This study evaluated the efficacy of Dexedrine for sustaining helicopter pilot performance during 64 hours of continuous wakefulness. Participants completed flight simulations and cognitive/mood assessments under Dexedrine or placebo conditions. Dexedrine maintained flight performance for up to 58 hours and lessened impairments in cognitive performance, mood, and physiological alertness compared to placebo. Some side effects like increased blood pressure and talkativeness occurred but did not negatively impact performance. Dexedrine is an effective countermeasure for sustained operations but should not replace sleep, which remained important for recovery.

1. USAARL Report No. 99-01
The Efficacy of Dexedrine@ for the
Sustainment of Helicopter Pilot
Performance During 64 Hours
of Continuous Wakefulness
BY
John A. Caldwell, Jr.
Nicholas K. Smythe
Patricia A. LeDuc
Brian F. Prazinko
J. Lynn Caldwell
David N. Norman
Evelyn Skoumbourdis
Arthur Estrada
William D. Sprenger
Peggy S. Ruyak
Siobhan Hoffman
Aircrew Health and Performance Division
October 1998
Approved for public release, distribution unlimited.
U.S. Army Aeromedical Research Laboratory
Fort Rucker, Alabama 36362.0577

2. Notice
Oualified reauesters
Qualified requestersmay obtaincopiesfrom the DefenseTechnical Information Center(DTIC), Cameron
Station, Alexandria, Virginia 223 14. Orderswill be expeditedif placedthroughthe librarian or other
person designatedto requestdocumentsfrom DTIC.
Change of address
Organizations receiving reportsfrom the U.S. Army Aeromedical ResearchLaboratory on automatic
mailing listsshouldconfirm correct addresswhen correspondingaboutlaboratoryreports.
Disnosition
Destroy this documentwhen it is no longerneeded. Do not return it to the originator.
Disclaimer
The views, opinions, and/orfindings containedin thisreportare thoseof the author(s)and shouldnot be
construedasan official Department of the Army position,policy, or decision,unlesssodesignatedby other
offkial documentation. Citation of tradenamesin thisreport doesnot constitutean official Department of
the Army endorsementor approval of the useof suchcommercial items.
Human use
Human subjectsparticipatedin thesestudiesafter giving their free and informed voluntary consent.
Investigators adheredto AR 70-25 andUSAMRMC Reg 70-25 on Use of Volunteers in Research.
Reviewed:
L-SEC-
I#
‘MORRIS R. LA-ITIMORE, JR.
Colonel, MS
Director, Aircrew Health &
Performance Division
Releasedfor publication:
,, I
/
Chairman, Scientific Review
Committee

3. Unclassified
jECUR1l-Y CLASSIFICATION OF THIS PAGE
REPORT DWUMENTATION PAGE I Form Approved
OMB No 0704-0186
la REPORT SECURITY CLASSIFICATION
Unclassified
lb. RESTRICTIVE MARKINGS
2a SECURITY CLASSIFICATION AUTHORITY
2b DECLASSIFICATION / DOWNGRADING’SCHEDULE
3 DISTRIBUTION I AVAILABILITY OF REPORT
Approved for public release, distribution
unlimited
4 PERFORMING ORGANIZATION REPORT NUMBER(S)
USAARL Report No. 99-01
5 MONITORING ORGANIZATION REPORT NUMBER(S)
6a NAME OF PERFORMING ORGANIZATION 6b. OFFICE SYMBOL 7a NAME OF MONITORING ORGANIZATION
U.S. Army Aeromedical c/rappkable) U.S. Army Medical Research and Materiel
Research Laboratory MCMR-UAS Command
6c ADDRESS (City, State, and ZIP Code) 7b. ADDRESS (CXy, State. and ZIP Code)
P.O. Box 620577 Fort Detrick
Fort Rucker, AL 36362-0577 Frederick, MD 21702-5012
6a NAME OF FUNDING/SPONSORING 6b. OFFICE SYMBOL
ORGANIZATION (If apphcable)
9. PROCUREMENT INSTRUMENT IDENTIFICATION NUMBER
EC. ADDRESS (Cfty, State. and Z/P Code)
11 TITLE (Indude Security Classificatron)
10 SOURCE OF FUNDING NUMBERS
PROGRAM PROJECT TASK WORK UNIT
ELEMENT NO NO NO. ACCESSION NO.
060278719 3M162787A879 oc 175
(U) The efficacy of Dexedrine for the sustainment of helicopter pilot performance during
64 hours of continuous wakefulness
12 PERSONAL AUTHOR(S)
J.A. Caldwell; N.K. Smvthe, P.A. LeDuc: B.F. Prazinko; J.L. Caldwell; D.N. Norman; et. al.
13a. TYPE OF REPORT 13b. TIMECOVERED 1 14. DATE OF REPORT (Year, Month, DayJ 1 15. PAGE COUNT
Final FROM TO I 1998 October I 66
16 SUPPLEMENTAL NOTATION
16. SUBJECT TERMS (Continue on reverse if necessary and identify by block number)
//LO1 SZ~~~~;;~S, aviators, in-flight performance, EEG, mood,
I I I
19 ABSTRACT (Continue on reverse if necessary and identify by block number)
The purpose of this investigation was to establish the efficacy of Dexedrine for
sustaining aviator performance despite 64-hours of extended wakefulness. Although earlier
flight studies yielded favorable results with no significant side effects, they were
restricted to sleep-deprivation periods of only 40 hours. Due to requirements for longer
periods of sustained wakefulness, it was necessary to study the efficacy of Dexedrine for
maintaining aviator performance during 3 days and 2 nights without sleep. To accomplish
this, computerized evaluations of aviator flight skills were conducted at regular
intervals as subjects completed standardized flights in a UH-60 helicopter simulator, both
under Dexedrine and placebo. Laboratory-based assessments of cognitive, psychological,
and central nervous system status were completed as well. Dexedrine (10 mg.) was given
prophylactically (prior to signs of fatigue) at midnight, 0400, and 0800 on both
deprivation days in one cycle, and placebo was given on both days in the other.
Results indicated simulator flight performance was maintained by Dexedrine for up to 58
hours, while performance under placebo rapidly deteriorated. The drug was most beneficial
PO_DISTRIBUTION /AVAllABlLlrY OFABSTRACT 21 ABSTRACT SECURITY CLASSIFICATION-
22a NAME OF RESPONSIBLE INDIVIDUAL
DD Form 1473, JUN 86
DTIC USERS Unclasslrled
22b. TELEPHONE (Include Area Code) 22c OFFICE SYMBOL
(334) 255-6907 MCMR-UAX-SS
Previous editions are obsolete. SECURITY CLASSIFICATION OF THIS PAGE
Unclassified

4. 19. Abstract, Continued
at 0500 and 0900 on the first deprivation day, but continued to attenuate
impairments throughout 1700 on the second deprivation day (after 58 hours
awake). Dexedrine likewise lessened the slowing of response times, the
impairments in problem identification, and the reductions in performance
capabilities which were evident in the cognitive data under placebo. The
positive effects of Dexedrine were noticeable after only 22 hours of
sustained wakefulness, but were most evident between 0500 and 1200 on both
deprivation days (the times at which performance under placebo suffered the
most). These were the same times at which the differences between Dexedrine
and placebo were most apparent in the flight data. Dexedrine suppressed the
increases in slow-wave EEG activity (associated with impaired alertness)
which began to occur under the placebo condition after 23 hours of
continuous wakefulness. The medication then attenuated a further increase in
sloti EEG activity that was present throughout 55 hours (and sometimes 59
hours) of deprivation. At the same time, Dexedrine (compared to placebo)
clearly sustained self-perceptions of vigor, alertness, energy, and
talkativeness, while reducing problems with fatigue, confusion, and
sleepiness. Mood declines were observed after 20 hours without sleep under
the placebo condition, and these were followed by further decrements which
were most noticeable after 48 hours of continuous wakefulness. Ratings
actually improved under Dexedrine at several times. Recovery sleep was
slightly less restful under Dexedrine even though the last dose was 15 hours
before bedtime (Dexedrine has an average half-life of 10.25 hours). Thus,
at least two nights of recovery sleep should be required after Dexedrine is
used to maintain alertness for 64 hours.
There were no clinically-significant side effects which caused the
discontinuation of any participant; however, one subject experienced an
increase in diastolic blood pressure that would have been cause for concern
had it not decreased when the subject was retested in a prone position.
Some aviators complained of palpitations and "jitteriness" under Dexedrine,
but this did not detract from their performance. One of the subjects became
very excitable and talkative under the influence of Dexedrine, but he did
not become reckless or dangerous.
In summary, prophylactic Dexedrine administration substantially reduced the
impact of sleep loss in the early morning hours and, for the most part,
preserved performance for the remainder of the day in a 64-hour bout of
continuous wakefulness. The beneficial effects of Dexedrine are most
apparent during the circadian trough where performance and alertness under
placebo are the worst. Thus, when proper restorative sleep is not available
due to operational constraints, Dexedrine should be considered an effective
countermeasure; however, it should not be used as a substitute for sleep.
Proper crew rest management must remain a top priority to preserve our
tactical advantage on the battlefield.

5. Generalobjective . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ..l
Militaryrelevance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ..l
Background . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ..l
Objectives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ...4
Methods ...............................
Subjects .........................
Apparatus ........................
Dosepreparation ............
Physiologicaldata ...........
UH-60 simulator ............
EEG evaluations.............
Desktop flight simulationtask . .
Mood questionnaires.........
Vigilance/cognitive tests ......
Polysomnography ...........
...........
...........
...........
...........
...........
...........
...........
...........
...........
Procedure ......................................
Flight performance.........................
EEG evaluations...........................
Desktopflight simulationtask ................
Mood Questionnaires(POMS andVAS) ........
Cognitive performanceevaluations ............
Polysomnography .........................
Testing schedule...........................
.....................
.....................
.....................
.....................
.....................
.....................
.....................
.....................
.....................
.....................
.....................
.........
.........
.........
.........
.........
.........
.........
.............
.............
.............
.............
.............
.............
.............
.............
. . 4
. . 4
. . 5
. . 5
. . 5
. . 5
. . 5
. . 5
. . 6
. . 6
. . 6
. . . 6
. . . 7
. . . 9
. . 10
. . 10
. . 10
. . 11
. . 11
Dataanalysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ...12
Results ................................................................... ..13
Flightperformancedata.. .............................................. ..13
Straightandlevels(SLs) ........................................... 13
Climbs ....................................................... ..15
Descents.. .................................................... ..15
Left standard-rateturns(LSRTs) ..................................... 16
Right standard-rateturns(RSRTs) .................................... 17
Left descendingturn (LDT) ......................................... 18
EEG ............................................................... ..18
Delta activity .................................................... 19
Theta activity ................................................... .2 1
III

6. le of cm
Alphaactivity.. ................................................ ..2 4
Beta activity .................................................... .27
Desktop flight simulator ................................................ .28
Scores.. ...................................................... ..2 8
Tones ........................................................ ..2 8
POMS.. ............................................................ ..2 9
Tension-anxiety scale............................................. .30
Depression-dejectionscale......................................... .3 1
Anger-hostility scale ............................................. .3 1
Vigor-activity scale .............................................. .3 1
Fatigue-inertiascale .............................................. .32
Confusion-bewildermentscale...................................... .33
VAS ............................................................... ..3 3
MATB ............................................................. ..3 6
Communications ............................................... ..3 6
Resourcemanagement ............................................ .3 8
Systemsmonitoring .............................................. .38
Tracking ...................................................... ..4 0
V~alsignsdata.........................................................4 2
Oral temperature ................................................ .42
Pulse.. ....................................................... ..4 4
Systolicblood pressure ........................................... .44
Diastolic blood pressure........................................... .44
Polysomnographicdata ................................................. .45
Discussion ................................................................ ..4 6
Flight performance ..................................................... .47
MATB anddesktopsimulatortasks........................................ .48
Physiologicalindicesof fatigue/alertness ................................... .48
Self-reportedmood andsleepiness ........................................ .49
Recovery sleep ....................................................... ..5 0
Subjectiveobservations ................................................. .5 1
Summaryandconclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ...53
Acknowledgments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ...54
References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ...54
Appendices
A.Flightmanuevers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ...59
iv

7. e of contents(contmued)
B. Manufacturer’s list . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
List of tables
1. Doseorders .................................................
2. Testing schedule.............................................
3. Statusof the automatictrim systemduringeachupper-air-workmaneuver
4. Scoringbandsfor flight performancedata .........................
...... 60
List of figures
1. Effectsof drugandsession,druganditeration,andsessionon flight performancein
theSLs ............................................................. ..14
2. Effectsof drugandsessionon theclimb ....................................... 15
3. Effectsof thecombinationof drugandsessionandthe effectsof session(with the
otherfactorscollapsed)on performanceof the descents ........................ 16
4. Effectsof the drug andsessioncombinedandsession(with the otherfactorscollapsed)
on the left standard-rateturns ............................................. 17
5. Effectsof drug andsessioncombinedandsession(with the otherfactorscollapsed)
on theright standard-rateturns ............................................ 18
6. Effectsof drugandsessionon the left descendingturn ............................ 19
7. Effectsof eye closureandsessionandthe effectsof eyeclosureanddrugon EEG
deltaactivity...........................................................l 9
8. The effectsof drugandsessionEEG deltaactivity at Fz, Cz, andPz ................. 20
9. Effectsof session(with all otherfactorscollapsed)on EEG delta activity at Fz, Cz,
andPz................................................................2 1
10. The effectsof drug, eye closure,andsessionon EEG thetaactivity at Cz andPz ........ 22
11. Effectsof eye closureandsessionon EEG thetaactivity at Cz. ..................... 22
12. Effectsof drug andsession(with the eyesconditioncollapsed)on EEG thetaat Fz,
Cz,andPz .......................................................... ..2 3
13. Effectsof session(with all otherfactorscollapsed)on EEG thetaactivity atFz, Cz,
andPz ............................................................. ..2 4
14. Effectsof drug, eye closure,andsessionon EEG alphaactivity at Fz andCz .......... 25
15. Effectsof eye closureandsessionon EEG alphaactivity at Fz, Cz, andPz ............ 25
16. Effectsof drugandsessionon alphaactivity at Fz ............................... 26
17. Effectsof session(with all otherfactorscollapsed)on EEG alphaat Fz, Cz, andPz ..... 27
18. Effectsof drugandsessionon betaactivity atPz, andthe effectsof session(with the
otherfactorscollapsed)on betaactivity at Fz ................................. 28
19. Effectsof drug andsession,andsession(with the otherfactorscollapsed)on the
numberof targetsmissedduringthedesktopflight simulationtask ................ 29
20. Effectsof drug andsession,andsession(with the otherfactorscollapsed)on
reaction times to target tones during the desktop simulation task .................. 30
V

8. 21. Effect of session(with all other factorscollapsed)on ratingsof POMS tension ......... 30
22. Effect of session(with all otherfactorscollapsed)on POMS depression-
dejectionratings........................................................3 1
23. Effects of drug and sessionand session(with the other factorscollapsed)on POMS
vigor-activity ratings ................................................... .32
24. Effects of drug andsession,andsession(with the otherfactorscollapsed)on POMS
fatigue-inertiaratings ................................................... .32
25. Effects of drug andsession,andsession(with the other factorscollapsed)on POMS
confusion-bewildermentratings........................................... .33
26. Effects of drug and sessionon VAS alertness,energy,irritability, sleepiness,and
talkativeness...........................................................3 5
27. Effect of session(with the other factorscollapsed)on VAS ratings. .................. 36
28. Effect of sessionon reactiontime for correctresponses,standarddeviation of
reactiontime, andtime out errorsin the MATB communicationstask .............. 38
29. Effects of drug and sessionon reactiontimes to lights anddials andtime outsfor
lights and dialson the MATB systemsmonitoring task ........................ .39
30. Effect of session(with the other factorscollapsed)on reactiontimes, standard
deviation of reactiontimes, andtime out errorsin the MATB systems
monitoringtask ...................................................... ..4 0
31. Effects of drug and session,and sessionwith the other factorscollapsedon the
MATB tracking task ................................................... .42
32. Effects of drug andsessionon temperature,pulse,andblood pressure............... .43
33. Effect of Dexedrine andplaceboon latencyto sleeponsetand sleepefficiency ........ .45
34. Effects of Dexedrine andplaceboon sleeparchitecture(minutes in eachstageand
percentageofeachstage).................................................4 6
35. Effects of Dexedrine andplaceboon the latencyto REM sleeponset ................ .46
vi

9. .
al oblecttve
The purposeof this investigationwasto establishthe efficacy of Dexedrine for sustaining
aviatorperformancedespiteextendedwakefulness(64 hours). Although an earlierin-flight study
andtwo laboratorystudiesof Dexedrineyielded favorableresultswith no significantsideeffects,
theseinvestigationswere restrictedto 40 hoursof continuouswakefulness. Due to requirements
for longerperiodsof sleepdeprivation,it wasconsideredimportantto studythe efficacy of
Dexedrine in termsof maintainingaviatorperformanceduring64 hourswithout sleep.
To explorethe efficacy of lo-mg dosesof Dexedrine for the sustainmentof alertnessduring3
daysand2 nightsof continuouswakefulness,computerizedevaluationsof aviatorflight skills
were conductedat regularintervalsassubjectscompletedstandardizedflights in a UH-60
helicoptersimulator. Laboratory-basedassessmentsof cognitive, psychological,andcentral
nervoussystemstatuswere conductedaswell.
Currentmilitary doctrinerequiresthatArmy aviationunitsoperatearoundthe clock during
timesof conflict becausesuccesson thebattlefielddependson maintainingthemomentum of
continuousday-nightoperations(Departmentof theArmy, 1997). In part, dueto the significant
improvementin night fighting capabilityofferedby night vision devices,night helicopter
operationsnow constitutea substantialcomponentof themodernaviationmission. Combining
efficient day andnight fighting capabilitiesacrosssuccessive24-hour periodsplacesa significant
strainon enemyresourcesandpresentsa cleartacticaladvantagefor U.S. forces.
However, therearedifficulties inherentin maintainingeffective around-the-clockoperations.
Although aircraftcanfunction for extendedperiodswithout adverseeffects,humanoperators
needperiodic sleepfor therestorationof bothbody andbrain(Home, 1978). Depriving humans
of properrestorativesleepproducesattentionallapsesandslowerreactiontimeswhich are
associatedwith poorperformance(Krueger, 1989).
Becauseit is virtually impossiblefor aviatorsto receiveadequatesleepandrestduring
combatoperations(especiallyin this eraof personnelforcereductions),it is essentialthatthe
military explorecountermeasuresto offsettheperformancedecrementsassociatedwith sleep
debt. Given thatpersonnelnumbersaredwindling while missiondemandsareexpanding,
pharmacologicalstimulantsmay be theonly viable alternativein somesituations.
Around-the-clockoperationsarecommonplacein modem societydueto technological
advancesandindustrial/economicdemands. In themilitary, 24-hour-per-dayactivitiesoften are
unavoidablebecauseof thetacticalfunctionthey serve. By requiringthe enemyto maintain a
defensive posture throughout the day and night, enemy personnel become increasingly sleepy
1

10. and fatiguedto the point of eventualincapacitation. Unfortunately, friendly forcescan sufferthe
samefate,particularly when inadequatenumbersof soldiersareavailable to properly staff
multiple duty shifts. Krueger (1989) reportsthe efficiency of combatantsin sustainedoperations
canbe significantly compromisedby inadequatesleep. Vigilance and attentionsuffer, reaction
time is increased,mood declines,and somepersonnelbegin to experienceperceptual
disturbances.Naitoh andKelly (1993) warn thatpoor sleepmanagementin extendedoperations
quickly leadsto motivational decrements,impaired attention,short-termmemory loss,
carelessness,reducedphysical endurance,degradedverbal communication skills, andimpaired
judgement. Angus andHeslegrave(1985) notethat cognitive abilities suffer 30 percent
reductionsafter only 1 night without sleep,and60 percentreductionsafter a secondnight.
Clearly, sleeplossandfatigue aremajor threatsto unit readinessin the operationalenvironment.
Various strategieshave beeninvestigatedto minimize fatigue-relatedperformance
decrements(Babkoff andKrueger, 1992), but the combatsituationremainsproblematicbecause
it is intenseandunpredictable. As Comum (1994) andAngus, Pigeau, andHeslegrave(1992)
have indicated,despitethe desirabilityof maintaining alertnesswith adequatesleepvia sleep
managementprograms,control of the timing anddurationof sleepperiodsoften is not feasiblein
the operationalsetting. As Caldwell (1992) reported,sleepdeprivationwas a problem for several
Army pilots during Desert Storm eventhoughthe combatperiod was shortand commandersdid
their bestto managethe crew restof aviation andotherpersonnel. It hasbeenreportedthat Air
Force F-1X pilots andC-141 aircrewsdeployedduringthe Gulf War alsosufferedsignificant
fatigue due to inadequaterestandotherfactors(Comum, 1994; Neville et al., 1994).
Becauseoperationalcontraintsfrequentlymake it impossibleto effectively maintain
performancevia sleepmanagement,variousotherstrategieshavebeenexplored.Unfortunately,
studiesof strategiesbasedupon behavioralor environmentalmanipulationshavenot produced
encouragingresults. For instance,brief periodsof exerciseappearto be only temporarily
effective for reducingthe negative effectsof sleeploss(LeDuc et al., 1998; Home andReyner,
1995a;andAngus et al., 1992). Noise andcold air seemto be eithertotally ineffective or, in the
caseof loud music, actually distracting(Home andReyner, 1995b). Attempts to attenuate
performanceand/or alertnesslossesby ensuringthephysical fitnessof sustainedoperations
personnellikewise haveproven futile (Angus et al., 1992).
At present,pharmacologicalcountermeasures(stimulants)appearto be the only reliable
method for maintaining performanceduring intenseoperationalscenariosthat involve significant
sleeploss. Despite debateon thistopic, dextroamphetamineprobably is one of the best
alternativesavailablebecauseits actionsarewell understoodandits effectivenessin sleep-
deprivedpersonnelhasbeen established.Caffeine, althougheasyto acquireand socially
acceptable,appearssuitablefor sustainingalertnessonly in relatively short(i.e, 37 hour) rather
than long (i.e., 64 hour) periodsof continuouswakefulness(Lagarde andBatejat, 1995). Also,
while caffeine is consideredby someto bepreferableto amphetaminefor promoting alertnessin
sleep-deprivedindividuals, othershave concludedthat caffeine is less-effectiveandmore prone
to produceunwantedsideeffectsthan amphetamine(Weiss andLaties, 1967). Modafinil, a new
psychostimulant,may eventually prove efficaciousfor sustainingperformancein prolonged
periodsof total sleeploss(LagardeandBatejat, 1995); however, this substanceis not yet
2

11. availablein theUnited Statesandtestingin militarily-relevant contextsis lacking. Thus, at
present,it appearsthatamphetaminesoffer the greatestpotential for counteractingperformance
decrementsattributableto sustainedoperations.
Laboratoryinvestigationshaveshownthatmethamphetaminesubstantiallyreducesfeelings
of fatigueanddifficulties in spatialprocessingduring60 hoursof work with only limited sleep
(Shappell,Net-i,andDeJohn, 1992). Single doses(20 mg) of dextroamphetaminehavebeen
shownto returncognitiveperformanceto baselinelevelsandmaintain thisrecoveryafter48
hoursof total sleepdeprivation(Newhouseet al., 1989). In addition,a single20 mg dosehas
beenfound to temporarily preventperformancedecrementsin subjectskept awake for
approximately34 hours(Pigeau,et al., 1995). Multiple IO-mg dosesof dextroamphetamine,
administeredprophylactically, areknown to sustaintheperformanceof helicopterpilots
throughout40 hoursof continuouswakefulness(Caldwell et al., 1995; Caldwell, Caldwell, and
Crowley, 1996; andCaldwell andCaldwell, 1997a). In eachof thesecases,unwantedside
effectswere minimal (mostoften consistingof cardiovascularstimulatoryeffectsratherthan
psychologicalor cognitive disturbances)andof little or no consequencein healthy young adults.
Although thereis a widely held view thatamphetaminesleadpersonnelto becomerecklessand
overconfident,the studiescited abovereportedno indicationof increasedrisk-takingbehaviors
or overestimationof performancecapabilitiesin subjectsgiven dextroamphetamine,a finding
which hasbeenconfirmed elsewhere(Higgins et al., 1975; BaranskiandPigeau, 1997). Thus,
amphetamineadministrationseemsa logical choicefor maintainingtheperformanceof aviators
who aredeprivedof the opportunityto sleep.
In the operationalenvironment,it hasbeenreportedthatEF-1 11A Ravenjet crewswho were
administered5 mg Dexedrine duringanAir Forcestrikeon Libya in April of 1986, were ableto
overcomethe fatigueof themissionitself andthe sleepdeprivationwhich occurredduringearlier
preparationfor themission(Senechal,1988). Therewere no in-flight or landingproblems,and
all of theseaircraftreturnedsafelyto base. F- I5C pilots, flying lengthycombatair patrol
missionsduring OperationDesertShield/Stormwhile sufferingfrom sleepdeprivationand
circadiandisruption,alsobenefitedfrom theuseof 5 mg tabletsof dextroamphetamineon an“as
needed”basis(Comum, 1992). The medicationwasfoundto effectively sustainperformance,
andin fact,the unit commanderultimately concludedthatdextroamphetamineadministration
contributedsignificantlyto the safetyof air operations.There were no reportedadverseeffects,
evenin personnelwho took 10 mg at a time, andno aviatorsreporteda needto continuethe drug
onceproperwork/sleepscheduleswere reinstated. This agreeswith theresultsof a largesurvey
of Air Forcepilots (at the conclusionof the Gulf War) which indicatedthat dextroamphetamine
washelpful in maintaining acceptablemissionperformanceduring sustainedoperationswithout
inducingunwantedsideeffects(EmonsonandVanderbeek, 1993).
Basedon the availableinformation, well-controlled administrationof dextroamphetamine
appearsto be an effective andsafemethodeitherfor recoveringtheperformanceof sleep-
deprivedpersonnelor for preventingfatigue-relateddecrementsin individualswho aredeprived
of adequatesleepdueto operationalconstraints.The performancesustainingactionof lo-mg
dosesof dextroamphetamineis clear,at leastfor relatively shortperiodsof time (40 hours).
What remainsto be determinedis how long dextroamphetaminecanbe expectedto staveoff the
3

12. negativeconsequencesof sleeplossbefore tolerancedevelopsor the drive for sleepoverpowers
the stimulanteffect. The presentinvestigationwasconductedto extendour understandingof the
usefulnessof dextroamphetaminefor maintaining performancein situationswhere more than40
hoursof continuouswakefulnessis required.
Qbi
This investigationexaminedthe effectsof Dexedrine for safely sustainingalertnessand
performanceof helicopterpilots despite64 hourswithout sleep.The primary objective wasto
determinewhetherprophylacticand frequentamphetamineadminstrationcould successfully
preventthe declinesin mood andperformanceexpectedto result from an extendedperiod of
continuouswakefulness. The studyemployed a variety of assessmentsto determinethe effects
of repeatedlo-mg dosesof Dexedrine versusplaceboon: fright performance measuredin a UH-
60 helicoptersimulator,central nervoussystem(CNS)function measuredby resting
electroencephalograms(EEG), psychomotorskill and attentionmeasuredby a desktopflight
simulator,moodmeasuredby the Profile of Mood States(POMS) and Visual Analog Scales
(VAS), vigilance& cognitiveskill measuredby the Multi-Attribute Test Battery (MATB), and
sleeparchitecturemeasuredby polysomnography.
Subjects
Five male and 1 female UH-60 qualified andcurrentaviatorswere recruitedto residein the
U.S. Army Aeromedical ResearchLaboratory(USAARL) testfacility for a period of 10 days
each. The mean agewas 33.3 years(ranging from 27-40), themean body weight was 173
pounds(ranging from 135 to 214), andthe mean total flight time was 1245 hours(ranging from
200-2700). Aviators were individually testedon the designatedtaskswhile remaining in the
Laboratorythe entiretime. Subjectswere requiredto passa medical evaluationwhich included a
review of medical recordsanda face-to-faceinterview with a flight surgeonprior to study
enrollment. The one female was given a pregnancytest(which wasnegative). Exclusionary
criteriawere currentsignificantillnessesof any type, pastpsychiatricproblems, sleepdisorders,
or any medical condition which would have interferedwith participation. None of the subjects
who were screenedwere rejected. Subjectswere not permitted to consumealcohol, caffeinated
beverages,or any type of medication (otherthanDexedrine, placebo,acetaminophen,or
ibuprofen) for the durationof theprotocol. Participantswho indicatedthey were caffeine users
during initial telephonicinterviews were askedto significantly reduceor completely eliminate
caffeine consumptionbeginning severaldaysprior to the study,althoughat leasttwo of the
volunteersobviously failed to heedthis advice(they both experiencedheadachesduring the first
3 daysof their participation). There was one subjectwho usedsmokelesstobacco;however, he
apparentlydiscontinuedthis habit during theprotocol (despitebeing told that he would be
allowed to usetobaccoduring the breaksbetweentestsessions).
4

13. Apparatus
Two orangegelatincapsuleswere administeredat eachdosetime with approximately8 oz. of
orangejuice. Eachof the activecapsulescontainedone 5-mg tabletof Dexedrine, andthe
placebocapsulescontainedonly lactosepowder. Ten mg doseswere usedbecauseoperational
experienceandpreviousinvestigationssuggestedthat5 mgswould be insufficient. Dosage
levelswere not adjustedaccordingto thebodyweightsof subjectssinceit is unlikely thatdose
titrationwould be performedin a field environment.
Oral temperatures,pulse,andbloodpressuredatawere collectedwith an IVAC vital signs
monitor (Model number4200).*
60 simulator
All simulatorflightswere conductedin a specially-instrumentedWI-60 flight simulator
which wasequippedwith a standardcomputer-generatedvisual display(setfor standarddaytime
flight), a six-degree-of-freedommotion base,anda multi-channeldataacquisitionsystem(for
analyzingvariousaspectsof simulatorcontrolsuchasheading,airspeed,andaltitudecontrol).
Digitized flight performancedatawere collectedandstoredon a Digital Equipment Corporation
VAX computerfor subsequentstatisticalevaluation.
FEG evaluations
The EEG evaluationsconductedduringeachsubjects’waking periodswere performedwith a
Cadwell Spectrum32 neurometricanalyzer. This devicecollected7 channelsof EEG datawhich
were storedon optical disk for subsequentanalysis. For the collectionof restingEEG, the low
filter wassetat 0.53 Hz, thehigh filter wassetat 70 Hz, andthe 60 Hz notchfilter wasused.
The desktopflight simulationtaskconsistedof the Microsoft Flight Simulator4.0@,
combinedwith a custom-designed,timed flight course(Microsoft Aircraft andScenery
Designer@).This taskwasrun on a 486 computerwith VGA graphics. Flight controlwas
accomplishedvia a Virtual Pilot flight yoke (CH Products’). During eachof the desktopflights,
toneswere presentedat 8 secondintervals. Forty percentwere targettones(6000 Hz) which
requiredthe subjectto pressa responsebutton,and60 percentwere non-targets(5000 Hz) which
requiredno response.Thesetoneswere generatedusinga Coulboume Modular Instrument
system. This samesystemwasusedto tally numbersof correctresponsesandreactiontimes.
* Seemanufacturers’list

14. Changesin mood were assessedwith the POMS (McNair, Lot-r,andDroppleman, 1981) and
VAS (Penetaret al., 1993). The POMS is a 65item paperandpencil testwhich measuresaffect
or mood on six scales: 1) tension-anxiety,2) depression-dejection,3) anger-hostility,4) vigor-
activity, 5) fatigue-inertia, and6) confusion-bewilderment. The answerswere scoredby hand
usingscoringtemplates.The VAS consistedof eight 100 mm lines centeredover the adjectives
“alert/able to concentrate,”“anxious,” “energetic,”“feel confident,” “irritable,” ‘jittery/nervous,”
“sleepy,” and“talkative.” At the extremesof eachline, “not at all” and “extremely” were printed
respectively. Subjectswere askedto indicatehow they felt by placing a mark along eachof the
lines. Scoresconsistedof the distanceof the mark from the left end of the line (in mm).
Changesin basiccognitive abilitieswere examinedwith the MATB, a computer-based,
aviation-related,synthetictaskbatterywhich wasdevelopedby NASA researchers(Comstock
andAmegard, 1992). The testwas implemented on a 486 computerequippedwith a game card
(Gamecard3, C.H. Products),a voice synthesizercard(Soundblaster16, Creative Lab.), stereo
speakers(Altec Lansing), ajoystick (Advance Gravis Computer Tech. LTD), and a standard
keyboardandcolor monitor. The testrequiredsubjectsto perform a tracking taskconcurrent
with monitoring simulatedindicatorsof fuel levels,pump status,engineperformance,andother
aspectsof “aircraft status.”Also, subjectswere requiredto periodically changeradio frequencies
asinstructedvia computer-generatedverbal commands.
Evaluationsof whether subjectswere experiencingsleepdisturbancesasa function of drug
and/or long-term wakefulnesswere made during subjects’recovery sleepperiodsusinga Nihon
Kohden electroencephalograph(model No. EEG-4321P). The EEG datawere collectedusinga
subsetof the sameelectrodesattachedfor the recordingof the waking EEG (C3, C4,01, and02,
referencesto contralateralmastoids,Al/A2). Four additionalelectrodes(SensorMedics),affixed
with adhesivecollarsimmediately prior to each=sleepperiod, were usedto collect
electrooculographic(EOG) andelectromyographic(EMG) data. The time constantfor the EEG
channelswas setat 0.3, andthe high filter was setat 35 Hz. For EOG (recordedfrom the outer
canthusof eacheye), the time constantwas 5.0 andthehigh filter was setat 10 Hz. For EMG
(recordedwith submentalelectrodes),a time constantof 0.003 and a high filter settingof 120 Hz
was used. The chartspeedwas 10 mm per second.
Procedure
Training sessionswere conductedat 0900, 1300, and 1700 on Tuesday-l following the
administrationof a 2.5 mg testdoseof Dexedrine. Vital signs,collectedbetweenthe tasksin
eachsession,were monitored closelyon this day. On Wednesday-l (control), Saturday-l
(recovery), and Sunday-2 (control), testingsessionsalsobeganat 0900, 1300, and 1700. On
Thursday-l andFriday-l (the first deprivationdays),andon Monday-2 andTuesday-2 (the
6

15. secondsleepdeprivationdays),testingsessionswere conductedat 0100, 0500, 0900, 1300, and
1700. On Thursday-l, Friday-l, Monday-2, andTuesday-2,drug or placebodoseswere
administered. On both daysof eachseries,doseswere administeredat 0000, 0400, and0800. At
eachdosetime, the subjectreceived2 orangecapsulescontainingeither 5 mg Dexedrine each
(for a total of 10mg per 2-capsuledose),or lactose. The medications/placeboswere
administeredwith 8 ouncesof orangejuice. The doseadministrationschemewasdoubleblind
andcompletely counterbalanced(seetable 1).
Doseorders.
Subjectnumber Dose for first deprivationperiod Dose for seconddeprivationperiod
1 Dexedrine Placebo
2 Placebo Dexedrine
3 Dexedrine Placebo
4 Dexedrine Placebo
5 Placebo Dexedrine
6 Placebo Dexedrine
A generaloverview of the testingscheduleanddose-administrationinterval is presentedin
table2. Note thatcounterbalancingwasusedin the actualstudy. Within eachtestperiod,there
were severaltaskspresentedin a standardizedorder. Eachtestsessionbeganwith a 1-hour flight
in theUH-60; continuedwith a restingEEG, thedesktopsimulator,the POMS andVAS; and
thenendedwith administrationof the MATB. The individual tasksarediscussedbelow.
Testing schedule.
Tune Mon-I Tue-I Wed-l Thu- I Frl-I Sat-l Sun-2 Mon-2 Tue-2 Wed-2
0000
0400
0800
1200
1600
2000
Sleep Sleep Sleep Sleep Sleep
h h DRUG DRUG h
h PLAC PLAC *
I h Test Test h h Test Test h
h h DRUG DRUG h
h PLAC PLAC h
h h Test Test h h Test Test h
Test Dose DRUG DRUG PLAC PLAC Disconn
Training Test Test Test Test Test Test Test Release
Trammg Test Test Test Test Test Test Test
Start Training Test Test Test Test Test Test Test
Bedtime Bedtime Bedtime Bedtlme Bedtime
The flight evaluationsrequiredsubjectsto perform a variety of precisionmaneuversof the
type typically flown in a UH-60 (seeappendixA). This flight profile consistedof four hovers
followed by low-level navigationto five checkpointsandupper-air-workin which the subjectwas
requiredto perform precisionmaneuversbaseduponinstrumentinformation. Eachflight
concluded with a formation segment in which the subject followed a lead aircraft. For the
7

16. presentreport, only the resultsfrom the upper-an-workmaneuversarepresented. All flights were
flown undersimulateddaylight conditionsregardlessof the time of day. The maneuversare
fully describedin the Aircrew Training Manual (Department of the Army, 1996).
There were a total of 15 upper-an-workmaneuversin the profile. These consistedof four
straight-and-levels,two left standard-rateturns,threeright standard-rateturns,two standard-rate
climbs, three standard-ratedescents,andone left descendingturn. Some of thesemaneuvers
were flown with the automatictrim systemengagedwhile otherswere flown with the trim
systemoff (seeTable 3). During eachmaneuver,the subjectswere requiredto maintain an
airspeedof 120 knots,but the specifictargetsfor otherparameterssuchasheading, altitude, roll,
slip, etc., changeddependingupon which maneuverwasbeing flown. However, subjectsalways
attemptedto maintain appropriateideal flight parametersduring eachmaneuver.
le 3,
Statusof the automatictrim systemduring eachupper-airwork maneuver.
Maneuver AFCS On/Off
Straightandlevel number 1 On
Left standard-rateturn number 1 On
Straightand level number2 On
Climb number 1 On
Right standard-rateturn number 1
Straightand level number 3
Right standard-rateturn number2
Climb number 2
Descentnumber 1
Left descendingturn
Descentnumber 2
Left standard-rateturn number2
Straightand level number4
On
On
On
On
Off
Off
Off
Off
Off
Right standard-rateturn number 3
Descentnumber 3
Off
Off
The flight lastedapproximately 1 hour. Each flight wascoordinatedandcontrolledby one of
two consoleoperatorswho instructedthe subjectsthroughthe standardizedmaneuversin a
uniform fashion(in fact, the flights of five of the six volunteerswere conductedby the same
operator). Consoleoperatorsensuredthat subjectswere flying correctheadings,altitudes,
airspeeds,etc.,prior to marking the beginningof eachmaneuverto minimize problemswith
largeoffset errorsattributableto improper setup. Consoleoperatorsattemptedto maintain a
quiet environment in the cockpit throughouteachflight; however, they did respondto subjects’
attemptsto converseandoccasionallyinitiated conversationin orderto maintain the motivation
and alertnessof volunteers. In the few instanceswhere subjectsfell asleep(or becamedrowsy
to thepoint of total inattention) during the executionof a flight maneuver, the consoleoperator
would awakenthe volunteer at the conclusionof the maneuver’s allotted time or when a
determinationwas made thatthe maneuverwould not be completedwithout operator
8

17. intervention. For instance,if the maneuvercalled for a climb from 2000 feet to 2500 feet,but
insteadthe subjectleveledoff at 2300 feet becauseof sleepiness,the consoleoperatorwould
remind the subjectof the targetaltitudeonceit wasapparentthatthe subjectwould not complete
themaneuverindependently.
Baseduponthedatacollectedbetweenthestartandstopmarkersthroughoutthe flight
profile, the computercalculatedflight scoresrangingfrom O-l00 (with 100 reflecting near
perfectaccuracy)for a variety of measureswithin eachof themaneuvers. Thesescores,based
uponthe extentto which subjectsdeviatedfrom targetvalues,expressedhow well subjects
maintainedspecificheadings,altitudes,airspeeds,andotherparameters.The scoringbandsfor
eachparameteraredepictedin table4. Individual parameterscoresfor eachmaneuverwere then
averagedtogetherto produceonecompositeflight scorefor eachiterationof eachmaneuver,and
thesecompositescoreswere analyzed.
Iable 4.
Scoringbandsfor flight performancedata.
Maximum deviationsfor scoresof:
Measure(units) 100.0 80.0 60.0 40.0 20.0 0
Heading (degrees) 1.0 2.0 4.0 8.0 16.0 > 16.0
Altitude (feet) 8.8 17.5 35.0 70.0 140.0 > 140.0
Airspeed(knots) 1.3 2.5 5.0 10.0 20.0 > 20.0
Slip (ball widths) 0.0 0.1 0.2 0.4 0.8 > 0.8
Roll (degrees) 0.8 1.5 3.0 6.0 12.0 > 12.0
Vertical Speed(feet/m) 10.0 20.0 40.0 80.0 160.0 > 160.0
Turn Rate (degrees/s) 0.3 0.5 1.0 2.0 4.0 > 4.0
FEG evaluations
EachEEG sessionlastedapproximately20 minutesandbeganwith a checkto ensure
electrodeimpedanceswere 5000 Ohmsor less. Any impedanceproblemswere correctedby
rotatinga bluntedneedlegently insideof theproblem electrodeuntil an adequatesignalwas
obtained. The subjectsthenwere instructedto relax andfocuson a fixation point for 1.5minutes
duringwhich datawere collectedwith eyesopen. This was followed by 1.5 minutesof eyes
closed. Therewere threecompleteiterationsof thisprocedure(eyesopen followed by eyes
closed)duringeachtestsession.Data were recordedfrom Fz, C3, Cz, C4, Pz, 01, and02
referencedto linked mastoids(Al andA2).
The EEGs for eyes-openandeyes-closedwere visually scannedfor threerelatively artifact-
free 2.5-secondepochs(per eyes-openandeyes-closediteration)onwhich absolutepower values
were calculatedfor eachof four bands. The resultswere averagedto produceone setof power
valuesfor eachelectrodesiteundereyesclosedandeyesopen. The activity bandswere defined
asfollows: delta(1.0-3.5 Hz), theta(3.5-8.0 Hz), alpha(8.0-13.0 Hz), andbeta(13.0-20.0 Hz).

18. Following the EEG, subjectscompleteda 30-minute sessionon the desktopflight simulator.
This taskrequiredsubjectsto fly a timed courseconsistingof 21 “gates”positionedat various
altitudesandheadings. The first 15 gateswere flown undernonturbulentconditions,while gates
16-21 were made more difficult by the addition of 20-knot winds emanatingfrom various
directions. While subjectswere flying the desktopsimulator,they were presentedwith high and
low tonesat 8-secondintervals. The high tonesrequiredsubjectsto pressa button locatedon the
controlyoke. The low tonesrequiredno response.
This taskproduceda summaryscoreat the conclusionof each“flight.” The scorewas
calculatedautomatically from the elapsedtime it took to fly the course,the number of gates
missed,andthe precisionwith which the subjectsflew througheachof the gates. The reaction
times to toneswere automaticallyprinted from a solid-statemodular programming system(and
averagesfor eachsessionwere calculatedvia a computerspreadsheet).
Mood Questionnaires(POMSand VASJ
The POMS was given shortlyafter eachdesktopflight simulation test. Subjectswere
presentedwith a seriesof 65 wordswhich describedmood states,and for each“mood state,”the
subjectindicatedon a standardizedanswersheethow well it describedthe way he/shewas
presentlyfeeling. This testtook approximately5 minutesto administerandyielded scoreson the
six factorsmentionedpreviously. The VAS was given afterthe POMS. Subjectswere presented
with eight adjective/descriptorsandaskedto indicatehow eachrepresentshow they were
currently feeling. This testtook approximately2 minutesto administerandyielded scoreson the
scalesdescribedearlier.
ive nerfannance evW
Following the POMS andVAS, subjectscompleteda 30-minute sessionon the MATB. The
MATB included a resource(fuel) managementtask,a communicationstask, a systems
monitoring task, andan unstabletrackingtask,eachof which waspresentedin a separate
quadrantof the computerscreen. Subjectswere instructedto perform the tracking taskwhile
simultaneouslymonitoring systemstatusandcommunicationchannelsandmanaging fuel
resources.Subjectswere not told that any onetaskwasmore or lessimportant than another,nor
were they advisedabouthow they shoulddivide their attentionamongthe different subtasks.
The communicationstaskrequiredsubjectsto respondonly to the call sign“NGT504”
(presentedover the speakers)andto make the instructedfrequencychangeon a simulated
Navigation and/or Communication radio. The Up andDown arrow keys on the keyboardwere
usedto move from “NAVl” through“COM2,” andtheLeft andRight arrow keys were usedto
changefrequency. The Enter key waspressedto acknowledgea completed frequency
adjustment. The resource(fuel) managementtaskrequiredsubjectsto maintain tanksA andB at
2500 units each(indicatedby numbersbelow the tanksandby a tick mark in the shadedbar on
the sidesof the two tanks). This was accomplishedby turning on or off any of the pumpslabeled
10

19. 1through8. Fuel wastransferredinto thetanksby activatingor deactivatingpumpsusing
correspondingnumberkeys. Periodically, a pump failure occurredandthepump turnedred,but
subjectswere taughtto correctthisproblemby pressingcontrol/K. The systemmonitoring task
requiredthatsubjectsattendto four gauges(dials)marked Fl, F2, F3, andF4; andtwo boxes
(lights) markedF5 (usuallygreen)andF6 (usuallyblank) on the computerscreen. Subjectswere
to pressF.5if the F5 box wasno longergreenandtheF6 key if the F6 box turnedred. They
were to pressthe correspondingF key wheneveroneof thepointersin the dialsdeviatedmore
thantwo minor or one major tick mark(s) aboveor below themid-line. The trackingtask
requiredsubjectsto usethejoystick to keep a targetin the centerof itswindow within thedotted
linesthat formed a rectangle.
In theresource(fuel) managementtask,eitherpump 2 or 4 failed onceevery 2 minutes. In
the systems-monitoringtask,therewaseithera dial or light indicationrequiringa responsefrom
the subjectthreetimesper minute. In thecommunicationstask,radio messageswere deliveredat
a rateof two messagesper minute. A responsewasrequiredfor half of thesemessages.
The sleeprecordingswere madeon non-deprivationnightswhile the aviatorwassleepingin
a darkened,privatebedroom. Eachnight on which sleepwasallowed, EOG andEMG electrodes
were placed,andthe subjectwasescortedinto his/herbedroomat thepropertime. Then the
electrodeswere pluggedin andthe signalquality waschecked. Afterwards,the lightswere
turnedout andthe subjectwaspermittedto sleepfor 8 hourswhile electrophysiologicaldata
were recorded. There were four nightsduringwhich polysomnographicdatawere collected. The
firstwasa baselinenight thatoccurredon Tuesday-l (following a Monday-l adaptationnight).
The secondandthird were the recoverynightson Friday-1 andSaturday-1, andthe fourthwas
therecoverynight on Tuesday-2. Data from eachof thesenightswere recordedon a standard
papertracefor analysisaccordingto therulessetforth by RechtschaffenandKales (1968). The
numberof minutesfrom lightsout to the appearanceof stage2 sleep(sleeponset),the numberof
minutesfrom lightsout to the first 2 minutesof REM sleep(REM latency),thepercentageof
time subjectsspentin stagesl-4 andREM sleep,theminutesof movement, andthepercentage
of time subjectswere awakeduringthenight were calculated.
The subjectreportedto the Laboratoryon Monday-l for medical examination,EEG electrode
attachment,andan adaptationsleepperiod. On Tuesday-1, the aviatorreceiveda 2.5mg test
doseof Dexedrine, andwhile he/shewasbeingperiodicallymonitored,he/shecompletedthree
trainingflights in theUH-60 simulator,eachof which wasfollowed by EEG, performance,
mood, andMATB testing. Afterwards,he/sheretiredfor the day (at 2300). On Wednesday-l,
therewere threemore testsessionswhich servedasbaseline(UH-60 simulatorflights, EEG,
performance,mood, andMATB), but the aviatorwasnot allowed to goto sleepin the evening.
Instead,he/shewas given his/herfirst drug/placebodoseat 0000 hoursandsubsequentdoses
were given at 0400, and0800 on Thursday-1. On Thursday-1, testsessionsbeganwith a flight 1
hour aftereachdrug/placeboadministration(for the first threesessions)andtherewere two
11

20. additionalnon-drug sessionsaswell, for a total of five equally-spacedtestsessions(beginning at
0100,0500,0900, 1300, and 1700). The aviatorrepeatedthis testscheduleon Friday-l during
which Dexedrine/placebowas given at 0000,0400, and0800 (this scheme--lastdoseat 0800--
was usedto avoid drug effectsinterfering with recoverysleepon Friday night). Subjectswere
continuouslymonitored during eachdeprivationperiod to ensurethatno sleepepisodesoccurred.
At the end of the day on Friday-l, the aviatorretired at 2300 andhis/her sleepwasrecorded. On
Saturday-l, subjectswere awakenedat 0700, afterwhich he/sheagaincompletedtestsessionsat
0900,1300, and 1700. The secondnight of recoverysleepbeganat 2300. Upon awakeningat
0700 on Sunday-2, subjectsbeganthe next 64-hour deprivationperiod. During this day, the
aviatorrepeatedthe sameschedulewhich wasusedon Wednesday-l when therewere threetest
sessionsduring the day andno sleepwas allowed at night. He/she was given the first dosein
his/her secondseriesof drug/placebodosesat 0000 (midnight). On Monday-2, the subject
repeatedthe Thursday-l schedule,beginningwith his/herfirst flight at 0100 and continuing
throughtestsessionsat 0500, 0900, 1300, and 1700 (with drug/placebodosesprecedingthe first
threesessions).There was no sleepon the night of Monday-2. Instead,subjectswere again
testedat 0100,0500,0900, 1300, and 1700 on Tuesday-2, andDexedrine/placebowas again
given prior to the first three sessions(aswasthe casepreviously). Eight hoursrecovery sleep
waspermitted on thenight of Tuesday-2 at 2300. On Wednesday-2,the aviatorwas awakenedat
0700, evaluated,andreleased.
Pata an&&
The datawere analyzedwith BMDP4V repeatedmeasuresanalysisof variance(ANOVA).
Huynh-Feldt adjusteddegreesof freedomwere usedto correctfor violations of the compound
symmetry assumptionwhere appropriate. Significant interactions(thosewith p valueslessthan
or equalto 0.055) were analyzedusinganalysisof simple effects. In caseswhere drug-by-
sessioninteractionswere found, analysisof simple effectswas usedonly to pinpoint differences
betweenthe two drug conditionsat eachlevel of the sessionfactor(testsfor differencesacross
sessionsat eachlevel of the drug factorwere not conductedfor the reasondescribedbelow). In
caseswhere analysisof simple effectspinpointeddifferencesacrossfactorsconsistingof more
than two levels (except for the sessionfactor),multiple pairwise comparisons(posthoctests)
were performed usingthe F-test (contrast)procedurein BMDP4V. Significant main effectsalso
were examinedwith pair-wisecontrasts(exceptfor sessionmain effects). This exceptionwas
basedon the fact thatthere areat least13 levels of the sessionfactor(for POMS andVAS there
were 16 levels), andconductingall possiblepairwise contrastswould have substantiallyinflated
the chancesof making a Type I error. Instead,sessionmain effectswere followed up with tests
for linear, quadratic,and cubictrendsusingthe contrastprocedurein BMDP4V. Although the
interpretationof main effectsis ill-advised when therearehigher-orderinteractions(Kirk, 1968),
they arepresentedin this report for the sakeof completeness.However, the readershould
exercisecautionwhen interpretingsucheffects.
All datawere analyzedfor the presenceof significantordereffects(i.e., Dexedrine first
versusplacebofirst) by including order asa between-subjectsfactorin eachof the ANOVAs
12

21. describedbelow. However, the small numberof drug-by-orderor drug-by-session-by-order
interactionssuggestedthatordereffectswere not a problem in this study.
All ANOVAs, exceptthepolysomnography,consistedof at leastthe 2 within-subjectsfactors
of drug (Dexedrine,placebo)andsession(3 baseline/controlsessions,5 sessionsfrom the first
deprivationday, and5 sessionsfrom the seconddeprivationday, for a total of 13). This wasthe
casefor themood, cognitive, andvital-signsdata. The flight performanceanalysesincludedan
additionalfactorcalled iteration for maneuverswhich were flown multiple times during each
flight profile (i.e., therewere four straight-and-levels,two climbs,threedescents,etc.).
For thesleepdata,theanalysiswasa one-way ANOVA. This testedfor differencesacross
nights (baseline,Dexedrinerecovery,placeborecovery).
Prior to analysis,the datawere examinedfor completeness,andany missingdatawere
estimatedwith BMDPAM (one of thecontrol-dayflights wasmissingdueto a simulator
malfunction, oneof the MATB testswasmissingdueto a power failure, andseveralof the EEG
valueswere setto missingdueto recordingartifactsin somevolunteers). Generally,however,
thepercentageof missingdatawassmall.
Flight performancedata
The flight performancescoresfrom 3 baselineflights (at 0900, 1300, and 1700) and 10
deprivationflights (0100,0500,0900, 1300, and 1700 on deprivationday 1; and0100,0500,
0900, 1300, and 1700 on deprivationday 2) underthe influenceof placeboversusDexedrine
were analyzedwith a 3-way ANOVA for drug,session,anditeration. The iterationfactorwas
addedto includeeachinstanceof maneuversthatwere conductedmore thanonceduringthe
flight profile.
Analysisof the compositescoresbasedonhow well subjectscontrolledheading,altitude,
airspeed,androll duringthe four iterationsof straight-and-levelflight (the lastof which was
flown without thebenefit of the AFCS trim system)revealedseveralinteractionsandmain
effects. There wasaninteractionbetweendrugandsession(F( 12,48)=2.34, p=.O189)dueto the
factthattherewere no differencesbetweenthetwo drugconditionsat baselineor at 0100 on the
first deprivationday,but substantialimpairmentsunderplaceborelative to Dexedrineoccurredat
0500 and 1300 (pc.05). Although performanceappearedto continueto sufferunderplaceboat
1700 on thisday (seefigure 1, firstpanel), therewasno statisticallysignificantdifference.
However, on the seconddeprivationday, decrementsunderplacebowere marked at 0100,0500,
0900, and 1300. Onceagain,therewasa recoveryin performanceunderplaceboatthe 1700
flight. However, generallyspeaking,flight controlaccuracywaspreservedfrom baselineuntil
the endof deprivationby Dexedrine.
13

22. There was an interactionbetweendrug anditeration (F(3,12)=13.97, p=.OOO3)which analysis
of simple effectsindicatedwas attributableto poorerperformanceunderplaceboversus
Dexedrine at SLs 2-4 (p<.O5),while a similar effect was absentat SL 1. This canbe seenbelow
in figure 1 (secondpanel).
There were main effectson the drug (F( 1,4)=23.61, p=.OO83),session(F( 12,48)=5.39,
p<.OOOl),anditeration (F(3,12)=21.41, p<.OOOl)factors. The drug effect was due to the fact that
performancewas lower overall underplaceboin comparisonto Dexedrine (the meanswere 74.0
vs 80.1, respectively). The sessioneffect resultedfrom thepresenceof significant linear,
quadratic,andcubictrends(pc.05). As canbe seenin figure 1 (third panel), averagingplacebo
andDexedrine conditionsat eachflight showeda generaldecline in control accuracyfrom
baselineto the end of the deprivationperiod which wasparticularly noticeablein the circadian
trough at 0500 and0900 on both deprivationdays(note thatthis wasprimarily due to decrements
underplacebo). The iteration effect occurredbecauseperformanceon SL 1 wasbetterthan
performanceon SLs 2-4 (p<.OS),performanceon SL 2 wasbetterthanperformanceon SL 4
(p<.O5), andperformanceon SL 3 tendedto be betterthanperformanceon SL 4 (p=.O578). The
meansfor the four straightandlevels were 82.5, 77.9, 74.7, and 73.1, respectively.
so
i
60
t
8
In
:: 70
5
E
f 60
a.
6
E
50
40 i
sor
60
!!
8
v)
s 70
f
E‘t
h 60
E
f
50
40 ISL1
l--lIteration
Figure 1. Effects of drug andsession(top left), drug anditeration (top
right), and session(bottom center)on flight performancein the SLs.
1

23. Climbs
Analysisof the compositescoresbasedon heading,airspeed,slip, roll, andvertical speed
controlduringboth iterationsof thismaneuver(one of which wasa 500-foot climb andthe other
of which wasa lOOO-footclimb) revealedthreedrug-relatedeffects. There was an interaction
betweendrugandsession(F( 12,48)=1.96, p=.O501)dueto the absenceof conditiondifferences
prior to the decrementsunderplaceboat 0900 and 1700 on the first deprivationday. On the
seconddeprivationday, flight scoreswere marginally lower underplacebothanDexedrine at
0500 (p=.O569),but therewere no effectsat subsequenttimes (seefigure 2).
90
1 t Dexednne
-C- Placebo
--_) DoseTame
40
-13oo17oo100
BaselIne Depnvation Day 1 Deprwatlon Day 2
Time of Day
Figure 2. Effectsof drugandsessionon the climb.
An interactionbetweendrugandclimb (F( 1,4)=8.36, p=.O445)was attributableto the
differencebetweenplaceboandDexedrineduringthe first (p<.O5),but not the secondclimb.
Aviators flew lesspreciselyunderplacebothanDexedrineonly on the first iterationof this
maneuver(the meanswere 61.4 and70.1, respectively).
Therewas a main effect on the drug factor(F( 1,4)=19.30, p=.Ol 18) which occurredbecause
of anoverall decrementin performanceunderplacebowhich wasattenuatedby Dexedrine. The
meansof theplaceboandDexedrine conditionswere 61.6 vs 67.1, respectively.
Analysisof the compositeof heading,airspeed,slip, roll, andvertical speedscoresfrom the
threedescents(two of which were 500-foot descentsandoneof which was a 1OOO-footdescent,
all flown without the aid of the AFCS trim system)revealedone interactionandtwo main
effects. The interactionwasbetweenthedrugandsessionfactors(F(12,48)=2.73, p=.OO67).
Analysisof simple effectsindicatedfirstthattherewere no differencesbetweenplaceboand
Dexedrine at any of thebaselinesessionsor at 0100 onthe first deprivationday. However,
15

24. performanceunderplacebowaspoorerthanperformanceunderDexedrine at 0500,0900, 1300,
and 1700 on the first deprivation day, andat 0500,0900, and 1300 on the seconddeprivation day
(p<.05). Performancetendedto bepoorer(p=.O563) at 1700 on this day aswell (seefigure 3).
There were main effectson the drug and sessionfactors. The drug effect (F( 1,4)=30.17,
p=.OO54)was due to an overall drop in performanceunderplacebothatwaspreventedby
administrationof Dexedrine (the meanswere 48.8 and 56.2, respectively). The sessioneffect
(F12,48)=3.14, p=.OO23)was attributableto the presenceof linear, quadratic,and cubictrendsin
the data(pc.05). The averagedplacebo/Dexedrinescoresfrom eachof the flights revealeda
generaldecline in performancefrom baselineuntil the end of the deprivation period (seefigure
3). The decrementswere more pronouncedat sometimes than at othersdue to circadianeffects.
Note thatmost of the changesin flight scoreswere the resultof averagingin the placebo
condition, sinceperformanceunderDexedrine did not drop substantially(relative to baseline).
Figure 3. Effects of the combinationof drug and session(left panel) andthe effectsof session,
with the other factorscollapsed,(right panel) on performanceof the descents.
Analysis of the compositescoresbaseduponhow well subjectsmaintained turn rate,
airspeed,slip, roll, andvertical speedduringthe two LSRTs (one of which was a 360-degreeturn
with the AFCS trim systemon andone of which was a 180-degreeturn with the trim systemoff)
showedseveraleffects. There was a drug-by-sessioninteraction(F( 12,48)=2.07, p=.O378)which
was examinedwith analysisof simple effects. This indicatedtherewere no drug versusplacebo
differencesduring any of thebaselinesessionsor the 0100,0500, and 0900 sessionson the first
deprivation day, but therewere differenceslater (seefigure 4). Specifically, flight controlwas
lessaccurateunderplacebothanDexedrine at 1300 (but not 1700) on the first deprivationday
and at 0900, 1300, and 1700 on the seconddeprivationday (~~05).
I
There was a marginally significantdrugmain effect (p=.O640) due to a tendencytoward
pooreroverall performanceunderplacebothanunderDexedrine (the meanswere 61.8 versus
16

25. 68.1). There wasa significantmain effect on the sessionfactoraswell (F( 12,48)=2.59,
p=.OO97).This wasdueto the presenceof a quadraticandcubictrendin the averaged
placebo/Dexedrinescoresat eachtesttime. As canbe seenin figure 4, flight-control accuracy
generallydeclinedfrom baselineto the endof deprivationandwasimpaired more at sometimes
of theday thanat others,probablybecauseof the impactof circadianrhythms. Most of these
changes,however,were attributableto theplaceboratherthantheDexedrine condition.There
wasa main effect on the iterationfactor(F( 1,4)=193.78, p=.OOO2)attributableto better
performanceon the first turn thanthe second(the meanswere 73.1 and 56.9, respectively).
%a-- sm-Im
B&m cppI-mDLy1 oepl@moa/2 B;srllne Cepl-mWl oeplmmory2
lirmdlhy TimofOay
Figure 4. Effects of the drugandsessioncombined(left panel) andsession,with
the otherfactorscollapsed,(right panel)on the left standard-rateturns.
The compositescoresfor the RSRTs (two of which were 180-degreeturnsflown with the
AFCS trim systemoff andone of which wasa 360-degreeturn flown with the trim system
engaged)were basedon the averageof turnrate,altitude,airspeed,slip, androll scores.There
wasa drug-by-sessioneffect (F( 12,48)=2.57, p=.O103)which wasdueto the absenceof a
differencebetweentheplaceboandDexedrineconditionsat baselineandat 0100 on the first
deprivationday followed by severaldrug-relateddifferencesafterward. Specifically,
performanceunderplacebowas lower relativeto Dexedrineat 0500 and 1700 on the first
deprivationday andat 0100,0900, and 1300 on the seconddeprivationday (seefigure 5).
There were main effectson the drug(F( 1,4)=21.25,p=.OlOO),session(F( 12,48)=3.17,
p=.OO22),anditeration(F(2,8)=15.72, p=.O103)factors. The drugeffect wasbecauseof a
decrementin performanceunderplacebothatwasattenuatedby Dexedrine (the meanswere 63.4
and68.2, respectively). The sessioneffect wasdueto significantlinear,quadratic,andcubic
trends(pc.05). The averagedplaceboandDexedrinescoresat eachof the flightsproduceda
performancecurvewhich steadilydeclinedfrom baselineto the endof the deprivationperiod
17

26. (seefigure 5). This wasmore pronouncedat sometimes of day than at othersdue to circadian
factors. The reductionsin averagedperformanceat thesetimes (following baseline)were largely
attributableto problemswithin theplacebocondition, althoughpeformanceunderDexedrine
declinedaswell toward the end of the testingperiod. The iteration effect was attributableto
betterperformanceduring the RSRTs which were shortand flown with the benefit of the AFCS
trim systemthan the one RSRT thatwas longer(a 2-minute, 360-degreeturn) and flown without
the trim systemengaged. The meansfor eachiterationwere 67.0, 68.5, and 61.8, respectively.
70’
60
Figure 5. Effects of drug and sessioncombined(left panel) and session,with
the other factorscollapsed,(right panel) on the right standard-rateturns.
The compositescoreon the LDT was an averageof scoresfor turn rate, airspeed,slip, roll,
andvertical speed. The ANOVA revealedaninteractionbetweendrug and session
(F912,48)=3.38, p=.OO13)which wasdueto the fact thattherewere no differencesbetween
placeboandDexedrine at the 0900 and 1300 flights on thebaselineday, but performancewas
poorerat the end of the placebobaselinethan at the end of the Dexedrine baseline(pc.05).
Flight controlwas clearly affectedby drug conditionduring severalof the deprivation-dayflights
(seefigure 6). Although flight accuracy(placeboversusDexedrine) was not different at 0100 on
the first deprivation day, the scoresunderplacebowere lower thanthoseunderDexedrine at
0500 (p<.O5),marginally lower at 0900 (p=.O653), andsubstantiallylower at 1300 (~~05).
Theseplacebo-relateddecrementswere not presentat 1700 or in the next flight which occurredat
0100. However, at 0500 and 0900 on the seconddeprivationday, flight control againdeclined
underplacebowhereasDexedrine attenuatedthis effect. There were no significantdifferences
betweenthe two drug conditionsat 1300 or 1700.
EEG
.
The absolutepower datafrom therestingeyes-open/eyes-closedEEG was analyzedin four
partsusinga seriesof 3-way ANOVAs (one eachfor delta, theta,alpha, andbeta activity).
18

27. Although the initial datasetconsistedof EEG recordingsfrom Fz, C3, Cz, C4, Pz, 01, and02,
only a subsetof theseelectrodeswere analyzedbecauseof thepresenceof recordingaritifacts
(primarily from muscle-activitycontamination). Visual inspectionof datafrom all sites
indicatedthatEEG activity from Fz, Cz, andPz wasof sufficientquality to warrantfurther
analysis(at themost, about 17percentof thedatawascontaminatedat someof the testingtimes,
andtheseinstanceswere setto missingin the datafile andthen estimatedusingthemean of the
“clean” databeforetheANOVAs were performed). The ANOVAs consistedof threefactors:
condition(placeboversusDexedrine), session(1015, 1415, and 1815 on baseline;0215,06 15,
1015, 1415, and 1815 on deprivationday 1;and0215,0615, 1015, 1415, and 1815 on
deprivationday 2), andeyes(eyesopen/eyesclosed).
70
E
s
in
i? 60
ii
E
s 50
L?
ii
.f
ii
40
30 '
I, II
900 1300 1700 100 500 900 1300 1700 100 500 900 1300 1700
BaselIne Deptivatm Day1 Depnvabon Day2
Time of Day
Figure 6. Effectsof drugandsessionon the left descendingturn.
Analysisof deltaactivity (1.5-3.0 Hz), the slowest-waveEEG indicative of fatigueor
sedationin awakesubjects,revealedseveraleffects. A session-by-eyesinteractionat Fz
(F( 12,48)=2.04, p=.O403)wasdueto significantdifferencesin the delta activity recordedunder
eyesopenversuseyesclosedat everytestingtime except0215 and 1015 on the first deprivation
day and 1415 on the seconddeprivationday. However, ascanbe seenbelow, thepatternof
effects(increaseddeltaasa functionsleepdeprivation)wasquite similar regardlessof whether
eyeswere openor closed. There wasa drug-by-eyesinteractionaswell atFz (F( 1,4)=7.99,
p=.O475). Thiswasdueto the factthat,althoughtherewasmore delta activity underplacebo
thanDexedrineboth with eyesopenandwith eyesclosed,the differencewas largerwith eyes
closed(pc.05). Both the session-by-eyesanddrug-by-eyesinteractionsaredepictedin figure 7.
19

28. Time of Day Eye Condition
Figure 7. Effects of eye closureand session(left panel) andthe effects
of eye closureanddrug (right panel) on EEG delta activity.
There were drug-by-sessioneffectsat Fz (F( 12,48)=2.50, p=.O124), CZ (F( 12,48)=2.15,
p=.O303), andPz (F( 12,48)=2.10, p=.O352). Analysis of simple effectsshowedthat at every
recordingsite,therewasmore delta underplacebothanDexedrine at 0615 and 1415 on the first
deprivation day andat 0215, 1015, and 1415 on the seconddeprivation day (pc.05 exceptfor Fz
delta at 1415 andPz delta at 1015 where thep valueswere .0665 and .0618, respectively). These
interactionsaredepictedin figure 8.
Time of Day Time of Day
Figure 8. The effectsof drugandsessionEEG delta activity at
Fz (top left), Cz (top right), andPz (bottom center).
20

29. There were main effectson the drug factorat Fz (F( 1,4)=11.58, p=.O272), Cz (F( 1,4)=12.67,
p=.O236),andPz (F( 1,4)=11.12, p=.O290)attributableto higherdeltapower underplacebothan
Dexedrine. There ’ .re main effectson the sessionfactorat Fz (F( 12,48)=6.97, p<.OOOl),Cz
(F(12,48)=7.45, p<.OOOl),andPz (F(12,48)=6.59, p<.OOOl)dueto thepresenceof significant
linear,quadratic,andcubictrends(pc.05) at all threesites. As canbe seenin figure 9, therewas
a deprivation-relatedincreasein deltaactivity which wasparticularlypronouncedat 1015 on the
first deprivationday and0615 on the secondday, probablydueto the influence of circadian
rhythms. There wasa main effect on the eyesfactorat Fz (1,4)=16.75, p=.O149), Cz
(F( 1,4)=14.69, p=.O186), andPz (F( 1,4)=9.71,p=.O356),all of which occurredbecausedelta
activity washigherundereyesclosedthaneyesopen.
Figure 9. Effectsof sessionwith all otherfactorscollapsedon EEG
delta activity at Fz (top left), Cz (top right), andPz (bottom center).
Analysisof thetaactivity (3.0-8.0 Hz), which is fasterthandeltabut still consideredto be
slow-waveEEG known to increasewith sleepdeprivation,showedtherewas a 3-way interaction
amongdrug,session,andeyesat Cz (F(12,48)=2.31,p=.O202)andPz (F( 12,48)=2.54, p=.Ol 10).
Analysisof simple effectsrevealeddrug-by-sessioninteractionsbothundereyesopenandunder
eyesclosedat Cz (p<.05), but atPz, therewasa drug-by-sessioninteractiononly undereyes
open(pc.05). Although the interactionsat Cz (within eachof the eyesconditions)appeared
21

30. similar, subsequentanalysesof simple effectsshowedtherewere minor differences. Under eyes
open at Cz, therewasmore thetaunderplacebothanDexedrine at 0615, 1015, and 1415 on the
first deprivation day andmore thetaunderplacebothan Dexedrine at 0215 and 1415 on the
seconddeprivation day (p<.05). Under eyesclosedat Cz, the effectswere similar, but often not
asrobust. There wasmore thetaunderplacebothanDexedrine at 0615, 1015 (p=.O55I), and
1415 on the first deprivation day andat 0215, 1015 (p=.O559), and 1815 on the second
deprivationday. Note that the difference at 1415 that appearedundereyesopenwasnot
significantwith eyesclosed. The interactionat Pz wasmore straightforwardin that therewasno
drug-by-sessioneffect at eyesclosed,whereastherewas one at eyesopen. Under eyesopen,
therewas more thetaunderplacebothanDexedrine at 0615, 1015, and 1415 on the first
deprivation day andat 0215, 1415, and 1815 on the seconddeprivation day. The interactions
betweendrug and sessionasa function of eye closurearedepictedin figure 10.
120
Eves Closed -o-c.?-
Figure 10. The effectsof drug, eye closure,and sessionon EEG
thetaactivity at Cz (top) andPz (bottom).
There was a session-by-eyesinteractionat Cz (F( 12,48)=1.92, p=.O549) becausetherewas
more thetaunder eyesclosedthan eyesopen at every testingsession,with the exceptionof 0215
on the first deprivation day and0215 and 1415 on the seconddeprivation day (seefigure 11).
22

31. rigure 11. Effectsof eye closureandsessionon
EEG thetaactivity at Cz.
There were drug-by sessioninteractionsat Fz (F( 12,48)=2.85, p=.OOSO),Cz (F( 12,48)=2.35,
p=.O183),andPz (F(12,48)=2.05, p=.O396). At eachsite,therewere no differencesbetween
placeboandDexedrineduringbaseline(predrug),but therewasmore thetaunderplacebothan
Dexedrineat 0615 and 1015on the first deprivationday andat 0215, 1415, and 1815 on the
seconddeprivationday (pc.05). In addition,therewasa differenceon the first deprivationday
betweenthe drugconditionsat 1415 for Cz (p<.O5),a marginally-significantdifferenceat 1415
for Pz (p=.O617),andno differenceat 1415 for Fz. On the seconddeprivationday, therewasa
significantdifferenceat 1015 for Fz (pc.05) a marginally-significantdifference for Cz
(p=.O608), dan no difference for Pz. Thesedrug-by-sessioninteractionsareshownin figure 12.
Figure 12. Effectsof drugandsessionon EEG thetaat Fz (top
left), Cz (top right), andPz (bottom center).
23

32. There were main effectson the drug factorat Fz (F( 1,4)=9.74, p=.O355), Cz (F( 1,4)=8.73,
p=.O41S), andPz (F( 1,4)=10.14, p=.O334) due to more thetaunderplacebothan Dexedrine.
There were main effectson the sessionfactorat Fz (F(12,48)=5.95, p<.OOOl),Cz
(F(12,48)=5.60, p<.OOOl),andPz (F(12,48)=5.9& p<.OOOl)attributableto significant linear,
quadratic,andcubictrendsat each(pc.05). As canbe seenin figure 13, therewas a gradual
deprivation-relatedincreasein thetaactivity thatwasmore pronouncedat sometimes than at
othersdue to the influence of circadianfactors. There were main effectson the eyesfactorat Fz
(F(1,4)=24.91, p=.OO75),Cz (F(1,4)=17.76, p=.O135), andPz (F(1,4)=14.51, p=.O190) all of
which were due to increasedthetaundereyesclosedversuseyesopen.
Figure 13. Effects of session(with other factorscollapsed)on EEG theta
activity at Fz (top left), Cz (top right), andPz (bottom center).
Analysis of alphaactivity (8.0- 13.OHz), which is predominantduring relaxedwakefulness
undereyesclosed,but is suppressedduring sleep,indicatedtherewas a drug-by-time-by-eyes
interactionat Fz (F(12,48)=3.56, p=.OOO8)andCz (F(12,48)=2.16, p=.O300). Analysis of simple
effectsrevealedthese3-way interactionswere attributableto the fact thattherewasno drug-by-
sessioninteractionundereyesopen at eitherFz or Cz; however, therewere drug-by-session
interactionsundereyesclosed(~~05). Further analysesshowedtherewere no drug-related
differencesat any of the baselinesessions(predrug)for eitherFz or Cz, but therewas
24

33. substantiallylesseyes-closedalphaunderplacebothanDexedrine at 0615 on the first deprivation
day (pc.05) andat 0215 on the seconddeprivationday (however,this lattereffect for Fz was
only marginally significant,p=.O597). In the lastsessionof the seconddeprivationday, there
wasa reboundeffect at Fz where therewasmore eyes-closedalphaunderplacebothan
Dexedrine(seefigure 14).
Figure 14. Effectsof drug,eyeclosure,andsessionon EEG
alphaactivity at Fz (top) andCz (bottom).
Therewasa session-by-eyesinteractionat Fz (F(12,48)=6.36, p<.OOOl),Cz (F(12,48)=8.45,
p<.OOOl),andPz (F(12,48)=16.07, p<.OOOl). Analysisof simple effectsshowedthat, in most
cases,alphaactivity wasmuch higherwith eyesclosedthaneyesopenduringbaseline,but the
differencebecamesmallerasdeprivationprogressed.There were significantdifferencesbetween
eyesopenandeyesclosedat all threeelectrodesat 1015, 1415, and 1815 duringbaseline,andat
0215, 0615, and 1815 duringthe first deprivationday (also,therewasa similar effect atFz and
Pz at 1415). By the seconddeprivationday,therewere no differencesat any of the sessionsat
Fz, only one at Cz (at 0215), andonly two at Pz (0215 and0615). Thesesession-by-eyeseffects
areshownin figure 15.
Therewas a drug-by-sessioninteractionatFz (F(1,4)=1.98, p=.O476)dueto the factthat
alphawashigherunderplacebothanDexedrineat 1415 on thebaselineday (predrug),but lower
underplacebothanDexedrine at 0615 on the first deprivationday (pc.05). There were no drug-
relateddifferenceselsewhere(seefigure 16).
25

34. limedDay
Figure 15. Effects of eye closureandsessionon EEG alphaactivity
at Fz (top left), Cz (top right), andPz (bottom center).
+ Dexedrme
I I
-0- Placebo
-XD Dose Time
T
Time of Day
Figure 16. Effects of drug andsessionon alphaactivity at Fz.
26

35. There were no main effectson thedrug factorfor alphaactivity. However, therewere
sessionmain effectsat Fz (F( 12,48)=3.12, p=.OO25),Cz (F( 12,48)=5.15, p<.OOOl),andPz
(F( 12,48)=9.76, p<.OOOl). Trend analysisshowedtherewere significantlinear, quadratic,and
cubictrendsat all threerecordingsites. As canbe seenin figure 17, therewas a gradualdecline
in alphaactivity asdeprivationprogressed,but therewererecoverypeaksat about 18 15 on both
dayswith troughsat about 1015 (probablybecauseof circadianrhythms). There were main
effectson the eyesfactorat Fz (F( 1,4)=30.21, p=.OO53),Cz (F( 1,4)=133.78, p=.OOO3),andPz
(F( 1,4)=53.47, p=.OO19),all of which were dueto greateralphaactivity undereyesclosedthan
undereyesopen.
Time of Day Time of Day
Figure 17. Effectsof session(with all otherfactorscollapsed)on EEG alphaat Fz
(top left), Cz (top right), andPz (bottom center).
. .
Beta a.&~@
Analysisof betaactivity (13.0-20.0 Hz), which is the fastesttype of EEG activity typically
analyzed(it occursduringincreasedmentalconcentrationandsometimesappearsto be increased
when contaminatedby muscletension),revealeda significantdrug-by-sessioninteractionatPz
(F(12,48)=2.33, p=.O191)which wasbecauseof lessbetaunderplacebothanDexedrine at 1815
on the first deprivationday andmore betaunderplacebothanDexedrineat the sametime onthe
seconddeprivationday (pc.05). There were no differencesbetweenthe drugconditionsat anyof
the othertimes (seefigure 18).
27

36. There were no drug or eyesmain effectson betaactivity; however, therewas a significant
sessioneffect at Fz (F( 12,48)=2.22, p=.O256) which occurredbecauseof marked quadraticand
cubictrendsin the data(pc.05). As canbe seenin figure 18, betaactivity decreasedfrom base
line to 1015 on the first deprivation day, thenrecoveredslightly before decreasingagainon the
seconddeprivation day.
Time of Day
Figure 18. Effects of drug and sessionon betaactivity at Pz (left), andthe effectsof
sessionwith the other factorscollapsedon betaactivity at Fz (right).
Desktop flight simulator
The desktopflight simulatortaskconsistedof two components. The first wasthe “flight”
portion that yielded a scorebasedon the accuracyand speedwith which subjectsflew the course.
The secondwasthe secondarytaskthat yielded the percentageof targettonesto which the
subjectfailed to respond(percentmisses)andthe reactiontime (RT) to the targettoneshit. Both
componentswere analyzedusing2-way ANOVA for drug (placeboversusDexedrine) and
session(13 levels: 1045, 1445, and 1845 on the baselineday; 0245,0645, 1045, 1445, and 1845
on the first deprivation day; and 0245,0645, 1045, 1445, and 1845 on the seconddeprivation
day).
The ANOVA on the “flight” scoresindicatedtherewere no significant interactionsor main
effects. An examinationof the meansshowedthatperformanceunderplaceboevidenceda slight
tendencyto be lower thanperformanceunderDexedrine, but the variability was far too large for
this difference to attainsignificance.
The ANOVA on the percenttargettonesthatwere missedrevealeda drug-by-session
interaction(F(12,48)=3.34, p=.OO14). Analysis of simple effectsshowedthis was due to the fact
thattherewere no differencesbetweenthe two conditionsatbaseline(predrug),but therewas an
increasein the numberof tonesmissedunderplaceboversusDexedrine at 0645 on the first
28

37. deprivationday andat 0645, 1045, and 1845 (~5.05) on the seconddeprivationday (seefigure
19).
There wasanoverall drug effect (F( 1,4)=20.65, p=.O105) becauseof an increasein the
numberof tonesmissedunderplaceboversusDexedrine(25.6 percentversus18.0 percent). In
addition,therewasa sessionmain effect (F( 12,48)=4.10, p=.OOO2)attributableto significant
quadraticandcubictrendsin the data(~~05). As canbe seenin figure 19, averaged
performancerevealeda circadianeffect which resultedin impairedperformanceat 0245 on the
first andseconddeprivationdays(relative to theothertimes). Note thatthis effect wasdue
largelyto the influenceof theplaceboconditionwhereasDexedrine attenuatedtheseproblems.
75 15 - cloreTOme
I
p 60
E
i
f 45
5I-
t
P&f30
E
E
&n. IS
0
--- -ii%---Depnvam”Day1 Depnvallo”Day2 DepnvatlonDay1
Time of Day
Time of Day
Figure 19. Effects of drugandsessionandsession(with the otherfactorscollapsed)on the
numberof targetsmissedduringthe desktopflight simulationtask.
The ANOVA on the RT to targettonesindicateda drug-by-sessioninteraction
(F( 12,48)=3.40, p=.OO12). Analysisof simpleeffects(comparingplaceboandDexedrine at each
testingtime) showedtherewere no differencesat any of thebaselinesessions,or any of the
sessionsonthe first deprivationday,but RT wassubstantiallyslowerunderplacebothan
Dexedrine(~~05) at 0645 and 1045 on the seconddeprivationday (seefigure 20). There wasno
overall drugeffect on thisvariable,but therewasa sessionmain effect (F( 12,48)=2.51, p=.O120)
which wasdueto thepresenceof significantquadraticandcubictrendsin the data. As canbe
seenin figure 20, RTs decreasedat about1045,probablyasa functionof circadian-related
changesin alertnesson both deprivationdays. RTs in betweenthesetwo times were similarto
thoseon thebaselineday (beforethe subjectswerewell-trained on thetask). This effect should
be interpretedcautiouslysincetherewasa higher-orderinteractionon RTs (behaviorunder
Dexedrinewasdifferent thanbehaviorunderplacebo).
POMS
The factorscorescollectedduring4 baselinesessions(1120, 1520, 1920, and2340) and 12
deprivationsessions(0320,0720, 1120, 1520, 1920, and2340 on deprivationday 1; andat 0320,
0720, 1120, 1520, 1920, and2225 on deprivationday2) underthe influenceof placeboversus
Dexedrine were analyzed in a series of 2-way ANOVAs for drug and session. The 2340 scores
29

38. andthe 2225 scoresfor eachscalewere placed in the samelevel of the sessionfactor for easeof
analysis(the earliertesttime at the end of deprivationday 2 wasnecessaryto ensurethat subjects
could initiate recovery sleepby 2300). Eachof the factors(tension-anxiety,depression-
dejection,anger-hostility,vigor-activity, fatigue-inertia,andconfusion-bewilderment)was
analyzedseparately.
-o- Dexednne
L--2- Placea
- Doss Time
- 2 Depnvatm Day 1 &ii=-h?pwatlo” Day 2
Time of Day
Figure 20. Effects of drug and session(left) and sessionwith the other factorscollapsed
(right) on reactiontimes to targettonesduring the desktopsimulation task.
The 2-way ANOVA on the tension-anxietyscale,which reflectsheightenedmusculoskeletal
tension,indicatedtherewas no drug-by-sessioninteractionandno drugmain effect. There was,
however, a significant sessionmain effect (F( 15,60)=2.60, p=.OO46)which was due to the
presenceof quadraticandcubictrendsin the datafrom this scale(p<.05). As canbe seenin
figure 21, tension-anxietyscoreswere relatively low during thebeginning, middle, andend of
eachsubject’s participation. However, at 0720 on both deprivation days,therewere increases
which were probably due to circadianeffects.
16
12
Time of Day
Figure 21. Effect of sessionon ratingsof
POMS tension-anxiety.
30

39. . .
eiectlon
The scoreson the depression-dejectionscale,which measuresdespondenceandsadness,also
indicatedno drug-by-sessioninteractionor drugmain effect. However, aswasthe casewith
tension-anxietyscores,therewas a significantsessionmain effect (F( 15,60)=1X3, p=.O506).
Trend analysisindicatedthiswasdueto a significantcubictrendwhich resultedfrom the
circadian-relatedpeaksin scoresat 0720 on both deprivationdays(seefigure 22).
20
+ Dose Tsmt
Time of Day
Figure 22. Effect of sessionon POMS ratings
of depression-dejection.
The 2-way analysisof varianceon anger-hostilityscores,which reflect angerandantipathy
towardsothers,indicatedno significantinteractionor sessionmain effect;however, therewasa
drugmain effect (F( 1,4)=9.76, p=.O354). This wasattributableto a slightdeprivation-related
increaseunderplacebowhich wasattenuatedby Dexedrine (the meanswere 0.4 and0.6,
respectively).
. .
activitv scale
The ANOVA on vigor-activity scores,which reflect energylevels,revealedseveraleffects.
Therewas a drug-by-sessioninteraction(F( 15,60)=4.69, p<.OOOl)which analysisof simple
effectsindicatedwasdueto the fact thattherewere no conditiondifferencesduring any of the
baselinesessions,but substantiallylower vigor scoresunderplacebothanunderDexedrine at
0320,0720, 1120, 1520, and2340 on the first deprivationday andat 0320 on the second
deprivationday (pc.05). There were no differencesbetweenthetwo drugconditionsafter0320,
towardthe end of the 64-hour deprivationperiod(seefigure 23). In addition,therewere main
effectsonboth the drug(F( 1,4)=8.19, p=.O458)andsessionF( 15,60)=10.78, p<.OOOl)factors.
31

40. The drug effect wasbecausevigor ratingswere lower overall underplaceboin comparisonto
Dexedrine (the meanswere 13.9 and 19.6, respectively). The sessioneffect was due to the
presenceof significantlinear, quadratic,andcubictrends(pc.05). As canbe seenin figure 23,
vigor-activity scoresgenerally declined from the begining to the end of deprivation, although
therewere intermittent plateausdue to the factthatwhile Dexedrine was improving vigor ratings,
substantialreductionswere occurringunderplacebo. Also, note that therewas an overall dropin
vigor ratingsat 0720 on the seconddeprivationday which was followed by an increaseat the end
of the deprivationperiod. Caution is advisedin interpretingthesesessioneffectssincetherewas
a significanthigher-orderinteraction.
24
6 6
Figure 23. Effects of drug and session(left) and sessionwith the other
factorscollapsed(right) on POMS vigor-activity ratings.
The 2-way ANOVA on fatigue-inertiascores,which signify wearinessandtiredness,
revealedan interactionbetweendrug and session(F( 15,60)=2.12, p=.O211), andmain effectson
the drug (F( 1,4)=8.60, p=.O427) and session(F( 15,60)=17.50, p<.OOOl)factors.As is shownin
figure 24, the interactionwas due to the fact thattherewere no differencesamongthe drug
conditionsduring baseline,but therewere higher levels of fatigue underplacebothanDexedrine
at 0720, 1120, and 1520 on the first deprivationday (pc.05). Fatigue alsotendedto be higher
underplacebothan Dexedrine at 2340 on this day (p=.O557). There were no differencesbetween
the drug conditionsat later times. The drugmain effect was consistentwith what was observedin
the drug-by-sessioninteractionin that fatiguewas generallyhigher underplacebothanDexedrine
(the meanswere 6.5 versus3.0, respectively). The overall sessioneffect evidencedsignificant
linear, quadratic,andcubictrends(~~05) which resultedfrom a combinationof cumulative
sleepdeprivation andcircadianfactors(seefigure 24).
32

41. I
I
161
12
16
lirEdlIE3j ?irTEdmy
Figure 24. Effects of drugandsession(left) andsessionwith the other
factorscollapsedon POMS fatigue-inertiaratings.
n-bewtldermentscale
Analysisof the confusion-bewildermentscores,which reflect difficulties in mental abilities,
showedseveraleffectssimilar to thoseseenwith theprevioustwo scales. Specifically, therewas
a drug-by-sessioninteraction(F( 15,60)=3.11, p=.OOO9),a drugmain effect (F( 1,4)=11.13,
p=.O289),anda sessionmain effect (F(15,60)=5.90, p<.OOOl). The interactionwasattributable
to the lack of condition-relateddifferencesduringthebaselinesessions,which was followed by
significantlyhigherconfusionscoresunderplacebothanDexedrine at 1120, 1520, 1920, and
2340 on the first deprivationday andat 0720 and 1920 on the seconddeprivationday (ps.05).
This drug-by-sessioninteractionis depictedin figure 25. The drugmain effect wasattributable
to the generalincreasein self-perceptionsof confusionwhich occurredunderplaceboin
comparisonto Dexedrine (the meanswere 4.1 versus2.0, respectively).The sessioneffect was
becauseof significantlinear, cubic,andquadratictrends(pc.05). Figure 25 showsthatthese
resultedfrom a gradualdeprivation-relatedincreasein mental confusionwith circadian-related
peaksat 0720 on both deprivationdays;however,thesetrendsshouldbe cautiouslyinterpretedin
light of the significantdrug-by-sessioninteractionon confusionscores.
VAS
The VAS ratingscollectedduring4 baselinesessions(1120, 1520, 1920, and2340) and 12
deprivationsessions(0320, 0720, 1120, 1520, 1920, and2340 on deprivationday 1; andat 0320,
0720, 1120, 1520, 1920, and2225 on deprivationday 2) underthe influenceof placeboversus
Dexedrinewere analyzedin a seriesof 2-way ANOVAs for drugandsession.The 2340 scores
andthe 2225 scoresfor eachscalewere placedin the samelevel of the sessionfactorfor easeof
analysis(the earliertesttime at the endof deprivationday 2 wasnecessaryto ensurethatsubjects
33

42. could initiate recovery sleepby 2300). Each of the ratings(alertness,anxiety, energy,
confidence,irritability, nervousness,sleepiness,andtalkativeness)was analyzedseparately.
kba of Day litlSOfDay
Figure 25. Effects of drug andsession(left) and sessionwith the other
factorscollapsed(right) on POMS confusion-bewildermentratings.
There were significantdrug-by-sessioneffectson five of the eight VAS items. The
interactionon the alertnessscale(F(15,60)=3.88, p=.OOOl)was due to the fact that therewere no
differencesamong any of thebaselinesessions,but ratingswere substantiallylower (p<.O5)
underplacebothanDexedrine at 0320,0720, and 1120 on the first deprivation day and at 0720
and 1920 on the seconddeprivation day (therewas a tendencyat 1120 (p=.O562) aswell). A
similar effect was observedon the energyscale(F( 15,60)=3.36, p=.OOO4)where analysisof
simple effectsindicatedno differencesat baseline(with the exceptionof the 2340 test),but
substantialdeclinesunderplaceboversusDexedrine (pc.05) at 0320,0720, 1120, 1520, and 1920
on the first deprivation day and at 0320 and0720 on the seconddeprivation day. On the
irritability scale,althoughtherewas a significantinteraction(F( 15,60)=2.27, p=.O130), none of
the simple effectsrevealeddifferencesbetweenplaceboandDexedrine at any of the testing
times. However, thereappearedto be increasedirritability underplaceboversusDexedrine at
0720 on both deprivation days(althoughit wasnot significant). There was a drug-by-session
interactionon the sleepinessscale(F(15,60)=2.43, p=.OO77)aswell. Analysis of simple effects
attributedthis to the fact thattherewere no differencesduring the baseline,but therewere
marked increasesin sleepinessunderplaceboin comparisonto Dexedrine (pc.05) at 0720, 1120,
and 1520 on the first deprivation day andat 0720 on the seconddeprivation day. The effectsof
drug and sessionon talkativenessratings(F( 15,60)=4.14, p<.OOOl)were somewhatsimilar to
thoseon sleepinessin that subjectsdid not ratethemselvesdifferently during the baseline
sessions,but felt they were lesstalkative (pc.05) underplacebothan Dexedrine at 0320,0720,
and 1120 on the first deprivation day andat 0320 on the seconddeprivation day. One curious
effect occurredon this scale,andthatwasthe reversalof the impact of drug at 1520 where
talkativenessactuallywashigher underplaceboversusDexedrine at this one time point (the
apparentlysimilar effect at 2225 wasnot significant). The drug-by-sessioneffectsfor all five
scalesare shownin figure 26.
34

43. 100 100 -
60 80
I Ml 60
er: F
w
40 40
1
20
Dcpnvabo” Da” 2
Time of Day
I + Del&me
0
100
Time ofDay
t DexedMe
4 macct”l
- Dose Tlrn
60 T
Time of Day
Figure 26. Effectsof drugandsessionon VAS alertnessandenergy(top),
irritability andsleepiness(secondrow), andtalkativeness(bottom).
There were drugmain effectson eachof thesefive scalesaswell--alertness(F(1,4)=13.59,
p=.O21l), energy(F( 1,4)=18.44, p=.O127),irritability (F( 1,4)=19.43, p=.O116), sleepiness
(F( 1,4)=9.80, p=.O352),andtalkativeness(F( 1,4)=7.73, p=.O498). Examination of the overall
meansunderplaceboandDexedrine in eachcaseshowedthatsubjectswere lessalert(59 versus
77) lessenergetic(50 versus71) more irritable(9 versus5) more sleepy(47 versus28), and
lesstalkative (45 versus53) afterreceivingplacebo. Dexedrine attenuatedtheseeffects.
35

44. There were sessionmain effectson alertness(F( 15,60)=13.52, p<.OOOl),energy
(F( 15,60)=11.33, p<.OOOl),confidence(F( 15,60)=3.40, p=.OOO4),irritability (F( 15,60)=3.18,
p=.OOO7),nervousness(F(15,60)=2.90, p=.OOlS),sleepiness(F(15,60)=12.75, p<.OOOl),and
talkativeness(F( 15,60)=4.45,p<.OOOl). Trend analysisshowedtherewere significant linear,
quadratic,andcubictrendsin the datafrom eachscale(p<.O5),with the exceptionof nervousness
where therewas no generalizedincreaseor decrease(no linear trend) asa function of deprivation
(the overall slopeof the line was flat). The sessioneffectson all of thesescalesshouldbe
cautiouslyinterpretedsincetherewere higher-orderinteractionson the majority of them;
however, generally speaking,therewere gradualdeclinesin alertness,energy, confidence,and
talkativenessasdeprivationprogressed.At the sametime, irritability and sleepinessincreased.
In every case,the influence of circadianrhythms could be seenassubjectsreportedthe most
problemsat 0720 on both deprivationdays,with a slightrecovery in betweenthesetwo time
points, andonceagainfollowing the 0720 teston the seconddeprivation day (seefigure 27).
MATB
The speedandaccuracywith which subjectscompletedthe MATB at 3 baseline(0330,0730,
and 1130) and 10 deprivationtimes (0330,0730, 1130, 1530, and 1930 on deprivation day 1; and
0330,0730, 1130, 1530, and 1930 on deprivation day 2) underthe influence of placeboversus
Dexedrine were analyzedwith 2-way ANOVAs. Eachtask(communications,resources
management,systemsmonitoring, andtracking) was analyzedseparately.
Three variablesfrom this subtaskwere analyzed. The first was the RT from when subjects
were given an instructionto “changea communicationsradio frequency”until when they
actually changedthe frequency. The secondwasthe standarddeviation of thesereactiontimes
(SDRT). The third wastime out (TO) errors,or the numberof times subjectsfailed to respondto
an instructionto changea radio frequency. There were no drug-by-sessioninteractions,but there
were main effectson the sessionfactorfor RT (F(12,48)=3.23, p=.OO19),SDRT (F(12,48)=3.59,
p=.OOOS),andTO errors(F(12,48)=5.76, p<.OOOl). Trend analysisrevealedsignificantquadratic
andcubic trendsfor the RT data(p<.O5) which were due to the fact that RT wasrelatively short
during baseline,increasedat 0730 on the first deprivationday, droppeduntil 0330 and 0730 the
next day (at which time it peaked), andthendecreasedagainafterwards. SDRT behaved
similarly to RT, but in this case,all threetrendswere significant(p<.O5), despitethe fact that the
linear effect is not especiallynoticeable. For TO errors,therealsowere significant linear,
quadratic,andcubictrendswhich resultedfirst from the gradualincreasein TO errorsasthe
deprivationperiod progressedandsecondfrom the circadianeffectswhich servedto produce
substantiallygreaterTO errorsat 0730 on both of the deprivationdays. All of thesesession
effectsaredepictedin figure 28.
36

45. 60
60
f
4
TimedDay
Figure 27. Effect of session (with the other factors collapsed) on VAS ratings.

46. 1130 1530 19x 330 730 1130 15% 19cg 330 730 1130 15M 19s
Basel,m oepnvabmmy, DEplvaaonmy2
Time of Day
12
+ Dose ke
10
T ,
Time of Day
Figure 28. Effect of sessionon reactiontime for correctresponses(top left), standarddeviation
of RT (top right), andtime out errors(bottom) in MATB communications.
One variable from this taskwas analyzed. This was a measureof the accuracywith which
subjectswere ableto maintain “fuel levels in their fuel tanks”at the ideal value of 2500 units
(mean deviation of tanksA andB from 2500). The ANOVA on thesedatarevealedno
significantinteractionsor main effects.
Six variablesfrom this subtaskwere analyzed. The first wasRT to lights which indicated
how long it took subjectsto respondto the onsetof one light with a key pressor the
extinguishingof anotherlight with a different key press. The secondwas SDRT for lights. The
third wasRT to dialswhich indicatedhow long it took for subjectsto entera key pressin
responseto an out-of-limits excursionof any of four dials. The fourth was SDRT for dials. The
fifth and sixthvariableswere TO errorsfor lights andTO errorsfor dials. The ANOVA on these
datashowedtherewere drug-by-sessioninteractionson RT to lights (F(12,48)=3.37, p=.OO13)
38

47. anddials(F(12,48)=3.3.5,p=.OO14),andTO errorsto lights(F(12,48)=2.61, p=.OO92),anddials
(F(12,48)=3.32, p=.OO15). Analysisof simpleeffectsindicatedthattherewere no differences
betweenthe Dexedrine andplacebobaselinesessionson any of the four variables. Instead,all of
the drug-relatedeffectsoccurredlaterduringthe deprivationperiod. RT to lightswas
significantlyslowerunderplaceboversusDexedrineat 0330 on the first deprivationday andat
0330, 0730, 1130, and 1530 on the seconddeprivationday. RT to dialswas slowerunder
placeboat 1130 and 1530 on the first deprivationday andat 0730, 1130, and 1730 on the second
deprivationday. TheseRT differencesaredepictedin figure 29. TO errorsfor both lightsand
dialswere not affectedby drugconditionon the first deprivationday, but were more numerous
underplacebothanDexedrine at 0730 on the seconddeprivationday (the effect for dialswas
marginally significantatp=.O6). Also, TO errorsto dialswere more numerousunderplacebo
thanDexedrineat 1530. TheseTO effectsareshownin figure 29.
Time of Day
1130-m
BZ3SFJtl”e DeprwAon Day 1 Deprwt~on Day 2
Time of Day
llcxlswlQ?a 310 7-m rrw l5-n1wrl TV 7v ~1-mlT?n~Q7n 111rll51” 1~vl3?” 7311 rv 3-n 7.m 11-c 1T-ml9-m
BaSelIne Deprwatm Day 1 Depnvatm Day 2 BZJShle Deprwatm Day 1 Depnvatmn Day 2
Time of Day Time of Day
Figure 29. Effects of drugandsessionon reactiontimesto lightsanddials(top) andtime
outsfor lightsanddials(bottom) on the MATB systemsmontioring task.
39

48. There were significantmain effectson the drug factor for RT to lights (F( 1,4)=24.70,
p=.OO77),RT to dials (F( 1,4)=9.25, p=.O384), andTO errorsfor dials (F( 1,4)=11.62, p=.O271).
In addition, therewas a drugmain effect on SDRT to lights (F( 1,4)=23.7 1, p=.OO82). In eachof
thesecases,performancewas slower,more variable,or lessvigilant underplaceboin comparison
to Dexedrine. There were significantmain effectson the sessionfactorfor RT to lights
(F(12,48)=6.66, p<.OOOl),RT to dials (F(12,48)=2.74, p=.OO66),SDRT for lights
(F(12,48)=4.31, p=.OOOl),TO errorsfor lights (F(12,48)=2.38, p=.O168) andTO errorsfor dials
(F( 12,48)=5.15, p<.OOOl). Most of theseappearedto be largely the result of performance
decrementsthat occurredunderthe placeboconditionwhich affectedthe overall sessionmeans.
Trend analysisindicatedtherewas a significantlinear, quadratic,and cubic trend (pc.05) for RT
and SDRT to lights. In both cases,therewas a decreasein performance(i.e., increasedRT and
variability) asthe deprivationperiod increased,aswell asa circadianeffect which especially
impaired performanceat 0730 on both of the deprivationdays. For RT to dials, therewas no
linear trend,but therewere significantquadraticandcubictrends(~~05) due to the sametype of
circadianeffect found with RT and SDRT for lights. There was only a significant linear trend
(pc.05) and a marginally-significant cubictrend (p=.O576)on TO errorsfor dials. Thesewere
becausetime out errorsgradually increasedasa function of deprivation,but after a sharppeak at
0730 on the seconddeprivation day, the time out errorsdeclined. Trend analysison TO errors
for lightsrevealedthatnone of the threetrendsanalyzedhereturnedout to be significant,
probablybecausethe sessioneffect on this variablewasnot aspronouncedasit was on the
others. The sessionmain effectson the systemsmonitoring taskare shown graphically in figure
30.
Tracking. Only one variable from the tracking taskwas analyzed,andthis was theroot mean
square(RMS) erroror the amountof deviation from where the subjectwas supposedto be
holding the cursoron the targetto where he/sheactuallyheld the cursor. The ANOVA on RMS
errorsindicatedtherewas a drug-by-sessioninteraction(F(12,48)=8.26, p<.OOOl). The analysis
of simple effectsattributedthis interactionto the fact thattracking performancewasthe same
during the placeboandDexedrine baselines,but deterioratedrapidly afterwardsunderthe
placebocondition while Dexedrine attenuatedthis effect. At every sessionduring the
deprivationperiod (with the exceptionof 0330 and 1930 on the first day), tracking accuracywas
impaired underplaceborelative to Dexedrine. In addition,RMS tracking errorstendedto be
greaterunderplacebothan Dexedrine at the two outstandingsessions,0330 and 1930 (p=.O587)
ascanbe seenin figure 31 (first panel).
40