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Evaluation of Several Common Antimotion Sickness Medications and Recommendations Concerning Their Potential Usefulness During Special Operations

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  • U.S. Navy Medicine

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NAMRL evaluated antimotion sickness medications to help the USSOCOM Biomedical Initiatives Steering Committee explore alternatives to meclizine. This double-blind, placebo-controlled study compared five groups (n = 30 per condition): 1) oral + transdermal placebo (control); 2) 50 mg oral meclizine + transdermal placebo; 3) 25 mg oral promethazine + transdermal placebo; 4) 0.8 mg oral scopolamine + transdermal placebo; 5) oral placebo + transdermal scopolamine (1.5 mg). Each condition included oral caffeine (200 mg). Medication efficacy was defined as the number of tilts tolerated upon reaching sustained moderate nausea during a Coriolis, cross-coupling stimulus. A past motion susceptibility rating was employed as a covariate. Performance was evaluated with cognitive and psychomotor test batteries derived from USSOCOM?s Mission-Related Performance Measures. MANOVA detected no medication-related performance differences in either battery. Planned contrasts compared meclizine to promethazine and scopolamine (oral or transdermal), while controlling for past susceptibility. The only observed difference was between meclizine (M = 170 tilts, SE = 13) and oral scopolamine (M = 217, SE = 13), p = .04; however, a post-hoc comparison failed to distinguish oral scopolamine from placebo. Lack of observed medication performance differences implied that USSOCOM may consider alternatives to meclizine; however, efficacy findings were inconclusive.
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EvaluationofSeveralCommonAntimotion
SicknessMedicationsandRecommendations
ConcerningTheirPotentialUsefulnessDuring
SpecialOperations
ARTICLE·DECEMBER2009
CITATIONS
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6AUTHORS,INCLUDING:
BenDLawson
UnitedStatesArmy
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UniversityofWestminster
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StevenJ.Kass
UniversityofWestFlorida
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Availablefrom:JohnFGolding
Retrievedon:16February2016
Lawson, B.D., McGee, H.A., Castaneda, M.A., Golding, J.F., Kass, S.J., & McGrath, C.M. 2009. Evaluation of several common
antimotion sickness medications and recommendations concerning their potential usefulness during special operations. NAMRL
Tech Report No. 09-15. Pensacola, FL: Naval Aerospace Medical Research Laboratory.
1
NAVAL AEROSPACE MEDICAL RESEARCH LABORATORY (NAMRL)
280 FRED BAUER STREET, BUILDING 1811, PENSACOLA, FLORIDA 32508
NAMRL TECHNICAL REPORT 09-15
EVALUATION OF SEVERAL COMMON ANTIMOTION SICKNESS MEDICATIONS AND
RECOMMENDATIONS CONCERNING THEIR POTENTIAL USEFULNESS DURING
SPECIAL OPERATIONS
Ben D. Lawson
Heather A. McGee
Michael A. Castaneda
John F. Golding
Steven J. Kass
Christopher M. McGrath
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1. REPORT DATE
02 DEC 2009 2. REPORT TYPE 3. DATES COVERED
4. TITLE AND SUBTITLE
Evaluation of several common antimotion sickness medications and
recommendations concerning their potential usefulness during special
operations
5a. CONTRACT NUMBER
5b. GRANT NUMBER
5c. PROGRAM ELEMENT NUMBER
6. AUTHOR(S)
B Lawson; H McGee; M Castaneda; J Golding ; S Kass 5d. PROJECT NUMBER
5e. TASK NUMBER
5f. WORK UNIT NUMBER
70509
7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES)
Naval Aerospace Medical Research Laboratory,280 Fred Bauer
Street,Pensacola ,FL,32508
8. PERFORMING ORGANIZATION
REPORT NUMBER
NAMRL-09-15
9. SPONSORING/MONITORING AGENCY NAME(S) AND ADDRESS(ES) 10. SPONSOR/MONITOR’S ACRONYM(S)
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Approved for public release; distribution unlimited.
13. SUPPLEMENTARY NOTES
14. ABSTRACT
NAMRL evaluated antimotion sickness medications to help the USSOCOM Biomedical Initiatives Steering
Committee explore alternatives to meclizine. This double-blind, placebo-controlled study compared five
groups (n = 30 per condition): 1) oral + transdermal placebo (control); 2) 50 mg oral meclizine +
transdermal placebo; 3) 25 mg oral promethazine + transdermal placebo; 4) 0.8 mg oral scopolamine +
transdermal placebo; 5) oral placebo + transdermal scopolamine (1.5 mg). Each condition included oral
caffeine (200 mg). Medication efficacy was defined as the number of tilts tolerated upon reaching sustained
moderate nausea during a Coriolis, cross-coupling stimulus. A past motion susceptibility rating was
employed as a covariate. Performance was evaluated with cognitive and psychomotor test batteries derived
from USSOCOM?s Mission-Related Performance Measures. MANOVA detected no medication-related
performance differences in either battery. Planned contrasts compared meclizine to promethazine and
scopolamine (oral or transdermal), while controlling for past susceptibility. The only observed difference
was between meclizine (M = 170 tilts, SE = 13) and oral scopolamine (M = 217, SE = 13), p = .04; however,
a post-hoc comparison failed to distinguish oral scopolamine from placebo. Lack of observed medication
performance differences implied that USSOCOM may consider alternatives to meclizine; however, efficacy
findings were inconclusive.
15. SUBJECT TERMS
16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF
ABSTRACT 18. NUMBER
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2
Executive Summary
The Naval Aerospace Medical Research Laboratory (NAMRL) evaluated several antimotion
sickness medications for the Biomedical Initiatives Steering Committee (BISC) of the U.S.
Special Operations Command (USSOCOM). The BISC wished to explore likely alternatives to
meclizine, its usual first-line defense against motion sickness. Hence, this study sought to
determine whether scopolamine (oral or transdermal) or oral promethazine were more effective
than oral meclizine and whether they induced unwanted performance decrements which might
render them unsuitable for further evaluation by Special Operations Forces (SOF).
This double-blind, placebo-controlled, double-dummy, randomized study evaluated five
independent groups (n = 30 per condition):1) 50 mg oral meclizine + transdermal placebo (the
comparison condition closest to the current USSOCOM regimen); 2) 25 mg oral promethazine +
transdermal placebo; 3) 0.8 mg oral scopolamine + transdermal placebo; 4) oral placebo +
transdermal scopolamine (1.5 mg); 5) oral + transdermal placebo (the control condition). The
BISC requested that each condition also include oral caffeine (200 mg) to counteract any
sedation from the treatment medications. Motion sickness was elicited via 12 roll tilts per
minute during continuous yaw rotation, with yaw starting at 6 dg/s (1 rpm) and increasing by
6dg/s each minute, up to a maximum of 240 dg/s (40 rpm). The main measure of medication
efficacy was the number of sickening roll head tilts tolerated upon reaching moderate nausea for
1 min. without abatement. A rating of past motion susceptibility was employed as a covariate
using the Motion Sickness Susceptibility Questionnaire (MSSQ-short, Golding, 2003).
Performance side-effects were evaluated with cognitive and psychomotor test batteries derived
mainly from the USSOCOM’s Mission-Related Performance Measures.
MANOVA detected no medication-related performance differences in the cognitive or
psychomotor test battery. Planned contrasts of medication efficacy compared meclizine (the
reference drug) to promethazine, oral scopolamine and transdermal scopolamine, while
controlling for past susceptibility (MSSQ) via ANCOVA. Three treatment conditions
(promethazine, oral scopolamine, transdermal scopolamine) were not planned for ANCOVA
comparison with one another a priori, because they yielded similar efficacy in the literature and
thus were not hypothesized to differ from one another. The planned comparisons detected a
significant difference between meclizine (M = 170 tilts, SE = 13) and oral scopolamine (M =
217, SE = 13), p = .039, implying that significantly more sickening head movements were
tolerated under oral scopolamine. Nevertheless, a post-hoc comparison failed to distinguish oral
scopolamine from placebo, so the efficacy findings are not conclusive.
Lack of observed medication-related performance side-effects in this large battery of
measures relevant to Special Operations Forces (SOF) implied that if the BISC of the
USSOCOM wishes to consider further evaluation of the tested medications, they may do so
without undue concern about major performance side-effects, i.e., based mainly on comparisons
of relative medication efficacy. Collectively, the literature, operational and logistical concerns,
and our experimental findings imply that oral scopolamine merits further evaluation under
conditions where a clear distinction from placebo can be established. However, we recommend
oral scopolamine should be used only if the first-line defense (meclizine) does not help the
patient sufficiently; also, it should be administered with an appropriate stimulant and it should be
tested before the mission, so the patient can be monitored for visual blurring or excessive
drowsiness.
3
Introduction
Prevalence and Magnitude of the Motion Sickness Problem.
Motion sickness is common in sea, air, and land operations and represents a significant
problem for the Department of Defense and NASA. Incidence estimates vary among different
platforms, conditions, duties, and personnel, but the problem is very common by any estimate.
Seasickness affects approximately 25% of military personnel adversely in moderate seas and
70% in rough seas (Pethybridge, 1982). Approximately 14-50% of personnel are affected by
airsickness (Acromite et al., 2004); while up to 64% of military parachutists are initially afflicted
(Antunano & Hernandez, 1989). Motion sickness even affects approximately 55% of Army
soldiers traveling by land in a command vehicle (Cowings et al., 1999).
Since motion sickness does not require actual body motion, it is often experienced by military
personnel outside the transportation setting. The vestibular brainstem is affected by stimuli other
than physical acceleration; hence, whole-field visual motion triggers a type of motion sickness
that afflicts roughly 30% of Navy simulator trainees and 60% of Virtual Environment users
(Lawson et al., 2002). Some individuals experience lasting effects even after the cessation of the
challenging visual or motion stimulus. For example, up to 8% of simulator users and 5% of sea
voyagers will experience effects lasting more than six hours after cessation of the stimulus.
Sometimes, such effects persist for several days (Lawson et al., 2002). Loss of normal gravity
alters vestibular functioning as well. Space sickness is reported by 67% of astronauts, incurring
tremendous cost (Davis et al., 1988). In fact, motion sickness medications are the most
commonly-prescribed drugs in space, accounting for 47% of all medications taken (Graebe et al.,
2004).
Motion sickness is costly to the government in terms of readiness, time, and money. A crew
member’s failure to perform required duties during rough seas is correlated with his or her past
history of motion sickness susceptibility (Colwell, 2000). The experience of stomach symptoms
in a moving ship simulator slows a subject’s performance and makes failure to complete tasks
more likely (Colwell, 2000). In fact, approximately 80% of personnel have difficulty working
while seasick (Pethybridge, 1982). During North Atlantic operations aboard a 3000 ton (U.K.)
Frigate, about 38% of the voyage time will be spent at Sea State 5 or above, leading to a loss of
productive days at a rate of about 1 day lost per 10 at sea (or about 15 days lost over the duration
of the average voyage). (Dobie, 2003.)
The distraction of nausea at sea is obvious, but a more insidious problem is motion-induced
loss of alertness. During NATO Atlantic Fleet operations, the most common symptoms were
fatigue and poor sleep, which were related to sea state and ship location, but not energy
expenditure (Colwell, 2000). This pattern of findings tends to implicate visual-vestibular
mechanisms more than simple physical fatigue due to muscular compensation for ship motion.
Even aboard an aircraft carrier, the USS Kennedy (CV-67), a Senior Medical Officer (E. Hopkins
III, personal communication, 2001) noted that motion-induced drowsiness indicative of sopite
syndrome (Graybiel and Knepton, 1976; Lawson and Mead, 1998) was common and the need to
take naps was not always traceable to sleep deprivation.
Motion sickness has operational ramifications beyond those triggered by the discomfort
associated with nausea. In fact, the most commonly documented motion-related performance
decrements occur in tasks that are directly relevant to situation awareness, such as tasks requiring
concentration, target tracking, navigation plotting, and time estimation (Lawson et al., 2003).
4
Motion stimuli even affect muscular coordination and equilibrium (Lawson et al., 2003). Of
special interest to USSOCOM, seasickness is known to be greatest for small vessels
(Pethybridge, 1982), such as those critical to expeditionary or special operations. Naval Combat
Demolition Unit 46 is a notable early example from WWII (Topics Entertainment, Markham
Interview, 2002); its officer was too seasick to organize the evacuation of his men from a sinking
LCT or to lead them into battle.
Countermeasures for Motion Sickness
Adaptation protocols or medications are the two most common countermeasures for motion
sickness. Adaptation protocols are effective and drug-free, but implementation is time-
consuming and relatively costly in terms of labor and equipment. Obviously, adaptation
protocols do not provide protection until adaptation has been acquired. Finally, adaptation must
be maintained via repeated exposure to motion, because much adaptation can be lost during a
long layoff.
Medications are generally the cheapest and fastest-acting means to control motion sickness
symptoms, but their efficacy against motion sickness is limited. Oral medications are the most
common means to control motion sickness symptoms; however, their onset time is slow
(compared to injectables), their efficacy varies, their absorption is disrupted by vomiting, and
they may elicit unwanted side effects (Graybiel & Lackner, 1987). Transdermal delivery offers
certain advantages over oral delivery (e.g., convenience, continued delivery over time, resistance
to loss by vomiting), but onset time is even slower and absorption is more variable (Parrot,
1989). Perhaps the most effective administration method is injection, which has become the
method of choice for astronauts in need. This method is highly effective with a relatively small
dose of medication; moreover, side-effects appear to be fewer than those associated with oral or
transdermal delivery (Graybiel & Lackner, 1987). However, invasive intramuscular injection
could be inconvenient for military soldiers in a dynamically moving vehicle setting, because of
difficulty with manual coordination, extra time required, the need for sterile handling/disposal
without fluid exchange, and problems with user acceptance. Hence, oral medications are most
commonly used in military operations, although faster-acting intranasal medications are being
investigated for possible future use (Simmons et al., 2007; Simmons et al., 2008a,b).
Medications the USSOCOM Wished to Compare to their Current Regimen of Meclizine
According to the BISC’s USSOCOM Biomedical R&D Task Statement #2005-4, several
Naval Surface Warfare units requested improved treatments for motion sickness, because the
currently recommended regimen of meclizine was not as effective as desired and was sometimes
sedating. The USSOCOM sponsor was interested in exploring medications beyond meclizine,
while still focusing on medications that were readily available on the market. Hence, the BISC
of the USSOCOM requested The NAMRL to carry out a study of several common antimotion
sickness medications, some of which were to be tested in combination with oral caffeine. The
BISC did not wish to evaluate a stronger stimulant than caffeine, but did agree with the
NAMRL’s recommendation that caffeine should be administered in all conditions of the
experiment in order to improve interpretation of the results concerning antimotion sickness
medication efficacy. Hence, the final study the BISC sponsored entailed monitoring motion
5
sickness symptoms and performance side-effects among groups of participants subjected to one
of five experimental conditions:
1. Current Regimen: Oral meclizine (50 mg) plus oral caffeine plus transdermal
placebo.
2. Alternative Medication: Oral promethazine (25 mg) plus oral caffeine plus
transdermal placebo.
3. Alternative Medication: Oral scopolamine (0.8 mg) plus oral caffeine plus
transdermal placebo.
4. Alternative Medication: Oral placebo plus oral caffeine plus transdermal
scopolamine patch (1.5 mg).
5. Control Condition: Oral placebo plus oral caffeine (200 mg) plus transdermal
placebo (Control Condition).
A Consideration of Meclizine (the Current Regimen)
Meclizine hydrochloride (Antivert, Bonine)., promethazine (Phenergan), and
scopolamine hydrobrimide (Scopace, Transderm-Scop) are three well-established antimotion
sickness drugs, with scopolamine or promethazine tending to offer stronger motion resistance
than meclizine (Wood & Graybiel, 1968; Graybiel & Lackner, 1987; Wood et al., 1992);
however, these medications have the potential for eliciting drowsiness (Wood et al., 1990). The
present study administered caffeine in all conditions to minimize drowsiness and also monitored
several measures of cognitive performance, subjective sleepiness, and sopite syndrome. Since
meclizine is the reference medication for this study, it is described in more detail below.
According to the Biomedical Initiatives Steering Committee (BISC) of the USSOCOM, the
first line of defense against motion sickness among special surface warfare units is typically
meclizine hydrochloride (Antivert, Bonine). The recommended dosage of this over-the-
counter medication is 25 to 50 mg, one hour before traveling, to be repeated every 24 hours as
needed [Physicians’ Desk Reference (PDR), 2000]. Meclizine is a good choice for a first-line
defense against motion sickness, due to the relatively mild side-effects most users experience
(PDR, 2000). However, it may not be appropriate for severe motion or for individuals of
greater-than-average susceptibility. Meclizine should not be taken with alcohol. It has been noted
(Kuver et al., 2004) that the depressant effects of some antimotion sickness drugs (e.g.,
promethazeine, meclizine) will be additive if alcohol is consumed.
The most common side-effects of meclizine are drowsiness and dry mouth; rare side-effects
include blurred vision (PDR, 2000). For both promethazine and meclizine, the sedating and
performance effects decrease with repeated administration for three or four days; however,
drowsiness may still be significant many days after starting treatment (up to seven days of
significant drowsiness has been observed with meclizine, according to the U.K. Department for
Transport, 2004). Meclizine can have measurable effects on evoked potentials and hand-eye
coordination (Lauter et al., 1999). When more than 25mg of meclizine are administered,
subjective drowsiness may occur, along with impairment of Choice Reaction Time (also called
“Complex Reaction Time”) and Digit Symbol Substitution. Of special concern for military
missions following transportation to the theater of operations is the finding that greatest
performance impairment occurs nine hours post-dose (Department of Transport, 2004).
Meclizine is slower to take effect than promethazine or scopolamine (Machen, 2004; Wood
et al., 1981; Canadian Committee to Advise on Tropical Medicine and Travel, 2003), making it less
6
suitable than these other oral medications as a prophylactic once transportation has begun, or as a
“rescue remedy” after the earliest warning symptoms of motion sickness are perceived.
However, since meclizine has fewer unwanted side-effects than promethazine, it is often
considered a first line of defense against weak to moderate motions (Hain, 2003). One
comparison of oral scopolamine, cinnarizine, and meclizine found that meclizine conferred the
most tolerance to the sickening stimulus, with no differences in the Digit-Span Test (memory)
between the different countermeasures (Bashyal et al, 1998). However, the majority of research
finds that promethazine and scopolamine are superior to meclizine for alleviating the symptoms
of motion sickness (Dahl et al., 1984). For example, Wood, Graybiel, and Kennedy (1966)
conducted a sickening test requiring the adjustment of dials arranged around the subject while he
was inside a rotating room. They found the most effective drug combination was scopolamine
plus amphetamine, second best was scopolamine alone, third best was amphetamine, and fourth
best was meclizine. Hence, meclizine was not a top performer in this test. Wood & Graybiel
(1970) compared eight drugs during the dial test in the Slow Rotation Room. They noted
meclizine was not a top performer and found that increasing the dose of meclizine did not
improve its effectiveness, which they asserted is a common finding with certain antimotion
sickness drugs. For this reason, the NAMRL did not propose to test higher doses of meclizine in
the current research, to see if greater protective benefit could be obtained while avoiding the side
effects associated with stronger drugs.
Wood et al., 1985 studied the baseline side effects of motion sickness drugs, in absence of
motion. Drowsiness was the side effect that appeared to have the best association with
performance decrement. Combining 5 mg amphetamine with 0.8 mg doses of scopolamine
or promethazine resulted in good (placebo level or better) performance on a visual pursuit
tracking task. Scopolamine alone at 0.8mg produced deficits. However, scopolamine alone at
0.6 mg or less produced no performance deficit versus placebo. Also, 50 mg of either cyclizine,
meclizine, or dimenhydrinate produced no deficit versus placebo (i.e., good performance).
Based on these findings, we conclude that meclizine does not always produce appreciable
baseline side-effects for performance and that the dosage of stronger drugs such as scopolamine
and promethazine can be controlled (or combined with other drugs) to avoid such effects.
Overall, we agree with the oral medication advice of Wood et al. (1981), who recommended
meclizine at 50mg for mild motions and scopolamine 0.6mg plus d-amphetamine 5mg for severe
motions.
The Purpose of the Current Study
The current study sought to determine whether oral scopolamine, transdermal scopolamine,
or oral promethazine would provide significantly improved resistance to sickening motion,
compared to oral meclizine. Hence, our planned comparisons were of meclizine versus the three
other medications. A placebo group was included to establish, post hoc, whether any medication
which was significantly more effective than meclizine would be distinguishable from placebo as
well.
Numerous measures of psychomotor and cognitive performance were evaluated to quantify
any medication side-effects. In fact, one of the key operational questions was whether the BISC
of the USSOCOM should consider field evaluations of antimotion sickness medication choices
beyond meclizine, or if a noticeable sacrifice in performance would make such evaluations not
7
worthwhile. This experiment attempts to answer these questions and provides eight
recommendations to the USSOCOM BISC.
Methods
Participants
The subjects consisted of 150 males ranging in age from 18 to 37 years, with the mean age of
participants being 24 years (SD = 3). No females were recruited, because the findings of this
study were meant to apply to Special Operations Forces (SOF). Based on a sample size estimate
using the data of Stott et al. (1989), 30 subjects were assigned to each of the five conditions of
the study. Volunteers were recruited from a pool of U.S. Naval Officer flight candidates and
enlisted aviation support students waiting to begin classes at Naval Air Station Pensacola, FL.
All participants were screened for past and present medical conditions, sensitivity to
medications, and current physical health. Each participant gave written informed consent prior
to participation. The study protocol was approved by the NAMRL Institutional Review Board,
in compliance with applicable federal regulations concerning the protection of human subjects.
Apparatus and Materials
Stimulus. The most reliable and widely-employed method for eliciting motion sickness in a
controlled manner was developed by Navy investigators in Pensacola, Florida (e.g., Miller &
Graybiel, 1970); it consists of seated rotation in the yaw axis at constant velocity, accompanied
by paced head movements out of the yaw axis. This stimulus is known as Coriolis cross-
coupling. The cross-coupling test elicits at least minimal stomach symptoms in the majority of
participants, usually in less than 30 mins. (Miller & Graybiel, 1970), but symptoms usually build
gradually enough that test can be terminated quickly to avoid vomiting.
The current study called for yaw-axis rotation up to 240 dg/s (40 rpm) maximum while paced
head movements in the roll axis were made (See Figure 1). The sickening stimulus was based
loosely on the protocol of Stott et al., 1989, which calls for frequent but small changes in yaw
velocity during head tilt. The rotation device is shown if Figure 2. Participants began rotating in
yaw at 6 dg/s (one rpm), made 12 roll head tilts (right, up, left, up, then repeat this sequence
twice more) of 40 degree-amplitude during 48 seconds of yaw rotation, then were allowed 12
seconds of rotation without head movements, during which motion sickness symptoms were
reported. If, at the conclusion of the symptom assessment, the participants were not
experiencing moderate nausea, they would begin rotating at 12 dg/2 (two rpm), and continue the
one-minute head tilt sequences, increasing yaw rotation velocity by 6 dg/s (one rpm) each
minute, up to a maximum of 240 dg/s (40 rpm). The yaw velocity profile and recorded roll head
tilt instructions were synchronized and controlled automatically using LabviewTM software.
Head movement amplitude was controlled by padded head stops above the subject’s
shoulders, which were calibrated to allow for the same amount of roll head movement to each
side, for each subject. The subject practiced the angle and timing of the head movements prior to
rotation and was observed by a chair-mounted video camera during rotation, to ensure safety and
strict compliance with the protocol. The subjects executed the head movements with their eyes
open, while viewing the interior of a chair-fixed canopy which eliminated room-referenced
8
ambient visual cues concerning self motion (Figure 2). The interior of the canopy was lit during
rotation, while the room which housed the rotating chair was dark.
Unless the subject asked to be removed from the study, this head tilt sequence was repeated
at increasing dwell velocity steps of chair rotation until 1) the participant experienced moderate
nausea which did not abate during one minute of cessation of head movements, 2) the participant
experienced three consecutive periods of moderate nausea during roll head movements (although
it abated during each one-minute rest), or 3) the participant reached 40 rpm or a total of 480 head
movements without meeting endpoint criteria #1 or 2, above.
Performance Measures.
Because of the potential for the antimotion sickness drugs in this study to elicit drowsiness
(Wood et al., 1990), we did post hoc comparisons of the relative degree of psychomotor and
cognitive side-effects elicited by the medication/stimulant combinations listed above. Many of
the measures were derived from Special Operations Forces Mission-Related Performance
Measures (MRPM) (Thomas et al., 1994; Shurtleff et al., 1994) and are based on widely-used
tests which are known to be reliable (Kane & Kay, 1992). We looked for differences in
performance across medication conditions (across subjects) and from baseline (no motion) to
post-motion (within subjects). We grouped the measures into those focusing on laboratory tests
of psychomotor performance and those focusing on computerized tests of cognitive performance.
This distinction allowed us to group similar performance tests for subsequent multivariate
analysis. We also tracked several aspects of subjective response using questionnaires. The
various performance tests and questionnaires are described below. The number and timing of the
administration of the tests is treated in the Procedures section.
Psychomotor Tests
Maximal Handgrip Strength and Endurance. As a measure of handgrip strength, subjects
performed a maximal voluntary contraction (MVC) three times with the dominant hand (Figure
3). The average of the three values was recorded. A value equal to 50% of the average MVC
was calculated and displayed on a computer screen. As a measure of endurance, subjects were
asked to maintain a force equal to 50 ± 5% of the average MVC for as long as possible. The
average MVC, duration, and integral (force multiplied by time) were recorded.
Shooting Skills. A specially modified weapon and target system (Figure 4) was used to
assess the ability of subjects to quickly acquire and hit a series of randomly presented targets.
The weapon, a demilitarized M-16 rifle, operated pneumatically. When the subject pulled the
trigger, a loud blast of gas was released (which mildly perturbed the sight picture) and a laser
beam shot at the target. Eight target disks were mounted 18 feet from the shooting line, on
computer-controlled pneumatically-activated targets. Targets were placed such that vertical and
horizontal adjustments of the rifle were necessary between shots. Targets were presented one at
a time and in pseudo-random order. Once a target was hit, the next target was presented. Subjects
were instructed to hit as many targets as possible during a two-minute session. Number of
targets hit and total number of shots taken were recorded by a laptop computer remotely
connected to the weapon. The two measures of shooting performance were as follows 1) the
USSCOOM MRPM (Thomas et al., 1994; Shurtleff et al., 1994) shooting score, which awarded
9
2 points for hitting the target in one shot, 1.4 points for hitting the target in two shots, 0.8 points
for hitting the target in three shots, etc); 2) the NAMRL measure of number of hits per second,
which was used because it captured speed and accuracy in one simple score and because it
avoided some of the potential drawbacks of the MRPM scoring method, such as the possibility
for a subject to achieve the same shooting score via different combinations of speed and
accuracy (for further details, see NAMRL’s evaluation of the MRPM apparatus in Appendix A).
Balance. Standing balance performance was assessed based on a portion of the Fregly
Ataxia Test Battery (Fregly, 1974). Participants stood on a slightly elevated balance beam, 30
in. x 2 ¼ in., approximately 6 inches off the ground (Figure 5). Subjects were instructed to stand
toe-to-heel with their legs straight and their arms crossed over their chests (known as the
Sharpened Romberg stance), while wearing a set of noise dampening headphones. Subjects
closed their eyes and tried to maintain balance as long as they could, for a period of up to 60
seconds. The time from eyes closed to stepping off the beam was measured with a stopwatch and
recorded for three trials per assessment. The subjects were closely observed to ensure that their
eyes remained closed during the task.
Visual Accommodation (VA). Near focus of Visual Accommodation was assessed using a
Royal Air Force Rule (Neely, 1956), shown in Figure 6. One end of the rule was rested on the
participants’ cheek bones, just under the eyes. At the other end of the rule there was a small
rectangular target, capable of sliding from one side of the rule to the other. Participants were
instructed to read a line of text printed on the target repeatedly as the box was moved towards
their eyes. Participants were instructed to say “stop” as soon as the line of text became blurred.
The distance of the target from the subject’s eyes was recorded (in cm).
Cognitive Tests
Five computerized tests were used to measure cognitive performance. The tests (described
below) are found in the Unified Tri-Service Cognitive Performance Assessment Battery (UTC-
PAB) (Englund et al., 1985) and the Walter Reed Army Institute of Research Performance
Assessment Battery (WRAIR-PAB) (Thorne, Genser, Sing, & Hegge, 1985). Tests in these
batteries have been used extensively (Kennedy & Bittner, 1977; Simmons & Kimball, 1982;
Naitoh, 1982; Edwards et al., 1985; Reeves & Thorne, 1988; Semple, 1992). These tests show
stable reliability and are generally viewed to be valid for the unique factor being measured by
each test (Kennedy, Turnage, & Osteen, 1989; Cambridge Cognition Limited, 2005). Three of
the tests below (Complex Reaction Time, Logical Reasoning, and Matching to Sample) were
administered as they appear in USSOCOM’s MRPM (Thomas et al., 1994; Shurtleff et al.,
1994). Two others (Simple Reaction Time and Time Estimation) were supplied by the NAMRL
due to their relevance to the detection of sedation (Simple Reaction Time) or motion side-effects
(Time Estimation) (Lawson et al., 2003).
Simple Reaction Time. Simple Reaction Time consisted of the subject viewing a
computer screen where the word “go” appeared on the screen (in large green font) at randomly-
timed intervals. The subject was instructed to press the spacebar on the keyboard as soon as they
saw the word “go” appear on the screen, at which point the word “stop” (in large red font) would
10
appear to confirm the button press. The amount of time (in milliseconds) from when the word
“go” appeared on the screen to when the spacebar was pressed was recorded.
Complex Reaction Time. In the Complex Reaction Time test (also called Choice
Reaction Time in the literature), participants were asked to use the up, down, left, or right arrows
key on the keyboard to follow a black square as it rapidly moved among four boxes arrayed
similarly to the arrows on the keyboard. The amount of time (in milliseconds) was recorded
from the onset of movement of the black square until the correct following key was pressed. An
example stimulus trial is shown in Figure 7.
Logical Reasoning. In Logical Reasoning (also called Semantic Reasoning in the
literature), participants were presented with two letters: A or B in random alternating sequences
(i.e. AB/BA). Statements such as: “A precedes B”, “B follows A”, “A does not follow B”, “B is
not preceded by A” were presented after each pair of letters and participants indicated whether
the statements were true or false by hitting the right or left arrow keys. Accuracy (percent
correct) and reaction time (in milliseconds) were recorded. An example trial is shown in Figure
8.
Matching to Sample. The Matching to Sample task measured short-term spatial memory
and pattern recognition skills by assessing an individual's ability to quickly and accurately
identify a comparison stimulus identical to a standard stimulus presented previously. The sample
stimulus (an eight-cell by eight-cell matrix) was presented on the screen for three seconds and
then removed from the screen. The presentation was followed by a delay interval (either one or
fifteen seconds). After the delay interval, two matrices were presented side by side on the
screen. One matrix matched the original, and one differed by two cells. The subject was
instructed to choose the matrix that matched the original. Twenty sample stimuli were presented,
ten for each of the two delay intervals. Accuracy data and response times were recorded for each
presentation. The second screen of a Matching to Sample trial is shown in Figure 9.
Time Estimation. Time Estimation was measured using a “time wall” task. The task
consisted of visually tracking a square which fell at a constant rate of decent from the top of the
computer screen and then disappeared behind a red “wall” about halfway down the screen.
Participants were asked to hit the “Enter” key at the time they believed the square would have
reached the bottom of the wall. The time estimated by the participant was recorded and used to
calculate the difference between the actual and estimated times. The stimulus is shown in Figure
10.
Questionnaires
Confidential Medical Questionnaire. The NAMRL’s Confidential Medical Questionnaire
(see Selected Documents and Forms, Appendix B) was a recruitment screening tool which
consisted of 24 questions concerning the existence of significant medical conditions, allergies, or
recent illnesses. It also asked about current level of fitness and current (last 24 hours) intake of
medications and/or alcohol.
11
Pre-Experiment Compliance Checks. The NAMRL’s Confidential Exclusionary Behavior
Questionnaire and Pre-Dose Compliance Checklist (both in Appendix B) verified compliance
with the behaviors required before the experiment. They consisted of questions concerning
recent alcohol consumption, medicine intake, use of nicotine or herbal products, consumption of
grapefruit juice, and caffeine consumption.
Motion Sickness Susceptibility Questionnaire Short-Form (MSSQ). The MSSQ-short form is
an 18-item questionnaire that reliably estimates how susceptible an individual is to motion
sickness based on prior exposure to motion stimuli, e.g., transportation aboard a car, boat,
airplane; or amusement park ride (Golding, 2006).
Simulator Sickness Questionnaire (SSQ). The SSQ is a multi-symptom motion sickness
checklist developed by Kennedy (1993) based on the Pensacola Motion Sickness Questionnaire
(Hardacre & Kennedy, 1963; Kennedy & Graybiel, 1965; Kennedy, Tolhurst, and Graybiel,
1965). The scale has been through many modifications over the years; the scale used for this
research was based on the expanded Kennedy list of all 26 symptoms appropriate for motion
challenges (rather than sharpened for simulator challenges), rated on a 1 to 4 scale (none, slight,
moderate, severe). A total score for was derived simply by summing the ratings for all 26 items.
Mild Motion Questionnaire (MMQ). The MMQ (Lawson et al., 2001; Wallace, Kass, &
Lawson, 2002) is a 39-item scale intended to assess the symptoms of sopite syndrome (Graybiel
& Knepton, 1976). Participants were asked to rate items on a 1 to 5 scale (not at all, a little,
moderately, fairly strongly, very strongly) regarding their reactions to mild or non-sickening
motions.
Stanford Sleepiness Scale (SSS). The SSS is a well established self-report measure of
alertness. Participants are asked to “choose the statement that best applies to your current state”.
A rating of 1 indicated “feeling active and vital; alert; wide awake” and a rating of 7 indicated
“almost in reverie; sleep onset soon; lost struggle to remain awake” (Hoddes et al., 1973).
NASA Task-Load Index. The NASA Task-Load Index is a semantic differential scale that
asks participants to rate their current state by marking a “ruler” between the semantic opposites
(Hart & Staveland, 1988). For the present study, we employed four (of six available) subscales,
measuring perceived level of a) Task Difficulty, b) Performance, c) Mental/Sensory Effort, and
d) Frustration associated with the computerized cognitive tests. This scale was employed
because we wished to determine whether a subjective increase in effort was required in any
experimental medication condition (i.e., separately from whether actual performance decrements
had been detected).
Rotation Data Sheet (RDS).. The RDS (Appendix B) was used to record motion sickness
symptoms (based on the diagnostic symptom criteria of Miller & Graybiel, 1970) just prior to
rotation, once a minute during rotation, and immediately after rotation. During each symptom
assessment, participants were asked to indicate if they were experiencing any stomach
awareness, stomach discomfort, or nausea. In addition to stomach/nausea symptoms,
participants were asked to report on common motion sickness symptoms including: dizziness,
cold sweating, increase salivation, warmth/flusing, drowsiness, and headache. Pallor was not
12
scored, because no direct face-to-face observations were possible during much of the experiment.
Participants were asked to rate each symptom as minimal, moderate, or major, based on
definitions provided prior to rotation (Lawson, 1993), with the exception of pre-nausea
symptoms (stomach awareness or discomfort), which were simply noted as present or absent
(Miller & Graybiel, 1970).
Procedure
Condition Randomization and Double Blinding. Study volunteers were randomly assigned to
conditions using assignment without replacement. Participants in all conditions were
administered both a patch and a capsule. There was no way for the participant or experimenter
to identify the medication condition based on the appearance of the patch or capsule.
Participant Recruitment. During the initial recruitment sessions, potential volunteers were
briefed on the purpose of the study, what the study entailed, and the risks and benefits associated
with participation. Recruits who chose not to volunteer were dismissed without penalty.
Recruits who decided to volunteer were asked to complete a Confidential Medical Questionnaire
(Appendix B). As a screening procedure, the Confidential Medical Questionnaires were
reviewed by a research assistant during recruitment sessions. Any questions pertaining to
exclusionary medical criteria were referred to the medical monitor, who made the final decision
concerning inclusion or exclusion. Volunteers who reported no exclusionary criteria were asked
to read and sign a consent form. The protocol, consent form, and recruitment procedures were
reviewed by the NAMRL Institutional Review Board. Participants were asked to refrain from, or
limit, certain behaviors listed on the Confidential Exclusionary Behavior Questionnaire
(Appendix B) for a specified number of days (three or seven days, depending on the behavior)
prior to participation. Recruitment sessions were concluded by scheduling two consecutive
participation days (one practice day, one test day) for each participant.
Practice Day (Day One). Each participant was asked to arrive at 1300 on his scheduled practice
day. Upon arrival, the participant was reminded about the nature of the experiment and what he
would be asked to do. The participant was asked to review, initial, and date the consent form
(which he previously signed during his recruitment session). A memorandum was then placed in
the participant’s medical records that described the possible medications ingested by the
participant during his participation in the study. This was done to enhance safety and to avoid
unwarranted penalty to any military participant who might be asked to engage in a urine test
during the period of his participation in the experiment. The Confidential Exclusionary Behavior
Questionnaire was completed by the participant and reviewed by the experimenter.
The participant then completed two computerized questionnaires (the MSSQ and the MMQ)
before beginning five performance practice sessions to become proficient at the performance
tests (see Practice Sequence Checklist, Appendix B). The number of times a given test appeared
in the practice sequences depended on how reliable the measure was and how quickly it became
stable with practice, as indicated by past studies (e.g., Kane and Kay, 1992; McGrath, Lawson, &
Kass, 2007) and by test-retest data provided by the custodians of the MRPM at Naval
Experimental Dive Unit, Panama City, FL (personal communication, Dr. Dale Hyde, 2005).
Additionally, logistical factors influenced the number of times a test was practiced. For
13
example, the maximal handgrip task is easy to learn, yet tiring to perform, so practice was
limited to three sessions to avoid fatigue as a confound during practice and muscle soreness as a
confound on Day 2 of testing.
During a given practice sequence, the participant performed a particular combination of
physical and cognitive tasks (Appendix B Practice Sequence Checklist). The practice sequences
were designed to familiarize the participant with the equipment and allow the participant to reach
his performance asymptote. At the completion of each practice sequence the participant was
given a ten minute break.
After all practice sequences were completed the experimenter reviewed a list of possible side
effects associated with the medications being studied. The participant was escorted to the
medical monitor’s office at approximately 1545. The medical monitor applied a patch behind
the ear of the participants’ non-dominate eye (e.g.., the patch was applied behind the left ear of
right-eye dominate participants). The participant was instructed on how to avoid disturbing or
dislodging the patch and asked to return the following morning at 0830 for his Test Day. This
protocol allowed complete absorption of the transdermal scopolamine, if any was present in the
patch.
Test Day (Day Two). Each participant was asked to arrive at 0830 on the day following his
practice day. Upon arrival, the participant was asked to initial and date his consent form (to
verify continued consent) and fill out a Pre-Dose Compliance Checklist (Appendix B). The
participant was then asked if he had experienced any symptoms (since departing the laboratory
the previous afternoon) which he would consider out of the ordinary or which caused him any
concern. To enhance experimenter blinding concerning medication condition assignment, this
symptom information (if any) was gathered and recorded in such a manner that it remained
unknown to the experimenter who would be recording the subject’s symptoms during rotation.
The participant’s response was recorded on an Adverse Event Form (Appendix B). If the
participant reported experiencing any symptoms, further documentation of the symptom,
duration, and severity was recorded. The participant then completed a set of computerized
questionnaires which included the SSS, the MMQ, and the SSQ. At approximately 0845, the
final pre-rotation assessments of performance began. The participant performed the physical and
cognitive performance batteries in the following order: Visual Accommodation, Balance test,
Cognitive Battery (including Simple Reaction Time, Complex Reaction Time, Logical
Reasoning, and Matching to Sample), Shooting, and Handgrip. Visual Accommodation and
Balance Test were performed first because they took very little time and were likely to show
subtle or transient disruption. Shooting and Handgrip were assessed towards the end of the
sequence because they were the most physically demanding tasks.
After completing the performance batteries the participants swallowed a capsule (medication
or placebo) with 240 ml of water. The capsules were administered between 0910 and 0920 and a
60 minute break followed to allow full absorption of the oral medication, if any. At
approximately 1010, the participant was reminded of the symptom definitions and was seated in
the chair. The participant practice executing the roll head tilts at the prescribed amplitude and
the same pace as the recorded instruction. An assessment of any symptoms or adverse events
was taken before rotation commenced (again, by a person other than the experimenter assessing
symptoms during rotation). At approximately 1025, the rotation test began. Hence, rotation
began approximately 75 minutes after capsule administration and 18.6 hours after transdermal
patch administration. Participants were rotated as described in the stimulus section above.
14
Following rotation, a final symptom report was recorded. The participant than began the
post-rotation assessment. The performance batteries were completed in the same order as in the
baseline assessment. After completing the performance tests, the participant filled out the same
set of computerized questionnaires that were completed pre-rotation (i.e., SSS, MMQ, SSQ).
The experimenter then removed the transdermal patch from the participant and took a final
symptom/adverse event report. The participant was debriefed and confirmed as symptom-free
before leaving the experiment. Any questionable cases were referred to the medical monitor.
Results
Stimulus Efficacy
The stimulus was very effective at producing motion sickness. Moderate nausea was
reported by 149 of the 150 participants. One participant reached 40 rpm (the maximum chair
velocity allowed in this experiment) without reporting moderate nausea, but he reported stomach
discomfort that was not strong enough to be called minimal nausea.
Medication Efficacy
The meclizine group had the smallest adjusted mean (M = 170, the fewest sickening head
movements tolerated) and the oral scopolamine group had the largest adjusted mean (M = 217,
the most head movements tolerated). Planned contrasts examined the difference in efficacy
between USSOCOM’s current meclizine regimen and the three other treatment medications
investigated, while partially controlling for past motion susceptibility (MSSQ score), via one-
way analysis of covariance (ANCOVA). The three other medications (promethazine, oral
scopolamine, transdermal scopolamine) tend to yield similar efficacy in the literature and were
not hypothesized to differ from one another. Hence, the following three comparisons were
planned: meclizine vs. promethazine, meclizine vs. oral scopolamine, and meclizine vs.
transdermal scopolamine. The independent variable was medication condition and the dependent
variable was number of sickening head movements tolerated. Results of the planned contrasts
from ANCOVA were Bonferroni-adjusted to control for multiple comparisons. A significant
difference was revealed between the meclizine group (M = 170) and the oral scopolamine group
(M = 217), p = .04 (1-tailed). No other contrasts were significant (See Figure 11).
It should be noted that overall conditional differences were not significant when all five
levels of the study (including three medications not hypothesized to differ from one another)
were evaluated via ANCOVA (placebo, meclizine, promethazine, oral scopolamine, and
transdermal scopolamine). The result of this omnibus ANCOVA fell short of significance, at
F(4, 144) = 2.09, p = .09, partial η2 = 0.06.
Following the significant meclizine versus oral scopolamine difference detected by the
planned comparisons, a post-hoc comparison was conducted on oral scopolamine vs. placebo,
controlling for MSSQ score. Although the oral scopolamine group (M = 217 head movements)
was the group with the largest number of head movements tolerated and the only group that
resulted in significantly more head movements than the meclizine group, a post-hoc comparison
to the placebo group (M = 181) failed to reveal a significant difference between the oral
scopolamine and placebo groups.
15
Performance Side Effects by Medication Condition
In general, the various performance measures were suitable for this experiment and a failure
to see a performance effect would not likely be due to a lack of stability or reliability in the
performance measures. More than half (6/12) of the measures were stable by the third practice
trial, and 92% (11/12) of the measures were stable by the last practice trial, as revealed by the
average Cohen’s d = 0.08 when the last two practice trials were compared to one another
(Turnage & Kennedy, 1992). The only measure that did not fully stabilize was Complex
Reaction Time, which still showed a small (11 ms) improvement on the last practice trial. The
performance measures showed good reliability as well. As in the literature and in our past
research (McGrath et al., 2007, summarized in Appendix C), speed of response was more
reliable than accuracy once subjects were practiced and proficient. The mean test-retest
reliability of response speed in the last two practice trials was good, with a Pearson’s r of 0.84.
Finally, our recent assessment (McGrath et al., 2007) suggests that the measures are sensitive to
environmental stressors, e.g., the first presentation of a loud, distracting noise had measurable
effects on performance.
Multivariate analysis of variance (MANOVA) was conducted to determine if there were
post-rotation medication condition differences detectable via the performance measures. The
performance measures were grouped (for MANOVA) into those which were mainly
physical/psychomotor and those which were part of the computerized cognitive test battery. Six
dependent measures of post-rotation physical performance were entered into the first MANOVA.
The six dependent measures of physical performance included: two measures of handgrip
performance (maximum grip score and grip endurance score), two measures of shooting
performance (MRPM shooting score and targets hit per second), score on the Fregly balance test,
and visual accommodation score. No significant differences in physical performance were found
among the five medication conditions; Pillai’s Trace = .15, F(24, 572) = .90, p = .61.
In addition, a one-way MANOVA was conducted to determine if there were conditional
differences (post-rotation) detected by the computerized cognitive performance measures. Five
dependent measures of post-rotation cognitive performance were entered into the MANOVA.
The five dependent measures of cognitive performance included; Simple Reaction Time,
Complex Reaction Time, Logical Reasoning, Matching to Sample, and Time Estimation. All
dependent cognitive variables were measured by reaction time (in milliseconds), which is more
stable (after practice) than accuracy (Kane & Kay, 1992). No significant differences were found
among the five conditions on cognitive performance measures; Pillai’s Trace = .12, F(20, 568) =
.90, p = .60.
Post-Rotation Questionnaire Findings by Medication Condition
Although no performance decrements were detected, it is possible that significant changes
may have occurred in the participant’s subjective well-being or perception of how hard he had to
work to maintain his concentration or performance. A Kruskal-Wallis was conducted on all
questionnaire data to determine if there were any conditional differences in subjective measures.
We checked questionnaire responses for SSQ, MMQ, Stanford Sleepiness, and mental effort
required to do the performance measures (NASA TLX). Of all these questionnaires, only the
MMQ (Factor A) revealed a statistically significant difference among conditions, yielding 2(4,
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N = 149) = 11.50, p = .02. To determine which conditions were significantly different from one
another in the MMQ, Mann-Whitney analyses were employed. These analyses revealed that
subjects in the oral scopolamine condition reported significantly higher scores on MMQ Factor
A after rotation, in comparison to all other conditions [p = (meclizine) .004, (placebo) .021,
(transdermal) .008, (promethazine) .006]. Nevertheless, it should noted that this statistically
significant increase was not likely to be operationally significant, since the observed MMQ
rating for this factor under oral scopolamine (2.3 on a scale from 1-5) was only 0.5 points higher
than the condition with the lowest rating (meclizine =1.8), and in either case, ratings near 2
would be considered “minimal.” Nevertheless, the small difference we detected in one of the
five questionnaires is displayed in Figure 12.
Pre Rotation versus Post Rotation Comparisons, Regardless of Condition
We did a repeated measures assessment of performance before and after rotation, regardless of
condition. This was done to determine whether the general experimental situation (medication
plus rotation) was sufficiently challenging to change performance. Paired t-tests (two-tailed)
detected three significant performance changes. First, Simple Reaction Time was significantly
slower (by 113.79 ms) immediately after rotation plus medication (t = -3.45, Bonferroni-
corrected p = .009). Second, Balance score (time on rail before stepping off) was significantly
shorter (i.e., worse by 312.71 ms) immediately after rotation plus medication (t = 7.45,
Bonferroni-corrected p < .001). Third, Grip Endurance was significantly longer (by 558.60 ms)
immediately after rotation plus medication (t = -3.38, Bonferroni-corrected p = .009). The
findings collectively imply that a failure to detect conditional performance differences in this
study was not entirely due to a lack of sensitivity of all the measures to a change in state of the
individual subject.
Discussion
Overall Medication Efficacy Findings and Study Limitations
This study evaluated several common antimotion sickness medications during a sickening
rotation stimulus. The stimulus proved effective at producing sickness in the participants, but
high variability was observed in the number of sickening head movements tolerated by
individuals across the five conditions (Figure 13). Thus, the only medication found to be more
effective than meclizine (the reference medication) was oral scopolamine, but this was not a
conclusive finding, due to the lack of difference detected between the oral scopolamine condition
and the placebo condition.
The independent design necessary for this large five-condition study contributed to the high
variability that was observed. Lower variability would have been obtained with a repeated
measures design. The sponsor requested five medication conditions, which we judged was too
many to execute under a repeated-measures design. This decision was partly based on the
observation that Benson and Bodin (1966) and Wood (2002) were not able to get more than 40-
66% of their subjects to complete each rotation trial (Benson) or all experimental conditions
(Wood) for their respective four-condition, repeated measures motion sickness studies.
17
Conversely, Denise et al. (1996) were able to successfully complete a six-condition motion
sickness experiment using an independent design.
The decision to employ an independent design for this five-condition study was also based on
considerations of subject recruitment and retention. A problem for any study of motion sickness
is subject recruitment. Although the NAMRL has reliable access to large pools of student
volunteers (e.g., Naval Aviation Schools Command, Marine Aviation Support Group, Naval
Aviation Technical Training Center), recruitment is not straightforward when a study involves
repeated exposures to a sickening stimulus while taking various medications. Moreover, since
the study participants are aviation students, they can be called away for primary flight training
before they have completed all the conditions of a repeated-measures experiment. Hence, as a
result of significant subject attrition or incomplete trials, it might not be possible to collect the
needed data for all five experimental conditions using a repeated measures design.
A third concern for a repeated measures design with five sickening exposures is the
possibility that confounding motion adaptation would build up which would carry over from one
session to the next (Graybiel & Miller, 1970; Denise et al., 1996), especially among subjects
were more resistant and thus likely to ride longer. The vestibular system is very adaptable; while
the confound due to adaptation can be distributed equally by balancing the order of presentation
of conditions, the error is still present and can wash out the overall findings. To minimize this
problem, it would be necessary to allow one week between rotation exposures if feasible, which
would have required each subject to be available for five weeks for this study, further increasing
the likelihood that data would be lost due to failure to complete all conditions.
For the reasons above, each subject in this study did just one baseline practice session and
one experimental session over the course of two days. Our military subjects were relatively
homogenous in age (most were 23-27 years old), sex (all male), education (most held a
bachelor’s degree), and health (all were screened for entry into a flight program), compared to
many of the motion sickness studies in the literature. Nevertheless, the actual variability
obtained was higher than expected, so it is possible that certain conditional differences existed
that were not detectable due to a lack of statistical power; hence, we recommend that any
subsequent independent design experiments of this type should employ approximately 39
subjects per condition, rather than the 30 per condition we employed (Appendix D).
Another possible reason for the failure to find more significant medication differences may
have been our choice of “sickness endpoint” or stopping criteria for the experiment, i.e.,
moderate nausea up to three times in a row, or moderate nausea for one minute without
abatement. We investigated several other criteria (minimal nausea without a pause, moderate
nausea without a pause, and moderate nausea with one or two pauses allowed, instead of the
original three). It was not possible to improve our findings regarding conditional differences
using these other stopping criteria. In fact, the original three-pause criterion seemed to work
best. Therefore, we concluded that our choice of sickness criteria was not the likely reason for
failure to observe more extensive medication efficacy differences.
This study employed a single control condition consisting of caffeine plus placebo (in place
of a motion sickness medication), followed by rotation. This allowed for comparison of
sickening rotation conditions with or without antimotion sickness medications. However, the
present study did not employ a placebo condition without any caffeine, so it is not possible to
ascertain (from this study alone) the effects of rotation in the absence of any drug at all.
While the three additional control conditions described above would have assisted the
interpretation of the effects of caffeine per se and rotation per se, they were not included because
18
the experiment requested by the sponsor already included five conditions requiring the testing of
150 subjects, with approximately eight hours of time experimenter time required to obtain data
from each subject, over the course of the recruitment day, baseline/practice day, and rotation day.
Hence, it was not feasible to add more conditions to the experiment with the resources available
for the project.
Fortunately, since caffeine has no proven protective value against motion sickness and its
affects on arousal have been very well documented for decades, limited benefit would be derived
from the inclusion of a no-caffeine control condition. In fact, given the ubiquitous use of
caffeine worldwide and especially during military operations, it could be argued that the
caffeine-only control condition in this study allows the most realistic generalization of our
findings to SOF, who have been advised to consider making limited doses of caffeine
supplements available during sustained operations (Letter 6710, 12 Sep., 1997, Commander
Naval Special Warfare Command).
For comparison, Table 1 shows the placebo condition results from two other recent motion
sickness studies at the NAMRL (Hoyt et al., 2008; Simmons et al., 2007) which employed a
placebo condition without caffeine. These experiments employed the same yaw rotation velocity
profile, the same number of roll head tilts per minute, and the same diagnostic symptom criteria
for obtaining ratings of motion sickness. The main difference was that the present study was the
only one of which used active, voluntary roll head tilts (instead of passive roll tilts through a
head-centered axis). A lesser difference is that the Simmons et al. (2007) study used somewhat
different criteria for establishing the motion sickness endpoint, requiring moderate nausea to be
reached even if more than three pauses were required. We conclude from the overlapping
placebo results in Table 1 and from the arguments made above concerning additional control
conditions that the absence of a no-caffeine placebo condition was not a serious limitation for the
present study, especially when one considers that medications such as promethazine and
scopolamine are generally administered by the military in combination with a stimulant of some
kind.
List of Recommendations to the USSOCOM
Recommendation 1: the Biomedical Initiatives Steering Committee (BSIC) of the USSOCOM
should consider further evaluation of medications other than meclizine. In simple rankings of
number of head movements tolerated in this study, meclizine tended to be at the bottom (fewest
head movements tolerated). When the findings from this study are expressed as the mean
percent improvement obtained with various medications vs. head movements tolerated under
meclizine (Figure 14), it appears that a trend towards large percentage improvements may
potentially be obtained with other medications, which should be evaluated further under
conditions where variability and statistical power are more favorable. For example, a three-
condition repeated measures comparison of just oral meclizine versus oral scopolamine versus
placebo may be warranted, preferably with a gap of at least one-week between each of the three
rotations tests is allowed, to reduce carry-over effects. It should be noted that Dahl, Offer-
Ohlsen, Lillevold, and Sandvik (1984) found that transdermal scopolamine provided better
protection than oral meclizine or placebo using a three condition repeated-measures study.
Recommendation 2: the BISC should consider further evaluation of oral scopolamine. Oral
scopolamine was the only medication to show significantly improved efficacy versus meclizine,
19
although this finding needs to be confirmed under conditions where the placebo comparison
works out favorably as well. Despite this limitation, there is much evidence from the literature
(Wood & Graybiel, 1968; Graybiel & Lackner, 1987; Wood et al., 1992) that oral scopolamine is
effective against motion sickness, and that it tends to be more effective than meclizine.
An interesting question is the extent to which this study is comparable to other recent
NAMRL studies and to past trends from the literature. Figure 15 displays the number of head
movements tolerated (head movement data lumped, regardless of experimental condition) in this
experiment (Lawson et al., 2008) versus three other experiments conducted at our laboratory
recently (Lawson et al., 2007; Simmons et al., 2007; Hoyt et al., 2008). All four experiments
used similar participant pools, step-wise yaw rotation velocity increases of 1 rpm per minute, 12
roll head tilts per minute, and similar diagnostic criteria for motion sickness. The main
difference was that the present study was the only one which used active, voluntary head
movements (instead of passive roll tilts through a head-centered axis). A lesser difference is that
the present study used slightly different criteria for establishing the motion sickness endpoint
versus the Simmons et al. (2007) study, which allowed for more than three pauses.
When the overall findings of the four NAMRL experiments are compared in Figure 15
(regardless of condition), it can be seen that the present study (dark/blue1 “SOCOM” histogram)
is approximately in the middle of the range of head movements tolerated among the four studies.
Moreover, when just the placebo groups from each study were compared with one another using
a Kruskal-Wallis test, there was no significant difference detected. These two observations
imply that the present USSOCOM study is not highly divergent from the other recent studies at
the NAMRL in terms of the number of head tilts tolerated overall.
A gross idea of the ranking of head movements tolerated among different medications in
these four NAMRL studies can be estimated in Figure 16. Medications tested in this study are
shown as the dark/blue histogram bars. While the methods and stimuli were not identical in each
NAMRL experiment, it is remarkable to see how closely the ranking of relative medication
efficacy (by number of sickening head movements tolerated) from Figure 16 agrees with the
earlier rankings established by Wood and Graybiel (1968) for comparable medications (Figure
17). In general, Figures 16 and 17 are displayed as general support for our recommendation that
oral scopolamine deserves further consideration by the BISC.
Recommendation 3: the BISC should be cautious concerning the use of transdermal
scopolamine. While transdermal scopolamine provides long-lasting relief from motion sickness
and is convenient for the user (no pills to carry or dose schedule to remember), oral scopolamine
offers greater ease of dosage adjustment than transdermal scopolamine (e.g., to body weight,
motion sensitivity, motion severity, or motion duration), which is a significant advantage in the
special operations setting, where dosage should be controlled carefully to achieve the best
therapeutic benefit obtainable without inducing performance decrements.
There are certain practical concerns with using transdermal scopolamine during water
immersion, an important aspect of Navy special operations. The Physician’s Desk Reference
instructs as follows: “Keep the patch dry, if possible, to prevent it from falling off. Limited
contact with water, however, as in bathing or swimming, will not affect the system.” (p. 2224:
PDR 57th edition, 2003). It goes on to say: “Patients who expect to participate in underwater
sports should be cautioned regarding the potentially disorienting effects of scopolamine. “ (p.
2222, PDR 57th edition, 2003). The PDR also counsels on the need to avoid cutting or blistering
1 The histogram bar will appear as darker than the others when printed in B&W and as blue when printed in color.
20
the patch and the need to wash one’s hands after application to avoid inadvertently transferring
the drug from one’s fingers to one’s eyes (Gahlinger, 1999).
Many of these operational disadvantages of transdermal scopolamine are not severe. The
patch is not that likely to become cut unintentionally (personnel are warned not to “trim the
dose” intentionally) and if the patch were worn under a wet suit, then prolonged water immersion
should not be a serious problem. Nevertheless, the long delay in absorption of transdermal
scopolamine (6-8 hours after application) requires precise prediction and timing of anticipated
operations. Since special operations must be flexible concerning their initiation, faster-absorbing
oral scopolamine may be more appropriate for such operations. Furthermore, high individual
variability of absorption has been seen with transdermal scopolamine (Gil et al., 2005), possibly
due to variation in the body size of the user receiving the fixed dose patch (Sherman, 2002).
Finally, it appears that unwanted side-effects occur less frequently with the oral form of
scopolamine (Sherman, 2002.) A final consideration against transdermal scopolamine is the
recent failure of a USSOCOM-sponsored study by Estrada et al. (2007) to detect better resistance
to airsickness when subjects used transdermal scopolamine instead of placebo (and better results
obtained with promethazine). For these various reasons, we recommend caution when using
transdermal scopolamine for special operations. Further possible drawbacks of transdermal
scopolamine will become apparent in the discussion of side-effects in Recommendation 4,
below.
Recommendation 4: Based on the measures, subjects, dosages and conditions employed in
this experiment, performance side-effects are not likely to be the main limiting factor in similar
future evaluations of medications such as oral scopolamine. Overall, no performance
decrements were detected by the psychomotor or cognitive test batteries. This is particularly
encouraging, since many of these tests were chosen specifically for their relevance to the basic
abilities needed for special operations or for their likely sensitivity to the medications used in this
experiment. Moreover, the literature (e.g., Kane & Kay, 1992) and our recent observations (e.g.,
McGrath et al., 2007; Appendix C) indicated that the measures were generally sensitive, stable,
and reliable.
To be fully confident concerning Recommendation 4, we explored medication side-effects in
more detail. Even though no significant mean performance decrements were seen for oral
scopolamine nor even a subjective increase in perceived effort, it is still possible that a few
people might be especially sensitive to the drug and their performance might be extremely
affected by oral scopolamine, even though this change would not be reflected in the averaged
group data. We explored this possibility by plotting a frequency histogram showing the number
of subjects at each time interval of speed of response in Matching to Sample (see Figure 18),
which was the performance measure that came closest to showing a significant difference
between meclizine and oral scopolamine. For comparison, the frequency histogram for
transdermal scopolamine is displayed also. Outliers were treated as evidence of possible subject
sensitivity to the drug.
On the left side of Figure 18, it is clear that oral scopolamine exhibits no extreme outliers,
while as right, transdermal scopolamine appears to exhibit some outliers. This implies that none
of the subjects in our sample were extremely sensitive to oral scopolamine (as reflected by
slowing of their speed on a Matching to Sample task), while it is possible that some of our
subjects were especially sensitive to transdermal scopolamine. In fact, the outlier shown on the
right side of Figure 18 was the largest observed in this study. Hence, even though no overall
21
performance decrements were seen in the batteries, nor even with this particular measure
(Matching to Sample) in the oral scopolamine condition, we recommend that care should be
taken when using transdermal scopolamine during operations, due to the possibility that certain
persons are more sensitive to the transdermal form of this medication.
Similar cautions can be inferred concerning transdermal scopolamine by considering the
open-ended reports of medication side-effects from the “adverse events” reporting sheets we had
each subject fill out. There were no serious adverse reactions caused by the medications used in
this study, but the record of clinical symptoms that were reported indicates that by far the
greatest number of reports were volunteered by subjects in the transdermal scopolamine
condition. Thirty reports of minimal-severity symptoms were recorded from the 30 subjects in
the transdermal scopolamine condition after medication absorption and prior to rotation (i.e.,
across all participants during the first and second pre-rotation assessments, cumulatively),
including six cases of dizziness, four of drowsiness, four of stomach symptoms, three of
headache, and two of dry mouth. By contrast, only 2 – 4 minimal symptoms were reported by
prior to rotation by any single group of subjects in the other four conditions (including placebo).
This suggests that subjective sensitivity to transdermal scopolamine may be more prevalent than
with oral scopolamine.
Recommendation 5: Special Operations Forces clinicians anticipating the use of any of the
medications from this study should carry out an assessment of medication tolerance prior to
recommending that the patient use the medication during mission-critical duties demanding
optimal performance. Overall, no performance deficits were detected in either of the
performance batteries across any of the medication conditions. Additionally, few and minimal
subjective effects were detected. Nevertheless, given the sensitive and demanding nature of
special operations missions, any medication that is intended for field use should be evaluated
carefully on shore first, when the individual is not out on a mission. Moreover, the few non-
significant performance trends in this experiment should be noted and considered as dependent
measures in future studies of motion sickness countermeasures intended for use by SOF. For
example, despite the fact that the MANOVA of performance speed in the computerized cognitive
test battery failed to detect significant decrement overall (and hence, individual tests were not
evaluated), we feel it is worth noting that one of the measures, Matching to Sample, would have
shown a significant slowing of performance under transdermal scopolamine, in comparison to
meclizine, had it been the only test conducted. (ANOVA n.s. at p = 0.27; Tukey’s post-hoc
significant at p = 0.01). Such a finding would not typically be reported in context of our study
design, but it is mentioned because the observed tendency for transdermal scopolamine to be
associated with a slowing of Matching to Sample performance is large enough to be clinically
worth further attention (531 ms slowing, see Figure 19). Also, the trend matches the literature
and a recent clinical evaluation we made of the Matching to Sample performance of an airsick
aviator (unpublished) under transdermal scopolamine. Hence, we recommend that Matching to
Sample performance be evaluated in further studies of this type, and we reiterate the point that
caution should be exercised in the use of transdermal scopolamine for special operations.
Recommendation 6: Evidence from this study implies that the BISC should not be concerned
that large deficits in the MRPM shooting test will result from these medications; however,
several improvements to the shooting test are recommended. We noted earlier that no significant
decrements were observed in shooting performance across conditions. Nevertheless, since
22
shooting performance is such a critical aspect of special operations and will factor heavily into
medication recommendations for SOF, the non-significant mean trends for shooting performance
are displayed in Figure 20. We analyzed the number of targets hit per second, because this was
the single best measure of accuracy and speed that we could devise, and it avoided some of the
drawbacks of the scoring system inherent in the MRPM (See Appendix A). However, for ease of
visual interpretation, hits per minute are displayed in Figure 20.
Note that in Figure 20, there is only a one hit per minute difference between the most
different conditions (placebo versus meclizine), and no visible difference for any other condition.
We conclude that this statistically insignificant result is not likely to be worth further concern
operationally, either. This is particularly useful news from a logistical standpoint, because this
dependent measure was the most difficult to set up of the measures employed in this study, as
well as the most trouble-prone, the most expensive to maintain (due to the need for regular gas
supplies), and the most susceptible to prolonged practice effects. Hence, it is useful for the BISC
to know that in future studies of this type, it should be possible to obtain much valuable
information concerning performance effects even in cases where the shooting measure cannot be
employed easily or fails during experimentation. Elsewhere (Appendix A), we provide the BISC
with specific recommendations concerning areas of suggested improvement to the existing
shooting measurement apparatus, recommend an improvement to the method of scoring shooting
performance, and make a suggestion concerning a new shooting system which may be a suitable
replacement for the existing apparatus.
Recommendation 7: The BISC should advise personnel to increase fluid intake when caffeine
is used in combination with antimotion sickness medications and advise limiting the number and
size of caffeine doses. The BISC also should consider a wider range of stimulants than caffeine.
Caffeine was the only stimulant requested for evaluation by the USSOCOM Task Statement of
the BISC. Caffeine is very much a part of our culture and a widely accepted adjunct to our
military operations. Caffeine has been shown to partially counteract the effect of scopolamine
on baseline performance (Riedel et al., 1995, from U.K. Department of Transport Report No. 24,
2004). Hence, caffeine may be a cheap, accepted, and convenient way to counteract some of the
drowsiness seen with common sedating antimotion sickness medicines (Canadian Committee to
Advise on Tropical Medicine and Travel, 2003). However, we recommend the BISC advise the
USSOCOM to have patients increase fluid intake when caffeine is taken with antimotion
sickness agents, since caffeine is a diuretic. Another reason for advising increased fluid intake is
that some antimotion sickness drugs cause dry mouth, and if vomiting occurs during challenging
motions, a significant amount of fluid may be lost.
Caffeine has other limitations. A sizable portion of the public is already tolerant to
caffeine and relatively immune to the benefits it could provide during administration of an
antimotion sickness drug. Moreover, physical dependency on caffeine develops rapidly, with
withdrawal causing profound headache and fatigue (Grifiths & Woodson, 1988), which could
detract from readiness for the next day’s duties. We recommend that the frequency and dosage
of caffeine should be limited by the BISC. A report from by DeJohn et al. (1992) notes that
while caffeine has been proven to enhance performance and alleviate the effects of sleep loss, the
duration and magnitude of its effects are less than other stimulants and the >200mg doses likely
to counteract fatigue can lead to tolerance, anxiety, tremor, and dysphoria. Along similar lines,
Kaplan et al. (1997) note that a 250mg dose of caffeine produces more favorable subjective and
23
cognitive performance effects than a 500mg dose. Hence, higher doses of caffeine should be
avoided. In general, we agree with the original USSOCOM Task Statement recommending the
use of 200mg caffeine as an adjunct to antimotion sickness medications and with an earlier
recommendation that caffeine supplements not exceed 200 mg per dose every 4-6 hours
(Commander, Naval Special Warfare Command letter 6710, 12 Sep, 1997). We would add to
this point that the total allowed number of doses should be carefully considered as well, and that
a maximum number of doses should be established by the BISC, at least in routine cases where
the costs of repeated dosing may outweigh the benefits.
While short-term use of caffeine should help minimize the sedative effects of certain
antimotion sickness, caffeine is not likely to ameliorate sedation as much as sympathomimetics
such as d-amphetamine, nor will it potentially amplify the resistance conferred by those drugs, as
some limited evidence suggests d-amphetamine may do (Wood & Graybiel, 1968). While very
little is known about the efficacy of coupling caffeine with antimotion sickness medications, a
great deal of literature has proven the efficacy of coupling d-amphetamine with such
medications. The Navy and NASA has had prolonged success coupling certain antimotion
sickness medications (such as scopolamine or promethazine) with d-amphetamine. For these
reasons, the BISC of the USSOCOM should consider coupling antimotion sickness medications
with a wider range of stimulants than caffeine.
Recommendation 8: The BISC should consider replacing the Complex Reaction Time
task in its MRPM battery with a Simple Reaction Time task.. Findings from the present study
and from McGrath et al. (2007) suggest that the Simple Reaction Time task takes less time to
learn and perform than Complex Reaction Time and is more stable and reliable. Moreover, the
Simple Reaction Time task is a widely-accepted and validated measure of cognitive arousal and
medication side-effects and is available as the well-established Psychomotor Vigilance Test
(Jewett et al., 1999).
Summary
It is difficult to identify the best medication countermeasure for treating motion sickness,
because the drug(s) of choice will depend on the user and the situation. There are a bewildering
number of factors to consider, including route of administration (pros and cons), safety of drug if
used properly (e.g., percent likelihood of serious adverse reactions, risk to special groups when
used outside the SoF setting (e.g., pregnant women, children), the presence of existing medical
conditions that contraindicate the drug, interactions with drugs already being taken, the
likelihood of misuse or abuse of certain drugs, severity of motion against which the drug is
effective, duration of sickening motion anticipated (vs. duration of drug action), latency to onset
of action of the drug, individual motion susceptibility of the user (high or low), the user’s task
demands (e.g., high alertness required or not), the predictability of onset of sickening motion
(e.g., unpredictable start to many military operations, predictable start to most recreational ocean
cruises), whether the symptoms have already begun by the time the medicine is taken, and
whether the drug interferes with normal motion adaptation processes (Canadian Committee to
Advise on Tropical Medicine and Travel, 2003). Simply selecting an anti-emetic drug that is
non-sedating may not be sufficient, because certain anti-emetic drugs are ineffective against
motion sickness (Reid et al., 1999; Stott et al., 1989). Moreover, some anti-emetic drugs that
24
prevent motion-induced emesis in animals do not do so in humans (Reid et al., 1999). The
situation is complicated, indeed.
Nevertheless, consideration of the literature, operational and logistical concerns, and our
experimental results collectively suggest that, of the medications tested in this experiment, oral
scopolamine appears to be of potential interest for further evaluation as a therapeutic during
special operations. We recommend that it be used only after a more conclusive experimental
evaluation is completed, it should be tried only if the usual “first-line defense” (meclizine) does
not help the patient sufficiently, and it should be tested by each patient on shore (before the
mission), during which time the patient should be monitored for visual blurring, excessive
drowsiness (the most common PDR side effects of relevance to special operations), and, when
feasible, working memory for visual patterns (Matching to Sample performance – the most likely
deficit to occur, based on our experimental findings). Finally, we recommend that oral
scopolamine should always be accompanied by an appropriate stimulant (the most common
choice being d-amphetamine).
In general, any antimotion sickness drug should be tried by the patient to assess tolerance
before his or her mission and many such drugs should be combined with an appropriate
stimulant. If the eight recommendations and related cautions in the discussion section of this
report are followed by the USSOCOM, then we expect that improved motion sickness protection
will become available to future SOF, without compromising mission effectiveness or safety.
25
Acknowledgements and Disclaimers
This effort was supported by work unit number 70509, initiated by USSOCOM Biomedical Initiatives
Steering Committee Biomedical R & D Task Statement #2005-4. We thank the Biomedical Initiatives
Steering Committee of the USSOCOM for allowing us to contribute to their important mission and the
Medical Technology Program of the Special Operations Acquisition and Logistics - Technology
Directorate for sponsoring this research.
We thank the following people for their excellent support of this study: Angus Rupert, CAPT MC
USN, retired (for project advice and liaison); Robert Hoyt, CAPT MC USN (for medical monitoring and
medication advice); Tom Allen, Casey Harris, and Neil Edmonston (for engineering support); Rita
Simmons, CDR MSC USN (for research support); Pavla Decoteau, Heather Horton (for research
assistance), Sarah Kinzbrunner, Emily Qualls and Shauna Legan (for research assistance and assistance
with the manuscript).
The views expressed in this article are those of the author and do not necessarily reflect the official
policy or position of the Department of the Navy, Department of Defense, nor the U. S. Government. The
study protocol was approved by the NAMRL Institutional Review Board, in compliance with applicable
Federal regulations governing the protection of human subjects. The first author, Dr. Lawson, is an
employee of the U.S. Government and this work was prepared as part of his official duties. Hence, under
Title 17 U.S.C. 101 & 105, copyright protection is not available.
26
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Simmons, RG, Lawson BD, Putcha L, McGrath C, Harmon-Horton, H, Rupert A. Comparison of oral
scopolamine, intranasal scopolamine and dextroamphetamine as motion sickness
countermeasures for young healthy aviation candidates. Proceedings, Aerospace Medical
Association, New Orleans, LA, March 2007.
Simmons, R. G., Putcha, L., Phillips, J. B., & Lojewski, R. Efficacy of intranasal scopolamine gel for
motion sickness treatment in aviation candidates. Proceedings, Aerospace Medical Association,
Boston, MA, May 2008.
Simmons, R. G., Phillips, J. B., Lojewski, R. A., & Lawson, B. D. (2008). A comparison of intranasal
and oral scopolamine for motion sickness prevention in military personnel. Technical Report
No. NAMRLTR0810, Pensacola FL, Naval Aerospace Medical Research Laboratory.
Stott, J. R. R., Barnes, G. R., Wright, R. J., & Ruddock, C. J. S. (1989) The effect on motion sickness and
oculomotor function of GR 38032F, a 5-HT3 receptor antagonist with anti-emetic properties. Br J clin
Pharmac, 27: 147-157.
Thomas JR, Schrot J, Butler FK, Curley MD. (1994). Quantification of special operations mission-
related performance: performance database. Technical report A632882, Jan 93 – Sep p4, Naval
Medical Research Institute, Bethesda, MD.
Thorne, D. R., Genser, S. G., Sing, H. C., & Hegge, F. W. (1985). The Walter Reed performance
assessment batter. Neurobehav Tocicol Teratol, 7(4), 415-418.
Topics Entertainment (2002). Interview with Chief Jerry N. Markham NCDU Omaha Unit 46, from CD2,
“Hit the Beach,” of the compilation “In Their Own Words –WWII: The European Theater. ISBN
1591500222.
Turnage, J.J. & Kennedy, R.S. (1992). The development and use of a computerized human performance test
battery for repeated-measures applications. Human Performance. Vol 5(4), 1992, 265-301.
30
U.K. Department for Transport. (2004). Over-the-counter medicines and the potential for unwanted
sleepiness (No. 24). Retrieved from:
http://www.dft.gov.uk/pgr/roadsafety/research/rsrr/theme3/overthecountermedicinesandth4772
August 8, 2008.
Wallace, J.C., Kass, S.J., & Lawson, B.D. (2002). Sopite syndrome: a distinct syndrome or just boredom
and inattention? NAMRL Technical Report #1414, 16 pages.
Wood, C. D., Cramer, D. B., Graybiel, A. (1981). Antimotion sickness drug. Otolaryngology – Head &
Neck Surgery; 89(6):1041-44.
Wood, C. D. & Graybiel, A. (1970). Evaluation of Antimotion Sickness Drugs: A New Effective Remedy
Revealed. Aerosp Med 41:932-3.
Wood, C. D. & Graybiel, A. (1968). Evaluation of sixteen antimotion sickness drugs under controlled
laboratory conditions. Aerospace Medicine, 39, 1341-1344.
Wood CD, Graybiel A, Kennedy RS. (1966). Comparison of effectiveness of some antimotion sickness
drugs using recommended and larger than recommended doses as tested in the slow rotation room.
Aerosp Med, 37(3): 259–262.
Wood, C. D., Manno, J. E., Manno, B. R., et al. (1985). Evaluation of antimotion sickness drug side
effects on performance. Aviat Space Environ Med, 56, 310-316.
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intramuscular antimotion sickness medications. J Clin Pharmacol. Nov;32(11):1008-12.
Wood, S. J. (2002). Human otolith-ocular reflexes during off-vertical axis rotation: Effect of frequency on
tilt-translation ambiguity and motion sickness. Neurosci Lett 2002; 323: 41-44.
31
Table 1
Means and Standard Errors of Number of Head Movements Tolerated for the
Control Conditions in Three Recent NAMRL Motion Sickness Studies
_______________________________________________________________
Study Condition M SE n
_______________________________________________________________
Present Study Placebo + caffeine 181* 13.21 30
Simmons et al., 2008 Placebo 210* 28.13 18
Hoyt et al., 2008 Placebo 213 23.48 20
_______________________________________________________________
* Estimated marginal mean (adjusted for MSSQ score) is reported.
32
Figure 1. The sickening Coriolis, cross-coupling stimulus: yaw-axis body rotation plus
roll-axis head movements.
Yaw
Roll
33
Figure 2. Rotating chair, showing adjustable head stops and visual canopy (being
closed).
34
Figure 3. Grip strength test.
35
Figure 4. Shooting test, depicting the shoot and the targets. In this case, the middle-right target has just
become visible and the shooter must shoot directly in the center of the disk.
36
Figure 5. The balance test.
37
Figure 6. The Visual Accommodation task (of near focus)
38
Figure 7. The Complex Reaction Time task. In this case, the “up” arrow should be selected.
39
Figure 8. The Logical Reasoning task. In this case, the left-pointing arrow should be selected.
40
Figure 9. Matching to Sample task. If the left pattern had just been observed in the last screen, then the
subject should select the left arrow in the final screen shown above.
41
Figure 10. Time Estimation task. The falling square is shown near the bottom of the stimulus.
42
Figure 11. Mean head movements tolerated by condition
p = .04
43
Figure 12. A significant, but small increase in subjective effect under oral scopolamine,
found in one of factors from one questionnaire (MMQ). Medians and 95% confidence intervals
are displayed, along with the size of the difference between oral scopolamine and meclizine.
=.5
p .02
44
Figure 13. Mean and standard deviation of head movements tolerated by condition,
showing high individual variability.
45
Figure 14. Percent increase in head movements tolerated under three medications,
relative to meclizine (as reference).
Percent Im
p
rovement in Motion Sickness Resistance
(vs. Meclizine)
0
5
10
15
20
25
30
Meclizine Promethazine Trans Scop Oral Scop
Condition
% Increase
46
Figure 15. Comparison of the present study (dark/blue “SOCOM” histogram) to three
other recent studies at the NAMRL (“Alcohol” = Lawson et al., 2007; “INScop” = Simmons et al.,
2007; “Modafinil” = Hoyt et al., 2008.)
47
Figure 16. Simple ranking of medication efficacy in the present study (the four dark/blue
histogram bars) versus other recent experiments at the NAMRL. More head movements implies a
possible trend towards greater efficacy.
Head Movements by Condition
150
175
200
225
250
275
Alcohol
Meclizine
Modafinil
Promethazine
Trans Scop
Amphetamine
Oral Scop
Oral Scop
IN Scop
Modafinil/Scop
Condition
Mean Head
Movements
48
Figure 17. Simple ranking of medication efficacy in experiments summarized by Wood
and Graybiel, showing a similar relative ranking of medications as in Figure 16. Note that oral
scopolamine consistently ranks higher than promethazine, which consistently ranks higher than
meclizine.
Wood & Graybiel (1968)
0
25
50
75
100
125
150
Meclizine (50mg) + Amph (10mg)
Meclizine (50mg)
Amphetamine (10mg)
Promethazine (25mg)
Scop (.6mg)
Scop (.6mg) + Amph (10mg)
Condition
Mean Head
Movements
49
Figure 18. Evaluation of whether any subjects were extremely sensitive to
scopolamine. Oral scopolamine at left, transdermal scopolamine at right.
50
Figure 19. Limited evidence concerning a possible performance decrement in one
measure (Matching to Sample); not significant in MANOVA with other measures.
p = .01
51
Figure 20. Shooting performance: no difference in number of hits across different
medication conditions.
Shooting: Hits per Minute
31
32
33
34
Post-Rotation
Trial
Hits/Minute
Meclizine
Promethazine
Oral Scop
Trans Scop
Placebo
52
Appendix A
NAMRL Evaluation of USSOCOM’s MRPM Apparatus
This appendix briefly summarizes the “lessons learned” after running 150 subjects with the MRPM
apparatus which is maintained by the Naval Experimental Diving Unit (NEDU, Panama City, FL) and is
recommended by the BISC for the assessment of human performance in USSOCOM-sponsored studies.
The main problems we encountered were with the shooting system. Lesser difficulties were encountered
with the handgrip system and the old laptops which ran the various measures of the MRPM. A brief
summary of problems and recommendations shown below; it is derived from a 19 September 2007
PowerPoint brief distributed to the BISC and NEDU.
Lessons Learned…
Afterthoughts Regarding
Shooting, Handgrip
&
Laptop Performance
Including:
Obstacles Encountered
Mitigations
&
Recommendations
53
Shooting: The Rifle
Trigger occasionally stuck
Trigger double fired
(randomly)
Problem fixed after rifle disassembly
Participants occasionally reported
being disturbed by the double fire
Double shots were not counted by
the scoring system
Shooting: Targets
Occasionally targets would
not flip
1st shooting test of the day:
presentation of 3rd target was
delayed
problem with gas flow to targets
problem only fixed with target
disassembly
(time consuming)
after the first session the
system worked fine
experimenters completed a
dry run prior to participant
arrival
the delay never occurred
during a participant run
54
Shooting: Gas System
Changing the tanks
Gas leaks (tank to rifle)
Blocks in gas lines
(tank to targets)
time consuming
heavy
expensive to replace empties
leaking gas = wasting $
easy to locate leak & fix
targets would not flip
Shooting: Scoring
Recording Errors
Lacks specificity
scores occasionally reported fewer shots
than target hits
(impossible : you can’t more
targets than you take shots)
different performances result in the same
score
alternative scoring procedures can be
adopted (e.g., # hits per second)
55
Shooting:
Common Participant Complaints
Rifle lacks realism
Lack of kick
Feel of the trigger (little resistance)
Random double firing
Shooting System
RECOMMENDATIONS…
• Consider an electronic based shooting system
Our #1 Recommendation…
Mini-RETS Range System by MPRI-Training Technology Group
(product information available @ www.beamhit.com)
56
Handgrip:
Calibration
daily calibration was necessary during
winter months
15 to 20 minutes to properly
calibrate
had to remind participants to
squeeze for 1 second
not a big problem – participants
were instructed to squeeze again
Temperature changes
affected calibration
Time consuming to calibrate
daily
Max grip not recorded if
squeezes were too quick
Handgrip: Data Recording
Handgrip:
Common Participant Complaints
• Slippery (if hands were slightly sweaty)
•Discomfort
participants experienced some pain during repeated grip tests
57
Handgrip:
RECOMMENDATIONS…
• Consider self-calibrating grip devices
• Improve on current grip device:
- rubber grip (less painful)
Laptops
• Slow
Frequently froze up
RECOMMENDATIONS…
• Upgrade
58
Appendix B
Selected NAMRL Documents and Forms Used in this Study
This Appendix shows several NAMRL documents or forms mentioned in the body of the paper, including
(in order) the Confidential Medical Questionnaire (for determine subject health status and safety to
participate), the Confidential Exclusionary Behavior Questionnaire (for determining if the subject has
engaged in any behaviors that would exclude him from participation until a wash-out period elapsed), the
Mild Motion Questionnaire (for determining reactions to mild or non-sickening motion), the Rotation
Data Sheet (for monitoring symptoms minute by minute during the study to determine when to end the
experiment), the Practice Sequence Checklist (for determining the number and sequence of cognitive
tasks during the practice session), the Pre-Dose Compliance Checklist (a last check before taking the
study medications to ensure the subject has not engaged in any exclusionary behaiors), and the Adverse
Event Form (for tracking any side-effects the subject experiences).
OVR - Confidential Medical Questionnaire
Subject Number: ______________ Gender: Male / Female
Age: __________ Hand Dominance: Right / Left
Height: ________ Weight: ________
Part I-
Directions: The following is a list of medical conditions. If you currently suffer from or have ever been
diagnosed with the condition, please circle Yes. If not, please circle No. If you are unsure, please discuss
the question with the experimenter. The only reason we are asking these questions is to be sure that it is
safe for you to be in this study.
1. Have you ever been diagnosed with an inner ear disorder? Yes No
(e.g. Menier’s syndrome)
2. Do you currently or have you ever been diagnosed with asthma? Yes No
3. Do you have a history of or currently suffer from severe allergies? Yes No
4. Have you ever been diagnosed with sleep apnea? Yes No
5. Have you ever been diagnosed with a seizure disorder? Yes No
6. Do you currently or have you ever suffered from liver/kidney problems? Yes No
7. Do you have a history of urinary retention? Yes No
8. Have you ever been diagnosed with heart/circulatory disease? Yes No
9. Do you currently suffer from high blood pressure? Yes No
59
10. Have you ever been diagnosed with glaucoma? Yes No
11. Have you ever been diagnosed with emphysema? Yes No
12. Have you ever been diagnosed with an enlarged prostate? Yes No
13. Do you have a history of gastrointestinal disorders? Yes No
(i.e. bowel distention, irritable bowel syndrome)
14. Have you been diagnosed with epilepsy? Yes No
15. Have you ever suffered from pneumonia? Yes No
16. Do you have a history of alcohol or drug dependency? Yes No
Part II-
Directions: The following is a list of medications. Please circle any medication to which you are allergic
or have ever experienced sensitivity.
Scopolamine ( Scopace)
Meclizine (Bonine, Antivert)
Promethazine (Phenergan)
Omeprazole (Prilosec)
Amphetamine (Adderal)
Isopropyl alcohol (Rubbing Alcohol)
Caffeine
Part III-
Directions: Please answer the following questions to the best of your ability.
1. Are you in your usual state of fitness? (Circle one) YES NO
If not, please indicate the reason:
2. Have you been ill in the past week? (Circle one) YES NO
If "Yes", please indicate:
a) The nature of the illness (flu, cold, etc.):
b) Severity of the illness: Very Very
Mild Severe
c) Length of illness: Hours / Days
d) Major symptoms:
60
e) Are you fully recovered? YES NO
3. How much alcohol have you consumed during the past 72 hours?
12 oz. cans/bottles of beer ounces wine ounces hard liquor
4. How much caffeine have you consumed during the past 72 hours? (please list the beverages/ food and
amounts)
____________________________
____________________________
____________________________
4. Have you engaged in any of the following activities during the past week?
a) Consumption of herbal products (including vitamins)
b) Consumption of prescription or over-the-counter medications
c) Tobacco / Nicotine use
d) Participation in an investigational drug study
e) Blood donation
f) NONE OF THE ABOVE
5. a) How many hours of sleep did you get last night? hours
b) Was this amount sufficient? (Circle one) YES NO
6. Please list any other comments regarding your present physical state which
might affect your performance on our test battery.
61
Confidential Exclusionary Behavior Questionnaire
Directions: Please answer the following questions honestly, and to the best of your ability. Some of the
questions relate to your past experiences. In the questions regarding a feeling or attitude you are to use a
rating from 1-5 with 1 being “strongly disagree” and 5 being “strongly agree”. Please circle the number
that best reflects your feeling or attitude.
Participant Number __________(last 4)
1. Have you consumed any alcoholic drinks in the last 3 days?_______
2. Have you taken any drugs or medications in the last 7 days? __________
(yes /no)
3. Have you consumed any tobacco products in the last 7 days?_________
(yes/no)
4. If you have consumed any herbal products in the last 7 days please list the products and
amounts.
___________________________________
___________________________________
___________________________________
___________________________________
5. Have you drank grapefruit juice in the last 7 days?___________
(yes/no)
6. How much caffeine have you consumed in the last 3 days? (please answer in number of 8oz
cups)_____________
7. If you have consumed any caffeine in the past 24 hours, please list the beverages/ food and
amounts.
___________________________________
___________________________________
___________________________________
___________________________________
Thank you for your participation in this research study.
62
Rotation Data Sheet
Baseline Fregly (in secs): a) b) c)
Post-Rotation Fregly: a) b) c)
Weight (lbs): Height (in):
Gender: M / F Hand Dominance: L R
Actual Run Date:
Awa Dis Min Mod Maj Min Mod Maj Min Mod Maj Min Mod Maj Min Mod Maj Min Mod Maj Min Mod Maj
Pre-exp
12123123123123123123123
Time 1 12123123123123123123123
Time 2 12123123123123123123123
Time 3 12123123123123123123123
Time 4 12123123123123123123123
Time 5 12123123123123123123123
Time 6 12123123123123123123123
Time 7 12123123123123123123123
Time 8 12123123123123123123123
Time 9 12123123123123123123123
Time 10
12123123123123123123123
Time 11
12123123123123123123123
Time 12
12123123123123123123123
Time 13
12123123123123123123123
Time 14
12123123123123123123123
Time 15
12123123123123123123123
Time 16
12123123123123123123123
Time 17
12123123123123123123123
Time 18
12123123123123123123123
Time 19
12123123123123123123123
Time 20
12123123123123123123123
Time 21
12123123123123123123123
Time 22
12123123123123123123123
ELAPSED: TOTAL PAUSED:
ID: Condition:
Dizziness Sweating
Age:
Practice Date: Baseline Visual Accommodation:
Post-Rotation Visual Accommodation:
Pallor
OVR-SOCOM DATASHEET
Salivation Warmth Drowsiness HeadacheStomach Nausea
Post-exp
HEAD MOVEMENTS:
12123123123123123123123
63
Awa Dis Min Mod Maj Min Mod Maj Min Mod Maj Min Mod Maj Min Mod Maj Min Mod Maj Min Mod Maj
Time 23
12123123123123123123123
Time 24
12123123123123123123123
Time 25
12123123123123123123123
Time 26
12123123123123123123123
Time 27
12123123123123123123123
Time 28
12123123123123123123123
Time 29
12123123123123123123123
Time 30
12123123123123123123123
Time 31
12123123123123123123123
Time 32
12123123123123123123123
Time 33
12123123123123123123123
Time 34
12123123123123123123123
Time 35
12123123123123123123123
Time 36
12123123123123123123123
Time 37
12123123123123123123123
Time 38
12123123123123123123123
Time 39
12123123123123123123123
Time 40
12123123123123123123123
ELAPSED: TOTAL PAUSED:
Post-exp
Stomach Nausea
HEAD MOVEMENTS:
Drowsiness Headache Pallor
Dizziness Sweating Salivation Warmth
12123123123123123132 312
64
USSOCOM Practice Sequence Checklist
The subject completes the following five practice sequences in order. The experimenter places a check in
the box when each sequence is completed.
Practice Item Code:
CB = Cognitive Battery
F = Fregly (balance task)
HG = Handgrip
S = Shooting System
VA = Visual Accommodation
Sequence # Practice Items_______________________________
1 VA, CB1, S, HG VA: HG:
2 VA, CB2, S, HG VA: HG:
3 F, VA, CB3, S VA
4 F, CB3, S, HG HG
5 F, VA, CB3, S VA
1 CB Sequence 1 contains: Logical Reasoning
2 CB Sequence 2 contains: Logical Reasoning, Match to Sample, Simple Reaction Time, Complex
Reaction Time
3 CB Sequence 3, 4 and 5 contain: Logical Reasoning, Match to Sample, Simple Reaction Time, Complex
Reaction Time, Time Wall
FREGLY Time 1 (in secs) Time 2 Time 3
Sequence 3
Sequence 4
Sequence 5
65
PRE-DOSE COMPLIANCE CHECKLIST
SUBJECT NUMBER: TEST DATE: / /
TRANSDERMAL TIME: : PO DOSE TIME: :
In the past 24 hours, have you consumed any of the following products (Please all the answers which apply):
Prescription
Yes
No
Over-the
counter (OTC)
Yes
No
If YES, please list the drugs: ________________
__________________________________________
Herbal
Yes
No
If YES, please list the drugs: ________________
__________________________________________
Alcohol Yes No
Caffeine Yes No If YES, please list the beverages/ food and amounts:
_____________________________________
_____________________________________
Tobacco/
Nicotine
Yes
No
If YES, please explain: ________________
______________________________________
Grapefruit juice
Yes
No
66
ADVERSE EVENT FORM
SUBJECT NUMBER: ADMIT DATE: / /
TRANSDERMAL TIME: : PO DOSE TIME: :
NONE
ADVERSE EVENT
SEVERITY
1= Mild 2= Moderate 3= Severe
ONSET DATE ONSET TIME
(24-hour clock) END DATE
DURATION
(sec, min, hrs, days)
PATTERN
1= Continuous 2= Intermittent
RELATIONSHIP
TO STUDY
DRUG
1= None
2= Remote
3= Possible
4= Probable
5= Definite
ACTION
TAKEN
1= None
2= OTC Drug
3= Non-Drug
4= Rx Drug
5= Hospitalized
6= Other
(Please
specify in
COMMENTS)
OUTCOME
1= Resolved
2= Ongoing
3= Alive w/
sequelae
4= Death
5= Other (Please
specify in
COMMENTS)
1.
//
:
//
2.
//
:
//
3.
//
:
//
4.
//
:
//
5.
//
:
//
6.
//
:
//
7.
//
:
//
8.
//
:
//
COMMENTS:
67
Appendix C
NAMRL Evaluation of Some of the Key Cognitive Measures of the MRPM
This appendix briefly summarizes the result of a separate study we did (Mc Grath et al., 2007) to
independently assess the sensitivity, stability, reliability, and platform sensitivity of some of the
key cognitive performance measures employed by USSOCOM in the MRPM. This appendix is
derived from the abstract and slide lecture delivered to the Aerospace Medical Association
annual meeting in New Orleans in May, 2007. These two items are shown respectively, below.
Abstract:
EVALUATING PERFORMANCE OF TWO COGNITIVE TEST BATTERIES UNDER
CONDITIONS OF DISTRACTING NOISE.
C. MCGRATH1, B. LAWSON1, S. KASS2,
1Naval Aerospace Medical Research Laboratory, Pensacola, Florida; 2University of West
Florida, Pensacola, Florida
INTRODUCTION. We evaluated two cognitive test batteries: a) a PDA-based battery provided
by NASA and b) a laptop-based battery provided by the U.S. Special Operations Command
(USSOCOM). Of four tests in each battery, three tested the same abilities. Mean reaction time
and percent correct measures from each test were assessed for reliability, practice effects, and
noise sensitivity. METHODS. Tests included reaction time (simple and complex), running
memory, matching to sample, and logical reasoning. On day 1, subjects (n = 26) practiced each
test six times (trials 1-6). On day 2, subjects were assigned to one of two conditions (n = 13
each): 1) A two-trial session (i.e., trials 7-8) wherein a distracting noise was introduced in the
first trial; 2) a two-trial session wherein the noise was introduced in the second trial. The noise
was a 95 dB random medley of noxious noises, including: cat screeching, woman screaming,
glass breaking, baby crying, gun firing, air raid siren wailing, and car alarm sounding.
RESULTS. Performance was high, averaging 91% correct. Average speed of response was
more reliable than percent correct: mean reliability of response speed was .88 overall. Practice
was effective: 88% of measures were stable by trial 4. Logical reasoning was the measure most
sensitive to noise. Running memory and complex reaction time were not sensitive to noise, and
the remaining measures produced mixed findings. DISCUSSION. The tests were reliable and
stable after practice. Logical reasoning was the most useful test for detecting distraction due to
noise. Though the NASA and USSOCOM batteries measured similar abilities, the tests were not
identical. Lack of test standardization is a common concern when data comparison is desired.
Currently, we are using these tests to determine whether there are performance decrements
following the use of certain antimotion sickness medications during a sickening motion stimulus.
The presentation follows:
68
Evaluating Performance of
Evaluating Performance of
Two Cognitive Test Batteries
Two Cognitive Test Batteries
Under Conditions of
Under Conditions of
Distracting Noise
Distracting Noise
C. McGrath, B. Lawson, & S. Kass
Purpose
Purpose
Compare two cognitive test batteries for
Compare two cognitive test batteries for
use in subsequent studies
use in subsequent studies
1.
1. Mission
Mission-
-Related Performance Measures
Related Performance Measures
(MRPM)
(MRPM)
2.
2. Automated Readiness Evaluation System
Automated Readiness Evaluation System
(ARES
(ARES
TM
TM
)
)
69
Platforms
Platforms
MRPM: Laptop
MRPM: Laptop
ARES
ARES
TM
TM
: PDA
: PDA
Test Assessments
Test Assessments
Stability
Stability
Reliability
Reliability
Sensitivity
Sensitivity
70
Participants
Participants
26 US Naval
26 US Naval
Aviation Candidates
Aviation Candidates
25 men, 1 woman
25 men, 1 woman
Average age 23,
Average age 23,
SD
SD
of 2.3
of 2.3
Eight Tests Evaluated
Eight Tests Evaluated
Similar tests in both platforms:
Similar tests in both platforms:
Matching to Sample (M2S)
Matching to Sample (M2S)
Logical Reasoning (LR)
Logical Reasoning (LR)
Simple Reaction Time (SRT)
Simple Reaction Time (SRT)
PDA ARES Only:
PDA ARES Only:
Running Memory Task (RM)
Running Memory Task (RM)
Laptop MRPM Only:
Laptop MRPM Only:
Complex Reaction Time (CRT)
Complex Reaction Time (CRT)
71
Simple Reaction Time (SRT)
Simple Reaction Time (SRT)
STOPSTOP
How quickly can you react to the word?
Matching to Sample (M2S)
Matching to Sample (M2S)
Which pattern on next slide matches this one?
72
Matching to Sample (M2S)
Matching to Sample (M2S)
Logical Reasoning (LR)
Logical Reasoning (LR)
73
Running Memory (RM)
Running Memory (RM) -
-PDA
PDA
Is next number different
Is next number different
or same?
or same?
Different Same
1
Different
4
Running Memory (RM)
Running Memory (RM) -
-PDA
PDA
74
Complex Reaction Time (CRT)
Complex Reaction Time (CRT) -
-Laptop
Laptop
Which direction is black box?
Which direction is black box?
Complex Reaction Time (CRT)
Complex Reaction Time (CRT) -
-Laptop
Laptop
75
Procedure
Procedure
Practice (Day 1)
Practice (Day 1)
One trial = Performing all 4 tests on each
One trial = Performing all 4 tests on each
platform (order balanced)
platform (order balanced)
5 minute rest between trials
5 minute rest between trials
Total of 6 trials
Total of 6 trials
First 4 trials included performance feedback
First 4 trials included performance feedback
Day 1 Results
Day 1 Results
Practice
Practice
Across both platforms:
Across both platforms:
Practice was effective
Practice was effective
7/8 measures stable by trial 4
7/8 measures stable by trial 4
(Differential stability using Cohen
(Differential stability using Cohen
s d)
s d)
Accuracy was high, but avg. speed more
Accuracy was high, but avg. speed more
reliable (0.88) than avg. accuracy (0.76)
reliable (0.88) than avg. accuracy (0.76)
These trends agree with literature
These trends agree with literature
Kane & Kay, 1992
Kane & Kay, 1992
Kennedy et al., 1992
Kennedy et al., 1992
Carter et al., 1986
Carter et al., 1986
76
Laptop vs. PDA Versions of Tests
Laptop vs. PDA Versions of Tests
Both batteries adequate
Both batteries adequate
Test
Test-
-specific observations:
specific observations:
SRT, M2S and LR faster & less variable on
SRT, M2S and LR faster & less variable on
PDA ARES
PDA ARES
M2S accuracy ceiling effect on PDA ARES
M2S accuracy ceiling effect on PDA ARES
Day 2: Sensitivity
Day 2: Sensitivity
Noise & no
Noise & no-
-noise conditions
noise conditions
Random medley of noxious noises
Random medley of noxious noises
95 decibels (well within OSHA safety limits)
95 decibels (well within OSHA safety limits)
77
Practice
Practice
(n=26)
(n=26)
Normal, then Distractor (n=13)
Normal, then Distractor (n=13)
Distractor, then Normal (n=13)
Distractor, then Normal (n=13)
Sensitivity
Sensitivity
DAY 1
DAY 1 DAY 2
DAY 2
Day 2 Results
Day 2 Results
All tests sensitive to noise
All tests sensitive to noise
Effect greatest when sound on first trial
Effect greatest when sound on first trial
of Day 2
of Day 2
Except logical reasoning: always sensitive
Except logical reasoning: always sensitive
78
Recommendations
Recommendations
Give
Give
4 practice sessions
4 practice sessions
Measure speed of response
Measure speed of response
Logical reasoning good performer
Logical reasoning good performer
Be aware that version/platform may
Be aware that version/platform may
affect performance of a given test
affect performance of a given test
79
Appendix D
Statistical Power Estimate
A Post hoc power analysis was computed using the program G*Power (Erdfelder, Faul, &
Buchner, 1996).2 Achieved power was calculated with the following parameters:
The analysis was conducted for a one-way fixed effects analysis of variance with five
levels*
Alpha level was set at .05 (1-tailed); .025 (2-tailed)
Total sample size: 150 (30 per condition)
Observed effect size f: .25 (effect size calculated from variance (i.e., partial eta
squared = .06)
o Effect Size Conventions (as given in G*Power program):
f = .10 = small
f = .25 = medium
f = .40 = large
Results:
Power = .68 (1-tailed) ; .57 (2-tailed)
We also wished to determine what sample size would have been needed (for this study) to
achieve a power of 0.80.
Results:
Sample size needed = 39 (1-tailed); 46 (2-tailed)
Note: The analsyses were conducted using all five treatment conditions; however, it should be
noted that the scopolamine and promethazine conditions were not predicted to differ significantly
from each other.
2 Erdfelder, E., Faul, F., & Buchner, A. (1996). GPOWER: A general power analysis program.
Behavior Research Methods, Instruments, & Computers, 28, 1-11.
... Dr. Wall suggested consideration of a task which involves moving and shooting, perhaps with the additional cognitive load created by shoot/no shoot decisions. Dr. Lawson agreed that shoot/no shoot decisions would increase the cognitive loading and mental stress of the testing and would add to military relevance, but he also noted that the task is essentially a choice reaction task, and that a measurement limitation of laboratory versions of choice reaction time tests is that they tend to be less reliable and take longer to stabilize than simple reaction tests (Lawson et al., 2009). They also are very susceptible to instruction set (subject motivation, etc.), while not adding all that much scientifically to the understanding of different specific aspects of neurological functioning, e.g., compared to a test which taps a totally different aspect of neurocognitive performance (such as visual pattern memory). ...
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