anterior!to!posterior;!voxel!size!=!0.9!x!0.9!x!0.9!mm;!TR!=!1900!ms,!TI!=!900!ms,!TE!=!2.32!

ms,!field!of!view!=!230!x!230!x!172.8!mm3!(sagittal),!flip!angle!=!9°.!!

To!extract!corpus!callosum!volumes,!we!used!Freesurfer!5.0!(Dale!et!al.,!1999),!

which!performs!automated!and!probabilistic2based!segmentation!of!cortical!and!

subcortical!matter!(Fischl!et!al.,!2002;!2004a;!2004b;!Desikan!et!al.,!2006).!Segmentation!

was!inspected!by!three!trained!individuals!and!corrected!accordingly!

(http://surfer.nmr.mgh.harvard.edu!/fswiki/!FsTutorial/!TroubleshootingData).!

Intracranial!volume!was!used!to!normalize!callosum!measures!(Jack!et!al.,!1989;!Buckner!et!

al.,!2004).!Freesurfer’s!automated!segmentation!included!dividing!the!corpus!callosum!into!

five!segments!(Figure!2.2):!the!first!two!segments!were!combined!to!yield!an!estimate!of!

anterior!corpus!callosum!size,!comparable!to!the!anterior!CC!measure!derived!in!Gratton!et!

!

29!

al.,!2009.!Age!was!negatively!correlated!with!anterior!CC!volume!(r=2.595,!p<.001).!To!

analyze!CC!volume!effects!we!conducted!a!stratified!analysis!by!assigning!participants!to!

large2!or!small2CC!groups!within!their!age!group!(Table!2.1).!!!!

Electrical!Recording!

' EEG!was!recorded!using!Ag/AgCl!electrodes!positioned!approximately!at!F3,!F4,!C3,!

C4,!P3,!P4,!OZ!in!the!10/20!system.!Electrodes!were!referenced!online!to!the!left!mastoid,!

and!re2referenced!offline!to!the!average!of!the!left!and!right!mastoids,!with!a!ground!

electrode!positioned!on!the!lower!middle!forehead.!Electrodes!were!positioned!above!and!

below!the!right!eye!and!at!the!outer!canthus!of!each!eye!to!monitor!eye!vertical!and!

horizontal!eye!movements,!as!well!as!on!the!left!and!right!inner!wrists!to!collect!

electrocardiography!data!(EKG).!Data!were!obtained!with!a!sampling!rate!of!200!Hz!and!

bandpass2filtered!online!at!.10!to!30!Hz.!!

EEG!data!were!processed!with!EEGLAB!11.0.4.3!(Delorme!&!Makeig,!2004)!and!

ERPLAB!!2.0.0.1!(Lopez2Calderon!&!Luck,!2014).!Offline!preprocessing!involved!

segmenting!data!into!8002ms!epochs!time2locked!to!pre2cue!onset,!with!baseline2

correction!using!200!ms!prior!to!the!pre2cue.!Artifacts!due!to!saturation!or!electrode!

displacement!were!identified!by!epochs!with!voltage!changes!larger!than!500!μV!and!

consequently!discarded!from!analyses.!Ocular!artifact!correction!was!performed!using!

regression!procedures!described!in!Gratton,!Coles,!and!Donchin!(1983).!To!further!

minimize!the!effect!of!artifacts,!epochs!with!voltage!changes!greater!than!150!μV!after!eye2

movement!correction!were!also!discarded!from!analysis.!Data!for!correct!trials!were!

averaged!for!each!subject,!condition,!and!electrode.!Outliers!were!defined!by!participants!

with!mean!amplitude!values!more!than!3!standard!deviations!from!the!mean.!Using!this!

!

30!

procedure,!one!subject!with!extreme!values!in!F3,!F4,!C3!and!C4,!and!another!subject!with!

extreme!values!in!P3!and!P4!!were!discarded!from!analyses.!!

Analyses!were!conducted!on!the!P3!component!(3002500!ms)!and!on!mean!

amplitude!measures!obtained!from!502ms!intervals!during!this!period,!during!which!

switch2related!frontal!negativity!effects!have!previously!been!found!(Baniqued!et!al.,!2013;!

Gratton!et!al.,!2009!and!unpublished!ERP!data).!These!502ms!intervals!were!used!to!

correlate!ERP!effects!with!EROS!and!behavioral!measures.!!

Optical!Recording!

Concurrent!with!behavioral!and!EEG!data!acquisition,!we!recorded!brain!activity!

using!two!Imagent®!frequency!domain!systems!(ISS!Inc.,!Champaign,!IL)!that!together!

afforded!a!total!of!24!detectors.!These!detectors!were!32mm!fiber!optic!bundles!connected!

to!photomultiplier!tubes,!and!measured!activity!from!64!laser!diodes!that!were!4002μm!in!

diameter!and!channeled!near!infrared!light!(830!nm)!modulated!at!110!MHz,!with!a!cross2

correlation!(i.e.,!heterodyning)!frequency!of!3.125!kHz.!!!This!allowed!for!recording!data!

using!a!50!kHz!A/D!conversion.!Measures!of!DC!(average)!intensity,!AC!(amplitude)!and!

relative!phase!delay!(in!picoseconds)!were!obtained!for!each!of!these!periods!by!applying!

Fast!Fourier!transforms!applied!to!small!segment!(1.6!ms!per!channel)!of!raw!optical!data.!!

As!data!were!time2multiplexed!across!16!channels!for!each!detector,!useful!optical!data!

were!recorded!continuously!with!an!effective!sampling!rate!of!39.!0625!Hz.!

A!customized!motorcycle!helmet!was!used!to!secure!all!sources!and!detectors!fibers!

on!a!participant’s!head.!The!configuration!of!sources!and!detectors!was!designed!to!

maximize!coverage!of!cortex,!with!all!source2detector!distances!falling!between!2.0!and!6.0!

cm.!To!avoid!cross2talk!between!channels,!no!two!sources!were!simultaneously!active!

!

31!

within!6.0!cm!of!the!same!detector.!!!The!source2detector!montage!was!designed!so!that!

most!channels!had!source2detector!distances!ranging!between!!15!and!60!mm,!since!

shorter!channels!measure!light!that!has!not!penetrated!cortex,!whereas!longer!channels!

result!in!less!light!measured!and!thus!less!reliable!optical!signals!(Gratton!et!al.,!2000).!

After!the!imaging!session,!each!source!and!detector!location!was!digitized!in!

relation!to!the!nasion!and!fiducial!preauricular!points!using!a!Polhemus!“3Space”™!Fasttrak!

3D!digitizer!(Colchester,!VT)!with!an!extended!stylus!and!Locator!4.1!software!(Source!

Signal!Imaging!Inc.,!San!Diego,!CA).!MPRAGE!scans!and!fiducial!markers!were!used!to!co2

register!the!digitized!optical!channels.!Data!then!underwent!standard!Talairach!

transformation!(Whalen!et!al.,!2008;!Chiarelli!etc!al.,!2014)!and!scalp2forcing!prior!to!

further!analysis.!Only!data!from!channels!with!source2detector!distances!between!15!and!

60!mm!were!analyzed.!

! This!paper!covers!phase!delay!(time2of2flight)!measures!recorded!from!cue!onset!to!

1000!ms!after!cue!onset.!Data!underwent!correction!for!phase!wrapping!and!pulse!artifacts!

(Gratton!&!Corballis,!1995),!adjusted!to!a!mean!of!zero!for!each!block,!and!bandpass2

filtered!between!0.10!and!10!Hz.!Correct!trial!data!were!segmented!into!epochs!time2

locked!to!cue!onset,!and!averaged!separately!for!each!subject,!condition!and!channel.!

Optical!data!were!baseline2corrected!using!a!102.42ms!period!(4!sampling!point)!preceding!

the!cue.!Only!channels!with!phase!standard!deviation!less!than!100!picoseconds!were!

included!in!the!analysis!(Gratton,!et!al.,!2006).!In2house!software!“Opt23d”!(Gratton,!2000)!

was!used!to!compute!statistics!and!combine!data!from!channels!whose!diffusion!paths!

intersected!a!given!voxel!(Wolf!et!al.,!2000).!Data!were!spatially!filtered!with!an!82mm!

Gaussian!kernel.!To!compute!statistical!maps,!group2level!t2statistics!were!derived!across!

!

32!

subjects!and!then!converted!into!z2scores,!with!appropriate!correction!for!multiple!

comparisons!using!random!field!theory!(Kiebel!et!al.,!1999).!Z2scores!were!orthogonally!

projected!onto!axial,!sagittal!and!coronal!surfaces!of!a!brain!in!Talairach!space.!Statistical!

significance!was!evaluated!by!effects!with!p<.05!(corresponding!to!critical!Z!value!–!Z!crit!–!

in!the!tables)!adjusted!for!multiple!comparisons.!ROI!coordinates!are!reported!in!Table!2.2.!

Cross2correlation!analyses'

! We!used!lagged!cross2correlations!to!examine!the!relationship!between!early!

switch2related!activation!in!the!left!MFG!and!subsequent!task2specific!activation!(for!

detailed!methods!see!Rykhlevskaia!et!al.,!2006;!for!similar!analyses!see!Baniqued!et!al.,!

2013;!Mathewson!et!al.,!2014).!For!each!subject,!we!took!the!time!course!of!activity!in!the!

voxel!of!peak!switch!activation!in!left!MFG!and!correlated!this!with!the!time!series!of!each!

remaining!voxel!across!the!brain!(voxels!from!surface!projection).!To!determine!the!areas!

that!commonly!and!differentially!respond!to!the!nature!of!switching!required,!we!used!the!

time!course!of!the!switch!effect!(difference!in!activity!between!switch!and!repeat)!and!

extracted!the!6002ms!segment!corresponding!to!an!interval!ranging!between!200!to!800!

ms!after!cue!presentation.!Correlations!were!computed!separately!for!the!meaning!and!

position!switch!effect,!and!at!15!lags!separated!by!25.6!ms!intervals!(0!to!358!ms)!to!

identify!not!only!regions!that!were!systematically!activated!with!the!seed!region,!but!also!

those!that!were!consistently!activated!after!a!specific!lag.!Since!this!analysis!does!not!rely!

on!localized!activity!occurring!at!exact!or!narrow!intervals!across!subjects,!it!can!better!

reveal!common!patterns!of!activation!across!subjects.!The!cross2correlation!!maps!were!

then!derived!by!first!subjecting!individual!correlation!coefficients!to!a!Fisher!r2to2z!

transformation,!computing!group!t2statistics,!and!converting!these!to!z2scores.!These!steps!

!

33!

were!conducted!for!each!lag!independently.!The!final!statistics!were!evaluated!separately!

for!each!ROI,!and!corrected!for!multiple!comparisons!within!each!ROI!using!previously!

described!random!field!theory!techniques!(Worsley!&!Friston,!1995;!Kiebel!et!al.,!1999).!

Statistically!significant!cross2correlation!peaks!were!then!identified!when!the!peak!z!score!

exceeded!the!criterion!z!value!corresponding!to!!!p<.05,!adjusted!for!multiple!comparisons.

! !

!

34!

Results'

Behavior!

! Spatial!Stroop!data!were!examined!with!a!repeated2measures!ANOVA!with!task!

[meaning,!position],!switch![switch,!repeat])!and!congruency![incongruent,!congruent]!as!

within2subject!factors,!and!age!group!and!CC!group!as!between2subject!factors.!Data!were!

collapsed!across!response!sides!(left/right)!to!increase!power!in!detecting!differences!in!

our!conditions!of!interest.!Separate!tests!were!conducted!for!accuracy,!median!RT!and!

accuracy2adjusted!RT!(IES2RT).!Overall,!the!behavioral!effects!(Table!2.3;!Figure!2.3)!

mirrored!the!results!of!Gratton!et!al.,!2009,!with!main!effects!of!task,!switch!and!

congruency.!Age!group!effects!were!observed!in!all!measures,!while!CC!group!effects!were!

observed!in!accuracy!and!IES!RT.!

Accuracy.'For!mean!accuracy!we!found!significant!main!effects!of!task!F(1,!

31)=19.484,!p<.001,!ηp2=.386,!!switch!F(1,!31)=29.756,!p<.001,!ηp2=.490,!and!congruency!

F(1,!31)=115.693,!p<.001!ηp2=.789.!Similar!to!previous!findings,!responses!were!more!

accurate!for!position,!repeat!and!congruent!trials.!There!were!significant!two2way!

interactions!of!task!and!congruency!F(1,!38)=16.066,!p<.001,!ηp2=.341,!with!greater!

congruency!effects!for!position!trials,!and!switch!and!congruency!F(1,!31)=12.265,!p=.001,!

ηp2=.283,!with!greater!switch!effects!for!incongruent!trials.!!

There!was!also!a!significant!three2way!interaction!of!switch,!age!group!and!CC!group!

F(1,!31)=12.627,!p=.001,!ηp2=.289,!with!greater!switch!accuracy!overall!for!young!adults!

and!especially!those!with!larger!CC!(Figure!2.3a).!No!other!significant!effects!were!found,!

but!there!were!marginal!interactions!of!task!and!age!F(1,!31)=3.430,!p=.074,!ηp2=.100,!as!

!

35!

well!as!a!marginal!four2way!interaction!of!task,!switch,!age!and!CC!F(1,!31)=3.224,!p=.082,!

ηp2=.094.!

Reaction'Time.'Median!RTs!revealed!main!effects!of!switch!F(1,!31)=21.933,!

p<.001,!ηp2=.414,!and!congruency!only!F(1,!31)=95.497,!p<.001,!ηp2=.755;!RTs!were!longer!

for!switch!and!incongruent!trials.!There!was!a!significant!two2way!interaction!of!task!and!

congruency!F(1,!31)=10.771,!p=.003,!ηp2=.258,!a!three2way!interaction!of!task,!congruency!

and!age!F(1,!31)=5.810,!p=.022,!ηp2=.158,!and!a!four2way!interaction!of!task,!switch,!

congruency!and!age!F(1,!31)=9.684,!p=.004!ηp2=.238.!There!was!a!marginal!interaction!of!

task,!switch!and!age!F(1,!31)=3.732,!p=.063!ηp2=.107.!In!general,!RTs!were!longer!for!

position,!switch!and!incongruent!trials,!especially!in!the!oldest!group.!

Inverse'Efficiency'Scores.'There!was!a!negative!correlation!between!RT!and!

accuracy!(r(33)=2.420,!p=.006,!one2tailed),!indicating!there!was!no!speed2accuracy!tradeoff!

that!would!decrease!the!reliability!of!the!IES2RT!measures.!

!For!accuracy2adjusted!RTs,!there!were!main!effects!of!switch!F(1,!31)=22.275,!

p<.001,!ηp2=.418,!and!congruency!F(1,!31)=91.658,!p<.001,!ηp2=.747,!and!two2way!

interactions!of!task!and!congruency!F(1,!31)=13.186,!p=.001,!ηp2=.298,!and!switch!and!

congruency!F(1,!31)=9.693,!p=.004,!ηp2=.238.!

Although!median!RTs!did!not!show!any!effect!of!CC,!accuracy2adjusted!RTs!revealed!

a!significant!four2way!interaction!of!switch,!congruency,!age!and!CC,!F(1,!31)=4.192,!

p=.049,!ηp2=.119!(Figure!2.3b).!There!was!also!a!significant!four2way!interaction!of!task,!

switch,!congruency!and!age!F(1,!31)=4.287,!p=.047,!ηp2=.121!and!a!marginal!three2way!

interaction!of!switch,!congruency!and!age!F(1,!31)=3.778,!p=.061,!ηp2=.109.'

! !

!

36!

ERP!Results!

Grand!average!waveforms!for!the!task,!switch!and!age!effects!are!shown!in!Figure!

2.4.!Overall,!the!results!parallel!the!time!course!of!ERP!and!EROS!switch!effects2!previously!

observed!in!the!foreperiod!of!spatial!Stroop!task!(Gratton!et!al.,!2009).!In!this!sample!of!

older!adults,!the!YO!group!mirrored!the!young!adults!with!greater!switch2related!frontal!

negativity,!while!the!OO!group!mirrored!the!older!adults!of!the!previous!study!that!showed!

the!opposite!switching!pattern.!Indeed,!in!the!frontally!distributed!P300,!there!was!a!

significant!switch!by!age!group!interaction!in!F3,!F(1,26)=4.819,!p=.037,!ηp2=.156.!For!the!

parietally!distributed!P300,!significant!effects!were!only!found!in!P4.!There!was!a!

significant!task!effect,!F(1,28)=8.422,!p=.007,!ηp2=.231,!and!a!near2significant!switch!by!age!

group!interaction!F(1,26)=4.104,!p=.052,!ηp2=.128.!!

F3'Analyses.'Since!the!switch2related!negativity!in!F3!overlapped!in!time!with!the!

frontal!P300,!we!took!a!closer!look!at!502ms!intervals!within!the!3002500!ms!post2cue!

interval.!From!3002350!ms,!only!the!task!by!CC!group!interaction!was!significant!

F(1,26)=4.670,!p=.040,!ηp2=.152.!The!switch!by!age!group!interaction!was!significant!from!

3502400!ms,!F(1,26)=5.013,!p=.034,!ηp2=.162,!from!4002450!ms,!F(1,26)=4.560,!p=.042,!

ηp2=.149,!and!from!4502500!ms!!F(1,26)=5.640,!p=.025,!ηp2=.178.!The!four2way!interaction!

of!task,!switch,!age!group!and!CC!group!was!significant!from!4002450!ms!F(1,26)=5.060,!

p=.033,!ηp2=.163.!

! Correlation'of'ERP'effects'and'behavior.'To!determine!if!the!switch2related!F3!

negativity!was!important!for!performance,!we!computed!correlations!between!the!F3!

switch!effect!and!the!behavioral!switch!effect!(Figure!2.5)!during!the!3502450!ms!interval!

2!F3!is!located!approximately!around!the!left!MFG!ROI.!

!

37!

where!the!switch!effect!was!maximal!for!both!meaning!and!position!tasks.!For!the!position!

task,!greater!F3!negativity!from!3502400!ms!predicted!smaller!switch!costs!(r(28)=.417,!

p=.011,!one2tailed),!even!after!controlling!for!age!(rp(27)=.468,!p=.005).!A!similar!

relationship!was!found!for!the!meaning!task!(r(28)=.445,!p=.007,!one2tailed)!from!4002450!

ms,!which!remained!significant!after!controlling!for!age!(rp(27)=.455,!p=.012,!one2tailed).!!

EROS!Results!

! Analyses!focused!on!the!interval!200!to!800!ms!after!cue!onset,!and!on!frontal!and!

parietal!ROIs!derived!from!related!studies!(Figure!2.6).!!

Main'switch'effects.!First!we!sought!to!replicate!the!pattern!of!greater!MFG!activity!

for!switch!versus!repeat!(Gratton!et!al.,!2009).!In!our!sample!of!older!adults,!we!found!a!

very!similar!left!MFG!switch!effect!at!358!ms,!albeit!at!a!slightly!more!posterior!location!

than!the!previous!study!(z(34)!=2.92;!zcrit!=!2.88;!peak!coordinates:!238,!21,!44).!The!full2

head!montage!in!the!current!study!also!revealed!trends!in!left!IPS!from!3002400!ms!and!

again!between!5002600!ms,!with!activity!peaking!at!563!ms,!(z(33)!=2.96;!zcrit!=!3.04;!peak!

coordinates:!246,!251,!40).!Beginning!256!ms,!right!SPL!also!showed!switch2preferential!

activation!that!lasted!until!409!ms!(peak!at!281!ms,!(z(34)!=3.11;!zcrit!=!2.92;!peak!

coordinates:!9,!266,!53).!!!

Task9specific'switch'effects.'The!later!task2specific!switch!effects!(Figure!2.6)!

mirrored!the!previous!study,!with!the!meaning!switch!effect!beginning!at!588!ms!and!

peaking!at!640!ms!in!a!more!inferior!region!of!left!MFG!closer!to!the!left!IFG!(left!MFG!ROI:!

z(28)!=2.95;!zcrit!=!2.80;!peak!coordinates:!251,!27;!left!IFG!ROI:!z(25)!=2.97;!zcrit!=!2.73;!

peak!coordinates:!253,!32,!19),!and!the!position!switch!effect!peaking!at!537!in!the!right!

MFG!(z(34)!=2.73;!zcrit!=!2.73;!peak!coordinates:!24,!14).!Critically,!the!task!and!switch!

!

38!

interaction!was!marginally!significant!in!the!left!IFG!at!640!ms!(z(29)!=2.74;!zcrit!=!2.95;!

peak!coordinates:!258,!29,!20),!and!significant!in!the!right!MFG!at!537!ms!(z(34)!=22.81;!

zcrit!=!22.80;!peak!coordinates:!24,!7,!46).!It!is!important!to!note!that!there!was!less!

coverage!of!inferior!brain!areas!overall,!which!may!explain!the!less!robust!effects!in!IFG.!

We!also!found!task2specific!switch!activity!in!parietal!cortex!(which!was!not!

recorded!from!in!the!Gratton!et!al.,!2009!study),!primarily!for!the!meaning!task.!The!task!by!

switch!interaction!showed!meaning2specific!switch!effects,!first!in!right!SPL/IPS!and!then!

in!the!left!IPS/SPL.!The!right!IPS!effect!peaked!at!358!ms!(z(32)!=!3.30;!zcrit!=!3.12;!peak!

coordinates:!42,!243,!46),!while!the!right!SPL!effect!peaked!at!614!ms!(z(34)!=2.80;!zcrit!=!

2.71;!peak!coordinates:!19,!261,!54).!!The!left!IPS/SPL!effect!peaked!at!614!ms!(IPS!ROI:!

z(33)!=3.30;!zcrit!(IPS)!=!3.23;!zcrit!(SPL)=!3.14;!!peak!coordinates:!231,!266,!48.!There!were!

trends!for!position2specific!switch!effects,!but!none!of!these!effects!were!significant!in!the!

parietal!ROIs.!!

Correlation'of'EROS'switch'effects'with'ERP'measures'and'behavior.!The!task2

general!left!MFG!effect!overlapped!in!time!with!the!switch2related!F3!negativity.!To!confirm!

the!correspondence!of!these!effects,!we!correlated!the!F3!switch!effect!(mean!amplitude!

between!3502400!ms)!with!the!left!MFG!switch!effect!at!384!ms!and!found!a!significant!

negative!correlation![r(28)=2.312,!p=.047,!one2tailed].!To!minimize!the!influence!of!

extreme!values!present!in!the!EROS!and!ERP!data,!we!ran!bootstrapped!correlations!and!

followed!this!up!with!nonparametric!correlations.!The!bias!corrected!and!accelerated!(BCa)!

95%!confidence!interval!(CI)!for!the!Pearson!correlation!did!not!include!zero![2.460,!2.265]!

and!the!Spearman!correlation!was!significant!at!r=2.401,!p=.014,!one2tailed.!!

!

39!

Similar!to!the!ERPs,!a!larger!left!MFG!switch!effect!also!corresponded!to!smaller!RT!

switch!costs!(r(33)=2.334,!p=.025,!BCa!95%!CI![2.523,!2.103],!rs!=!2.283,!p=0.05!],!even!after!

accounting!for!age!(r(32)=2.350,!p=.021,!BCa!95%!CI![2.507,!2.121].!When!computed!

separately!for!the!meaning!and!position!task,!the!correlations!did!not!reach!significance,!

although!both!showed!the!same!negative!trends.!!

Cross9correlation'analyses.'Having!replicated!the!basic!switch!findings!in!our!

sample!of!middle2to2older!adults,!we!turned!to!examining!the!interplay!between!the!task2

general!FPN!and!task2specific!effects.!In!these!cross2correlation!analyses,!we!used!the!peak!

voxel!of!the!general!switch!effect!as!a!seed!region!(x=238,!y=21).!Separately!for!the!meaning!

and!position!task,!we!then!correlated!the!switch!effect!in!this!seed!voxel!with!the!switch!

effect!in!other!voxels.!Significance!tests!were!conducted!separately!for!each!lag,!and!

analyses!focused!on!the!frontal!and!parietal!ROIs.!For!brevity,!we!do!not!report!the!

significant!positive!correlations!of!the!seed!voxel!within!its!encompassing!ROI!at!the!0!ms!

lag.!Main!results!are!summarized!in!Figure!2.7.'

Cross&correlations!of!meaning!switch!effect.!Left!MFG!activity!predicted!switch2

related!activity!for!the!meaning!task!in!left!MFG2IFG,!with!positive!correlations!at!the!128!

ms!lag!(z(15)!=3.02;!zcrit!=!2.71;!peak!coordinates:!261,!29,!60)!and!again!beginning!at!the!

230!ms!lag,!peaking!at!the!256!ms!lag!(z(28)!=2.86;!zcrit!=!2.73;!peak!coordinates:!258,!14,!

27).!There!was!also!a!negative!correlation!in!the!left!MFG!seed!region!at!a!lag!of!76!ms!

(z(34)!=25.84;!zcrit!=!22.89;!peak!coordinates:!238,!21,!44)!and!179!ms!(z(33)!=23.08;!zcrit!=!

22.89;!peak!coordinates:!231,!1,!49).!We!did!not,!however!find!a!significant!negative!

correlation!in!the!frontal!cortex!of!the!opposite,!position2specific!hemisphere.!There!were!

hints!of!a!negative!correlation!beginning!at!the!256!ms!lag,!but!this!effect!did!not!reach!

!

40!

significance!(z(32)!=22.40;!zcrit!=!22.92;!peak!coordinates:!39,!22,!39).!Interestingly,!a!

negative!correlation!was!found!with!right!IPS!at!the!179!ms!lag!(z(31)!=23.22;!zcrit!=!23.13;!

peak!coordinates:!52,!246,!38).!!

The!seed!region!was!also!positively!correlated!with!the!right!IPS!at!the!0!ms!lag!

(z(23)!=3.19;!zcrit!=!3.10;!peak!coordinates:!59,!246,!33)!and!with!the!right!SPL!at!the!51!ms!

lag!(z(20)!=2.84;!zcrit!=!2.84;!peak!coordinates:!29,!281,!33).!

Cross&correlations!of!position!switch!effect.!Left!MFG!activity!predicted!switch2

related!activity!for!the!position!task!in!right!MFG!at!a!lag!of!256!ms!and!281!ms!(peak!at!

281!ms:!(z(34)!=3.11;!zcrit!=!2.86;!peak!coordinates:!37,!27).!We!also!found!a!negative!

correlation!starting!at!the!153!ms!lag!in!more!inferior!MFG!that!was!found!to!be!active!for!

the!meaning!task!(peak!lag!at!179!ms:!(z(25)!=2.92;!zcrit!=!2.90;!peak!coordinates:!261,!22).!

Consistent!with!previous!findings,!we!also!see!a!negative!correlation!in!our!seed!region!at!

the!76!ms!lag!z(34)!=!4.94;!zcrit!=!2.85;!peak!coordinates:!236,!2,!49)!and!again!at!the!179!

ms!lag!(z(33)=4.170,!zcrit=2.85,!231,!1,!49).!!

! Corpus'callosum'predicts'right'MFG'up9regulation'for'position'switching.'Both!

previous!studies!and!the!cross2correlation!analyses!point!to!the!importance!of!the!anterior!

CC,!especially!in!the!position!task.!To!test!the!role!of!the!anterior!CC!in!the!interaction!

between!left!MFG!and!later2onset!right!MFG!activity,!we!correlated!the!size!of!the!anterior!

CC!with!the!strength!of!the!left!MFG!and!right!MFG!coupling!at!the!peak!lag!of!281!ms.!!

! For!the!position!task,!anterior!CC!positively!correlated!with!the!strength!of!the!

correlation!between!the!seed!left!MFG!voxel!and!the!peak!right!MFG!voxel,!r(33)=.292,!

p=.044!(Figure!2.8).!Although!the!anterior!CC!was!correlated!with!age,!there!was!no!

significant!relationship!between!age!and!the!left!MFG!and!right!MFG!coupling.!The!

!

41!

correlation!between!CC!and!coupling!was!near2significant!after!accounting!for!age,!rp=.246,!

p=.081,!df=32.!!

For!the!meaning!task,!the!correlation!between!CC!volume!and!the!peak!left!MFG2IFG!

voxel!for!the!meaning!task!was!not!significant.!Since!the!meaning!task!is!not!specialized!to!

the!right!hemisphere,!the!anterior!CC!may!play!less!of!a!role!in!predicting!the!within2

hemisphere!functional!interaction.!

! To!further!test!the!association!between!anterior!CC!and!activation!of!the!right!MFG,!

we!ran!a!univariate!analysis!to!determine!how!switch2related!up2regulation!of!the!right!

MFG!for!the!position!task!differed!as!a!function!of!anterior!CC,!now!using!the!stratified!CC!

groupings!(within!age!group)!employed!for!the!behavioral!and!ERP!analyses.!!Consistent!

with!the!current!results,!the!large!CC!group!showed!greater!a!greater!position!effect!in!the!

right!MFG!when!compared!to!the!small!CC!group!(Figure!2.9).!Notably,!this!effect!was!found!

earlier!in!the!preparatory!interval!at!486!ms!(z(33)!=3.18;!zcrit!=!2.92;!peak!coordinates:!

37,!21,!50),!compared!to!the!overall!activation!findings!that!peaked!at!around!537!ms.!At!

563,!there!was!a!hint!of!greater!activation!in!the!right!MFG!for!the!smaller!CC!group,!

although!this!effect!did!not!reach!significance.!!

Although!the!structural!and!functional!connectivity!measures!were!related!for!the!

position!task,!neither!connectivity!measure!was!directly!correlated!to!behavioral!switch!

costs.! !

!

42!

Discussion'

! Here!we!unpacked!the!importance!of!structural!connectivity!in!aging!by!examining!

the!functional!interactions!of!brain!regions!that!rely!on!the!anterior!corpus!callosum,!a!

region!that!undergoes!significant!age2related!decline.!Using!cross2correlations!to!examine!

the!flow!of!activity!in!a!switching!task,!we!found!that!left!MFG!activity!preceded!up2

regulation!of!task2relevant!lateralized!processes!in!frontal!regions.!The!current!study!

extended!previous!findings!(Gratton!et!al.,!2009;!Baniqued!et!al.,!2013)!by!not!only!

replicating!the!task2general!and!task2specific!activations!in!frontal!cortex,!but!also!showing!

the!relationship!between!the!two—confirming!their!relative!timing!of!activation!and!

statistical!dependence.!More!importantly,!the!degree!to!which!older!adults!engaged!

lateralized!task2relevant!processes!was!related!to!the!volume!of!the!anterior!CC,!the!main!

connection!between!frontal!regions!of!the!two!hemispheres.!

! Cue2locked!left!frontal!negativity!observed!in!parallel!to!left!MFG!optical!activity!

significantly!predicted!switch!costs!for!both!meaning!and!position!tasks,!with!greater!

switch2related!negativity!predicting!smaller!reaction!time!switch!costs!even!after!

accounting!for!age.!The!ERP!and!EROS!switch!effects!were!not!only!correlated,!but!also!

associated!with!smaller!RT!switch!costs.'That!such!early!activity!predicts!later!behavioral!

effects!highlights!the!importance!of!a!domain2general!mechanism!that!initiates!specific!

preparatory!processes.!Gratton!et!al.!(2009)!proposed!the!existence!of!both!domain2

general!and!task2specific!processes!operating!in!parallel!to!enable!successful!task2

switching!performance,!speculating!that!increased!practice!may!develop!more!task2specific!

processes!that!operate!early!and!in!parallel!to!domain2general!instantiated!processes.!In!

the!current!study,!which!included!a!significant!practice!session,!we!still!found!evidence!for!

!

43!

task2general!mechanisms!in!left!frontal!switch!effects,!suggesting!that!the!left!MFG!plays!a!

critical!role!in!shifting!attention.!Indeed,!lesion!studies!point!to!the!criticality!of!the!left!

MFG!in!top2down!control!of!task!sets!in!switching!paradigms!(Aron,!Monsell,!Sahakian!&!

Robbins,!2004;!Rossi,!Pessoa,!Desimone!&!Ungerleider,!2009).!

Task2specific!frontal!activation!was!evident!later!in!the!preparatory!interval!around!

5402640!ms,!with!greater!switch2related!up2regulation!in!left!IFG!for!the!meaning!task,!and!

in!the!right!MFG!for!the!position!task.!What!is!most!interesting!however,!was!how!these!

activations!relate!back!to!the!earlier!switch!modulation!in!left!MFG.!Cross2correlation!

analyses!showed!that!the!task2general!MFG!activity!correlated!with!later!engagement!of!

task2specific!lateralized!processes,!with!increased!coupling!to!the!left!IFG!when!switching!

to!the!meaning!task,!and!greater!coupling!to!the!right!MFG!when!switching!to!the!position!

task.!Importantly,!for!position!switching,!anterior!CC!volume!predicted!the!degree!to!which!

left!MFG!coupled!to!right!MFG.!This!was!confirmed!in!the!overall!activation!analyses!when!

looking!back!at!the!position!switch!effect!in!the!later!interval!of!the!preparatory!period:!not!

only!did!those!with!larger!CC!show!greater!recruitment!of!right!MFG,!but!there!was!

evidence!to!suggest!that!right!MFG!activation!also!onset!earlier!for!the!large!vs!small2!CC!

group.!!

! The!current!study!covered!parietal!regions,!but!only!frontal!activity!was!predictive!

of!switching!costs.!This!frontal!dependence!may!in!part!be!due!to!the!older!demographic!of!

our!participants,!especially!as!bilateral!frontal!activation!is!a!common!finding!in!tasks!that!

tax!frontal!control!mechanisms!(Reuter2Lorenz!et!al.,!2000,!2008;!Cabeza,!2002;!Schneider2

Garces!et!al.,!2010).!Similar!to!the!previous!study!(Gratton!et!al.,!2009),!we!also!found!

trends!for!greater!bilateral!frontal!activation!in!individuals!with!smaller!CC!for!the!

!

44!

lateralized!tasks,!hinting!at!a!lack!of!cross2hemispheric!inhibition!(Rykhlevskaia!et!al.,!

2006;!see!also!Hasher!et!al.,!2008).!As!revealed!by!the!cross2correlation!analyses,!left!MFG!

activity!is!also!preceded!by!deactivation!in!the!task2irrelevant!hemisphere,!although!this!

did!not!reach!significance!in!all!cases.!Taken!together,!these!findings!suggest!that!the!CC!

does!not!only!support!transfer!of!information!to!engage!processes,!but!also!inhibitory!

mechanisms!that!feed!back!across!to!inhibit!processes!that!are!now!in!conflict!with!the!

current!trial.!It!is!also!important!to!note!that!the!switching2related!accuracy!benefit!for!

larger!CCs!was!evident!in!the!YO!group!but!not!the!OO!group.!While!no!switch!trial!benefit!

was!observed!for!the!OO!group,!the!OO!participants!with!larger!CCs!showed!a!benefit!for!

repeat!trials.!Why!might!this!be!the!case!when!the!CC!is!presumably!less!involved!when!

there!is!no!need!for!a!switch?!It!is!plausible!that!a!more!intact!CC!is!also!more!able!to!hold!

on!to!current!rules!and!continue!to!inhibit!the!irrelevant!modality,!perhaps!especially!in!the!

position!task!where!one!must!override!reading!and!thus!processing!the!meaning!of!the!

target!stimulus.!

! Unlike!the!current!study,!many!switch!paradigms!find!small!or!no!local!switch!costs!

(switch!vs!repeat)!in!the!presence!of!mixing!costs!(mixed!vs!repeat!blocks),!proposing!that!

older!adults!treat!all!trials!like!a!switch!trial!or!change!in!context!(Karayanidis!et!al.,!2011).!

The!results!of!the!current!study!provide!a!potential!framework!from!which!to!interpret!

these!findings!by!highlighting!the!importance!of!the!frontal!cortex.!While!many!other!brain!

regions!undergo!decline,!behavioral!manifestations!may!not!be!apparent!in!tasks!that!

preferentially!engage!relatively!intact!areas!such!as!parietal!cortex.!Moreover,!the!

importance!of!white!matter!in!a!cognitive!task!may!depend!on!the!nature!of!the!tasks!

involved.!For!example,!the!integrity!of!the!left!superior!longitudinal!fasciculus,!a!frontal2

!

45!

parietal!connector,!predicted!reaction!time!switch!costs!in!a!task!that!required!number!or!

letter!judgments,!processes!that!involve!more!posterior!regions!(Gold!et!al.,!2010).!

Knowledge!about!the!specificity!of!these!brain2behavior!relationships!can!help!guide!

development!of!systems!catered!to!older!adults,!for!example!in!capitalizing!on!processes!

that!rely!on!less!susceptible!regions!or!brain!interactions.!!

Although!CC!effects!were!observed!for!accuracy!and!accuracy2adjusted!reaction!

times,!neither!connectivity!measure!(anterior!CC!and!functional!connectivity!via!cross2

correlations)!was!directly!predictive!of!performance.!One!reason!for!the!lack!of!CC’s!

predictive!power!may!be!due!to!the!more!limited!range!in!our!sample!of!older!adults.!

Alternatively,!it!is!plausible!that!CC’s!effects!are!more!evident!in!terms!of!brain!function!or!

activity!as!we!found,!rather!than!behavior.!Moreover,!Monsell!(2003)!proposed!that!

residual!switch!costs!observed!in!the!presence!of!preparation!time!may!reflect!“retroactive!

set!adjustment,”!particularly!when!bivalent!stimuli!are!used!in!the!switching!paradigm!(as!

in!this!case).!This!study!only!focused!on!the!preparatory!period!and!as!such!did!not!capture!

processes!that!may!be!additionally!engaged!once!the!reaction!stimulus!appears—processes!

which!can!exert!a!direct,!additive!effect!on!performance!metrics!and!may!be!differentially!

influenced!by!the!size!of!the!corpus!callosum.!!

In!summary,!in!older!adults,!difficulty!engaging!preparatory!control!accompanied!by!

weaker!structural!connections!between!brain!regions!may!lead!to!sub2optimal!

performance.!Aging!is!characterized!by!a!confluence!of!changing!biological!and!

psychological!factors,!yet!the!degree!to!which!an!individual!experiences!age2related!

cognitive!effects!may!be!significantly!accounted!for!by!pre2existing!differences!in!lifestyle!

and!brain!structure.!Here!we!highlight!the!importance!of!the!anterior!CC,!which!undergoes!

!

46!

profound!decline!in!older!age.!Interestingly,!the!anterior!CC!has!also!been!observed!to!be!

among!the!most!malleable!of!brain!structures,!showing!significant!associations!with!

aerobic!fitness!(Voss!et!al.,!2012;!Burzynska!et!al.,!2014)!and!changes!as!a!function!of!

aerobic!exercise!from!a!yearlong!walking!intervention!(Voss!et!al.,2012).!Future!directions!

include!investigating!to!what!extent!fitness,!via!its!action!on!brain!structure!and!function,!

may!determine!performance!in!similar!attention!and!frontal2demanding!situations.!

!

47!

Tables!!!Table!2.1.!Demographics.!Standard!deviations!are!shown!in!parentheses,!followed!by!range.!! Young2Old!(YO)! Older2Old!(OO)!! Small!CC! Large!CC! Small!CC! Large!CC!N!(analysis!max)! 10! 8! 10! 7!Gender!(female)! 7!female! 3!female! 4!female! 3!female!Mean!age!(yrs)! 64.18!(3.07)!

59267!61.42!(4.12)!

55267!78.39!(4.05)!

71285!72.25!(4.98)!

67282!Anterior!CC!!volume!(mm3)!

1241.39!(144.66)!1027!21402!

1540.36!(71.08)!

147221656!

1121.18!(81.97)!95521239!

1384.15!(86.14)!

130421530!Education!(yrs)! 18!(3.40)!

12220!17.13!(2.85)!

12220!17.6!(2.41)!13220!

16.21!(2.94)!12219!

Modified!MMSE!! 55.7!(0.67)!54256!

56.13!(1.13)!54257!

55.20!(1.55)!52257!

54.86!(1.35)!53256!

KBIT! 116.10!(7.87)!1022126!

119.38!(15.85)!952142!

120!(9.97)!1072138!

117.71!!(7.02)!1082126!

!

! !

!

48!

Table!2.2.!Talairach!coordinates!of!Frontal!and!Parietal!ROIs.!ROI! X!!(left,!right)/!Y!(anterior,!posterior)!/!Z!(inferior,!superior)!

Left!MFG2SFG! 250!230!/!0!30!/!20!40!Right!MFG2SFG! 25!45!/!0!30!/!20!40!Left!MFG2IFG! 260!45!/!10!40!/!10!30!Right!MFG2IFG! 235!55!/!10!40!/!10!30!Left!IPS2IPL! 260!230!/!270!–!40!/!20!40!Right!IPS2IPL! 30!60!/!270!240!/!20!40!Left!SPL! 230!210!/!280!255!/!42!52!Right!SPL! 10!30!/!280!255!/!42!52!!

! !

!

49!

Table!2.3.!Median!RT!and!Mean!Accuracy!effects.!

AGE! CC! task! switch! con!

Median!RT!

Mean! RT!SE!

ACC!

Mean! ACC!SE!

YO! Small!CC! Meaning! Switch! Inc! 730.925! 33.731! 0.905! 0.021!

Con! 625.025! 28.433! 0.988! 0.005!

Repeat! Inc! 697.125! 27.967! 0.948! 0.014!

Con! 620.225! 26.453! 0.992! 0.005!

Position! Switch! Inc! 756.775! 54.895! 0.891! 0.023!

Con! 605.625! 29.925! 0.981! 0.009!

Repeat! Inc! 663.150! 58.787! 0.915! 0.025!

Con! 574.825! 30.790! 0.995! 0.013!

Large!CC! Meaning! Switch! Inc! 679.063! 37.713! 0.938! 0.023!

Con! 609.656! 31.790! 0.983! 0.006!

Repeat! Inc! 665.531! 31.268! 0.952! 0.015!

Con! 577.719! 29.575! 0.992! 0.006!

Position! Switch! Inc! 655.344! 61.374! 0.911! 0.025!

Con! 518.531! 33.457! 0.986! 0.01!

Repeat! Inc! 587.813! 65.726! 0.917! 0.028!

Con! 495.031! 34.425! 0.983! 0.015!

OO! Small!CC! Meaning! Switch! Inc! 746.575! 33.731! 0.905! 0.021!

Con! 663.650! 28.433! 0.976! 0.005!

Repeat! Inc! 714.375! 27.967! 0.939! 0.014!

Con! 631.050! 26.453! 0.987! 0.005!

Position! Switch! Inc! 767.050! 54.895! 0.835! 0.023!

Con! 624.850! 29.925! 0.969! 0.009!

Repeat! Inc! 756.600! 58.787! 0.839! 0.025!

Con! 585.625! 30.790! 0.948! 0.013!

Large!CC! Meaning! Switch! Inc! 739.071! 40.316! 0.882! 0.025!

Con! 643.893! 33.984! 0.976! 0.006!

Repeat! Inc! 712.429! 33.427! 0.917! 0.017!

Con! 620.143! 31.617! 0.985! 0.006!

Position! Switch! Inc! 751.893! 65.612! 0.859! 0.027!

Con! 613.143! 35.767! 0.97! 0.011!

Repeat! Inc! 742.679! 70.264! 0.906! 0.03!

Con! 581.679! 36.801! 0.978! 0.016!

!

!

50!

Figures!

Figure!2.1.!Spatial!Stroop!Paradigm.!Stimuli!are!not!drawn!to!scale.!

!

Precue&M:#meaning#P:#posi.on#500#ms#

#

1500#ms#

Reac)on&S)mulus&ABOVE:#right#hand#BELOW:#le;#hand#

200#ms#

M&+&M& P&+&P&

+& +&

+&BELOW&

+&BELOW&

trial#n# trial#n+1#

!

51!

Figure!2.2.!Approximate!subdivision!of!anterior!CC!on!one!subject!(left),!relationship!of!anterior!CC!volume!with!age!(right)!!

Anterior(CC!r=.595,&p<.001&

800#

1000#

1200#

1400#

1600#

1800#

55# 60# 65# 70# 75# 80# 85# 90#

Anterio

r(CC(Vo

lume((normalized

)(Age(

r=.*595,&p<.001&

!

52!

!Figure!2.3a.!ThreeBway!interaction!of!switch,!age!group!and!CC!group!in!accuracy.!Error!bars!are!SEM.!!

'!

0.8

0.9

1

switch repeat switch repeat

YO OO

Accu

racy

small CC large CC

!

53!

Figure!2.3b.!FourBway!interaction!of!switch,!congruency,!age!group!and!CC!group!in!accuracyBadjusted!reaction!times!(IESBRT).!Error!bars!are!SEM.!!

!

0

200

400

600

800

1000

inc con inc con inc con inc con

switch repeat switch repeat

YO OO

Accu

racy

-adj

uste

d re

actio

n tim

es (m

s) small CC large CC

!

54!

Figure!2.4.!Interaction!of!task!and!switch!according!to!age!group.!For!graphing!purposes,!data!were!lowBpass!filtered!at!8!Hz.!!

'

f3

−100 100 200 300 400 500 600

−1

2

4

6

f4

−100 100 200 300 400 500 600

−1

2

4

6

c3

−100 100 200 300 400 500 600

−1

2

4

6

c4

−100 100 200 300 400 500 600

−1

2

4

6

p3

−100 100 200 300 400 500 600

−1

2

4

6

p4

−100 100 200 300 400 500 600

−1

2

4

6

BIN1: SW2MBIN2: NSW2MBIN3: SW2PBIN4: NSW2P

f3

−100 100 200 300 400 500 600

−1

2

4

6

f4

−100 100 200 300 400 500 600

−1

2

4

6

c3

−100 100 200 300 400 500 600

−1

2

4

6

c4

−100 100 200 300 400 500 600

−1

2

4

6

p3

−100 100 200 300 400 500 600

−1

2

4

6

p4

−100 100 200 300 400 500 600

−1

2

4

6

BIN1: SW2MBIN2: NSW2MBIN3: SW2PBIN4: NSW2P

YO Adults

p3

−100 100 200 300 400 500

−1

2

4

6

p4

−100 100 200 300 400 500

−1

2

4

6

SW2M

NSW2M

SW2P

NSW2P

p3

−100 100 200 300 400 500

−1

2

4

6

p4

−100 100 200 300 400 500

−1

2

4

6

SW2M

NSW2M

SW2P

NSW2P

time in milliseconds, time-locked to precue

SWITCH REPEAT

SWITCH REPEAT

Meaning Position

OO Adults

µv

!

55!

Figure!2.5.!Greater!F3!switchBrelated!negativity!predicts!smaller!RT!switch!costs!!

'!

! !

-120

-80

-40

0

40

80

120

160

-6 -4 -2 0 2 4 6 8

Med

ian

RT s

witc

h-re

peat

MEANING F3 switch-repeat, 400-450 ms

-120

-80

-40

0

40

80

120

160

-6 -4 -2 0 2 4 6 8

Med

ian

RT s

witc

h-re

peat

POSITION F3 switch-repeat 350-400 ms

!

56!

Figure!2.6.!Univariate!analysis:!general!and!taskBspecific!switch!effects!!

!!! !

!

57!

Figure!2.7.!CrossBcorrelation!analyses!of!the!switch!effect!in!left!MFG!!

!!! !

VOCAL&

MANUAL&

lag$ 0$ms$ 76$ms$$ 102$ms$ 179$ms$ 230$ms$

lag$ 0$ms$ 76$ms$$ 128$ms$ 179$ms$ 256$ms$

+3.0$

z$

!3.0$

MEANING'

POSITION'

0"ms"

0"ms"

230"ms" 256"ms"

153"ms" 256"ms"

lag"

lag"

!

58!

Figure!2.8.!Relationship!between!anterior!CC!and!leftBtoBright!PFC!coupling!in!position!task!!!

!!! !

!0.6%

!0.4%

!0.2%

0%

0.2%

0.4%

0.6%

0.8%

1%

800% 900% 1000% 1100% 1200% 1300% 1400% 1500% 1600% 1700%

le#$MFG

$($rig

ht$M

FG$correla1o

n$

Anterior$CC$volume$(mm3)$

Anterior$CC$predicts$$lMFG(rMFG$coupling$in$posi1on$task$

!

59!

Figure!2.9.!Hot!spots!are!areas!where!large!CC!participants!show!a!greater!position!switch!effect.!Cool!spots!are!where!the!smaller!CC!group!shows!a!greater!switch!effect.!!

!! !! !

!

60!

CHAPTER'3 CONTROL'ADJUSTMENTS'IN'AGING:'BEHAVIORAL'AND'ERP'FINDINGS'

Introduction'

! Cognitive!control!involves!the!ability!to!adapt!and!adjust!behavior!to!deal!with!

currently!pertinent!demands.!This!adaptability!can!be!extended!to!the!implementation!of!

attentional!control!processes!itself,!as!certain!tasks!can!sometimes!be!completed!more!

optimally!with!minimal!control,!for!example!in!the!context!of!reading!or!in!a!congruent!

Stroop!trial!where!the!word!“green”!is!also!written!in!green!ink.!Moreover,!a!series!of!

experiments!have!shown!that!on!average,!participants!select!a!course!of!action!they!

perceive!to!be!less!cognitive!demanding!(Kool,!McGuire,!Rosen!&!Botvinick,!2010;!McGuire!

&!Botvinick,!2010;!Botvinick,!Huffstetler!&!McGuire,!2009;!Westbrook,!Kester!&!Braver,!

2013).!This!strategic!aspect!of!when!to!implement!attentional!control!has!not!been!studied!

in!the!context!of!aging,!which!is!characterized!by!declines!in!attentional!control!but!

relatively!preserved!automatic!processes!such!as!attentional!capture!(Kramer,!Hahn,!Irwin!

&!Theeuwes,!2000)!and!many!language2related!functions!(Park!et!al.,!2002).!!In!the!current!

study,!we!investigate!strategic!control!in!terms!of!cue2related!behavioral!adjustments—

specifically!when!to!apply!more!focused!or!selective!attention,!and!when!to!relax!this!

attentional!control!to!allow!more!low2cost!and!low2effort!automatic!processing!to!occur.!!

! Here!we!use!a!flanker!paradigm,!previously!shown!to!elicit!behavioral!adjustments!

in!young!adults!(Gratton!et!al.,!1992;!Ghinescu!et!al.,!2010).!In!this!paradigm,!participants!

are!primarily!tasked!to!indicate!the!identity!of!a!central!stimulus.!The!target!stimulus!can!

be!surrounded!by!identical!stimuli,!called!a!compatible!trial!(SSSSS!or!HHHHH)!or!by!

different!stimuli,!called!an!incompatible!trial!(SSHSS!or!HHSHH).!Performance!on!

incompatible!trials!is!characterized!by!lower!accuracy!and!longer!reaction!times,!although!

!

61!

performance!during!this!type!of!trial!has!been!shown!to!benefit!from!immediate!prior!

experience!with!an!incompatible!trial!(for!a!review,!see!Egner!2008).!This!phenomenon,!

coined!“conflict!adaptation”!is!thought!to!reflect!increased!recruitment!of!control!triggered!

during!the!incompatible!trial!that!carries!over!to!the!subsequent!trial!(Ullsperger,!Bylsma!&!

Botvnicik,!2005).!Gratton!and!colleagues!suggested!a!strategic!or!expectancy!account!

wherein!subjective!expectations!regarding!the!nature!of!the!upcoming!trial!drove!them!to!

regulate!behavior,!with!a!greater!tendency!to!select!a!focused!strategy!(foveate!on!middle!

letter/target)!after!a!high!conflict!incompatible!trial,!and!default!to!a!“parallel”!or!less!

focused!strategy!after!a!low2conflict!compatible!trial!(as!flanker!information!in!this!case!is!

consistent!with!the!target!and!may!facilitate!faster!responses).!In!a!series!of!experiments!

that!aimed!to!rule!out!stimulus!repetition!or!response!priming,!they!confirmed!that!

expectancy!did!relate!to!strategy!selection,!such!that!a!high!probability!of!congruent!trials!

led!to!an!“early!selection”!strategy!that!allowed!for!greater!processing!of!flankers!to!

facilitate!performance,!while!a!high!probability!of!incompatible!trials!led!to!a!more!focused!

selection!strategy.!To!better!probe!the!role!of!expectancies!in!producing!behavioral!

changes,!this!paradigm!was!modified!to!include!cues!at!the!beginning!of!each!trial!that!

indicate!the!probability!that!the!target!will!be!surrounded!by!incompatible!or!compatible!

stimuli.!Like!the!conflict!adaptation!effect,!flanker!effects!were!reduced!following!cues!that!

predicted!incompatible!trials—suggesting!an!up2regulation!of!attention!during!the!

preparatory!period!(Gratton!et!al.,!1992;!Ghinescu!et!al.,!2010).!Interestingly,!this!has!been!

found!to!occur!without!awareness!(Ghinescu,!et!al.,!2010)!in!a!paradigm!that!manipulated!

whether!subjects!were!aware!of!the!predictive!utility!of!the!cues!that!preceded!stimulus!

onset.!It!is!not!known,!however,!whether!older!adults!are!able!to!similarly!benefit!from!the!

!

62!

cues.!Here,!we!employ!the!cued!flanker!paradigm!in!young!and!older!adults!and!use!cues!

predicting!compatible!stimuli,!incompatible!stimuli,!and!neutral!cues!that!indicate!that!the!

target!is!equally!likely!to!be!compatible!or!incompatible.!

! A!line!of!research!on!cognitive!control!makes!the!distinction!between!preparatory!

“proactive”!control!and!more!bottom2up!“reactive”!control,!finding!that!although!older!

adults!show!a!decline!in!the!former,!reactive!mechanisms!remain!relatively!intact!(Braver,!

Gray!&!Burgess,!2007;!Bugg,!2014).!Nonetheless,!when!trained!to!shift!to!a!more!proactive!

mode,!older!adults!are!able!to!override!the!tendency!to!use!reactive!control!and!instead!

learn!how!to!use!advanced!information!to!better!perform!the!task!(Braver,!Paxton,!Locke!&!

Barch,!2009).!Although!implementation!of!control!is!required!in!both!cases,!the!aging!

findings!in!this!framework!suggest!that!when!cued,!older!adults!can!shift!strategies!and!

override!the!tendency!to!engage!in!a!more!reactive!mode!of!control.!In!the!current!study,!

we!investigate!if!such!flexibility!can!extend!to!a!paradigm!where!the!choice!is!between!a!

strategy!that!requires!attentional!control!(“focused”)!and!a!strategy!where!attentional!

control!may!be!less!optimal!for!performance!(“parallel”).!!

! In!this!experiment,!we!also!probe!the!neurocognitive!processes!related!to!engaging!

(or!being!unable!to!engage)!these!strategies.!Event2related!potentials!(ERPs)!provide!a!nice!

tool!to!study!preparatory!brain!activity,!given!the!extant!literature!on!electrical!markers!or!

components!associated!with!preparation.!One!such!well2understood!component!is!the!

lateralized!readiness!potential!(LRP),!an!increase!in!electrical!activity!prior!to!a!motor!

responses!that!is!maximal!around!central!recording!sites!(Kornhuber!&!Deecke!1965;!Coles!

1989;!Gratton!et!al.,!1989;!De!Jong,!Wierda,!Mulder,!&!Mulder,!1988;!Gehring,!Gratton,!

Coles,!&!Donchin,!1992;!Gratton,!Coles,!Sirevaag,!Eriksen,!&!Donchin,!1988;!Kutas!&!

!

63!

Donchin,!1980).!!LRPs!are!often!observed!earlier!for!compatible!compared!to!incompatible!

trials,!reflecting!faster!activation!of!the!correct!response!in!the!absence!of!competing!

flankers.!In!this!experiment,!if!greater!control!is!deployed!after!predict!incompatible!trials,!

we!expect!LRP!onsets!for!incompatible!stimuli!to!be!earlier!compared!to!incompatible!

stimuli!preceded!by!predict2neutral!or!predict2compatible!cues.!!

! As!control!is!a!function!often!related!to!the!frontal!cortex,!we!also!expect!to!find!cue!

modulation!in!frontal!electrode!sites!during!the!preparatory!period.!In!a!cued!flanker!

paradigm!similar!to!the!one!employed!in!this!study,!Gratton!and!colleagues!(1992)!

observed!that!cues!predicting!compatible!trials!showed!a!sustained!negativity!in!frontal!

and!central!electrodes!when!compared!to!cues!predicting!neutral!or!incompatible!trials.!In!

this!previous!study!however,!strategy!instructions!were!explicitly!provided!to!participants.!

If!we!obtain!similar!behavioral!adjustments!in!the!current!experiment!where!no!explicit!

strategies!are!provided!(only!the!probabilities!associated!with!each!cue),!we!will!examine!

whether!any!frontal!modulations!track!with!cue.!Given!that!participants!are!not!explicitly!

told!to!engage!in!a!parallel!strategy!for!cues!predicting!compatible!trials,!the!sustained!

frontal!negativity!found!previously!may!be!attenuated!if!present.!Nonetheless,!the!

literature!points!to!the!importance!of!frontal!and!parietal!regions!in!the!control!of!

attention—and!the!presence!of!cue2driven!behavioral!differences!is!likely!to!be!

accompanied!by!electrophysiological!modulation!during!the!preparatory!period.!

' !! !

!

64!

Methods!Participants!

Fifteen!young!adults!(18237)!and!12!older!adults!(57277)!have!participated!in!the!

study!and!received!compensation!of!$15/hr.!Participants!were!native!English!speakers,!

right2handed!as!assessed!by!the!Edinburgh!Handedness!Inventory,!had!normal!or!

corrected2to2normal!vision!and!signed!informed!consent.!Twenty2three!participants!were!

recruited!from!a!pool!of!subjects!who!participated!in!a!larger!multi2session!study!within!

the!Cognitive!Neuroimaging!Lab!at!the!University!of!Illinois,!and!four!young!adults!were!

recruited!from!a!list!of!participants!in!the!Lifelong!Brain!and!Cognition!lab!who!have!

agreed!to!be!contacted!for!future!studies.!Eligibility!was!determined!using!criteria!similar!

to!the!previous!experiment!(Chapter!2),!and!confirmed!by!a!phone!screening!that!assessed!

any!changes!in!health!and!lifestyle.!Participants!had!no!serious!or!chronic!medical!or!

psychological!conditions.!Selection!criteria!consisted!of!the!following:!1)!no!serious!or!

chronic!medical!or!psychological!conditions,!2)!no!history!of!drug!abuse,!3)!no!signs!of!

dementia!as!reflected!in!a!score!of!at!least!51!on!the!modified!Mini2Mental!Status!

examination!(Mayeux!et!al.,!1981),!4)!no!signs!of!depression!as!indexed!by!a!score!of!less!

than!14!on!the!Beck!Depression!Inventory!(Beck!et!al.,!1996),!5)!no!habitual!consumption!

of!alcohol!or!cigarette,!or!at!least!of!no!more!than!2!alcoholic!drinks!per!day!and/or!half!a!

pack!of!cigarettes!per!day,!and!6)!normal!or!corrected2to2normal!vision!and!7)!being!a!

native!English!speaker.!!

Cued!Flanker!Task!

! The! experimenter! first! presented! sample! stimuli! from! the! experiment,! informing!

participants!that!they!will!view!letter!strings!(targets)!that!were!either!compatible!(SSSSS!

or! HHHHH)! or! incompatible! (SSHSS! or! HHSHH),! and! that! their! task!was! to! indicate! the!

!

65!

identity!of!the!middle!letter!using!either!a!left!or!right2hand!button!press.!They!were!also!

told!that!later!in!the!task,!the!targets!will!be!preceded!by!shapes,!and!that!these!shapes!may!

be!useful!in!performing!the!task.!Participants!then!viewed!an!example!of!each!target!type!

and!indicated!their!responses!to!the!experimenter.!Participants!were!instructed!to!respond!

quickly!and!accurately!by!pressing!a!button!with!their! left!or!right!hand,!with!one!button!

representing!“H”!and!the!other!“S.”!Hand!assignment!was!counterbalanced!across!subjects,!

and!consistent!within!subject.''

On! the! computer,! participants!were!positioned!82! cm! from! the! screen.!All! stimuli!

were!white! presented! on! a! black! background.! Letters!were! displayed! in! Lucida! Console!

font.!First,!participants!completed!two!trials!of!each!target!type.!They!were!then!introduced!

to!three!shapes!(triangle,!square,!diamond—referred!to!here!as!A,!B,!C)!and!informed!of!the!

target!probability!associated!with!each:!20%!incompatible!(PC)!for!A,!50%!for!B!(PN)!and!

80%! for! C! (PI).! The! probability2cue! assignments! were! pseudo2counterbalanced! across!

subjects.! For! each! cue! separately,! participants! completed! ten! trials! that! contained! letter!

targets!with!compatibility!frequency!according!to!the!associated!cue!probability!(e.g.,!eight!

compatible! trials! and! two! incompatible! trials! for! PC).! On! each! trial! (Figure! 3.1),! a! cue!

positioned! on! both! sides! of! fixation! (triangle,! square! or! diamond)! appeared! for! 200!ms.!

After!a!1500!ms!interval,!participants!responded!to!the!flanker!stimulus!by!indicating!the!

identity!of! the!central! letter.!The! inter2trial! interval!was!1600!ms!and!accuracy! feedback!

was!provided!at!the!end!of!the!thirty!trials!(ten!for!each!cue).!To!ensure!that!participants!

remembered! the! shape2probability!mapping,! they! then! completed!24! forced2choice! trials!

that!asked! them! to! choose!which!of! two! letter! strings!was!more! likely! to!appear!given!a!

certain! shape! cue.! For! PN! trials,! either! choice! was! correct.! Feedback! was! provided!

!

66!

automatically! after! each! response.! For! incorrect! responses,! the! experimenter! provided!

additional! feedback! and! explanation! to! reinforce! the! shape2probability! mapping! and! to!

ensure!that!participants!understood!the!task.!!

Prior!to!beginning!the!recording!session,!participants!then!completed!a!block!of!60!

trials!where! cues! and! targets! occurred! randomly! and! equiprobably.! Parameters!were! as!

described! above,! except! for! a! 3000! ms! interval! in! between! cue! and! target.! They! then!

completed!another!practice!block!of!60!trials!with!the!experimental!timing!of!1500!ms!in!

between! cue! and! target.! Participants! were! instructed! to! keep! their! eyes! on! the! fixation!

cross!throughout!the!experiment.'

For!the!EROS2ERP!recording,!participants!completed!20!blocks!of!60!trials!each.!At!

the!beginning!of!each!block,!a!reminder!screen!displayed!the!shape2probability!and!hand2

letter!mappings.!At!the!end!of!each!block,!the!screen!displayed!overall!accuracy!and!

performance2based!instructions.!If!mean!accuracy!was!less!than!70%,!participants!were!

instructed!to!respond!more!slowly!and!more!accurately.!If!mean!accuracy!was!less!than!

90%!but!greater!than!70%,!they!were!told!to!continue!to!respond!as!quickly!and!

accurately.!If!mean!accuracy!was!over!90%,!they!were!instructed!to!respond!more!quickly.!

Electrical!Recording!and!Preprocessing!

! EEG!data!was!collected!using!13!Ag/AgCl!electrodes.!Six!electrodes!approximately!

located!at!F3,!F4,!C3,!C4,!P3!and!P4!according!to!the!10/20!system,!were!secured!onto!the!

scalp!by!wrapping!each!conductive!end!with!a!small!porous!sponge,!filling!it!with!gel!and!

inserting!the!wrapped!electrode!into!a!pre2assigned!hole!on!the!custom!foam!helmet.!All!

electrodes!were!referenced!to!the!left!mastoid!online,!and!re2referenced!offline!to!the!

average!of!the!left!and!right!mastoid,!with!a!ground!electrode!positioned!on!the!forehead.!

!

67!

To!monitor!eye!movements,!electrodes!were!also!positioned!above!and!below!the!right!eye,!

and!at!the!outer!canthi!of!the!left!and!right!eye.!Data!were!obtained!with!a!sampling!rate!of!

250!Hz!and!bandpass2filtered!between!.01!and!30!Hz,!using!Brain!Vision!Recorder!software!

and!Brain!Vision!V2Amp!(Brain!Products).!Electrode!impedances!were!maintained!below!

20!kΩ,!with!the!head!electrodes!all!falling!below!10!kΩ.!

! EEGLAB!13.2.1!and!ERPLAB!4.0.2.3!were!used!to!process!the!EEG!data.!Data!were!

segmented!into!10002ms!epochs!time2locked!to!stimulus!onset,!with!a!200!ms!pre2event!

baseline.!Segments!containing!artifacts!due!to!electrode!saturation!or!displacement!as!

identified!by!voltage!changes!larger!than!700!μV!were!discarded!from!analyses.!Eye!

movements!were!regressed!out!using!procedures!described!in!Gratton,!Coles!&!Donchin!

(1983).!The!data!was!further!cleaned!by!discarding!epochs!with!voltage!changes!greater!

than!200!uv.!Only!data!for!correct!trials!were!analyzed.!

!' '

!

68!

Results'

Behavioral!

The!average!RT!and!accuracy!data!summarizing!cue!and!target!compatibility!effects!

are!presented!in!Table!3.1.!Accuracy!and!reaction!time!were!analyzed!with!a!repeated2

measures!ANOVA,!with!cue!type!and!stimulus!type!as!within!subjects!factors!and!age!group!

as!between2subjects!factor.!Median!RTs!were!computed!to!limit!the!effect!of!extreme!

values.!

For!median!reaction!times!(Table!3.1,!Figure!3.2),!there!was!a!main!effect!of!

stimulus!F(1,!25)=212.355,!p<.001,!ηp2=.895,!with!longer!RTs!for!incompatible!trials.!There!

was!a!near2significant!stimulus!and!age!interaction!F(1,!25)=4.179,!p=.052!ηp2=.143,!with!

greater!flanker!effects!for!the!older!group.!Despite!the!lack!of!specific!instructions!

regarding!how!to!use!the!cues!(unlike!Gratton!et!al.,!1992!and!Ghinescu!et!al.,!2010),!the!

cue!and!stimulus!interaction!approached!significance!F(2,50)=2.714,!p=.076,!ηp2=.098:!

smaller!flanker!effects!were!observed!for!PN!and!PI!trials.!Although!Figure!3.2!shows!that!

this!effect!was!greater!in!the!older!adult!group,!there!was!no!significant!three2way!

interaction!of!cue,!stimulus!and!age—perhaps!due!to!the!smaller!sample!size.!The!apparent!

smaller!effects!of!cue!in!the!young!adult!group!may!reflect!ceiling!effects!in!reaction!time.!

For!percent!correct!measures,!accuracy!was!higher!on!compatible!trials!

F(1,25)=15.626,!p=001,!ηp2=.385.!We!also!computed!inverse!efficiency!scores!(Townsend!&!

Ashby,!1983;!Bruyer!&!Brysbaert,!2011),!which!provide!a!measure!of!RT!that!takes!into!

account!accuracy.!For!each!subject,!we!divided!the!median!RT!by!accuracy!(proportion!

correct).!These!accuracy!adjusted!RTs!revealed!the!same!trends!as!the!median!RT!analyses!

(Figure!3.2).!There!was!a!still!significant!effect!of!stimulus!compatibility!F(1,!25)=82.665,!

!

69!

p<.001,!ηp2=.768,!and!although!not!significant,!the!stimulus!compatibility!by!age!interaction!

(F(1,25)=2.218,!p=.149,!ηp2=.081)!also!showed!a!trend!for!bigger!flanker!effects!in!older!

adults,!while!the!cue!by!stimulus!interaction!(F(2,!50)=1.399,!p=.256,!ηp2=.053)!showed!the!

same!trend!of!smaller!flanker!effects!in!PI!and!PN!trials.!

Taken!together,!these!findings!show!that!despite!the!absence!of!explicit!instructions!

and!more!than!half!of!participants!reporting!not!finding!the!shape!cues!useful!(14!out!of!27;!

7!young),!cue!information!had!some!effect!on!task!performance.!Incompatible!RTs!were!

faster!after!PI!and!PN!cues,!and!suggest!strategic!engagement!of!control!to!reduce!

interference!from!flankers!during!target!onset.!Although!the!interaction!of!cue,!stimulus!

and!age!did!not!reach!significance!presumably!due!to!a!lack!of!power,!the!cue!modulation!

effect!was!more!pronounced!in!the!older!adult!group.!The!weaker!effect!in!the!younger!

group!may!reflect!floor!effects!in!reaction!time.!It!is!also!plausible!that!older!adults!were!

more!likely!to!use!the!cue,!however,!only!5!out!of!the!12!older!adults!(vs!8!out!of!the!15!

young!adults)!reported!using!the!cue.!Nonetheless,!Ghinescu!et!al.,!2010!demonstrated!that!

cue2related!modulations!can!be!observed!in!the!absence!of!explicit!knowledge!regarding!

the!stimulus!probabilities!associated!with!the!shape!cues.!!

EEG!Results!

! Cue&locked!analyses.!The!grand!average!waveforms!for!each!cue,!noise,!and!age!

condition!are!presented!in!Figure!3.3.!!The!analysis!was!conducted!by!averaging!intervals!

(separately!for!each!electrode,!and!applying!ANOVA!to!each!interval!data).!!252ms!intervals!

were!used!to!derive!mean!amplitude!measures!used!for!analyses.!Main!effects!of!cue!were!

observed!primarily!in!F3,!C4,!P3!and!P4!(Table!3.2).!In!F3,!the!early!effects!were!

characterized!by!greater!positivity!for!PI!vs!PC!and!PN!trials—effects!mirrored!in!more!

!

70!

posterior!electrodes.!The!later!effects!in!F3!were!more!sustained!and!showed!a!graded!

effect!of!cue,!with!PI!showing!the!greatest!positivity!and!PC!the!greatest!negativity,!while!

the!later!effects!in!C4!and!P4!showed!sustained!negativity!for!PC!and!PN.!

Although!cue!modulation!around!300!ms!was!observed!in!young!adults!but!not!in!

older!adults,!significant!interactions!of!age!and!cue!were!found!only!in!5752625!ms!in!F3!

and!F4.!These!effects!were!driven!by!greater!negativity!for!PC!and!PN!trials!in!the!older!

adults.!

To!determine!whether!this!effect!in!F3!was!related!to!performance,!we!derived!cue!

effects!for!median!reaction!time!(PI2PC)!and!F3!(PI–PC!mean!amplitude!over!6002625!ms).!

We!found!that!the!RT!cue!effect!was!related!to!the!cue!effect!in!F3!(Figure!3.4),!with!greater!

cue!modulation!or!greater!PI!positivity!predicting!smaller!cue2related!RT!differences!

(“costs”).!This!effect!was!significant!before!controlling!for!age!r(26)=2.361,!p=.032,!and!

after!taking!chronological!age!into!account!r(24)=2.358,!p=.036.!Since!behavioral!effects!

were!primarily!seen!for!incompatible!trials,!we!re2ran!the!correlation!with!only!

incompatible!RTs.!The!correlation!was!still!significant!before!controlling!for!age!r(26)=2

.337,!p=2.043,!and!after!r(24)=2.331,!p=2.049.!

! Target&locked!analyses.!For!analyzing!activity!time2locked!to!the!target,!we!

computed!the!LRP!by!first!averaging!activity!(separately!for!each!hand)!from!central!

electrodes!contralateral!to!the!correct!response!hand!and!then!averaging!activity!from!

central!electrodes!ipsilateral!to!the!response!hand.!For!computation!of!the!contralateral!

and!ipsilateral!waveforms,!responses!were!collapsed!across!left!and!right!hand!responses.!

Ipsilateral!waveforms!were!then!subtracted!from!contralateral!waveforms!to!create!the!

LRP.!Figure!3.5!shows!that!overall,!LRPs!to!incompatible!trials!onset!later,!replicating!

!

71!

previous!findings!and!confirming!the!current!study’s!behavioral!results!of!delayed!

responses.!We!conducted!a!repeated2measures!ANOVA!with!age!group!as!a!between2

subjects!factor,!and!time![latency,!2502400!ms,!4002550!ms],!cue!and!stimulus!

compatibility!as!within2subjects!factors.!It!is!important!to!note!that!these!targetBlocked!

analyses!may!not!be!very!meaningful!given!the!10!ms!or!less!RT!effect!and!the!250!Hz!(4!ms)!

sampling!rate!for!the!EEG.!!

! Main!effects!revealed!that!LRPs!were!larger!in!older!adults!F(1,!25)=8.611,!p=.007,!

ηp2=.256,!in!the!later!time!window!F(1,!25)=31.144,!p<.001,!ηp2=.555,!and!for!incompatible!

trials!F(1,!25)=90.372,!p<.001,!ηp2=.783.!The!LRPs!were!significantly!later!for!incompatible!

trials!as!shown!by!a!significant!time!and!stimulus!interaction!F(1,!25)=42.873,!p<.001,!

ηp2=.632.!The!interaction!between!time!and!cue!was!also!significant!F(2,!50)=4.047,!p=.023,!

ηp2=.139.!Overall,!mean!LRPs!were!larger!for!PI!trials!and!pronounced!in!the!later!interval.'

PN!trials!showed!the!smallest!LRP!in!the!early!interval,!but!the!largest!in!the!later!interval.!

Notably,!the!PC!and!PI!trials!showed!larger!LRPs!for!compatible!trials!and!suggest!that!

participants!also!engaged!in!a!parallel2processing!strategy!for!PC!trials.!

Age!interacted!with!time!F(1,!25)=8.175,!p=.008,!ηp2=.246,!and!stimulus!F(1,!

25)=8.514,!p=.007,!ηp2=.254.!The!three2way!interaction!of!age,!time!and!stimulus!was!also!

significant!F(1,!25)=11.952,!p=.002,!ηp2=.323,!with!the!greatest!stimulus!compatibility!

effect!occurring!at!the!later!interval!in!older!adults.!Finally,!the!three2way!interaction!of!

time,!cue!and!age!was!marginally!significant!F(2,!50)=2.676,!p=.079,!ηp2=.097.!In!young!

adults,!the!LRP!was!delayed!for!PC!compared!to!PN!and!PI!trials.!In!older!adults,!PN!trials!

differentiated!the!most—with!smaller!LRPs!in!the!later!interval.!To!summarize!the!

!

72!

aforementioned!interactions,!Figure!3.6!displays!the!waveforms!according!to!cue,!stimulus!

and!age!even!though!the!four2way!interaction!with!time!did!not!reach!significance.!!

! For!each!cue!type,!we!then!correlated!the!magnitude!of!the!later!window!LRP!

flanker!effect!with!the!behavioral!RT!flanker!effect.!However,!it!is!important!to!note!that!

given!the!behavioral!effects!which!were!10212!ms!in!magnitude!(incompatible!trials!in!

older!adults),!the!resolution!of!the!ERP!may!not!be!sufficient!to!capture!differences.!

Moreover,!analyses!here!are!time2locked!to!the!target!and!not!to!response,!which!may!

better!meaningful!differences!in!the!LRP.!For!all!cue!types,!a!smaller!LRP!flanker!effect!

(more!positive!difference!waveform!between!compatible!and!incompatible!trials)!

predicted!smaller!RT!flanker!effects:!r(25)=2.327,!p=.049!for!PC,!r(25)=2.414,!p=.016!for!PN,!

r(25)=2.325,!p=.049!for!PI!.!It!is!also!important!to!note!that!after!removal!of!the!subject!

whose!data!for!all!three!cue!types!was!the!most!extreme!in!both!ERP!and!RT,!the!

correlations!were!no!longer!significant,!although!they!were!in!the!same!negative!direction.!

The!correlations!were!also!no!longer!significant!after!accounting!for!age—presumably!due!

to!the!shared!variance!between!age!and!the!magnitude!of!the!flanker!effect.!It!is!also!

possible!that!the!current!sample!was!not!sufficient!for!this!analysis,!and!that!analyzing!

LRPs!time2locked!to!the!response!may!yield!more!robust!and!reliable!effects.!No!

correlations!were!found!for!the!early!window!LRP.!

' Although!the!relationship!between!LRP!and!behavioral!performance!was!not!robust,!

we!examined!whether!the!F3!cue!effect!previously!found!to!relate!to!performance!is!related!

to!cue2related!LRP!effects.!For!the!LRP,!we!also!computed!a!cue!effect!by!subtracting!PI!

from!PC!trials.!For!the!early!time!window!there!was!a!marginally!significant!positive!

correlation!r(25)=.261,!p=.094!which!persisted!after!accounting!for!chronological!age!

!

73!

r(25)=.258,!p=.102.!The!correlation!was!in!the!same!direction,!albeit!weaker!and!did!not!

approach!significant!for!the!later!LRP!window.!A!closer!look!showed!that!this!effect!was!

driven!by!the!compatible!LRPs,!as!the!F3!cue!effect!was!highly!correlated!with!the!LRP!cue!

effect!on!compatible!(Figure!3.7),!but!not!incompatible!trials!r(25)=.561,!p<.001,!even!after!

controlling!for!age!r(25)=.598,!p=.001.!Thus,!greater!cue2related!modulation!in!F3!

predicted!greater!LRP!modulation!on!compatible!trials—suggesting!employment!of!

strategic!control!during!the!preparatory!period.!The!lack!of!correlation!for!incompatible!

trials!is!likely!due!to!a!combination!of!greater!variability!across!time!and!across!subjects!

and!the!relative!instability!of!the!cue!effects!(as!opposed!to!relative!stability!of!the!

compatibility!effects)!beginning!mid2500!ms!post2target!onset.!

! !

!

74!

Discussion'

Despite!the!absence!of!explicit!instruction!strategies,!we!found!some!evidence!for!

cue2related!behavioral!adjustments!in!the!flanker!task.!Flanker!compatibility!effects!were!

smaller!after!PI!and!PN!trials—driven!by!faster!RTs!for!incompatible!trials,!and!these!

benefits!were!most!evident!in!older!adults.!The!behavioral!advantage!for!PI!trials!was!

related!to!modulation!in!F3!around!600!ms!after!cue!presentation,!which!suggests!

recruitment!of!control!processes!to!reduce!flanker!interference.!This!is!the!first!study!to!

our!knowledge!to!characterize!these!expectancy2related!brain!and!behavior!modulations!in!

the!absence!of!strategy!instructions!and!show!that!older!adults!are!also!able!to!use!

information!about!the!cue!to!improve!performance.!

The!findings!of!PC!negativity!and!PI!positivity!parallel!ERP!results!in!the!original!

paradigm!that!included!explicit!instructions!on!how!to!use!cues!(Gratton!et!al.,!1992).!The!

effects!here!are!not!as!robust!however,!and!is!likely!related!to!the!variability!in!strategies!

employed!during!the!task.!!Indeed,!more!than!50%!of!participants!reported!that!they!did!

not!find!the!shapes!useful,!and!only!two!participants!reported!using!the!parallel!strategy!

explicitly!provided!in!previous!studies!(Gratton!et!al.,!1992;!Ghinescu!et!al.,!2010).!

Nonetheless,!the!observation!of!cue2related!behavioral!modifications!speaks!to!the!relative!

subconscious!nature!of!such!control!of!behavior!that!does!not!rely!on!effortful!

implementation!of!attentional!processes.!This!finding!is!especially!promising!in!the!context!

of!aging,!which!is!characterized!by!declines!in!inhibitory!control!(Hasher!&!Zacks,!1988;!

Hasher,!Zacks!&!May,!1999;!Zacks!&!Hasher,!1994).!!In!the!current!study,!although!older!

adults!showed!a!larger!flanker!effect!than!the!young!adults,!they!were!nevertheless!able!to!

take!advantage!of!the!cue!and!showed!reduced!interference!effects!on!PI!and!PN!trials.!!

!

75!

In!the!ERPs,!young!adults!showed!cue2driven!differentiation!earlier!in!the!

preparatory!period!unlike!older!adults!whose!cue!effects!emerged!only!around!600!ms.!

While!only!the!later!effect!at!600!ms!correlated!with!behavior,!it!is!plausible!that!the!earlier!

cue2effects!also!play!a!functional!role—but!their!effects!were!not!measurable!due!to!RT!

ceiling!effects!particularly!in!the!young!adults!who!show!the!early!ERP!differentiation.!In!

this!same!regard,!any!effects!of!the!cue!on!the!LRP!may!not!be!discernible!for!several!

reasons.!First,!the!ERP!sampling!rate!of!250!Hz!(4!ms)!may!not!be!sensitive!enough!to!

capture!RT!differences!in!the!order!of!10!ms!or!less!(Table!3.1).!It!is!worth!noting,!however,!

that!the!target2locked!LRP!was!sensitive!to!differences!in!flanker!compatibility!and!age—

where!large!behavioral!differences!were!found!(RT!differences!greater!than!50!ms).!Older!

adults!showed!larger!LRPs,!consistent!with!previous!findings!in!non2flanker!speeded!tasks!

(Vallesi!&!Stuss,!2010;!Falkenstein,!Yordanova!&!Kolev,!2006;!Yordanova,!Kolev,!Hohnsbein!

&!Falkenstein,!2004)!that!attribute!age2related!slowing!to!reduced!excitability!of!motor!

cortex,!or!a!greater!level!of!activation!needed!for!responding.!!Second,!target2locked!LRPs!

may!not!yield!meaningful!differences!given!the!robust!compatibility!and!age!differences!in!

response!times.!Thus,!response2locked!LRPs!may!better!capture!any!cue2driven!differences!

in!motor!response!preparation.!Moreover,!a!jackknife2based!approach!for!estimating!LRP!

onset!latencies!may!yield!more!reliable!measures!(Miller,!Patterson!&!Ulrich,!1998;!Stahl!&!

Gibbons,!2004).!Third,!if!control!adjustments!are!indeed!implemented!during!the!

preparatory!period!as!we!see!here,!there!may!be!minimal!additional!effects!in!the!LRP.!

Indeed,!we!find!that!the!cue!modulation!600!ms!post2cue!presentation!predicted!RT!cue!

effects.!In!the!next!chapter,!we!take!a!closer!look!at!the!neurocognitive!mechanisms!that!

accompany!these!changes!in!behavior.!

!

76!

Future!directions!include!increasing!the!sample!size!and!investigating!individual!

differences!that!may!moderate!cue!and!compatibility!effects.!Cardiovascular!fitness!

(Colcombe!&!Kramer,!2003),!working!memory!and!fluid!intelligence!have!all!been!related!

to!the!ability!to!tune!and!engage!control!(Brumback2Peltz!et!al.,!2011;!Kane!et!al.,!2004;!

Unsworth!&!Spillers,!2010).!Knowledge!of!the!mechanisms!of!control!and!its!moderating!

factors!can!be!leveraged!to!improve!the!quality!of!life!throughout!the!lifespan.!

! !

!

77!

Tables!!

Table!3.1.!Mean!accuracy!and!reaction!times!with!standard!errors.!Age! Cue! Stimulus! RT! SE!RT! Accuracy! SE!Accuracy!

Young! PC! Com! 462.100! 23.402! 2.607! .190!

Inc! 515.633! 25.622! 2.332! .242!

PN! Com! 466.200! 22.784! 2.820! .203!

Inc! 512.433! 24.484! 2.096! .176!

PI! Con! 460.933! 23.103! 2.779! .224!

Inc! 511.267! 23.951! 2.098! .174!Older! PC! Com! 482.250! 26.165! 2.742! .213!

Inc! 556.125! 28.646! 2.326! .270!

PN! Com! 480.792! 25.473! 2.788! .227!

Inc! 544.375! 27.374! 2.081! .197!

PI! Com! 484.625! 25.830! 3.072! .250!

Inc! 546.250! 26.778! 2.065! .194!!

!

78!

Table!3.2.!Summary!of!mean!amplitude!cue!effects.!Interval!start!(ms)! F3! F4! C3! C4! P3! P4!

150! ! ! ! ! +! +!175! *! +! **! **! **! **!200! +! ! ! ! ! !225! ! ! ! ! ! !250! ! ! ! ! ! !275! *! ! ! ! ! !300! ! ! ! ! ! +!325! ! ! ! ! ! !350! ! ! +! *! *! *!375! +! ! ! ! +! !150! ! ! ! ! ! !175! ! ! ! ! ! !450! +! ! ! *! ! *!475! *! +! *! **! **! *!500! ! ! ! *! ! +!525! *! ! ! ! ! !550! *! ! ! *! ! +!575! ! ! ! +! ! +!600! *! ! ! *! +! !625! *! ! ! ! *! !650! ! ! ! ! ! !675! ! ! ! ! ! !700! ! ! ! ! ! !725! ! ! ! ! ! !750! ! ! ! *! *! *!775! ! ! ! *! ! *!

!**,!*!and!+!denote!significance!at!the!level!of!p<.01,!p<.05!and!p<.10!respectively.!

!

'' '

!

79!

Figures''Figure!3.1.!Cued!flanker!task!paradigm.!!

!

!''' '

+

+

+

SSSSS +

+

HHHHH +

+

+

!

80!

Figure!3.2.!RT!flanker!effects!and!IESBRT!flanker!effects!as!a!function!of!cue!and!age!!

'' '

30

40

50

60

70

80

90

100

110

PC PN PI

Flan

ker E

ffect

(ms)

OLDER IES-RT YOUNG IES-RT OLDER median-RT YOUNG median-RT

!

81!

Figure!3.3a.!ERP!Results!for!the!young!adults!(Blue:!PC,!Black:!PN,!Red:!PI).!Data!were!filtered!at!8!Hz!for!graphing!purposes.!

!! !

F3

−200 200 400 600 800

−1

1

F4

−200 200 400 600 800

−1

1

C3

−200 200 400 600 800

−1

1

C4

−200 200 400 600 800

−1

1

P3

−200 200 400 600 800

−1

1

P4

−200 200 400 600 800

−1

1

BIN1: PC

BIN2: PN

BIN3: PI

!

82!

Figure!3.3b.!ERP!Results!for!the!older!adults!(Blue:!PC,!Black:!PN,!Red:!PI).!Data!were!filtered!at!8!Hz!for!graphing!purposes.!

!'' '

F3

−200 200 400 600 800

−1

1

F4

−200 200 400 600 800

−1

1

C3

−200 200 400 600 800

−1

1

C4

−200 200 400 600 800

−1

1

P3

−200 200 400 600 800

−1

1

P4

−200 200 400 600 800

−1

1

BIN1: PC

BIN2: PN

BIN3: PI

!

83!

Figure!3.4.!F3!cue!modulation!predicts!behavioral!differences!!

!'' '

!50$

!40$

!30$

!20$

!10$

0$

10$

20$

30$

!2$ !1$ 0$ 1$ 2$ 3$ 4$

Reac%o

n(%m

e(cue(eff

ect((PI0PC)(

F3(cue(effect(at(6000625(ms((PI0PC)(

!

84!

Figure!3.5.!Lateralized!readiness!potential!as!a!function!of!cue!and!compatibility!!(Blue:!PC,!Black:!PN,!Red:!PI.!Dashed!lines:!compatible,!Solid!lines:!incompatible)!

!

!' '

C3/C4

−200 200 400 600 800

−2

−1.5

−1

−0.5

BIN1: PC−con

BIN2: PN−con

BIN3: PI−con

BIN4: PC−inc

BIN5: PN−inc

BIN6: PI−inc

!

85!

Figure!3.6.!LRPs!according!to!cue,!stimulus!and!age.!

!

' !

C3/C4

−200 200 400 600 800

−3.5

−3

−2.5

−2

−1.5

−1

−0.5

0.5

BIN1: PC−con

BIN2: PN−con

BIN3: PI−con

BIN4: PC−inc

BIN5: PN−inc

BIN6: PI−inc

C3/C4

−200 200 400 600 800

−3.5

−3

−2.5

−2

−1.5

−1

−0.5

0.5

BIN1: PC−con

BIN2: PN−con

BIN3: PI−con

BIN4: PC−inc

BIN5: PN−inc

BIN6: PI−inc

C3/C4

−200 200 400 600 800

−3.5

−3

−2.5

−2

−1.5

−1

−0.5

0.5

BIN1: PC−con

BIN2: PN−con

BIN3: PI−con

BIN4: PC−inc

BIN5: PN−inc

BIN6: PI−inc

C3/C4

−200 200 400 600 800

−3.5

−3

−2.5

−2

−1.5

−1

−0.5

0.5

BIN1: PC−con

BIN2: PN−con

BIN3: PI−con

BIN4: PC−inc

BIN5: PN−inc

BIN6: PI−inc

YOUNG

OLDER

!

86!

Figure!3.7.!Correlation!between!F3!cue!effect!and!compatible!LRP!cue!effect!!

'

' '

!1.5%

!1%

!0.5%

0%

0.5%

1%

1.5%

2%

2.5%

!1.5% !1% !0.5% 0% 0.5% 1% 1.5% 2% 2.5% 3% 3.5%PI#>#PC#in#LRP

##

PI#>#PC#in#F3#(600/625#ms#post#/cue)#

!

87!

''

CHAPTER'4'CONTROL'ADJUSTMENTS'IN'AGING:'EROS'FINDINGS!

!Introduction!

In!this!section,!we!examine!the!neurocognitive!dynamics!that!relate!to!the!

behavioral!adjustments!observed!in!the!previous!chapter.!In!the!conflict!adaptation!

literature,!which!emphasizes!the!experience!of!conflict!over!an!expectancy!account,!

reconfiguration!of!behavior!has!been!linked!to!up2regulation!of!frontal!regions.!Experience!

of!high2conflict!trials!(e.g.,!incompatible!flanker!targets)!triggers!activation!of!the!anterior!

cingulate!cortex!(ACC,!or!dACC!for!dorsal!ACC)!that!is!then!found!to!correlate!with!up2

regulation!of!the!dorsolateral!prefrontal!cortex!(dlPFC,!Kerns!et!al.,!2004,!2006)!either!on!

the!subsequent!trial!or!during!the!following!inter2trial!interval.!In!a!review,!Egner!and!

Hirsch!(2005)!highlighted!the!role!of!the!dACC!in!monitoring!performance!and!detecting!

conflict,!and!its!interaction!with!the!dorsolateral!prefrontal!cortex!in!deploying!greater!

control!on!the!next!trial!(Botvinick!et!al.,!2001;!Botvinick,!Cohen!&!Carter,!2004;!Kerns!et!

al.,!2004;!Hanslmayr!et!al.,!2008).!More!recently!however,!the!dACC’s!importance!has!been!

extended!beyond!conflict!detection!to!a!more!general!role!involving!evaluation!of!the!value!

of!or!need!for!control!(Shenhav,!Botvinick!&!Cohen,!2013).!As!such,!we!hypothesize!greater!

activation!of!the!dACC!in!the!current!experiment!for!the!predict2incompatible!cues!

associated!with!a!greater!need!for!attentional!control.!

Although!the!dACC!may!play!an!important!functional!role!in!initiating!control!

processes,!the!implementation!of!control!is!thought!to!lie!with!the!dlPFC!that!then!specifies!

the!preparatory!processes!in!the!task2relevant!brain!regions.!Little!is!known!however,!

about!the!dynamics!of!these!processes:!how!activity!in!the!anterior!cingulate,!prefrontal!

!

88!

cortices!and!other!task2relevant!regions!interact!across!time,!and!how!these!processes!

might!change!with!old!age.!This!study!seeks!to!fill!in!these!missing!links.!!

The!conflict!adaptation!and!expectancy!accounts!both!rely!on!the!idea!that!

prefrontal!cortex!acts!to!bias!activity!in!other!regions.!However,!fMRI!and!EEG!parardigms!

are!limited!in!characterizing!the!dynamics!between!the!two!regions,!with!the!majority!of!

analyses!limited!to!correlations!of!absolute!activity!or!correlations!at!the!zero2lag!order.!A!

particular!novel!aspect!of!this!experiment!is!the!use!of!optical!imaging,!a!method!that!can!

measure!both!neuronal!activity!(EROS)!and!blood!flow!in!the!cortex.!As!EROS!is!a!direct!

measure!of!neuronal!activity,!we!can!detect!rapidly!changing!activity!in!the!course!of!

milliseconds!and!characterize!potentially!interacting!activity!in!regions!like!the!prefrontal!

cortex!and!anterior!cingulate!cortex.!Moreover,!we!use!this!technique!in!conjunction!with!

electroencephalography!(EEG/ERP),!which!helps!guide!and!supplement!analyses!of!the!

optical!imaging!data!by!identifying!time!intervals!of!interest!and!providing!complementary!

indices!of!preparatory!neural!markers.!

Given!the!findings!of!left!frontal!modulation!in!the!ERPs!and!the!literature!on!

conflict!adaptation,!we!expect!to!observe!up2regulation!of!dlPFC!during!the!preparatory!

period,!particularly!for!PI!cues!that!require!more!implementation!of!strategic!control!over!

behavior.!If!the!dACC!does!track!the!need!for!control,!it!should!similarly!show!up2

regulation!for!PI!trials.!Moreover,!we!hypothesize!that!lagged!cross2correlation!analyses!

will!confirm!the!coupling!of!these!two!regions,!as!well!as!reveal!the!specific!interactions!of!

dlPFC!with!motor!regions!involved!in!executing!responses!to!the!target!stimuli.!

' '

!

89!

Methods'

Optical!Recording!and!Planned!Analysis!

Concurrent!with!behavioral!and!EEG!data!acquisition,!we!recorded!brain!activity!

using!two!Imagent®!frequency!domain!systems!(ISS!Inc.,!Champaign,!IL)!that!together!

afforded!a!total!of!24!detectors.!These!detectors!were!32mm!fiber!optic!bundles!connected!

to!photomultiplier!tubes,!and!measured!activity!from!64!laser!diodes!that!were!4002μm!in!

diameter!and!channeled!near!infrared!light!(830!nm)!modulated!at!110!MHz,!with!a!cross2

correlation!(i.e.,!heterodyning)!frequency!of!3.125!kHz.!!!This!allowed!for!recording!data!

using!a!50!kHz!A/D!conversion.!Measures!of!DC!(average)!intensity,!AC!(amplitude)!and!

relative!phase!delay!(in!picoseconds)!were!obtained!for!each!of!these!periods!by!applying!

Fast!Fourier!transforms!applied!to!small!segment!(1.6!ms!per!channel)!of!raw!optical!data.!!

As!data!were!time2multiplexed!across!16!channels!for!each!detector,!useful!optical!data!

were!recorded!continuously!with!an!effective!sampling!rate!of!39.!0625!Hz.!

A!customized!foam!helmet!was!used!to!secure!the!sources!and!detectors!fibers!on!a!

participant’s!head.!Two!source2detector!montages!were!created!for!each!participant!using!

in2house!software!(NOMAD,!Mathewson,!2012).!Three!helmets!of!different!size!were!

designed!for!the!study,!and!two!montages!were!created!for!each!of!the!three!helmets.!Each!

montage!consisted!of!64!sources!and!24!detectors!that!covered!the!majority!of!cortex!

(Figure!4.1!for!an!example!of!coverage).!All!source2detector!distances!fell!between!2.0!and!

6.0!cm!and!each!montage!was!designed!to!maximize!the!channels!with!distances!of!3.024.0!

cm!and!avoid!cross2talk!between!Imagent!systems.!The!first!10!blocks!were!run!with!the!

first!montage,!and!the!last!10!blocks!were!run!with!the!second!montage,!with!montage!

order!was!counterbalanced!across!subjects.!Prior!to!recording,!the!front!of!the!helmet!was!

!

90!

marked!with!an!eyeliner!pencil!to!align!the!helmet!and!assist!with!repositioning!if!the!

helmet!moved!between!blocks!or!montages.!!

After!the!imaging!session,!each!source!and!detector!location!was!digitized!in!

relation!to!the!nasion!and!fiducial!preauricular!points!using!a!Polhemus!“3Space”™!Fasttrk!

3D!digitizer!(Colchester,!VT)!with!an!extended!stylus!and!Locator!4.1!software!(Source!

Signal!Imaging!Inc.,!San!Diego,!CA).!MPRAGE!scans!(obtained!with!similar!parameters!as!

the!previous!study)!and!fiducial!markers!were!used!to!co2register!the!digitized!optical!

channels.!Data!then!underwent!standard!Talairach!transformation!(Whalen!et!al.,!2008;!

Chiarelli!etc!al.,!2014)!and!scalp2forcing!prior!to!further!analysis.!Only!data!from!channels!

with!source2detector!distances!between!15!and!55!mm!were!analyzed.!

! This!paper!covers!phase!delay!(time2of2flight)!measures!recorded!from!precue!onset!

to!1000!ms!after!precue!onset.!Data!underwent!correction!for!phase!wrapping!and!pulse!

artifacts!(Gratton!&!Corballis,!1995),!then!adjusted!to!a!mean!of!zero!for!each!block,!and!

bandpass2filtered!between!0.10!and!10!Hz.!Correct!trial!data!were!segmented!into!epochs!

time2locked!to!precue!onset,!and!averaged!separately!for!each!subject,!condition!and!

channel.!Optical!data!were!baseline2corrected!using!a!150!ms!period!preceding!the!precue.!

Only!channels!with!phase!standard!deviation!less!than!100!picoseconds!were!included!in!

the!analysis!(Gratton,!et!al.,!2006).!In2house!software!“Opt23d”!(Gratton,!2000)!was!used!to!

compute!statistics!and!combine!data!from!channels!whose!diffusion!paths!intersected!a!

given!voxel!(Wolf!et!al.,!2000).!Data!were!spatially!filtered!with!an!82mm!Gaussian!kernel.!

To!compute!statistical!maps,!group2level!t2statistics!were!derived!across!subjects!and!then!

converted!to!z2scores,!with!appropriate!correction!for!multiple!comparisons!using!random!

!

91!

field!theory!(Kiebel!et!al.,!1999).!Z2scores!were!orthogonally!projected!onto!axial,!sagittal!

and!coronal!surfaces!of!a!brain!in!Talairach!space.!!

' For!all!results!presented!here,!although!data!is!sampled!every!25.6!ms,!we!

conducted!analyses!on!smoothed!data!down2sampled!by!a!factor!of!two.!This!reduces!noise!

given!the!relatively!lower!signal2to2noise!ration!of!EROS!and!the!relatively!smaller!sample!

in!the!current!experiment,!as!well!as!reduces!the!number!of!comparisons!across!time!

points.!

EROS!results!

! Cue&locked!activity.!Analyses!focused!on!1502800!ms!interval!after!the!cue,!as!this!

interval!carried!the!largest!voltage!changes!in!the!ERP!data.!First!we!examined!which!areas!

showed!greater!activation!for!PI!trials,!which!according!to!!“conflict!adaptation”!fMRI!

studies,!should!reveal!up2regulation!in!the!dACC!followed!by!up2regulation!in!dorsolateral!

PFC.!Overall,!similar!results!were!obtained!for!the!contrasts!of!PI>PC,!PI>PN!and!

PI>PC&PN.!For!brevity,!we!present!results!from!the!PI>PC!contrast!(Figure!4.2),!as!these!

showed!the!greatest!differences!in!the!behavioral!and!ERP!results!and!were!more!likely!to!

produce!more!consistent!strategies!in!participants.!

Beginning!around!153!ms,!we!observed!cue!modulation!in!the!dACC.!A!pattern!of!

greater!activation!for!PI!vs!PC!trials!peaked!at!several!points,!first!at!204!ms!(z(26)!=!3.43,!z!

crit!=!3.41,!21/29/42),!then!at!460!ms!(z(26)=3.79,!zcrit=3.44,!23/32/43)!and!finally!at!665!

ms!although!this!effect!did!not!reach!significance!(z(26)=3.70,!zcrit=3.51,!213/37/46).!

Around!these!same!times,!greater!activity!for!PI!vs!PC!trials!was!also!observed!in!a!region!

bordering!left!MFG!and!SFG,!with!significant!peaks!at!153!ms!(z(26)=3.22,!zcrit!=!3.21,!2

48/27/27),!and!near2significant!effects!at!256!ms!(z(26)=2.75,!zcrit=2.90,!238/29/36)!and!

!

92!

614!ms!(z(26)=2.92,!zcrit!=!3.00,!246/4/41).!The!time!course!of!these!frontal!modulations!

corresponded!to!the!ERP!intervals!during!which!significant!cue!effects!were!found!in!

frontal!and!central!electrodes.!Like!the!ERPs,!there!was!little!modulation!of!right!PFC,!

except!for!a!significant!negative!effect!in!the!area!bordering!right!MFG!and!SFG,!where!PC!

trials!showed!greater!activation!at!256!ms!(z(26)=23.78,!zcrit!=!23.30,!44/21/38)!and!409!

ms!(z(26)=24.17,!zcrit!=!23.28,!42/14/145).!

Similar!to!the!ERPs,!we!also!found!greater!parietal!activity!for!PI!vs!PC!trials,!with!

significant!effects!in!the!right!IPS!ROI!at!153!ms!(z(26)!=!3.62,!zcrit!=!3.22,!29/258/51),!409!

ms!(z(26)!=!4.27,!zcrit!=!3.52,!42/246/45)!and!665!ms!(z(26)!=!3.31,!zcrit!=!3.18,!52/2

58/34).!Meanwhile,!left!IPS!showed!marginally!greater!activity!for!PC!trials!at!153!ms!

(z(22)=23.25,!zcrit!=!23.27,!231/261/52)!and!then!significantly!greater!activity!for!PI!trials!at!

460!ms!(z(24)!=!3.50,!zcrit!=!3.13,!246/263/37).!

! Dorsal!ACC!or!dlPFC2initiated!strategic!control!likely!exerts!some!effect!in!motor!

cortex!given!the!manual!responses!required!during!the!task,!so!we!also!analyzed!ROIs!in!

the!hand!areas!of!motor!cortex.!These!motor!cortex!ROIs!showed!greater!activity!for!PI!vs!

PC!trials,!with!a!peak!at!307!ms!around!the!border!of!the!right!motor!cortex!ROI!(z(25)!=!

3.05,!zcrit!=!2.96,!29/228/52,!and!another!peak!at!512!ms!in!the!right!motor!cortex!(z(26)!=!

3.65,!zcrit!=!3.10,!29/216/54).!The!left!motor!cortex!effect!peaked!at!665!ms!(z(26)!=!3.76,!

zcrit!=!3.02,!236/226/56).!Overall,!these!findings!suggest!that!PI!cues!may!“prime”!motor!

cortices!to!facilitate!responses!to!the!target.!!

Group!analyses!showed!that!similar!to!the!ERPs,!activity!diverged!according!to!age!

in!the!frontal!cortex!shortly!after!cue!presentation,!with!young!adults!overall!showing!

greater!cue2related!modulation!of!PFC!(Figure!4.3).!The!age!x!cue!interaction!was!

!

93!

significant!in!the!left!MFG!ROI!from!1532256!ms!(peak!at!153:!z(26)!=!3.28,!zcrit!=!3.27,!2

46/12/41),!at!409!ms!(z(26)!=3.25,!zcrit!=!3.17,!238/21/44)!and!at!665!ms!(z(26)!=!3.30,!

zcrit!=!3.15,!246/24/34).!The!dACC!was!also!sensitive!to!age,!though!the!interaction!did!not!

approach!significance!at!153!ms!(z(26)=3.09,!zcrit!=!3.26,!2/34/44)!and!256!ms!(z(26)!=!

3.01,!zcrit!=3.43,!2/27/45).!It!is!important!to!note!that!optical!coverage!of!a!deeper!brain!

region!such!as!the!dACC,!is!more!sensitive!to!head!size.!That!is,!although!there!may!be!

enough!power!to!detect!an!overall!cue!effect,!there!may!not!be!sufficient!data!to!test!an!

interaction.!Indeed,!the!four!participants!who!wore!the!smallest!helmet!tended!to!show!

greater!activity!on!average!in!the!dACC!ROI,!although!the!correlation!between!helmet!size!

and!activation!was!not!significant.!!

Interestingly,!older!adults!showed!greater!modulation!for!PI!trials!in!the!right!PFC.!

This!effect!was!significant!in!the!right!MFG2SFG!ROI!at!614!ms!(z(26)!=!23.21,!zcrit!=!3.13,!

42/24/37).!Since!bilateral!frontal!activation!is!a!common!finding!in!aging!studies,!we!

tested!whether!older!adults!activated!right!PFC!instead!of!left!PFC!like!young!adults,!or!if!

they!tended!to!activate!both!hemispheres!of!frontal!cortex!to!prepare!for!the!task.!For!the!

PI!>!PC!contrast,!older!adults!did!not!show!any!significant!effects!or!trends!for!left!or!right!

PFC!activation!at!614!ms,!but!bilateral!PFC!activation!was!observed!at!665!ms,!although!the!

ROI!analysis!did!not!reach!significance!during!this!interval.!Looking!into!the!pre2

subtraction!results,!we!find!that!this!bilateral!effect!at!665!ms!is!driven!by!greater!bilateral!

activation!for!PI!vs!PC!cues,!although!again!the!ROI!analysis!did!not!reach!significance.!!

! !Cross&correlations.!!According!to!the!Botvinick!et!al.!(2001,!2004;!Kerns!et!al.,!

2004)!view!of!the!processes!occurring!during!conflict!adaptation!or!congruency!effects,!

dACC!activation!after!high2conflict!trials!should!be!followed!or!correlated!with!dlPFC!

!

94!

activity.!To!test!whether!the!dACC!and!left!MFG2SFG!activations!were!related!in!the!current!

cue!expectancy!paradigm,!we!conducted!cross2correlation!analyses!on!the!period!

immediately!after!the!cue.!Cross2correlations!were!conducted!on!the!cue!effect—or!the!

difference!between!activity!on!PI!v!PC!trials.!!

With!the!peak!dACC!activation!(at!204!ms)!voxel!at!as!a!seed,!we!found!a!near2

significant!correlation!with!the!left!MFG2SFG!(Figure!4.4)!at!a!lag!of!460!ms!(z(26)=!2.87,!

zcrit!=!2.89,!246/24/34),!which!is!consistent!with!the!univariate!analysis!that!found!a!left!

MFG2SFG!cue!effect!around!6142665!ms.!It!is!also!important!to!note!that!dACC!was!

correlated!with!activity!in!parietal!cortex:!with!right!SPL!at!the!0!ms!lag!(z(26)!=!3.15,!zcrit!

=!3.08,!24/256/53)!and!512!ms!lag!(z(26)!=!3.33,!zcrit!=!2.96,!19/276/45)!and!with!the!

right!IPS!at!a!lag!of!563!ms!(z(23)!=!3.41,!zcrit!=!3.10,!59/263/23).!The!relationship!with!the!

left!parietal!cortex!shown!in!Figure!4.4!was!not!significant!in!the!left!IPS!and!left!SPL!ROIs.!!

The!univariate!analyses!showed!that!the!earliest!activations!in!dACC!and!left!PFC!

overlapped!in!time.!Thus,!we!also!conducted!forward!cross2correlations!using!the!peak!left!

PFC!early!activation!as!a!seed.!This!left!PFC2seeded!analysis!yielded!more!regions!with!

significant!or!near2significant!correlations,!which!supports!the!idea!that!the!dlPFC!

implements!or!executes!specifics!control!commands,!while!the!dACC!primarily!provides!the!

initial!step!of!evaluating!the!degree!of!control!required!(see!Shenhav,!Botvinick!&!Cohen,!

2014).!

We!observed!significant!correlations!in!frontal!and!parietal!areas!(Figure!4.5):!in!the!

left!IPS!at!the!51!ms!lag!(z(23)!=!3.19,!zcrit!=!3.15,!231/251/47),!the!left!MFG2SFG!ROI!at!the!

153!ms!lag!(z(26)!=!3.49,!zcrit!=!3.00,!231/19/42),!and!the!dACC!at!the!307!ms!lag!(z(24)!=!

3.22,!zcrit!=!3.18,!213/44/39).!!

!

95!

Trends!were!also!found!in!the!motor!cortex!hand!area!ROIs,!but!neither!the!left2

hemisphere!effect!at!409!ms!(z(24)!=!!2.25,!zcrit!=!2.74,!236/221/54)!nor!the!right!

hemisphere!effect!at!512!ms!(z(26)!=!2.85,!zcrit!=!2.91,!47/213/46)!reached!significance.!

Overall,!the!cross2correlation!analyses!confirm!the!results!of!the!univariate!

analyses—both!in!terms!of!when!and!where!PI!cues!elicit!greater!activity!than!PC!cues.!

Importantly,!the!cross2correlations!show!that!cue2related!up2regulation!in!these!regions!is!

in!part!driven!by!left!PFC.!Together!with!the!univariate!analyses,!these!results!also!suggest!

that!the!dACC2left!PFC!relationship!may!be!bi2directional,!and!that!cue2related!control!up2

regulation!of!the!PFC!may!occur!early,!independent!of,!and!in!parallel!to!dACC!activation.!

! Does!connectivity!vary!with!age?!!First!we!tested!whether!both!groups!showed!a!

cue2modulated!dACC2lPFC!coupling.!In!young!adults,!a!significant!correlation!with!left!MFG2

SFG!was!found!at!the!563!ms!lag!(z(13)!=!3.03,!zcrit!=!2.96,!233/14/45),!while!in!old!adults,!

the!correlation!was!significant!at!the!102!ms!lag!(z(11)!=!3.01,!zcrit!=!2.95,!246/17/37).!

Note!that!in!the!univariate!analyses,!dACC!activation!in!older!adults!was!not!only!weaker,!

but!also!tended!to!onset!at!a!later!time!point!compared!to!young!adults!and!closer!in!time!

with!the!left!PFC!activity.!Overall,!while!dACC!and!lPFC!activity!are!related!in!both!groups,!

the!dynamics!are!not!similar!and!likely!reflect!a!different!pattern!of!preparatory!control!in!

older!adults.!

! With!the!left!MFG2SFG!cue!effect!as!a!seed,!young!adults!showed!a!similar!pattern!as!

that!shown!in!Figure!4.5,!with!trends!for!dACC!coupling!at!307!ms,!and!motor!cortex!

coupling!at!the!later!lags.!However,!with!this!reduced!sample!size,!the!ROI!analyses!for!

these!areas!were!not!significant.!In!older!adults,!the!dACC!coupling!was!significant!at!the!

204!ms!lag!(z(11)!=!3.25,!zcrit!=!3.25,!2/37/44).!Older!adults!showed!widespread!coupling!

!

96!

to!other!frontal!areas—particularly!right!PFC.!This!right!MFG2SFG!coupling!was!significant!

at!the!358!ms!lag!(z(11)!=!3.30,!zcrit!=!2.87,!24/24/46)!and!approached!significance!at!the!

lags!of!102!ms!(z(11)!=!2.41,!zcrit!=!2.87,!44/27/31)!and!563!ms!(z(11)!=!2.55,!zcrit!=!2.87,!

29/29/37).!Thus,!although!bilateral!recruitment!could!not!be!reliably!found!in!the!

univariate!analyses,!lagged!cross2correlations!showed!that!cue!modulation!in!left!PFC!

predicted!similar!modulations!in!right!PFC.!Older!adults!also!showed!a!significant!coupling!

between!left!PFC!and!motor!areas,!with!trends!in!the!hand!ROIs!of!both!hemispheres!and!a!

significant!effect!at!the!153!ms!lag!in!the!right!motor!ROI!(z(11)!=!3.23,!zcrit!=!2.96,!34/2

16/51).!

! !

!

97!

Discussion!

This!is!the!first!study!to!our!knowledge!that!has!examined!the!neural!correlates!of!

cued!control!adjustments!in!aging.!Our!results!parallel!conflict!adaptation!paradigms!in!

showing!that!like!“high2conflict”!trials,!PI!cues!lead!to!greater!activation!in!dACC!and!dlPFC.!

While!previous!studies!show!across2trial!correlations!between!the!activations!in!these!two!

regions,!here!we!show!through!lagged!cross2correlations!not!only!their!trial2dependent!

relationship,!but!also!their!within2trial!relative!order!of!activation.!Moreover,!we!find!that!

like!young!adults,!older!adults!also!engage!preparatory!processes!in!response!to!the!cue!

and!are!able!to!adjust!their!behavior,!despite!weaker!upregulation!of!dACC!and!dlPFC!when!

compared!to!younger!adults.!!

The!cross2correlation!analyses!with!dACC!as!a!seed!mirror!the!univariate!analyses!

that!found!the!greatest!cue!modulations!in!left!MFG!and!right!parietal!cortices.!We!also!find!

that!other!regions!of!the!fronto2parietal!network!are!recruited!in!relationship!to!dACC,!

namely!the!right!parietal!cortex!which!has!long!been!known!to!be!important!in!selective,!

sustained!spatial!attention!(Beck!et!al.,!2006;!Behrmann,!Geng!!Shomstein,!2004;!Coull!&!

Frith,!1998;!Yantis!et!al.,!2002).!

This!experiment!elucidates!long!proposed!theories!of!dACC2dlPFC!interactions!from!

conflict!adaptation!paradigms.!First,!we!show!here!that!conflict!per!se!is!not!the!driving!

force!for!activation!in!dACC.!Our!cue2related!findings!support!an!emerging!view!of!the!

dACC!as!evaluating!the!need!for!control!(Shenhav,!Botvinick!&!Cohen,!2013).!Moreover,!we!

find!that!dACC!not!only!predicts!up2regulation!of!dlPFC,!but!also!other!regions!known!to!be!

involved!in!the!control!of!attention.!Specifically,!dACC!cue!modulation!also!predicted!up2

regulation!in!right!IPS2SPL,!which!has!been!related!to!attention!orienting!or!shifts!of!spatial!

!

98!

attention!(Yantis!et!al.,!2002).!The!IPS/SPL!and!the!dlPFC!are!commonly!considered!core!

regions!of!the!“dorsal!attention!fronto2parietal!network”!(DAN,!see!Sczepanski,!et!al.,!2013!

for!a!review)!that!is!preferentially!engaged!in!control2demanding!situations.!These!DAN!

regions!are!thought!to!bias!activity!in!other!brain!regions!to!optimize!performance!on!a!

given!task.!Indeed,!cross2correlation!analyses!of!the!dlPFC!not!only!revealed!relationships!

with!frontal!and!parietal!regions,!but!also!trends!for!associations!with!regions!of!motor!

cortex,!specifically!in!regions!related!to!the!manual!responses!required!in!the!flanker!task,!

with!PI!cues!“priming”!hand!area!ROIs.!!

! Although!older!adults!showed!less!up2regulation!in!dACC!and!dlPFC!as!a!function!of!

cue,!they!still!showed!cue2related!RT!benefits.!Univariate!analyses!showed!hints!of!greater!

bilateral!frontal!recruitment!in!older!adults,!which!was!confirmed!in!the!cross2correlational!

analyses.!Thus,!consistent!with!previous!research,!older!adults!show!“compensatory”!

activation!by!modulating!both!hemispheres!of!frontal!cortex.!Separate!cross2correlation!

analyses!within!the!older!group!also!revealed!trends!for!up2regulation!in!the!hand!areas!of!

motor!cortex.!As!older!adults!may!need!a!higher!threshold!to!execute!a!response!(bigger!

LRPs),!one!preparatory!strategy!may!involve!“priming”!the!motor!areas.!

Future!plans!include!examining!whether!the!frontal!activations!observed!here!are!

related!to!the!F3!modulations!found!in!the!ERP!data—modulations!that!predicted!the!cue2

modulated!RT!effects.!Future!plans!include!increasing!the!sample!size!and!probing!whether!

the!activations!in!dACC!or!dlPFC!similarly!track!performance,!and!whether!connectivity!

measures!related!to!these!regions!are!a!better!predictor!of!performance,!especially!given!

the!behavioral!adjustments!observed!in!older!adults!despite!lower!overall!activation.!

' '

!

99!

Figures!!

Figure!4.1.!Example!of!overall!brain!coverage!obtained!from!one!subject’s!session.!Figure!rendering!courtesy!of!Kyle!Mathewson.!

!

!' '

!

100!

Figure!4.2.!PI!>!PC!cue!effect!during!preparatory!period!!

!!

153$ms$

VOCAL&

MANUAL&

lag$ 0$ms$ 76$ms$$ 102$ms$ 179$ms$ 230$ms$

lag$ 0$ms$ 76$ms$$ 128$ms$ 179$ms$ 256$ms$

+3.0$

z$

!3.0$

+3.5%

&%3.5%

204$ms$ 409$ms$

512$ms$ 614$ms$ 665$ms$

PI#

PC#>#

!

101!

Figure!4.3.!Age!x!cue!interaction!(YOUNG>OLD!&!PI>PC!are!hot!spots)!in!preparatory!period!!

!'' '

VOCAL&

MANUAL&

lag$ 0$ms$ 76$ms$$ 102$ms$ 179$ms$ 230$ms$

lag$ 0$ms$ 76$ms$$ 128$ms$ 179$ms$ 256$ms$

+3.0$

z$

!3.0$

153$ms$ 204$ms$

409$ms$ 614$ms$

Young&>&Older&(PI>PC)&

!

102!

Figure!4.4.!dACCBseeded!crossBcorrelation!confirms!coupling!with!left!PFC!!

!' '

0"ms" 460"ms"

VOCAL&

MANUAL&

lag$ 0$ms$ 76$ms$$ 102$ms$ 179$ms$ 230$ms$

lag$ 0$ms$ 76$ms$$ 128$ms$ 179$ms$ 256$ms$

+3.0$

z$

!3.0$

Cross*correla/ons:"dACC"&"lMFG"rela/onship"

lag$

!

103!

Figure!4.5.!Left!PFCBseeded!crossBcorrelations!!!

!

'' '

VOCAL&

MANUAL&

lag$ 0$ms$ 76$ms$$ 102$ms$ 179$ms$ 230$ms$

lag$ 0$ms$ 76$ms$$ 128$ms$ 179$ms$ 256$ms$

+3.0$

z$

!3.0$

Cross%correla*ons:-le.%PFC-seeded-results-

0-ms- 51-ms- 153-ms-

307-ms- 409-ms- 512-ms-

lag$

lag$

!

104!

CHAPTER'5'CONCLUSIONS'

'In!two!paradigms,!we!confirm!the!importance!of!prefrontal2driven!cognitive!control!

in!aging:!left!PFC!drove!preparatory!process!in!a!switching!task!(Chapter!2)!and!in!a!cued!

flanker!task!(Chapters!3!&!4).!This!region!was!not!only!up2regulated!during!the!more!

attention2demanding!trials,!such!as!during!switch!trials!or!trials!predicting!incompatible!or!

high2conflict!stimuli,!it!also!showed!greater!connectivity!to!task2specific!regions!involved!in!

executing!a!response!upon!target!presentation.!Lagged!cross2correlations!provide!a!unique!

view!into!the!dynamics!of!control!that!is!most!often!characterized!in!neuroimaging!studies!

in!terms!of!co2activations,!without!examination!of!areas!that!may!not!be!synchronously!

activated,!but!whose!activity!is!heavily!correlated!with!the!seed!region,!albeit!at!a!later!

point!in!time.!Here!we!not!only!show!the!relative!timing!of!activations,!but!demonstrate!the!

flexible!nature!of!prefrontal!connectivity!as!it!varies!with!task!demands.!In!Chapter!2,!we!

find!that!the!connectivity!of!left!PFC!is!determined!not!only!by!the!amount!of!control!

required!as!shown!by!greater!activity!on!switch!trials,!but!also!by!the!specific!task!to!be!

performed!on!that!trial:!coupling!to!left2lateralized!regions!for!the!meaning!task,!and!

coupling!to!right2lateralized!regions!for!the!position!task.!Moreover,!converging!evidence!

for!the!importance!of!such!functional!interactions!was!provided!by!the!finding!that!

structural!connectivity!of!the!left!to!right!PFC!predicted!their!task2dependent!coupling.!

Chapter!4!examines!the!role!of!the!dACC!in!relaying!control!information!to!the!dlPFC—in!

this!case!the!left!PFC.!Again,!cross2correlations!confirmed!the!relationship!between!these!

two!regions!and!further!elucidated!the!specificity!of!their!effects.!While!dACC!was!primarily!

related!to!left!PFC!up2regulation,!left!PFC!activity!predicted!cue2dependent!up2regulation!of!

parietal!and!motor!regions!relevant!to!processing!and!responding!to!the!target!stimulus.!

!

105!

Future!directions!include!investigating!the!importance!of!structural!connections!to!these!

functional!interactions,!as!well!as!examining!individual!differences!(fitness,!working!

memory!capacity,!fluid!intelligence)!that!may!moderate!the!degree!to!which!individuals!

apply!strategic!control.!

The!importance!of!the!corpus!callosum!discussed!in!Chapter!2!highlights!the!value!

of!studying!individual!differences!in!aging.!Although!behavioral!and!ERP!differences!were!

observed!between!older!adult!age!groups,!the!functional!interaction!of!left!and!right!PFC!

was!not!related!to!chronological!age,!but!to!the!volume!of!the!corpus!callosum.!

Furthermore,!the!effect!of!this!structural!connection!on!behavioral!switch!costs!was!

evident!even!in!the!younger2old!adults.!These!findings,!as!well!as!the!robustness!of!the!

brain2behavior!relationships!even!after!accounting!for!age,!point!to!the!unique!and!

important!variance!captured!by!examining!neurocognitive!mechanisms.!Aging!is!a!

heterogeneous!phenomenon!and!studies!such!as!these!not!only!shed!light!on!why!certain!

individuals!display!relatively!preserved!abilities,!but!also!provide!a!first!step!into!

identifying!how!this!may!be!achieved!through!lifestyle!or!intervention.!

One!long2term!goal!of!this!line!of!work!is!the!exploration!of!cardiovascular!health,!

physical!activity,!and!brain!function.!We!know!that!cardiovascular!fitness!impacts!cognition!

via!change!in!brain!activation,!increase!in!cortical!thickness,!and!even!connectivity!in!

prefrontal!cortices!(Voss!et!al.,!2010).!In!an!optical!imaging!study,!older!adults!were!found!

to!have!lower!arterial!brain!elasticity!compared!to!young!adults,!with!the!greatest!effect!in!

prefrontal!areas!(Fabiani!et!al.,!2014).!Lower!fit!individuals!also!showed!reduced!elasticity!

in!prefrontal!regions.!Future!directions!include!integrating!these!physical!health!and!

intervention!findings!with!analyses!of!functional!and!structural!brain!connectivity.!

!

106!

Different!lifestyle!factors!may!selectively!influence!distinct!aspects!of!brain!function,!and!a!

multi2modal!approach!can!provide!insight!into!which!factors!or!interventions!may!be!more!

beneficial!and!practical!for!different!groups!of!individuals.!

!

! !

!

107!

REFERENCES!

Adrover2Roig,!D.,!&!Barceló,!F.!(2010).!Individual!differences!in!aging!and!cognitive!control!modulate!the!neural!indexes!of!context!updating!and!maintenance!during!task!switching.!Cortex,!46(4),!4342450.!!

Allport,!D.!A.,!Styles,!E.!A.,!&!Hsieh,!S.!(1994).!Shifting!intentional!set:!Exploring!the!dynamic!control!of!tasks.!!

Aron,!A.!R.,!Monsell,!S.,!Sahakian,!B.!J.,!&!Robbins,!T.!W.!(2004).!A!componential!analysis!of!task2switching!deficits!associated!with!lesions!of!left!and!right!frontal!cortex.!Brain!:!A!Journal!of!Neurology,!127(Pt!7),!156121573.!doi:10.1093/brain/awh169!!

Astle,!D.!E.,!Jackson,!G.!M.,!&!Swainson,!R.!(2006).!Dissociating!neural!indices!of!dynamic!cognitive!control!in!advance!task2set!preparation:!An!ERP!study!of!task!switching.!Brain!Research,!1125(1),!942103.!doi:http://dx.doi.org/10.1016/j.brainres.2006.09.092!

Badre,!D.,!&!Wagner,!A.!D.!(2006).!Computational!and!neurobiological!mechanisms!underlying!cognitive!flexibility.!Proceedings!of!the!National!Academy!of!Sciences!of!the!United!States!of!America,!103(18),!718627191.!doi:10.1073/pnas.0509550103!!

Banich,!M.!T.!(2009).!Executive!function.!Current!Directions!in!Psychological!Science,!18(2),!89294.!doi:10.1111/j.146728721.2009.01615.x!!

Baniqued,!P.!L.,!Low,!K.!A.,!Fabiani,!M.,!&!Gratton,!G.!(2013).!Frontoparietal!traffic!signals:!A!fast!optical!imaging!study!of!preparatory!dynamics!in!response!mode!switching.!Journal!of!Cognitive!Neuroscience,!25(6),!8872902.!!

Barcelo,!F.,!Escera,!C.,!Corral,!M.!J.,!&!Periáñez,!J.!A.!(2006).!Task!switching!and!novelty!processing!activate!a!common!neural!network!for!cognitive!control.!Journal!of!Cognitive!Neuroscience,!18(10),!173421748.!!

Beck,!A.!T.,!Steer,!R.,!&!Brown,!G.!(1996).!Beck!depression!inventory.!the!psychological!corporation.!San!Antonio,!TX,!!

Beck,!D.!M.,!Muggleton,!N.,!Walsh,!V.,!&!Lavie,!N.!(2006).!Right!parietal!cortex!plays!a!critical!role!in!change!blindness.!Cerebral!Cortex!(New!York,!N.Y.:!1991),!16(5),!7122717.!doi:bhj017![pii]!!

Behrmann,!M.,!Geng,!J.!J.,!&!Shomstein,!S.!(2004).!Parietal!cortex!and!attention.!Current!Opinion!in!Neurobiology,!14(2),!2122217.!!

Bookheimer,!S.!Y.,!Zeffiro,!T.!A.,!Blaxton,!T.,!Gaillard,!W.,!&!Theodore,!W.!(1995).!Regional!cerebral!blood!flow!during!object!naming!and!word!reading.!Human!Brain!Mapping,!3(2),!932106.!doi:10.1002/hbm.460030206!!

!

108!

Botvinick,!M.!M.,!Braver,!T.!S.,!Barch,!D.!M.,!Carter,!C.!S.,!&!Cohen,!J.!D.!(2001).!Conflict!monitoring!and!cognitive!control.!Psychological!Review,!108(3),!624.!!

Botvinick,!M.!M.,!Cohen,!J.!D.,!&!Carter,!C.!S.!(2004).!Conflict!monitoring!and!anterior!cingulate!cortex:!An!update.!Trends!in!Cognitive!Sciences,!8(12),!5392546.!!

Botvinick,!M.!M.,!Huffstetler,!S.,!&!McGuire,!J.!T.!(2009).!Effort!discounting!in!human!nucleus!accumbens.!Cognitive,!Affective,!&!Behavioral!Neuroscience,!9(1),!16227.!!

Botvinick,!M.,!Nystrom,!L.!E.,!Fissell,!K.,!Carter,!C.!S.,!&!Cohen,!J.!D.!(1999).!Conflict!monitoring!versus!selection2for2action!in!anterior!cingulate!cortex.!Nature,!402(6758),!1792181.!!

Brass,!M.,!Ullsperger,!M.,!Knoesche,!T.!R.,!von!Cramon,!D.!Y.,!&!Phillips,!N.!A.!(2005).!Who!comes!first?!the!role!of!the!prefrontal!and!parietal!cortex!in!cognitive!control.!Journal!of!Cognitive!Neuroscience,!17(9),!136721375.!doi:10.1162/0898929054985400!!

Brass,!M.,!&!von!Cramon,!D.!Y.!(2004).!Decomposing!components!of!task!preparation!with!functional!magnetic!resonance!imaging.!Journal!of!Cognitive!Neuroscience,!16(4),!6092620.!doi:10.1162/089892904323057335!!

Braver,!T.!S.,!Gray,!J.!R.,!&!Burgess,!G.!C.!(2007).!Explaining!the!many!varieties!of!working!memory!variation:!Dual!mechanisms!of!cognitive!control.!Variation!in!Working!Memory,!,!762106.!!

Braver,!T.!S.,!Paxton,!J.!L.,!Locke,!H.!S.,!&!Barch,!D.!M.!(2009).!Flexible!neural!mechanisms!of!cognitive!control!within!human!prefrontal!cortex.!Proceedings!of!the!National!Academy!of!Sciences!of!the!United!States!of!America,!106(18),!735127356.!doi:10.1073/pnas.0808187106!

Braver,!T.!S.,!Reynolds,!J.!R.,!&!Donaldson,!D.!I.!(2003).!Neural!mechanisms!of!transient!and!sustained!cognitive!control!during!task!switching.!Neuron,!39(4),!7132726.!!

Bressler,!S.!L.!(1995).!Large2scale!cortical!networks!and!cognition.!Brain!Research.Brain!Research!Reviews,!20(3),!2882304.!!

Bruyer,!R.,!&!Brysbaert,!M.!(2011).!Combining!speed!and!accuracy!in!cognitive!psychology:!Is!the!inverse!efficiency!score!(IES)!a!better!dependent!variable!than!the!mean!reaction!time!(RT)!and!the!percentage!of!errors!(PE)?!Psychologica!Belgica,!51(1),!5.!!

Buckner,!R.!L.,!Head,!D.,!Parker,!J.,!Fotenos,!A.!F.,!Marcus,!D.,!Morris,!J.!C.,!&!Snyder,!A.!Z.!(2004).!A!unified!approach!for!morphometric!and!functional!data!analysis!in!young,!old,!and!demented!adults!using!automated!atlas2based!head!size!normalization:!Reliability!and!validation!against!manual!measurement!of!total!intracranial!volume.!Neuroimage,!23(2),!7242738.!!

!

109!

Bullmore,!E.,!&!Sporns,!O.!(2009).!Complex!brain!networks:!Graph!theoretical!analysis!of!structural!and!functional!systems.!Nature!Reviews.Neuroscience,!10(3),!1862198.!doi:10.1038/nrn2575!!

Burzynska,!A.!Z.,!Preuschhof,!C.,!Bäckman,!L.,!Nyberg,!L.,!Li,!S.,!Lindenberger,!U.,!&!Heekeren,!H.!R.!(2010).!Age2related!differences!in!white!matter!microstructure:!Region2specific!patterns!of!diffusivity.!Neuroimage,!49(3),!210422112.!!

Burzynska,!A.!Z.,!Nagel,!I.!E.,!Preuschhof,!C.,!Li,!S.!C.,!Lindenberger,!U.,!Backman,!L.,!&!Heekeren,!H.!R.!(2011).!Microstructure!of!frontoparietal!connections!predicts!cortical!responsivity!and!working!memory!performance.!Cerebral!Cortex!(New!York,!N.Y.:!1991),!21(10),!226122271.!doi:10.1093/cercor/bhq293![doi]!!

Cabeza,!R.!(2002).!Hemispheric!asymmetry!reduction!in!older!adults:!The!HAROLD!model.!Psychology!and!Aging,!17(1),!85.!!

Carter,!C.!S.,!&!Van!Veen,!V.!(2007).!Anterior!cingulate!cortex!and!conflict!detection:!An!update!of!theory!and!data.!Cognitive,!Affective,!&!Behavioral!Neuroscience,!7(4),!3672379.!!

Cashdollar,!N.,!Fukuda,!K.,!Bocklage,!A.,!Aurtenetxe,!S.,!Vogel,!E.!K.,!&!Gazzaley,!A.!(2013).!Prolonged!disengagement!from!attentional!capture!in!normal!aging.!Psychology!and!Aging,!28(1),!77.!!

Cohen,!A.!L.,!Fair,!D.!A.,!Dosenbach,!N.!U.,!Miezin,!F.!M.,!Dierker,!D.,!Van!Essen,!D.!C.,!.!.!.!Petersen,!S.!E.!(2008).!Defining!functional!areas!in!individual!human!brains!using!resting!functional!connectivity!MRI.!Neuroimage,!41(1),!45257.!doi:10.1016/j.neuroimage.2008.01.066!!

Colcombe,!A.!M.,!Kramer,!A.!F.,!Irwin,!D.!E.,!Peterson,!M.!S.,!Colcombe,!S.,!&!Hahn,!S.!(2003).!Age2related!effects!of!attentional!and!oculomotor!capture!by!onsets!and!color!singletons!as!a!function!of!experience.!Acta!Psychologica,!113(2),!2052225.!doi:http://dx.doi.org/10.1016/S000126918(03)0001922!

Colcombe,!S.,!&!Kramer,!A.!F.!(2003).!Fitness!effects!on!the!cognitive!function!of!older!adults:!A!meta2analytic!study.!Psychological!Science,!14(2),!1252130.!doi:10.1111/146729280.t0121201430!!

Coles,!M.!G.!(1989).!Modern!mind2brain!reading:!Psychophysiology,!physiology,!and!cognition.!Psychophysiology,!26(3),!2512269.!!

Corbetta,!M.,!&!Shulman,!G.!L.!(2002).!Control!of!goal2directed!and!stimulus2driven!attention!in!the!brain.!Nature!Reviews.Neuroscience,!3(3),!2012215.!doi:10.1038/nrn755!!

!

110!

Coull,!J.,!&!Frith,!C.!(1998).!Differential!activation!of!right!superior!parietal!cortex!and!intraparietal!sulcus!by!spatial!and!nonspatial!attention.!Neuroimage,!8(2),!1762187.!!

Courchesne,!E.,!Chisum,!H.!J.,!Townsend,!J.,!Cowles,!A.,!Covington,!J.,!Egaas,!B.,!.!.!.!Press,!G.!A.!(2000).!Normal!brain!development!and!aging:!Quantitative!analysis!at!in!vivo!MR!imaging!in!healthy!volunteers!1.!Radiology,!216(3),!6722682.!!

Craik,!F.!I.,!&!Byrd,!M.!(1982).!Aging!and!cognitive!deficits.!Aging!and!cognitive!processes!(pp.!1912211)!Springer.!!

Dale,!A.!M.,!Fischl,!B.,!&!Sereno,!M.!I.!(1999).!Cortical!surface2based!analysis:!I.!segmentation!and!surface!reconstruction.!Neuroimage,!9(2),!1792194.!!

Davatzikos,!C.,!&!Resnick,!S.!M.!(2002).!Degenerative!age!changes!in!white!matter!connectivity!visualized!in!vivo!using!magnetic!resonance!imaging.!Cerebral!Cortex!(New!York,!N.Y.:!1991),!12(7),!7672771.!!

Davis,!S.!W.,!Dennis,!N.!A.,!Buchler,!N.!G.,!White,!L.!E.,!Madden,!D.!J.,!&!Cabeza,!R.!(2009).!Assessing!the!effects!of!age!on!long!white!matter!tracts!using!diffusion!tensor!tractography.!Neuroimage,!46(2),!5302541.!!

De!Jong,!R.,!Wierda,!M.,!Mulder,!G.,!&!Mulder,!L.!J.!(1988).!Use!of!partial!stimulus!information!in!response!processing.!Journal!of!Experimental!Psychology:!Human!Perception!and!Performance,!14(4),!682.!!

de!Pasquale,!F.,!Della!Penna,!S.,!Snyder,!A.!Z.,!Lewis,!C.,!Mantini,!D.,!Marzetti,!L.,!.!.!.!Corbetta,!M.!(2010).!Temporal!dynamics!of!spontaneous!MEG!activity!in!brain!networks.!Proceedings!of!the!National!Academy!of!Sciences!of!the!United!States!of!America,!107(13),!604026045.!doi:10.1073/pnas.0913863107!!

Desikan,!R.!S.,!Ségonne,!F.,!Fischl,!B.,!Quinn,!B.!T.,!Dickerson,!B.!C.,!Blacker,!D.,!.!.!.!Hyman,!B.!T.!(2006).!An!automated!labeling!system!for!subdividing!the!human!cerebral!cortex!on!MRI!scans!into!gyral!based!regions!of!interest.!Neuroimage,!31(3),!9682980.!!

Desoto,!M.!C.,!Fabiani,!M.,!Geary,!D.!C.,!&!Gratton,!G.!(2001).!When!in!doubt,!do!it!both!ways:!Brain!evidence!of!the!simultaneous!activation!of!conflicting!motor!responses!in!a!spatial!stroop!task.!Journal!of!Cognitive!Neuroscience,!13(4),!5232536.!!

DiGirolamo,!G.!J.,!Kramer,!A.!F.,!Barad,!V.,!Cepeda,!N.!J.,!Weissman,!D.!H.,!Milham,!M.!P.,!.!.!.!Webb,!A.!(2001).!General!and!task2specific!frontal!lobe!recruitment!in!older!adults!during!executive!processes:!A!fMRI!investigation!of!task2switching.!Neuroreport,!12(9),!206522071.!!

Dosenbach,!N.!U.,!Visscher,!K.!M.,!Palmer,!E.!D.,!Miezin,!F.!M.,!Wenger,!K.!K.,!Kang,!H.!C.,!.!.!.!Petersen,!S.!E.!(2006).!A!core!system!for!the!implementation!of!task!sets.!Neuron,!50(5),!7992812.!doi:10.1016/j.neuron.2006.04.031!!

!

111!

Egner,!T.!(2007).!Congruency!sequence!effects!and!cognitive!control.!Cognitive,!Affective,!&!Behavioral!Neuroscience,!7(4),!3802390.!!

Egner,!T.!(2008).!Multiple!conflict2driven!control!mechanisms!in!the!human!brain.!Trends!in!Cognitive!Sciences,!12(10),!3742380.!!

Egner,!T.,!&!Hirsch,!J.!(2005).!Cognitive!control!mechanisms!resolve!conflict!through!cortical!amplification!of!task2relevant!information.!Nature!Neuroscience,!8(12),!178421790.!!

Egner,!T.,!&!Hirsch,!J.!(2005).!The!neural!correlates!and!functional!integration!of!cognitive!control!in!a!stroop!task.!Neuroimage,!24(2),!5392547.!!

Eppinger,!B.,!Kray,!J.,!Mecklinger,!A.,!&!John,!O.!(2007).!Age!differences!in!task!switching!and!response!monitoring:!Evidence!from!ERPs.!Biological!Psychology,!75(1),!52267.!!

Fabiani,!M.,!Low,!K.!A.,!Tan,!C.,!Zimmerman,!B.,!Fletcher,!M.!A.,!Schneider2Garces,!N.,!.!.!.!Gratton,!G.!(2014).!Taking!the!pulse!of!aging:!Mapping!pulse!pressure!and!elasticity!in!cerebral!arteries!with!optical!methods.!Psychophysiology,!51(11),!107221088.!

Fabiani,!M.!(2012).!It!was!the!best!of!times,!it!was!the!worst!of!times:!A!psychophysiologist's!view!of!cognitive!aging.!Psychophysiology,!49(3),!2832304.!!

Fabiani,!M.,!&!Friedman,!D.!(1995).!Changes!in!brain!activity!patterns!in!aging:!The!novelty!oddball.!Psychophysiology,!32(6),!5792594.!!

Falkenstein,!M.,!Yordanova,!J.,!&!Kolev,!V.!(2006).!Effects!of!aging!on!slowing!of!motor2response!generation.!International!Journal!of!Psychophysiology,!59(1),!22229.!doi:http://dx.doi.org/10.1016/j.ijpsycho.2005.08.004!

Fischl,!B.,!Salat,!D.!H.,!Busa,!E.,!Albert,!M.,!Dieterich,!M.,!Haselgrove,!C.,!.!.!.!Klaveness,!S.!(2002).!Whole!brain!segmentation:!Automated!labeling!of!neuroanatomical!structures!in!the!human!brain.!Neuron,!33(3),!3412355.!!

Fischl,!B.,!Salat,!D.!H.,!van!der!Kouwe,!André!JW,!Makris,!N.,!Ségonne,!F.,!Quinn,!B.!T.,!&!Dale,!A.!M.!(2004).!Sequence2independent!segmentation!of!magnetic!resonance!images.!Neuroimage,!23,!S692S84.!!

Fischl,!B.,!van!der!Kouwe,!A.,!Destrieux,!C.,!Halgren,!E.,!Segonne,!F.,!Salat,!D.!H.,!.!.!.!Dale,!A.!M.!(2004).!Automatically!parcellating!the!human!cerebral!cortex.!Cerebral!Cortex!(New!York,!N.Y.:!1991),!14(1),!11222.!!

Foust,!A.!J.,!&!Rector,!D.!M.!(2007).!Optically!teasing!apart!neural!swelling!and!depolarization.!Neuroscience,!145(3),!8872899.!doi:10.1016/j.neuroscience.2006.12.068!!

!

112!

Fox,!M.!D.,!Snyder,!A.!Z.,!Vincent,!J.!L.,!Corbetta,!M.,!Van!Essen,!D.!C.,!&!Raichle,!M.!E.!(2005).!The!human!brain!is!intrinsically!organized!into!dynamic,!anticorrelated!functional!networks.!Proceedings!of!the!National!Academy!of!Sciences!of!the!United!States!of!America,!102(27),!967329678.!doi:10.1073/pnas.0504136102!!

Freitas,!A.!L.,!Bahar,!M.,!Yang,!S.,!&!Banai,!R.!(2007).!Contextual!adjustments!in!cognitive!control!across!tasks.!Psychological!Science,!18(12),!104021043.!doi:PSCI2022![pii]!!

Friedman,!D.,!Nessler,!D.,!Johnson!Jr,!R.,!Ritter,!W.,!&!Bersick,!M.!(2007).!Age2related!changes!in!executive!function:!An!event2related!potential!(ERP)!investigation!of!task2switching.!Aging,!Neuropsychology,!and!Cognition,!15(1),!952128.!!

Fukuda,!K.,!&!Vogel,!E.!K.!(2011).!Individual!differences!in!recovery!time!from!attentional!capture.!Psychological!Science,!22(3),!3612368.!!

Gazzaley,!A.,!Cooney,!J.!W.,!Rissman,!J.,!&!D'Esposito,!M.!(2005).!Top2down!suppression!deficit!underlies!working!memory!impairment!in!normal!aging.!Nature!Neuroscience,!8(10),!129821300.!!

Gehring,!W.!J.,!Gratton,!G.,!Coles,!M.!G.,!&!Donchin,!E.!(1992).!Probability!effects!on!stimulus!evaluation!and!response!processes.!Journal!of!Experimental!Psychology:!Human!Perception!and!Performance,!18(1),!198.!!

Gevins,!A.!S.,!Schaffer,!R.!E.,!Doyle,!J.!C.,!Cutillo,!B.!A.,!Tannehill,!R.!S.,!&!Bressler,!S.!L.!(1983).!Shadows!of!thought:!Shifting!lateralization!of!human!brain!electrical!patterns!during!brief!visuomotor!task.!Science!(New!York,!N.Y.),!220(4592),!97299.!!

Ghinescu,!R.,!Schachtman,!T.!R.,!Stadler,!M.!A.,!Fabiani,!M.,!&!Gratton,!G.!(2010).!Strategic!behavior!without!awareness?!effects!of!implicit!learning!in!the!eriksen!flanker!paradigm.!Memory!&!Cognition,!38(2),!1972205.!!

Gilbert,!S.!J.,!&!Shallice,!T.!(2002).!Task!switching:!A!PDP!model.!Cognitive!Psychology,!44(3),!2972337.!doi:10.1006/cogp.2001.0770!!

Gold,!B.!T.,!Powell,!D.!K.,!Xuan,!L.,!Jicha,!G.!A.,!&!Smith,!C.!D.!(2010).!Age2related!slowing!of!task!switching!is!associated!with!decreased!integrity!of!frontoparietal!white!matter.!Neurobiology!of!Aging,!31(3),!5122522.!!

Gordon,!B.!A.,!Rykhlevskaia,!E.!I.,!Brumback,!C.!R.,!Lee,!Y.,!Elavsky,!S.,!Konopack,!J.!F.,!.!.!.!Gratton,!G.!(2008).!Neuroanatomical!correlates!of!aging,!cardiopulmonary!fitness!level,!and!education.!Psychophysiology,!45(5),!8252838.!!

Grady,!C.!L.!(2008).!Cognitive!neuroscience!of!aging.!Annals!of!the!New!York!Academy!of!Sciences,!1124(1),!1272144.!!

!

113!

Grady,!C.!L.,!Protzner,!A.!B.,!Kovacevic,!N.,!Strother,!S.!C.,!Afshin2Pour,!B.,!Wojtowicz,!M.,!.!.!.!McIntosh,!A.!R.!(2010).!A!multivariate!analysis!of!age2related!differences!in!default!mode!and!task2positive!networks!across!multiple!cognitive!domains.!Cerebral!Cortex!(New!York,!N.Y.:!1991),!20(6),!143221447.!doi:10.1093/cercor/bhp207![doi]!!

Gratton,!C.,!Nomura,!E.!M.,!Pérez,!F.,!&!D'Esposito,!M.!(2012).!Focal!brain!lesions!to!critical!locations!cause!widespread!disruption!of!the!modular!organization!of!the!brain.!Journal!of!Cognitive!Neuroscience,!24(6),!127521285.!!

Gratton,!G.,!Coles,!M.!G.,!&!Donchin,!E.!(1989).!A!procedure!for!using!Multi2Electrode!information!in!the!analysis!of!components!of!the!Event2Related!potential:!Vector!filter.!Psychophysiology,!26(2),!2222232.!!

Gratton,!G.,!Coles,!M.!G.,!&!Donchin,!E.!(1992).!Optimizing!the!use!of!information:!Strategic!control!of!activation!of!responses.!Journal!of!Experimental!Psychology:!General,!121(4),!480.!!

Gratton,!G.,!Coles,!M.!G.,!Sirevaag,!E.!J.,!Eriksen,!C.!W.,!&!Donchin,!E.!(1988).!Pre2and!poststimulus!activation!of!response!channels:!A!psychophysiological!analysis.!Journal!of!Experimental!Psychology:!Human!Perception!and!Performance,!14(3),!331.!!

Gratton,!G.,!Brumback,!C.!R.,!Gordon,!B.!A.,!Pearson,!M.!A.,!Low,!K.!A.,!&!Fabiani,!M.!(2006).!Effects!of!measurement!method,!wavelength,!and!source2detector!distance!on!the!fast!optical!signal.!Neuroimage,!32(4),!157621590.!doi:10.1016/j.neuroimage.2006.05.030!!

Gratton,!G.,!Coles,!M.!G.,!&!Donchin,!E.!(1983).!A!new!method!for!off2line!removal!of!ocular!artifact.!Electroencephalography!and!Clinical!Neurophysiology,!55(4),!4682484.!!

Gratton,!G.,!&!Corballis,!P.!M.!(1995).!Removing!the!heart!from!the!brain:!Compensation!for!the!pulse!artifact!in!the!photon!migration!signal.!Psychophysiology,!32(3),!2922299.!!

Gratton,!G.,!&!Fabiani,!M.!(2010).!Fast!optical!imaging!of!human!brain!function.!Frontiers!in!Human!Neuroscience,!4,!52.!doi:10.3389/fnhum.2010.00052!!

Gratton,!G.,!Wee,!E.,!Rykhlevskaia,!E.!I.,!Leaver,!E.!E.,!&!Fabiani,!M.!(2009).!Does!white!matter!matter?!spatio2temporal!dynamics!of!task!switching!in!aging.!Journal!of!Cognitive!Neuroscience,!21(7),!138021395.!doi:10.1162/jocn.2009.21093!!

Gratton,!G.,!&!Fabiani,!M.!(2001).!The!event2related!optical!signal:!A!new!tool!for!studying!brain!function.!International!Journal!of!Psychophysiology,!42(2),!1092121.!doi:http://dx.doi.org/10.1016/S016728760(01)0016121!

Green,!J.!J.,!&!McDonald,!J.!J.!(2008).!Electrical!neuroimaging!reveals!timing!of!attentional!control!activity!in!human!brain.!PLoS!Biol,!6(4),!e81!EP!2.!!

!

114!

Greenwood,!P.!M.,!Parasuraman,!R.,!&!Alexander,!G.!E.!(1997).!Controlling!the!focus!of!spatial!attention!during!visual!search:!Effects!of!advanced!aging!and!alzheimer!disease.!Neuropsychology,!11(1),!3.!!

Gross,!J.,!Kujala,!J.,!Hamalainen,!M.,!Timmermann,!L.,!Schnitzler,!A.,!&!Salmelin,!R.!(2001).!Dynamic!imaging!of!coherent!sources:!Studying!neural!interactions!in!the!human!brain.!Proceedings!of!the!National!Academy!of!Sciences!of!the!United!States!of!America,!98(2),!6942699.!doi:10.1073/pnas.98.2.694!!

Gunning2Dixon,!F.!M.,!Brickman,!A.!M.,!Cheng,!J.!C.,!&!Alexopoulos,!G.!S.!(2009).!Aging!of!cerebral!white!matter:!A!review!of!MRI!findings.!International!Journal!of!Geriatric!Psychiatry,!24(2),!1092117.!!

Guttmann,!C.!R.,!Benson,!R.,!Warfield,!S.!K.,!Wei,!X.,!Anderson,!M.!C.,!Hall,!C.!B.,!.!.!.!Wolfson,!L.!(2000).!White!matter!abnormalities!in!mobility2impaired!older!persons.!Neurology,!54(6),!127721283.!!

Hanslmayr,!S.,!Pastötter,!B.,!Bäuml,!K.,!Gruber,!S.,!Wimber,!M.,!&!Klimesch,!W.!(2008).!The!electrophysiological!dynamics!of!interference!during!the!stroop!task.!Journal!of!Cognitive!Neuroscience,!20(2),!2152225.!!

Hasher,!L.,!&!Zacks,!R.!T.!(1988).!Working!memory,!comprehension,!and!aging:!A!review!and!a!new!view.!Psychology!of!Learning!and!Motivation,!22,!1932225.!!

Hasher,!L.,!Zacks,!R.!T.,!&!May,!C.!P.!(1999).!Inhibitory!control,!circadian!arousal,!and!age.!!

Head,!D.,!Buckner,!R.!L.,!Shimony,!J.!S.,!Williams,!L.!E.,!Akbudak,!E.,!Conturo,!T.!E.,!.!.!.!Snyder,!A.!Z.!(2004).!Differential!vulnerability!of!anterior!white!matter!in!nondemented!aging!with!minimal!acceleration!in!dementia!of!the!alzheimer!type:!Evidence!from!diffusion!tensor!imaging.!Cerebral!Cortex!(New!York,!N.Y.:!1991),!14(4),!4102423.!!

Herd,!S.!A.,!Banich,!M.!T.,!&!O'Reilly,!R.!C.!(2006).!Neural!mechanisms!of!cognitive!control:!An!integrative!model!of!stroop!task!performance!and!FMRI!data.!Journal!of!Cognitive!Neuroscience,!18(1),!22232.!doi:10.1162/089892906775250012!!

Hillman,!C.!H.,!Kramer,!A.!F.,!Belopolsky,!A.!V.,!&!Smith,!D.!P.!(2006).!A!cross2sectional!examination!of!age!and!physical!activity!on!performance!and!event2related!brain!potentials!in!a!task!switching!paradigm.!International!Journal!of!Psychophysiology,!59(1),!30239.!!

Hopfinger,!J.!B.,!Buonocore,!M.!H.,!&!Mangun,!G.!R.!(2000).!The!neural!mechanisms!of!top2down!attentional!control.!Nature!Neuroscience,!3(3),!2842291.!doi:10.1038/72999!!

Jack,!C.!R.,Jr,!Twomey,!C.!K.,!Zinsmeister,!A.!R.,!Sharbrough,!F.!W.,!Petersen,!R.!C.,!&!Cascino,!G.!D.!(1989).!Anterior!temporal!lobes!and!hippocampal!formations:!Normative!

!

115!

volumetric!measurements!from!MR!images!in!young!adults.!Radiology,!172(2),!5492554.!doi:10.1148/radiology.172.2.2748838![doi]!!

Jamadar,!S.,!Hughes,!M.,!Fulham,!W.!R.,!Michie,!P.!T.,!&!Karayanidis,!F.!(2010).!The!spatial!and!temporal!dynamics!of!anticipatory!preparation!and!response!inhibition!in!task2switching.!Neuroimage,!51(1),!4322449.!doi:10.1016/j.neuroimage.2010.01.090!!

Jersild,!A.!T.!(1927).!Mental!set!and!shift.!Archives!of!Psychology,!!

Jost,!K.,!Mayr,!U.,!&!Rösler,!F.!(2008).!Is!task!switching!nothing!but!cue!priming?!evidence!from!ERPs.!Cognitive,!Affective,!&!Behavioral!Neuroscience,!8(1),!74284.!!

Kane,!M.!J.,!Hambrick,!D.!Z.,!&!Conway,!A.!R.!(2005).!Working!memory!capacity!and!fluid!intelligence!are!strongly!related!constructs:!Comment!on!ackerman,!beier,!and!boyle!(2005).!!

Kane,!M.!J.,!Hambrick,!D.!Z.,!Tuholski,!S.!W.,!Wilhelm,!O.,!Payne,!T.!W.,!&!Engle,!R.!W.!(2004).!The!generality!of!working!memory!capacity:!A!latent2variable!approach!to!verbal!and!visuospatial!memory!span!and!reasoning.!Journal!of!Experimental!Psychology:!General,!133(2),!189.!!

Karayanidis,!F.,!Provost,!A.,!Brown,!S.,!Paton,!B.,!&!Heathcote,!A.!(2011).!Switch2specific!and!general!preparation!map!onto!different!ERP!components!in!a!task2switching!paradigm.!Psychophysiology,!48(4),!5592568.!!

Karayanidis,!F.,!Jamadar,!S.,!Ruge,!H.,!Phillips,!N.,!Heathcote,!A.,!&!Forstmann,!B.!U.!(2010).!Advance!preparation!in!task2switching:!Converging!evidence!from!behavioral,!brain!activation,!and!model2based!approaches.!Frontiers!in!Psychology,!1,!25.!doi:10.3389/fpsyg.2010.00025!!

Karayanidis,!F.,!Coltheart,!M.,!Michie,!P.!T.,!&!Murphy,!K.!(2003).!Electrophysiological!correlates!of!anticipatory!and!poststimulus!components!of!task!switching.!Psychophysiology,!40(3),!3292348.!doi:10.1111/146928986.00037!!

Kerns,!J.!G.,!Cohen,!J.!D.,!MacDonald,!A.!W.,3rd,!Cho,!R.!Y.,!Stenger,!V.!A.,!&!Carter,!C.!S.!(2004).!Anterior!cingulate!conflict!monitoring!and!adjustments!in!control.!Science!(New!York,!N.Y.),!303(5660),!102321026.!doi:10.1126/science.1089910!

Kerns,!J.!G.!(2006).!Anterior!cingulate!and!prefrontal!cortex!activity!in!an!FMRI!study!of!trial2to2trial!adjustments!on!the!simon!task.!Neuroimage,!33(1),!3992405.!doi:http://dx.doi.org/10.1016/j.neuroimage.2006.06.012!

Kerns,!J.!G.,!Cohen,!J.!D.,!MacDonald,!A.!W.,!Cho,!R.!Y.,!Stenger,!V.!A.,!&!Carter,!C.!S.!(2004).!Anterior!cingulate!conflict!monitoring!and!adjustments!in!control.!Science,!303(5660),!102321026.!doi:10.1126/science.1089910!!

!

116!

Kiebel,!S.!J.,!Poline,!J.!B.,!Friston,!K.!J.,!Holmes,!A.!P.,!&!Worsley,!K.!J.!(1999).!Robust!smoothness!estimation!in!statistical!parametric!maps!using!standardized!residuals!from!the!general!linear!model.!Neuroimage,!10(6),!7562766.!doi:10.1006/nimg.1999.0508!!

Kieffaber,!P.!D.,!&!Hetrick,!W.!P.!(2005).!Event2related!potential!correlates!of!task!switching!and!switch!costs.!Psychophysiology,!42(1),!56271.!!

Kim,!C.,!Cilles,!S.!E.,!Johnson,!N.!F.,!&!Gold,!B.!T.!(2012).!Domain!general!and!domain!preferential!brain!regions!associated!with!different!types!of!task!switching:!A!meta2analysis.!Human!Brain!Mapping,!33(1),!1302142.!doi:10.1002/hbm.21199;!10.1002/hbm.21199!!

Kim,!C.,!Johnson,!N.!F.,!Cilles,!S.!E.,!&!Gold,!B.!T.!(2011).!Common!and!distinct!mechanisms!of!cognitive!flexibility!in!prefrontal!cortex.!The!Journal!of!Neuroscience!:!The!Official!Journal!of!the!Society!for!Neuroscience,!31(13),!477124779.!doi:10.1523/JNEUROSCI.5923210.2011!!

King,!J.!A.,!Korb,!F.!M.,!&!Egner,!T.!(2012).!Priming!of!control:!Implicit!contextual!cuing!of!top2down!attentional!set.!The!Journal!of!Neuroscience!:!The!Official!Journal!of!the!Society!for!Neuroscience,!32(24),!819228200.!doi:10.1523/JNEUROSCI.0934212.2012![doi]!!

Kool,!W.,!McGuire,!J.!T.,!Rosen,!Z.!B.,!&!Botvinick,!M.!M.!(2010).!Decision!making!and!the!avoidance!of!cognitive!demand.!Journal!of!Experimental!Psychology:!General,!139(4),!665.!!

KORNHUBER,!H.!H.,!&!DEECKE,!L.!(1965).!Changes!in!the!brain!potential!in!voluntary!movements!and!passive!movements!in!man:!Readiness!potential!and!reafferent!potentials.![HIRNPOTENTIALAENDERUNGEN!BEI!WILLKUERBEWEGUNGEN!UND!PASSIVEN!BEWEGUNGEN!DES!MENSCHEN:!BEREITSCHAFTSPOTENTIAL!UND!REAFFERENTE!POTENTIALE]!Pflugers!Archiv!Fur!Die!Gesamte!Physiologie!Des!Menschen!Und!Der!Tiere,!284,!1217.!!

Kramer,!A.!F.,!Fabiani,!M.,!&!Colcombe,!S.!J.!(2006).!Contributions!of!cognitive!neuroscience!to!the!understanding!of!behavior!and!aging.!Handbook!of!the!Psychology!of!Aging,!6,!57283.!!

Kramer,!A.!F.,!Hahn,!S.,!Irwin,!D.!E.,!&!Theeuwes,!J.!(1999).!Attentional!capture!and!aging:!Implications!for!visual!search!performance!and!oculomotor!control.!Psychology!and!Aging,!14(1),!135.!!

Kramer,!A.!F.,!Larish,!J.!L.,!Weber,!T.!A.,!&!Bardell,!L.!(1999).!Training!for!executive!control:!Task!coordination!strategies!and!aging.!!

Kray,!J.,!Eppinger,!B.,!&!Mecklinger,!A.!(2005).!Age!differences!in!attentional!control:!An!event2related!potential!approach.!Psychophysiology,!42(4),!4072416.!!

!

117!

Kutas,!M.,!&!Donchin,!E.!(1980).!Preparation!to!respond!as!manifested!by!movement2related!brain!potentials.!Brain!Research,!202(1),!952115.!!

Lancaster,!J.!L.,!Rainey,!L.!H.,!Summerlin,!J.!L.,!Freitas,!C.!S.,!Fox,!P.!T.,!Evans,!A.!C.,!.!.!.!Mazziotta,!J.!C.!(1997).!Automated!labeling!of!the!human!brain:!A!preliminary!report!on!the!development!and!evaluation!of!a!forward2transform!method.!Human!Brain!Mapping,!5(4),!2382242.!doi:224!!

Lancaster,!J.!L.,!Woldorff,!M.!G.,!Parsons,!L.!M.,!Liotti,!M.,!Freitas,!C.!S.,!Rainey,!L.,!.!.!.!Fox,!P.!T.!(2000).!Automated!talairach!atlas!labels!for!functional!brain!mapping.!Human!Brain!Mapping,!10(3),!1202131.!!

Larson,!M.!J.,!Kaufman,!D.!A.!S.,!&!Perlstein,!W.!M.!(2009).!Neural!time!course!of!conflict!adaptation!effects!on!the!stroop!task.!Neuropsychologia,!47(3),!6632670.!doi:http://dx.doi.org/10.1016/j.neuropsychologia.2008.11.013!

Liston,!C.,!Matalon,!S.,!Hare,!T.!A.,!Davidson,!M.!C.,!&!Casey,!B.!(2006).!Anterior!cingulate!and!posterior!parietal!cortices!are!sensitive!to!dissociable!forms!of!conflict!in!a!task2switching!paradigm.!Neuron,!50(4),!6432653.!!

Lustig,!C.,!Hasher,!L.,!&!Zacks,!R.!T.!(2007).!Inhibitory!deficit!theory:!Recent!developments!in!a!“new!view.”.!Inhibition!in!Cognition,!,!1452162.!!

Maclin,!E.!L.,!Low,!K.!A.,!Fabiani,!M.,!&!Gratton,!G.!(2007).!Improving!the!signal2to2noise!ratio!of!event2related!optical!signals.!IEEE!Engineering!in!Medicine!and!Biology!Magazine!:!The!Quarterly!Magazine!of!the!Engineering!in!Medicine!&!Biology!Society,!26(4),!47251.!!

Maclin,!E.!L.,!Low,!K.!A.,!Sable,!J.!J.,!Fabiani,!M.,!&!Gratton,!G.!(2004).!The!event2related!optical!signal!to!electrical!stimulation!of!the!median!nerve.!Neuroimage,!21(4),!179821804.!doi:10.1016/j.neuroimage.2003.11.019!!

Madden,!D.!J.,!Costello,!M.!C.,!Dennis,!N.!A.,!Davis,!S.!W.,!Shepler,!A.!M.,!Spaniol,!J.,!.!.!.!Cabeza,!R.!(2010).!Adult!age!differences!in!functional!connectivity!during!executive!control.!Neuroimage,!52(2),!6432657.!!

Madden,!D.!J.,!Whiting,!W.!L.,!&!Huettel,!S.!A.!(2005).!Age2related!changes!in!neural!activity!during!visual!perception!and!attention.!Cognitive!Neuroscience!of!Aging:!Linking!Cognitive!and!Cerebral!Aging,!,!1572185.!!

Madden,!D.!J.!(2007).!Aging!and!visual!attention.!Current!Directions!in!Psychological!Science,!16(2),!70274.!doi:10.1111/j.146728721.2007.00478.x![doi]!!

Mathewson,!K.!E.,!Beck,!D.!M.,!Ro,!T.,!Maclin,!E.!L.,!Low,!K.!A.,!Fabiani,!M.,!&!Gratton,!G.!(2014).!Dynamics!of!alpha!control:!Preparatory!suppression!of!posterior!alpha!

!

118!

oscillations!by!frontal!modulators!revealed!with!combined!EEG!and!event2related!optical!signal.!!

Mayeux,!R.,!Stern,!Y.,!Rosen,!J.,!&!Leventhal,!J.!(1981).!Depression,!intellectual!impairment,!and!parkinson!disease.!Neurology,!31(6),!6452650.!!

Mayr,!U.,!Awh,!E.,!&!Laurey,!P.!(2003).!Conflict!adaptation!effects!in!the!absence!of!executive!control.!Nature!Neuroscience,!6(5),!4502452.!!

Mayr,!U.,!Kuhns,!D.,!&!Rieter,!M.!(2013).!Eye!movements!reveal!dynamics!of!task!control.!Journal!of!Experimental!Psychology:!General,!142(2),!489.!!

McGuire,!J.!T.,!&!Botvinick,!M.!M.!(2010).!Prefrontal!cortex,!cognitive!control,!and!the!registration!of!decision!costs.!Proceedings!of!the!National!Academy!of!Sciences!of!the!United!States!of!America,!107(17),!792227926.!doi:10.1073/pnas.0910662107![doi]!!

Meiran,!N.!(1996).!Reconfiguration!of!processing!mode!prior!to!task!performance.!Journal!of!Experimental!Psychology:!Learning,!Memory,!and!Cognition,!22(6),!1423.!!

Meiran,!N.!(2000).!Modeling!cognitive!control!in!task2switching.!Psychological!Research,!63(324),!2342249.!!

Mesulam,!M.!M.!(1990).!Large2scale!neurocognitive!networks!and!distributed!processing!for!attention,!language,!and!memory.!Annals!of!Neurology,!28(5),!5972613.!doi:10.1002/ana.410280502!!

Miller,!J.,!Patterson,!T.,!&!Ulrich,!R.!(1998).!Jackknife2based!method!for!measuring!LRP!onset!latency!differences.!Psychophysiology,!35(01),!992115.!!

Miller,!E.!K.,!&!Cohen,!J.!D.!(2001).!An!integrative!theory!of!prefrontal!cortex!function.!Annual!Review!of!Neuroscience,!24,!1672202.!doi:10.1146/annurev.neuro.24.1.167!!

Milner,!A.!D.,!&!Goodale,!M.!A.!(1993).!Visual!pathways!to!perception!and!action.!Progress!in!Brain!Research,!95,!3172337.!!

Monsell,!S.!(2003).!Task!switching.!Trends!in!Cognitive!Sciences,!7(3),!1342140.!!

Moussa,!M.!N.,!Vechlekar,!C.!D.,!Burdette,!J.!H.,!Steen,!M.!R.,!Hugenschmidt,!C.!E.,!&!Laurienti,!P.!J.!(2011).!Changes!in!cognitive!state!alter!human!functional!brain!networks.!Frontiers!in!Human!Neuroscience,!5,!83.!doi:10.3389/fnhum.2011.00083!!

Mueller,!S.,!Swainson,!R.,!&!Jackson,!G.!(2007).!Behavioural!and!neurophysiological!correlates!of!bivalent!and!univalent!responses!during!task!switching.!Brain!Research,!1157,!56265.!!

!

119!

Nagel,!I.!E.,!Preuschhof,!C.,!Li,!S.,!Nyberg,!L.,!Bäckman,!L.,!Lindenberger,!U.,!&!Heekeren,!H.!R.!(2011).!Load!modulation!of!BOLD!response!and!connectivity!predicts!working!memory!performance!in!younger!and!older!adults.!Journal!of!Cognitive!Neuroscience,!23(8),!203022045.!!

Nelson,!J.!K.,!Reuter2Lorenz,!P.!A.,!Persson,!J.,!Sylvester,!C.!Y.,!&!Jonides,!J.!(2009).!Mapping!interference!resolution!across!task!domains:!A!shared!control!process!in!left!inferior!frontal!gyrus.!Brain!Research,!1256,!922100.!doi:10.1016/j.brainres.2008.12.001!!

Nicholson,!R.,!Karayanidis,!F.,!Bumak,!E.,!Poboka,!D.,!&!Michie,!P.!T.!(2006).!ERPs!dissociate!the!effects!of!switching!task!sets!and!task!cues.!Brain!Research,!1095(1),!1072123.!!

O'Sullivan,!M.,!Jones,!D.!K.,!Summers,!P.!E.,!Morris,!R.!G.,!Williams,!S.!C.,!&!Markus,!H.!S.!(2001).!Evidence!for!cortical!"disconnection"!as!a!mechanism!of!age2related!cognitive!decline.!Neurology,!57(4),!6322638.!!

Park,!D.!C.,!Lautenschlager,!G.,!Hedden,!T.,!Davidson,!N.!S.,!Smith,!A.!D.,!&!Smith,!P.!K.!(2002).!Models!of!visuospatial!and!verbal!memory!across!the!adult!life!span.!Psychology!and!Aging,!17(2),!299.!!

Pastötter,!B.,!Dreisbach,!G.,!&!Bäuml,!K.!T.!(2013).!Dynamic!adjustments!of!cognitive!control:!Oscillatory!correlates!of!the!conflict!adaptation!effect.!Journal!of!Cognitive!Neuroscience,!25(12),!216722178.!!

Peltz,!C.!B.,!Gratton,!G.,!&!Fabiani,!M.!(2011).!Age2related!changes!in!electrophysiological!and!neuropsychological!indices!of!working!memory,!attention!control,!and!cognitive!flexibility.!Frontiers!in!Psychology,!2,!190.!doi:10.3389/fpsyg.2011.00190!

Perianez,!J.!A.,!Maestu,!F.,!Barcelo,!F.,!Fernandez,!A.,!Amo,!C.,!&!Ortiz!Alonso,!T.!(2004).!Spatiotemporal!brain!dynamics!during!preparatory!set!shifting:!MEG!evidence.!Neuroimage,!21(2),!6872695.!doi:10.1016/j.neuroimage.2003.10.008!!

Posner,!M.!I.,!&!Petersen,!S.!E.!(1990).!The!attention!system!of!the!human!brain.!Annual!Review!of!Neuroscience,!13,!25242.!doi:10.1146/annurev.ne.13.030190.000325!!

Pulvermuller,!F.,!Huss,!M.,!Kherif,!F.,!Moscoso!del!Prado!Martin,!F.,!Hauk,!O.,!&!Shtyrov,!Y.!(2006).!Motor!cortex!maps!articulatory!features!of!speech!sounds.!Proceedings!of!the!National!Academy!of!Sciences!of!the!United!States!of!America,!103(20),!786527870.!doi:10.1073/pnas.0509989103!!

Raz,!N.,!Gunning2Dixon,!F.!M.,!Head,!D.,!Dupuis,!J.!H.,!&!Acker,!J.!D.!(1998).!Neuroanatomical!correlates!of!cognitive!aging:!Evidence!from!structural!magnetic!resonance!imaging.!Neuropsychology,!12(1),!95.!!

Raz,!N.,!Lindenberger,!U.,!Rodrigue,!K.!M.,!Kennedy,!K.!M.,!Head,!D.,!Williamson,!A.,!.!.!.!Acker,!J.!D.!(2005).!Regional!brain!changes!in!aging!healthy!adults:!General!trends,!individual!

!

120!

differences!and!modifiers.!Cerebral!Cortex!(New!York,!N.Y.:!1991),!15(11),!167621689.!doi:bhi044![pii]!!

Rector,!D.!M.,!Carter,!K.!M.,!Volegov,!P.!L.,!&!George,!J.!S.!(2005).!Spatio2temporal!mapping!of!rat!whisker!barrels!with!fast!scattered!light!signals.!Neuroimage,!26(2),!6192627.!doi:10.1016/j.neuroimage.2005.02.030!!

Rector,!D.!M.,!Poe,!G.!R.,!Kristensen,!M.!P.,!&!Harper,!R.!M.!(1997).!Light!scattering!changes!follow!evoked!potentials!from!hippocampal!schaeffer!collateral!stimulation.!Journal!of!Neurophysiology,!78(3),!170721713.!!

Reitan,!R.!M.!(1958).!Validity!of!the!trail!making!test!as!an!indicator!of!organic!brain!damage.!Perceptual!and!Motor!Skills,!8(3),!2712276.!!

Reuter2Lorenz,!P.!A.,!Jonides,!J.,!Smith,!E.!E.,!Hartley,!A.,!Miller,!A.,!Marshuetz,!C.,!&!Koeppe,!R.!A.!(2000).!Age!differences!in!the!frontal!lateralization!of!verbal!and!spatial!working!memory!revealed!by!PET.!Journal!of!Cognitive!Neuroscience,!12(1),!1742187.!!

Reuter2Lorenz,!P.!A.,!&!Park,!D.!C.!(2010).!Human!neuroscience!and!the!aging!mind:!A!new!look!at!old!problems.!The!Journals!of!Gerontology.Series!B,!Psychological!Sciences!and!Social!Sciences,!65(4),!4052415.!doi:10.1093/geronb/gbq035![doi]!!

Rieckmann,!A.,!Karlsson,!S.,!Fischer,!H.,!&!Bäckman,!L.!(2011).!Caudate!dopamine!D1!receptor!density!is!associated!with!individual!differences!in!frontoparietal!connectivity!during!working!memory.!The!Journal!of!Neuroscience,!31(40),!14284214290.!!

Rissman,!J.,!Gazzaley,!A.,!&!D'Esposito,!M.!(2004).!Measuring!functional!connectivity!during!distinct!stages!of!a!cognitive!task.!Neuroimage,!23(2),!7522763.!!

Rossi,!A.!F.,!Pessoa,!L.,!Desimone,!R.,!&!Ungerleider,!L.!G.!(2009).!The!prefrontal!cortex!and!the!executive!control!of!attention.!Experimental!Brain!Research,!192(3),!4892497.!!

Rossi,!S.,!Miniussi,!C.,!Pasqualetti,!P.,!Babiloni,!C.,!Rossini,!P.!M.,!&!Cappa,!S.!F.!(2004).!Age2related!functional!changes!of!prefrontal!cortex!in!long2term!memory:!A!repetitive!transcranial!magnetic!stimulation!study.!The!Journal!of!Neuroscience!:!The!Official!Journal!of!the!Society!for!Neuroscience,!24(36),!793927944.!doi:10.1523/JNEUROSCI.0703204.2004![doi]!!

Rushworth,!M.!F.,!Walton,!M.!E.,!Kennerley,!S.!W.,!&!Bannerman,!D.!M.!(2004).!Action!sets!and!decisions!in!the!medial!frontal!cortex.!Trends!in!Cognitive!Sciences,!8(9),!4102417.!doi:10.1016/j.tics.2004.07.009!!

Rykhlevskaia,!E.,!Fabiani,!M.,!&!Gratton,!G.!(2006).!Lagged!covariance!structure!models!for!studying!functional!connectivity!in!the!brain.!Neuroimage,!30(4),!120321218.!doi:10.1016/j.neuroimage.2005.11.019!!

!

121!

Rykhlevskaia,!E.,!Gratton,!G.,!&!Fabiani,!M.!(2008).!Combining!structural!and!functional!neuroimaging!data!for!studying!brain!connectivity:!A!review.!Psychophysiology,!45(2),!1732187.!doi:10.1111/j.146928986.2007.00621.x!!

Rypma,!B.,!&!D'Esposito,!M.!(2000).!Isolating!the!neural!mechanisms!of!age2related!changes!in!human!working!memory.!Nature!Neuroscience,!3(5),!5092515.!!

Salthouse,!T.!A.!(1996).!The!processing2speed!theory!of!adult!age!differences!in!cognition.!Psychological!Review,!103(3),!403.!!

Schneider2Garces,!N.!J.,!Gordon,!B.!A.,!Brumback2Peltz,!C.!R.,!Shin,!E.,!Lee,!Y.,!Sutton,!B.!P.,!.!.!.!Fabiani,!M.!(2010).!Span,!CRUNCH,!and!beyond:!Working!memory!capacity!and!the!aging!brain.!Journal!of!Cognitive!Neuroscience,!22(4),!6552669.!!

Shenhav,!A.,!Botvinick,!M.,!&!Cohen,!J.!(2013).!The!expected!value!of!control:!An!integrative!theory!of!anterior!cingulate!cortex!function.!Neuron,!79(2),!2172240.!doi:http://dx.doi.org/10.1016/j.neuron.2013.07.007!

Smith,!E.!E.,!Jonides,!J.,!&!Koeppe,!R.!A.!(1996).!Dissociating!verbal!and!spatial!working!memory!using!PET.!Cerebral!Cortex!(New!York,!N.Y.:!1991),!6(1),!11220.!!

Smith,!S.!M.,!Fox,!P.!T.,!Miller,!K.!L.,!Glahn,!D.!C.,!Fox,!P.!M.,!Mackay,!C.!E.,!.!.!.!Beckmann,!C.!F.!(2009).!Correspondence!of!the!brain's!functional!architecture!during!activation!and!rest.!Proceedings!of!the!National!Academy!of!Sciences!of!the!United!States!of!America,!106(31),!13040213045.!doi:10.1073/pnas.0905267106!!

Sohn,!M.!H.,!Ursu,!S.,!Anderson,!J.!R.,!Stenger,!V.!A.,!&!Carter,!C.!S.!(2000).!The!role!of!prefrontal!cortex!and!posterior!parietal!cortex!in!task!switching.!Proceedings!of!the!National!Academy!of!Sciences!of!the!United!States!of!America,!97(24),!13448213453.!doi:10.1073/pnas.240460497!!

Sole2Padulles,!C.,!Bartres2Faz,!D.,!Junque,!C.,!Clemente,!I.!C.,!Molinuevo,!J.!L.,!Bargallo,!N.,!.!.!.!Valls2Sole,!J.!(2006).!Repetitive!transcranial!magnetic!stimulation!effects!on!brain!function!and!cognition!among!elders!with!memory!dysfunction.!A!randomized!sham2controlled!study.!Cerebral!Cortex!(New!York,!N.Y.:!1991),!16(10),!148721493.!doi:bhj083![pii]!!

Stahl,!J.,!&!Gibbons,!H.!(2004).!The!application!of!jackknife2based!onset!detection!of!lateralized!readiness!potential!in!correlative!approaches.!Psychophysiology,!41(6),!8452860.!!

Stern,!Y.!(2002).!What!is!cognitive!reserve?!theory!and!research!application!of!the!reserve!concept.!Journal!of!the!International!Neuropsychological!Society,!8(03),!4482460.!!

Swainson,!R.,!Cunnington,!R.,!Jackson,!G.!M.,!Rorden,!C.,!Peters,!A.!M.,!Morris,!P.!G.,!&!Jackson,!S.!R.!(2003).!Cognitive!control!mechanisms!revealed!by!ERP!and!fMRI:!

!

122!

Evidence!from!repeated!task2switching.!Journal!of!Cognitive!Neuroscience,!15(6),!7852799.!doi:10.1162/089892903322370717!!

Swainson,!R.,!Jackson,!S.!R.,!&!Jackson,!G.!M.!(2006).!Using!advance!information!in!dynamic!cognitive!control:!An!ERP!study!of!task2switching.!Brain!Research,!1105(1),!61272.!doi:http://dx.doi.org/10.1016/j.brainres.2006.02.027!

Szczepanski,!S.!M.,!Pinsk,!M.!A.,!Douglas,!M.!M.,!Kastner,!S.,!&!Saalmann,!Y.!B.!(2013).!Functional!and!structural!architecture!of!the!human!dorsal!frontoparietal!attention!network.!Proceedings!of!the!National!Academy!of!Sciences!of!the!United!States!of!America,!110(39),!15806215811.!doi:10.1073/pnas.1313903110![doi]!!

Townsend,!J.!T.,!&!Ashby,!F.!G.!(1983).!Stochastic!modeling!of!elementary!psychological!processes!CUP!Archive.!!

Travers,!S.,!&!West,!R.!(2008).!Neural!correlates!of!cue!retrieval,!task!set!reconfiguration,!and!rule!mapping!in!the!explicit!cue!task!switching!paradigm.!Psychophysiology,!45(4),!5882601.!!

Ullsperger,!M.,!Bylsma,!L.!M.,!&!Botvinick,!M.!M.!(2005).!The!conflict!adaptation!effect:!It’s!not!just!priming.!Cognitive,!Affective,!&!Behavioral!Neuroscience,!5(4),!4672472.!!

Unsworth,!N.,!&!Spillers,!G.!J.!(2010).!Working!memory!capacity:!Attention!control,!secondary!memory,!or!both?!A!direct!test!of!the!dual2component!model.!Journal!of!Memory!and!Language,!62(4),!3922406.!!

Vallesi,!A.,!&!Stuss,!D.!T.!(2010).!Excessive!sub2threshold!motor!preparation!for!non2target!stimuli!in!normal!aging.!Neuroimage,!50(3),!125121257.!!

Van!Gaal,!S.,!Lamme,!V.!A.,!&!Ridderinkhof,!K.!R.!(2010).!Unconsciously!triggered!conflict!adaptation.!PLoS!One,!5(7),!e11508.!!

Walker,!J.!A.,!Low,!K.!A.,!Cohen,!N.!J.,!Fabiani,!M.,!&!Gratton,!G.!(2014).!When!memory!leads!the!brain!to!take!scenes!at!face!value:!Face!areas!are!reactivated!at!test!by!scenes!that!were!paired!with!faces!at!study.!Frontiers!in!Human!Neuroscience,!8!!

Wang,!L.,!Liu,!X.,!Guise,!K.!G.,!Knight,!R.!T.,!Ghajar,!J.,!&!Fan,!J.!(2010).!Effective!connectivity!of!the!fronto2parietal!network!during!attentional!control.!Journal!of!Cognitive!Neuroscience,!22(3),!5432553.!doi:10.1162/jocn.2009.21210!!

Weissman,!D.!H.,!Warner,!L.!M.,!&!Woldorff,!M.!G.!(2004).!The!neural!mechanisms!for!minimizing!cross2modal!distraction.!The!Journal!of!Neuroscience!:!The!Official!Journal!of!the!Society!for!Neuroscience,!24(48),!10941210949.!doi:10.1523/JNEUROSCI.3669204.2004!!

!

123!

West,!R.!(2004).!The!effects!of!aging!on!controlled!attention!and!conflict!processing!in!the!stroop!task.!Journal!of!Cognitive!Neuroscience,!16(1),!1032113.!!

West,!R.,!&!Moore,!K.!(2005).!Adjustments!of!cognitive!control!in!younger!and!older!adults.!Cortex,!41(4),!5702581.!!

West,!R.,!&!Travers,!S.!(2008).!Differential!effects!of!aging!on!processes!underlying!task!switching.!Brain!and!Cognition,!68(1),!67280.!!

Westbrook,!A.,!Kester,!D.,!&!Braver,!T.!S.!(2013).!What!is!the!subjective!cost!of!cognitive!effort?!load,!trait,!and!aging!effects!revealed!by!economic!preference.!PloS!One,!8(7),!e68210.!!

Whalen,!C.,!Maclin,!E.!L.,!Fabiani,!M.,!&!Gratton,!G.!(2008).!Validation!of!a!method!for!coregistering!scalp!recording!locations!with!3D!structural!MR!images.!Human!Brain!Mapping,!29(11),!128821301.!doi:10.1002/hbm.20465!!

Wolf,!M.,!Wolf,!U.,!Choi,!J.!H.,!Gupta,!R.,!Safonova,!L.!P.,!Paunescu,!L.!A.,!.!.!.!Gratton,!E.!(2002).!Functional!frequency2domain!near2infrared!spectroscopy!detects!fast!neuronal!signal!in!the!motor!cortex.!Neuroimage,!17(4),!186821875.!!

Worsley,!K.!J.,!&!Friston,!K.!J.!(1995).!Analysis!of!fMRI!time2series!revisited—again.!Neuroimage,!2(3),!1732181.!!

Wylie,!G.,!&!Allport,!A.!(2000).!Task!switching!and!the!measurement!of!"switch!costs".!Psychological!Research,!63(324),!2122233.!!

Wylie,!G.!R.,!Javitt,!D.!C.,!&!Foxe,!J.!J.!(2006).!Jumping!the!gun:!Is!effective!preparation!contingent!upon!anticipatory!activation!in!task2relevant!neural!circuitry?!Cerebral!Cortex!(New!York,!N.Y.:!1991),!16(3),!3942404.!doi:10.1093/cercor/bhi118!!

Yantis,!S.,!Schwarzbach,!J.,!Serences,!J.!T.,!Carlson,!R.!L.,!Steinmetz,!M.!A.,!Pekar,!J.!J.,!&!Courtney,!S.!M.!(2002).!Transient!neural!activity!in!human!parietal!cortex!during!spatial!attention!shifts.!Nature!Neuroscience,!5(10),!99521002.!!

Yordanova,!J.,!Kolev,!V.,!Hohnsbein,!J.,!&!Falkenstein,!M.!(2004).!Sensorimotor!slowing!with!ageing!is!mediated!by!a!functional!dysregulation!of!motor2generation!processes:!Evidence!from!high2resolution!event2related!potentials.!Brain!:!A!Journal!of!Neurology,!127(Pt!2),!3512362.!doi:10.1093/brain/awh042!!!

Zacks,!R.!T.,!&!Hasher,!L.!(1994).!Directed!ignoring:!Inhibitory!regulation!of!working!memory.!!

Zanto,!T.!P.,!Rubens,!M.!T.,!Thangavel,!A.,!&!Gazzaley,!A.!(2011).!Causal!role!of!the!prefrontal!cortex!in!top2down!modulation!of!visual!processing!and!working!memory.!Nature!Neuroscience,!14(5),!6562661.!!

!

124!

Zimmerman,!B.,!Sutton,!B.!P.,!Low,!K.!A.,!Fletcher,!M.!A.,!Tan,!C.!H.,!Schneider2Garces,!N.,!.!.!.!Gratton,!G.!(2014).!Cardiorespiratory!fitness!mediates!the!effects!of!aging!on!cerebral!blood!flow.!Frontiers!in!Aging!Neuroscience,!6!!

!