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AFRL-HE-BR-TR-2004-0003
--:.; ir"T; ~
..
.--
.
.i. -l.
-
I
United
States
Air
Force
Research
Laboratory
THE
EFFICACY
OF
MODAFINIL
FO R
SUSTAINING
ALERTNESSAND
SIMULATORFLIGHTPERFORMANCEIN
F-117
PILOTS
DURING
37
HOURS
O F
CONTINUOUS
WAKEFULNESS
John
Caldwell
Lynn
Caldwell
Jenni ferSmith
LindaAlvarado
Tara
Heintz
Jeffery Mylar
David
Brown
HUMAN
EFFECTIVENESS
DIRECTORATE
BIOSCIENCES
ANDPROTECTION
DIVISION
FATIGUE
COUNTERMEASURES
BRANCH
2485
GILLINGHAM
DRIVE
BROOKS
CITY-BASE
TX
78235-5105
Janua ry
2004
Approved
fo rpublic
release,
distribution
unlimited.
2 0 0 4 0 2 2 6
0 4
-
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NOTICES
This
r ep o r tis
publ ished
inth ei n te res t
o f
scienti f ic
an d
t echn ica l
i n f o rma t i on
exchange
an dd oe sn o tconst i tu te
ap p rova lo r
d isapprova l
o fit sideas
o rf ind ings .
Thisrepor t
ispubl ished
as
rece ivedan d
h asn o t
been
ed i ted
by
th epubl icat ion
s ta f fo f
th e
Ai rForce
Research
Labora to r y .
UsingG o v e r n m e n t r aw i ngs , pecif icat ions,
r t h e r a ta
nc luded
nh is
d o c u m e n t
fo r
a n y
purposeo t h e rt h anG ove rnmen t - re l a t edprocu remen
t
do es
n o t
in
a n y
w ay
obl iga te
th e
US
G o v e r n m e n t .h e
fac t
that
th e
G o v e r n m e n t
f o rmu la tedo r
suppliedh e
d raw i ngs , pecif icat ions,
o r
o t h e r
d a t a ,
o es
n o tl icense
th e
o ld e r
o r
a n y
o t h e r
person
o r
corpora t i on ,o r
co n v ey
an yr ights
o r
permiss ion
to
manu fac tu re ,
use,o r sel l
a n ypa ten ted
i nvent ion
that
m a yre la teto
t h e m .
Th e
Officeo f
Public
Affairs
h asr ev i ewed
th ispaper ,an d
itis
re leasab le
toth e
Nat iona l
Technicaln f o r m a t i o nServ ice,w h e r etwi l lbe
va i lab le
o
h e
gene ra l
public,
including
foreign
nat iona ls .
This
repor t
has
b eenr ev i ewed
an d
is
approved
fo rpubl icat ion.
//SIGNED//
JOHNA.
CALDWELL,
Ph.D.
Project Scient ist
/ /SIGNED//
THOMAS
L .
CROPPER
Co l
USAF,BSC
Chief ,
Biosciences
an d
Protect ion
Division
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REPORT
DOCUMENTATION
PAGE
Form
Approved
MB
No.
0704-0188
maintaining
the
dataneedednd completing and reviewingthis
collection
of
information.
en dcommentsregarding thisburdenestimateoranyother
aspect
of this
collection
ofinfomnation,
including
suggestions
for redudng
this burden toDepartment
of
Defense,
Washington
Headquarters
Services,Directoratefor
Infomiation
Operationsand Reports
0704-0188),
1215JeffersonDavis
Highway,Suite
1204,
Arlington,
VA
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4302
Respondents
should
be avrarethat
notwithstanding
any other provisionof
law,
nopersonshallbe subjecttoany penalty
forfailingtocomply
with
a
collection ofmfomiationif
itdoesnot
display
a
cun-ently
valid
OM B
control
nunOer.
LEASE
DO
NO T
RETURN
YOUR
FORM
T OTH EABOVEADDRESS.
1.RE P ORTDATE(DD-MM-YYYY)
J a n u a r y2004
2.
REPORT
TYPE
Interim
4.
TITLE
AN D
SUBTITLE
T he
Efficacy
of
Modafinil
for
Sustaining
Alertness
an dSimulator
Flight
Performance
In F-117
Pilots
During
37
Hours
ofContinuous
Wakefulness
6.AUTHOR(S)
Caldwell,John,Caldwell,
Lynn,
Smith,Jennifer,Alvarado,Linda,Heintz,Tara,
Mylar,
Jeffery,
Brown,
David
7.
PERFORMINGORGANIZATIONNAME(S)AND
ADDRESS(ES)
Human
Effectiveness
Directorate
Biosciences
an dProtection
Division
FatigueCountermeasiu-esBranch
2785
GilUngham
Drive
Brooks
City-Base,
T X
78235-5105
9.
SPONSORING
/
MONITORING
AGENCY
NAME(S)
AND
ADDRESS(ES)
12 .DISTRIBUTION
/
AVAILABILITY
STATEMENT
Approved
fo r
public
release,
distribution
imlimited.
3.
DATESCOVERED
(From-To)
Jul2003-Jan
2004
5a .
CONTRACT
N U MB E R
5b .GRANTNUM BE R
5c .P ROGRAM
ELEMENT
NUMBER
62202F
5d .PROJECTNUM BE R
7757
5e .TASKNUM BE R
P9
5f .WORK
UNIT
N U MB E R
04
8.PERFORMINGORGANIZATIONREPORT
NUM BE R
AFRL-HE-BR-TR-2004-0003
10 .
SPONSOR/MONITOR'S
ACRONYM(S)
A F RL / H E
11 .SPONSOR/MONITOR'SRE P ORT
NUMBER(S)
13 .
SUPPLEMENTARY
NOTES
14 .
ABSTRACT
T hepresentstudydetermined whethermodafinil(100-mgsafter17
,22,an d27 hourswithoutsleep)attenuated theeffects
of
fatigueon
fighter-pilot
alertness
an d
performance.
quasi-experimental,
single-blind,
counterbalanceddesign
w as
used
in
which5pilotsfi-oma
previoxisF-117
fatiguestudy
(in
which
no
fatigue
remedy
w asemployed)were
retested
with
modafinil.
heirdata
werecombinedwith
th
datafi-om5newly-recruited
F-117
pilotsw howereevaluatedundermodafmilan dthen
placebo.
Modafinilimprovedvigilancean d
tracking
performance
in
adivided-attention task,
CNS
activation,
oculomotor
performance,
an d
aspects
ofsubjective
mood.light
performancedecrements
were
mitigated
on
six
ofeight
maneuvers.enefits
were
most
noticeable
after
24 to32
hoursofcontinuous
wakefulness.
lthough
modafinil
didno t
sustain
performanceat pre-deprivationlevels,
its
numerous
positive
effectsmakeitauseful
adjunct
to
thecurrently-approvedfatigue
countermeasure
dextroamphetamine.owever,modafinil
should
notbeconsidereda
replacemen
fo r
thisolder
on5)ound.
follow-onin-flightstudyisrecommended.
15 .
SUBJE C T
TERMS
Fatigue,
Sustained
Operations,
Modafmil,
Provigil,
Aviation,FighterPilots,Countermeasures
16 .
SECURITY
CLASSIFICATIONOF:
a .
REPORT
Unclass
b.A BST R A C T
Unclass
c.
THISPAGE
Unclass
17 .LIMITATION
O F
ABSTRACT
Unclass
18 .
NUM BE R
OF
PAGES
97
19a.NAMEO FRESPONSIBLEPERSO
John
Caldwell
19b.TELEPHONE
NUMBER
includearea
code)
(210)536-8251
Stan d a rdForm29 8(Rev .
8-98)
Prescribed
by
ANSI
Std.
Z39.18
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T A B L E
OF
CONT E NT S
Page
B A C K G R O U N D
TheCauses
of
Fatigue
in
Operational
Contexts
The
Impact
of
Fatigue
on
MiUtary
Performance
Fatigue
Remedies
fo r
Operational
Settings
Nonpharmacological
Strategies
PharmacologicalStrategies
Amphetamines
Caffeine
Modafmil
OB JE CT I VE S
0
M E T H O D S 1
Subjects 2
Apparatus
3
Compound
to
be
evaluated
(modafinil)
4
Multi-Attribute
Test
Battery
( MA T B ) 4
Mathematical
Processing
5
Oculomotor
(FIT
Workplace
Safety
Screening)
Evaluation5
Physiological
datarecording
6
ProfileofMood
States
6
Visual
Analog
Scales
7
Side
effectsrating
scale/SimulatorSickness
Questioimaire(SSQ)7
Flight
Simulator
8
W A M
(Wrist
Activity
Monitors)... 0
Procedure 1
In-processing
1
General
approach
1
General
schedule
fo r
re-recruitedpilots
2
Generalschedulefo r
newlyrecruited
pilots 3
Schedule
forbothgroupsofpilots 5
D A T A
AN ALYSIS 0
R E S U L T S 8
General
Participant
Characteristics 9
Sleep
Estimates
9
Multi-Attribute
Task
Battery
0
Communications 1
Systems
monitoring
3
Fuel
monitoring 3
Unstabletracking 4
Mathematical
processing 5
Reactiontime
fo r
correct
responses 6
Standarddeviationof
R T
fo r
correct
responses
6
Accuracy 6
Throughput
6
u
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Oculomotor
(FIT)
data
6
Pupil
diameter
- 7
Pupil
constriction
amplitude
g
Pupil
constriction
latency
4g
Saccadicvelocity
49
Resting
E EG
data
Q
Delta
activity Q
Theta
activity
2
Alpha
activity 5
Profile
ofMood
States 57
Tension/anxiety 57
Depression/dejection
7
Anger/hostility g
Vigor/activity 59
Fatigue/inertia 50
Confusion^ewilderment 0
Visual
Analog
Scale 2
Alertness
62
Energy
'
6
3
Anxiety 4
Irritability 4
Jitteriness 4
Sleepiness 4
Confidence 5
Talkativeness
5
In-flight(simulator)E E G ' 1"65
Simulator
Flight
Performance 6
Straight
climb
7
Straight
descent 8
Left72 0
turn
69
Left
climbing
turn 9
Left
360 turn
0
Right
descending
turn 1
Right
360
turn
Z". ." 72
Straightan d
levels 2
Composite
flight
performance 3
Simulator
Sickness
Questionnaire 4
Side
Effects
Questionnaire 5
DISCUSSION .
ZI"'Z I'ZIIZZ"l76
General
Fatigue
Effects 7g
Efficacy
of
modafmil
79
Cognitive
effects
g O
Physiological
status O
Subjective
ratings
gl
Simulator
flight
performance 3
Modafinil
sideeffects
4
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S U M M A R Y
A N DCONCL USI ONS 5
A C K N O W L E D G M E N T S
8
R E F E R E N C E S
9
LISTOFF I GUR E S
Page
Figure
L Schematicofeach
of the
sleep
deprivation
testcycles
8
Figure2. T hecombinedeffectsoftreatment
conditionan d
testing
timesonTO
errors
during th eM A T Ecommunications
task 2
Figure
3.
T he
effectsofsleep
deprivation
(with
treatment
conditioncollapsed)on
R T
(left)
an d
SDR T
(right)
during
th e
M A T Esystems-monitoringtask
3
Figure
4.
T he
effects
of
sleep
deprivation
(with treatment
condition
collapsed)
on
th e
deviations
offuellevelsin
tanks
A
an d
Bduringth eM A T Efuel-monitoring
task....44
Figure
5.
T he
combinedeffectsof
treatment
condition
an d
testing
time
(left)an dth e
overall
effectoftimeon
M A T H
tracking
(right) 5
Figure
6.
T he
combined
impact
of
treatment
condition
an dtesting
time
(left)
an d
th e
overalleffectof testing
time(right)on
FIT
pupildiameter7
Figure
7.
T he
overall
effectof
sleep
deprivation
(testingtime)
on
FIT
pupil
constriction
latency 48
Figure
8.
T hecombinedimpactoftreatment
condition
an d
testing time
on
FITsaccadic
velocity 9
Figure
9.
The
interactive
effectsof
treatment
condition
an d
eye
closureon
restingE E G
delta
activity
atCzan d
Pz 1
Figure10.The
overall
condition
main
effects
(modafinil
versus
placebo)
on
resting
E E G
delta
activity
at
Cz,
Pz,an d
Oz
1
Figure
11.
The
overall
effects
ofsleep
deprivation
(testing
time)
on
resting
E E Gdelta
activity
at
Pz
an d
Oz
2
Figure
12.
The
interactive
effectsofcondition,
testing
time,an dey e
closure
on
resting
E E G theta
activity
at
Pz 3
Figure
13.The
combined
effectsof
testing
time
an deyeson
restingE E G thetaactivity
at
PzandOz 3
Figure
14.The
combined
effectsoftreatment
conditionan d
testingtimeon resting
E E G
theta
activityat
Oz 4
Figure
15.The
overall
effects
of treatmentcondition
(modafinil
versusplacebo)
on
resting
E E G
theta
activity
at
Cz,
Pz,an dOz 4
Figure
16.The
effectsof
time
on
restingE E G
theta
activityat
Pzan d
O z
5
Figure
17.The
combined
effects
oftestingtime
and ey e
on
restingE E G
alpha
activity
at
CzandPz
6
Figure
18.Themarginally-significant
interactive
effects
oftreatment
condition
an d
ey e
closureon
restingE EG
alphaactivityat
Oz
6
Figure
19.
The
interactive
effectsoftreatment
conditionand
testingtime
on POM S
depression-dejection
ratings 8
Figure
20.
T he
overall
impactoftreatmentcondition
(modafinil
versusplacebo)
on
P O M Sanger-hostilityratings 9
IV
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Figure21 .Theseparateimpactof
treatmentcondition(modafinilversusplacebo)an d
sleepdeprivation(testingtime)onPOMS
vigor-activity
ratings
0
Figure22 .
Theimpactof
sleep
deprivation(testing
time)
an dconditiononPOMS
fatigue-
inertiaratings i
Figure
23 .
The
overallimpact
ofsleepdeprivation
(testing
time)
on
POMSconfusion-
bewilderment
ratings
2
Figure24 .T he
effects
ofsleepdeprivation
(testingtime)onVA Salertness,energy,
jitteriness,sleepiness,confidence,an dtalkativenessratings
.
3
Figure
25 .The
independent
effects
oftreatment
condition
an d
testing
time
on
performance
of
th e
straight
climb 5g
Figure
26.The
independent
effects
of treatment
condition
an d
testing
time
on
performance
of the
straightdescent
58
Figure
27 .
The
interactive
effects
ofboth
treatment
condition
an dsleep
deprivation
on
performanceoftheleft720-degreeturn 9
Figure
28.The
independent
impactoftreatmentcondition(modafinil
versusplacebo)
on
performance
of th eleft
climbing
turn 0
Figure
29 .
The
non-significant
pattern
of
condition
an d
time
effects
on
performance
on
th e
left
360-degree
turn i
Figure30 .Themarginally-significantinteractive
effects
oftreatmentcondition
an d
sleep
deprivation
(testing
time)
on
th e
performance
oftheright
descendingturn
1
Figure
31 .
T he
overall
impact
of
treatmentcondition
(modafinil
versus
placebo)
on
th e
performance
of
th e
right
360-degree
turn 2
Figure
32 .The
overall
impactof
treatment
condition(modafinil
versus
placebo)
on
th e
performance
ofthe
straight-and-level
maneuvers 3
Figure
33 .T he
overall
effectsof
treatment
conditiononeach
maneuver
(left)an dthe
interactive
effects
oftreatmentconditionan dsleepdeprivationacrossall
maneuvers
combined(right) 4
Figure
34 .
The
general
impact
of
sleep
deprivation
(testing
time)
on
visuomotor
scores
(left)an dtotal-discomfortscores(right)onth eSSQ 5
LISTOFT A B L E S
Page
Table
1 .Measured
simulatorflightparameters 20
Table
2.lightmaneuvers 7
Table3.
arameters
evaluated
in
each
oftheflight
maneuvers4
Table4. gean d
flight
experience
datafor
thetw o
groups 9
Table5.
ctigraph-based
estimatesof
sleep
times
."."40
Table
6.
ide
effects
reported
under
the
modafinil
an d
placebo
conditions
6
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CKGROUND
U.S.
superiorityintoday's
battle
space
in
partstems
fromourability
to
maintain
pressureontheenemyby making
them
fight
aroundtheclock.yforcing
our
adversariestomaintaina24-hour-a-day
operational
tempo,
enemy
forces
will
suffer
from
severe
sleepiness,leading
to
procedural
errors,
sloppy
judgment,
poorplanning,
and
a
generalinability
to
react
properlyto
rapidly
changing
situations.
his
provides
a
tactical
advantagefor
theU.S.
and
is part
ofthe
reason
that
the
A irForceChief of
Staff
noted
thatpersistent
and
sustained
operations,
24
hours
aday,
7
days
a
week,areessential
to
establishing
and
maintaining
superiority
in
today's
combat
envfromnent
(Elliot,
2001).
Simply
forcing
our
enemies
to
perform
continuously without
the
benefit
ofsufficient
daily
sleep
is
a
very
effective
weapon
in
andofitself
TheCausesof
Fatigue
inOperational
Contexts
Unfortimately,theconduct
of
continuous
and
sustained
operations
ca n
pose
significant
hazards
toour
ow n
troopsif we
aren't
carefiil
to
properlymanage
fatigue
among
ourselves.
ersoimel
andresource
cutbackswithinthe
U.S.Department
of
Defense
overthe
past
severalyears
have
resulted
in
force
reductions
of
over
30
percent
in
the
Army
(Department
of the
Army,
1996)
and
inthe
A irForce(Congressional
Research
Service,2002),
while
theoperationaltempo
ha s
increasedbyas
much
as
400
percent
(Correll,
1998).
Needless
to
say,
U.S.military
capabilities
areincreasinglysfrainedas
understaffed
units
strive
to
accomplish
more
work
with
fewer
resources.
om e
feel
that
this
has
resultedin
diminished
military combat
readiness(Spencer,
2000),
in
part,
becauseofincreased
cognitive
fatigue.
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There
is
little
doubtthat
existing
manpower
constraints
have
madeit
difficult
to
continuously
staff
th e
requiredworkshiftswithwell-rested
personnel
aroundth eclock.
Thus,
prolonged
work
bouts
havebecome
common,
shorter-than-normal
sleepperiodsare
unavoidable,an dfatiguefrom
both
of thesefactorsthreatenstoimpact
operational
readiness(Departmentofth eArmy,1994).
t
iswell
established
that
sustained
wakefiilness
an d
th e
resulting
cumulative
sleep
debt
increase
th e
likelihood
that
personnel
will
briefly
(and
uncontrollably)
no d
off
on
th ejob,even
during
demanding
tasks(Angusan d
Heslegrave,
1985).
helonger
personnel
remainawake,
th e
more
likely
these
"sleep
attacks"
become.
n
addition,
sleepiness
takes
a
heavy
toll
on
reaction
time,
motivation,
attention,
memory,endurance,
an d
judgment
(Krueger,1991).
ve nin
peacetime,overlytiredsoldiers
an d
aviatorsare
thought
to
be
responsiblefor numerous
fatigue-related
incidents
an d
accidents
every
year
(personalcommunication,LtCol
Thomas
Luna,
U.S.
A ir ForceSafety
Center,
May,2003).
T he
Impact
of
Fatigue
on
MilitaryPerformance
Although
predictionsabout
th e
exacteffectsoffatiguearedifficult
tomake,most
researchersagree
thatfatigue-related performance
an d
alertnessdecrementsfollow
a
fairly
reliabletime
course.
anadian
researchers
have
reported
that
certain
mental
abilities
decline
by
about
30
percentafter1
night
without
sleep
and
60
percent
after
2
nightswithoutsleep(Angus,
Pigeau,
an dHeslegrave,
1992).
cientistsat
th e
Walter
Reed
Army
Institute
of
Research
predict
soldiers
lose
about
25
percent
of
their
ability
to
perform usefiilmental
work
forevery24hoursofcontinuouswakefiilness
(Belenky
et
al.,1994).
recent
A ir
Force
Research
Laboratory
study
revealed
that
current,
active-
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duty
fighterpilotssuffered
flight-performance
declines
of45
percent
below
normalafter
only2 6hours
withoutsleep(Caldwell
et
al.,
2003).
Fatigue
Remedies
for
OperationalSettings
It
isclear
that
fatigue
isa
significant
problem
insustained
mihtary
operations,
especiallyinthe
aviation
sector
where
a
high
levelof cognitiveperformance
is
essential
forsafetyand
effectiveness.
owever,
fatigue
can
be managed
with
scientifically-
vaUdated
countermeasures.
everal
differentstrategies
have
beenproposed
for
this
purpose.
Nonpharmacological
Strategies
Emphasizing
proper
work/rest
management
isone
strategy
that
the
military
ha s
rightfiiUy
focused
upon
for many
years.owever,when
the
intensity
of combat
reaches
acertainpoint,
itcanbe
very
difficulttoproperly
controlsleep
periods,
and
thiscan
lead
to
a
substantial
problem
with
on-the-job
fatigue
(Comum,
1997;
Angus,
Pigeau,
and
Heslegrave,1992).venduringpeacetime,
a
recent
surveyofU.S.
Armypilots
revealed
that
26percentcomplainedofpoorsleep
while
in
the
field
or
whiletravelingawayfi-om
home
compared
toonly
5percent
complaining
ofpoor
sleep
attheir
home
post(Caldwell
et
al.,2001).imilardifficultiesare
no-doubtpresent
inthe
U.S.
A ir
Force,although
published
documentation
on this
point
is
unavailable.
Strategic
napsca nhelpalleviatesleep-deprivation-related performance
decrements
in
situations
where
naps
are
feasible
(Dinges
et
al.,
1988).
owever,scheduling
naps
is
not
asimple
matter
in
thatoperationalconstraints
can
make
it
very
difficultto
ensure
proper
control
over
nap
timing(placementof
naps
atoptimalpomts
in
the
sleep-
deprivationperiod),
na pduration
(ensuring
sufficientsleep
time),and napscheduling
-
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(placing
napsat
appropriatepointsin
th e
circadian
cycle)(Caldwell,2001).n
addition,
it
can
be
difficultto
establish
a
restful
an d
isolated
environmentinwhich
effective
naps
ca n
takeplace.
Brief
periodsofexercisem ay
offer
somebenefit
insituationswhere
fullsleep
periods
an dnaps
arenotpossible,
bu t
this
strategy
onlytemporarilyreduces
th e
impactof
sleeploss(LeDucetal.,
2000;
H o m ean dReyner,1995a;Angusetal.,1992).
lso,there
issome
indication
that
th e
short-term
benefits
of
exerciseare
not
sufficiently
robust
to
outweighth e
alertness
decrements
thatexerciseproduces
lateron.
Exposure
to
environmental
stimulation
suchas
cold
air
or
noise
is
another
strategy
thatha sbeentriedin
laboratory
studiesof
driver
fatigue.
esults
have
shown
thatsuch
measures
are
virtually
ineffectivefo rmaintaining
alertness
(Home
an d
Reyner,
1995b).
Finally,
high
levels
of
physical
fitness,
while
goodfor
sustaining
physicalendurance,
have
beenfound
to
havelittle
impact
on
th e
ability
to
maintain
cognitiveperformance
(Angus
etal.,1992).
hus,
physical
fitness
isnot
aneffectivefatigue
countermeasure.
Pharmacological
Strategies
Pharmacologicalcountermeasures(alertness-enhancing
compounds)
mayb e
theonly
reliablemethodfor maintaining
th e
performance
of
personnel,
especially
aviators,in
sustainedoperations.hese
compounds
are
effective
an d
easy
touse,
an dtheir
feasibility
is
no t
dependent
upon
environmental
manipulationsorschedulingmodifications.
hi s
explains
w hy
dmgs
such
as
th e
amphetamines
have
been
usedextensively
in
several
militaryconflicts(Comum,
Caldwell,
an d
Comum,
1997),an dw hy
th ecompounds
caffeinean d
modafinil
are
of
greatinteresttoboth
th e
Army
an dth eA ir
Force
today.
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Amphetamines.mphetamines
havebeenonth e
market
in
the
U.S.
since
1937
an d
havebeenwidely
used
to
treat
th e
symptoms
ofmedical
conditions
such
as
narcolepsy
(a
disorder
of
excessive
daytime
sleepiness)
and hyperactivity/attention
deficit
disorder
(Comum,Caldwell,an d
Comum,
1997).
he U.S.
A ir Force
officially
authorized
th e
use
of5-10
m g
doses
of
amphetamine
to
sustain the performanceofsleep-deprived pilots
as
early
as1961,
an d
dextroamphetamine
(marketed
under
th e
brand
name
Dexedrine)
continuestobe
authorized
under
A ir Force
poUcy
fo r
certain
situationstoday.
Laboratory
studies
have
shown that
singledoses
(2 0
mg)
ofdextroamphetamine,
administered
after
48
hours
of
continuous
wakefiilness,
return
alertness
an d
cognitive
performance
to
nearbaseline
levels
an d
maintainthis
recovery
fo r
7to
12
hours
(Newhouse
et
al.,1989).n
addition,
asingle20
mg
dosehasbeen
foundto
temporarily
prevent
performance
decrements
insubjects
kept
awake
fo r
approximately
34hours,
an d
torestore
th eperformance
of
volunteers
deprived
of
sleep
fo r
4 8
hours
(Pigeauet
al.,
1995).
Multiple
10-mg
dosesof
dextroamphetamine,
administered
prophylactically,
are
known
to
sustain
th eperformance
of
heUcopter
pilots
throughout40hours
of
continuous
wakefulness
(Caldwell
et
al.,1995;Caldwell,Caldwell,
an d
Crowley,1996;Caldwell
an dCaldwell,
1997),an deven
throughout64
hours
withoutsleep(Caldwelletal.,
1999).
Field
experiencewiththis
compoundh as
generally
been
positive
as
well
(Comum,
1997;
Emonson
an d
Vanderbeek,
1995).
There
is
virtually
n o
evidence
that
properly-administered
amphetamine
increases
risk-takingbehaviors
or
overestimation
of
performance
capabilities
(Caldwell
etal.,
1999;
Higgins
et
al.,1975;
Baranski
and Pigeau,1997).n
fact,there
appears
to
belittle
reason
that
dextroamphetamine
should
not
continueto
be utilized
asan
effective
fatigue
-
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countermeasure.
owever,
intheinterestof
providing
flexibility
tomilitaryoperational
personnel,
it
is
important
toevaluate
potential
alternativesto
dextroamphetamine.
lso,
concerns
remain
about
th e
riskof
abuse
thatca n
lead
topsychological
or
physical
dependence
in
a
subset
of
susceptible
individuals(Akerstedtan d
Ficca,
1997).
.o p
Dexedrine
Placebo
Dose
Time
50 hrsawake
without
Dexedrine
18-22
hrs
awake
without
Dexedrine
UL
-22230 noo
Baseline
LA
10 0 50 0
900
1300 1700 10 0
500
900
1300 1700
DeprivationDa y eprivationDa y2
Time
of
Day
Efficacyof10-mg
Doses
of
Dexedrinefo r
SustainingPilot
Performance(from
Caldwelletal.,
1999).
Caffeine .affeine
ha s
traditionally been
th efirst-line
alternative
to
dextroamphetamine,
primarily
because
it
iseasy
toacquire
and
socially
acceptable.
Research
suggests
caffeine
is
suitablefo r
sustaining
alertness
in
relatively
short
(i.e.,
37
hour)
rather
thanlong(i.e.,64 hour)periodsofcontinuous
wakefuhiess
(Lagardean d
Batejat,1995).affeine
appearsless
effective
than
amphetamine
an d
more
prone
to
produce
unwanted
side
effects
suchas
tremorsan d
diuresis
(Weissan dLaties,1967),
an d
it
m ay b eless
optimal
in
individuals
w ho
normally
consume
moderate
to
high
amounts
in
coffee,
softdrinks,
nutritionalsupplements,and/or
food
products
(this
ha s
notbeen
empirically
established).owever,it
is
known
that
tolerance
to
th e
sleep-disrupting
-
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effects
ofcaffeine
(one
indication
ofits
stimulant
potency)
ca n
occuri n
aslittleas7
days
in
individuals
given
high
doses(1200
mgs
per
day). lthough mostadultsconsvimeless
thanthis
amount,
about80
percent
of
th e
U.S.
aduU populationregularlyingests
a
behaviorallyactive
dose
ofcaffeine
(Griffithsan d
Mumford,
1995).
typical
single
6-
ounce
serving
ofcoffee
contains
60-150m gcaffeine,
teacontains
20-50
mg,
chocolate
contains5-35
mg,
an d
on e
Coke
contains
46
m g
ofcaffeine
(Lieberman,
1992).
Thus,
somedegree
of
tolerance
is
inevitable,an dthism aymeanthatmore
thanth eminimum
recommended
dose
of
200
mg
caffeine
wouldbe required
to
noticeablyimprove
wakefulness
in
sleep-deprived
pilots
(especially
those
w ho
are
chronic
caffeine
users).
Even
if
thiswerenotth e
case,
problems
related
to
caffeine's
diuretic
effects
an dits
tendency
to
impairfinemotorcontrolmake
it
ofquestionablevalue
fo r
sustaining th e
alertness
ofhigh-performance
jetpilots.owever,caffeine
can
significantly
improve
th e
performance
of
sleep-deprived
people
w ho
donot
normally
consume
highdosesof
this
compound,
an dit
is
safe
an d
widely
available
(Penetar
etal.,1993).
20
18 -
CM
6
CO
' 4
2
O
All
subjects
beforedrug
Placebo
A
Caffeine
150nrig/70kg
)
Caffeine
3O0nig/70kg
_
Caffeine
600mg/7Clkg
^ .N
(3.
ET'
Day
Drug
Administration
Day2
ay3
-I
R
-1
^
Q Q ?5
o> ^
S
S
R
S
Timeof
Day
Efficacy
ofThree
DifferentDosesofCaffeinefo rProlonging
Onset
toStage2Sleep
(fi-om
Penetar
et
al.,1993).
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Modafinil.
Modafmil
is
a
relativelyne w
alertness-enhancing
compound
that
appears
efficaciousfor
sustainingperformance
duringprolongedperiods
of
total
sleep
loss
(Lagarde
an d
Batejat,
1995).
his
substance
became
available
in
th e
United
States
in
December
of
1998
when
itwasapproved
by
the
Food
an d
Drug
Administration
(FDA)
for
the
treatment
of
excessive
daytimesleepiness
associatedwith
th e
sleep
disorder
narcolepsy.
ince
that
time,
modafmil
ha s
beenFD A
approved
fo r
th e
treatment
of
sleepiness
associated
with
shift
work.
everal
studies
in
sleep-deprived
subjectshave
provided
evidence
thatmodafmil
is
aneffective
fatigue
countermeasure
thatproduces
few
problematicside
effects.or
instance,Lagardeet
al .
(1995)an d
Lagarde
an d
Batejat
(1995)
found
that
modafinil
reducedth e
frequencyof
involuntary
sleep
lapsesan d
maintained
cognitive
performance
during
60
hours
of
continuous
wakefulness.
igeauet
al.
(1995)
reported
that
modafinil
(300
mg)w asaseffecfive
as
dextroamphetamine
(2 0
mg)fo r
maintaining
mood,alertness,and
performance
throughout64 hoursofsleep
deprivation.
dd y
et
al.
(2001)
reported
that
modafinileliminated
fatigue-related
performance
decrements
on
a
vigilance
task
in
people
kept
awake
fo r
22hours,
an d
Wesenstenet
al.
(2002)
indicated
that
modafinil
(200
m g
an d400
m g)
effectively
counteracted
cognitiveperformance
decrements
resultingfrom
41.5
hours
of
continuous
wakefulness.
In
th eaviationarena,
modafinil
has
not
ye t
beensufficiently
tested.owever,
the
on e
aviator
performance
studyconducted
prior
to
th e
present
evaluation
(with
60 0mg
modafinilgiven
in
3
divided
200
m g
doses)indicated
modafinil
w as
capable
of
sustainingsimulator
flightperformance
at
or
near
rested
levels
despiteover30hours
of
-
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sleep
loss
(Caldwell
etal.,
2000).
nfortunately,
this
same
study
alsoproducedevidence
ofside
effects
(nausea,
vertigo,
and
dizziness)
thatmay havebeen
modafmil-related
in
somepilots.
t
thispoint,studiesthathave
focused
on
ground-basedpersonnel
suggest
that
such
side
effects
werelikely
an
idiosyncratic
reactionor
that
they
resulted
fromthe
high
dosage
levels
givenin
the
earlierCaldwell
et
al.(2000)study,i
fact,
Buguet,
Moroz,and
Radomski(2003)
andothers
havepresented
evidence
thatmodafmil-related
sideeffectsof nausea
andvomiting
are
clearlydose
dependent.
owever,empirical
validation
ofwhetherthese
side
effectswould
occur
atproblematic
levels
with
100-or
200-mg
doses,
in
an
aviation
context,
was
previously
unavailable.
? 2.5
-Placebo
-ModaflnlllOO
m g
-Modaflnll200
m g
-ModaflnlUOO
m g
-Caffeine
600
m g
Modafinil
or
caffeine
w as
administered
after
41.5
hours
ofsleep
loss.
oa oo40 0
TimeofDay
0200 0500 0800 1100
Efficacy
of
100,200,and
40 0mg
of
Modafinil
Compared
toPlacebo
and
600
mg
Caffeine
(from
Wesensten
et
al.,
2002).
Modafinil
is
ofparticular
interest
to
the
Air
Force
(and
other
communities)
because
it
lacksthe
abuse potential
oftenassociatedwithamphetamine,and
it
appears
lesslikely
to
disrupt
recovery
sleep(Cephalon,
1998).
i
addition,
modafinildoes
no tproduce
the
cardiovascular
stimulation
commonly
associated
with
caffeine
and
dexfroamphetamine
-
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(Saletu
et
al.,
1986),
making
it
abetter
fatigue
countenneasure
forpersonnel
w ho
are
suffering
from
hypertension
(although
thisis
not
usually
a
factor
in
aviator
populations).
Despitethefactthatmodafmilmay
bebettersuitedtocountertheeffectsofshorter
versus
longer
periods
ofsleep
deprivation
(Buguet,
Moroz,
an dRadomski,
2003),
its
otherattributes
likely
will
make
it
a
valuable
addition
to
the
A ir
Force's
armament
of
aviation
fatigue
countermeasures.
n
fact,
on
02
December
2003
modafmil
w as
approved
forus e
in
certain
A ir
Force
bomber
missions;
however,
approval
forth e
us e
of
modafmil
in
fighter
operations
w as
delayed
pending
additional
research
(Memorandum,
Department
of
th e
A ir
Force
Headquarters,
2003).
OBJECTIVES
Modafmilclearly hasalertness-enhancing
properties
ofinterest
to
th emilitary
aviation
community,and
recentstudiessuggest
that
side
effects
are
minimaleven
with
200-mg
doses(aslong
as
th e
200
mg
doses
are
spacedat8-hour
intervals).
Complicationsfromthe
10 0
mg
doseareeven
less
likely
(personalcommunicationan d
unpublished
datafrom
M r.
Jeff
Whitmore,
BrooksCity-Base,
July,
2003).
hus,ifit
wereclear
thatmultiple,10 0
mg
doses
ofmodafmil
offered
therequired
level
of
alertness
enhancement
and
performancesustainment
insleep-deprived
fighter
pilots,
modafinil
could
be
offered
as
an
alternative
tocaffeine
and/ordextroamphetamine
as
a
fatigue-countermeasure
fo r
us ein
"fast
jet"
military
aviation
sustainedoperations.
The
purpose
of
th e
present
investigation
w as
to
assess
the
utility
of
this
(100-mg)
dosage
ofmodafmilfor maintaining
fighter-pilotperformance
in
situations
devoid
of
adequate
sleep
opportunities.
o
accomplish
this
objective,th e
effectsof
no-
treatment/placebo
versusth e
effects
of3separate
10 0
mg
dosesof
modafinil
were
10
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examinedin
active-dutyF-117
pilots
undergoing
37-38hoursof
continuous
wakeflilness.
T he
specific
dataof interest
were:
bjectively-measured
pilotperformanceduring th e
completion
ofstandardized
flight
maneuvers
ina
specially-instrumented
flightsimulator;
entralnervous
system
CNS)
arousal
basedon
electroencephalographic
(EEG)
assessments
of
th e
amounts
of
delta,
theta,
and
alpha
activity;
arasympathetic/sympathetic
activation
baseduponmeasures
of
pupil
diameter,
constriction
amplitude,
constriction
latency,
an dsaccadic
velocity;
elf-reported
measures
of
psychological
mood
states,
alertness,
sleepiness,
energy,an d
otheraspects
of
subjective
status;
nd
general
cognitive
status
in terms
ofth e
ability
to
perform
simple
mathematical
evaluations
as
wellas
th e
ability
to
accomplish
aviation-related
divided-attentiontasks.
M E T H O D S
The presentstudy
employeda
quasi-experimental,
single-blind,counterbalanced,
repeated-measures
designto
ascertain
the
efficacy ofmodafinil
fo r
attenuating
fatigue-
related
degradations
associatedwithprolongedwakefuhiess. lthough
the
single-blind
strategy
is
less
optimal
than
th e
double-blind
approach,
th e
single-blind
optionw as
chosen
here
as
amatter
of
necessitybasedon
th etime
demands
imposed
on
th e
active-
duty
pilot
volunteers.
ach
of
th e
flight
squadrons
from
which
th e
volunteers
were
recruited
hadonly
a
limited
numberofpilotsto
completeth e
squadron's
normally-
scheduledmissions.
herefore,
th e
operations-group
commander
rightfullyemphasized
th e
importance
ofminimizingth eresearch-related
time
demands
(a
secondary
1 1
-
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requirement)
on
his
routine
squadron'sprimary
mission
requirements.
ne
of
th e
best
waysto
accomplish
this
objectivew as
to
include
some
of
th e
data
that
alreadyhadbeen
collected
earlieron
asubsetof
his
F-117pilotswho
had
undergone
sleep
deprivation
withouttheaidofafatigueintervention,andtous e
these
data
as
th eno-treatmentcontrol.
Since
th e
procedures
used
in
that
previous
studywere
identicalto
those
employed
in
the
present
investigation,
fiveoftheseindividuals,w ho
had
previously
receivedno
fatigue
countermeasure,
were
re-recruited
an d
given
modafmilin
thisphase
of
the
study.
heir
no-treatment/treatment
data
were
thencomparedtoth edata
collected
from
five
newly-
recruited
pilots,
each
of
whom
were
exposed
to
two
sleep-deprivation
periods
in
which
they
received
modafmil
firstan dplacebo
second.
his
strategyresulted
inonly3
days
of
lost
time
forth e
re-recruited
pilots
(halfofth e
sample)compared
to
a
full
5
days
of
lost
time
for
th enewly-recruitedpilots(the
other
halfofth e
sample)
while
still
providing
experimental
control
for
th e
potentiallyconfounding
effects
ofdrug-administration
order.
Subjects
Ten
qualified
pilots(mean
ag e
of36.6years,
rangingfrom
30-43
years
old)
w ho
were
members
ofth e49'^Fighter
Wingat
Holloman
A ir
Force
Base,N M ,servedas
participantsafter
signing
an
informed
consent
agreement
which
detailedth e
procedures
of th e
study.
ll
participants
were
in
possession
of
a
current"u p
slip"
(AirForce
Form
1042,medicalpermissiontoengageinmilitaryflying
duties)
atth etimeof
their
admission,
and
all
were
current
an d
qualified
in
the
F-117A
aircraft.
he
participants
possessed
an
average
of
2,730
total
flight
hours
(ranging
from
800to
5,800hours)an d
431.5
F-117
flight
hours
(ranging
from14 0to89 0
hours).
No
restrictions
on
experience
wereimposed
because
thisfactorh as
no tbeen
shown
to
impactth eresistance
to
sleep
12
-
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deprivation,
nor h as
itbeen
shown
to
affect
th e
relationship
between performance
capacity
an d
electrophysiological,
mood,
orcognitive-performance
variables
instudies
conducted
over
th e
past
17years
by
th e
principal
investigator of
th e
presentresearch. ll
of the participants
were
male
becausethere
currently
are
no
femaleF-117A pilots.rior
to
th e
study,
most
of
th e
participants
werereportedly
ona
late-daytimeschedulein
which
they
generally
reported
to
work
between
0900
an d
1000
an d
often worked
orflewuntil
2100or
2200.on eofth e
pilots
were
working
a
classicnightshift(i.e.,
2300-0700)
or
other
schedule
requiring
dutyinto
th e
predawnhours.ccording
to
actigraph
data,
th e
participants
acquired
an
average
minimum
of
7
hours
an d
20
minutes
of
sleep
prior
to
th e
beginningof
any of
th e
continuouswakefiilnessperiods
(fiirtherinformation
on
sleep
timesis
provided
in
the
Results
section).
one
were
taking
an y
type
of
medication
known
to
impact
mentalalertness
(sedating
antihistamines,
sleep
medications,
prescription
stimulants,etc.). total
of10
pilotswere
evaluated
becausethis
nimiber
of
participants
w as
determined
to
yield
sufficient
statisticalpower
based
on poweranalyses
conducted
on
data
fi-oman
earlier
study
in
which
a
similar
design
w as
employed.
Apparatus
The researchprotocol was
conducted inside
ofthe F-117
WeaponSystem
Training
(WST)facility at
HoUomanA ir
Force
Base,
NM .
he
flight-performance
data
were
collected
with thesimulator and
ancillary
equipment.
he remainingmeasures were
collected
with
various
laboratory
testing
devices which
were
set
up
in
a
co-located
sound-
attenuated
testing
room
within
the
simulator
facihty.
his
same
facility
arrangement
w as
used
inthepreviousstudy onF-117 pilots
which
w asconducted
earUerthis
same
calendar
year
(Caldwellet
al.,2003).
etween the
previous
study
an d
the
presentmvestigation,
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every
effort
was
made
to
exactly
duplicate
the
testing
conditions
since
aportion
of
the
data
(no-treatment
data
fromfive
participants
in
th e
earlier
investigation)
were
included
in
the
present
dataset(in
which
these
five
participants
werere-recruited
to
undergo
sleep
deprivationwithmodafinil).
Compound
tobe
evaluated
(modafinil)
The
medication
was
modafinil
(Provigil,
Cephalon,
Inc.,
WestChester,
PA),
2-
[(diphenylmethyl)
sulfinyl]
acetamide,
in
th eform
of
10 0
mg
tablets. teach
ofth e
dose-administration
times,the
newly-recruited
participantsreceivedon etablet
consisting
of
either
placeboor
active
compound
(a tmidnight,
0500,
an d
1000).
he
placebo
tablet
w asan
exact
replicaofth e
activetablet
so
that
the
participants
would
remain
blindtoth e
drug.he
re-recruited
participants
did
no t
receive
an y
type
offatigue
countermeasure
(o r
placebo
tablets)
during
theirfirst
deprivationperiod
(from
th e
earlier
F-117
study),
but
during
their
return
tothe
testfacility(for
thissecond
study),
they
all
received
active
compound
at
each
dose
time
(midnight,
0500,
an d
1000).
ephalon,Inc.suppliedboth
th emodafinilan d
placebo
freeofcharge
an dwithout
obligation
ofan ysortwhatsoever.
Multi-Attribute
Test
Battery
CMATB)
T heM A TH(Comstockan dAmegard,
1992)
isa
computerized
aviation
simulation
test
that
requires
participants
toperform
anunstabletrackingtask
while
concurrently
monitoringwarning
lightsan d
dials,responding
to
computer-generated
auditory
requests
to
adjust
radio
frequencies,
an d
managing
simulated
fiael
flow
rates
(using
various
key
presses).
hi s
test
w as
controlled
by aMicron
Pentium-based
computer
equipped
with
a
standardkeyboard,a joystick,an da
mouse.
ata
onfrackingerrors,response
times.
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-
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time-outs,false
alarms,
an d
accuracy rateswere
calculated
vi atheuse
of th eM A T E
processing
software.
Mathematical
Processing
T he
MathematicalProcessing
subtest
from
th eAutomated
Neuropsychological
AssessmentMetrics( A NA M)
battery
(Reevesetal.,
1993)is
a
basic
cognitive
test that
requires
participants
tosolvearithmetic
problemspresented
in the
middleof
th ecomputer
screen.
hetask
involves
deducingan
answertoanequationsuchas
"5+
3-4
="
an d
then
deciding
if
the
answer
is
greater-thanorless-thanth enumber
5.
asedon
the
calculation,
the
participant
then
presses
on e
of
tw o
specified
response
buttons
on the
mouse.
This
testw as
controlled
by
a
standard
Pentium-based
desktop
computer
equippedwith
a
keyboard
and
a
mouse
(whichw as used
to
maketh erequiredresponses
to
eachitem). ata
on
performance
accuracy,
response
speed,and throughput
were
calculatedbycomputervia
STATVIEW^'^ software
atthe
conclusion
of testing.
Fitness
Impairment
Tester
(FIT)
Workplace
Safetv
Screening
Evaluation
T he
FIT
(PMI,
Inc.,
1999)
is
a
computerized
fitness-for-duty test
that
requires
participants
to
peerintoa
device
in
whichvisual
stimuli
(bothmoving
an d
stationary)
are
presented.he
device
detects
changesin
pupil
size
(assmallas
0.05m m )
an d
movements
of
th e
ey e
(as
smallason e
degree)in
response
to
controlled
flashesoflight
and moving
hght
targets.
Measures
of
saccadicvelocity,
pupil
diameter,
pupil-
contraction
latency,
an d
pupil-constriction
amplitude
were
calculated
by
th e
FIT
device
an d
then
downloaded
to
a
Pentium-based
computer
fo rprocessing
in
arelational
database.
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Physiologicaldata
recording
Electroencephalographic
(EEG),electro-oculographic(EOG),
and
electrocardiographic
(EKG)
recordings
were
collectedwith
a
Grass-Telefactor
Instruments
Aurora
recording
system(West
Warwick,
R I)
running
TWin
collection
an d
analysis
software.or the
E E G
data,
Grassgold-cupelectrodesfilled
with
Mevidon
electrolyte
gel
were
used(21E E G
channels
were
referenced
to
Alan d
A 2during
recording).or th e
EOG
data.
Grass
F-E9M-60-5
1-mm
Silver/Silver
Chloride
electrodes
filled
with
Grass
EC2electrolyte
paste
were
used.or
theE KGdata,Kendall
MediTrace
disposable,self-adhesive
E K Gelectrodeswereused.
ata
were
digitized
ata
rateof200samplesper
second.T he
recording
filters
were
se tat
1.0-70
H zfor th e
E E G,
0.3-35H z
forth e
E O G ,
and
1.0-35
H z
for
the
E K G.
uringall
data
collection
(whether
inth e
simulator
or
inth eco-located
testing
room),
th e
quality
ofthe
recordings
w as
monitoredcontinuously
inreal
time
in
an
effort
to
make
corrections
of
an yproblems
which
were
encountered(i.e.,excessive
body/eye
movements
or
muscle
artifact).
Nevertheless,
in
the
caseof
the
data
recorded
in
th e
simulator,allactivityabovethe
alpha
band
(morethan13
H z)
ultimately
w as
disregarded
fi-om
analysisdu eto
the
presence
of
muscle
tension
that
couldnot
beeliminated
while
th e
pilots
were
actively
concentrating
on
the
flight
tasks.
Profile
ofMoodStates
(POMS)
Subjective
evaluations
of
mood
were
made
with
th e
Profile
of
Mood
States
(POMS)
(McNair,Lorr,an d
Droppleman,
1981).he
POMS
is
a65-item
questionnaire
which,
when
scored
according
tothe
specified
templates,measures
affect
or mood
on
6
scales:
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1)
tension-anxiety,
2)
depression-dejection, 3)
anger-hostility,
4)vigor-activity,5)
fatigue-inertia,an d6)
confusion-bewilderment.
actor
scoresoneach
scale
areanalyzed.
Visual
Analog
Scales
(VAS)
In
addition
to
th e
POMS,
subjectivesleepiness
an dalertness(and
other
parameters)
weremeasured
via
th eVA S
(a n
adaptationof th e
on e
developed
by
Penetar
etal.,
1993).
This
questionnaire
consistsof
8
lines,
100-millimetersin
length,eachofwhichi s
labeled
at
on e
en d
with
th ewords"not
at
all"
an dat
th eother
en d
withth eword
"extremely."
Centeredundereach
line
areth etest
adjectives
which
are
as
follows:"alert/able
to
concentrate,"
"anxious,"
"energetic,"
"feel
confident,"
"irritable,"
"jittery/nervous,"
"sleepy,"
an d"talkative."
he
participant
indicatedth epoint
on
the
linewhich
corresponded
to
how
he
feltalong
th e
specified
continuum
at
th e
timeat
which
th etest
is
taken.
he
score
fo r
each
item
consisted
of
th enumber
of
millimetersfromth e
left
side
of
th e
line
toth e
location
at
which
th e
participant
placed
his
mark.
Side
effects
rating
scale/Simulator
Sickness
Questionnaire
(SSO)
Once
during
each
of th etest
sessions,
participantswere
asked
to
complete
aside-
effects
rating
scale.This
rating
scale
includes
atotal
of71possible
symptoms
(including:
rapidheartbeats,
perceptual
disturbances,over
stimulation,
nausea,
dizziness,
vertigo,
euphoria,
tremors,
headaches,dryness
ofmouth,
upset
stomach,
an d
fatigue),each
of
which
wererated
on ascaleof none,
slight,
moderate,
or
severe.
rior
to
administration
of
th e
side-effects
scale,
participants
were
asked
to
complete
a
computerized
version
of
th e
Simulator
SicknessQuestionnaire
(Goweran d
Fowlkes,
1989;
Kennedy
et
al.,
1993).
This
questionnaire
(abbreviated
as
th eSSQ)
consists
of27
items,
but
only
16of
these
ar e
actuallyused
to
calculate
th e
SSQscores
based
on
self-reported
symptom
severity
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(rangingfrom
none,
to
slight,to
moderate,
tosevere).
actor
scores
on
symptoms
of
nausea
(gastrointestinaldistress),visuomotor
problems
(eye-strain
symptoms
including
headache),
disorientation
(vestibular
disturbances),
an dtotal
severity
ofproblems
(overall
discomfort)ar e
calculated.
Flight
Simulator
The
F-117A
Weapon
System
Trainer
(L-3Communications/Link
Simulation
an d
Training,
Binghamton,
NY)was
used
to
conduct
all
oftheflight-performance
assessments.
The
WeaponSystemTrainer (WST)isa
stationarydigital
device
thatsimulatesthe
characteristics
and
operations
of
the
F-117A
stealth
fighter
aircraft
that
is
currently
in
the
U.S.
A ir
Force
equipmentinventory.he
WST
providesa
fully-fiinctioning
replica
ofthe
interior
cockpit
oftheactualaircraft,including
allprimary
an d
secondary
flight
controls,
auralcues(enginesounds),
an d
cockpitlighting(L-3Conmiunications,
1993).
he
componentsofthe
W STincludethe
simulator
itself
as
well
asan
instructor/operator
station
(lOS),
a
computer complex
that
includes
an
Alpha
Server
8200
an d
Input/Ouput
(I/O)
cabinets,
an d
the
equipmentnecessary for
the
generationofout-of-the-window
an d
ffi.visual
scenes.
he
actual
F-117A
aircraft
(simulatedb y
this
WST )
is
atwin-turbofan
powered,
low-radar,
ground-attack
fighterwitha
single-seat
cockpit.he
F-117A
W ST
faithfiilly
simulates
the
F-117Aaircraft
to
theextent
that
trainingin
th eW ST
isdirectly
transferable
in
terms
of
instrument
flights,takeoffsan dlandings,instrument
navigation,
systemoperations,
an d
air-to-ground
attack
procedures.
n
the
present
study,
only
the
instrument-flight
simulation
capabihtyw as
utilized.
All
W STflights
were
setup
fornightilluminationconditions
with zerovisibilityan d
no
visiblelighting
onth e
horizon.hiswas
doneto
ensurethat
allpilotsremained
focused
on
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the
flight
instruments
(simulated
Instrument-FUght-Rules
conditions)throughout the
entire
testperiod.n addition,
th e
W ST
wassetup
to
generate
zero
airturbulence
with
no
wind
gusts
in
orderto
preventnon-pilot-related
flight-path
deviations.he
auto-throttle
an d
auto-
pilot modeswere
disengaged
to
force
all
participants
to
"hand
fly"
the
simulator.
Consistent
with
th e
earher study,
on e
ofthe
map
lightsin
th e
cockpit
remained onthroughout the
flight
profile
so
thatthe
cockpit
w as
dimlyilluminated
(thiswas
done
becausethe
earUerstudy
included
eye-tracking
assessments
thatimposed
an
instrumentation-based
requirement
for
additionalUghting).
Objective
flight
performance
data
were
collected
using
th e
Coherent
Automated
Simulation
Test
Environment
(CoASTE)
tool a
set
ofsoftware
routines
that
normally
provide the
capability
to
evaluate
simulator
performance,
display/manipulate various
data
from
simulator
data
pools,and/or
trace
and
correct
problems.heCoASTE's
trace
utility
w as
used
tocapture
various
parameters
offlightperformance
data
(see
Table1)at
a
rate
of2
Hz throughout
each
flight.
ne
complete
data filew as
generated
for each
simulator
flight,
an d
thisfile
contained
all
ofthe
data
collected
from
th e
beginningto
the
end
ofth e
given
simulation
session.ac hrecord
in th e
file
containedthe timeatwhich
eachdata
sample
w as
collected,the
actual
datapoints themselves,
an d
an identification
field
which
consisted
ofth e
subject
number,
th etesting
day,
an d
the
testingsession.he
completed
data
files
were
downloaded
toaReadAVriteCompact
Disk
(CD)at th e
conclusion
ofdata
collection
before being transferred
to
a
standard
desktop
Pentium-based
computer
where
each
file
w as
segmented
into
th e
individual
maneuvers
that
comprised
the
overall
flight
profile.
Afterwards,
root
mean
square
(RMS)
errors
for
maneuver-relevant
parameters were
calculated
for
statistical
analysis.
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The
measures(datapoints)
recorded
for
flight-performance
data
analysis
are
shown
in
the
tablebelow.
he
individual
flight
maneuvers
(and
the
measures
scored
foreach)
are
laterdescribedin
the
Proceduressectionofthis
report.
Table
1 .Measuredsimulatorflight
parameters
Number
Parameter
Range
1
hidicated
altitude
0-30,000feet
2
Indicated
airspeed
30-600
KIAS
3
Indicated
verticalspeed
0+/-5,000fjjm
4
Magneticheading
0-360
degrees
5
Pitch
angle
0+/-
90
degrees
6
Roll
angle
0
+/-
90
degrees
7
Slip
0+/-2balls
8
Localizer/course
deviation
0
+/-
2dots
9
Glideslope/course
deviation
0+/-2dots
Wrist
ActivityMonitors
( W A M )
Wrist
monitors
(Ambulatory Monitoring,
Inc.,
Ardsley,
N Y)
were
usedtotrack
sleep/activity
rhythmsina
relatively
unobtrusivefashion.n
thisstudy,
th e
W A M s
(which
are
battery-powered
devices
about
thesize
of
a
vmst
watch)wereused
primarily
to
motivate
subjects
to
follow
admonishments
no t
to
sleep
beyond
th e
designated
wakeup
timeon
th e
morning
of
theirtest
da y
untilthetime
atwhich
they
reportedto
th e
Laboratory
for
testing(i.e.,
at
1800).n
addition,
these
monitorswereusedto
ensurethe
volunteersobtained
sufficient
sleep
on
th e
night
prior
to
testing.ctivitydatawere
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-
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downloaded
once
theparticipant
arrived
at
th esimulator
facility
for
electrodeapphcation
(prior
to
the
sleep-deprivation
period).
hecomputer-generated
actigraphswerevisually
inspected
to
ensure
compliance withthe
"nonap"
rule
and
thestated
pre-study
or
recoverysleeptimes.
hedata
from
theWAMs were
no t
further
analyzed.
Procedure
hi-processing
Prior
to
being
admittedtothestudy,
each
participant's
medical
records
were
screened
for
current
illnessesor
disqualifying
medicationsby
themedicalmonitoror
his
designee
at
the
HoUoman
AFB
medical
clinic.
fterwards,
participants
signed
the
informed
consent
agreementand
were
briefed
on
allof
the
upcomingstudyprocedures.
One
of
the
investigators
met
one-on-one
with
each
participanttoaddressany
questionsor
concernsthat
the
participant
may
havehad.
General
approach
Thereweretwogroupsofparticipants
inthis
investigation.negroupconsistedof
five
of
the
F-117
pilots
who
were
re-recruitedfrom
a
previous
fatigue
study
in
which
identical
testing
timesandprocedures
were
used
(with
the
exceptionthatnofatigue
intervention
was
provided).nother
groupconsisted
offive
newlyrecruited
F-117
pilots
whowere
testedin
the
present
study
bothwitha
fatigue
intervention
(modafinil)
and
without
a
fatigueintervention(placebo).hus,the
re-recruited
subjectsexperiencedonly
one
sleep-deprivation
cycle
in
the
present
investigation
(during
which
they
received
modafinil)becausetheir
previously-collected,no-freatmentdatafromanearUersleep-
deprivationstudywere
used
as
the
comparison
condition.he newlyrecruited
subjects
experienced
tw o
sleep-deprivation
cyclesseparated
by a
period
of
recovery sleep
in
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-
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which
modafinil
was
administered
in
thefirst
cycle
and
placebo
w as
administered
inth e
second. lthough
thisis
no t
the
best
possible
experimentaldesign,itprovided
a
compromise
between
operationaldutyrequirements
(minimally
conflicting
with
th e
squadron's
missionschedule)
an d
researchnecessities(partiallycontrolling
fo r
subject
expectancies,
an dfullycontrolling
for
the
potential
treatment/no-treatment
order
confound),
asdiscussedearlier.
Without
thiscompromise,the
investigation
wouldnot
have
been
approvedor
conducted.
Eachparticipantcompleted
training/familiarity
sessions
priortoth e
beginningofthe
deprivation
cycles,
and
after
a
suitable
night
of
sleep,
he
completed
five
testing
sessions
during
each
ofthe
sleep-deprivation
cycles
towhichhewas
exposed.
heschedulesfor
re-recruited
volunteers
an dnewly-recruited
volunteersar e
described
below.
General
schedule
for re-recruitedpilots
Inth ecaseofth e
re-recruited
volunteers,only
tw otrainingsessionswereconducted
since
these
volunteershad completedthreetraining
sessions
an d
five
testingsessions
(usingth e
same
tests/methodologies) less
than
six
monthsprior
to
the
present
investigation.his
training
began
atapproximately
1630
on
th etraining
da y
an d
ended
at
approximately2030
on
this
sameday.
efi-esher
flightsfor
th e
re-recruited
subjects
were
conductedat
1700an d
1900.articipants
were
guided
through
th e
standardized
flight
maneuvers
by
members
ofthe
research
staffw ho
monitored
eachflight
an d
communicated
instructions
to
the
pilot
vi a
intercom.
long
with
these
flights,
there
was
training
on
the
other tests.
During
each
training
session,
re-recruitedparticipants
completed
tw o
iterationsofth e
M A T B ,
A N A M ,
VA S,
POMS,
an dFIT torefi-eshtheir
knowledge
an d
proficiencyonthese
evaluations.
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Followingtheafternoon/evening
of re-training,and
after
an
average
of
7
hoursand
40
minutesofsleep,
thesepilots
returned
to
the
testing
faciUtytocomplete
the5testing
sessions
that
occurred
duringtheir
single
sleep-deprivation
cycle.he
first
of these
was
a
pre-deprivation
sessionwhich
began
at
2100onthe
dayonwhichtheyreportedbackto
thesimulatorfacility,andthelastofthese
was
a
sleep-deprivation
session
thatendedat
2000,after
36-37
hours
withoutsleep(the
actuallengthof the wakefiilness
period
was
somewhatdependentonthe
exact
wakeuptime
that
was
necessarytoensurethevolunteer
acquired
approximately
8hours
of
pre-study
sleep).
Modafmil
was
administeredin
100
mg
doses
at
midnight,
0500,
and
1000.
Nosleep
was
permitted
throughout
the
deprivationperiod,
and
theparticipants
were
admonished
notto
napfi-om
the
time
at
which
they
awoke
on the
testmorning
until
the
timeatwhich
they
reported
for
testing.
Notethat
the
participantshad
akeady
beenawake
for
approximately14
hours
before
the
first
test
session
began.
A
more
detailed
overview
of
the
actual
sleep-deprivation
testing
schedule
is presented
after
thegeneralschedule
for
the
newly-recruitedpilots
is
discussed.
Generalschedule
for
thenewly-recruited
pilots
The
newly-recruited
volunteers(those
who
did
not
participate
in
theearUer
F-117
fatigue
study)
completed
three
trainingsessionsjust
like
the
ones
that
were
originally
providedfor the
participants
in
the
previous
investigation.he
training
began
at1330
on
the
training
da y
and
ended
at
approximately
2100
on
the
same
day.
raining
flights
for
the
newlyrecruitedsubjects
were
conductedat
approximately1400,1700,and1900.
Alongwith
these
flights,there
was
training
ontheothertests.
Newly-recruited
participants
completed
six
iterations
of the
M A TE,
nine
ANAM
tests,
three
VAS,three
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POMS,
an d
tw o
FIT evaluations
during
training,th esameasthe
previously-recruited
participantsreceived
on
their
original
training
day.
hus,
at
the
conclusion
of
th e
training
day,
newly-recruited
participants
hadreceived
three
full
training
sessions
on
th e
flights,
withmoreofth eotherevaluations,dependingonth e
number
estimatedtobeneededto
reachasymptotic
performance.
ollowing
th e
afternoon/eveningof
training,
an dafter
approximately
8hours
of
sleep,
these
pilots
retumed
to
th e
testingfacility
to
complete5
testing
sessionsforth efirst
oftheir2sleep-deprivation
cycles.hefirst
sessionw as
a
pre-deprivation
sessionwhichbegan
at
2100on
th e
da y
on
whichtheyreportedback
to
th e
simulator
facility,
an d
the
last
of
these
w as
a
sleep-deprivationsession
that
ended
at
2000,after
36-37hours
without
sleep
(the
actual
length
of th e
wakefiilnessperiodw as
somewhat
dependent
on
th e
exact
wakeup
time
that
w as
necessary
to
ensure
th e
volunteer
acquired8hours
ofpre-study
sleep).
Modafinil
w as
administered
in10 0
mg
dosesat
midnight,
0500,
an d
1000to
all
of the
newly-recruited
pilotsduring
this
first
testing
cycle.
fterreleasefi-omthis
cycle
of testing,andafter
approximately9-10
hours
of
recovery
sleep,
th e
volunteerretumedfor
asecond
sleep-deprivation
cycle
whichbegan
with
testing
at
2100
on
this
evening
an d
lasted
until2000
on
th e
evening
of th e
next
day.
Placebotablets
were
administered
at
midnight,0500,
an d
1000toall
ofthenewly-
recruited
pilots
during
this
second
testing
cycle
despite
th e
factthat
the
subjectsweretold
th e
drug/placebo
orders
would
be
randomized.
leep
w as
no tpermitted
on
either
of
th e
test
nights,
and,
as
w as
th e
case
fo rth e
re-recruited
participants,
these
pilots
were
admonished
no t
to
na p
between
the
timeat
whichthey
awoke
in
th e
morning
until
the
time
at
which
theyreportedfortesting.
ot e
that
a
minimum
of
approximately
9hours
of
recovery
sleep
w as
required
between
the
tw otest
cycles,
an ddependingupon
th e
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wakeup
times
necessaryto
gain this
recovery
sleep,
th e
total
subsequent period
of
continuouswakeflilness
fluctuated
between
36an d
37
hours.
lso
note
thatth e
volunteerswere
awake
for
approximately
13-14
hours
before
thefirst
test
session
began.
Schedule
fo r
both
groups
ofpilots
Prior
to
reporting
to
th e
simulatorbuilding,participantswere
evaluatedby
a
flight
surgeon
at
th e
Hollomanmedical
clinic
at
1200
to
ensure
theirfitness.iaddition,
informed
consent
w as
obtained.
ext,
th e
volunteers
reported
toth e
simulatorbuilding
at
designatedtimes
for theirafternoonan devening
training
sessionsas
described
above.
On
th e
testing
days,
all
of
th e
participants
were
asked
to
wake
up
at
0600
(o r
0700
if
necessary
toobtain
