DistalCoolingandSustainedAttention
RyanSixtus
Athesissubmittedforthedegreeof
MasterofPhysicalEducation
attheUniversityofOtago,Dunedin,
NewZealand
20/01/2016
i
ABSTRACT
Introduction:Vigilanceisdirectlyrelatedtocoreandskintemperatures(TCandTsk).Biological
dayreflectsahighTCandalertness;nightreflectsviceversa.Atrest,TCisregulatedlargelyby
controllingbloodflow(andhenceTsk)inextremities;theirvasodilationstronglypredicts
reducedvigilance(Raymannetal.,2007b)andfastersleeponset(Kräuchietal.,1999).In
narcolepsy,highdaytimeextremitytemperaturesandasmallerdistal-to-proximalgradient
(DPG)indicateshighersleeppropensity(Fronczeketal.,2006b).Coolextremitieshavebeen
linkedobservationallytodelayedsleeponsetintheelderly,andexperimentallyshowntoreduce
sleeppropensityinnarcolepsy(Fronczeketal.,2008).Therefore,theaimofthisstudywasto
testthehypothesisthatcoolingthefeetwouldmaintainvigilanceduringextendedwakefulness
inhealthyadults.
Methods:Arandomisedcross-overexperimentwascompletedusingninehealthyyoungadult
participantswithnormalsleeppatterns.Afterprovidinginformedconsent,andadaytime
familiarisation,theyundertookthree4-hlaboratorysessionsinwhichwater-perfusedbooties
wereusedtoprovideMildcooling,Moderatecoolingornocooling(Control).Sessionswereina
dimly-litroom,beginningat2230.Each30minconsistedofquietrestinterspersedwitha10minpsychomotorvigilancetask(PVT),7-minKarolinskaDrowsinessTest(KDT),andratingsof
sleepiness,perceivedbodytemperatureandthermaldiscomfort.EEGspectralpowers(theta,
alphaandbeta)weredeterminedwithinthePVTandKDT.Analyseswerebyrepeatedmeasures
ANOVA(α=0.05)withpost-hoccontrasts.
Results:FoottemperaturesinControlandMildandModeratecoolingaveraged34.5±0.5,30.8
±0.2and26.4±0.1OC(allP<0.01).Yet,theupper-limbDPGremainedstable(at~0.3OC)
regardlessofcondition(P=0.57).ThedeclineinTC(~0.35OC)wasalsounaffectedbycondition
(P=0.84),aswasvigilance(interactionforresponsespeed:P=0.45).Asmallandtransient
reductioninsleepinesswasevidentwithcooling(P=0.046);otherwisesleepinessandvigilance
ii
deterioratedinconjunctionwiththefallinTCineachcondition(r>0.80).Participantsfeltcooler
throughoutbothcoolingtrials,butthermalcomfortwasunaffected(P=0.43),aswerealmostall
EEGparametersduringtheKDT.Alldependentmeasureswereaffectedbytime.
DiscussionandConclusion:Inhealthy,youngadults,coretemperatureandvigilancedecline
duringtheperiodofnormalsleeponsetandearlysleepregardlessofmildormoderatecooling
ofthefeet,andanyeffectonsleepinessissmallandtransient.
iii
ACKNOWLEDGEMENTS
TherearemanypeopletowhomIowethanks.Firstandforemostaremysupervisors,for
whomIcouldnothavecompletedthisprojectwiththedepthofthoughtanddetailpresented.
Evenmoreso,IwouldnothavebegunthisjourneywithoutJimCottertofirstlysupportmeinto
postgraduatelevelandthensecondlysetmedownthispathbygivingmetheproject.
Ifeelasthoughabackgroundtothisprojectisrequired.FormanyyearsJimhasbeendriving
homeaftermulti-dayenduranceevents,severelysleepdeprivedandhasresortedtomanyforms
ofcooling–fromdirectingtheairconditioningtohisfeet,tojumpinginrivers–tomaintainhis
alertness.Thisformedthebasisformyquestioning.Jimhasforalongtimebeena
thermoregulatorydictionaryformeandwithouthishelpIsincerelydoubtthatthisproject
wouldhavegottenofftheground.
BarbaraGallandallowedmetointroduceelectroencephalographyandvarioussleep
measures,whichallowedmetoprogressthisstudyintosomethingserious.Barbarasourcedall
mymaindependentmeasures–thePVTandEEG,aswellastheActicals–fromaroundthe
country.Idon’tknowwhatthisstudywouldhaveturnedouttobehadBarbaranothelpedmein
acquiringthisequipmentandunderstandingthecircadianandsleepaspectsofthisresearch.
IoweCarmenLobb,myacticaljuggler,aheapofthanksforarrangingtheacquisitionofmy
acticals.Whilealwaysbusywithotherstuff,shewasalwayscapableofassistingmeinsetting
theseup.
ThePEschooltechteam,alwaysworkinghardforuspostgrads,didagreatjoboftrackingmy
equipmentdown,includingtheneoprenefromwhichmybootiesweremade.
Fortheloanofequipment,IhaveAucklandUniversity,andMassyUniversitytothank.The
compumedicsEEGequipmentallowedmetobetterrecordmyelectrophysiologicalmeasures.
LeighfromMassy,fortheextendedloanofthePVT,Ioweabigthanks.
Finally,GavinKennedy,Matlabwizard,abigthanksforanalysingmyEEGsignalwithMatlab.
IwouldprobablyhavenoEEGdatatoaddtothisthesiswithouthim.
CONTENTS
ABSTRACT………………………………………………………………………………………………………. i
ACKNOLEDGEMENTS………………………………………………………………………………………. iii
ABREVIATIONS………………………………………………………………………………………………… viii
LISTOFTABLES……………………………………………………………………………………………….. x
LISTOFFIGURES……………………………………………………………………………………………….xi
1.0
INTRODUCTION……………………………………………………………………………………..1
2.0
LITERATUREREVIEW…………………………………………………………………………… 5
2.1
Driving………………………………………………………………………………………………………6
2.2
Thermoregulation………………………………………………………………………………………8
2.2.1
Homeostasis…………………………………………………………………………………..8
2.2.2
Sensation………………………………………………………………………………………..13
2.2.3
Vasomotion..…………………………………………………………………………………..20
2.2.4
ArteriovenousAnastomoses……………………………………………………………25
2.2.5
Summary………………………………………………………………………………………..26
2.3
CircadianRhythms……………………………………………………………………………………..29
2.3.1
Sleeppermissive/wakepromotingfactors………………………………………31
2.3.2
Homeostatichourglass–ProcessS…………………………………………………..33
2.3.3
Centralcircadianclock–ProcessC………………………………………………….35
2.3.4
InteractionofProcessSandProcessC…………………………………………….36
2.3.5
Circadiantemperaturerhythm………………………………………………………..40
2.3.6
Narcolepsy……………………………………………………………………………………..43
2.4
Vigilance……………………………………………………………………………………………………44
2.4.1
Psychomotorvigilance..…………………………………………………..………………45
2.4.2
Validityofthepsychomotorvigilancetask……………………………………….47
2.5
Sleeponset………………..……………………………………………………………………………….49
2.6
Electroencephalographyandelectro-oculogram.…………………………………….......51
2.6.1
Alphaandthetarhythms………………………………………………………..............53
2.6.2
Agerelatedalphafrequencychanges……………………..………………………..55
2.6.3
Betarhythm……………………………………………………………………..…………….56
2.6.4
10/20electrodepositioning……………………………………………………...........58
2.6.5
Theelectro-oculogram(EOG)………………………………………………………….59
2.7
Conclusion...………….……………………………………………………………………………………60
3.0
METHOD………………………………………………………………………………………………..62
3.1
ExperimentalProtocol………………………………………………………………………………. 64
3.2
Participants……………………………………………………………………………………………….66
3.4
ApparatusandMeasures…………………………………………………………………………….67
3.4.1
Psychomotorvigilancetask……………………………………………………………..67
3.4.2
Electrophysiologicalmeasures(EEG,EOG,ECG)………………………………67
3.4.3
Sleeponsetstaging…………………………………………………..…………………......69
3.4.4
Temperature……………………………………………………………………………….....69
3.4.5
Actigraphyandsleepdiary……………………………………………………………...71
3.4.6
Subjectivequestionnaires……………………………………………………………….71
3.4.7
Hydrationstatus………………………………………………………………………….....72
3.5
DataAnalysis……………………………………………………………………………………………..73
3.5.1
Datareduction………………………………………………………………………………..73
3.5.2
Statisticalanalyses………………………………………………………………………….74
4.0
RESULTS……..………………………………………………………………………………………….76
4.1
Participantcharacteristicsandcompliance………………………………………………….76
4.1.1
Screening………………………………………………………………………………………..76
4.1.2
Adherence……………………………………………………………………………………...76
4.1.3
Sleepdiaries–sleeponset………………………………………………………………77
4.1.4
Moodstatecharacteristicsandhydration………………………………………...78
4.2
Inducedtemperatures………………………………………………………………………………..80
4.2.1
Temperaturemanipulation……………………………………………………………..81
4.2.2
Foottemperatures………………………………………………………………………….81
4.2.3
Upperlimb……………………………………………………………………………………..82
4.2.4
Coretemperature………………………………………………………………………......82
4.2.5
Temperaturegradients………………………………………………………………......85
4.2.6
Temperatureperception………………………………………………………………...87
4.3
Subjectivesleepiness………………………………………………………………………………….89
4.4
Vigilance……………………………………………………………………………………………………91
4.4.1
Reciprocalreactiontime…………………………………………………………………91
4.4.2
Variability………………………………………………………………………………….......92
4.4.3
Lapses……………………………………………………………………………………………92
4.4.4
Coretemperatureandvigilance………………………………………………………94
4.4.5
CoretemperatureandSleepiness……………………………………………………94
4.5
Cognitivearousal…………………………………………………………………………………….....96
4.5.1
KarolinskaDrowsinessTest……………………………………………………………96
4.5.2
C4-A1…………………………………………………………………………………………….97
5.4.3
O2-A1………………………………………………………………………………………….... 98
4.6
HeartRate………………………………………………………………………………………………… 101
5.0
DISCUSSION……………………………………………………………………………………………103
5.1
Temperatureandvigilance…………………………………………………………………………104
5.1.1
Temperatureeffects……………………………………………………………………….104
5.1.2
Vigilanceandarousal.……………………………………………………………………..106
5.2
TransientEffects………………………………………………………………………………………..110
5.3
Limitations………………………………………………………………………………………………...111
5.3.1
Ordereffect……………………………………………………………………………………111
5.3.2
Laboratory/Equipmentsetup…………………………………………………………112
5.3.3
Statisticalpower…………………………………………………………………………….112
5.3.4
Electroencephalography…………………………………………………………………113
5.3.5
Temperature………………………………………………………………………………….114
5.3.6
Vigilance……………………………………………………………………………………….. 115
5.4
VariableTemperaturesacrossthermistorlocationsonthefeet……………………115
5.5
PracticalApplication…………………………………………………………………………………..116
5.6
ConclusionsandRecommendationsforfutureresearch………………….……………117
7.0
REFERENCES………………………………………………………………………………………….120
8.0
APPENDICES…………………………………………………………………………………………..133
AppendixA:ParticipantInformationandconsentform.………………………………….133
AppendixB:Activitymonitoringandsleepdiary.………………………………………......137
AppendixC:Depictionofparticipantsetup………………………………………………………..141
AppendixD:Criteriaforanalysisofthe10minPVT.……………………………………………142
AppendixE:Outlinefordrowsinessscoring……………………………………………………….143
AppendixF:Pilottemperatures…………………………………………………………………………144
AppendixG:Waterperfusedbooties…………………………………………………………………..146
AppendixH:KarolinskaSleepinessScale……………..………………….………………………….147
AppendixI:ThermalSensationandThermalDiscomfort…………………………………….148
AppendixJ:TheBrunelmoodstatequestionnaire..................................................................149
AppendixK:AdditionalData………………………………………………………………………………150
AppendixL:Participanteight……………………………………………………………………………..151
viii
ABREVIATIONS
AAS
AscendingArousalSystem
ANOVA
AnalysisofVariance
AVA
ArteriovenousAnastomoses
BRUMS
BrunelMoodStateQuestionnaire
CSN
ColdSensitiveNeuron
DPG
DistalProximalGradient
ECG
Electrocardiogram
EEG
Electroencephalogram(ScalpabbreviationsinFigure3.3)
EOG
Electro-oculogram
ISI
Inter-stimulusInterval
KDT
KarolinskaDrowsinessTest
KSS
KarolinskaSleepinessScale
LH
LateralHypothalamus
N1
SleepStage1
N2
SleepStage2
N3
SleepStage3/4
NREM
NonRapidEyeMovementSleep
PCG
ProximalCoreGradient
POAH
PreopticAnteriorHypothalamus
PSG
Polysomnography
PVT
PsychomotorVigilanceTask
REM/R
RapidEyeMovementSleep
RRT
ReciprocalReactionTime[RRT=1000/RT]
RT
ReactionTime
SCN
SuprachiasmaticNucleus
ix
SD
standarddeviation
SEM
SlowEyeMovement
SWS
SlowWaveSleep
Tamb
AmbientTemperature(drybulbtemperature)
T C
CoreBodyTemperature
TFoot
Foottemperature
TForehead
Foreheadtemperature
TSk
Skintemperature
TNZ
ThermoneutralZone
TRPChannel
TransientReceptorPotentialChannel
TRPA
TransientReceptorPotentialAnkyrin
TRPM
TransientReceptorPotentialMelastatin
TRPV
TransientReceptorPotentialVanilloid
Tsk
SkinTemperature
USG
UrineSpecificGravity
VLPO
VentrolateralPreopticHypothalamus
WEM
WakingEyeMovement
WSN
WarmSensitiveNeuron
x
LISTOFTABLES
Page
3.1:Participantdetails.………………………………………………………………………………………………………66
4.1:Sleephours:sleeponset,waking,totalsleeptime.………………………………………………………….79
4.2:Preandpostsubjectivesleepinessandhydration.…………………………………………………………..79
4.3:Ambientandwatertemperatures.………………………………………………………………………………..81
AppendixD:Table1:Criteriafortheanalysisof10-minPVT…………………………………………………..142
AppendixE:Table1:Outlineforsignificanteventsinprogressingdrowsiness…………………………143
AppendixF:Table1:TrialcoolingprotocolforapplicationtoMildandModerateconditionsin
mainstudy.…………………………………………………………….…………………………………………………………144
xi
LISTOFFIGURES
Page
2.1:SchematicrepresentationofthermoTRPchannelactivation………………………………………….16
2.2:Correlationbetweenskintemperatureandrestingbloodflowvelocity…………………………26
2.3:TimecourseofProcessesSandCafterregularandextendedwakingperiods………………..29
2.4:Diagrammaticrepresentationofnormallyentrainedendogenousrhythmsofcorebody
temperature,melatoninandsleeppropensity.……………………………………………………………………40
3.1:Protocoloverview…………………………………………………………………………………………………
62
3.2:Studyoverview…………………………………………………………………………………………………
62
3.3:Manipulatedtestingcycle.……………………………………………………………………………….…………..65
3.4:International10/20system,electrodepositions…………………………………………………………. 68
4.1:averagefoot,upperlimbandcoretemperatureacrossconditions…………………………………83
4.2:Localisedfoottemperatureparameterscomprisingaveragefoottemperatureacross
conditions…………………………………………………………….…………………………………………………………...84
4.3:Timecourseofindividualfootthermistorsacrossconditions………………………………………..84
4.4:Upperandlowerlimbdistalproximalgradients,andPCG.…………………………………………….86
4.5:Differencesinupperlimbgradientsbetweenconditions………………………………………………86
4.6:Thermalsensationandthermalcomfort………………………………………………………………………88
4.7:Progressionofsubjectivesleepiness.…………………………………………………………………………...90
4.8:CeilingeffectofKarolinskasleepinessscale.………………………………………………………………..90
4.9:ChangeinsubjectivesleepinesspreandpostPVT.………………………………………………………..91
4.10:1minaveragesofreciprocalreactiontime,andvarianceacrossPVTs………………………….93
4.11:AveragePVTlapsesacrossconditions.……………………………………………………………………….95
xii
Page
4.12:CorrelationofchangeincorebodytemperatureandchangeinRRT…………………………….95
4.13:Correlationofchangeincorebodytemperatureandsubjectivesleepiness………………….96
4.14:Theta,alphaandbetaEEGfrequenciesfromC4-A1derivationacrossKDTseyesopen
andeyesclosed.…………………………………………………………….………………………………………………… 99
4.15:ThetaandalphaEEGfrequenciesfromO2-A1derivationacrossKDTseyesopenand
eyesclosed.…………………………………………………………….………………………………………………………...100
4.16:ChangeinthetaandalphaEEGfrequenciesbetweeneyesopenandeyesclosedwithin
eachKDT…………………………………………………………….…………………………………………………………….101
4.17:Changeinheartrateacrosseachcondition…………………………………………………………………102
4.18:HeartrateprepostPVT……………………………………………………………………………………………..102
AppendixC:Figure1:Depictionofparticipantsetup…………………………………………………………..141
AppendixF:Figure1:Originalstudy,foottemperaturesacrosswarmingandcooling
conditions.…………………………………………………………….………………………………………………………….145
AppendixF:Figure2:CollatedEEGforpeakalphaandbetafrequenciespreandpostcooling
andwarmingprotocols.…………………………………………………………………………………………………….145
AppendixG:Figure1:Viewofinternaltubingliningthecustomfittedbooties……………………. 146
AppendixG:Figure2:Customfittedbootiesworn.……………………………………………………………..146
AppendixK:Figure1:BrunelMoodstatecharacteristicofvigouracrossconditions……………..150
AppendixK:Figure2:BrunelMoodstatecharacteristicoffatigueacrossconditions.……………150
AppendixL:Figure1:Participanteightcoretemperaturerecordingsacrossconditionswith
comparisontogroupconditions.…………………………………………………………….…………………………151
AppendixL:Figure2:ParticipanteightsDPGacrossconditions,comparedtothegroup
trend.…………………………………………………………….…………………………………………………………………151
1
1.0
INTRODUCTION
Sleepdeprivationanditsassociatedmentalfatiguemaybeincreasinglyprevalentinmodern
society(Alvarezetal.,2004;Gradisaretal.,2011;Halson,2014;Oldsetal.,2010;Zealand,
2001).Amoremechanisedindustryandmoreartificiallightinghasallowedfor24-hour
operation,expandingbothworkandplayhoursfarintothenight(Wrightetal.,2013).Fatiguerelatedincidentsareespeciallyconcerninginsituationsofhighrisksuchasshiftworkordriving
(Jonesetal.,2010;Laletal.,2001;Reyneretal.,2012),astheunderlyingstateofsleepinesscan
leadtoseriousdecrementsinperformancecapabilities(Laletal.,2002;Lohetal.,2004).Indeed,
ahighincidenceofinjuryappearstosurroundtasksofprolongedmonotonousnatureand
operatinghoursoutsideofthe“biologicalday”(Jonesetal.,2010;Lohetal.,2004).Drowsy
drivingaccountsfor~14%oftheNewZealand’sfatalroadtrafficaccidents(Transport,2011b),
withshiftwork-relatedaccidentspresumablycontributingasimilarpercentage,especiallyin
sustainedoperationsandduringnightshifts(Lohetal.,2004).Interventionsforfatigue-related
incidents,especiallytheroaddeathtoll,appearlimitedandpotentiallyineffectivewithregardto
adherence,indicatingagreaterfocusonwakefulnessorvigilancepromotingmethodsmerits
furtherinvestigationandinsight(Horneetal.,1996;Jonesetal.,2010).
Vigilanceischaracterisedbycognitivearousalandattention,with(sustained)attention
encompassingthetemporalanddirectional(focal)components(Laletal.,2001).Vigilanceis
commonlydefinedbyitsantonyms;drowsiness,fatigue,andsleepiness,whichareused
synonymouslytomeantheneurobiologicalprocessregulatingcircadianrhythmsandthedrive
tosleep.Mentalfatigueisacumulativeprocess,whichfirstaffectsthetop-downprocesses
(Lorist,2008),resultingingreaterinconsistencyduringtasks,aninabilitytobiasrelevantfrom
irrelevantinformation,andageneralslowingofreactiontimes(Boksemetal.,2005;Dorrianet
al.,2005;Limetal.,2008;vanDongenetal.,2000).
Thewakingarousalstateistonicallyaffectedbytheinteractionofboththehomeostatic
hourglassandthecircadianclock–processesSandC,respectively.ProcessSisthehomeostatic
2
drivetosleep,believedtobeinfluencedbysomestructureorsubstance(probablyadenosine),
whichincreasessleeppropensityaswakingtimeincreases.ProcessCisthecircadianinfluence
onsleepandwakefulnesscontrolledbythesuprachiasmaticnucleus(SCN)locatedinthe
anteriorhypothalamus(Jinetal.,1999;Reppertetal.,2002).TheSCNisregulatedbylightinput
fromtheretinaduringtheday,andmelatoninsecretionfromthepinealglandduringthedark
cycle(Cassoneetal.,1986).TheprocessSpressuretosleeprisesexponentiallyacrossthe
wakingday(Moore,2007;Porkka-Heiskanenetal.,2011;Romeijnetal.,2012a),whereasthe
processCdriveforwakingpeaksduringthebiologicaldayandtroughsduringbiologicalnight,
enforcinga~24-hourrhythmentrainedtothelight-darkcycle(Johnsonetal.,1988).Inhealthy
individuals,theadditiveeffectsofProcessesSandCareevidentintheevening,withgreater
slowingandinconsistencyinreactiontime,indicativeofvigilancedecay(Dorrianetal.,2005;
Limetal.,2008).
Wakingfromsleepispromotedbyagroupofcellsoriginatinginthebrainstemthatactivate
thethalamusandcerebralcortexviaanetworkofcellgroupsknownastheascendingarousal
system(AAS).Wakefulnessisreinforcedbytheneuropeptideorexin(alsoknownashypocretin),
produced exclusively by a cluster of neurons in the posterior lateral hypothalamus. Inpatients
sufferingfromnarcolepsy(describedinmoredetailinsection2.3.6),thewakingstateis
destabilisedduetolossoforexin,therebyallowingtheirrapidtransitionbetweenwakingand
sleepingstates(Fronczeketal.,2006b;Overeemetal.,2012).
ProcessCislinkedtocognitivearousalviatheAAS,butisalsooneofthenon-thermalfactors
thatmodulatecorebodytemperature(TC(Sciences,2001)).ThecircadianoscillationofTCis
drivenbytheSCNandcontrolledviasystemsthatalterheatlossandheatgain,withTCreaching
maximumduringthedayandminimumduringthenight.ThechangesinTCrespondtoboth
thermalandnon-thermalcues.TheextremitiesalsoplayalargeroleinmodulatingTCthrough
theiranatomicalspecialisationsforheatloss;however,itisincreasinglyevidentthatthedistal
skintemperaturemayindependentlymodulatevigilanceandsleepiness(seereviewbyVan
Someren,2006).Thismodulatoryroleofthedistalskintemperatureisfurthersupported
3
practicallybytheuseofabeddingmicroclimatetomaintainhighdistaltemperatures(~34-35
OC)wheninitiatingsleep(VanSomeren,2006).
Vigilanceismultifactorial,andisoftenbrokenintoitsconstituentcomponents,cognitive
arousalandsustainedattention,whichareobservableusingelectroencephalography(EEG)and
psychomotorvigilancetasks(PVT),respectively.TheEEGisoftenpurportedtobethegold
standardoftrackingvigilancedecay,however,thePVThasalternatelybeendescribedasthe
‘archetypeneurocognitiveassayofattentionaftersleeploss’((Limetal.,2008),p.306).Thus,
EEGandPVTeachofferimportantinsightsintodifferentaspectsofvigilance.EEGprovides
directrecordingsofcognitivearousalbutislimitedbypoorsignal-to-noiseratiosandalackof
anatomicalandphysiologicalanchorstoparticularfrequencies(e.g.,alphafrequency(Pizzagalli,
2007))(Callaway,1966).PVTprovidesinsightintosustainedattentionandthusfunctional
effectsofmentalfatigueanddrowsiness(Basneretal.,2011;Limetal.,2008).Sleepdeprivation
furtheraccentuatesfatigue-relatedchangesinPVTandEEGashomeostaticsleeppressureis
raised(Limetal.,2008;Santamariaetal.,1987),andassuch,bothtechniquesbecomemore
sensitivemeasuresofvigilanceanditsdecay.
Interventionsconductedonvigilancehavetypicallyinvolvedeitherattenuatingorfacilitating
itsdecline.Suchinterventionshaveincludedposturalchange(Caldwelletal.,2003;Cole,1989),
stimulantssuchascaffeineandamphetamines(Limetal.,2008),mealsizeandsatiety(Reyner
etal.,2012),andmorerecentlysubtlethermalmodulation(Fronczeketal.,2008;Kräuchietal.,
1999;Raymannetal.,2007b;VanSomeren,2006).Indeed,somearousalalteringdrugsmay
workbywayoftheireffectsonthethermoregulatorysystem(e.g.,Atenolol(VanDenHeuvelet
al.,1997).Severalstudieshavefocussedonfacilitatingsleepthroughdistalwarming,observing
eithertime-on-taskdegradation,orappearanceofsleepstages(Kräuchietal.,1999;Kräuchiet
al.,2008;Raymannetal.,2007a;Raymannetal.,2007b),asdemonstratedusingthePVTand
EEG.FacilitatingtheeveningdeclineofTChasbeenshowntoassistsleeponset(Kräuchietal.,
1999).Corecoolingandsleepinesshasalsobeendemonstratedduringtheday(Fronczeketal.,
4
2008;Gilbertetal.,2000).Assuch,inhibitingtheevening-relatedreductioninTCresponsemay
causetheoppositeeffect,i.e.,maintainedvigilance.Thispossibilityremainslargelyunexplored.
(Fronczeketal.,2008))addressedthisveryquestioninanarcolepticindividuals,whohave
distaltemperaturesassociatedwithdrowsiness(Fronczeketal.,2006b).Subtlerangesof
temperaturemanipulationmayofferthemostpromisingfindings(Fronczeketal.,2008;
Raymannetal.,2005),asmanipulationsinvolvingwhole-bodyorexcessivetemperatureshave
beenshowntoimpairpsychomotorfunction(Enander,1987),atleastpartlybytheirdistraction
effect(Cheungetal.,2007).
Theaimofthecurrentstudywastoexaminetheeffectsofcoolingoftheextremities–
specificallysubtleandmoderatecoolingofthefeet–onsustainedattentionandsleepinessin
healthyindividuals.Changesinvigilance/arousalstatewereassessedusingEEGandPVT.Itwas
hypothesisedthatfootcoolingwouldproducegreaterwakefulness(indicatedfromEEG)and
attenuatethedeclineinvigilance(indicatedfromPVT),relativetothenormal/controlstate.
Changeinthevigilancestatewasconsideredtobeduetoeitherorbothofchangesindistalskin
temperatureperse,orresultantchangesintherateofTCdecline.
5
2.0 LITERATUREREVIEW
Fatigueduetoprolongedmentalorphysicalworkprecipitatesdrowsinessandsleeponset.
Thetermsfatigue,drowsinessandsleepinessareusedsynonymouslytodescribethereduction
invigilancestate(Dinges,1995).Fatigue,theantonymofvigilance,canbedescribedasa
disinclinationtocontinueperformingatask,orasaneffort-to-rewardimbalance,whereby
motivationtoperformdeclineswithincreasingdurationand/ordifficulty(Brown,1994;
Guyton,1991;Topsetal.,2004).Amyriadoffactorsinfluencevigilanceandfatigability,manyof
whicharebeyondthescopethecurrentreview.Ofparticularinterestaretheinternalregulatory
processesSandC,andtheirassociatedarousalandthermoregulatorychanges;i.e.,vigilanceand
fatigabilityaretightlyrelatedtocircadian(ProcessC)oscillationofcorebodytemperature.
Coretemperatureapproximates37±1OC(Waterhouseetal.,2005),andismaintained
largelybyadjustingskintemperature(Tsk).Inanevolutionarysense,thermoregulationistiedto
vigilancetomaintainhomeostaticfunctioningwhenthermoneutralityisthreatened(Romeijnet
al.,2012a).Coretemperatureisperturbedbythermal(e.g.,heat)andnon-thermal(e.g.,Process
C)factorsthatchangetheinterthresholdzonewithinwhichTCnormallyresides.ProcessCalters
corebodytemperaturethroughadjustmentsinheatlossandheatgainsystems(andhenceTsk)
acrosstheday.Thelevelofthermalresponsetoenvironmentaltemperaturecaninducechanges
invigilance(Fronczeketal.,2008;Kräuchietal.,2008).
Thecurrentstudyisfocussedonmaintainingvigilancethroughmodulation(cooling)offoot
temperatureintheevening.Coolinghasbeendemonstratedtobeaneffectivestrategyfor
vigilanceandmaintenanceofwakefulnessinNarcoleptics(Fronczeketal.,2006a;Fronczeket
al.,2008).Similarly,findingsfromanobservationalstudyindicatethatthermaldiscomfortfrom
coldextremitiesrelatestodifficultyinitiatingsleepinhealthypopulations(Kräuchietal.,2008).
Equally,warmingtheextremitieshasbeenshowntodecreasevigilance(Raymannetal.,2007b)
andsleeponsetlatency(Kräuchietal.,1999;Raymannetal.,2007a).Sincesubtlewarming
6
potentlypromotessleepinessresponses,doescoolinghaveasimilarcapacityforaltering
(increasing)thevigilancestate?
2.1
Driving
In2010,NewZealandhad337fatalcrashes,with47(14%)beingcausallyrelatedtofatigue
(Transport,2011a,2011b).Thisproportionremainedconsistentin2011,at13%(Transport,
2012).Fatigueisthestateofdeterioratingvigilanceorattentiontoasustainedtask(Eohetal.,
2005),and/orbeingunabletomaintainperformanceonatask(Dinges,1995).Thesesituations
however,donotnecessarilyresultinsleep.Fatiguehasalsobeenshowntoraisereactiontime
(RT)(Caldwelletal.,2003;Dingesetal.,1985;Fronczeketal.,2008;Schier,2000;VanDongenet
al.,2003)andincreasethenumberoflapses(i.e.RT>500ms)inpsychomotorvigilancetasks
(Fronczeketal.,2008;VanDongenetal.,2003),alongwithdecreasinginformationprocessing
speedandmemorycapacity(Eohetal.,2005;Klimesch,1999).Reducedtaskperformance
occurringwithfatiguehasbeenresearchedthoroughly(Altenaetal.,2008;Belyavinetal.,1987;
Dingesetal.,1985;Eohetal.,2005;Fronczeketal.,2008;Laletal.,2002;VanDongenetal.,
2003).Withnegativeimplicationsoffatigueanddrowsiness,itbecomesprudenttofurther
assessmechanismsinvolvedandpossiblemethodsofattenuation,especiallywithregardto
driving,wheretheresultsofraisedreactiontimeandlowerinformationprocessinghave
potentiallydevastatingrepercussions(Dinges,1995).
CurrentregulationsinNewZealandprohibitlong-hauldriversfromexceeding13hoursof
operation,andrequire10hoursofrestbetweenworkperiods(Jonesetal.,2010;Transport,
2011a).Nosuchregulationisrequiredforcommuters(Jonesetal.,2010).Drivers,arguablyhave
goodinsightintoincreasingdrowsinessandarealwaysawareofsleepinesspriortoincidents
(Filtnessetal.,2012;Horneetal.,1996),yetyoungeverydaycommutershavethehighest
fatigue-relatedincidenceofcrashes(Filtnessetal.,2012;Reyneretal.,2012;Transport,2011a,
7
2011b).Technologicaladvanceshaveallowedthelong-haulindustrytoimplementsensors
withinmanycabstodetectsleepinessandfatiguethroughshortandlongblinks(e.g.,Driver
FatigueMonitor,HaoNaiIndustrialCo,China).Thecurrent“goldstandard”methodof
preventingfatigueforgeneralcommutersinvolvesapowernap(Horneetal.,1996),however
worldwidethisisfoundtohaveminimaladherence(Jonesetal.,2010),andmaybeoflimited
benefit(Gillbergetal.,1996).Researchregardingfatiguepreventionfocusesonpolicychange
anddrivingconditions,withfewstudiesinvestigatingthecontributionofthedriverperse(Jones
etal.,2010).Currently,themostresearcheddriver-orientedfatiguepreventionmethodis
caffeine,foritsadenosineinhibiting,andsympatheticstimulatingeffects(Eohetal.,2005;Horne
etal.,1996;Porkka-Heiskanenetal.,2002;Reyneretal.,1998).However,anecdotalreports
havelongsuggestedthatcoolingoftheskin(suchasairconditioning)aidsdrivingperformance
whendrowsy.
Previously,coldconvectiveairflowdirectedatthefacehashadminimalimpactonfatigue
preventionwhiledriving(Reyneretal.,1998),however,thedistalextremitiesappeartobemore
intimatelyrelatedtoheatlosspathwaysandsleepiness(discussedbelow),andthereforemay
offeranalternatemethodoffatigueprevention.Unfortunately,itisdifficulttoevaluatefatiguepreventionmethodsandtheirunderlyingmechanismsforuseinmotorvehicles.Driving
simulatorshavethusbeendevelopedandvalidatedastoolstotestsustainedattentionforthe
laboratorysetting(Gillbergetal.,1996).Thistoohaslimitations,despiteitsexternalvalidity,
duetothedifficultyofcombiningdrivingsimulationwithotherequipmentandrecordings,such
astheelectroencephalogram(EEG).Thecurrentstudyreducedthesustainedattention
componentofdrowsydrivingtoasimplepsychomotorvigilancetask(Dingesetal.,1985)in
conjunctionwithEEG,toassessthevigilancedecrement,asatestofconcept.
8
2.2
Thermoregulation
2.2.1
Homeostasis
Humans,likeothermammals,are,homeotherms(Gaggeetal.,1996;Refinettietal.,1992;
Romanovsky,2007).Thatis,weself-regulatetheinternalthermalstatethoughvarious
metabolicprocesses(e.g.,basalmetabolism,dietaryintake,exercise,shiveringandnonshiveringthermogenesis,andlikelybrownadiposetissue(Nagashimaetal.,2000))(Gaggeetal.,
1996;Lvetal.,2007).TheTCisideallymaintainedwithinatightrangeofaround37OC,subject
tooscillationsfromthermalandnon-thermalfactors(Mekjavicetal.,2006;Romanovsky,2007).
Attheextremes,corebodytemperaturesoutside35-41OCcannotbetoleratedforlong(Taylor
etal.,2008a),although,overheatingisofgreaterimmediatephysiologicalconcernthan
overcooling(Romanovsky,2007).Thesmallrangeofcontrolnecessitatesmultipleregulatory
mechanismstoensurethermalstability.Deviationsof~1OCawayfromneutralTCareenoughto
fullyactivatethermoeffectors(Mekjavicetal.,1989;Tayloretal.,2014).Maintenanceofthe
corewithinsuchrangesoccursattheexpenseoftheskinifnecessary(Werneretal.,1980).
Despitetheskin’stightoptimalrange(30-33OC)(Clineetal.,2004;Mekjavicetal.,1989),itcan
toleratewidedeviationsto~10OCand~50OCwithoutdamage(See(Werneretal.,1980)).Such
deviationsinskintemperatureinvolvethickeningorthinningofa“shell”layerthroughfine
adjustmentsofcutaneousandsubcutaneousbloodflows.
Thethermoregulatorycentremaintainingcorebodytemperaturelieswithinthepreoptic
anteriorhypothalamus(POAH),andhasbeenwellestablished(Nagashimaetal.,2000;PorkkaHeiskanenetal.,2002;Raymannetal.,2005;Raymannetal.,2007b;Romanovsky,2007;
Romeijnetal.,2012a).ThePOAHcontainsthelargestcentralconcentrationofwarm-sensitive
neurons(WSN)andcold-sensitiveneurons(CSN).WSNsaredominantwithinthePOAH
(Boulant,1996),andaremostresponsivetochangesinheatingandcooling(Nagashimaetal.,
2000).Warm-andcold-sensitiveneuronsarereactivetochangesincoreandskintemperatures,
facilitatingmanyparallelthermoregulatoryresponsestodeviationsinskinandcorebody
9
temperature.TheWSNshaveaninhibitoryactiononCSNs,suchthattheactivityassociatedwith
thermalchangeisactuallydrivenbyincreasesordecreasesinWSNactivityandtheirinhibitory
actiononCSNs(Furtherdiscussedin(VanSomerenetal.,2002;VanSomeren,2004)and
(Romanovsky,2007)).WSNexcitation,occurringwithbodyheating,resultsinhierarchical
recruitmentofthermoeffectorresponses.Whereas,WSNinhibitionresultsinCSNexcitationand
hierarchicalactivationofthermoeffectorresponsesassociatedwithcooling.Theextentof
thermoafferentsignallingdeterminesrecruitmentofthermoeffectorresponse(Romanovsky,
2007;Stevensetal.,1979;Stevensetal.,1974).Suchsignallingshowsgradedinputfromany
thermosensitivestructure,andspatialsummationofthermoafferentfeedbackforcoldand
somewhatforwarmth(Romanovsky,2007;Stevensetal.,1979;Stevensetal.,1974).
Previoustheoriesofthermoregulation,encouragedbyengineeringterminologyfor
thermostats,utilisedtheideaofasetpoint(Ranson,1939;Romanovsky,2007;Werner,1980).
Although,thebeliefinasetpointhasbeenchallenged(Kobayashietal.,2006;Mekjavicetal.,
1989;Mekjavicetal.,1991;Mekjavicetal.,2006;Romanovsky,2007).The2001glossaryof
termsforthermalphysiology(Sciences,2001)statesthatthesetpointreferstothevalueofa
regulatedvariablethatisstabilisedatbywayofregulatoryprocesses.Theintegrativecontrolfor
thethermoregulatorysetpointwasoriginallysuggestedtobethehypothalamus(Benzinger,
1961);however,todate,nointegrationcentreforcomparingidealtoactualtemperatureshas
beendiscovered(Nagashimaetal.,2000;Romanovsky,2007).Rather,thesystemregulating
homeostatictemperaturerangesappearstoberegulatedbyheatlossandheatgainsystems,
actingsemi-independentlybutregulatingeithersideofanideallevel(Kobayashietal.,2006).
ThesetwosystemsappeartooperatefromwithinthePOAH,withallthermoreceptors
ultimatelytransmittingthermalsignalstohypothalamicneurons(Kräuchi,2002).WhileWSNs
andCSNswithinthePOAHarelikelytobetheregulatorsoftheheatgainandheatlosssystems,
littleisknownoftheirprojectingpathways(Nagashimaetal.,2000).Thecriticalcore
temperaturetheory,originatingfrombeliefinasetpointvariable,initiallyheldthatdeviations
awayfromthesetpointinstigatedthermoeffectorresponses.Resultantsignificanteffector
10
signallingwoulddriveheatlossorheatgainmechanismstoamendthechanges.(Sciences,2001;
Waterhouseetal.,2005).
InBenzinger’sseriesoforiginalstudies(Benzinger,1961a,1961b,1963),thetermsetpoint
waswidelyused,despiteathermoregulatory‘nullzone’of~0.5OCbetweenTCsweatingand
shiveringthresholdswhenskintemperaturewasbetween28OCand32OC(Mekjavicetal.,
1989).Thenotionofanullzonehasbeendiscussedthoroughlyinmanystudies(See(Kingmaet
al.,2012)forareview).Thenullzone,formallyreferredtoastheinterthresholdzoneor
thermoeffectorthresholdzone,is‘thetemperaturerangebetweentwothresholdbody
temperatures,foractivationofanythermoeffectorresponses’((Sciences,2001)p.273).
Consolidationoftheinterthresholdzoneoccurredfollowinganinvestigationby(Cababacetal.,
1977),whoobservedaninterthresholdzonenegligibleenoughtojustifythetermsetpoint.
OtherresearchbyMekjavicandcolleagues(Mekjavicetal.,1989;Mekjavicetal.,1991;Mekjavic
etal.,2006)alsoestablishedtheeffectorinterthresholdzone.Complicationsincurredintheir
firststudy(Mekjavicetal.,1989)encounteredsignificantmethodologicalerrors,whichwere
refinedintheirsecondstudy(Mekjavicetal.,1991).UsingaprotocolinwhichTskwasclamped
usingimmersed(28OCwater)cycling,experimentalobservationwasmadeofa“nullzone”of
~0.5OC,asmeasuredintheoesophagusandrectum(Mekjavicetal.,1991).Assuch,thenotion
ofaninterthreshold(null)zonehasbecomeincreasinglyprominentasanexplanationof
thermoeffectorresponsetothermalcues.
Distinctfromtheinterthresholdzone,thethermoneutralzone(TNZ)istheambient
temperatureatwhichdeviationsinTCarecontrolledbysensibleheatloss(discussedlater)
(Mekjavicetal.,2006;Sciences,2001).Thethermoneutralrangeisnotrigidbutaltersaccording
toendogenousthermalandnon-thermalfactors,suchaspostureorbasalmetabolicrate,oreven
clothing(Crawshawetal.,1975;Sciences,2001).Wengeretal(1976)observedaloweringofthe
thermoeffectorthresholdatnight,requiringearlieronsetofsweatingtomaintainthelower
circadian-associatedTC.Outsidethethermoneutralzone,thermalhomeostasisismaintained
11
throughincreasesinthermoeffectoractivity(i.e.,sweating,non-shiveringthermogenesis,and
shiveringthermogenesis,additionaltofurtherchangesinvasoconstrictortone),withgraded
increasesbeinglinearlyproportionaltotheperturbation(Mekjavicetal.,2006;Werner,2010).
Whilethermalfactorchanges(i.e.,ambienttemperaturedeviation)obviouslyleadto
thermoregulatoryopposition,sotoodonon-thermalfactors,someofwhichoscillatein
modulatingTC(Kräuchi,2002;Tayloretal.,2008a;Waterhouseetal.,2005).Suchnon-thermal
factorsincludediurnalfluctuationssuchasactivity-reststates(Refinettietal.,1992;Sciences,
2001),circadianfluctuationssuchashormonalandsleep-wakeregulation(Karaseketal.,2006;
Kräuchietal.,1994;VanSomeren,2006;Waterhouseetal.,2005),andultradiancyclessuchas
theovulatorycycle(Charkoudian,2003;Refinettietal.,1992).Brightlight,bywayof
modulationofsuchcircadianhormonerelease,produceschangesinTC(Cajochenetal.,2000).
Agingalsoactsasanon-thermalfactorduetodecreasedresponsivenesstodeviationsinTC,
alteredsurface-to-volumeratiosandreducedthermoeffectorcapacities(i.e.,reducedvasomotor
tone,etc.)(Raymannetal.,2005;VanSomerenetal.,2002).Theconfoundingeffectsof
thermoregulationoftenmaskthenon-thermalfactors(Kräuchietal.,1994).Forthepurposeof
thecurrentreview,onlythecircadian-relatedofthenon-thermalfactorswillbeconsidered.
DailyTCoscillationisdrivenbythenon-thermalcentralcircadianclock(discussedin2.3.5
Circadiantemperaturerhythm),andservesasanexcellentindirectmarkerofthecircadian
systemtiming(Helleretal.,2011;Kräuchietal.,1994;Refinettietal.,1992).Theoscillation
occurswithin-andmodulates-thethermoneutralzone,withanamplitudeofbasalTC
fluctuationbetween~0.5-1.0OC(Aschoff,1983;Wrightetal.,2002).Thisrhythmisachieved
mainlybymodifyingheatexchange(Waterhouseetal.,2005),whichnecessitatesinteractionof
thermalandnon-thermalsystems.Non-thermalfactorsinteractwiththermoregulationtoeither
enhanceorimpairtemperature-inducedvasomotoractivity(Mekjavicetal.,2006).This
interactionhasbeenshowninhumansperformingnocturnalexercise(Wengeretal.,1976).
12
ThermoregulationissignificantlyimpairedduringREMsleep(newterminology,stageR)in
humans;andtoalesserextentinNREMsleep(Helleretal.,2011).Manyanimalstudiesshow
reducedresponsestothermalcues,ordisruptedsleepinordertomaintainhomeothermy
(Helleretal.,2011).Parmeggianietal(1970)werethefirsttonotereductionsinstageRsleepin
catsathighandlowambienttemperatures,aswellascessationofthermoeffectoractivityupon
onsetofREMsleep.InNREMsleepthermoeffectorthresholds(forbothnon-shiveringand
shiveringthermogenesis)areloweredduringNREMsleepcomparedtowaking,inboththecold
andtheheat(Helleretal.,2011).Followinginvestigationoftheeffectofarangeofambient
temperatures(21-34OC)onsleepinmen,Haskelletal(1981)assertedthatthermoregulationis
incompatiblewithstageRsleep.Participantshadthehighestrateofsleepdisruptionsat
ambienttemperaturesof21OC,withtheleasttimespentatNREMstages3and4,andinstageR
sleep,andthelargestsleeponsetlatencyandshortesttotalsleep.Similarsleepdisruptions
occurredat34OC(Haskelletal.,1981).Observationsonwomenproducedcomparableresults
(Sewitchetal.,1986).However,menselectedfortheirabilitytosleepincoolenvironments,
showednodecreaseinRsleepincoolcomparedtothermoneutralconditions(Palcaetal.,1986).
Insummary,sleepsubstantiallyreducesthecapacityforbothheatlossandheatgain(Haskellet
al.,1981),profoundlysoduringRsleep(Helleretal.,2011;Refinettietal.,1992).Thedetailed
natureofthermoregulationinsleepiscomplexandisbeyondthescopeofthecurrentreview
duetodisassociationsfromthewakingstate(see(Driveretal.,2000;Helleretal.,2011)for
extensivereviewsofexercise,thermoregulationandsleep).
Thetiming,natureandextentofphysicalactivitythroughoutthedayaltertheamplitudeofTC
oscillation,therebyimpactingthesleep-associatednadir.Innocturnalrodents,theuseofa
runningwheelinconstantroutinedarkenvironmentshasbeenshowntophase-advancetherest
periodofthecircadianclock(Yamanakaetal.,2006).Exerciseinducingphasemodulationis
furthersupportedinmen,withexerciseintheafternoonenhancingsleep,andviceversainthe
evening(Driveretal.,2000).Theplacementofsleepenhancingexercisemaybeinpartdueto
thepyrogeniceffectsofexerciseenhancingtheTCoscillation,howeverexerciseintheevening
13
hasalsobeenshowntoassisttheheatlosscomponentoftheTCcycle.Yoshidaetal(1998)
demonstrated1hoflateevening(20:30-21:30h)exerciseat50-60%𝑉"#$%& significantly
reducedsleeponsetlatency.Tanaka(2001)similarlydemonstratedimprovedsleeponset
latenciesinelderlyindividualsfollowingalunchtimenap(30minat~1300h)andexercisein
theevening(30minat~1700h).Thenon-thermalTCcycleactivelypromotesheatloss.Toriiet
al(1995)demonstratedthiswithsignificantlyhigherheartratesandsweatratesinmen
exercisingat30%and60%𝑉"#'() intheevening(2000h)whencomparedtothemorning
(0900h).Thesethermoregulatoryresponseswererelatedtochangesinthecircadianphaseof
TC(oral),withlowintensitymorningexercisefacilitatingamuchmorerapidriseinTC(Toriiet
al.,1995).ThebluntedriseineveningTCinthemildintensityreflectsthelowernon-thermal
thermoeffectorzones(Toriietal.,1995).
Thermalhomeostasisismaintaineddespitethermalandnon-thermalfactorsimpingingupon
it.ThermalhomeostasisisfocussedonmaintainingTCwithinanullzoneof~0.5OC.Duetononthermalfactors,thisnullzoneisnotstaticbutoscillatesthroughoutthecycle.Temperaturecan
significantlymodulatethiscycleandtherebyimpactsleep.Thethermalfactorscanbeambient
temperaturesorthetimingexercise.
2.2.2
Sensation
Thermosensationisamodalityoftheskin(Schepersetal.,2010).Thermosensitivereceptors
drivethermoeffectorfunctionbyprovidinginputofbothstate(static)andchange(dynamic)of
internalandexternalenvironments(Tayloretal.,2008a).Receptorslocatedinthecoreare
primarilywarmsensitive,whilethoselocatedintheskinarepredominantlycoldsensitive
(Romanovsky,2007;Werner,2010).Thisreflectstheasymmetricalnatureofcoretemperature,
residingclosetotheuppertemperaturelimitofsurvivalwhilecomparativelyfarfromthelower
limit(Romanovsky,2007;Tayloretal.,2008a).Inthermoneutralenvironments,cutaneouscold
thermoreceptorsdisplayatonicfiringpatterntocodeforthecutaneoustemperaturestate
14
(Boulant,1996;Schepersetal.,2010),whilehypothalamicthermalpacemakercellsdisplay
burstfiringtocodeforbraintemperature(Pierau,1996).
Thehighprevalenceofcoldrelativetowarmthermoreceptorsintheskinismorerelevantto
thethermoregulatorysystemincombattingchangeincoretemperature.Bothcoldandwarm
receptorsdisplayabell-shapedcurveofactivationwithregardtotheirrespectivetemperature
ranges.Coldreceptorsdisplaymaximumdischargeintherangeof20-30OC(Boulant,1996;
Pierau,1996;Schepersetal.,2010;VanSomerenetal.,2002),whilewarmreceptorsdisplay
maximumdischargebetween40-45OC(Schepersetal.,2010;Tayloretal.,2008b;VanSomeren
etal.,2002).Beyondthesereceptorfiringranges,supplemental(e.g.,highthresholdcold
receptors;see(Schepersetal.,2010))andpainreceptorsareactive.
Coldreceptorsarelocatedwithinthedermal/epidermalborderat~150µmfromthesurface,
andconductprimarilyalongmyelinatedAδfibres.Warmreceptorsarelocatedslightlydeeperin
thedermallayerandconductsignalsalongunmyelinatedC-fibres.Coldreceptoractivityis
transducedmuchmorerapidlytothePOAH.Assuch,peripheralthermoregulationisfurther
sensitisedtocooling.Peripheralthermoafferentstravelviatheanterolateral,spinothalamic
pathways(Pierau,1996).Centrally,thecorethermoreceptorsarearrangedsoastodetectbrain
temperatureoscillations,particularlyfluctuationstowardbrainwarming(Romanovsky,2007).
Centralthermoreceptorsarearrangedhorizontallywithdendriteslocatedmediallyatthe3rd
ventricleandlaterallyatthemedialforebrain(Tayloretal.,2008a),butcanbefoundalloverthe
brain(Nagashimaetal.,2000).Theorientationofcentralthermoreceptorsoptimisesdetection
ofcerebrospinalfluidtemperatureandthetemperatureofbloodsupplyflowingaroundthe
brain.Thisrelationshipbetweenwarmcentralandcoldperipheralthermoreceptors,allowsfor
efficientdetectionofthemostlikelyadversethermalchallenges,frominternalandexternal
sources,respectively.
Twoeffectorsystemsaredrivenbythermo-sensitivity:autonomicandperceptual/
alliesthesialsensation.Autonomicthermo-sensitivitydescribesthephysiologicalresponses
15
whereasalliesthesialthermo-sensitivitydescribes‘thechangedperceptionofagivenperipheral
stimulusresultingfromthestimulationofinternalsensors’((Sciences,2001),p.247).Thesetwo
effectorsystemsaredifferentiallydrivenbetweencoreandskin,andbetweenskinsites,as
showninbothclosedloopandopenloopsettings(Cotteretal.,1996;Cotteretal.,2005;
Crawshawetal.,1975;Greenspanetal.,1993;Simmonsetal.,2008).Theratiobetweenthecore
andskinindrivingautonomicthermoeffectorsis~9:1(Tayloretal.,2008b),however,this
differsbetweenautonomiceffectors.Forexample,theTC:Tskratioisbetween6:1and20:1in
drivingthesweatingresponse(Nadeletal.,1971;Wyssetal.,1974),and3:1to5:1formetabolic
heatproduction(Chengetal.,1995;Mekjavicetal.,1986).Theratioforbehavioural/alliesthesial
effectorstimulusiscloserto1:1(Bulcaoetal.,2000).Thegreatercontributionoftheskintothe
behaviouralstimulationminimisestheenergeticallycostlymetabolic/autonomicresponses
broughtaboutthroughcorebodystimulation.Despitetheirtypicallysmallerrelative
contribution,skinreceptorsconstituteaprimaryinputforbothautonomicandalliesthesial
thermoregulation(Crawshawetal.,1975),especiallyinstableenvironments(Caldwelletal.,
2014).
Clarificationofthethermosensitivebasisofthermoreceptorshascomewiththediscoveryof
TRP(TransientReceptorPotential)channels(Boulant,1996;Romanovsky,2007;Schepersetal.,
2010).TRPchannelsarenon-specificcationchannelsthataredividedintosixsubfamilies
dependentontheirreceptivity(Figure2.1)(Romanovsky,2007).Withinthesesubfamilies,
TRPM8(melastatin)andA1(ankyrin)areresponsivetocold,andTRPV(vanilloid)andsome
additionalMchannelsareresponsivetowarm(Romanovsky,2007).Togetherthesechannels
(TRPM,TRPA,TRPV)arereferredtoasthermoTRPchannels(Romanovsky,2007;Scheperset
al.,2010).CollectivelyTRPV4andTRPM4&5appeartobefocalforresponsetoinnocuouscool
stimuli,whereasTRPV3,1&2respondtoincreasinglywarmstimuli(Romanovsky,2007;
Schepersetal.,2010).Thearrangementofthesethermoreceptivechannelsissuchthat
individuallytheycovermodesttemperatureranges,butoverlapinactivationtocumulatively
coveralargeactivetemperaturerange(Romanovsky,2007).ActivationofanyTRPchannel
16
resultsininwardioncurrentssuchthatrestingmembranepotentialisdepolarised
(Romanovsky,2007).Inresponsetocoldstimuli(menthol),Reidetal(2001)observedthis
inwardionfluxtobepredominantlycalciummediated.ThermoTRPM8isselectivelyexpressed
withinCSNs(Boulant,1996).InhibitionofK+channels,asaresultofcoolinghasalsobeen
observed,whichfacilitatesthedepolarisationandsignallingofcold-sensitivethermoreceptors
(Boulant,1996).
Mammalianthermoreceptorsarespecialisedatdetectinginnocuoustemperaturesimpinging
ontheskin(Boulant,1996).ThisisreflectedintheconvergenceofthermoTRPchannels
sensitisedintheseranges(Romanovsky,2007;Schepersetal.,2010).Wheninnocuouschangein
thermalstateisdetected,receptorsrespond
dynamicallybytransiently,butvigorously
increasingfiringrate(Pierau,1996;
Schepersetal.,2010).Thefiringrateof
thermoreceptorsduringtemperature
changeisasmuchas5-10timesgreater
thanatsteadystate(Hensel,1982).The
thresholdfordetectionappearstosensitize
withincreasedrateofcoolingaswell
Figure2.1:Schematicrepresentationofthe
dependenceoftheactivityofthecoldactivated
(blue)andwarmactivated(red)thermoTRP
channels.FromPatapoutianetal(2003)
(Greenspanetal.,1993),althoughsomepostulatethatthisisambiguous(Crawshawetal.,
1975).Followinginitialreceptorresponses,thermoreceptorsrapidlyadapttonewsteadystates
(Zhangetal.,2010c).Beyondinnocuousranges,however,thermosensorsdonotadapt
(Schepersetal.,2010).
Detectionofthermalchangeisdependentonthelocationandarealextentofstimulation;e.g.,
theface,handsandfeethavegreaterreceptordensities,improvingtheirsensitivity.Spatial
summationcanalsoreducethethresholdandincreasedetectabilityandtheperceivedintensity
ofaparticulartemperature(Greenspanetal.,1993).Peripheralthermosensitivityisbetterat
17
detectingchangemorethanactualtemperature(See(Kobayashietal.,2006)forcomparator
theory).Clineetal(2004)arguedthathumansare‘poorestimatorsoftheirownthermalstate’
(p.2302).Cline’s(2004)assertioniscorroboratedbyGreenspanetal(1993),whonotedthat
individualsaremoreaptatrecognisingtemperaturedecreasethandetectingstaticcoolnessper
se,followinganexperimentinwhichthemajorityofparticipantsfailedtocompletecooling
staircasesduetoratesofcoolingbeingperceptuallyunbearable.Behaviouralresponsesto
changesinthethermalenvironmentalsoappeartobebimodal(Humphreysetal.,1999),with
adjustmentsconsistentlyovershootingthermoneutral(Clineetal.,2004).Arensetal(2006a,
2006b)andZhangetal(2010a,2010b,2010c)havedemonstratedinbothuniformandnonuniformenvironmentsthatindividualsrespondedinordinatelytoonsetofcoolingorheatingin
bothlocalandwhole-bodymanipulationsettings.Bimodal,exaggeratedbehaviouralstimulation
servestoprotectthebodyagainstpotentiallydamagingtemperatures(Weissetal.,1961),
especiallyatbodylocationsmostpronetoenvironmentalinfluence.
Thethermalsensationassociatedwithsuddenchangeintemperatureislikelyduetothe
magnitudeofthedynamicthermoreceptorresponsementionedabove(Arensetal.,2006b;
Zhangetal.,2010a).Theovershoottotemperaturechangeismorepronouncedforthermal
comfortthanforthermalsensation,andforlocalthanoverallthermalcomfort(Arensetal.,
2006b;Zhangetal.,2010c).Despiteanovershootforthermalcomfort,thermalsensation
displaysaroughlylinearrelationshiptoskintemperatureintherange29OCand34OC(Zhanget
al.,2010c).Outsidethisrange,thermalsensationdisassociatesfromskintemperature,
exaggeratingtheperceivedchange(Zhangetal.,2010c).Asawhole,thermalcomfortthresholds
outsidetheneutralrangearehighlydependentuponwhole-bodythermalsensation/stateand
comfort,sizeoftheaffectedareaandtherateatwhichwarmingorcoolingisoccurring(Cotter
etal.,1996;Greenspanetal.,1993;VanSomerenetal.,2002;Wangetal.,2007).
Ofallskinregions,thefacehasthegreatestalliesthesialandautonomicsensitivity(Arenset
al.,2006a;Cotteretal.,1996;Cotteretal.,2005;Crawshawetal.,1975;Simmonsetal.,2008);
18
thisismoreapparentincoolingthanwarming(Cotteretal.,2005;Zhangetal.,2010c).The
face’ssensitivityisinpartduetothepredominanceofnon-convergentthermalafferents–a
greatnumberofwhicharestillunaccountedfor-whichisnotpresenttothesameextentinother
regions(Cotteretal.,2005;Nagashimaetal.,2000;Romanovsky,2007).Itisthedistributionof
thermoafferentsthatdeterminesthedominanceofwhole-bodythermalsensitivityandcomfort
(Arensetal.,2006b;Cotteretal.,1996).Headtemperatureappearstobecriticalforwhole-body
thermalcomfort(Arensetal.,2006a),andcoolingtheheadappearstobethebestmethodof
reducingthermaldiscomfortassociatedwithheat,irrespectiveofcorebodytemperature
changes(Simmonsetal.,2008).Inuniformambientheatstress,theheadisalsolesscomfortable
thantherestofthebody,promptingcorrectivebehaviour(Arensetal.,2006a).Arensetal’s
(2006a,2006b)appraisalofthehead’sroleinwhole-bodythermalsensationandcomfort
corroboratesstudiessuchasCotteretal(1996)andSimmonsetal(2008).Simmonsetal(2008)
arguefacialcoolingismoreefficientatdissipatingheat,reducingthermalstrain,andimproving
comfortthanbodyareasofequalsize(i.e.,10%oftotalbodyarea(Duboisetal.,1916)).
Theheadandfacehavemajorthermoafferentandthermoefferentrolesalsoforautonomic
thermoregulation.Heatingthefacegeneratespowerfulsudomotorresponses(Cotteretal.,
2005);presumablyfacialcoolingwouldelicitasimilarlypowerfulshiveringresponse.Thelarge
vascularsupplyinconjunctionwithspecialisedskinontheface(discussedlater)alsofacilitates
vasomotorandsudomotor-mediatedcooling(Cotteretal.,2005).Thismaybewhyinwarm
environments(i.e.,32OC),theheadandfacebecomesignificantlywarmerthantherestofthe
bodyexceptingthehands(Arensetal.,2006a)andtoes(Love,1948;Werneretal.,1980).
Coolingtheheadinhotenvironmentscanbluntthecoretemperaturerisebyupto50%
(Simmonsetal.,2008)despiteseeminglycounterintuitivesuppressionofsweating,whichis2-5
timesmorepowerfulthanotherskinareas(Cotteretal.,2005).WhileCotteretal(2005)agree
thatfacialcoolingcanbeusedtooptimallyreducethermaldiscomfort,theyindicatethatthe
extremitiesarebetterforalleviatingheatstorage,inpartduetotheirminimalautonomicdrive
(Cotteretal.,1996).
19
Thehandsandfeethavelargeperceptualrepresentationstoprovideearlyawarenessof
temperaturechange;furthermore,thehandsaremoresensitivetotemperaturechangesthan
thefeet(Cotteretal.,2005;Tayloretal.,2014).Thedistanceoftheextremitiesfromthecore
makesthemmostsensitivetoenvironmentalchange.However,thesensitivityoftheextremities
doesnotnecessarilytranslatetoautonomicthermoregulation(Cotteretal.,1996;Crawshawet
al.,1975),asthiswouldbecounterproductivetomaintainingthermalhomeostasisinactive
humans.Theextremitiesundergothegreatesttemperaturefluctuationofallbodyareas
(Greenspanetal.,1993;Werneretal.,1980),whichmaybeinstrumentalinthefeet’shigh
thresholdsfortemperaturerecognitionandlowthermosensitivity(Crawshawetal.,1975;
Greenspanetal.,1993).Conversely,thehandsappeartohavesignificantlylowercoolness
thresholdsthanotherlimbsegmentsobserved(arm,leg,foot)(Greenspanetal.,1993).Atlocal
skintemperaturesof~26OCthermalsensationsareofslightlycoolandneutralforthefeet
(Arensetal.,2006b);thissuggeststhatdiscomfortthresholdwouldoccuratmuchlower
temperatures.Thehandsreachtheirdiscomfortthresholdat20.7OC(Candasetal.,2007).The
apparentlyattenuatedthermalsensationofthefeetcanbebeneficialforstudiesconducting
subtlemanipulationsastheydonoteasilyinducethermoregulatoryorbehaviouralresponses,
however,thismayyetbedetrimentalforsleeponset(See2.3CircadianRhythms).
Theextremitiesareabletohavesomeimpactwhole-bodythermaldiscomfort.In
observationsofwhole-bodyandlocalthermalsensationsandcomfort,(Arensetal.,2006a)
observedthatoverallperceptionisdominatedbytheoneortwomostuncomfortablelocations.
Inhotambientsituationswhereboththebodyandtheheadarehot,thenthetemperatureofthe
headhasbeendemonstratedtodominatethermalcomfort;likewiseinwarmsituationswith
warmwhole-bodyandsegments,coolingthefeetisabletoremediatethethermaldiscomfort
(Arensetal.,2006b).Incoolenvironments(TAmb=20OC),thegreatestincreaseinlocaland
overallthermalcomfortisproducedbywarmingthefeetasopposedtotheneckorhead(Arens
etal.,2006b)(i.e.,bywarmingthecoolestregion).
20
Themagnitudeofthermalsensationdiffersdependingonthebodylocationundergoingthe
thermalstimulusandthetypeofreceptoractivatedatthatparticulartemperature.Thisisin
regardtoboththesensitivityofthereceptoraswellthedominantthermoafferentfeedbackit
delivers;autonomicoralliesthesial.Theextremitiesaremostheavilyinfluencedbythe
environmentandthereforearemostcapableofprovidingperceptualinformation,tominimise
theneedforphysiologicaleffectorresponses.Ifsufficientthermoafferentfeedbackarrivesto
driveanautonomicthermoeffectorresponse,however,thevasomotorresponseisthemost
energeticallyefficientthermoeffector.
2.2.3
Vasomotion
Inhumans,thereareessentiallythreeautonomiceffectorcategoriesforthermoregulation:
metabolicheatproduction,sweatingandactivevasodilation,andreleaseofvasoconstriction
(Werner,2010).Variousbehaviouralmechanismsactinsynergywiththeseautonomiceffectors.
Thesystemsofefferentcontrolofeffectororganscanbesimilar,asforactivevasodilationand
sweating(Charkoudian,2003),orbrownadiposetissueandskinvasculature(Romanovsky,
2007),butareoftenfunctionallyindependentofeachother(Charkoudian,2003;Nagashimaet
al.,2000;Romanovsky,2007).Thethermoeffectorsystemsoftenoperateinparallel,inresponse
toperturbations(actualorimpending)oftheTC.Almostallthermalafferentsconvergeatthe
POAH,whichalsodrivesthermoeffectors,thoughcompletepathwaysarenotyetfully
understood(Nagashimaetal.,2000).Incompleteknowledgeofintegrativeandefferent
pathwaysappliestoallthermoeffectors.
WithinTNZs,TCismodulatedsolelythroughvasodilationandvasoconstrictiontocontrol
sensibleheatloss.Atrest,thesethermallyinducedchangesarerestrictedtothecutaneous
compartment(Caldwelletal.,2014;Edholmetal.,1956);thesearepresumablyviawithdrawal
ofvasoconstrictortone.Neuralpathwaysforvasomotionareknowntotransmitdirectlytothe
medulla,throughthemedialforebrainbundle(Nagashimaetal.,2000;Romanovsky,2007).
Withinthemedulla,thereappearstobeafunctionalseparationinvasoconstrictionand
21
vasodilationpathways.Experimentalstudieshaveidentifiedtwomedullaryareasdifferentially
responsivetoheatingorcoolingsignals(Kanosueetal.,1999);thesearethecaudalprojection
fromthelateralhypothalamustothereticularformation,andtheventraltegmentalarea.The
anatomicaldivisionsinheatlossandheatgainpathwayssupportscurrenttheoryof
thermoregulatorycontrol.Nagashimaetal(2000)postulatethatWSNslikelysendexcitatory
signalstothevasodilatoryheatlosspathwaysandinhibitorysignalstothevasoconstrictoryheat
gainpathways.
Efferentpathwaysarelargelyinhibitory(Romanovsky,2007).Assuch,thermoeffector
activationrequiresdisinhibitionoftonicallyinhibitedneurons.Uponactivationofsuchneurons,
excitatorysignalstypicallyflowthroughsympatheticganglionicpathways(Folkow,1955).
Evidenceindicatesthatdilatorypathwaysalsousesympatheticnerves(Tayloretal.,2014),
especiallythosesupplyingvesselswithinglabrousskin.Theexistenceofsympatheticallyactive
vasodilationhasbeenapparentsincethe1930’s(Grantetal.,1938;Lewisetal.,1931).However,
vasodilatorycontrolisnotorganisedsolelythroughtheganglionicpathway,asshowninlesion
studiesinmammals(Folkow,1955).Currentevidenceindicatesthatvasodilationismediated
throughco-transmissioninsympatheticcholinergicnerves(Charkoudian,2003).Theexact
mechanismsofactivevasodilationarestillelusivedespitemanyproposedmechanisms.Some
possiblecontributorsthathavebeenproposedincludeacetylcholine,nitricoxide,vasoactive
intestinalpeptideand/orsubstanceP(Charkoudian,2010).
Changesinvasomotortonearedrivenlargelybycentralsympatheticoutflow,viaeither
cholinergicoradrenergictransmittingfibres.Innormothermia,centralmodulationislargelyvia
sympatheticadrenergicnervesmodulatingvasoconstrictortone(Charkoudian,2003).
Disinhibitionofthissympatheticadrenergicdriveistermedpassivedilation(Caldwelletal.,
2014;Tayloretal.,2014).WithintheTNZ,neuralinputisconstantlychangingvasomotorand
venomotortone,leadingtohighlyunstableskintemperatures(Tayloretal.,2014;Werner,
2010)asobservedbyKräuchietal(1994).Indeed,withinnormothermicenvironments,
22
cutaneousbloodflowfluctuatesmoreoftenthanitdoesatextremes.Fagrell(1985)observed
periodicfluctuationsinthecapillariesof6-10cycles/min.Similarly,Wangetal(2007)observed
frequentfluctuationsinfingertemperatureof~1-2OC,occurringat2-5minintervals;
presumablytoalterTCheatexchange.
Thecontrolofskinvasomotionisdeterminedbycentral(neuraloutflowandhydrostatic
pressure)andlocalfactors(e.g.,nitricoxide,andendocrineadrenaline)–asidefromthefactthat
localTskisalsopartofthethermoafferentdrive.Whilelocalfactorsarepowerful,theycannot
abolishordominatethecentraldrive(Tayloretal.,2014).Thedegreeoflocalandcentral
controldiffersbetweenskinlocations.Withheating,Kingmaetal(2012)observedbloodflow
increasesof~29-foldinthehandsintheheat,butonly~3-foldincreasesintheforearm.
Conversely,incoldenvironments,theheadreducesheatlossby17%,thearmsandlegsby25%
andthehandsandfeetby50%(Kingmaetal.,2012).Suchdifferencescanbeattributedto
differingskintypes,asthedegreeofcentralcontrol,andpresenceofspecialisedvessels(AVA’s;
discussedlater)differswidely.Thecontrolofskinvasculaturefrombothcentralandlocal
factorsinconjunctionwithspecificvascularadaptation(AVAs)allowsfortheextravagant
rangesinskinbloodflow.
Theratioofcontrolinthehandsandfeetisdominatedbycentralthermoefferentswith
minimallocalmodulatorycontrol.Thismeansthatwhilelocalfactorscan–anddo–sensitise
regionalvesselsintheextremitiestheydosotoalesserextentduetothecontrolexhibitedby
thecentralthermoeffectors.Thevolarsurfaces(palmarandplantaraspects)areinnervated
solelybyadrenergicconstrictortone(Caldwelletal.,2014;Tayloretal.,2014).Innon-glabrous
skin(ondorsalaspectsofhands/feet),passivedilation,broughtonthroughwithdrawalof
constrictortoneisaccompaniedbyactive(perhapscholinergic)dilation.Activedilationis
responsiblefor80-95%oftheflowincreaseinnon-glabrousskin(Tayloretal.,2014).
Incoldenvironments(e.g.,10OC),vasoconstrictionofthelimbsismaximalinlightlyclothed
individualsatrest,leadingtogreaterenvironmentalinfluence.Eveninmoderateair
23
temperatures(e.g.,20OC)cold-inducedvasoconstrictortonecanbemaximal(Tayloretal.,
2008b).Theinter-regionaldifferencesinlocalskintemperaturescanbeasgreatas17OC(foot
toforehead),whereasinwarmenvironments(40OC)thedifferencebetweenthecoreandskin
temperaturesandalsobetweenskinregionsisassmallas~2OC,duetochangesinvasomotor
control(Werneretal.,1980).Thesympatheticadrenergicoutflow,actsonarterialvasculature
(arteriolesandAVAs)andalsotheveins.Thereservoirsinveinsliedistally(i.e.,legsandfeet);
assuch,constrictionofveinsreducesthesereservoirsandhasanamplifyingeffectofcentral
constrictoryinput.
Thehandsandfeethavespecificmorphologicalcharacteristicsallowingthemtoserveas
excellentradiators(Charkoudian,2003;Tayloretal.,2014),whilealsobeingcapableof
significantwithdrawalofheattoinsulatethecore.Thebones,inthehandsandfeet,actasheat
sinks,whileminimalinternalmusclethatisalsorelativelyinactivemakesforminimallocalheat
production.Largesurfacearea-to-volumecoefficientsinthehandsandfeetalsomaximiseheat
losscapacity;i.e.,fingershavecoefficientsof2.2,whereasproximalskinsiteshavecoefficientsof
~1.0(Aschoffetal.,1958).Comparedtoproximalsegmentsofsimilarsize,thehandhasa
surfacetomassratio4.1–5.2timesgreater(female–male),whilethefootis2.9-3.2times
greater(Tayloretal.,2014).Suchmorphologicalandphysiological(e.g.,highAVAandsweat
glanddensities)characteristicsmakethehandsandfeetthebestcapablesitesforheat
dissipation,yettheyrepresent4.4–4.6%and7.1–7.4%,respectively,oftotalbodysurfacearea
(Kingmaetal.,2012;Tayloretal.,2014).
Thehandsandfeetarewellsuppliedbyarteries.Thehandreceivesflowdirectlyfromthe
ulnarandradialarteries,whichprogressintothesuperficialanddeeppalmararches(Standring,
2008).Thepalmararchesjoinatthedigitalbranches,tosupplythefinger(Standring,2008).The
footissuppliedbythemedialplantarandlateralplantararteries,whichprogressbehindtheir
respectivemalleolarprominences,andbythedorsalispedis,progressingalongthedorsalaspect
ofthefoot(Standring,2008).Alongthedorsalaspect,thedorsalispedisformsthemedialand
24
lateraltarsalarteries,andthearcuatearteryandfirstdorsalmetatarsalartery(Standring,
2008).Branchingfromthesearethearteriessupplyingthetoes.Oftheplantararteries,the
medialplantararterysuppliesthefootmusclesandmedialskin,whilethelateralplantarartery
suppliestheheelandlateralsole,beforeprogressingdeepandformingtheplantararchwiththe
dorsalispedis(Standring,2008).Theplantardigitalarteriessupplythetoes(Standring,2008).
Bloodflowtothefeetisconsistentlylowerthanflowtothehands(Caldwelletal.,2014).
Deepandsuperficialveins,aswellasamoresuperficialvenousplexus,drainthehandsand
feet.Suchredundancyallowsforthewithdrawalofbloodflowfromsuperficialtodeepareas,
“thickening”theshellagainstheatloss.Theveins,beingcapacitancevessels,canstore70-80%
oftotalbloodvolumeinthedistalregionsinTNZs(Tayloretal.,2014).Itisprimarilyby
constrictionofthesedrainagevessels,inthecold,thatreducestheheatoffloadfromthedistal
extremities(Tayloretal.,2008b).Inaddition,withinthelimbstheproximityofthearteriesto
theveins(arguably)allowsforacountercurrentheatexchangetooccur,whichfurtherhelpsto
limitheatloss(Tayloretal.,2014).
Ambientcoldgeneratesvasoconstrictionbeginningintheextremitiesandprogressing
proximallyasrequiredtominimiseheatexchangewiththeenvironment.Ambientheatproduces
amuchmoregeneralisedvasodilation.AtrestinTNZs,skinbloodflowis~0.250L/min(~0.35L
inmales;Tayloretal.,2014),andcanrangefromcloseto0L/minto6-8L/minunderextreme
thermalstress(Charkoudian,2003;Hardyetal.,1938;Rowell,1970).Theminimumbloodflow
requiredtosupportcutaneoustissuehasbeenestimatedtobe~0.8mL/100mL/min
(Abramson,1965).Basalbloodflowatthehandsis~6.7mL/100mL/min,whileatthefeetitis
~2.8mL/100mL/min(inmales(Caldwelletal.,2014)).Thisvolumeissufficienttoallowforthe
appropriaterateofsensibleheatloss(~1.5W/kg)inarestingstate(Charkoudian,2003).
Thechangesinvasomotortonealtertheinteractionsofheatlossbetweenthecoreandskin,
andtheskinandenvironment.Theskinservesasashelllayertoprotectthecore,toits
detrimentifnecessary.Theskintemperaturetypicallyresideslowerthanthecore,effectively
25
providingagradientforheattoflowfromthecoretoskinandfinallyenvironment.Distalproximaltemperaturegradients(DPGs)areimpededbyreducedcutaneousbloodflow,despite
largergradients,whereasdilationfacilitatesDPGbyincreasingtheskin-environmentgradient,
makingheatremovalmorepermissible.Inwiderangesofambienttemperaturestheshell
typicallycomprises10-20%ofthehumanbody,however,whencoldstressed,theshelllayer
increasesasmuchas30-40%(Gaggeetal.,1996).Thethickeningoftheshellisduetothe
gradualwithdrawalofcutaneousflow(Raymannetal.,2007b;Romeijnetal.,2012a;
Waterhouseetal.,2005).
2.2.4
Arteriovenousanastomoses
Thearteriovenousanastomoses(AVAs)aredenselylocatedinregionsmostcapableofheat
offload(asalludedtoabove)andarecontrolledsolelybycentralsympatheticadrenergicinput
(Charkoudian,2003).ThemajorityofglabrousskincontainsAVAs,howeverAVAsaremost
denselypackedinacralskin.Examplesofacralskinincludethenose,ears,palmsandsolesofthe
feet(Gaggeetal.,1996;Tayloretal.,2008b).Insuchregions,anastomoseslierelativelydeepto
thepapillarycapillaries,andserveasshuntstothepoorlyinsulatedvenousplexus(Hales,
1985).Thecomparativelylargediametersallowforthevastlygreaterflow(AVAshave~25-125
µm,comparedtothetypicalcutaneouscapillariesof~10µm);thisequatestoroughly10000
timesgreaterbloodflow(PoisseuillesLaw;(Tayloretal.,2014)).
Atthermalneutrality,anastomosesdisplaysomevasomotortone;constrictingapproximately
threetimesperminute(Kingmaetal.,2012).Inthecold,AVAsarecontinuouslymaximally
constricted;however,whenheatingisappliedAVAsdilatepassivelyat~34OC(Figure2.2)
(Fagrelletal.,1977;Gaggeetal.,1996).TheAVAsareprimarilyresponsibleforthealterationsin
theDPGandassociatedalterationsinTCheatloss.Thisisespeciallyapparentinresponsetothe
non-thermalcircadianrhythm(discussedin2.3.5Circadiantemperaturerhythm)(VanSomeren,
2006).
26
Asstatedabove,thehandsandfeetarespecialisedforheatoffload,andinconjunctionwith
anatomical/morphologicaladaptations,alsohavearichcutaneousvascularitythatreflectsthis–
between40-70vessels/mm2(Tayloretal.,2014).Themostcomplexandlongestanastomoses
residewithinthesolesandpalms,with
2014).Atrest,basalhandbloodflow,when
normalisedforsegmentalsurfaceareasis
morethanthreetimesgreaterinthehands
(550mL/m2/min)thanintherestofthebody
(Tayloretal.,2014).Increasesinbloodflowin
SkinBloodflowvelocity(mm/sec)
between30and200AVAs/cm2(Tayloretal.,
thehandsandfeet(amongotheracralskin
sites)arefacilitatedbyAVAs.Byshuntingsuch
largevolumesofbloodtothevenousplexus,
thehandsandfeetareabletoeffectively
radiateoffvastquantitiesofheatintothe
Figure2.2:Correlationbetweenskin
temperatureandrestingbloodflowvelocity
(CBV)inonenailfoldcapillaryofahealthy37year-oldman.Figureandlegendextracted
from(Fagrelletal.,1977),whoinvestigated
theeffectofskinwarmingonskinbloodflow
environment(Gaggeetal.,1996;Halesetal.,
1978).
2.2.5
Summary
Thermoregulationisalargeandcomplexsystem,ofwhichonlytherelevantaspectsare
discussedhere.Thermoregulationattemptstomaintainhomeostasisofcoretemperaturein
responsetoperturbationsfromthermalandnon-thermalfactors(i.e.,theperturbationsonTC
areultimatelythermal,butmodulatinginfluencesonthermoregulationcanbenon-thermal).
One’sthermoregulatorystateistransducedbycoreandskinthermoreceptors,whichprovide
differingautonomicandperceptualdrivebasedonlocation(e.g.,theTCisapowerfulautonomic
driver,whereashandsandfeetprovidehighperceptualdriveforlocalisedthermalsensations
butperhapsnotforbehaviouralthermoregulation,andthefaceprovidesstrongdriveforallof
27
these).Autonomic,andtoalesserdegree,perceptualdrivers,inducethermoeffectorresponses
inoppositiontothedirectionofchange.
Alteredvasomotortoneistheprimaryphysiologicalthermoeffectorresponse.Vasomotionis
capableofproducingfluctuationsincutaneousbloodflowfrom6-8L/min(Rowell,1970)to~0
L/min(minimalvolumespecificflowinhandsandfeetisapproximately0.8mL/100mL/min;
(Abramson,1965)),allowingmoreheattobemostlyconvectedandradiatedfromthe
extremitieswhenbloodflowishigh,whilebeingcapableofminimalheatloss(butalsopotential
damagetotheextremities)atlowflow.Thermoregulationisstillincompletelyunderstood,
particularlywithregardtothetransferofheatfromthecoretothelimbsegments,especiallythe
feet.Thetemperatureprofilesoftheextremitiesareofparticularinterestwithinthesleepfield.
Discomfortthresholdsoftheextremitiesarewidelyrecognisedinregardtosleeponset
(Haskelletal.,1981;Kräuchietal.,2008;Palcaetal.,1986;Raymannetal.,2005,2008;Sewitch
etal.,1986).Theextremitiesarehighlysusceptibletocoolingduetotheirstrong
vasoconstriction,locationandlackofheatgeneratingcapacity.Thethermoregulatory
contributionoftheextremitiesinuniformandtransientenvironmentshasbeenelucidatedby
Arensetal(2006a,2006b)andZhangetal(2010a,2010b,2010c),andinparticularbythe
recentreviewbyTayloretal(2014).However,researchontheextremitieshaspreviously
focussedonthehands(Candasetal.,2007;Clineetal.,2004;Tayloretal.,2014),withfew
studiesonthefeet.Studiesexploringtemperatureprofilesoftheextremitieshavefound
differentialresponsestointerventions(e.g.,tosleepdeprivation(Romeijnetal.,2012b)),such
thatupperlimbresponsescannotbeassumedtoapplytothelowerlimbs.Thermaldiscomfort
hasprovidedinsightintotheroleoftheextremitiesinsleeponsetand,clinically,insleep
difficultiesinvolvingvasospasticsyndrome(Flammeretal.,2001),thermaldiscomfortofcold
extremities(Kräuchietal.,2008),agingandinsomnia(Raymannetal.,2007a;Raymannetal.,
2007b),andnarcolepsy(Fronczeketal.,2008).
28
Thermalcontrolofdistalextremitieshasbeenfurtherimplicatedwithsleep.Anelegantstudy
byKräuchietal(1999)identifiedacausalrelationoffoottemperatureonsleeponsetlatency.
Broadlystated:‘vasodilationofdistalextremitieswasthebestpredictorofthebody’sreadiness
forsleep’(Kräuchietal.,1999,p.37).FurthermoreRomeijnetal(2012b)sleepdeprivation
studyrevealedsustainedcircadianrhythmicityinfoottemperaturecyclesacrossdayandnight,
whilethehandslostrhythmicity.Thelossofwhole-bodycircadiantemperaturerhythmicity
reciprocateddramaticsleepdeprivation-inducedchangesinarousallevelstosustained
attentiontasks(Romeijnetal.,2012b).Suchfindingswarrantmoreattentioninregardtotheir
contributiontothermoregulatoryknowledgeperse,andwithregardtosleepknowledge.An
increasingnumberofsleepresearchstudiesareaddressingthermoregulatoryaspects,and
throughtherelationbetweentemperatureandarousal,havefocussedonfacilitatingsleep.
Unfortunately,therehasbeenalmostnoresearchintothepossiblevalueoflowextremity
temperaturesinpreventingsleepandmaintainingarousal.Fronczeketal(2008)haveutilised
corewarmingandperipheralcoolingtoinducereciprocalincreasesinvigilanceandsleeponset
latencyinnarcoleptics(furtherdiscussedin2.3.6Narcolepsy).Fronczeketal’s(2008)findings
havenotbeenappliedtoahealthypopulation.Thepresentthesisisthatlower-limbextremity
coolingwouldalsobeapplicableforinterruptingthethermoregulatoryprofileassociatedwith
sleeponset,andhencehelpinmaintainingvigilanceinhealthyindividuals.
Subtletemperaturemanipulationisoftenoverlookedformoreaggressivetemperature
manipulationstrategies.Subtle,orinnocuous,temperaturemanipulationaffectslocalvasomotor
tone,withoutimpingingsubstantiallyonthermalsensation.Thermalsensationofthe
extremitiesalsodoesnot(necessarily)implementautonomicchange(Arensetal.,2006;Cotter
etal.,2005;Simmonsetal.,2008),thereforeinsubtleranges,localvasomotortoneisthe
primarymeansofinnocuouscolddefence.Inhealthypopulations,thermoafferentinputwould
beexpectedtooverridenon-thermalinputsindrivingthermoregulatoryresponse,evenassleep
pressureaccumulates.However,non-thermalinputappearstomodulatethethermoregulatory
effectorthresholds,suchthattheTNZoscillatesaccordingtothecircadianrhythmofTC(See
29
(Helleretal.,2011;Wengeretal.,1976;Yamanakaetal.,2006)).Inturn,thermalfactorsappear
toimpaircircadianprocesses(Kräuchi,2007),orexacerbateunderlyingcircadianor
thermovascularissues(e.g.,narcolepsy,insomnia,vasospasticsyndrome).Non-thermalfactors
relyonthehealthyfunctionofAVA’stoallowcircadianoscillationofTC,yetlocaltemperatures
lessthan30OCinducevasoconstrictionofAVAs.
2.3
CircadianRhythms
Themostovertandhighlystudiedcircadianrhythmisthesleep-wakecycle,including
vigilanceanddrowsiness(Okenetal.,2006).In1916encephalitislethargica,studiedbyVon
Economo,sparkedinterestinhypothalamicpathologydirectlyrelatedtothedisruptionofsleepwakeregulation(Moore,2007;VonEconomo,1931).Thetwo-processmodelofsleepregulation
wasintroducedbyBorbelyin1982(Borbely,1982),andpervadesthroughallmodels
addressingregulationoffatigueandperformance(Achermann,2004).Thetwo-processmodel
describestheinteractionofthe
timingofalternationbetweenthe
sleepandwakecycles(Beersma,
1998).Thetwoprocessesthat
comprisethemodelarethe
homeostaticandcircadianaspects
ofsleepandwaking,termedprocess
S,andprocessC,respectively
Figure2.3:TimecourseofProcessesSandCafterregular
andextendedwakingperiods.From(Borbely,1982).
ShadedarearepresentssleepandrecoveryofProcessS.
(Borbely,1982).Thehomeostatic
hourglass,processSinteractswiththecircadianclock,ProcessC,toregulatethepressureto
sleep(Figure2.3)(Porkka-Heiskanenetal.,2002;Romeijnetal.,2011;Tononietal.,2006).
Thesetwoaspects,asdescribedoriginallybyVonEconomolieprimarilywithinthe
30
hypothalamus.Specifically,theventrolateralpreoptichypothalamus(VLPO)istheprimarysite
forthehomeostatichourglassandthesuprachiasmaticnucleus(SCN)isthesiteofthecentral
circadianclock(Moore,2007;Saperetal.,2005).VonEconomooriginallydescribedtheanterior
hypothalamusandtheposteriorhypothalamusaptlyasthesleepcentreandthewakecentre
(Moore,2007;Saperetal.,2005).
Thetwo-processmodelrefersnotonlytotheprocessesindividuallyinstitutedbythe
homeostaticandcircadianprocesses,butmoreimportantly,theirinteractionandintegration
(Achermann,2004);forexample,theflip-flopswitchinhibitingtheVLPOandfacilitatingthe
ascendingarousalsystem(AAS),whichswitchesrapidlytoaidsleepbyallowingtheVLPOto
inhibittheAAS(Gausetal.,2002).Originallyproposedinrats,thetwo-processmodel
‘postulatesthat…processSrisesduringwakinganddeclinesduringsleep,andinteractswith
processC’(SeeFigure2.3)((Borbetal.,1999),p.560).ProcessCisindependentofwakingand
sleepingbutregulatesthedurationofeachaccordingtomodulationviathelight-darkcycle.A
furtherprocessrepresentingsleepinertia,andtheinteractionbetweenProcessesSandC,was
institutedtotheoriginalmodeltoeffectivelycreateathree-processmodelthatappearstobe
morereflectiveofhumandiurnalcycles(Achermann,2004).Thisthirdcomponentwasusedto
furtherdescribetheultradiandynamics,ofwhichsleepinertiaisonecomponent(Borbely,
1982).Theultradiandynamicshelptoencompassthetwosleepcycles,RandNREM,butalsothe
timecourseofdaytimevigilancebroughtaboutthroughtheinteractionbetweenthe
homeostaticandcircadianprocesses(Borbely,1982).
Boththehomeostatichourglassandthecentralcircadianclockarethetwoprimarysitesof
oscillationthatinfluencesleep-wakeregulation.Saperetal(2001;2005)putforwardamodel
proposingthatthehypothalamusactsasthe“sleepswitch”allowingsharptransitionsbetween
thesleepandwakingstates.Theswitch,knownasthe“flip-flop”switch,alternatesbetweenthe
wake-promotingascendingarousalsystemthatactivates“wake-active”neuronsduringawake
periods,andthe“sleep-active”neuronsinthePOAH,morespecificallytheVLPOarea.This
31
switchisstabilisedbyorexin/hypocretinneuronsinthelateralhypothalamus,thelossofwhich
resultsinnarcolepsy(See2.3.6Narcolepsy).Thephysiologicalalterationsbetweenwakingand
sleepingstatesoccuralongsidefacilitativebehaviouralcues.Suchbehaviouralfactorsarecalled
sleep-permissiveorwake-promotingfactors,andincludelightintensity(Burgessetal.,2001;
Karaseketal.,2006),posture(Raymannetal.,2007a;Romeijnetal.,2012a),temperature
change(Fronczeketal.,2008;Raymannetal.,2007a;Romeijnetal.,2011)anddietaryintake
(Fronczeketal.,2008;Reyneretal.,2012).
2.3.1
Sleeppermissive/wakepromotingfactors
Behaviouralactionsmodulatecircadianandhomeostaticprocessestopermitorprevent
changesinvigilanceandsleep.Suchactionscanmoderatethetonicchangesinthesleep-wake
cycle,broughtaboutbyProcessesSandC.Thesefactorsarecrucialtoallowingorwithholding
thechangingofstate.Somesuchconditionsfoundtoalterthedegreeoftonicchangeinclude
cold(Haskelletal.,1981;Palcaetal.,1986;Sewitchetal.,1986),heat(Haskelletal.,1981;
Kräuchietal.,1999;Liao,2002;Raymannetal.,2005),immediatedanger(Yerkesetal.,1908),
andposture(Caldwelletal.,2003;Cole,1989).
Asawake-promotingfactor,lightintensityisinstrumentalingeneratingsleeponsetillnesses,
duetosuppressionofmelatoninwithincreasedlightintensity.Theeffectoflightingisfurther
compoundedasworkinghoursareincreasedintothenight,wherebypeoplespendmoretimein
upright,seatedposturesasafunctionoflighting,furtherdisruptingsleeponsetbehaviour.Light
intensitymodulatesthecircadianprocessC,throughdirectsynapsestransmittedviathe
retinohypothalamictracttotheSCN(Arendtetal.,2005;Brzezinski,1997;Carpentierietal.,
2012);essentiallyinstigatingorinhibitingnight-timemelatoninsecretion(furtherdiscussedin
2.3.4InteractionofProcessSandProcessC).Byremovingartificiallighting(e.g.,2weeksof
camping)thecircadiansleepwakesystemandlight-darkcyclecanresynchronise(Wrightetal.,
2013).Byresynchronisingthesesystems,Wrightetal(2013)wereabletoimprovebothsleep
32
onsetandmorningvigilance;essentiallyrestoringthetimingofwakepromotingandsleep
permissivelighting.
Aslightcanmodulatesleeponsetandmaintenancesignificantly,itisapparentthat
temperaturemayalsomodulatesleeponsetandmaintenance(Kräuchietal.,1999;Raymannet
al.,2005;VanSomeren,2004).Asalludedtoabove(in2.2.1Homeostasis),eithersideofanideal
(e.g.,~29OC;(Haskelletal.,1981)),ambienttemperaturebecomesaninadvertentwake
promotingfactor.Thishasbeenevidencedacrossarangeoftemperaturesinbothmenand
women,byHaskelletal(1981)andSewitchetal(1986),butalsoindicatedbyKräuchiina
questionnaireofaSwisspopulation(Kräuchietal.,2008).Typicalbed-timebehaviour
minimisestemperaturevariationbyusingbeddingtogenerateamicroclimate,ensuringsleeppermissivetemperatures(Goldsmithetal.,1968).
Similarly,skintemperaturehaslongbeenconsideredanindicatorofsleeppreparednessand
assuch,asleeppermissivefactor(Fronczeketal.,2006b).Theassociationbetweencorebody
anddistaltemperatureflux,initiatingsleeponset,hasnowbeenlargelyelucidated,andcausal
implicationsoftemperatureonsleephavebeenbothdebunkedexperimentally(Fronczeketal.,
2008;Kräuchietal.,1999;Kräuchietal.,1994;McDonnelletal.,2014;Raymannetal.,2005,
2008)andreviewedthoroughly(Aschoff,1983;Kräuchi,2007;Kräuchietal.,2010;Refinettiet
al.,1992;Romeijnetal.,2012a;VanSomerenetal.,2002;Waterhouseetal.,2005)(discussedin
2.3.5Circadiantemperaturerhythm).AsarguedbyLiao(2002)andRomeijnetal(2012a),body
temperature,coreandskin,aresleeppermissiveand/orawakepromotingfactors.The
behaviouraladjustmentsintheeveningservetofacilitatetheoscillationincorebodyandskin
temperatures,andtherebyenhancetheirsleeppermissiverole.Moreimportantly,itisargued
thatcircadiancyclescanbeentrainedbyskintemperaturefluctuations(Romeijnetal.,2012a).
Thecrucialroleofsleeppermissiveorwakepromotingconditionsincodingfortonic
neuronalchangeisoftenoverlookedbutveryimportanttoalteringormaintainingthearousal
state(Romeijnetal.,2012a).Thereisamyriadoffactorsthatareabletosignificantlyalterthe
33
arousalstate;amongtheseareposturalchanges,lightintensity,andthermalstatus.
Pharmacologicalmethodsarealsocapableofalteringarousalstate;however,theseaspectsare
beyondthescopeofthecurrentstudy.Thermalfactorsarethemostimportanttothecurrent
study,withskintemperaturebeingmanipulated.Phasiccuessuchaslightingortemperature
servetoaltertheunderlyingrhythmsofprocessSandCthroughtheirtightneurologicalinput
withthecriticalareasofsleep-wakeregulation.
2.3.2
HomeostaticHourglass–ProcessS
Thereasonforsleepisstillunknown;howeveritsrestorativeeffectsareobvious(Saperetal.,
2005).ProcessS,wasderivedfromobservationsofslowwavesleep(SWS),inwhichSWS,
representedbyelectroencephalographicdeltapower(0.5-4Hz),roseduringinitialNREM
phasesofsleepinresponsetolongerpriorwakingperiods(Borbetal.,1999;Borbely,1982).
SWSpowerthenreducedacrossthedurationofsleep.ProcessSreducesasafunctionofbothR
andNREMsleep,makingitsdeclineslowanddisjointed(Achermann,2004;Borbely,1982).
StudiesdebunkingNREMandRsleepcomponentsofProcessSfoundthatthereisaspecific
reboundofanyofthesleepstatestoselectivedeprivation(Borbely,1982).Forinstance,
following40hofsleepdeprivation,SWSwasobservedtorebound,butRsleepwasn’t
(Nakazawaetal.,1978).Rsleepdoes,however,produceareboundtospecificRsleep
deprivation(Dement,1960).Although,reboundhasalsobeendemonstratedtospecific
deprivationtostage4(Agnewetal.,1964;Agnewetal.,1967).Theassociationbetweenwaking
hoursandreboundSWSappearstobepredominantlyassociatedwithNREMsleep(Borbely,
1982),howeveritappearsalllevelsofsleepareimportant.TheriseinpotencyofProcessS
acrossthedaydemonstratesanexponentiallysaturatingsleepinesstoberemediatedbySWS
(Figure4)(Beersma,1998).
Substancesknowntoraisethissleeppressurearedefinedassleepfactors.Asleepfactorisa
substancethataccumulatesinthebrainacrosswakinguntilitreachesathreshold,whereby
sleepisinduced(Porkka-Heiskanenetal.,2002).Manysleepfactorshavebeenprofferedthat
34
mayadditionallyserveassleepfactors,suchassynaptichomeostasis(Tononietal.,2006).
Howeveronlyrelativelyrecentlyhasacausativesubstratebeenlargelyaccepted;namely,
adenosine(Porkka-Heiskanenetal.,2011).Therearelikelymanysleepfactorsthatare
unknownandlikelytobeverycomplicated(Moore,2007;Porkka-Heiskanenetal.,2002).
Adenosineaccumulatesduringwakefulnessanddecreasesduringsleepandisthusconsidered
themostlikelysleepfactor/substance(Moore,2007;Porkka-Heiskanenetal.,2011).
Importantly,theareasinthebrainwithwhichadenosineismostimplicatedarethebasal
forebrainandthethalamus;bothkeyneuronalgroupsinvolvedintheascendingarousalsystem.
Forexample,theinhibitoryeffectofadenosineonthebasalforebrainmayplayalarge
contributoryroleintheflip-flopswitch(Saperetal.,2005).Localadenosineadministrationto
thePOAHareainratshasalsobeenshowntoinducesleep,whileacrosssleepdurationincats,
adenosinelevelsinthebasalforebrainandthalamusdecreaseby75-80%(Porkka-Heiskanenet
al.,2002).Asasleepfactor,theriseandfallinadenosinelevelsinthebasalforebrainarespecific
tothisneuronalpopulation(Porkka-Heiskanenetal.,2011).Adenosinehasthereforebeen
proposedasthemechanismdrivingthisswitchtoinhibitionofarousalthroughitsactionon
boththebasalforebrainandtheVLPO(Limetal.,2008).Theinteractionofadenosinewiththe
VLPOisfurthernotedinSection2.3.4InteractionofProcessSandProcessC.
ProcessStrackstheinternalneedsofthebody,drivinggreatersleeppropensitywith
progressingwakefulness.Italsomodulatestherest-activitycyclethroughitscorticalinhibition
(Porkka-Heiskanenetal.,2002).Thisobviouslyhasalargeassociativeeffectonvigilanceinthe
evening,asthepressuretorestandsleepincrementallybuildsacrosstheday.Individuals
involvedinmentallystressfultasks,especiallyacrossthebiologicalnightdisplayamuchgreater
rateofdecline,andlossofattention.Thislossofattentionisinpartduetobuildupofsleep
pressureacrossdays,asthesleeprestrictionlimitsthetimeforsleepfactorstoreturnto
baseline.Moore(2007)identified‘sleephomeostasis’bywhichsleeppropensityismodulatedby
35
precedingsleepamountstoprovideanaverage“referencelevel”ofsleep.Ifsleepisdeferredthe
sleepdriveaugmentspropensity,whereasexcessivesleepsupressessleeppropensity.
Overaday,thedrivetosleepalsoundergoesfluctuationsasitsassociationwithprocessC
servestominimiseormodulateitspotency(Figure3).Reyneretal(2012)observedonesuch
component,knownasthebi-circadianor‘postlunch’dip.Thisdip,whilenotoverlysignificant,
wasapparentindriverswhohadconsumedaheavymeal,afteronly30minofdriving.ThebicircadiandipisafunctionofdecreasedprocessCarousaldriveratherthananyincreasein
ProcessS.AnotherdipinvigilancecomeswiththeeveningchangeinProcessCfromarousalto
sleep,allowingprocessStodrivesleeponset.Thischangeleadstosignificantdeclinesin
vigilance,asprocessSisnolongerchallenged.
2.3.3
CentralCircadianClock–ProcessC
WhileprocessSregulatestheinternalsleep-wakeenvironment,processCregulates
accordingtotheexternalenvironment.ProcessCfluctuatesinaroughly25-hourfrequency,but
isentrainedtothe24-hourcyclethroughdiurnalfluctuationsinlightintensity(Jinetal.,1999;
Johnsonetal.,1988;Reppertetal.,2002).Inthisway,ProcessCregulatessleepandwakingby
constrainingProcessSsleeppropensity.TheSCNservesprimarilyaspacemakerandintegrator,
byprocessingthevariousdiurnalsignals(e.g.,light)andsignallingthesleepandwakingchanges
(Moore,2007;Saperetal.,2005).Whileotherpacemakershavebeenfoundtoexist,forinstance
oneintheeye,andanotherrelatedtotimingofdietaryintake,aswellasindividualclock
neurons(Bassetal.,2010;Raymannetal.,2007a;Raymannetal.,2007b;Romeijnetal.,2012a),
thesearehierarchicallygovernedbytheSCNanddonotappearto,inandofthemselves,relate
toregulationofsleeptiming(Beersma,1998;Burgessetal.,2001;Romeijnetal.,2012a).
ProcessCregulatesthetimingofonsetandcessationofsleepandhormonalfunctions–in
particularpinealmelatoninandorexin/hypocretin(Hurwitzetal.,2004;Limetal.,2008;PandiPerumaletal.,2008)-thoughitdoesnotdeterminethefunctionoftheseprocesses(Achermann,
36
2004).ProcessCalsoregulatesthesleep-wakecycle,ofwhichvigilanceanddrowsinessare
components.Thechangeinthesleep-wakecycleisinstigatedbyneuronal(ascendingarousal
drive;seebelow)andhormonal(pinealmelatonin)changes(Cagnaccietal.,1992;Cassoneetal.,
1986;Jinetal.,1999).Thesleep-wakecycleisalsomodulatedby,andmodulates,theTCcycle.
Thestateofvigilance/drowsinessistightlyrelatedtocorebodyheatfluctuation.Thecircadian
rhythmofTCisveryrobust.Inmodifieddailycycles(~26-hours,ornolight),circadianrhythm
desynchronisationoccurswithinaminorrange,butretainsitsinternalsynchronisationof
physiologicalfunctions(Aschoff,1983).Inthisway,thetwo-processmodelhasbeenappliedto
theunderstandingofthetemporalprofileofneurobehaviouralfunctioningacrossdaysofsleep
deprivation(VanDongenetal.,2003).Duringthebiological“day”TCisatitspeak,while
biologicalnightoccurswithTCdecliningintoitsnadir(VanSomeren,2006;Waterhouseetal.,
2005).TheoscillationinTCisahighlyreliabletoolbywhichtoassessthetimingofthecentral
circadianclock,especiallywithregardtothetransitionperiodbetweensleepingandwaking
states.
2.3.4
InteractionofProcessSandProcessC
Thebalancebetweenwakingandsleepingstatesreliesontheinteractionsofthemain
hormonesandneurotransmittersofProcessesSandC.Thepredominantdriversforcircadian
changearetwohormonesorexinandmelatonin,whereastheproffereddriverofhomeostatic
changeisadenosine.Figure2.3bestillustratestheinteractionbetweenProcessSandProcessC,
astheyoffseteachotheracrossthedayandfacilitateoverthenight,withthe“flip-flop”switch
allowingthetransitionbetweenthewakingandsleepingstates.
Orexin/hypocretinsecretingneurons,withinthelateralhypothalamus(LH),stabilisethe
wakingstatethroughaxonalprojectionsspreadingdiffuselythroughoutthecortex(Hassaniet
al.,2009;Sakuraietal.,2010).Theyprojectintoaventralpathway-progressinganteriorlyinto
theprefrontalcortexandspreadingposteriorly-whichaidscorticalactivationandfacilitates
thalamicinputs(Saperetal.,2005).Thethalamicpathwaystemsfromreticularactivating
37
neurons(Saperetal.,2005).TogetherthesetwopathwaysproducetheAAS,whichexcitesmany
neuronalpopulationsandallowssmoothfunctioningofthecortex(Moore,2007;Saperetal.,
2005).Orexinneuronsaremostexcitedduringactivewakingandprogressivelydownregulate
asstimulidecrease(Sakuraietal.,2010).DuringNREMsleep,orexinneuronsareinactive,with
burstfiringoccurringasanindividualprogressesthroughRphasesofsleep(Leeetal.,2005).
OrexinstabilisestheASS,andoffsetstheriseinadenosine(Sakuraietal.,2010).The“wakeactive”neuronsoftheLHinteractwiththehomeostaticVLPObymutuallyinhibitoryprojections,
thepotencyofwhichdeterminesthedirectionoftheaforementioned“flip-flop”switchtoeither
wakingorsleepingstate(Saperetal.,2001).TheVLPOovercomesthisinhibitionintheevening,
“triggering”theflip-flopswitch(Limetal.,2008;Saperetal.,2005).Adenosine,asmentioned
above,isthoughttobethemaincontributortoVLPOdisinhibitionbydirectlyreducing
GABAergicinputfromcholinergicaxonalcellsfromthemidbrainneuronalpopulations(the
lateralcoeruleus)(Porkka-Heiskanenetal.,2011;Saperetal.,2001).OncetheVLPOinhibitionis
overcome,itsGABAergicprojectionsup-regulate.TheVLPOprojectionssendinhibitorysignals
tomanyareasofthehypothalamus,andbrainstemareasattheoriginoftheascendingreticular
activatingsystem,namelythemonoaminergicnuclei,therapheandthelateralcoeruleus
(Moore,2007;Sakuraietal.,2010).
ConcurrentwithdestabilisationoftheAAS,releaseofpinealmelatoninisstimulated
indirectlybyProcessC(Arendtetal.,2005;Karaseketal.,2006).Melatoninstimulates
vasodilationandTCdrop,eitherthroughitsroleoncardiacautonomicactivity,orthroughdirect
activationinthevasculature(Cardinalietal.,1998).Pinealmelatonincouldbeconsideredan
antagonisttoorexin,beingsecretedatnight,andfacilitatingsleeponsetprocesses(Arendtetal.,
2005;Burgessetal.,2001;Carpentierietal.,2012;Hassanietal.,2009).Whenmelatonin
secretionisstimulated,orexinistypicallyinhibited;howevertheseareonlyassociativechanges
(Hassanietal.,2009).
38
Sinceitsdiscovery,melatoninhasbeenfoundtohaveanumberofroleswithinthebody
includinginteractionwithfreeradicals,theimmunesystemandthegastrointestinaltract
(Carpentierietal.,2012).Itisalsosecretedforthesedifferentrolesbymanyorgans,however
thepinealsynthesisandsecretionofmelatoninappearstobethemostpervasivethroughoutthe
bodyduringnightlysecretion(Karaseketal.,2006;Pandi-Perumaletal.,2008).Eightypercent
ofitssecretionisatnight(Karaseketal.,2006).Duringtheday,brightlight(>600Lux)inhibits
melatoninsynthesis;howeverevenwithincontinuousdarkness,melatoninsynthesisexhibitsa
near-24-hourcycle(Brzezinski,1997).Conversely,substantialevidencealsosupportsanacute
suppressionofeveningmelatoninsynthesisinresponsetobrightlight(>5000lux)exposure
(Cajochenetal.,2000;2005;Wrightetal.,2000).AsbrightlightentrainstheSCN,itfollowsthat
SCN-inducedmelatoninreleaseisalsoentrainedbylightasafunctionofthis.Thelossoflightentrainmentofthecircadianclockisexhibitedindisorders/disabilitiescausing“freerunning”
sleepwakecyclessuchasincompleteblindness,wheremelatoninsecretion,amongvarious
otherprocesses,isnotentrainedtotheregular24-hourcycle(Brzezinski,1997;Karaseketal.,
2006).
Nightlyonsetofmelatoninsynthesisandreleasebeginsafterdark,peakingbetween2-4am
(or12pm-3am(Carpentierietal.,2012;Karaseketal.,2006)),duringthemidpointofsleep
(Brzezinski,1997;Hurwitzetal.,2004;Pandi-Perumaletal.,2008).Onsetandoffsetof
melatoninappearstotypicallyoccurbetween9-10pmand7-9am,respectively(Cagnaccietal.,
1992;Hurwitzetal.,2004;Karaseketal.,2006);howeverthedurationofmelatoninreleaseis
alsoalteredaccordingtodurationofnightandcodingforlength-of-day(Arendtetal.,2005;
Pandi-Perumaletal.,2008).
Lightinhibitsmelatoninthroughneuralactivationofparaventricularnucleiandsympathetic
activationviaSCNpathways(Carpentierietal.,2012).Thethresholdforinhibitionis200-400
luxwithmaximalinhibitionoccurringat600lux(Brzezinski,1997).Maximalwakinglight
exposureinaconstructedenvironmentis~900lux(Wrightetal.,2013),wellabovethemaximal
39
inhibitionofmelatonin.TheretinallightinfluxcausessynchronisationoftheSCNtothelightdarkcycle(Pandi-Perumaletal.,2008).Thelight-darkcycleco-varieswithTCandmelatonin
change,howevertheTCcycleappearstohaveastrongercorrelationtomelatoninsecretionthan
thatofthelight-darkcycle(seeFigure2.4)(Burgessetal.,2001;Cagnaccietal.,1992;Karaseket
al.,2006).Itisbelievedthatmelatonincouldinfactserveasaninternalsynchroniserableto
stabilizeorreinforcerhythms(Karaseketal.,2006).AsstatedbyKaraseketal(2006)
“biologicalday”correspondstoalackofmelatoninsecretionaccompaniedbyanincreaseinTC
andadecreaseinwakingthetaactivity,whereasthe“biologicalnight”melatoninsecretionis
associatedwithdecreasedTCandincreasedwakingthetaactivity(Figure2.4).
TherelationshipbetweenmelatoninandTCappearstobecausative,with(Burgessetal.,
2001)observingariseinfoottemperature30minafteradministrationofanoralmelatonin
load,followedanhourlaterbyadropinTC(Figure2.4).Thiseffectisalsoobservablewith
daytimeadministrationofmelatonin(Hurwitzetal.,2004).Similarly,night-timeadministration
ofatenolol,suppressingmelatoninsynthesis,alsoreducesthedeclineinTC;infusionof
melatonin,offsettingtheatenololrestoresnormalreductions(VanDenHeuveletal.,1997).
Nocturnalmelatoninsecretionaccountsfor~40%ofthedropinTC(Cagnaccietal.,1992).
Thereappearstobealotofsupportfordirectmodulationofthecardiacautonomicactivity,
howeverBurgessetal(2001)argueswithhisfindingsusingsyntheticmelatoninadministration
thatmelatonindoesnotdirectlyinteractwiththeautonomicsystembutratheractsonreceptors
intheheartandperiphery.Melatoninreceptorshavebeenidentifiedwithincoronaryarteries,
ventriclesandsystemicarteries(Pandi-Perumaletal.,2008).Assuch,pinealmelatonin
synthesisisdeterminativeoncutaneousvasodilationandsubsequentDPGdevelopmentor
abolition(Kräuchietal.,1997;Pandi-Perumaletal.,2008).Theeffectofmelatoninonthe
systemiccirculationislinkedtothermoregulationandappearstolowerbloodpressurethrough
vasodilation(Pandi-Perumaletal.,2008).Collectivelytheseinterventionsandobservations
supportthenotionthatmelatoninislargelyresponsibleforfacilitatingsleeponset.
40
Figure2.4:Circadianrhythm,withassociatedmelatoninandsleeppropensitycycles.FromLack
etal.,2008 2.3.5
Circadiantemperaturerhythm
Temperaturefluctuation,whilenotdirectlycontrolledbythecentralcircadianclock,is
modulatedbydirectneuronalconnectionsbetweentheSCNandPOAH,viaarostralprojection
oftheSCN(Mooreetal.,2002).ThesynapsingofthePOAHwiththeSCNallowsforthecircadian
fluctuationinTC(Figure2.4).Tonicup-regulationofSCNfiringstimulatesWSNfiring,whichhas
beendemonstratedtospontaneouslyincreaseatsleeponset(Raymannetal.,2007a).Circadian
oscillationofTCoccursthroughmodificationsinheatloss,whichisstimulatedbyWSNexcitation
(Kräuchietal.,1994).TCvariationonlyoccurswithinnormothermicrangesasafunctionofSCN
input,withsleeponsetoccurringaroundthemaximumrateofTCdecline(Kräuchietal.,1999;
Murphyetal.,1997).Neuralstimulationofeveningheatlossoccurswithhormonalfluctuations
suchasmelatonin,which,alongwithincreasesinskintemperaturecontributetotheassociated
rhythmofTCandsleep(Arendtetal.,2005;Cagnaccietal.,1992).Acausalrelationshipbetween
skintemperatureandsleeponsethasgainedevidentialsupport(Raymannetal.,2005;Van
Somerenetal.,2002;VanSomeren,2004).Skintemperaturerisesasafunctionofvasodilation,
allowingtheTCtodecline.Indilatingthedistalbloodvessels,skintemperatureformsaninverse
relationshipwithTC.Itiscurrentlydebatedwhetheritisthelevelofdistalskintemperaturethat
41
isessential(Fronczeketal.,2006b;Raymannetal.,2005)orthegradientthatisinduced(Fagrell,
1985;Kräuchietal.,1999).
WhilethecyclesofsleepandwakingareintimatelyrelatedwiththerhythmofTC(Van
Someren,2006),theyarenotdirectlycausative(Aschoff,1983).Thenatureoftherelationship
hasbeenchallengedbyconstantroutineprotocolspreventingsleep,wherebyTCcontinuesto
oscillate,butatareducedrate(~50%)(Waterhouseetal.,2005).Gillbergetal(1982),further
demonstratedTCindependencefromrest-activitycycles,bypromptingsleepatdifferenttimes
ofday,andtherebydifferentphasesoftheTCrhythm.Sleepduringthebiologicalday,causesa
dropinTCacrossthefirsthourofsleep,whereuponitrealignswiththenormalrhythmacross
sleepduration(Gillbergetal.,1982).ThetypicalrhythmofTCpeaksbetween2-8pmand
troughsat5am(Figure2.4).
TheroleofmaximalrateofdeclineinTConsleeponsetwasfirstdeterminedby(Murphyet
al.,1997),inyoungandoldindividualsbyusingadisentrainmentstudydesign.Acrossthree
daysoftime-cueisolation,participantstypicallywenttosleep~60minfollowingthemaximum
rateofTCdecline(Murphyetal.,1997).Thisrelationshipcouldbeoverriddengivenenough
motivation.Kräuchietal(1999;1994)expandedonthetemperatureandsleeprelationshipby
demonstratingthatthedegreeofdilationofbloodvesselsinthehandsandfeet,andsubsequent
DPGdevelopmentarethebestphysiologicalpredictorsofrapidsleeponset.Raymannand
colleaguesfurtherdemonstratedtheroleofraisingskintemperatureoninducingsleep,ina
seriesofstudies(Raymannetal.,2005,2007a,2008;Raymannetal.,2007b).Withuseofa
water-perfusedthermosuit,Raymannetal(2005),demonstrated26%fastersleeponset
latencieswithsubtlemanipulation(0.8±003OC)ofproximalskinsitesthroughouttheday.This
hasbeenfurtherappliedinanecologicallyvalidsetting,usingbedsockstopromotedistal
warmingandabeneficialDPGforsleeponset(Raymannetal.,2007a).Evenmorerecently,
(McDonnelletal.,2014)hasaddedtothegrowingliteratureinabedreststudyinvolvingeffects
ofhypoxicversesnormoxicconditions.Theyobservedpersistenceofthenon-thermal
42
mechanismmediatingeveningvasodilation,regardlessofinducedvasoconstriction(McDonnell
etal.,2014).
AnumberoffactorsarecapableofimpingingonTCandimpairingsleeponset.Coolingmay
perhapsbeonesuchfactor,assleep-relatedprocessesappeartobedifficulttoinitiatein
susceptibleindividuals.InaquestionnaireofaSwisspopulationthermaldiscomfortofcold
extremitieswascorrelatedwithdifficultyinitiatingsleep(Kräuchietal.,2008);thishas
previouslybeenobserved(asmentionedabove2.2.1Homeostasis)acrossarangeofambient
temperatures,withbothcold(21OC)andhot(34OC)ambienttemperaturesdisturbingsleep
onset(Haskelletal.,1981).
Furthermore,susceptibilitytoambienttemperaturemaybesexspecific,withwomen
typicallyhavingalowerdistaltemperature(~3OC)(Candasetal.,2007),andthereforesuffering
greatercomplaintsofthermaldiscomfortanddifficultyinitiatingsleep(Kräuchietal.,2008).
Additionally,theeffectsofagingappeartogeneratesimilardifficultiesinitiatingsleep,whichare
improvedbydistalwarming(Raymannetal.,2007a).Decliningsynthesisofmelatonin(from
~65years)furtherexacerbatestheeffectsofagingonthecircadianrhythmofTC(Brzezinski,
1997;Pandi-Perumaletal.,2008;Raymannetal.,2007a;VanSomerenetal.,2002).
Insummary,therhythmofTCishighlycorrelatedtothecircadiansleepwakerhythm.Indeed,
therhythmofTCappearstobecausativeinhealthysleeppatterns,moresothroughthe
fluctuationsinskintemperatureanditsroleonTC.Bothhormonalandneuronalnon-thermal
factorsmaintainandentraintheTCcycle,whichinturninfluencetherateofsleeponsetandthe
depthofsleep.Conversely,minimisedfluctuationsinTCorthermalfactorsgenerating
vasoconstrictionappeartoreducesleeppropensity.Thisdisruptionmayhavearolein
influencingmaintenanceofvigilance,asevidencedbythealteredthermoregulationandsleepwakephysiologyobservedinnarcoleptics(Fronczeketal.,2008).
43
2.3.6
Narcolepsy
‘Narcolepsyisclinicallycharacterisedbyexcessivedaytimesleepinessandcataplexy’
(Fronczek,2006,p.1444).Narcolepsyreflectsadysfunctionoftheorexin/hypocretinsystem,
with~95%ofnarcolepticpatientshavingverylowlevelsofhypocretin-1incerebrospinalfluid
(Overeemetal.,2012).Thelossof“normal”levelsoforexinleadstothedestabilisationofthe
wakingstate,astheflip-flopswitchbecomesdestabilised(Saperetal.,2001).Withouttheinput
providedbyorexin,theflip-flopswitchtriggersrapidchangesinsleep-wakestatesacrossthe
day,typifiedinnarcolepsy.
Therelationbetweentemperatureandsleephasbeenestablished,bothwithevidential
causationofdistalskintemperatureandsleeponset(Fronczeketal.,2006;Kräuchietal.,1999;
Raymannetal.,2005),andwithsynapticinputbetweentheSCNandPOAH(Wrightetal.,2002).
Asorexinisanactivecomponentofthecircadianclock,lowlevelsmayultimatelycontributeto
decreaseddistalsympatheticconstrictortone,whichisindicatedbyalteredDPGs(Fronczeket
al.,2006).Therelationbetweenorexindeficiencyanddecreasedsympathetictonehasbeen
demonstratedinorexinknockoutmice(Kayabaetal.,2003).Fronczekandcolleaguesexplored
therelationshipbetweendistaltemperaturesandsleepinessinnarcolepticsinaseriesofstudies
(Fronczeketal.,2006a;Fronczeketal.,2006b;Fronczeketal.,2008).Incomparingdaytime
sleeppropensitybetweennarcolepticsandhealthyindividuals,Fronczeketal(2006b)observed
arelationshipbetweenhighdistalskintemperatureandrapidsleeponsetduringaMultiple
SleepLatencyTest.WhenfocussingonvigilanceFronczeketal(2006a)experimentally
manipulatedbothTCandTSktorestorenormaldaytimetemperatures;thiswasachieved
throughingestionofhotdrinksanduseofawaterperfusedsuit.Byingestingahotdrink,the
participantswerebetterabletoraisevigilance(~24%),andbycoolingtheskinsleeppropensity
wasreduced.Fronczeketal’s(2006;2008)studiesservetofurtherdemonstratetheroleof
temperatureonsleepandindicatethepermissivenessofcoolingasatechniqueformaintaining
wakefulness.
44
2.4
Vigilance
Vigilancecontrastssleep,butformsamorecomplexrelationshipwithTC.Thevigilancestate
reflectscorticalexcitationandmaintenanceofattention(Klimesch,1999;Laletal.,2002).Some
factorsinvolvedinalteringneuronalexcitabilityarethedurationofwakingstate(ProcessS)
(Klimesch,1999;Porkka-Heiskanenetal.,2002;Romeijnetal.,2012a;Tononietal.,2006),time
ontask(Fronczeketal.,2008;Laletal.,2002),andsatiety(Reyneretal.,2012).Vigilanceis
greatestduringthecircadianphaseofincreasedTC,anddeclineswithcoretemperature.Asthe
relationshipbetweenTCandthecircadianclockareentwined,thecoreandskintemperature
phaserelationshipcanthereforebeusedtoinfertheseunderlyingvigilanceprocesses
(Raymannetal.,2007b;Romeijnetal.,2012a).Indeedthishasbeenobservedwithnarcoleptics
asaforementioned(Fronczeketal.,2006b).Thedailyrhythmintemperaturefluctuationresults
inareciprocalfluctuationinvigilance(Fronczeketal.,2008;Romeijnetal.,2012a).
Vigilanceappearstobedirectlyrelatedtothermalandnon-thermaltemperaturechanges
withintheTNZ.AcausalrelationshiphasbeenobservedbetweenthecircadianTCpeakand
cognitivetaskproficiency(Wrightetal.,2002);additionally,the‘postlunch’bi-circadiandipin
TCappearstoresultinreductionsinvigilance(Reyneretal.,2012).Furtherfacilitatingthe
circadiandeclineofTCintheevening(distalskintemperature~34OC,comparedto~31OC)
appearstogenerategreaterdeclinesinvigilance(Raymannetal.,2007b).BeyondTNZsofTCrhythm,bothcoolingandheatingappearstoexhibitaninverted-Urelationship(Cheungetal.,
2007;Raymannetal.,2007b).Inacoldpressortest(2-3OCwater),Patiletal(1995)observed
raisedalertnessbutdecreasedshorttermmemory.Similarly,Cheungetal(2007)foundthat
mildwhole-bodycooling(Twater≈18-25OC,∆Tre=0,-0.5,-1.0OC),viawaterimmersion,ledto
performanceimpairmentduetodistraction,butgreatercolddidnotrelatetoworse
performance.Thisledtothesuggestionthatcoolingperse,ratherthantemperature,is
distracting.
45
Themostdramaticchangesinvigilanceareseenintheevening,assleepisphysiologically
facilitated.Ifsleepisdeprived,thegreaterProcessS-associatedsleeppropensityproduces
greatervigilancedecline(Basneretal.,2011).Anumberofstudiesusesleepdeprivationasa
meanstogenerategreatersensitivityinvigilancemeasures(VanDongenetal.,2003).
2.4.1
Psychomotorvigilance
Psychomotorvigilanceisastateofarousalandattentivenesstotasks(Laletal.,2001;Warm
etal.,2008),orsimplysustainedattention(Okenetal.,2006).Maintainingattentiontoataskis
energydemandingandrequiresconsiderablecognitiveprocessingdedicatedtomaintaining
vigilance(Lorist,2008;Warmetal.,2008).Theabilitytomaintainattentionisspecifically
affectedbymentalfatigue–fatiguefromprolongedcognitiveprocessing(Boksemetal.,2005;
Dinges,1995;Laletal.,2001).Thepsychomotorvigilancetask(PVT)isthebestmeasureof
assessingmentalfatigueassociatedwithincreasingtime-on-task(Wrightetal.,2002).
Psychomotorvigilancedecayhasbeenobservedwithtemperaturemanipulation(Fronczeket
al.,2008;Raymannetal.,2007b),withchangestobodyposture(Caldwelletal.,2003),and
brightlightexposure(Cajochenetal.,2005;Kaidaetal.,2006),followingsleepdeprivation(Van
Dongenetal.,2003),andwithmorecomplextaskssuchasdrivingorflying(Dinges,1995;
Gillbergetal.,1996;Horneetal.,1995;Schier,2000).
Attentionallowsusto,firstly,biasincominginformationsoastoprivilegerelevant
informationforachievinggoals,andsecondly,activelyignoreirrelevantinformationcapableof
interferingwithgoalperformance/completion(Boksemetal.,2005).Attentionsharesmany
commoncharacteristicswitharousal,howeverwherearousalreferstonon-specificactivationof
thecortex,attentionincludescognitiveprocessing(Okenetal.,2006).Inarestingsituation,
neurologically,anindividualcanstillbevigilantandalertwithoutthestressorsrequiring
attention.Whentaskdemandsareapplied,individualsareforcedtodirectattentionand
considerablecognitiveprocessingtomaintainvigilantattentioninreadinesstorespond;thisis
fatiguingandstressful(Warmetal.,2008).Thetopdownprocessesinvolvedincoordinating
46
accuratetimingofactivitiesaremostaffectedbyfatigue,whichresultinalossofperformance
efficiency(Lorist,2008).
Themajorityofresearchdefinesvigilancebyitsdeclination(Okenetal.,2006).Thereare
manytermsusedtodefinethedeteriorationofvigilance,asoutlinedinChapter1,andwhile
sleepinessismoreprecise,fatigueismoreinclusiveofthespectrumofprocessessurrounding
decreasedalertnessandperformance(Dinges,1995;Horneetal.,1995;Jonesetal.,2010).
Fatigue,inthecontextofthecurrentstudy,canbedescribedasthetransitoryperiodbetween
awakeandsleep(Laletal.,2001),markedbyreducedefficiencyandgeneralunwillingnessto
continue(Grandjean,1979,1988).Unwillingnesstocontinueataskcanbedescribedasan
effort/rewardimbalance,resultinginlossofmotivationandfeelingsoffatigue(Topsetal.,
2004).
Monotonoustasksarepronetogeneratingfatigue.Duringamonotonousdrivingtask,Brown
(1994)observedagradualwithdrawalofattentionastaskdurationincreased.Duringdrivingof
amonotonousloopedtrack,Schier(2000)observedwithdrawalofattentionandfatigueas
participantsbecamefamiliartothetrack.Thiswithdrawalofattentionfromthetask,dueto
familiarityorlossofmotivation,generateserrorsinperformancewiththelossofefficiency.
WithinPVTtests,familiarisationtothetaskisminimised,allowingfatiguetobeobserved
separatelyfromfamiliarity;theseareobservedaslapsesorincreasedreactiontimesasthetask
progresses(Fronczeketal.,2008;Raymannetal.,2007b;VanDongenetal.,2003).
Asalludedtoabove,tonicfactorssuchassleepdeprivation,circadianrhythmphase,
environmentalfactorsandtheindividual’scharacteristics,alsoimpingeonthevigilancestate
andfatigability(Boksemetal.,2005;Eohetal.,2005;Laletal.,2001;Transport,2011a).The
inputoftonicfactorsisminimisedbyconstantroutineprotocols,whichmaintainconstant
conditions.TheconstantroutineprotocolwasdesignedbyMillsetal(1978)andwasmodified
byCzeisleretal(1986).Theconstantroutineprotocol,minimisesextraneousfactorsnotdirectly
requiredfortheobservancesofthestudy;e.g.,Kräuchietal(1994)maintainedconstant
47
ambienttemperatureandhumidity,lightlevels,motoractivity,vigilancestateandfoodintaketo
unmasktheendogenouscircadiantemperaturerhythms.
Ontopofconstantroutineprotocolssleepdeprivationisoftenusedtosensitisetests.Okenet
al(2006)warnedthatmanystudiesmightbenegativelyaffectingmotivation,byinducingsleep
deprivation.Sleepdeprivationartificiallyraisesfatigueandaltersmotivation,andmaytherefore
becreatinganunrealisticconflict.VanDongenetal(2003)andOkenetal(2006)arguethat
sleepdeprivationisacommonoccurrenceintoday’ssociety;assuch,inducingfurthersleep
deprivationmayreducethevalidityofvigilancestudies.However,thehighprevalenceofsleep
deprivationindrivingaccidentsmaybebetterunderstoodwithfurthersleepdeprivation.
Insummary,thedefinitionsencompassingvigilanceandfatiguevary,howeverthecausative
factorsremainconsistent.Fatigueappearstocompriseanumberofagreedcharacteristics,
including:Lossofefficiencyandalertness;difficultymaintainingattentionandfiltering
irrelevantinformation;aswellasalossofmotivation.Eachcharacteristicoffatiguedescribes
thedeteriorationofvigilance.Vigilanceistheabilitytomaintainsustainedattention,without
noticeabledeclineinefficiency.Maintainingvigilanceiscostly,anddrowsinessimpactsthetopdownprocessesmost.
2.4.2
Validityofthepsychomotorvigilancetask
ThePVTisthemostwidelyusedmeasureofbehaviouralalertness(Basneretal.,2011).It
providesanexcellentmarkerofattentionaldeficitinmoststates(i.e.sleepdeprivation,
followingstimulants,circadianmeasures)(Limetal.,2008).ThePVTisaportabledevicethat
containsabrief,ecologicallyvalidandreliabletaskthatisalmostdevoidoflearningeffects
(Basneretal.,2011;Limetal.,2008;Lohetal.,2004).InessencethePVTprovidesaseriesof
simplereactiontimetasks,suppliedatarandominter-stimulusinterval(ISI),whichrequires
sustainedattention.Duetoitshighsignal-loadratio,10minallowscollectionofalargeamount
ofinformationwithoutitbeingtooonerous(Limetal.,2008).Whenshortenedorlengthened,
48
nofurtherinformationisgleaned,andmoreoftensensitivityislostduetolossofmotivation,or
lackofdata(Limetal.,2008;Lohetal.,2004).
ThePVTismadespecifictovigilance,throughtherandomalternationbetween2and10s,in
theISI.Areactiontimethatislongerthanstandardoccurswhenanindividualisunpreparedfor
thestimulus.Asmoretrialsareperformedanindividual’scapacityforcontinuous,concentrated
attentionisrevealed(Wilkinsonetal.,1982).Asstatedabove,thecognitiveloadappliedto
maintainvigilanceisonerousandincreaseswithfatigue.TheISIisthestressorwithregardto
maintenanceofvigilance,asitsinconsistencyrequirestheindividualundergoingtestingto
maintainastateofreadinesstorespond.ThisallowsthePVTtobesensitivetosmallchangesin
attentionalfunction(Limetal.,2008).
Themetricsutilisedtounderstandtheeffectofexperimentalconditionsortime-on-taskon
vigilantattention,aretypicallyassessedasreactiontime,orlapses.Lapsesaredenotedby
reactiontimesof>500ms.Theseareconsiderederrorsofomission,wheretheindividualhas
failedtomaintainvigilance,resultingfromdistractionormicro-sleeps(Basneretal.,2011;Lim
etal.,2008).Lapsesaremostcommonlyobservedinsleepdeprivationstudies,inwhichthePVT
hasdemonstrateditsabilityasthe‘archetypeneurocognitiveassayofattentionaftersleeploss’
(Limetal.,2008),p.306).VanDongenetal(2003)foundthatacross14-daysofsleeprestriction,
lapsesdifferedsignificantlybetweenthoserestrictedto4,6and8hourspernight.Moreover,
Limetal(2008)demonstratedthatsleepdeprivationandassociatedsleeppressure
incrementallyaddstolapses,withthegreatestnumberoflapsescorrespondingtothe
summationofcircadiandropinTCandarousal,andhomeostaticpressuretosleep.The
combinationofcircadiancycleandpressuretosleepcompoundtheeffectoffatigueand
significantlyalterthenumberoflapsesbroughtonbyattentionloss.
Reactiontime(oftenexpressedasreciprocalreactiontime[RRT=1000/RT](Fronczeketal.,
2008)),theothermetricobtainedfromthePVT,alsoservestoelucidateattentionalchange.
Reactiontimeincreaseswithtime-on-task.TheRRTservestoemphasiseresponsespeedinthe
49
normaltofastresponsedomain,therebyavoidinginfluenceoflonglapses(Basneretal.,2011).
AworseningRRTdecreasestowardzero.AssuchRRTprovidesaperformanceindicatorofthe
levelofalertnessprecedingstimulus.Fronczeketal(2008)observedsignificantdeclinesinRRT
asafunctionoftime-on-task.Inconjunctionwithasteadyincreaseinthenumberoflapses,and
reductioninresponsespeed,fatiguealsoproducesmorefrequenterrorsof
commission/omission,andmorevariabilityinRRTwithincreasingtime-on-taskandsleepiness
(Basneretal.,2011;Limetal.,2008).Thesefatigue-relatedperformancedeclinesareoften
exaggeratedfurtherbyusingsleepdeprivationtodemonstratelargereffects,viatheadditional
sleeppressure.
2.5
Sleeponset
Inthetransitionfromfullyalerttosleeponset,aseriesofclearlyobservableandreliable
processesoccur(Chokrovertyetal.,2005).ThesechangesarepredominantlyfoundedinEEG,
withmarkedincreasesofslowwavethetaactivity,andalphaanteriorisation,signallingsleep
onset(Caldwelletal.,2003;Klimesch,1999;Okenetal.,2006).Asanindividualprogresses
furtherintosleep,sleepspindlesoccur,denotingsleepN2(Chokrovertyetal.,2005).Stages1
and2arenowtermedN1andN2respectively(Iberetal.,2007).AlthoughN1sleepprecedes
N2,itisdifficulttodetectduetorelapseintoandoutofthewakingstate.Assuch,somestudies
definesleepfrommorethanoneconsecutiveoccurrenceof30sofN1sleep,orN2sleepwiththe
firstoccurrenceofasleepspindletoensurecertaintyofsleeponset(Fronczeketal.,2008).
Althoughsleeponsetisdefineddifferentlybetweenstudies,epochsinN1orentryintoN2sleep
arealwaysamongcriteria(Fronczeketal.,2008;Kräuchietal.,1999).Stage3and4sleepare
characterisedbyincreasingfrequencyanddepthofdelta(slow)waves.Howeverstages3and4
arenolongerrecognisedasdistinctstates,butaremergedasslowwavesleep,ortermedN3
sleep,accordingtochangesintheAmericanAcademyofSleepMedicineguidelines(Iberetal.,
50
2007).Typically,asubjectentersstageRsleep;afterslowwavesleep.Rsleepischaracterised
bymixedfrequencylowvoltageEEG,lossofmuscletoneandburstsofrapideyemovement.
Awarenessofdrowsinessoccursafterphysiologicallyobservable(e.g.,EEG)changes
(Santamariaetal.,1987).ApatientlapsingintoN1oftenhasnorecollectionofsleeponset,and
whenqueriedareoftenadamantthatnosleeponsetoccurred(Horneetal.,1995).In
conjunctionwiththis,subjectswithincreasingdrowsinessbecomeincreasinglylessresponsive
toexternalstimuli(Okenetal.,2006).Thisreflectsaworryingstateofawareness,asadeclinein
reactiontimeandlapsesarecommonoccurrencesindrowsiness(Dinges,1995).Filtnessetal
(2012)observedgoodinsightintodrivers’increasingsleepiness.Howeverthisinsightappears
tobelimited,asVanDongenetal(2003)observednodifferenceinperceptualawarenessin
sleepinessbetweenindividualsrestrictedto4and6hoursofsleep,despiteamarkeddifferences
invigilancemeasures.Assuch,electrophysiologicalchangesprovideamoredirectmeasureof
sleepinessprogression,asopposedtorelianceinperception.
Thewakingstateischaracterisedbysmallamplitude,fastfrequencybrainwaveactivity
predominantlyinvolvingbetaandgammaactivitywithinterspersedalphafrequency.Asan
individual’sstateofalertnessdecreasesthefrequenciesareincreasinglyinfiltratedbyalpha,and
thetaactivity(Chokrovertyetal.,2005).Thewakingstateincludes~50%observablealpha
activity,mixedwithbetaactivity(Chokrovertyetal.,2005).Assleeponsetoccurs,alphapower
reduces,andthetaanddeltapowerincreases(Klimesch,1999).Incasesofsleepdeprivation
participantsmayforgotraditionalentryintosleepthroughN1andN2,andprogressstraight
intoRifthepressuretosleepishigh(Chokrovertyetal.,2005).WhenN1doesoccur,EEG
recordingstypicallyshowverylowamplitude,fastfrequencywithatleast15%thetafrequency
andtheappearanceofdeltasubsumingalphafrequency(Chokrovertyetal.,2005).N2sleepis
easilydefinable,asitbecomespredominantlythetaactivityanddelta,interspersedwithsleep
spindles(Chokrovertyetal.,2005).
51
Recognitionofsleepinessoccurringfromwakingstatetosleeponsetshowsanumberof
reliableeventsthatallowthesleepspecialisttobesureofsleepinessandfinally,sleeponset.
Thisisdemonstratedbytheslowincreaseofalphafrequencyinthewakingstatedueto
reducingarousal,followedbyinfiltrationofthetafrequency,reductionsinalpha,andfinallythe
disappearanceofalphafrequencyandintroductionofdelta.Theseparticular,reliableeventsare
discernibleonlywithEEG,andcontributetotheunderstandingofdifferencesinclassifications
betweensleepinessandfatigue.
2.6
Electroencephalography(EEG)andtheelectro-oculogram(EOG)
EEGisperhapsthemostdirectmethodofdeterminingthebiologicaldecayinvigilancein
humans(Horneetal.,1995;Laletal.,2002),andremainsthestandardmethodologyfor
assessingbehaviouralstate(Moore,2007).Thedominantpolysomnographictechniquesused
fordeterminingvigilanceanddrowsinessareEEG,EOGandECG,astheyarehighlyresponsive
tochangesinwakingvigilancestate,andprovideinsightintounderlyingneuronalexcitability
(Chuaetal.,2012;Eohetal.,2005;Laletal.,2002;Schier,2000).EEGpowerisaffectedbyboth
phasicandtonicchanges,suchasopeningandclosingtheeyes,orcircadianrhythms(Klimesch,
1999).Phasicelectro-ocularandcardiographicchangeswithfatigueanddrowsinessare
consistentandreliable,withanobservablechangeinblinktype/ratesandeyemovements,and
largereductionsinheartratewithfatigueprogression.EEGrecordsthegeneralneuronal
excitabilityacrossthescalpthroughtheuseofelectrodesplacedoveranatomicallandmarks
denotingspecificareasofthebrainassetbytheinternational10/20EEGsettings(Chokroverty
etal.,2005;Himanenetal.,2000;Niedermeyer,1999).Thevarioussynchronisationsand
desynchronisationsofneuronalactivitycanbemeasuredasarangeofvariousfrequencies,
whichcanchangedependingonelectrodepositioning(Ruehlandetal.,2011).Assuch,electrode
positioningdirectlyoversitesofinterest(i.e.O1/O2forvisualtasks)maximisethesignal-noise
52
ratioandprovidesmorespecificinformationofchangeinneuronalactivity.Byaltering
electrodepositioningtotheconstraintsofthetask,EEGisbetterabletoregisterchangesin
vigilance-relatedEEG.
EEGisaminutesignal,easilymaskedbynoiseduetoscalpmuscleactivityorthe
environment(Niedermeyer,1999).StudiesoftenuseEMGplacementonthechinand/orEOGto
clarifyphasesintheEEGsignal(Hakkinenetal.,1993;Santamariaetal.,1987).Electrodes
placedmorelaterallyorinferior/posterior(i.e.,T7,T8,O1,Oz,O2),arealsoexposedtomore
muscularnoisethanaremidlineelectrodes(McEvoyetal.,2000).EEGalsopresentshighinterindividualvariability,withvariationssuchasskullthicknessandcerebrospinalfluidflow
affectingthesignalreceived(Klimesch,1999;Niedermeyer,1999).However,test-to-retest
reliabilityhasbeenvalidatedinrelationtovigilance(PVT)andworkingmemorytasks(McEvoy
etal.,2000).Inconjunctionwiththeanatomicalchanges,variabilitycanpresentwithinthe
specificfrequencies(Klimesch,1999).Theobserveddiscrepanciesinsynchronisingand
desynchronisingpowersarereflectiveofhighinter-individualvariabilityinherentinEEG
(McEvoyetal.,2000;Niedermeyer,1999;Santamariaetal.,1987).Indeed,Chokrovertyetal
(2005)notedthatasmallpercentageofpatientspresentnoalphaactivity,withtheirdominant
frequencypresentingwithinthebetafrequencyrange.
Electroencephalographyisusedinbothclinicalandresearchsettings.ResearchutilisesEEG
todeterminevigilancestate(Filtnessetal.,2012;Laletal.,2002;Reyneretal.,2012;Schier,
2000),memorycapacity(Klimesch,1999;Rayetal.,1985a,1985b),orcognitiveperformance
andintelligence(Boksemetal.,2006;Klimesch,1999),alongwithaforementionedinsightsinto
onsetofsleep.EEGisoftenusedtodocumentthetransitionfromwakingstatetosleep
(Chokrovertyetal.,2005),orfromrelaxedtoattentivestates(Filtnessetal.,2012;Klimesch,
1999;Laletal.,2002).Changesincognitivestateareofteninterpretedthroughbrainwave
frequencyandamplitude.Themostcommonlyobservedfrequenciesaredelta(0.5-4Hz),theta
(5-7Hz),alpha(8-13Hz),andbeta(15-35Hz).Traditionally,deltafrequencywasignoreddueto
53
thesusceptibilityofthelowfrequencytobeinfluencedbyartefactsandnoise(Laletal.,2002).
Theta,alphaandbetafrequenciesareusedpredominantlytoassessdrowsiness,vigilance,
pressuretosleep,andattentionalfocusthroughobservationofpowerchangesineachband
(Burgessetal.,2001;Filtnessetal.,2012;Klimesch,1999;Schier,2000).
2.6.1
AlphaandThetarhythms
Alpharhythmisthedominantfrequencyonthehumanscalp(Klimesch,1999),andis
generatedfromtheposteriorportionofthebrain(Klimesch,1999;Niedermeyer,1999).In
healthyadults,alphatypicallyhasanamplitudebetween10and45µV(Pizzagalli,2007).Alpha
amplitudeisbestobservedoverparietalandoccipitalregionsinquietwaking,witheyesclosed,
andtendstoprogressanteriorlyinfatigue(Chokrovertyetal.,2005;Klimesch,1999;Pizzagalli,
2007;Teplan,2002).Alphaactivityisparticularlysensitivetochangesinstate(i.e.,opening
closingeyes,changeinattention,waketosleepstate)(Klimesch,1999;Schier,2000)andis
abolishedbyalertingstimuliandtasks(Teplan,2002).
Thephysiologicalroleofalpharemainslargelyunknown(Pizzagalli,2007),despitemany
attemptstodefineit.Widespeculationuponthephysiologicalbasisofalphaincludes,among
otherexplanations,reflectionofbrainmaturity,andcognitiveandmemoryperformance(Eohet
al.,2005;Klimesch,1999).Alphasynchronisationhasbeensuggestedtoreflectcortical
inactivity(Pizzagalli,2007).Indeed,alphaattenuationoccurswhenalertnessdecreasesinto
drowsiness(Pizzagalli,2007),howeverthisisalsosomewhatduetoslowingoffrequencies
(Klimesch,1999;Pizzagalli,2007).Duringactualtaskperformance,alphapoweristypically
depressedordesynchronisedrelativetorestingstates(Klimesch,1999);thisisreferredtoas
“alphablocking”(Chokrovertyetal.,2005;Niedermeyer,1999;Pizzagalli,2007).The
suppressionofalpharhythmsduetoattentionaldemands(Filtnessetal.,2012;Pizzagalli,2007;
Schier,2000),orevenbylightinflux(Klimesch,1999),andcanlastfromsecondstocessationof
thestimulus(Niedermeyer,1999).Inprolongedrepetitivetasksalphasynchronisationoccurs
whenattentionaldemandsreduce.Schier(2000)observedareturnofalphasynchronisation
54
towardtheendofmonotonous,repetitivesimulateddriving(lap5of6)asparticipantslost
attentivenesstothetask.
Furthermore,understandingofthephysiologicalbasisofalphahasbeencomplicatedby
emergingevidenceofalphasub-bands,heavilyadvocatedby(Klimesch,1999).Klimesch(1999)
andothers(Cooperetal.,2003)havearguedthatalphapowerisalsohighlycorrelatedtospeed
ofcognitiveprocessingintheformofreactiontime.Thepowerofaspecificfrequencyis
generallydeterminedthroughthepeakfrequencywithinarange(i.e.,thepeakfrequencyinthe
alphabandisgenerally10.89Hz).Ithasbeenpostulatedthatanindividualwithafasteralpha
frequencywillconsistentlyrespondfasterthananage-matchedindividualofsloweralpha
frequency(e.g.,apeakfrequencyof9.49Hzcomparedto10.89Hz)(Klimesch,1999).Although,
task-relatedshiftsinalphapowerobservedinthemajorityofresearchappearnottoberelated
tointelligenceorspeedofprocessing(Klimesch,1999).
Thetapowerisoftenstudiedinconjunctionwithalpha.Similartoalphapower,thetacanbe
separatedintosubcategories,whichcloudsitsdefinition.Duringwakefulness,twotypesoftheta
havebeendescribed(Schacter,1977).Thefirst,frontalmidlinethetaappearstobeassociated
withfocussedattention,whereasthesecondhaswidespreadscalpdistributionandislinkedto
drowsinessandimpairedinformationprocessing(Pizzagalli,2007).Klimesch(1999)notesthe
formerthetasynchronisesupontaskonset,reflectingagreaterattentivestate.However,ina
studyobservingtheeffectoforthostaticchangeonvigilance,Caldwelletal(2003),ascribingto
thelatterthetacategoryfoundthegeneralriseinpowerastaskdurationcontinued,tobe
reflectiveofincreasinginhibitionofCNSexcitation,indicativeoflowarousal.Caldwelletal’s
(2003)notionissupportedbyLimetal(2008),whosuggestthatthetaactivityisrelatedtothe
homeostaticdrivetosleep.
Physiologically,thetaactivityhasbeenimplicatedwiththesepto-hippocampalsystem
(Pizzagalli,2007).Thetapowercanberecordeddifferentiallyinnumerousotherlimbicregions
(e.g.,anteriorcingulatecortex,medialseptum)(Pizzagalli,2007).Thedifferentsourcesoftheta
55
powermayexplainthesometimesconflictingresponsetotaskdemandsbetweenrecording
sites.Thetapowerhasbeenspeculatedtosubserveagatingfunctionontheinformation
processingflowwithinthelimbicsystems(Vinogradova,1995).
Thetaandalphabandsinparticularreflectcognitiveandmemoryperformance(Eohetal.,
2005;Klimesch,1999),whilebetabandindicatesincreasedprocessingdemands(Eohetal.,
2005;Pizzagalli,2007;Prinzeletal.,2003).Alphaandbetarhythmsappeartohaveaninverse
relationshipsuchthatwhenbetapowerincreasesalphadecreases(Schier,2000).Alphapower
desynchroniseswithtaskonset,asalphabandsynchronicityrepresentsgeneralisedneuronal
activityunrelatedtoattention(Klimesch,1999).Thishasledresearcherstoarguethatalpha
powerreflectsexternalevents,whereasbetareflectsintrinsicevents(Rayetal.,1985b).Inlight
ofconflictingsynchronisations/desynchronisationsoccurringwithinfrequencybands,authors
mustbecarefultodefinethefrequencypatterntowhichtheyareascribingtheirspecific
correlations.
2.6.2
Agerelatedalphafrequencychanges
Thealphafrequencydoesnotappeartopresideasthedominantpoweroverthescalpuntil
12yearsofageatearliest,andgainsdominanceat~16yrsold,whereuponitdevelops
predominanceovertheposteriorcranium(Klimesch,1999).Priorto12yearsofage,studies
conductedonalphapowerhavenotedthatathetapeakat~4.5Hz,appearsequaltoanalpha
peakat~9Hz(Klimesch,1999).Asadolescent’sage,thethetapeakdecreasesalongwitha
residingwakingdeltafrequency,andalphacontinuestorise(Klimesch,1999).Afterrisingto
dominancesby~16yrs,alphafrequencythenbeginstoslowwithaging,progressivelyreducing
fromperhapsasearlyas30yearsofageanddefinitivelyfrom50yearsofage(Klimesch,1999)
(suchthatthefrequencyslowsfrom~10.89Hz,to~8Hz(Kopruneretal.,1984)).Kopruneretal
(1984)foundalinearrelationshipbetweenmaturealphafrequencyandaging.
56
Theprogressiveslowingofalphafrequencymaynotberelatedtoalossofcognitivepower,
butratherduetootherneurologicalissues(Klimesch,1999).Theslowingalphafrequency
meansthatthetraditionalalpharangeresidingbetween8-13Hzmissesadominantportionof
theloweralphabandinelderlyindividuals.Thisslowingdownisalsointerpersonallyvariable
suchthatdeterminingnewalphabandsmustbeeitherwidenedtoencompassvariability,or
determinedindividually(Klimesch,1999).Inconjunctionwithtemporalchanges,spatial
changesalsotakeplaceinagingindividuals,withashiftfromparietalandoccipitaldominance
towardatemporallobeshift.Asaconsequence,EEGstudiesfocussingonagingpopulations
outsidethe20-30yearoldrangemustfocuselectrodeplacementfromparietalandmidline,to
temporaltoencompassthisshiftinspatialalphaactivity(Chokrovertyetal.,2005).
Theagerelatedchangesinalphaactivity–bothfrequencyandpower–altertheEEGactivity
awayfromthetraditionalalpharangeof8-13Hz.This‘traditional’rangecanonlybetrulysaid
toholdtrueforarelativelylimitedagerangeacrossthespanofmostindividual’slifetime.As
such,therangebetweenfullmaturationofthealpharhythmat~16yrs,anditsdegradationat
~30yrs,providesresearchersarelativelyclear–albeitlimited–cross-sectiontoobserve
healthypopulations.
2.6.3
BetaRhythm
Thebetafrequencyinadultsispredominantlyfocussedinthefrontalandcentralregionsof
thecraniumandinterspersedwithalphafrequenciesintheposterior(Chokrovertyetal.,2005).
Betapowertypicallyincreasesattaskonsetasattentionaldemandsarefocussedandprocessing
demandsincrease,whileitdecreaseswhenfewercognitiveresourcesarerequiredtomaintain
adequateperformance(Eohetal.,2005;Schier,2000).Insituationsoflong,sustainedattention
orsleepdeprivation,fatigueinertiaisalsoassociatedwithbetapowerreduction(Laletal.,
2002).FatigueinertiaistheprocessofincreasingpressuretosleepasaresultofProcessS
mechanisms(Klimesch,1999;Marzanoetal.,2011).Betaindicatesthechangeofvigilance,and
brainactivityintheprefrontallobe(Limetal.,2008).
57
BetaactivityisarguablythemostusefulEEGdiscriminatorofworseningvigilance.Belyavin
etal(1987)foundbetapowertobethegreatestindicatorofattentionandarousal,andthishas
sincebeensupportedbySchier(2000)andOkenetal(2006).Whenattentionaldemandsare
presentbetapowersynchronises,respondingtothetaskdemandsonsensorycorticalareas;
betaisespeciallyprevalentwhenparticipantsengageworkingmemorytasks.PriortoBelyavin
andWright(1987),studiessuchasTownsendetal(1979)foundthedecreaseinbetafrequency
priortostimuluspresentationtobeabettermarkerthanthetafrequency,despitemore
consistencyfoundinthealphaandthetafrequencies(Okenetal.,2006).HoweverEEGshows
greatinter-individualvariabilityasdescribedbyNiedermeyer(1999).Thisvariationseen
betweenfrequencysensitivitymaybeduetodifferingtaskconstraintsasopposedtovariable
EEG.Forexample,tasksrequiringsustainedattentionwithworkingmemorywillproduce
greaterbetaactivitythanatasksimplyrequiringvisualcues(Limetal.,2008;Okenetal.,2006).
However,despitechangesintaskdemands,McEvoyetal(2000)foundEEGtobehighlystable
andreliableduringperformanceofalloftheirtasks(PVT,andeasyversushardworking
memorytasks).
Betarhythmisusedtodeterminealertnessandarousal;thetwomaincomponentsof
vigilance(Eohetal.,2005;Limetal.,2008).Assuch,betarhythmisnottypicallypresentduring
restwitheyesclosed,butappearsoverfrontalsitesandspreadsposteriorlywhentasksare
performed.Astaskdurationincreases,betaactivitytendstoreduceduetodecreasedattention
andlowerarousal(Prinzeletal.,2003).Betaactivityismoststronglyassociatedwithchangein
vigilance(Limetal.,2008).Schier(2000),notedthatastaskdurationincreasedparticipants
requiredlessworkingmemorytomaintaintaskperformance,whichwasreflectedasadecrease
inbetaandariseinalphafrequency.Asthepressuretosleepincreases,betapowerdropsout,
untilsleeponset.Ifsleepisprevented,however,betaactivityappearstoreflectthebrainactivity
focussedonmaintainingthewakingstate(Marzanoetal.,2011).Upononsetofanoveltask,beta
activitysynchronisesinresponsetoattentionaldemands.Followinginitialsynchronisation,beta
powerdeclinesastaskproficiencyincreases,requiringlessattention.Alatepeakinbetaactivity,
58
seeninstatesofsleepinessisoftenattributedtothegreaterfocusonmaintainingthewaking
state(Niedermeyer,1999;Schier,2000).
2.6.4
10-20EEGelectrodepositioning
The10-20systemforelectrodepositioningwasoriginallydesignedbyJasper(1958).The
majorityofstudiesobservingchangeinthewakingstateuseatleastfourelectrodes
encompassingvarioussitesoverthescalp(e.g.,C3-M2,C4-M1,O1-M1,O2-M2)(Chokrovertyet
al.,2005).Otherstudieswilluse8-10electrodestoencompassareaspertainingtoabnormalities
inEEGfrequencies(Chokrovertyetal.,2005).Electrodepositioningisinreferencetoanatomical
landmarksdenotingthelobebeneath,andisrecognisedasthestandardisedsystemfor
observingEEG(Chokrovertyetal.,2005).Electrodepositionscorrespondtoanatomicalfeatures
ofthebrain,suchaslobes(e.g.,O1,O2),withoddandevennumbersrepresentingtheleftand
righthemispheres,respectively.
Thechoiceofelectrodepositioningisimportantasitallowslocalisationofspecificrhythms
fromcorticalsitesinvolvedinanygiventask(e.g.,betarhythmlocatedoverfronto-central
regions,alphapredominanceoveroccipitalregions)(Madridetal.,2010).EEGpositions
commonlyusedincludeO1/O2duetothenatureofmosttasksinvolvingvisualstimuli.For
example,Belyavinetal(1987)recordedfromposteriorpositions(P3-O1,P4-O2)measuring
theta,alphaandbetachange,duringavisualvigilancetask.Whenmemorytasksareincluded
withinsuchtestsfrontalelectrodesareusedtomeasureexcitabilityfromtheprefrontallobe
encompassingtheworkingmemory(Klimesch,1999).Schier(2000)foundF4tobethemost
sensitivesiteforassessingworkingmemory,ascommonlyaccepted(Klimesch,1999).
Rayetal(1985b)foundnohemisphericbiasinanintakeverserejectiontask,butobserved
differentialrepresentationsofattentional,cognitiveandemotionalfactors,intermsofEEG
frequencyandsite.However,righthemispheredominancehasbeendemonstratedthrough
observationofcerebralbloodflow(Deutschetal.,1987).Despitethisfinding,similaractivation
59
occursbilaterallyacrossthescalp,withtheelicitedlefthemisphereonlyslightlylessactive
comparedtotheright(Mesulam,1986;Schier,2000).Vigilancetasksengageavarietyof
systemsincludingworkingmemory,visual,andmotorresponses,andleadstudiestorecord
frommultiplesites.Thesesitestypicallycoverarangefromfrontalsitestooccipital
(Chokrovertyetal.,2005).
Electroencephalographicactivityisvariableaccordingtothecorticalsitebeingassessed
(Gillbergetal.,1996).EEGisalsodependentonthetaskdemandsanddegreeofpressureto
sleep(Caldwelletal.,2003).Assuchelectrodeplacementandstimulationmustbeverycarefully
performedtoensurethatinterpretationofthewaveformscanbeassessedaccuratelyand
validly.Forexample,inanexperimentbyCaldwelletal(2003),thetasynchronisationwas
arguedtobeassociatedwithcognitivedecline,asdeltaandthetaactivityhadpreviouslybeen
associatedwithprolongedwakefulness,andreductionofarousal(Gillbergetal.,1996;Laletal.,
2002).Conversely,otherstudieshavenotedthatthetasynchronisationisassociatedwith
increasingtaskdemands(Eohetal.,2005;Klimesch,1999).Assuch,theparadigmorapproach
totheinterpretationbecomesimportant.However,beforetheseapproachescanbemade,the
electrodepositioningisthemostimportantconsideration.
2.6.5
Electro-oculogram(EOG)
Theelectro-oculogramiscommonlyusedasareferencewhenfocussingonfrontalEEGsites,
andprovidesinsightfulmeasuresinitsownright.Itistypicallyrecordedfromtheoutercanthus,
1cminferior,and1cmlateraltothecorneaonthelefteye,and1cmsuperior,and1cmlateralto
thecorneaontherighteye(Hakkinenetal.,1993).Therearethreemaincategoriesofblinks:
wakingeyemovements(WEM),sloweyemovements(SEM),andREMs(Chokrovertyetal.,
2005).WEMsareassociatedwithblinksandsaccadiceyemovements,whereasSEMsare
recordedconsistentlyinthehorizontalaxisatonsetofN1sleep.Thechangeinblinksappearsto
displayaconsistentchangewithfatigue,providingmeaningfulinferenceofdecliningsustained
attention(Stern,1994).TheefficacyofEOGisfurthersupportedbyLaletal(2002),who
60
displayedachangefrominitialfastblinksandWEMtowardincreasingslowblinksandnoeye
movementastheirmonotonousdrivingtaskprogressed,indicatingalossofattentionand
fatigueadvancement.Santamariaetal(1987)alsoarguethatEOGprovidessignificant
observationalchangesasfatigueprogresses.EOGprovidesclearindicesoffatigueduring
continuoustasks,suchasdriving(Schier,2000;Stern,1994).EOGwhencoupledwithEEGcan
strengthenthefindingsbydirectlycorrelatingeyemovementandblinkdurationataparticular
timewithEEGbandsseen(Santamariaetal.,1987).Thisallowsgreaterinsightintothecauseof
theapparentbandsobserved.
2.7
Conclusion
Peripheralvasculartoneishighlycontrolled,withthetwomaincontrollingfactorsbeing
thermoregulationandcircadianneuronalrhythmicity.Whenmaintainedinanormothermic
environment,thecorebodyandskintemperatureswillundergoreciprocalinversefluctuations
asaresultofthecircadianrhythm.HormonalandneuralmediationbytheSCNaccountsforthe
non-thermalmodulationoftheTCcyclicrhythmicity.Eveningcorenadirisachievedthrough
vasodilationofspecialisedskinbloodvessels(AVA’s)asaresultofmelatoninsynthesis,
parasympatheticandPOAHinnervation,seeminglytofacilitateaDPGcapableofgenerating
maximalrateofheatloss-andthroughthis-sleeponset(Kräuchietal.,1999).Theriseofdistal
skintemperaturealsoappearstoindependentlyfacilitatesleeponset.Phasicexternal
perturbationsthatopposethiscircumstance,suchasfootcoolingintheevening,willresultin
vascularresponsesinversetothatfacilitatingsleeponset(Fronczeketal.,2008;Kräuchietal.,
2008;Raymannetal.,2005).Despitetheroleofcircadianrhythms,homeostaticpressureto
sleepamplifiesanysleepfacilitativeprocessfollowingextendedwakinghours,regardlessof
phaseinbiologicaldayornight.Sinceextended(lateevening)wakingappearstoresultin
continuingdeclineincoretemperaturewithcontinuingrobustcircadianfluctuation,theeffectof
61
relativelypassivewake-promotingtemperaturemodulationmaybeoutweighedbythe
aggressivesleeppermissivemetabolicandneuronalfactorssuchasadenosine,and/orsynaptic
density(Hurwitzetal.,2004;Porkka-Heiskanenetal.,2002;Tononietal.,2006)
Sinceskintemperatureishighlyinfluencedbytheenvironmentaltemperature,andasnoted
byHaskelletal(1981),thermoregulationisincompatiblewithsleep,itisthereforeintegralto
furtherexploretheimpactresultingfromthermalmodulationwithinthephysiologicalrangesof
thermoregulatoryresponses.Aspreviouslyobservedinsleepresearch,manipulatingskin
temperaturecanreducesleeponsetlatency(Kräuchietal.,1999;Raymannetal.,2005,2007a;
Romeijnetal.,2012a),orvigilancecanbemaintained(Fronczeketal.,2008;Raymannetal.,
2007b).Theonlystudythatappearstohavedirectlyattemptedtomaintainvigilancethrough
subtletemperaturemanipulation,wasperformedonnarcoleptics,withFronczeketal(2008)
greatlyalteringdaytimesleepinessandvigilancewithtemperaturemanipulationwithinthe
normothermicrange.Asnarcolepticcyclesresemblethesleeponsetpatternsofnormal
individuals,itcouldbepostulatedthattemperaturemanipulationmayoverridecircadianand
homeostatichourglassprocesses.Maintenanceofvigilancehasbeenofcriticalimportance
withindrivingorientedresearch,however,asofyet,peripheralcoolingappearsnottohavebeen
investigatedasamethodformaintainingvigilanceinthenormalhealthypopulation.More
importantly,theinvestigationofsubtlesystematicdistalcoolinghasnotyetbeenperformedina
controlledsetting.
Thus,whilewarminghasbeenexploredforvariousmeasures,cooling,asawake-promoting
factorappearstohavereceivedalmostnoconsiderationdespiteitswidespreadrelevance.The
currentstudyaimstoexaminesucheffects.
62
3.0
METHOD
Thepurposeofthecurrentstudywastoexaminetheeffectofdistallowerlimb(foot)cooling
ontheeveningvigilancedecline.Theaimwastopreventeveningdistaltemperaturerise.The
associatedeffectonTCdeclinemayhaveanimportantroleinsleeppropensity,howevergiven
themultifacetednatureofsleepphysiologyoutlinedpreviously(Chapter2),manipulatingskin
temperaturewasdeemedsufficient.Apartiallyblinded,crossoverdesignwasutilised,inwhich
healthyparticipantsundertookapsychomotorvigilancetaskduringthreeeveningsessionswith
differentextentsoftemperaturemanipulationoftheirfeet,inatemperate,controlledthermal
environment(~25OC,Humidity:33%).Theprotocoloverviewisdetailedschematicallyin
Figure3.1.Asacomponentoftheexperimentaldesign,participantswereexpectedtomaintaina
sleepdiaryandwearanaccelerometerforthepurposeofmonitoringprior(totestnight)sleep
wakecircadianrhythm.
7-daysleepdiary
Testnight
Circadian
rhythm
Night/daycycle
Equipmentsetup(i.e.,accelerometry)/laboratorysetup
Durationoftestnightprotocol
Figure3.1:Protocoloverview
TheexperimentaldesignisdetailedschematicallyinFigure3.2.Environmentaltemperature
andhumidityweremaintainedusinganenvironmentalchamber(SchoolofPhysicalEducation
SportandExerciseSciences,UniversityofOtago,NZ).Thethreetestnightswereseparatedby7
daysofnormalsleep,withtheexceptionofonemalewhowasdelayedafortnightinhisthird
trialduetosickness.Femalesparticipatedinthefollicularphase(days4to12)oftheir
63
menstrualcycleallowingonemonthbetweensessions.Onefemaleexperiencedalapseinher
cycleduetoexcesstraining,andthereforeparticipatedinthezonebaseduponherprevioustwo
cycles.ThisstudywasapprovedbytheOtagoHumanEthicsCommittee(Protocol13/087).
Figure3.2:Studyoverview
Participant
Test1(++/+/≈) Test2(++/+/≈)
Test3(++/+/≈)
Prep
Base
VigilanceTesting
Post
Block1
2
3
4
5
23:00
00:00
01:00
02:00
21:00
22:30
PVT
rest
KDT
rest
23:00
00:10
00:25
00:33
00:18
00:00
Stim
Feedback Inter-stiminterval EyesOpen
EyesClosed
1s
1s
2-10s
5min
2min
++ Moderatecondition
+
Mildcondition
≈
Controlcondition
64
3.1
Experimentalprotocol
Familiarisation:Afamiliarisationsessionwasconductedtointroducetheparticipantstothe
equipmentandprocedureofthetestnight.Allfamiliarisationsessionstookplaceduring
daytime.ParticipantsunderwentafullsetupofEEGelectrodesandperformedone2-min
practicePVTfollowedbyafull10-minPVTtrial.Participantswereurgedtorespondasquickly
aspossibletothetask.Nothermistorswerefittedinthefamiliarisation.Participantswerealso
screenedforage,heightandmass;thesecharacteristicsofthecohortareshowninTable3.1.
Sleep/wakecyclesweremonitoredbothobjectively,usingaccelerometry(Actical
accelerometer, Mini-Mitter Co., Inc., Bend, OR), andsubjectivelyusingasleepdiaryforsix
dayspriortotesting.Actigraphicdatawereassessedandanalysedusingacustom-madeMatlab
programme.
Testingsessions:Ontheeveningoftesting,participantsarrivedat21:00toundergoastatus
assessment(Brunelquestionnaire,hydrationstatus[USG],subjectivesleepiness[KSS]).Mood
statewasassessedpriortogoingtothebathroomtoinserttherectalthermistorandproviding
urineforhydration.Onceseated(~21:15),participantswereserved250mLofa749kJ
chocolatemilkdrink(Calci-Strongchocolatemilk,MeadowFresh,NZ),whileEEG(includingECG
andEOG)electrodesandthermistorswerefitted.Duringsetup,participantswereplayeda
podcast(TEDRadioHour,andTheJoeRoganExperience).
Followingsetup,participantswereafforded~15minquietreadingofchosenmaterials
(noveloracademicliterature)priortothe22:30starttime.Thetestingproceduretookplacein
adimroomlitfrombehindthroughawindowbylightingoftheadjoinedroom(SeeAppendixC
forphotosofsetup).Participants,forbiddenfromfacingthelightsource,received0.25nW/m2in
theirfieldofview.Participantsworeearplugsthroughoutthetesttominimiseextraneousnoise.
BaselinedataconsistedofaPVT(at22:30),followedbyaquestion,“howsleepydoyoufeel?”
ParticipantsthenperformedtheKDT,beforebeingaskedfourquestions:“Howdoesthe
65
temperatureofspecificallyyourfeetfeel?”“Areyoucomfortablewiththis?”“Howdoesthe
temperatureoftherestofyourbodyfeel?”“Areyoucomfortablewiththis?”
Participantsthencommencedoneofthethreethermalconditions:moderatecoolingofthe
feet(25OC),mildcoolingofthefeet(30OC)or,un-manipulated/control(~35OC).Thermal
manipulationswereviacustom-madewater-perfusedbooties,asdescribedinApparatusand
Measuresbelow.Manipulationbeganwithstatement“ten-minutesofmanipulation;youmay
read”.Followinginitialreductionoftemperaturesparticipantsbeganvigilancetesting(~23:00);
depictedinFigures3.2and3.3.Feetwerekeptattheirassignedtemperatureforthedurationof
testing.
Participantswereassessedforvigilance,sleepiness,andcognitivearousalusing
electroencephalography,andthermalperceptionsusingthevalidatedtestsandscalesdescribed
inApparatusandMeasures,attimingsshowninFigure3.2.Inbrief,alternatingvigilanceand
drowsinesstaskswereseparatedby8minrestperiods,duringwhichparticipantsreadquietly
(Figure3.3).ThesubjectivequestionnaireswereaskedbetweenthePVTandtheKDT.ThePVT,
KDTandassociatedrestandsubjectivequestionnairescomprisedasingleblock.PVTwas
repeatedfivetimes,whileKDTwasrepeatedsix,withtheextraKDTperformedimmediately
afterthe10-minmanipulationperiod.
Participantsweremonitoredconstantly(visuallyandusingelectrophysiolographicvariables)
forsignsofsleeponset.Atanystageintheeveningwheresleeponsetappearedimminent
participantswererousedafter~5swiththe
statement“eyesopen,please”.DuringthePVTthis
8-minRest
perceptualQs
Vigilance
(PVT)
10-min
Drowsiness
(KDT)
7-min
8-minRest
perceptualQs
intervalwastypicallyshorter(~2-4s).Participants
mostcommonlysufferedfromsleeponsetduringthe
eyesclosedKDT,atwhich,theywereallowedtodrift
forthedurationoftheperiod(2min).
Figure3.3:Manipulatedtesting
cycle
66
3.2
Participants
Ninehealthyparticipants(6males,3females),withnosleepcomplaintsandnormalised
sleeprhythms,completedthestudy(ofatotal13recruitedandscreened).Contraindicationsto
participationinthestudyincludedtheusesofvaso-activedrugsorsleepmedications,or
participantsdisplayingtendenciestowardlatenightbehaviour(i.e.,frequentlyuplaterthan
12am).Participantscomplainingofbrokenupsleepandexcessivedaytimesleepinesswerealso
excluded.ParticipantswerenotscreenedforabnormalEEGrhythmspriortotesting.
Expectationsofsleep/wakecycleandalcohol/caffeineintakewerediscussedwithparticipants.
Expectationsrestrictedonlyparticipants’alcoholconsumptionandsleeppatterns48hours
beforethetestnight.Adherencetotheserestrictionswascheckedbyquestioningbefore
beginningthenightsession.
Table3.1:Participantdetails
Number
Age
Height(cm)
Mass(kg)
BMI(kg/m2)
Male
6
19.2±0.8
180.03±5.96
80.40±9.11
24.75±1.81
Female
3
21.3±2.1
161.80±5.90
59.77±5.93
22.82±1.64
67
3.4
ApparatusandMeasures
3.4.1
PsychomotorVigilanceTask
VigilancewasmeasuredusingthePsychomotorVigilanceTask(PVT-192,
AmbulatoryMonitoringInc.,NewYork,USA),originallydesignedbyWilkinsonetal
(1982)andvalidatedforvigilanceassessmentbyDingesetal(1985)andforsleep
deprivationbyBasneretal(2011).ThePVTassessessustainedattentionacrossa
relativelybriefperiod(10min).Itwasperformedwhileseated,withthedeviceresting
inparticipants’handsandagainstthetableatanapproximatedistanceof40cmfrom
theface.Thetaskconsistsofasimple4-digitcounterthatappearsandincrementsin
milliseconds,towhichparticipantsrespondbytappingthebuttonwiththeirright
thumb.Thestimuliappearatrandomintervalsof2-10s(seeAppendixD).Participants
wereremindedtorespondasquicklyaspossiblepriortobeginningthebaselinetest.
Thenumberoflapses(RTs>500msoramissedresponse)per10mintaskwascounted
asameasureofperformancedecrement,indicativeofbehaviouralawareness(Van
Dongenetal.,2003).ReactiontimeswererepresentedastheReciprocalofResponse
Time(RRT=1000/RT),toprovideanormativedistribution,andminimisebiaswithin
validresponses(Caldwelletal.,2003;Fronczeketal.,2008).Thus,consistentlylarger
numberswithfewlapsesindicatebettervigilance.Averageswerecalculatedperminute
toquantifythetypicalperformancedeclineacrossthecourseofthetime-on-task
(Fronczeketal.,2008).
3.4.2
Electrophysiologicalmeasures(EEG,EOG,ECG)
Cognitivearousalwasmeasuredusingelectroencephalographyatsevenscalp
locations:F3,F4,C3,C4,Pz,O1,andO2,andreferencedtoM1,M2(A1andA2onFigure
3.3),andFpzaccordingtotheinternational10/20system.BipolarEOGwasfittedtothe
outercanthioftheeyes2cmaboveandlateraltotherighteyeand2cmbelowand
68
lateraltothelefteye,accordingtotheprotocolofHakkinenetal(1993).Athree-lead
ECGwasalsoappliedandreferencedintotheEEG/EOGsystem.Allscalpsiteswere
inkedbeforecleaningsitesandfixingtheelectrodes.Electrodeswerenotfixedinplace
butinsteadheldfirmbyaheadwrap.Preppingsitesinvolvedabrasionoftheskinsite
(NuPrep,Weaver&Co,Colorado,USA),followedbycleaningwithanalcoholswab
(AlcoholPreps,TycoHealthcare,Mansfield,USA).Salinepaste(10/20Paste,Weaver&
Co,Colorado,USA)filledthegoldcupelectrodesforconductivity.Acceptableimpedance
levelswere<5kΩ.Electroencephalographywasrecordedcontinuously,withmarkers
indicatingonsetofcognitivetests.Thetest-retestreliabilityofEEGhasbeenvalidated
(McEvoyetal.,2000).
CognitivearousalwasassessedusingtheKDT(Akerstedtetal.,1990).TheKDT
involves5mineyesopenfollowedby2mineyesclosed.Duringtheeyesopensection
participantsfixateduponanon-movingpoint(e.g.,drawingpin)approximately1min
frontofthem.FrequenciescommonlyassociatedwiththeKDTaretheta(4-7Hz)and
alpha(8-12Hz).Allelectrophysiologicalsignallingwascompiledinthe
polysomnography(PSG)system(CompumedicsE-series,CompumedicsLtd,Victoria,
Australia).Withinthesoftwareused,sampleratesforEEG,EOG,andECGwere256Hz.
High(0.3Hz)andlow(70Hz)bandpassandnotch(50Hz)filterswerealsoapplied.
LateranalysesusedFastFourierTransformandpowerspectralanalysistoderivethe
frequenciesofinterest.
ElectrocardiographicrecordingsoftheR-Rintervalwereobservedto
obtainahighlyreliableandvalidmeasureofthesleeponset
associatedheartratedecline.Thiswasperformedusingtwo
leadECGaddedtothePSGsoftware.ECGwasanalysedas
changeoverboththetestsessionaseachPVTwithinsessions.
Figure3.4:International10/20
system.Scalplocationsusedare
circled.
69
3.4.3
Sleeponset/staging
SleepscoringwasbasedupontheReichtshaffen-Kalescriteria(Rechtschaffenetal.,
1968)foranalysingsleepstagesusingEEGandmodifiedfordrowsinessusing
(Santamariaetal.,1987)definitionsfordrowsinesszones(SeeAppendixDforoutlines).
Stagewake(W)wasdefinedascontaininglowvoltage,mixedfrequencies,including
predominantlyalphaband.ThedrowsinessperiodsbetweenwakefulnessandNIsleep
arenotwelldefined,butthecurrentstudyusedtheguidelinesprovidedby(Santamaria
etal.,1987).Specifically,infollowingfromwakingintodrowsinessalphaslows,as
fatigueprogressesbetafrequencydisappears,alphacontinuestoslowlosingamplitude,
thenbecomesmorediffuse,progressinganteriorly.Finally,alphaamplitudeminimises
ordisappearsintoN1sleep.Witheyesclosed,alphadominates~50%,withlowvoltage,
highfrequenciespresent.N1presentslowvoltage,mixedfrequencywiththeta
frequencyrisinginpowerandappearanceofoccasionalvertexsharpwaves.N2was
recognisedasincludingatleastoneKcomplexbutlessthan20%deltafrequency.
ParticipantswerenotexpectedtoprogressintosleepstagesbeyondN1,however
clarificationwasbeneficialduringeyesclosedKDTperiod.
3.4.4
Temperature
Coretemperaturewasmeasuredusingaflexible,sterilethermistor(Mallinckrodt
400generalpurpose,MallinckrodtMedicalInc.StLouis,USA)placedintherectumprior
toequipmentsetupeachnight.Participantswereinstructedontheinsertionoftheir
ownthermistor(10cmpasttheanus).Eachparticipantreusedhisorherownrectal
thermistorforeachofthetestnights,followingitsdisinfection.Factorycalibrationwas
assumedforthermistors.Asthermistorswerereusedwithinparticipants,absolute
accuracywaslessimportant.
70
Skintemperaturewasrecordedatnineskinsites:dorsalandventralaspectsofthe
firstdistalphalanxofthefoot,mid-plantaraspectofthefoot,1sttarsometatarsaljoint,
midlateralcalf,midanteriorthigh,chest(atxiphisternum),midanteriorforearm,
palmarsurfaceofthehand,firstdistalphalanx,andtheforehead.Temperaturewas
recordedfrominsulatedskinthermistors(EUthermistors,GrantInstrumentsLtd,
Cambridge,UK),tapedtotheskin.
Alltemperaturedatawerecollectedusingaportabledatalogger(2020Squirrel,
GrantInstruments,Cambridge,UK)in1minintervals.Ambientdrybulbandwater
temperatureswerealsomeasuredthroughout.Distal-proximalgradientwasderived
fromskintemperatures.Distalsiteswereseparatedintoupperlimb(forearm,palm,and
hand),andlowerlimb(toepad,toetop,footarch,foot1stMT,andcalf).Proximalskin
sitesforthegradientincluded:thigh,chestandforehead.
Temperaturemanipulationswerebaseduponpilotdata(AppendixF).Manipulation
wasachievedthroughuseofcustom-builtwater-perfusedbooties(SeeappendixG).
Thesebootieswerecustomfitting,andlaceupwithelasticliningtheoutsideofthearch
toensurecontactofwater-perfusiontubesthroughthemidfoot.Thesewereperfused
withcooledwaterinthemanipulatedsessions,suchthatthetemperaturemodulations
achievedreachedapproximately-5OCand-10OClessthantheeveningdistal
temperatureof35OC.DPGsassociatedwithdistaltemperatureswereseparated
betweenupperandlowerlimbs.Anurnservedtoprovideareservoirforthecirculating
water,andthemeansbywhichwatertemperaturewasaltered.Thewatertemperature
requiredtomaintainconstantskintemperatureswerevariableandhadtobeconstantly
reassessed.Temperatureofthewaterwasmonitoredbeforeitenteredthebooties.
71
3.4.5
Actigraphyandsleepdiary
Eachparticipant’ssleep-wakecyclewasmeasuredusingbothaccelerometryand
sleepdiaries(SleepdiaryandactivitymonitoringprovidedinAppendixB).The
specialisedaccelerometersusedwerewornagainsttheskinaroundthewaistusing
belts(Actical,PhilipsRespironics,USA).Theaccelerometersweredesignedtobeworn
atalltimes(e.g.,includingshower).Ifremovedforlongerthan5-10min,participants
wereexpectedtorecordtimeoffandtimebackonaswellasreasonforremoval/activity
whilenotworn.Accelerometrywasrecordedfortheweekpriortotesting,in
conjunctionwiththe7-daysleepdiary.Accelerometrywasusedtoensurevalidityof
sleepwakecycleandtoaccompanythe7-daysleepdiary.Thedatawereanalysedfor
standardsleep-wakevariablesusingthecount-scaledalgorithmincorporatedwithin
Matlabscript(Gallandetal.,2012).The7-daysleepdiaryincluded:startdate,bedtime,
andwakeuptime.48hourspriortotestingparticipantswereexpectedtoadhereto
normalsleeptimes.
3.4.6
Subjectivequestionnaires
SubjectivemeasureswereassessedeithersideofeachPVT,withsleepinessrecorded
immediatelypreandpost.Sleepinesswasrecordedusingthe9-pointKarolinska
SleepinessScale(KSS):1=extremelyalert,2=veryalert,3=alert,4=ratheralert,5=
neitheralertnorsleepy,6=somesignsofsleepiness,7=sleepy,noefforttostayawake,
8=sleepy,someefforttostayawake,9=verysleepy,greatefforttokeepawake,fighting
sleep(AppendixH).TheKSShasbeenvalidatedagainstobjectivephysiological
measures,specificallythatoftheKDT(Akerstedtetal.,1990;Kaidaetal.,2006;Putilov
etal.,2013).
Perceivedtemperaturewasrecordedusingamodified13-pointThermalSensation
Scale:1=unbearablycold,2=extremelycold,3=verycold,4=cold,5=cool,6=slightly
72
cool,7=neutral,8=slightlywarm,9=warm,10=hot,11=veryhot,12=extremelyhot,
13=unbearablyhot(Cotteretal.,2005).Thermalsensationwasaugmentedbythe
thermaldiscomfortscale:1=comfortable,2=slightlyuncomfortable,3=uncomfortable,
4=veryuncomfortable,5=extremelyuncomfortable(AppendixI).Thequestionswere
askedatthebeginningofeachrestperiod,“howdoesthetemperatureofyourbody
feel?”Atbaseline,adjustedbaseline,andpost,participantswerealsoaskedtoseparate
thesensationoftheirfeetfromtherestofthebody;“howdoesthetemperatureof
specificallyyourfeetfeel?”“Howdoestherestofyourbodyfeel?”Extendedfromthe
scalesdesignedandvalidatedbyGaggeetal(1996).Thermalsensationanddiscomfort
questionnairesarehighlyvalidatedtoreflectunderlyingthermoregulatorychanges
(Candasetal.,2007;Clineetal.,2004;Kräuchietal.,2008),butcanbepronetoskew
(e.g.,focusofperceptiononotherbodyregions)andareoftentemporallydelayed(Cline
etal.,2004;Cotteretal.,2005).
MoodstatewasassessedbytheBrunelMoodStatequestionnaire(BRUMS;Appendix
J)(Terryetal.,1999).TheBRUMSassesseschangesinparticipants’currentstate(Lalet
al.,2002).Thereare24adjectivescomprisingsixelementsofmood(anger,confusion,
depression,fatigue,tension,andvigour).Forthesakeofbrevityandspecificityonlythe
constituentsofvigourandfatiguewereanalysed.TheBRUMS(AppendixJ)wasasked
uponentryintothelab,andpost-test,toassessemotionalstatusoftheparticipantsfor
potentialconfoundingfactors.Participantswereaskedtoratehowtheyfeelrightnow
onafive-pointLikertscale.Scaleswereanchoredtoverbalcuesof:“notatall”,“alittle”,
“moderately”,“quitealot”and“extremely”.
3.4.7
HydrationStatus
Hydrationstatuswasmeasuredpre-andpost-testasurinespecificgravity,usinga
portablerefractometer(Atago,Astra,ZenecaPtyLtd,Japan).AUSGbelow1.020(range:
73
1.001-1.025)denoteseuhydration.Above1.030indicatesthebeginningofdehydration.
Noparticipantneededtoemptytheirbladderduringanyofthetests.
3.5
Dataanalysis
Apriorideterminationofsamplesizewasnotperformedinthecurrentstudy.A
samplesizeof14wasinitiallyselectedbasedupon(a)themuchhigherstatisticalpower
achievedwitharepeatedmeasuresdesign,and(b)priorresearchaddressingasimilar
questionobtainingstatisticallysignificantfindingswith~8participants(rangingfrom
n=7-16)(Caldwelletal.,2003;Fronczeketal.,2008;Krauchietal.,1994;Raymannetal.,
2005).Duetotimeandparticipantconstraintsthiswasloweredtonine,following
prolongeddifficultywithrecruitmentandretentionofprospectiveparticipants(e.g.,
recruitmentwasundertakenforadurationof12months).
3.5.1
DataReduction
Missingdatawereinterpolatedwhenrequired(thiswaslessthan10%ofthedata).
Specifically,coefficientofvariationwaschecked,andifsufficientlysmall(i.e.,<10%)
participantdatawereinterpolatedbyaveragingthedifferenceofadjacentdatapoints.
DatasetswereanalysedprimarilyinSPSS(SPSS,IBM,NewYork,USA),andPrism
(Prism,GraphPadSoftware,California,USA).
Priortoanalysis,PVTreactiontimeswereconvertedintoReciprocalreactiontime
(RRT=1000/RT).DuetotherandomISItherewasvariousnumbersofresponses.As
such,responseswerecondensedinto1minblocks.Lapses(responses>500ms)were
removedfromRRTanalysis.
74
Electroencephalographyrequiredsignificantdataprocessingpriortostatistical
analyses.DerivationsofsignificantcomponentsofEEGweremadeusingMatlab.
AnalysedchannelswereminimisedtoC4-A1,O2-A1.Fromthecontinuousrecording,
datawereminimisedintosevenblocksofKDTforeachchannel.KDT’swerevisually
scannedforartefactsand,whereproblematic,wereremovedfromanalysis.Blinkswere
automaticallyremovedinMatlabusinganalgorithmalongwithartefacts.KDTdata
werefurtherminimisedinto15sepochs(20foreyesopenand8foreyesclosed)using
theHanningcosinewindow.AFastFourierTransformwasthenperformedtoderive
powerfrequenciesfromeachblock.OftheseblocksAbsolutepowerdensity(uV2)was
calculatedforthetaandalphaandbetafrequencybandsoverderivations:C3,C4,O1,
andO2.Datawasfurtherreducedbyaveragingthe15sepochsintowholetrialperiods
(KDT1eyesopen,KDT1eyesclosed,etc.);wherebytherepeated-measuresANOVA
couldbeapplied.
3.5.2
StatisticalAnalyses
Wheresphericitywasviolated,asdeterminedbyMauchly’stest,degreesoffreedom
werecorrectedusingGreenhouse-Geisserestimatessoastodeterminesignificance
(P<0.05).Theanalysesthatrequiredcorrectionwere:Footlocations,Thermal
discomfort,KSS,RRT,andrelationofTCandRRT.
Two-wayandthree-wayrepeatedmeasureANOVAwasusedformostanalyses.TwowayANOVAwasusedtoassessordereffectinsleeppatternsofthe6-dayspreceding
eachsession.Contrastsweremadetoobservedifferencesbetweensixnightsandtwo
nightsbeforesession,toassessdifferencesbetweennormalsleeppatternsand
adherencetosleeprecommendations.PairwisecomparisonswithBonferronicorrection
werecarriedout.Temperaturedatawerealsoanalysedusingatwo-wayANOVA,to
assesstheeffectsofconditionsonvarioustemperatures(individualfootmeasures,core,
upperlimb,DPG,PCG).OthermeasuressuchasECG,andsubjectivescaleswere
75
analysedusingatwo-wayANOVA.Athree-wayANOVA(3x6x10)wasusedtoassess
theeffectofthermalconditionsonPVToutcomeparameters(RRT,lapses).Subjective
questionnaireswerealsoanalysedastwo-wayANOVA,butwithordinalvariables.EEG
wasanalysedusingtwo-wayANOVA.
76
4.0
RESULTS
Resultsarepresentedinasequenceprogressingfromstandardisationvariables(e.g.,
complianceandsleepdiary)tofoottemperature(i.e.,theindependentvariable)and
associatedbodytemperature,thenvigilance,andelectroencephalography.Relations
betweenphysiologicalandperceptualmeasuresarereportedlast.Dataaremean±S.D.
unlessstatedotherwise,with95%confidenceintervalsforcomparisonsofinterest.
Variabilitybars(e.g.,SD)areomittedfromsomefiguresforclarity,andbecausethey
wouldtypicallyillustratebetween-participantvariabilitywhereasthevariabilityof
majorinterestisthewithin-subjectvariability(ofthemeandifferencebetween
conditions).
4.1
Participantcharacteristicsandcompliance
4.1.1
Screening
Oftheparticipantsscreened,twocompletedasinglenightoftesting.Boththese
participantswerefemalesandsufferedboutsofextremesleepinessduringthetest,such
thattheywereunabletocompleteasinglePVTwithoutprompts.Bothparticipants
subsequentlyexpressedanunwillingnesstoperformanothertest,andweretherefore
removed.Onefurtherscreenedparticipantprofessedtobeepilepticandwastaking
vasoactivedrugs,whileanotherwasobeseandsufferedfromsleepapnoea,soboth
wereexcluded,leavingn=9whocompletedalltesting.
4.1.2
Adherence
Adherencetocaffeineandalcoholrestrictionswascheckedverballyatthebeginning
ofeachtestingsession.Ofthosenotcomplyingfully:P1consumedcaffeineatmiddayof
herControltestday;P5consumedcaffeineat9amofhisModeratetestday;andP6,
77
beforenoon.P6alsoconsumedonebeerthenightbeforeeachtest.Visualcheckingof
theirdataproducednoobviousoutlierdata.
4.1.3
Sleepdiaries–sleeponset
Sleepdiariesandaccelerometerswereprovidedtoensure“normal”healthysleepwakecyclesoccurredbeforetestnights.Participantswerenotexpectedtocomply
completelytoregimentedsleeptimes,particularlywellaheadoftheirtestnight.
Participantsthatsufferedaweekofpoorsleep(e.g.,assignmentdue,orsickness)were
deferreduntilasuitabledate.Compliancetoregularsleeponsetscheduleswasvariable
betweenaswellaswithinparticipants.Sleepdatacompriseaccelerometryandsleep
diaries.Completesetsofaccelerometryanddiarieswereobtainedfromthreeandsix
participants,respectively.Sevenparticipantsprovidedacompleterecordforatleastone
ofthesemethodsofdailysleepmonitoring.Resultingsleepdataarecomprisedofan
averageofbothaccelerometryandsleepdiariesduetothepooradherenceofsubjectsto
fillingouttheirdiariesandwearingtheaccelerometer.Table4.1(p.79)summarises
normalsleepbehaviourinallgroupsandthevariabilityisdescribedinmoredetail
below.
Bedtime:Atrendtowardearlierbedtimesoccurredacrossthesixtestingdays
(F(5,30)=2.363,P=0.064),butnotdifferentiallybetweenconditions(F(2,12)=1.77,
P=0.211).Astherewasnointeractioneffect,itisevidentthattherewasnosignificant
displacementofbedtimebetweenregulatedandunregulatednights(i.e.,day1verseday
5or6).Onthetwonightsbeforetesting(days5,and6)participantsgottosleepon
averageat23:22(hh:mm)(±41min)and22:45(±43min),whereassixnightsoutfrom
testing(day1)participantswenttosleeponaverageat23:43(±49min).
78
Waking:Therewasnointeractioneffectonwakeuptime(F(10,60)=0.97,P=0.482).The
meanwakeuptimeonthedayoftestingwas08:21(±42min).Thelargebetweensubjectvariabilityreflectsearliertypicalwakeuptimeoftherowersinthegroup.
Duration:Sleepdurationaveraged8.7±0.2hourspernight,withnodifference
betweenconditions(F(2,12)=0.11,P=0.894).Sleepdurationrangedfromaminimumof5
hononeoccasionand~6hforseveralparticipants,toamaximumof12hfortwo
participantsononeoccasion.Controlwasthemostconsistentconditionforsleephours,
whereasMildandModeratebothtendedtoshowincreasedsleephoursbetweendays5
(8.10±1.29h,8.3±1.6h,respectively)and6(9.6±1.66h,9.8±1.2h,respectively);
thisdidnotshowanordereffect.
Timing:Sixparticipantsadheredtotherecommendationofgoingtosleepbefore
midnightthroughoutthesixdaysprecedingatestnight,buttheotherthreeparticipants
stillaccruedanequivalent(unpairedt-test:P=0.21)totaldurationofsleepinthis
period.Withinthetwodaysbeforetestnight,wheretherecommendationwasexpected
tobeadheredto,twoparticipantsdidnotconformtosleeponsettimes,buthadsimilar
totalsleeptimes(group:8.8h;n=2:8.7h).
Ordereffects:Noordereffectswereevidentacrossthethreepre-trialperiodsfor
sleeponsettime(F(2,12)=0.49,P=0.368),wakeuptime(F(2,12)=0.11,P=0.896),ortotal
sleeptime(F(2,12)=0.44,P=0.652).
4.1.4
Moodstatecharacteristicsandhydration
Moodstateandhydrationweretestedbeforeandfollowingeachtest.Theelements
ofmoodanalysedfromtheBRUMSwerevigourandfatiguebecauseoftheirrelevancein
thisstudy.Vigourdeclined(F(1,8)=44.70,P<0.0001);notdifferentiallysobetween
conditions(F(2,16)=2.31,P=0.131),buttherewasamaineffectofcondition(F(2,16)=5.01,
P=0.021).Specifically,vigourwashigherinControlthaninMild(AppendixK:Figure1).
79
Fatigueincreasedsignificantlyacrossthetest(F(1,8)=40.13,P<0.0001),butnot
differentially(interaction:F(2,16)=1.99,P=0.168),andwasnotdifferentbetween
conditions(F(2,16)=0.56,P=0.584;illustratedinAppendixK:Figure2).
Participantsenteredthetesthydratedandendedthetestmildlyhypohydrated
accordingtoUSGvalues(Table4.2)
Table4.1:Bedtime,wakingtimeandtotalsleeptime(TST)determinedfromthe7-day
sleepdiaryandaccelerometry.
Condition
Bedtime(±min)
Wakingtime(±min)
TST(hours(±min)
Control
23:05±125
08:21±139
8.70±0.40
Mild
23:44±132
08:11±146
8.66±0.59
Moderate
23:08±141
08:09±132
8.64±0.76
Note:Dataarecompiledfrombothmeasures,asrecordedfrom7ofthe9participantsdueto
pooradherencetoreportinginthediaryandwearingtheaccelerometer.Wherebothmeasures
wereobtainedconcurrently,thedataappearedtobecomparable(nottestedformally).
Table4.2:Subjectivesleepinessandhydrationintestingsessions
Pre
Manipulated
Post
Control
6.8±1.1
7.2±1.1
8.3±0.7
Mild
6.4±2.1
6.2±1.5
8.6±0.7
Moderate
7.3±1.2
6.6±1.7
8.3±0.8
1.019±0.002
1.026±0.004
SubjectiveSleepiness
USG
Note:“Manipulated”referstothefirstmeasuresfollowinginitial10minmanipulationperiod.
SleepinessdataarefromtheKarolinskasleepinessscale(KSS),whichhasarangefrom1–
“extremelyalert”to9–“Verysleepy,greatefforttostayawake,fightingsleep”.USGisurine
specificgravity.DataarethemeansandSDforn=9.
80
IntheControlcondition,P1sufferedavasovagalepisodefollowingthefinalPVT.The
participant’sdataforthisconditionareretainedbecausetheyotherwiseshowedno
atypicalresponsesinanydependentvariableuptothispoint(i.e.,forTC,heartrate,
perceptions,PVTorEEG).
4.2
InducedTemperatures
Theambienttemperatureintheenvironmentalchamberwasequivalentbetween
conditions;averaging24.4±1.1OC.RelativeHumiditywassetat33%(Setpointratio
8.1).Bothambientandwatertemperatureforeachofthethreeconditionsare
representedinTable4.3.Temperaturedidnotdeviatesignificantlyacrosstheevening.
Foottemperaturesatbaselinewere35.1±0.3OC.Participant8displayedaTCrhythm
(showninAppendixL)contrarytoallotherparticipantsandtheexpectedpatternfor
thistimeofday(seeFigure2.4Circadiantemperaturerhythm).ThisunusualTCrhythm
wasthoughttonotbecausedbyerrorsinexperimentaldesign(i.e.,timingofmenstrual
cycle)ortechnicalproblems(e.g.,moistureaccumulatingintheelectricaljunction).Her
temperaturedatahavebeenomittedfromthemean,butherotherresultsretained
becauseherresponsedataforalldependentmeasureswerecheckedagainstthoseof
theremainingparticipantsandwerenotoutliers.
81
Table4.3:Ambientandwatertemperaturesofassociatedconditions.
Condition
Tamb(OC)
Twater(OC)
Baseline
Manip(i)
Manip(f)
Control
24.46±0.24
19.92±0.21
18.87±0.07
22.70±0.01
Mild
24.57±0.17
20.46±0.28
13.52±0.28
22.00±0.15
Moderate
24.16±0.30
20.29±0.24
3.21±0.31
16.37±0.32
Note:Manip(i)referstotheperiodimmediatelyfollowing10minreductionoffoottemperature
toassignedcondition,whileManip(f)referstotheendofthemanipulationandtestperiod.
4.2.1
Temperaturemanipulation
Foottemperature(Figure4.1)wasmanipulatedbycontrollingurntemperatures
(Table4.3),withwaterflowthroughthebootiesturnedonfollowingbaseline
recordings.Coolingprotocol(watertemperature)variedbetweenparticipants
dependingontheirfoottemperaturesusceptibilitytothemanipulation.
4.2.2
FootTemperatures(Figures4.1a,4.2and4.3)
Foottemperaturedeclinedtoadifferentextentbetweenconditions(interaction
effect:F(40,280)=39.58,P<0.0001)(Figure4.1).Contrastsrevealedthatdifferencesfrom
baselineweresignificantbythe~30thminuteforthemildcondition(F(1,7)=32.90,
P=0.001),andbythe20thminutefortheModeratecondition.Therateofskincooling
acrossminute20throughtominute40wasapproximatelydoubledbetweenMildand
Moderatecooling(Figure4.1a:slope=-0.14OC/minverses,-0.26OC/min).Foot
temperaturewasthereaftermaintainedat30.8±0.2OC,and26.4±0.1OC,forMildand
Moderatecoolingconditions,andat34.5±0.5OCintheun-manipulatedControl
condition(Figure4.1a).LargervariabilityevidentinControlisduetolowerfoot
temperaturesinsomeparticipants(P6:32.19±1.00OC;P8:29.27±1.26OC).
82
Foottemperaturedifferedsignificantlybetweenthermistorlocationandcondition
(Interaction:F(6,42)=13.79,P<0.0001)(Figure4.2).Temperaturesonthefootbecameas
muchas5.4±0.6OC(Moderate)belowthoseofthetoe(Figure4.3).Temperaturesdid
notdiffersignificantlybetweendifferenttoes(difference:0.05OC,P=1.00),orbetween
differentlocationsonthefootitself(difference:0.17OC,P=1.00).
4.2.3
Upperlimb
Upperlimbtemperaturesremainedintherange34-35OCforallconditions.Although
ANOVAshowedacleardifferenceinresponsebetweenconditions(Interaction:
F(40,280)=2.064,P<0.0001;Figures4.1b,and4.5a),contrastsdidnotrevealthesourceof
thesedifferences.
4.2.4
Coretemperature
BaselineTC’swere36.94OC(±0.22),36.91OC(±0.32),and36.91OC(±0.30)for
Control,MildandModerate,respectively.TCdeclinedacrosstheevening,displayingno
differentialtrends(Figure4.1c).TherateofTCdeclinewasonaverage-0.002±0.00015
OC/minacrossallconditions,suchthatfinalTCwasapproximately36.5±0.1OC.There
wasnointeractioneffectonTC(F(40,280)=0.768,P=0.843).TCdidnotdiffersignificantly
betweenconditions(F(2,14)=0.188,P=0.831),howeveritdecreasedacrossthetest(F(20,
140)=27.77,P<0.0001).
83
40
a
Ŧ
Foot temperature (OC)
35
^
30
***
25
Control
Mild
Arm temperature (OC)
36
****
Moderate
20
0
50
100
150
200
b
35
Ŧ
34
33
32
0
50
100
150
200
Core temperature (OC)
37.2
c
37.0
36.8
36.6
36.4
****
36.2
0
50
100
150
Time (min)
200
Figure4.1:Averagefoot(a),averageupperlimb(b)andcore(c)temperaturesacross
thethreeconditions;Control(n),Mildcooling(Δ)andModeratecooling(¢).Timeis
measuredinblocksof10minutes.DataaremeanandSDforeightparticipants.
*=P<0.05,***=P<0.001****=P<0.0001,Ŧ=SignificantinteractionforbothLLandUL.
^-Increasedvariabilityobservedatthe150thminuteinMildisduetoP4foottemperatures
risingacross20-minutestothephysiologically“normal”eveningtemperature.Thisexperimental
errorwasquicklyremediatedfollowingthe150thminute.
84
Temperature (OC)
35
30
*
25
****
Foot Arch
Toe Top
Toe Pad
Ŧ
Foot 1MT
20
Control
Mild
Moderate
Thermode location
Figure4.2:Localisedfoottemperatureparameterscomprisingaveragefoottemperature
acrossconditions:Control;Mildcooling;andModeratecooling.DataaremeanandSD
foreightparticipants.
Note:Thermistorlocationsare:TP=toepad,TT=toetop,FA=footarch,FM=1sttarsometatarsal
joint.
*=P<0.05,***=P<0.001****=P<0.0001,Ŧ=Significantinteraction
Ŧ
Temperature (OC)
35
30
toe pad
toe top
foot arch
foot 1MT
25
20
10
100
Control
****
*
200 10
100
Mild
Time (min)
200
10
100
Moderate
200
Figure4.3:Temperatureacrosstimeandconditionsoffourindividualfootthermistors
comprisingaveragefoottemperature.DataaremeanandSDforeightparticipants.
*=P<0.05,****=P<0.0001,Ŧ=Significantinteraction
85
4.2.5
TemperatureGradients
Thedistal-proximalgradient(DPG)forthelower-limbwasmeasuredbetweenthe
manipulateddistalsite(fourthermistorscomprisingaveragefoot,aswellascalf),minus
proximalsites(thigh,chest,andforehead;Figure4.4a).TheupperlimbDPGwas
calculatedasfinger,handandforearmminusaforementionedproximalsites.Baseline
DPGwasslightlypositive,0.71±0.44and0.32±0.07forthelowerandupperlimbs
respectively.Thelowerlimbgradientalteredinaccordancewithfootcooling,whereas
theupperlimbgradientremainedunchangedthroughoutthetrial(Figure4.4a).
Specifically,theupperlimbDPGshowednosignificanttimeeffect(F(20,80)=1.65,
P=0.062),oraninteractioneffect(F(40,160)=0.95,P=0.566),butasignificantcondition
effect(F(2,8)=7.30,P=0.016).ThelowerlimbDPGshowedaninteractionbetween
conditionandtime(F(40,280)=46.53,P<0.0001),reflectingtheMildgradientbecoming
significantlylargerthaninControlbythe30thminute(F(1,7)=104.61,P<0.0001),after
whichitstabilisedat4.05OClarger(C.I.:2.65,5.45),andlargerinModeratethanControl
bythe20thminute,afterwhichitstabilisedat8.6OC(CI=7.32,9.81).
Theproximalskin-to-coregradient(PCG)differedsignificantlyasafunctionof
conditionandtime(F(40,280)=1.67,P=0.010)(Figure,4.4b).Despiteapparentdifferences
invariabilityillustratedinFigure4.4b,sphericitywasnotviolated(χ2(2)=0.284,
P=0.883).ContrastsrevealedthattherewasnosignificanteffectwithinMildcondition,
butthatModeratedifferedsignificantlyfromControlbythe30thminute(F(1,7)=7.67,
P=0.028).ThePCGwasalwaysnegative(Control:-2.90±0.07,Mild:-2.6.10±0.11,
Moderate:-2.49±0.12),butModerateconditionwasslightlylessso.Thedifferencefrom
Controlwas-0.20(C.I.:-0.53,0.13,P=0.287)forModerate,whereasMildwas-0.08(C.I.:
-0.46,0.30,P=1.000).
86
a
5
DPG (OC)
0
-5
***
Upper Limb
Lower Limb
-10
-2.0
10
Control
21010
Time (min)
Mild
21010
****
Moderate
b
210
PCG (OC)
-2.5
-3.0
Ŧ
-3.5
Figure4.4:(a)Upper(¢)andLowerlimb(n)distalproximalgradients(DPG)acrossthe
threeconditions:Control;Mildcooling;andModeratecooling.(b)Proximaltocore
gradients(PCG)acrossthethreeconditions.DataaremeanandSDforeightparticipants.
Note:Eachdatapointrepresentsaten-minuteaverage.
***=P<0.001****=P<0.0001,Ŧ=SignificantinteractionforPCG
Difference (OC)
1
0
Control-Mild
-1
Control-Moderate
Figure4.5:DifferenceinMildandModerateupperlimbgradientsfromControl.
Note:ApositivedifferencereflectsamorenegativeDPG.Eachdatapointrepresentsa
ten-minuteaverageasmeanandSDforeightparticipants.
87
4.2.6
TemperaturePerception
Participants’thermalsensationshowedasignificantinteractionbetweencondition
andtime(F(22,154)=2.52,P=0.001).Participantsbeganthetestwithathermalsensationof
“warm”(9.1±0.0),withanassociatedthermaldiscomfortof“slightlyuncomfortable”
(1.9±0.2)(Figure4.6).Followingmanipulation,thermalsensationunderwentaninitial
decreaseinallconditions.ItdecreasedbelowControlforbothMildandModerate
(F(1,7)=25.74,P=0.01;F(1,7)=21.13,P=0.002)withsensationsof“slightlycool”(6.5±0.9)
and“cool”(5.5±1.3),respectively,bymin30andremainedlowerthaninControl
thereafter(P<0.05).TheinitialsensationofcoolinginMildandModeratebecame
sensationsofneutrality(7.6±0.4;7.1±0.4),representingadifferenceof1.2scores(C.I.:
-0.3,2.8,P=0.107),and1.7scores(C.I.:0.1,3.3,P=0.039),respectively(Pairwise
comparison).
Thermaldiscomfortwasnotdifferentiallyalteredbythefootcoolinginterventions
(Interactioneffect:F(22,154)=1.04,P=0.425;Figure4.6).Therewasalsonomaineffectof
condition(F(2,14)=1.63,P=0.242)ortime(F(11,77)=1.55,P=0.133)onthermaldiscomfort.
ParticipantsrankedControlasmostuncomfortablywarm.
88
Thermal Sensation
10
8
Ŧ
6
Thermal discomfort
4
4
Control
Mild
Moderate
3
2
200
150
50
0
100
1
Time (min)
Figure4.6:Whole-bodythermalsensationandthermaldiscomfortacrossthetest
durationforeachcondition:Control,MildandModerate.DataaremeanandSDfornine
participants.
Note:Thegreyareaindicatesthemanipulationperiod.Thermalsensationrangesfrom1-
“unbearablycold”to13-“unbearablyhot”.Thermaldiscomfortrangesfrom1-“comfortable”to
5-“extremelyuncomfortable”.
Ŧ=Significantinteractionforthermalsensation
89
4.3
Subjectivesleepiness
Subjectivesleepinessrosesteadilyduringtestingirrespectiveofcondition(Figure
4.7).Thesubjectivesleepinessscore(KSS)waspronetoaceilingeffect,withanumber
ofparticipantsreachingmaximumearlyinthetest(Figure4.8).Forexample,one
participant(P9,mildcondition)reachedmaximumsleepinessbybaselinemeasures,
progressingfromKSSscoresof5onentryto9.Adjustingforthosethatreachedceiling
earlyproducednochangetotheprogressionofsleepiness.
Progressionofsubjectivesleepinesswassignificantlyaffectedbydurationoftesting
(F(13,104)=28.91,P<0.0001),anddespiteatrendforthistointeractwithcondition,itwas
notstatisticallysignificant(F(26,208)=1.45,P=0.080).Thetrendforaninteractionis
presumablyduetoapparentearlyreductioninKSSscoreswithinthetwointervention
conditions(Figure4.7).Participantsenteredthelabat21:00feeling“ratheralert”(4.7±
0.4);KSSthenrose2(±0.6)scoresbybaseline.
90
9
8
7
KSS
****
6
control
mild
5
0200
2100
4
2230
moderate
Duration (hh mm)
Figure4.7:Progressionofsubjectivesleepinessacrosstestingforeachcondition:
Control,Mild,andModerate.
Note:Theslashedlineindicatesequipmentsetup.Thegreyareaindicatesonsetofmanipulation.
2100isentrytolab,while2230isbaselinemeasures.0200iscessationofthetest.KSSranges
from1to9.DataaremeanandSDfornineparticipants.
****=P<0.0001effectoftime
Control
Mild
Moderate
6
4
2
0
30
2
29
2
28
9
25
9
24
6
22
6
21
3
19
3
18
0
14
0
13
0
12
90
0
0
Number of participants
8
Time (min)
Figure4.8:Numberofparticipantsreachingmaximalsubjectivesleepinessrating(9–
“verysleepy,greaterefforttokeepawake,fightingsleep”)duringtesting,ineach
condition:Control,Mild,andModerate.Thenumbersdonotnecessarilyreflectthesame
participantsremainingatmaximalratingacrosstime.Dataaremeanforeight
participants.
91
9
7
control
6
mild
PVT1
PVT3
PVT2
PVT4
Post
Pre
Post
Pre
Post
Pre
Post
Pre
5
Post
moderate
Pre
KSS
8
PVT5
PVT number
Figure4.9:ChangeinsubjectivesleepinessscorepreandpostPVTacrossthenightfor
eachcondition.DataaremeanandSDforeightparticipants.
Note:TheKSSrangesfrom1–“extremelyalert”to9–“Verysleepy,greatefforttostayawake,
fightingsleep”.
4.4
Vigilance
Eight(ofthenine)participantswereincludedinthePVTanalysis;P7was,omitted
duetomissingbaselinerecordings,whileamissingbaselineinControlforP1andP5
wereestimatedastheaverageoftheirothertwobaselinerecordings.Therewasno
ordereffectonPVT(F(2,14)=1.97,P=0.177).
4.4.1
Reciprocalreactiontime
Reactiontimeswereconvertedtoreciprocalreactiontime(RRT).TheRRTdidnot
responddifferentlybetweenconditionsacrossthesession(F(90,630)=0.98,P=0.448)
(Figure4.10);nordiditshowmain-effectdifferencesbetweenconditioneffects
(Interaction:conditionandtest;F(10,70)=0.75,P=0.550;Interaction:conditionandtime;
92
F(18,126)=1.07,P=0.391).WhileRRTdeterioratedduringeachtest(maineffect)this
deteriorationbecamemorepronouncedwithprogressionacrosstheevening
(interactionoftestandtime:F(45,315)=1.88,P<0.0001).Groupingofthedifferent
conditionsremainedtightwithminimaldifference(grandmean:3.54±0.12).
ReciprocalreactiontimesignificantlydecreasedacrossthesuccessionofPVTs
(F(9,63)=11.95,P<0.0001).Theslopeofdecreaseacrossthedurationofatestwas
greatestinthebaselinewithmeandeclineof-0.60±0.005RRT/min.Followingwithin
testslopeswerenolessthan-0.036RRT/min.Mildconditiontypicallyhadthegreatest
rateofdeclineoncemanipulationhadbegun,withControlconditionhavingthesmallest
slope.
4.4.2
Variability
AllconditionsproducedhighvariabilityinRRT(Figure4.10a/b).Variabilitywas
greatestinControl(Figure4.10b);however,despitethisapparentdifference,therewas
nointeractioneffect(F(10,70)=0.72,P=0.703)orcondition(F(2,14)=1.16,P=0.342)on
variability.VariabilityofRRTfluctuatedgreatlyminute-to-minuteaswell;again,this
fluctuationwasmostapparentintheControlcondition.
4.4.3
Lapses
Lapseswereclassedasreactiontimes>500ms.Figure4.11indicatesthecollated
numberoflapsesthatoccurredinconsecutivetestsundergoingeachconditionof
manipulation.Themeannumberoflapseswas8(±2)pertest.Therewasnointeraction
effect(F(10,80)=1.30,P=0.299),noranyconditioneffect(F(2,16)=0.812,P=0.462),ortest
effects(F(5,40)=0.93,P=0.388).
Anumberoflapsesmyhavebeenduetoactualsleeponset.Thisisindicatedby
consecutivelapsesproducinglargespikesinnumbersoflapses.Forexample,P6
93
producing46lapsesintheirControlbaseline(KSSrating:8–“sleepy,someefforttostay
awake”).ThesespikesinlapsestypicallyoccurredlateinthePVT(i.e.,8-9thmin)and
hadaskewingeffectonthemean.
a
5.0
Control
Mild
Moderate
RRT (1000/RT)
4.5
4.0
3.5
3.0
2.5
Ŧ
0.8
b
0.4
PVT5
PVT4
PVT3
PVT1
0.0
PVT2
0.2
Baseline
Variance
0.6
PVT
Figure4.10:PVTreciprocalreactiontimes(a)andvariance(SD)(b)acrosssixPVTs
betweenconditions:Control(n),Mild(Δ),andModerate(¢).DataaremeanandSDfor
eightparticipants.
Note:EachPVTcontainsten1minaveragesofthereciprocalreactiontimes
Ŧ=SignificantinteractionbetweentestandtimeforRRT
94
4.4.4
CoretemperatureandVigilance
ThecorrelationbetweencoretemperatureandRRTisdisplayedinFigure4.12.RRTs
weresimilaratbaselinewithamaximumdifferencelessthanone(unit:1000/RT).
Similarly,therewasminimaldifferencebetweencoretemperatures(TCdifference<0.1
OC).
Therewasnointeractioneffect(F(10,70)=0.51,P=0.875),andnomaineffectsof
condition(F(2,14)=0.02,P=0.978)orPVT(F(5,35)=2.87,P=0.92).Manipulationproducedan
initial,insignificantriseinreactiontimeinMild.Moderateconditionhadthegreatest
slopeinRRT(-0.19),withControlfollowing(-0.12),andMildhavingthesmallestslope
(-0.1).ChangeinPVTcorrelatedwellwithchangeinTC,with-0.85,-0.81,-0.85,Control,
MildandModerateconditions,respectively.
4.4.5
CoretemperatureandSleepiness
TherelationbetweenTCandsubjectivesleepiness(KSS)isdisplayedinFigure4.13.
Therewasasignificantinteractioneffectbetweenconditionandtime(F(24,192)=1.59,
P=0.046).Thisinteractioneffectisapparentinthedynamicresponsetocooling
conditions.Mildsubjectivesleepinessdecreasedby0.2(unit:KSSscores;range1-9)
andshowedanimmediatesignificantdifferencefrombaseline,contrastedwithControl
(F(1,8)=8.00,P=0.022).Moderatedecreasedinitiallyby0.8butbecamesignificantly
differentfrombaseline,incontrasttoControl,at~20min(Figure4.13,point3:
F(1,8)=7.10,P=0.029);ControlKSSrosecontinuallyacrossthetest.Theinitialdipin
subjectivesleepinesswas0.2and0.8scoresinMildandModerate,respectively.Change
insleepinesscorrelatedwellwithchangeinTCwith0.90,0.96,ad0.85,forControl,Mild,
andModerateconditions,respectively.
95
60
15
40
10
20
5
0
Control
Mild
Moderate
Mean PVT Lapses
PVT Lapses
0
PVT Number
Figure4.11:PVTlapses(RT>500ms)acrosscumulativewaking.DataaremeanandSD
foreightparticipants.
Note:P6Controlbaselineof41lapseswasomitted.
Percent change in RRT (%RRT)
5
Temperature change (OC)
0
0.1
0.2
0.3
-5
control
mild
-10
moderate
Figure4.12:Relationofchangeincorebodytemperatureandpercentagechangein
ReciprocalReactionTime.EachRRTpointrepresentsa10-minPVT.Dataaremeanfor
sevenparticipants.SDomittedduetolossofclarityoftrend.
Note:greyindicatesmanipulatedperiod
96
Change in subjective sleepiness
3
2
1
0
0.0
-0.2
*
-1
*
*
*
Change in Tc
Ŧ
-2
-0.4
Control
Mild
Moderate
Figure4.13:Thecorrelationbetweenchangeinandchangeinsubjectivesleepiness
(KSS;range:1-9).Dataaremeanfornineparticipants,SDomittedfromfiguredueto
misrepresentationofwithinparticipantvariability.
Note:greyindicatesmanipulatedperiod
*=P<0.05,Ŧ=Significantinteraction
4.5
Cognitivearousal
Issuesinelectrodeconductancegeneratederrorsinoutputpowers;withthetapower
themostvulnerabletonoise.SixparticipantswereincludedinC4-A1(referential
electrodeplacement)derivationpowers,andeightparticipantswereincludedinO2-A1.
Powerfrequencieswerewithintheirnormativeranges.Oftheremainder,Coefficientof
Variationwastoohightointerpolatefigures.AnalysesforC4werebasedonfour
participants,andO2wasbaseduponsevenparticipants.
4.5.1
KarolinskaDrowsinessTest
SevenKDTs–includingbaseline-weretested,withepochsreducedtoasingleeyes
openpowerandasingleeyesclosedpower.ThesewerefurtheranalysedforbothC4
andO2derivations,toobservestableprogressionofspecificfrequenciesacrossthe
97
evening(Figures4.14and4.15).Additionally,comparisonofthechangespectralpower
fromeyes-opentoeyes-closedwasobservedforboththetaandalphafrequencies
(Figure4.16).
Thetaandalphapowersshowedthegreatestchangeintheeyesclosedcondition,
whilebetashowedthegreatestchangeacrosseyesopentests.Acrosstheeyesclosed
tests,thetapowerdecreased,andalphapowerincreasedinC4,whilethetapower
increasedandalphapowerdecreasedinO2.
4.5.2
C4-A1
Figures4.14and4.16:a/brepresentthesumofinteractionsbetweentesteyesopen
andeyesclosedattherightcentral(C4)electrodederivationforeachcondition.Theta
powerdisplayedasignificanteffectofinteraction(F(12,36)=2.20,P=0.034)duringeyesopen.Contrastsandcomparisonscouldnotidentifythesourceofdifference.Eyes-closed
thetapowershowednointeraction(F(12,36)=1.12,P=0.377),andnoeffectsofcondition
(F(2,6)=0.02,P=0.980)ortest(F(6,18)=0.99,P=0.463).
Alphapower,eyes-openshowednointeractionbetweenconditionandtest
(F(12,36)=1.49,P=0.174),orofeithercondition(F(2,6)=1.11,P=0.389)ortest(F(6,18)=0.80,
P=0.581).Similarly,alphaeyes-closedshowednoeffectsofinteraction(F(12,60)=1.09,
P=0.386),orofcondition(F(2,10)=0.73,P=0.506),althoughahighlysignificantdecrease
occurredacrosstesting(F(6,30)=5.652,P=0.001).
Betapowerindicatednointeractioneffects,foreyesopenandeyesclosedstates
(interaction:F(12,60)=0.65,P=0.794;F(12,60)=1.45,P=0.168),howeverdisplayeda
significanteyesopentrendacrosstests(F(6,30)=4.31,P=0.003)andindicatedatrend
duringeyes-closedacrosstests(F(6,30)=2.14,P=0.078).
98
Thechangeinthetapowerbetweeneyesopenandeyesclosedstatesdemonstrated
nointeraction(F(10,70)=0.72,P=0.703),noraneffectofcondition(F(2,14)=1.16,P=0.342)
ortest(F(5,35)=0.78,P=0.572).Therewasnointeractionoccurringinalpha(F(12,60)=0.76,
P=0.687)orbetafrequencieseither(F(12,48)=0.786,P=0.662).Althoughalphafrequency
indicatedaneffectacrosstests(F(6,30)=2.80,P=0.028).
4.5.3
O2-A1
Figure4.15and4.16:c/drepresentthesumofinteractionsbetweentesteyesopen
andeyesclosedattherightoccipital(O2)electrodederivationforeachcondition.Theta
powerdisplayedahighlysignificantdifferenceacrosstests(F(6,36)=10.84,P<0.0001),but
nointeractionineyesopen(F(12,72)=1.12P=0.340),whileeyesclosedshowednoeffect
(interaction:F(12,72)=0.407,P=0.957).Thedifferenceineyes-openthetapowerappears
tobeduetoasignificantincreaseinpowerbetweenbaselineandtheseventhKDT
(difference:-5.84,C.I.:-9.86,-1.82,P=0.003).Similarly,alphapowerdisplayedno
interactioneffectforeithereyesopen(F(12,72)=0.77,P=0.679)oreyes-closed
(F(12,72)=1.07,P=0.402).However,eyes-closedshowedasignificantreductioninalpha
powerasaneffectacrosstests(F(6,36)=5.91,P=0.0002).
Thechangeinthetapowerbetweeneyes-openandeyes-closedshowedsignificant
differencesinbothtests(F(6,42)=3.06,P=0.014)andcondition(F(2,14)=3.90,P=0.045),but
nointeractionbetweenthetwo(F(12,84)=1.05,P=0.416).Similarly,alphapowershoweda
significanteffectoftestsacrossthenight(F(6,30)=3.75,P=0.0067),withinitiallarge
increasesinalphapoweruponclosingeyes,mellowingbythethirdKDT.Noothertrend
wasapparent(interaction:F(12,60)=0.63,P=0.807).
99
Theta power (uV)
35
30
25
20
Ŧ
Alpha power (uV)
50
40
30
80
***
Eyes open
Beta power (uV)
Eyes close
70
60
50
40
*
1 2 3 4 5 6 7
Control
1 2 3 4 5 6 7
Mild
1 2 3 4 5 6 7
Moderate
KDT
Figure4.14:EEGspectralpowerchangesacrossKDTsandconditions,andbetweeneyesopen
andeyesclosed.Dataaremeanforfourparticipants.Standarddeviationomittedduetohigh
inter-individualvariabilityinherentinEEG.
Interactioneffect(Ŧ)ofthetaonlypresentineyesclosed,nootherinteractionspresent.
Timeeffect(***=P≤0.001,*=P<0.05)onlypresentineyesclosedalphaandbeta.
100
Theta power (uV)
16
14
12
****
10
Eyes open
Alpha power (uV)
8
50
Eyes close
40
***
30
20
10
1 2 3 4 5 6 7
Control
1 2 3 4 5 6 7
Mild
1 2 3 4 5 6 7
Moderate
KDT
Figure4.15:EEGspectralpowerchangesacrossKDTsandconditions,andbetweeneyes
openandeyesclosed.Dataaremeanforsixparticipants.Standarddeviationomitted
duetohighinter-individualvariabilityinherentinEEG.
Timeeffect(****=P<0.0001,***=P<0.001)presentinthetaeyesopenandalphaeyesclosed.
101
C4-A1
30
28
26
14
12
24
10
Control
Mild
Moderate
40
KDT6
KDT5
KDT4
KDT3
KDT2
KDT1
Baseline
KDT6
20
30
KDT5
25
KDT4
35
30
KDT3
40
35
KDT2
Alpha Power (uV)
45
KDT1
50
Baseline
22
Alpha Power (uV)
O2-A1
16
Theta Power (uV)
Theta Power (uV)
32
Figure4.16:ChangeinEEGspectralpowerfromeyesopentoeyesclosedacrossconditions.Theta
powerisrepresentedinthetopfiguresandalphainthelower.Originoffrequenciesstatedabove
respectivefiguresaschannelsC4andO2.Dataaremeanforeightparticipants.Standarddeviation
omittedduetohighinter-individualvariabilityinherentinEEG.
4.6
HeartRate
HeartratemeasuresarederivedfromECG,recordedacrossthenightoftesting.Further
analysesofindepthcardiographicchangeswerenotmadeduetotechnicaldifficultiesextracting
thedata.Heartratedeclinedsignificantlyacrossthedurationofthenightinallconditions(F(26,
208)=7.412,P<0.0001)(Figure4.15).Therewasnodifferencebetweenconditions(F(52,416)=0.92,
P=0.631).HeartratedeclinedinallbutControlPVT3andPVT5.Therewasnointeraction
betweenconditionandheartrateassociatedwithPVT(F(10,80))0.57,P=0.830).
102
100
Control
Mild
Moderate
Heart rate (beats/min)
****
90
80
70
60
50
50
100
Time (min)
150
200
Figure4.17:Heartratedecline(±SD)acrossthenightforeachcondition.DataaremeanandSD
fornineparticipants.
****=P<0.0001maineffectoftime
80
70
PVT5
PVT4
PVT3
baseline
60
PVT2
Control
Mild
Moderate
PVT1
HR (beats/min)
90
Figure4.18:HeartratechangepreandpostPVTperformanceforeachcondition.Dataaremean
fornineparticipants.
103
5.0 DISCUSSION
Severallinesofevidenceimplicatearolefordistaltemperatureineveningvigilancechanges;
recentresearchtendstohaveexploredeffectsandbenefitsoffacilitatingariseindistalskin
temperatureinpopulationsthatstrugglewithsleeponset(insomniacs(Raymannetal.,2007a),
theelderly(Raymannetal.,2007a),andpoorsleepers(Refinettietal.)),beitfromthesource
(Orexinsecretingcells,melatonindeficiencies)orfromeffectors(vasculature).Theeffectofboth
spontaneousandinducedrisesinskintemperatureonimpairingvigilanceandpromotingsleep
hasbeenthoroughlydemonstratedasbeneficial(Fronczeketal.,2008;Kräuchietal.,1999;
Raymannetal.,2005;Romeijnetal.,2012b;VanSomeren,2006).Theinherentroleofcold
extremitiesinacutelypreventingsleeponset–whileseeminglyobviousandintuitive–appearsto
havebeenignoredinallbutthreestudies:oneexploringsubtletemperaturemanipulationsin
narcoleptics(Fronczeketal.,2008);anotherobservingapparenttrendsofthermaldiscomfortdue
tocoldextremitiesleadingtodifficultyinitiatingsleep(Kräuchietal.,2008);andathirdapplying
coolairdirectedatthefaceasanin-carcountermeasuretofatigue(Reyneretal.,1998).
Thepurposeofthecurrentstudywastosimilarlyfocusnotonbodytemperature
manipulationsfacilitatingsleep,butthosethatacutelyinhibitsleep.Therefore,theeffectofdistal
temperaturemanipulation(specificallycooling)onvigilancemarkerswasexamined,innine
healthyvolunteers,acrossthedurationofnaturalsleeponsettime.ThehypothesiswasthatMild
andModeratecoolingwouldincrementallyattenuatethedeclineincoretemperatureand
improvevigilanceparameters,orthatvigilancewouldbeimprovedbytheskincoolinginitself.
Themainfindingwasthat,inapparentlyhealthyindividuals,TCandvigilance–measuredas
sustainedattention(PVT)andcognitivearousal(KDT)-declinedirrespectiveofsignificant
reductionsindistalskintemperature.Therefore,incontrasttosignificanteffectsonvigilanceand
sleeponsetlatenciesduetosubtledistaltemperaturemanipulationsobservedinclinical
populations(insomniacsandnarcoleptics),thecurrenthealthyparticipantsbufferedeven
Moderatedistalcooling(to~25OC)withrobustcircadiandrivesprogressingtowardsleep.
104
5.1
Temperatureandvigilance
5.1.1
Temperatureeffects
Thefeetwerecooledsuccessfully,to30.8OCand26.5OCdegreesinMildandModerate,
respectively,andmaintainedat34.5OCinControl(Figure4.1a).However,TCremainedunaffected
bycondition,decliningfrom36.9OCto~36.5OC.ThisdeclineinTCwashighlycorrelatedwiththe
declineinsustainedattention(Figure4.12;correlation>0.80acrossconditions)andsubjective
sleepiness(KSSCorrelation>0.80acrossconditions),butnotcognitivearousal(EEGcorrelations
<0.50).ThecircadiandeclineofTCthereforeappearstobecapableofbufferingmoderate
localisedthermalcooling(oftheperipheryanyway).Increasedvasomotortoneinthelowerlimbs
perhapsincreasedtocompletelyoffsetthelocalheatextraction,suchthattheTCprofilewas
unaffected.
Thefunctionalthermalinterdependencebetweenthecoreanddistalskiniswellknownand
understood.TheTCismodulatedbythermalandnon-thermalinputfromtheSCNtothe
thermoregulatorycentreofthePOAH(Mooreetal.,2002),suchthatnon-thermalfactorsalterthe
interthresholdzonebywhichthermoefferentresponsesaremodulated(Mekjavicetal.,2006)
(See2.2.1Homeostasis).Heatlossbecomesdominantintheevening,raisingdistalskin
temperaturethroughcentrally-mediateddilationofAVAs,asshownbyKräuchietal(2000).The
temperatureofdistalskinfollowsaninversepatterntothatofthecore,whileproximalskin
oscillatesinunisonwiththecore.Inthecurrentstudy,consistentwithKräuchietal’s(2000)
findings,theControlconditionfollowedthedescribedtrend,withnon-thermalcutaneousdilation
alreadydrivingheatlossfromthecore(distaltemperatures:~34OC).
TheDPGreflectstheunderlyingrelationbetweentheskinandcore,andbetweenheatlossand
heatgainpathwaysinthermoregulation.Typically,heatgainpathwaysdominateacrosstheday,
whileheatlosspathwaysdominateacrossthenight(Seesection2.3.5Circadiantemperature
rhythm).TheeveningheatlossminimisestheDPGastheextremitiesoffloadheatradiantlyand
105
convectivelyaidedbydilationofAVAsinthevolarsurfacesofthehandsandfeet(Kräuchietal.,
1999).However,asmallDPGismoredifficulttoattainincoolercircumstances(Werneretal.,
1980),asindicatedinthecontextofsleepinesswithinthisstudy(Figure4.4:MildandModerate),
andinferredbyKräuchietal(2008).Asthefeet(andhands)providehighlocalthermal
perceptualsensationbutminimalautonomicdrive(Cotteretal.,2005;Simmonsetal.,2008),
individualsaremadeawareofcoolingbutdonotinvokeautonomicresponses.WithinMildand
especiallyinModerate,distalskintemperaturereductionproducedobservablevasoconstriction
indicatedbyreductionsinDPGandincreasesinPCG,asimpliedbyothers(Fronczeketal.,2006b;
Kräuchietal.,1999;Raymannetal.,2005;Romeijnetal.,2012b;VanSomeren,2006).The
decreaseinfoottemperatureenlargedtheassociatedDPGsto-4OCand-9OC,inMildand
Moderate(Figure4.4a),incontrasttoapositiveDPGof0.8OCintheControlcondition.
Localskintemperaturemanipulationhasbeenpreviouslydemonstratedtoalterlocalblood
flow(Fagrelletal.,1977).Localfactorssensitisethevesselstoefferentconstrictoractivity,
increasingtheDPG.Caldwelletal(2014)demonstratedthatthefeetarereactivetocoolingonly
whenthewhole-bodyisinaheatlossstate(hyperthermiaTC≈39OC).Thecontributionoflocal
factorsisunclearinthecurrentstudybecauseparticipantswereclearlylessheatstressedthanin
Caldwelletal’s(2014)study,butwereinaheat-lossphaseoftheircircadianrhythm.AstheTC
declinecontinuedregardlessofcondition,thecoolingmayhavesimplyfacilitatedheatloss.
Vasoconstrictionhasbeenassumedratherthanmeasuredinthecurrentproject,andisfurther
assumedtobemediatedbylocaleffectsbecausenoincreaseinDPGwasevidentintheupperlimb
(Figure4.4;Tsk~34OC,DPG:0.7±0.1).However,itcannotnecessarilybeassumedthatan
autonomically-mediatedvasoconstrictioninthefeetwouldbeevidencedbyasimilarprofilein
theupperlimb,becausepreviousstudieshaveshownthatthesegradientscandemonstrate
opposingeffectsinsleepdeprivedsubjects(Romeijnetal.,2012b).Inastudyoftheeffectofsleep
deprivationonthevascularprofile,Romeijnetal(2012b)identifieddisassociatedupperand
lowerlimbtemperaturegradients.Theupper-limbheatlossprofilewasattenuatedfollowing
106
sleepdeprivationwhereasthelower-limbheatlossgradientwasenhanced.Thecurrentfindings
contrastwiththoseofRomeijnetal(2012b).WhileRomeijnetal’s(2012b)reasoningmayapply
tothecurrentstudy,itisequallylikelythatanyconstrictionwasreactivetocooling.Lowerlimb
coolingcouldonlyreasonablyaffectupperlimbtemperaturesifother,moreautonomically-active
areasinstigatedacentralthermoregulatoryresponse.Assuch,itisunsurprisingthatthefeetdid
notinduceachangeespeciallyinMildbecausetheyhavebeenpreviouslybeenestablishedto
havelowthermosensitivityforautonomic(sweating)responses(Cotteretal.,2005).
Insummary,theinferredlocalvasoconstrictionofthefeetdidnotaltertheheatlossprofileof
thecore.Energetically,heatextractionmayhavefurtherfacilitatedtheobserveddeclineinTC,ina
reciprocalmannertogeneratedlocalconstriction(Figure4.1c).However,asTCdeclined
regardlessofcondition,manipulationsappearedineffectiveininstitutingageneralised
thermoregulatoryresponse.
5.1.2
Vigilanceandarousal
AsTCremainedunaffectedbydistalcooling,itisunsurprisingthatvigilancealsotherefore
remainedunaffected,atleastbasedontherationalediscussedinSection2.4.Thecurrentstudy
maythereforeprovidesupportfortheassociationofvigilancewithTC(unlesslocalperceptual
effectsareimportantbutweretoosmalltohaveshownupdespitecoolingto~25OC).The
relationshipbetweenbodytemperatureandvigilance/arousalstateis,however,complexwiththe
extremitiesundoubtedlyplayingalargerole.Theextremitiesmayprovideameansbywhichcore
bodycanloseheat(viaDPG)(Kräuchietal.,1999),ormaybeimportantasanindependentfactor
alteringvigilance/arousal(VanSomeren2006;Raymann2005,2007).Thecurrentstudydoesnot
supportorrefuteeitherposition.Despitemoderatelocalisedcooling,vigilancedemonstratedno
overalleffect.ThismaybepredicatedbytheaforementionedTCchange,ormayindicatethelack
ofstimulusatthefeettodriveaperceptualdistractioneffect.
107
Evidenceofthecausalroleofdistalskintemperatureonsleepinessintheeveninghasbeen
demonstrated(discussedin2.3.5Circadiantemperaturerhythm).Perhapsmostrelevanttothis
study,coolingthehandsandfeetdelayedsleeponsetlatenciesby~24%innarcoleptics,although
thiseffectwastestedwithinasinglePVTcomparisononly,duringthedaytime(Fronczeketal.,
2008).Thealteredtemperatureregulationinnarcolepticsiscomparativetohealthyindividualsin
theeveningandisconsideredtoincreasetheirsleeppropensity(Fronczeketal.,2006b).The
currentstudydidnotgeneratesignificantreactiontime,orlatencychangesbetweenconditions;
however,limitingmanipulationstothefeetonlymayhavebeenthecontributingfactor.Greater
spatialmanipulationproducesgreaterassociatedthermoafferentdrive(Crawshawetal.,1975).
Includingthehandsmayhavegeneratedsufficientcoolingtoimpairthecircadianheatloss
characteristics.WheredistalTSkmanipulationshavebeenusedtoalterthearousalstate–beitfor
vigilanceorsleepinduction–subtlemanipulationshaveproveneffectiveinsusceptible
populations(e.g.,narcoleptics,insomniacs),however,moderatemanipulationshaveproved
distracting.Thedistractioneffectmustnotbeoverlooked,ifitmaintainsarousal.Whilea
potentialdetrimentincomplextasks,distractionispotentiallybeneficialtomaintainwakefulness
ifinsimplevigilancetasks.Thedistractioneffectmayfurthermorebebeneficialinhealthy
populations,asraisingvigilancethroughthermalmodulationofthecircadianrhythmappears
difficult.InhibitingtheheatlossprofileofTCappearstoberelativelydifficult,andevenmoderate
coolingdoesnotappeartoattenuateTC.
Overall,distalcoolinginthepresentstudyresultedinonlytransientchangesinsleepiness
(discussedin5.2Transienteffects).Whilereactiontimesupportedthedecayinsustained
attention,thiswasnotreinforcedbyresponsevariabilityorlapses,whichbothremainedequally
highacrossthenight.Sleepinessrosesteadilyacrosstheevening,asindicatedbysubjective
sleepiness(Figure4.7)andEEGparameters.Subjectivesleepinesssaturatedinthemajorityof
participants(Figure4.8).EEGdidnotsupportanyinitialmanipulationeffectasobservedin
subjectivesleepiness,howevertheassociationbetweensubjectivesleepinessorperformanceis
108
lessapparentwhensleepinessvarieswithinnormallimits(from“alert”tosome“signsof
sleepiness”)(Akerstedtetal.,1990).Asanytransienteffectoccurredwithinnormalrangesof
subjectivesleepiness,itisunsurprisingthatsuchamodestresponsewasnotobservedwithin
EEG.
Cognitivearousal(indicatedbythetaandalphafrequencies)declinedacrossthetrial,
irrespectiveofcondition,forallmarkersexceptC4andO2theta(whichshowedacondition*time
interaction:P<0.05andP<0.0001,respectively).Thesemarkersshowedlargerincreasesintheta
powerinModerate.Thetapoweriswidelyacknowledgedtoindicatedecreasingalertnessand
impairedinformationprocessing(Pizzagalli,2007;Caldwelletal.,2003;LalandCraig,2001;
Klimesch,1999),indicatingthatparticipantsbecamemorefatiguedbytheModeratecondition.
ThismaybesupportedbyatrendforPVTtodeclinemorestronglyinModerate:7%worseby
PVT4,albeitthiseffectwasunclear(P=0.92).
Alphapowerdidnotindicateanytrendsofincreasingdrowsinesswithineyesopen;however,
sleepinessprogressedwitheyesclosed(Figure4.15).Duringrelaxedwakefulnessalphapower
synchronisesuponeyeclosure(Klimesch,1999);thisisalsotrueforearlyonsetdrowsiness
(Figure4.16)(Santamaria&Chiappa,1987;Gilberg&Akerstedt,1982).Alphasynchronisation
earlyinthesessionwasindicativeofearlydrowsiness,howeverthepowerofsubsequenteyesclosedalphapowersdeclinedrapidly.Typically,alphapowerfailstosynchroniseandeyes-closed
alphapowerreducesasdrowsinessprogresses(Pizzagalli,2007;Santamariaetal.,1987).Alpha
powerreductionsalsooccuralongwithfrequencyslowing(Pizzagalli,2007);thismayhave
causedsomeofthelaterincreasesinthetapowerinthepresentstudy.Similartotheobservations
ofAkerstedtetal(1990)andfurthersupportedbyLaletal(2002),itislikelythattheparticipants
wererapidlyfallingasleepduringeyesclosedbymidtest,andnotpresentingthetypicalalpha
increase;evidencedbyrapiddeclinesinalphapoweruponeyeclosurelaterinthesession(such
asFigure4.16:KDT4).GilllbergandAkerstedt(1990)suggestedthatalphapowermighthave
beensorapidlyreplacedbythetathattheir1minresolutionwouldhavefailedtodisplaythe
109
change;thismayhavealsobeenthecaseinthecurrentstudy.Participantsprogressedfrominitial
relaxed(early)drowsiness,intomiddle,andmaybelatedrowsinesstosleeponset,bymidsession.
Followingthisinitialdip,participantsmayhaveundergoneareboundindrowsiness,asindicated
byC4alphapowers.Theassociatedincreaseddrowsinesssupportsthechangesinsubjective
sleepinessandperformancemeasuresacrossthenight.
Insummary,despitesignificantdistalcooling,TC,vigilanceandsleepinessremainedlargely
unaffected.Contrarytopreviousindicationsofimprovedvigilanceandwakefulnesswith
temperaturemodulationinnarcoleptics,thecurrentstudyachievednoprolongedeffectsfrom
distalcooling.Certainconsiderationsneedtobehighlightedincomparingthesetwopopulations,
andstudies.Firstly,narcolepticshavegreaterroomforimprovement,astheyshouldbeawake
andalertduringtheday–whentheprotocolshavebeenimplemented–assuchmanipulations
restorethemtonormativetemperaturelevels.Thecurrentstudyaimedtoimpairnormative
temperaturelevels,atatimewhentonicpressureswereinstigatingsleep.Secondly,circadian
rhythmsinnarcolepsyareweakenedandthereforelikelysusceptibletomanipulation,whereas
thecurrentstudy’spopulationwasyoungandhealthywithnoticeablyrobustrhythms.Distraction
effectsofcoolingperceptuallydominantskinregionssimilarlyprovedineffectiveingeneratinga
prolongedriseinvigilanceorwakefulness.Finally,thenarcolepticpopulationwasonlytestedin
responsetoacutemeasures(asinglePVT),whereasthecurrentstudyobservedtheprolonged
responsetocoolingoverthreehours(fivePVTs).Thedifferenceinstudyoutcomescouldbe
determinedbythedurationofobservation,wherebytheinitial,dynamicthermoreceptorfiring
inducesgreaterperceptualawareness,andeventuallyadapts.Thecurrentstudyobserveda
dynamiceffectthatmayhaveproducedimprovedvigilance,similartoFronczeketal’s(2008)
study,whichinModeratemayhaveindicatedadistractioneffectfromcooling.EEGfurther
reflectedworseningcognitivearousalandincreasingsleepiness.
110
5.2
Transienteffects
Achangingambienttemperaturecausescutaneouscold-sensitivethermoreceptorstoproduce
adynamicthermoafferentfiringthatisfive-toten-foldabovethatofstaticthermalstates(as
discussedin2.2.2Sensation)(Hensel,1982).Theperceptualstimulusassociatedwiththedynamic
thermoreceptorresponsefollowsasimilarprofile(Arensetal.,2006a,2006b;Zhangetal.,2010a,
2010b,2010c).Inthepresentstudy,subjectivesleepinesswassignificantlyreduced(Figure4.13),
whileeffectsonvigilancewerepossiblebutunclearduringthedynamicphaseofMildand
Moderatecooling(Figure4.12).Steadystatetemperaturewasattainedafter~10mininboth
coolingconditions,withtheinitialrateofcoolingbeingtwiceasfastinModeratethaninMild.
Associatedoverall/whole-bodyperceptualresponseswerealsomarkedinthisperiod,with
sensationdecliningfrom‘warm’(~9)to‘cool’(~6.5),and‘cold’(~5.5.)forMildandModerate,
respectively(Figure4.6).Asthemanipulatedtemperatureswerenotsevereandremainedstable
followingtheinitialdecline,participantsthereaftermaintainedthermalcomfortnomorethan
‘slightlyuncomfortable’.
TheobservedtrendinsleepinesswassimilartoReyneretal(1998)observedresponsestoincarcountermeasures,andinfactsimilartoFronczeketal’s(2008)acutefindings.Reyneretal
(1998),usingcoldair(10OC)directedattheface,observedinsignificantdecreasesinsubjective
sleepiness(KSS)ofslightlylargertothoseinthecurrentstudy’sModeratecoolingcondition(2
KSSscores(Reyner&Horne1998),comparedwith0.8)butofsimilarduration(~15minutes
comparedwith~20minutes,respectively).Reyner&Horne’s(1998)2-pointdropinsubjective
sleepinesswaspresumablyduetothedynamicthermoreceptorresponse,mademorepowerfulby
theface’shighperceptualandautonomicthermosensitivity.Reyneretal’s(1998)studywas
conductedduringtheafternoonandstillproducedsubjectivesleepinesslevelsof~7“sleepy,no
efforttostayawake”(KSSrange:1-9).
111
5.3
Limitations
5.3.1
Ordereffect
Withinthecurrentstudy,ordereffectwasalargeconcern,consideringthedegreeof
motivation-relatedmeasures.AccordingtoTopsetal(2004),motivationisintrinsicallyrelatedto
mentalfatigue,inwhichanimbalanceintheeffort-rewardrelationshipdecreasesmotivation,
resultinginmentalfatigue.Theboredomassociatedwiththecurrentprotocolwasanticipatedto
generatealargeordereffectduetolossofmotivationinsubsequenttrials.Tothisend,a
crossoverdesignminimisedthesystematicimpactofanordereffect.Taskswerealsocarefully
chosentominimiselearningormotivationeffects.ThePVThasbeenvalidatedinmentally
fatiguing,andsleepdeprivedsituationstoserveasahighlysensitivemarkerofsleepinessand
vigilancedeclinewithminimallearningeffects(Dinges,1995;Basner&Dinges,2011).ThePVT
hasbeenutilisedasavigilancemeasureinavarietyofstudiestodemonstrateefficacyofstanding
(Caldwelletal.,2003),temperaturemanipulation(Fronczeketal.,2008,Raymannetal.,2005;
2007a,2007b),andsleeprestriction(VanDongenetal.,2003).Similarly,EEGisoftenusedin
parallelwithPVTasagoldstandardmeasureofsleepiness,andvigilancedecline(Caldwelletal.,
2003;Dorrianetal.,2005;Fronczeketal.,2008;Raymannetal.,2007b;VanDongenetal.,2003).
TheKDThasbeenrepeatedlyusedasastandardisedtechniquewithinEEG,ofteninconjunction
withKSS(Cajochenetal.,2000;Gillbergetal.,1982;Grenecheetal.,2008;Kaidaetal.,2006).
Amongthedifferentfields,bothEEGandPVThavebeenarguedtobethebestmeasureof
drowsiness/fatigue/sleepiness(EEG,see(Horne&Reyner,1996);PVTsee(Limetal.,2008)).
Fortunately,PVT,perhapsthemaindependentmeasure,didnotshowanordereffectofsession
(P=0.177).
Carefulstandardisationinlinewithconstantroutineprotocolstandardswasalsoattempted,
forexample,inminimisingnoise,light,posturalchange,socialinteraction,andknowledgeoftime;
allofwhichhavebeendemonstratedtoinfluenceperformanceandarousal(Millsetal.,1978;
112
Kräuchietal.,1999).Sleeppatternswerealsomonitoredforvariabilityandordereffects,and
standardisedbyaskingparticipantstocontrolsleeppatterns48hoursbeforetesting.Participants
wereinitiallyscreenedfornormalisedsleeppatterns,andonaverage,wenttosleepat23:40and
slept~8h.Allparticipantsmaintainedanormalsleeppatternasassessedfromaccelerometry
andsleepdiaries(albeitwithonlyamodestproportionofdataobtained).Noordereffectwas
apparentinthesleepdataobtained.
5.3.2
Laboratory/Equipmentsetup
Distractionandarousalbothmayhavebeenpresentintheoutcomesasaresultofinterference
fromtheexaminer.Manystudiescurrentlyconductedonvigilancemaintainacomputerinterface,
andseverelylimitexaminerinput.Thisistominimisealterationstointer-testprotocoltimelines,
andexperimentalerrorbutimportantlytoreducetheverbalinputwhichmayotherwise
confoundoutcomes.Thecurrentstudy,whileattemptingtominimisehumaninputusedan
examinertoverballycueparticipantsintosubjectivequestionnaires.Theexamineralsoremained
presenttopromptparticipantstowakeupthroughouttesting,whichisnotuncommon(e.g.,
(Fronczeketal.,2008)),butremainsabarrier.
Anotherissuewasmaintenanceofcooling.Asonlyrudimentaltechnologywasusedinthe
coolingprotocols,temperatureshadtobeconstantlyassessedandadjustedmanually.This
resultedintheoccasionalerror(SeeFigure4.1a:Mildcondition,minute150).However,in
conjunctionwithexperimentalerror,thelackofthermostatmeanticewasrequiredtocoolthe
circulatingwater.Dumpingiceintotheurnproducedunnecessarynoise,which,despite
participantswearingearplugs,wasaudible.
5.3.3
Statisticalpower
Therewassomeindicationtowardaneffectofdistalcoolingonvigilance.TheeffectinRRT
wasnotstatisticallysignificant(P=0.875;effectsize=0.27),whereastheKSSshowedareliable
effectofcooling(P=0.046),albeitwithmodesteffectsize(0.17).Alackofpowerarisingfroma
113
smallsamplesizeisanobviouslimitation.Thenatureofsuchstudies–multipletestingnightsof
longduration,andinvasiveprocedures–makesrecruitment,retentionandadherenceof
participantsdifficult.Increasingsamplesizeisnotaneasytask;however,itmaybeessentialto
determinethenatureoftherelationshipbetweenalertnessandbodytemperature,andtofurther
delineatetheefficacyofcoolinginincreasingalertnessandreducingtheriskofaccidents.Future
studiesapproachingsuchresearchwillhavebearinmindthebarrierstosuchdesigns.Asa
similardynamiceffectofcoolingonhasbeenpreviouslyobservedwith16participants(Reyneret
al.,1998)itisreasonabletosuggestthatsuchnumbersmayhavebeenrequiredtofurther
delineatethedifferencesobservedbetweenthelevelsofthestatisticalanalyses–Control,Mild,
andModerate.Despitethis,promisingtrendsindicateamorein-depthstudyintotheeffectof
coolingonvigilancemaybeworthwhile.
5.3.4
Electroencephalography
Characterisingfrequenciesasfarasspecificrecordingsites,andfiltering,transformingand
analysingmethodsarehugelyvaried.Thesedifferencesareconvolutedandintimidatingforthose
entertainingusingEEGasatechnique.Alotofmethodsarenowout-dated,howeveritwas
cumbersomeanddifficulttoassesswhich.Thecurrentstudyutiliseddefinedboundariesfor
traditionaltheta(4-7Hz),alpha(8-1Hz),andbeta(13-30Hz)frequencybands,howeverthereis
mountingevidenceforHz-Hzpoweranalyses(Pizzagalli,2007),orindividuallydefinedfrequency
bands(Klimesch,1999),whichmayrefuteorenhancethecurrentobservedEEGoutcomes.
ClinicalEEGprovidesexcellent,currentbestpracticeguidesforobservingandsleepstagingEEG
criteria,howeveranequivalentisdifficulttofindinquantitativeEEG;especiallyquantitativeEEG
relatedtodrowsiness.ThecurrentstudyutilisedguidelinesfromSantamariaandChiappa(1987).
Debunkingcorrectmethodologiesprovedtimeconsuminganddifficult.Thiswasmade
considerablysowithoutcorrecttechnicalsoftwaretoperformdatareduction,spectralanalyses
and,noise/artefactscanningandrejection.Timeconsumingtechniqueslimitedthescopeand
versatilityoftheEEGanalysis,anotherwisehighlypowerfulmeasurethatisarguably
114
underappreciatedoutsideitsclinicalsetting.Matlabwasutilisedfordatareduction.Whilea
highlyversatileandpowerfulprogram,Matlabrequiresconsiderabletimetoinputcodefor
interpretationofdata,aswellasmuchgreaterinvolvementtounderstandandlearntouse.
Additionally,itisdifficulttoensurevalidoutcomesfromMatlabcoding.AssuchutilisingaMatlab
specialistallowedfortheinputandoutputofEEGdata,atthecostofversatilityinEEGspectral
analyses
Additionalunusedelectrodesbecameredundantastimeandsoftwareprovedinsufficientto
accomplishadditionalanalyses.Additionally,asanalysesprovidedgeneratednoeffect,further
analyseswouldhaveprovedcumbersomewithoutaddingtotheknowledge.Frontalderivations
wereoriginallyproposedtoanalysecognitivearousalduringPVTtaskshoweverthecollected
frontalPVTdatawasomittedfromanalysesfortheaforementionedreason.
5.3.5
Temperature
Thedegreeofthermalclampingwasdifficultduetoequipmentlimitationsallowingatbest1OC
ofdeviationfromintendedvalues.Coupledtothisproblematiccontrolwasaninteresting
physiologicaluncouplingoffoottemperatureswhilecoolingwasoccurring.Werneretal(1980)
observeduponcoolingthatalargedivergenceintemperaturerangeoccurred,with~17OCof
differencebetweenskintemperatures(Tfoot–Tforehead)inacoldenvironment(TA=10OC),when
comparedtoatotalcoretoskindifferenceof~2OCwhenunder~50OCambientload.However,
theydidnotobservethevariationofchangewithinthefeetalone,nordidLove(1948)while
observingbloodflowchangesinthefeetacrosshotandcoldconditions.Inthecurrentstudy,
undermoderatecooling(T=25OC),therangeinfoottemperatureswasasgreatas~9OC,withthe
footarchdecreasingtotemperatures~19OCandventraltoerestingat~29OC.Thisvariabilityof
foottemperaturescreatedconsiderabledifficultywhenattemptingtogainareliableaveragefoot
temperature.
115
5.3.6
Vigilance
Vigilanceisknowntobestressfulandfatiguing(Warmetal.,2008).However,fatiguewas
aimedtobeexacerbatedinsleeppermissivesettingsatnormalbedtime.Anumberof
participantswereanticipatedtodropintoearlystagesofsleeponset(Stage1,andStage2),
howeverforsomeparticipantsthisoccurredintheextremesuchastoleadtotheirremoval.The
argumentforremovingparticipants(originalP2andP9[theseparticipantswerereplaced])was
thelossofvalidityduetocontinuousinteractionwiththeexperimenter(i.e.,continuallyrousing
theparticipantsfromslumber).OriginalP9inhersecondPVT(postintervention)inthe
moderatetrialresultedinherasleepafter5-minduration,requiringcontinuousrousingupon
eachstimulus.Whileshereflectsacertainpopulationoftheexperiment,thevalidityofhertest
wasconsideredtobealtered.
AswithP9whorapidlyreachedtheceilingeffectinhisMildcondition,participants’subjective
sleepinessoscillatedthroughoutthenight.Although,Figure4.7showsageneralprogressionof
sleepinessacrossthenight,Figure4.8showsthenumberofparticipantsskewingthistrendtobe
muchgreaterinControlandMildconditionsthaninModerate,withoverhalfparticipantsin
ControlandMildreachingceilingby300minutes,withMildconditionshowingasubsequent
decline.Moderateconditionmaintainedtwoparticipantshavingreachedceilingby190minutes
untilthefinalmeasurewhereupon3subjectsreachedKSSscoreof9(Figure4.8).
5.4
VariableTemperaturesacrossthermistorlocationsonthefeet
Coolingwassomewhatheterogeneousacrossthefoot;thearchcooledmorethanthetoes,
moresoinModerate(~5OCdifference)thaninMild(~2OCdifference).Thebloodsupplytothe
toesarisesfromthedorsalispedis,whichdividesinto,amongothers,thefirstdorsalmetatarsal
artery(Standring.2008).Thefirstdorsalmetatarsalarterysuppliesthefirstandsecondtoes.The
coolingappliedtothefeetwasassumedtocausevasoconstrictionandtherebyrestrictcutaneous
116
bloodflow.Whilenervouscontrolofthefeetdiffersbetweenvolaranddorsalskinregions,
coolingatbelowTNZsgeneratesgeneralisedadrenergicvasoconstrictionacrossthewholefoot.
Theobserveddifferenceswerenotdivisiblebythevolaranddorsalskinregionswhichare
expectedtoprovideregionaldifferencestolocalcoolingduetotheirdifferingneuralcontrol
(Tayloretal.,2014).Whilevolaranddorsalregionsaredifferentiallycontrolled,bothsurfaces
receivegeneralisedadrenergicinputuponintroductiontocooling.
Theobserveddifferencesinthecurrentstudywereconsideredtobeveryunlikelytohave
beenduetodesignofthewater-perfusedbooties(seeAppendixEforphotos).Thespacingof
tubingwasconsistent,andcondensedasthefrontofthesockfoldedaroundthetoes.Thearch
waselasticatedtoprovidebettercontactthroughthemidfoot.Thetubingflowedaroundthe
anklesandoverthelateraldorsalfootbeforeprogressingintothesoleattheheelandprogressing
forwardoverthetoesandbackoverthedorsalaspectofthefootbeforeflowingbacktotheheel,
overthemedialfoot,andoutattheposterioraspectoftheankle.Ifheatexchangewiththewater
wereresponsibleforthedifferencesintoetemperature,thenthearchthermistorwouldalsobe
affected.
Thedifferentialthermalchangesobservedinthefeetaredivergentfromtheexpected
thermoregulatoryresponse.Theinputofnon-thermalheatlossfromtheSCNmayberesponsible
forthediscrepancyinfoottemperatures,howeverdespitetheconfidenceinthewaterperfused
booties,theycannotberuledoutasaninfluencingfactor.Iftheobserveddifferencesinfoot
temperatureacrosslocationsisarealeffect,thenitwouldbecomparativelyeasytoassess,and
thereforeworthinvestigation.
5.5
Practicalapplication
Inlightofthecurrentfindings,subtletomoderatecoolingofthefeetdoesnotappearto
increasevigilance.Greatercoolingprovesinadequateforotherreasons;moderatecoolingis
117
distracting(Cheungetal.,2007),assuch,althoughcoolingincreasesalertnessitislikelyto
distractindividualsawayfromtaskdemands.Greatercoolingalsodiminishesdexterity,bywhich
afunctionalresponsemayalsobehampered;thisisalsoareasonfornotusinghandsasamethod
ofcooling.Previousexperimentationdirectingcoolairtothefacehasprovensimilarlyinadequate
forimprovingperformanceinattentionaltasks,despitethegreaterperceptualandautonomic
thermoafferentdrivers(Reyner&Horne,1998).Caffeineandpowernapsremainthebest-proven
sleepinessinhibitors(Horne&Reyner,1996);withstandingversessitting(Caldwelletal.,2003)
andexposuretobrightlight(Cajochenetal.,2003;Kaidaetal.,2006;Czelsieretal.,1986)also
providingmeansforreducingdrowsiness.
Conversely,inaneraofincreasingsleepdisturbances,andreducedsleepduration,theresults
ofthecurrentstudyareencouraginginthathealthyyoungadultsmaintaintemperaturerhythms
relatedtosleeponset,regardlessofmoderateexposuretocoldatlocalisedregions(i.e.,bare-feet
onacoldevening).Providedtherestofthebodyiswarm,evenmoderatelycoldfeet(Tsk~25OC)
havenoeffectonTCdecline,despiteconsiderablevasoconstrictionoccurringinthelowerlimbs.
Whileconsiderabledifficultyinitiatingsleephasbeencorrelatedwithcoldextremities(Kräuchiet
al.,2008),thecurrentstudyindicatesthatthismaybelessofanissueinhealthyyoung
populations.
Insummary,althoughperipheralwarminghasafacilitativeeffectonsleepinitiation,the
implicationthatcoolingbyassociationmayreducesleeppropensityappearstenuous.Rather,
thermoregulationassociatedwithsleeppressureappearscapableofresistingcoolinginhealthy
youngadults.
5.6
ConclusionsandRecommendationsforfutureresearch
ItiswidelyacceptedthatreducingtheDPGbywarmingtheextremitiesimprovessleeponset
latencyandworsensvigilance.ThisassociationreliesontherelationshipbetweenTCandarousal
118
state,mediatedthroughskintemperaturechange.LargerperturbationsinTSkmightalsobe
expectedtohavedistraction-inducingeffectsfromthermalperceptionsarisingfromTSkitself.
Despitethenumerouslinesofevidenceindicatingrelationshipsbetweenvigilanceandbody
temperature,thecurrentstudywasunabletosupportorrefuteanyinfluenceofthedistal
extremitiesorassociatedgradientsonTCorarousalstate.Warmingextremitiescanapparently
influenceTCandarousaldecline,howeverunlikeinFronczeketal’s(2008)narcoleptic
population,coolingdidnotappeartoperformtheinversefunctioninhealthysubjectsforthe
reasonsdescribedabove(5.1.2summary).Coolingthedistalextremitiesduringthecircadian
phaseofnon-thermalheatlossdidnotimprovevigilanceandproducedonlymild,transient
improvementsinsubjectivesleepiness.Asstatedprior,thefactorsthatmayberesponsiblefor
thisisthatcoolingmayhaveassistedheatlossdespitelocalconstrictionfactorsandbloodflow
reductionsfromAVAconstriction,howeveritcannotberuledoutthatmomentummayhave
alreadyinstigatedsufficientheatlosstorendertheprotocolinsufficient.Itappearsthathealthy
individualsmaybemorecapableofbufferingmoderateperturbationsindistalextremities,
withoutaffectingtheeveningdeclineintemperature,thanthepopulationsusedincomparative
studies.
Despitethelargelynullfindingscurrently,thereisstillacompellingbasisforfutureresearch
surroundingtheinteractionbetweenvigilance/wakefulnessandtemperature,withramifications
foreasilyapplicablestrategies.Asstatedinthediscussion,theeffectofdistractioncannotbe
overlookedasapotentialmeanstomaintainvigilanceorwakefulnessacrossextendedperiods.
Distractionfromtemperaturemanipulationwouldperhapsbebestappliedbymanipulationsof
thedistalextremities,whichhavehighperceptualthermoafferentdrive,attemperaturesresiding
closetothermaldiscomfortthresholds(e.g.,TSk~20OC).Cheungetal(2007)demonstratedthe
distractioneffectfrommild(TSk~23OC;TCnormal)whole-bodytemperaturemanipulation,and
Kräuchietal(2008)hasindirectlyinferredthattheeffectoffootandhandcoolingaroundthe
thermaldiscomfortthresholdimproveswakefulness–oratleastimpairssleepinduction.
119
However,minimallydistractingtemperaturemanipulationswouldbemoreappropriatewhere
vigilanceisrequiredforcomplextasks;thismaybeachievablethroughmanipulationsofTCthat
donotevokeordirectawarenesstothethermalmanipulations.
6.0
120
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7.0 APPENDICES
AppendixA:Participantinformationandconsentform
Referencenumber:13/087
April2013
PARTICIPANTINFORMATIONSHEET
DistalSkinTemperatureandCognitivePerformance
Thankyouforexpressinganinterestinthisproject.Pleasereadthefollowing
informationcarefullybeforedecidingwhethertoparticipateinthestudy.Ifyouhave
anyquestions,pleasedonothesitatetoask.
AimoftheStudy:
Toexaminewhethercognitivefunctionisaffectedbytemperatureofthefeet.This
studyisbeingundertakenforaMastersofPhysicalEducationresearchproject,underthesupervision
oflecturerswithintheSchoolsofPhysicalEducationandMedicine.Theresearchwilltakeplaceinthe
SchoolofPhysicalEducation(LaboratoryB01or113,55UnionStWest).
TypeofParticipantsNeeded:
Healthyyoungadults(18-30years)residinginDunedin,whoarewillingtostayuplateonthreenights
toperformamonotonouspsychomotorvigilance(sustained,prolongedreactiontime)taskwhilealso
havingtheirbrainfunctionandbodytemperaturemeasured(seebelow).
WhatWillTheParticipantsBeDoing?
Ifyouarewillingtoparticipate,youwillneedtoattendthelabonuptofouroccasions;onebeinga
familiarisationsessionof~1hourduration,andthen2or3datacollectionsessionsofupto3hours
each(spacedoneweekapart).Thedatacollectionsessionswillbeginat~10pm,therebyrequiringyou
tostayup~2-3hourslaterthanusual,toperformamonotonousmentalfunctiontaskfor~40minutes
oneachoccasion.Oneachofthesedaysyouwillneedtoavoidexerciseandcaffeinatedandalcoholic
drinksfrommidday,andfollowthesamedietaryregime(includinghydration).Youwillberemindedof
theserequests.
Duringeachsessionyouwillhavetheelectricalactivityofyourbrain(EEG)andeyes(EOG)recorded
usingelectrodesattachedviaacapandgluedtoyourscalp,yourheart’selectricalactivity(ECG)
recordedfromelectrodesattachedtoyourskin,andyourbodytemperaturemeasuredusingelectrical
thermometerswornonyourskinandwithinyourrectum.Youwillneedtoinsertthethermistor;itis
sterile,flexibleanddisposable,andshouldnotbeuncomfortable.Periodicassessmentwillbemadeof
yourmentalfunctioning(performanceonavigilancetask),perceivedtemperature,thermalcomfort
andmoodstate.Thetaskwillinvolveaprolongedsustainedreactiontimeperformancetask,whichwill
beperformedwhilethetemperatureofyourfeetisaltered.
BenefitsofthisResearch:
Mentalfunctionandthermoregulationarelinked,butthenatureoftheselinksisnotyetwell
understood.Ourresearchisfocussedonimprovingsociety’sknowledgeofhowstronglyandinwhich
directionrelationsexistbetweendistalskintemperatures(esp.thefeet),mentalfunctionandarousal
state.Someimmediatebenefitsofthisknowledgeareinhelpingprovidetheevidencefor
recommendationsaimedatreducingsleepdeprivation,andconversely,inpreventingsleeponset(e.g.,
inreducingfatigue-relatedroaddeaths).
RisksandBenefitstotheParticipant
Therearenodiscernible,knownrisksorbenefitsofparticipation,otherthan:
• Thesocialandperhapstransientphysicaldiscomfortofrectaltemperaturemeasurement;
134
•
Theinconvenienceanddiscomfortofremaininguplateandtheprolongedtask;
•
Sleep-deprivationonthedayfollowingeachtestingsession,therebyincreasingyourriskof
impairedvigilance(e.g.,higherlikelihoodofhavingamotorvehicleaccident,orconcentrating
inlecturesorotherwork)andimpairingyourimmunefunction(e.g.,possiblyhigher
susceptibilitytoupperrespiratorytractinfection);
•
Milddiscomfortoffootcooling.
Therecordingequipmentcarriesnoriskordiscomfort.
Youwillbeinformedoftheresultsofthisproject,andtheirpracticalimplications,following
completionofthedatacollectionandanalysis.
DataInformationRequired
•
•
•
•
Nameandphonenumber:Forcontactreasons.
Ageandbodymass:Forparticipantcharacteristicspurposes.
Usualsleeppatterns(viaa7-daysleepdiary).
Heartrate,corebodyandskintemperatures,brainandeyeelectricalactivity,sustainedreaction
timeperformanceandperceptionsofmoodandtemperature.Thisinformationisrequiredto
examinethephysiological,perceivedandperformance-relatedeffectsofincreasinganddecreasing
foottemperature.
Alldataobtainedwillbeusedsolelyforthepurposesdescribedabove.Resultsofthisprojectwillbe
includedinaMaster’sdegreethesis(whichwillbeavailableintheUniversityofOtagoLibrary)and
maybepublishedinthescientificliterature,butanydataincludedwillnotbelinkedtoaspecific
participant.Yourdatawillbeassignedapersonalidentificationnumbertoensureanonymityinboth
theanalysisanddocumentationofresults.Thedataobtainedinthisstudywillonlybeavailabletothe
MPhEdstudent(MrRyanSixtus),AssocProfJimCotter,AssocProfBarbaraGallandandDrJon
Shemmell.
Thedatacollectedwillbesecurelystoredinsuchawaythatonlythosementionedabovewillbeable
togainaccesstothem.Dataobtainedasaresultoftheresearchwillberetainedforatleast5yearsin
securestorage.Anypersonalinformationheldonparticipants(name,age,bodymass,phonenumber)
willbedestroyedlatein2013whereasmeasurement/responsedatawillberetainedforatleastfive
yearsfollowingpossiblepublicationofthereport.
CanParticipantsChangetheirMindandWithdrawfromtheProject?
You may withdraw from participation in the project at any time and without any disadvantage to
yourselfofanykind.
135
ContactInformation
Pleasefeelfreetocontactusatanytimewithquestionsandconcernsyoumayhaveabout
participatinginthisresearchstudy.
AssocProfJimCotterMrRyanSixtus
SchoolofPhysicalEducation SchoolofPhysicalEducation Phone:479-9109
Phone:479-8991
email:[email protected] email:[email protected] Ifyouwishtocontactanindependentpersonregardinganyaspectofyourparticipation,please
contact:ProfessorDouglasBooth,Dean,SchoolofPhysicalEducation,Otago,Phone:479-8995
ThisstudyhasbeenapprovedbytheUniversityofOtagoHumanEthicsCommittee.Ifyouhave
anyconcernsabouttheethicalconductoftheresearchyoumaycontacttheCommittee
throughtheHumanEthicsCommitteeAdministrator(ph.034798256).Anyissuesyouraise
willbetreatedinconfidenceandinvestigatedandyouwillbeinformedoftheoutcome.
136
Referencenumber:13/087
April2013
CONSENTFORMFORPARTICIPANTS
DistalSkinTemperatureandCognitivePerformance
IhavereadtheInformationSheetconcerningthisprojectandunderstand
whatitisabout.Allmyquestionshavebeenansweredtomysatisfaction.I
understandthatIamfreetorequestfurtherinformationatanystage.
Iknowthat:
1.
2.
3.
Myparticipationintheprojectisentirelyvoluntary;
Iamfreetowithdrawfromtheprojectatanytimewithoutanydisadvantage;
Thedatawillbedestroyedattheconclusionoftheprojectbutanyrawdataonwhichtheresults
oftheprojectdependmayberetainedinsecurestorageforuptofiveyearstoassistinchecking
theaccuracyofthisresearchordevelopingfutureresearch,afterwhichtheywillbedestroyed;
4. Iwillberequiredtofollowsleepanddietaryrestrictionsonuptofouroccasions;
5. Iwillhavemymood,heartrateprofiles,cognitiveperformance,deepbodyandskin
temperatures,andbrainandeyemuscleactivitymeasuredonuptofouroccasions,threeof
whicharelateatnight,approximately1weekapart;
6. Iwillnotbereceivinganyrewardorcompensationformyparticipationinthisstudy.
7. TheresultsoftheprojectmaybepublishedandwillbeavailableintheUniversityofOtagoLibrary
(Dunedin,NewZealand)buteveryattemptwillbemadetopreservemyanonymity.
Iagreetotakepartinthisproject.
.............................................................................
...............................
(SignatureofParticipant)
(Date)
ThisstudyhasbeenapprovedbytheUniversityofOtagoHumanEthicsCommittee.Ifyouhaveanyconcerns
abouttheethicalconductoftheresearchyoumaycontacttheCommitteethroughtheHumanEthicsCommittee
Administrator(ph.034798256).Anyissuesyouraisewillbetreatedinconfidenceandinvestigatedandyouwill
beinformedoftheoutcome.
137
AppendixB:Activitymonitoringandsleepdiary
ActivityMonitoringandSleepDiary
Pleasestartfillingoutthetablebelowonthefirstnightbeforeyougotosleepandthenas
soonasyouwakeinthemorning,andcontinuetodosoforthedurationofthestudy.It
wouldbegreatifyoucouldattempttomaintainacontinuoussleeptimebetween
weekdaysandweekendsforthedurationofthestudytoensureyouarewellrestedfor
theprotocolintheeveningoftheseventhday.
Somenotesthatmayhelp:
Alcohol:Excessivealcoholintakeisnotadvisedregardless,howeverifyoufeelyoumust,
ittakes48hourstonormalisesleeppatternsfollowinga“latenightout”,assuchwe
wouldaskyoutodosowithinthefirstthreedaysofyoursleepdiaryandjustrecord
thetimeyouwenttosleep.
Caffeinecontainingdrinks:energydrinks,softdrinkslikecokeandPepsi,coffee,tea(there
aredecaffeinatedoptions).
Physicalactivity:Ifyoudoexerciseregularly,thenitmaybeadvisabletohaveaneasy/off
dayonthenightoftheexperiment,asthelatenightwillconsiderablyfatigueyouanyway.
Thisismoreaconcernwhenyouareheadinghomefollowingthelab.
Hydrationlevels:adequatehydrationpriortothetestcanbegainedthroughintakeofa
goodglassofwater,orjuicewiththeeveningmeal.Weaskthatyoualsohaveagood
dinnerbeforecominginbecausethetestwillrequireafewextrahoursoftimeoutofyour
day/night.
Ifyoucouldwashyourhairpriortocominginthatwillsavealotofabrasionnecessary
tolowerimpedance.
Date
138
Timetobed
Timeoutofbed
Dayone:
Startingdate:
Daytwo:
Daythree:
Dayfour:
Dayfive:
Pleasestopcaffeine
intakeuntilexperiment
night
Daysix:
Howwelldoyoufeelyouslept?IfBadlypleasecontactme0273220250
Extraday:
Dayseven:
Experimentalnight
Pleasemaintain
hydration,andrefrain
fromalcoholandcaffeine
today
Additionalnotes:
Whathaveyoueatentonight???ANDwhen???
Whatareyouwearing???(e.g.,sweatersandwarmhoodie)
139
SecondWeek
Startingdate:
Dayone:
Daytwo:
Daythree:
Dayfour:
Dayfive:
Pleasestopcaffeine
intakeuntilexperiment
night
Daysix:
Howwelldoyoufeelyouslept?IfBadlypleasecontactme0273220250
Extraday:
Dayseven:
Experimentalnight
Pleasemaintain
hydration,andrefrain
fromalcoholandcaffeine
today
REMEMBERTOEATANDWEAR
WHATYOUDIDTHEFIRSTTIMEJ
140
thirdWeek:
Startingdate:
Dayone:
Daytwo:
Daythree:
Dayfour:
Dayfive:
Pleasestopcaffeine
intakeuntilexperiment
night
Daysix:
Howwelldoyoufeelyouslept?IfBadlypleasecontactme0273220250
Extraday:
Dayseven:
Experimentalnight
Pleasemaintain
hydration,andrefrain
fromalcoholandcaffeine
today
REMEMBERTOEATANDWEAR
WHATYOUDIDTHEFIRSTTIMEJ
Thankyouforparticipating.
141
AppendixC:Participantsetup
Figure1:Depictionofparticipantsetupfromviewofexperimenter.
AppendixD:Criteriaforanalysisofthe10minPVT.
Table1:Criteriafortheanalysisofthe10-minPVT.Extractedfrom
BasnerandDinges,2011(Basneretal.,2011)
142
143
AppendixE:Outlinefordrowsinessscoring
Table1:Outlineforsignificanteventsinprogressingdrowsiness
144
AppendixF:Pilottemperatures
Table1:TrialcoolingprotocolforapplicationtoMildandModerateconditionsinmainstudy.
cooling30
cooling25
pre
inboot
Tpad
31.2
34.1
32.45
31.7
31
30.4
29.95
29.95
30.6
31.05
30.85
0
5
10
15
20
25
30
35
40
45
50
55
60
65
70
75
80
85
90
29.2
27.25
25.9
25
24.25
23.75
23.5
23.5
23.8
23.9
Ttop
Farch
F1mt
average water
difference
30.8
32.45
30.95
31.35
21.6
9.75
33.35
33.55
32.65
33.41
21.65
11.76
32.3
32.05
31
31.95
22.15
9.80
31.6
31.35
30.25
31.23
22.4
8.83
31.05
30.75
29.65
30.61
22
8.61
30.45
30.3
29.25
30.10
22.25
7.85
30
29.9
28.9
29.69
22.85
6.84
30
29.7
28.9
29.64
23.6
6.04
30.55
29.7
29.15
30.00
24.75
5.25
30.95
29.75
29.45
30.30
24.95
5.35
30.8
29.65
29.45
30.19
25
5.19
29.1
28.4
28.05
28.69
16.9
11.79
27.35
27.15
26.35
27.03
14.45
12.58
26
26.45
25.25
25.90
14.15
11.75
25.1
25.9
24.6
25.15
14.65
10.50
24.4
25.55
24.25
24.61
15.35
9.26
23.85
25.4
24.1
24.28
17.55
6.73
23.55
25.4
24.25
24.18
17.85
6.33
23.5
25.5
24.45
24.24
20.5
3.74
23.7
25.7
24.9
24.525
21.2
3.33
23.8
25.75
25.1 24.6375
21.35
3.29
Originalpilotstudyconsistedofasimulateddrivingtask,withEEGcomprisingarousal
markers,whileundergoingfandirectedcooling.Testingtookplaceovertwohoursstartingat
23:30.Fourparticipantstookpart.Coolingintheoriginalstudyconsistedoftwophases:Foot
bath,eitherwarm()orcool(),followedbywearingwarmsocksordirectedfanblowingoverice
(Figure1).Coolingmethodsweredeemedtobeinadequatefortestingthehypothesis,whichled
totheabovepilottestingofamoresustained,andreliablemethod.MuchoftheEEGinputwaslost
duetonoise(likelyelectrostaticandmechanical,aswellasduetonoviceprotocol),butan
indicationisprovidedinFigure2.
145
33
31
Temperature(oC)
29
27
25
Warming
23
Cooling
21
19
pre
2
4
6
8
10
Post
10
20
30
40
50
60
70
80
90
100
110
120
Post
17
Figure1:Originalstudyfoottemperaturemanipulationsforbothcoolingandwarmingprotocols.
EEG Power (uV)
250
200
150
Cooling Alpha
Cooling Beta
Warming Alpha
Warming Beta
100
50
0
Pre
Post
Condition
Figure2:CollatedEEG(referentialelectrodederivationsF4,FCz,O2toA1),ofbothpeakalpha(812Hz),andpeakbeta(13-30Hz)powersPre-andPost-test,forbothwarmingandcooling
protocols.
146
AppendixG:Waterperfusedbooties
Figure1:Viewofinternaltubingliningthecustomfittedbooties.
Figure2:Customfittedbootiesworn.
Thewaterperfusedbootiesopenedouttorevealinnertubing(Figure1)andwhileworn(Figure
2).Lacesandwhitepatchonmedialborderareelasticated(indicatedbyredarrow).
147
AppendixH:KarolinskaSleepinessScale
KarolinskaSleepinessScale(KSS)
1========== extremelyalert
2=========== veryalert
3=========== alert
4=========== ratheralert
5=========== neitheralertnorsleepy
6=========== somesignsofsleepiness
7=========== sleepy,noefforttostayawake
8=========== sleepy,someefforttostayawake
9===========verysleepy,greatefforttokeepawake,fightingsleep
148
AppendixI:Thermalsensationandthermaldiscomfortscales
PERCEIVED TEMPERATURE SCALE
THERMAL DISCOMFORT SCALE
“How%does%the%temperature%of%your%
“How%comfortable%do%you%feel%with%the%
Body%[feet]%feel?”%
temperature%of%your%body?”%
1
2
Unbearably cold
Extremely cold
3
Very cold
4
Cold
5
Cool
6
Slightly cool
7
Neutral
8
Slightly warm
9
Warm
10
Hot
11
Very hot
12
Extremely Hot
13
Unbearably hot
1
Comfortable
2
Slightly uncomfortable
3
Comfortable
4
Very Uncomfortable
5
Extremely uncomfortable
149
AppendixJ:TheBrunelMoodStatequestionnaire
Extremely
Quiteabit
Moderately
Alittle
Notatall
TheBrunelMoodscale
Belowisalistofwordsthatdescribefeelings.Pleasereadeachonecarefully.Thencross
theboxthatbestdescribesHOWYOUFEELRIGHTNOW.Makesureyouanswerevery
question.
Name …………………………………….. Date __/__/2009
1
Panicky…………………………………………….
q
q
q
q
q
2
Lively……………………………………………...
q
q
q
q
q
3
Confused………………………………………….. q
q
q
q
q
4
Wornout………………………………………….. q
q
q
q
q
5
Depressed…………………………………………. q
q
q
q
q
6
Downhearted……………………………………… q
q
q
q
q
7
Annoyed…………………………………………... q
q
q
q
q
8
Exhausted…………………………………………. q
q
q
q
q
9
Mixed-up………………………………………….. q
q
q
q
q
10
Sleepy……………………………………………..
q
q
q
q
q
11
Bitter……………………………………………….
q
q
q
q
q
12
Unhappy…………………………………………... q
q
q
q
q
13
Anxious……………………………………………
q
q
q
q
q
14
Worried…………………………………………… q
q
q
q
q
15
Energetic………………………………………….. q
q
q
q
q
16
Miserable………………………………………….. q
q
q
q
q
17
Muddled……………………………....................... q
q
q
q
q
18
Nervous…………………………………………… q
q
q
q
q
19
Angry……………………………………………...
q
q
q
q
q
20
Active……………………………………………...
q
q
q
q
q
21
Tired……………………………………………….
q
q
q
q
q
22
Badtempered……………………………………... q
q
q
q
q
23
Alert……………………………………………….
q
q
q
q
q
24
Uncertain…………………………………………. q
q
q
q
q
Howmuchsleephaveyouhadinthelast24hours?.......hours......minutes
150
AppendixK:Additionaldata
Moodstates,vigourandfatigue
Figure1:BRUMSmoodcharacteristic:Vigourprepost.Condition1=Control,2=Mild,3=Moderate
Figure2:BRUMSmoodcharacteristic:Fatigueprepost.Condition1=Control,2=Mild,3=Moderate
151
AppendixL:Participanteight
38
P8
Core temperature (OC)
Group
37
36
35
50
100 150 200
50
control
100 150 200
mild
50
100
150
200
moderate
Condition
Figure1:Participanteightcoretemperatureacrossconditions,comparedtothegrouptrend.
Condition
2
DPG (OC)
0
control
50
100 150 200
mild
50
100 150 200
moderate
50
100
150
200
-2
-4
-6
P8
Group
-8
Figure2:ParticipanteightDPGacrossconditions,comparedtothegrouptrend.