VECTION-INDUCED GASTRIC DYSRHYTHMIAS AND MOTION SICKNESS

Annual Report for Year 1

(May 1, 1985 to April 30, 1986)

NASA Contract

NAG 9-118

Date Submitted: April 1, 1986

(NASA-CR-176620 ) VECTICN-INDUCE D

.DYSBHYTBHIAS AN D MOTIO N SICKNESS

Report, 1 May 1.SC5 - 30 Apr . 1986

(Hilton S.) Medical Center) 64 p

HC 1Q4/HF A.0.1. '

GASTRIC

Annual

{Hershey

CSCL 06S G3/52

N86-22095

Unclas

05744

Principal Investigator: Kenneth L. Koch, M.D.

Division of Gastroenterology

The Milton S. Hershey Medical Center

The Pennsylvania State University

P.O. Box 850

Hershey, Pennsylvania 17033

717-534-6261

Co-Investigator: Robert M. Stern, Ph.D.

Psychology Department

417 Moore Building

The Pennsylvania State University

University Park, Pennsylvania 16802

814-865-9514
TABLE OF CONTENTS

Page

I. Abstract 2

II. Introduction 4

III. Background 4

IV. Plan of Research - Year I 5

V. Results

A. Subjects with Intact Stomach 8

B. Subjects with vagotomy and gastric resections 11

VI. Discussion 14

VII. Summary 18

VIII. References 19

IX. Figures and Tables 22

X. Publications Resulting from NASA Support: Appendix A
Abstract

Gastric responses to motion stimuli have been neglected since the 1940's.

The overall objective of our three year proposal is to investigate gastric

electrical and mechanical activity during vection-induced motion sickness.

Specific aims during the first year were: (1) to measure simultaneously the

contractile events of the gastric antrum and gastric myoelectric activity in

healthy subjects exposed to vection; (2) to determine symptomatic and

myoelectric responses of subjects with vagotomy and gastric resections during

vection stimuli; and (3) to develop laboratory-based computer systems for

analysis of the myoelectric signal. Gastric myoelectric activity was recorded

from cutaneous electrodes, i.e. electrogastrograms (EGGs), and antral contractions were measured with intraluminal pressure transducers. Vection was

induced by a rotating drum. Gastric electromechanical activity was recorded

during three periods: 15 min baseline, 15 min drum rotation (vection), and

15-30 min recovery.

Fifteen healthy men were studied: seven subjects reported mild to severe

nausea during vection. In 6 of 7 subjects (86%), nausea was associated with

the onset of abnormally rapid EGG frequencies termed tachygastrias. The number

of antral contractions did not change significantly during vection, although

the trend was toward fewer contractions during vection and recovery. A burst

of phasic duodenal contractions was recorded in one subject during severe

nausea and retching during vection. Eight healthy subjects reported no

symptoms during vection; 6 of the 8 (75%) maintained normal 3 cpm EGG patterns,

1 had respiratory artifact, and 1 had tachygastria. In these asymptomatic

subjects, antral contractions did not change significantly during vection or

recovery. Preliminary results showed that catecholamine responses in nauseated

versus symptom-free subjects were divergent and pretreatment with metoclopramide HC1 (Reglan) prevented vection-induced nausea and reduced tachygastrias

in two previously symptomatic subjects.

Six subjects with previous vagotomy and various gastric resections were

studied. Five of six postoperative subjects reported mild-moderate nausea

during vection, and in 3 subjects the EGG frequency and amplitude increased

during nausea. The EGG signal was unchanged in two subjects. Intraluminal

pressures measured in three subjects were quiescent in all test periods. Only

the subject with total gastrectomy was symptom-free during vection.

Running spectral analysis was accomplished with laboratory-based computer

systems. The plots are presented herein.

We conclude: In subjects with intact stomachs - (1) Onset of tachygastria or maintenance of 3 cpm EGG patterns discriminates subjects with

vection-induced nausea or no symptoms, respectively; (2) Antral contractility

did not distinguish symptomatic from asymptomatic groups, but severe nausea and

retching were associated with duodenal contractions; and in postoperative

subjects - (1) All subjects with vagotomy and gastric remnants were susceptible

to vection-induced nausea, indicating a role for non-vagal pathways or other

neurohormonal fluxes in the genesis of motion sickness; (2) Total gastrectomy

appeared protective, suggesting a gastric remnant was necessary for vectioninduced nausea.

-2-
Gastric electromechanical events induced by vection represent brain-gut

interactions which may be relevant to the pathophysiology and treatment of

motion sickness and space adaptation syndrome.

-3-
II. Introduction

The following report presents accomplishments during the first year (May

1985 - April 1986) of our three year project entitled, "Vection-Induced Gastric

Dysrhythmias and Motion Sickness" (NASA Grant NAG 9-118).

Objectives for the first year were:

(1) To measure electrical and mechanical (i.e. contractile) activity of

the gastric antrum during vection in healthy subjects (Protocol A4, p. 22 of

original proposal); (2) To examine symptomatic and gastric myoelectric

responses of subjects with vagotomy and various gastric resections during

vection stimuli (Protocol A3, p. 22 of original proposal); and, (3) To develop

laboratory-based computer systems for analysis of the gastric myoelectric

signals (p. 26 original protocol).

III. Background

As described in the original proposal, gastric responses to motion stimuli

have been virtually ignored for the past 40 years. In the 1940's, several

investigators described loss of gastric tone and peristaltic contractions in

subjects who developed symptoms of motion sickness while positioned in various

movement devices (1,2). Despite the fact that most individuals describe

symptoms of motion sickness as vague epigastric discomfort and nausea, the

relationship between stomach motility and motion sickness has been neglected.

The present investigators have reported that almost 2/3 of subjects who

experience illusory self motion or vection develop sweating, epigastric

distress and nausea, i.e. symptoms of motion sickness (3). Moreover, normal 3

cycle per minute (cpm) gastric slow wave frequency or "pacemaker" activity

shifted to more rapid frequencies (i.e. 5-9 cpm) prior to or concomitantly

with the onset of nausea during vection (3). (The 5-9 cpm frequencies, termed

tachygastrias, have been previously described in patients with idiopathic

nausea and vomiting (4) and gastroparesis (5)). Gastric slow wave frequencies

recorded by mucosal or EGG electrodes are virtually identical (6,7). Furthermore, after drum rotation and vection stopped, the nausea resolved, the

tachygastrias disappeared and the 3 cpm rhythm usually returned within 20 min

in these healthy individuals (3). Thus, the central nervous system (CNS)

responses elicited by visual-vestibular mismatch of vection induced symptoms of

motion sickness and the objective finding of a shift from 3 cpm EGG activity to

tachygastria. Equally important, other individuals remained asymptomatic and

maintained a normal 3 cpm gastric rhythm. Thus, measurement of gastric

electromechanical events during vection provides a unique setting to

investigate brain-gut interactions during motion stimuli.

These findings may be particularly relevant to the space adaptation

syndrome (SAS). Symptoms of SAS mimic motion sickness, and visual-vestibularcerebellar interactions with altered otolithic function may have roles

in the SAS (8). Moreover, a recent report indicated Space Lab I astronauts

experienced an enhanced sense of vection in microgravity when compared with

ground tests (9). Brain-gut interactions such as vection-induced tachygastria

may be relevant to the physiology of and treatment approaches to SAS as well as

earthly motion sickness.

-4-
The neurohormonal changes evoked during vection which disrupt normal 3 cpm

gastric pacemaker function are unknown. Labyrinthine stimulation was associated

with increased levels of plasma epinephrine and endorphins and with a delay

in gastric emptying of a meal (i.e. decreased gastric contractility) (10).

Infusion of glucagon disrupts normal gastric rhythms in man (6). Infusion of

epinephrine, prostaglandin Ep> and glucagon in dog also causes a shift from

normal pacemaker frequency of 5 cpm to canine tachygastrias of 12 cpm (11).

The roles of parasympathetic and sympathetic nervous system responses in

eliciting or preventing human tachygastria and symptoms of motion sickness

during vection are unknown.

Our vection-gastric myoelectric data suggested three related hypotheses

regarding the gastric responses to motion stimuli:

Hypothesis 1;

Visual-vestibular sensory mismatch, which occurs during vection, stimulates

a "neuro-hormonal" response and outflow from the CNS which disrupts a peripheral

physiologic process - normal 3 cpm gastric pacemaker activity. That is, in

subjects who develop nausea the normal 3 cpm pattern is disrupted and shifts to

tachygastrias. On the other hand, asymptomatic subjects may have different CNS

neuro-hormonal outflow in response to vection, or they have "resistant" 3 cpm

gastric pacemaker function.

Hypothesis 2:

Vection-induced gastric dysrhythmias are ultimately perceived as epigastric

distress and nausea (possibly via vagal afferents) and reinforce or potentiate

the ongoing visual-vestibular neural mismatch.

Hypothesis 3:

The preservation of normal 3 cpm gastric rhythm may prevent or diminish

symptoms of motion sickness elicited by vection or other motion stimuli.

The studies performed during Year 1 provided data which was relevant to

these underlying hypotheses.

IV. Plan of Research - Year 1

Two of the original ten protocols were funded for the first year. The

methods and design of investigations are briefly reviewed below:

(1) Methods:

a) Vection - Vection was induced by rotating a drum (91.5 cm x

76.0 cm) around the subjects who were seated within. A chin rest was

used to stabilize the head. The inner surface of the drum is covered

with 48 alternating black and white vertical stripes, each black and

white stripe subtending 15 degrees of the surface (Figure 1). The drum

was rotated 60 degrees per second.

-5-
b) Electrogastrography - Gastric myoelectric activity was recorded

from three electrodes in bipolar configuration positioned on the abdomen

as shown in Figure 2. The resulting electrogastrograms or EGGs were

recorded simultaneously on a rectilinear recorder (Beckman R612) and

magnetic tape (Honeywell 101-1B tape recorder) for visual and computer

analysis. The frequency of EGG waves is virtually identical to the

frequency of gastric slow waves measured with mucosal electrodes (6,7).

Normal slow wave frequency is 3 cpm; tachygastrias range from 4-9 cpm.

Additional information concerning EGG recording techniques may be found in

Reference (12).

c) Intraluminal pressures - Pressures were recorded from the gastric

body and antrum with three solid-state pressure transducers located 5 cm

apart on a 6 French flexible catheter (Figure 2). Catheter position

within the stomach was verified by fluoroscopy.

d) Respiratory rate was recorded in all subjects with a bellows

pneumograph.

e) Computer instrumentation and analysis in the EGG laboratory - The

output of the Beckman polygraph was routed to a Sperry Model 500 Personal

Computer for purposes of data analysis. The Sperry PC is equipped with a

10 megabyte fixed disk drive, 640 kilobytes of Random Access Memory (RAM),

an Intel 8087 math co-processor chip, and a high resolution color monitor.

Additional peripheral devices are a Variant Technologies Model VT-700, 26

megabyte streaming tape cartridge drive for mass storage of data; a

Metrabyte Model Dash-16 analog to digital (A/D) conversion board which

allows acquisition of up to 8 true differential channels of data as well

as 4 channels for digital input and output which allow control of

laboratory equipment; a Sperry Model 5 dot-matrix printer for rough copies

of graphs and hard copies of data; an Everex expansion chassis which

provides additional slots for the peripheral device controller cards; and

a Hewlett-Packard Model HP7470A plotter for presentation quality and

camera ready data plots.

From the polygraph or magnetic tapes, the EGG signal was channeled

to the A/D conversion board where it was digitized into a series of

discrete numerical voltage levels. Thus, the analog EGG signal was

converted to a digital time series which can then be subjected to a wide

range of analyses. The A/D conversion unit allowed sampling at a wide

range of speeds and the EGG was sampled at a rate of 1 Hertz or once per

second. This rate allowed definition of frequencies up to 30 cpm which

was more than adequate for the EGG. Once the signal was digitized, it was

stored first on disk and then transferred to magnetic tape for long term

storage.

The analysis of the EGG signal: The digital signal was first zero

centered and linearly detrended. In other words, a simple linear

regression line was fitted to the time series and then subtracted. The

zero centering procedure was conducted so the time series varies around

the value zero which ensured that the time series fulfills the

assumptions inherent in spectral analysis. The linear detrending removed

-6-
any remaining linear shifts in the signal. The time series may also be

subjected to digital filtering to provide a "clearer" time series. That

is, any remaining frequencies in the signal higher than those in the EGG

may be removed. The time series was then Fourier transformed and the

spectral density estimates were calculated. This spectral analysis

provided information concerning the frequencies contained in the signal.

The typical output of a spectral analysis is a graph showing the strength,

or power, of the frequencies present in the original time series. Power

may be considered an index of the amplitude of the sine waves of a

particular frequency that would be required in order to recreate the

original signal. The 0-1 cpm low frequency spectra are difficult to

evaluate during the vection experiments because vigorous high amplitude

EGG signal responses were often evoked during vection. 'Thus, if the

recording pens "pegged out" for more than 20 s and created "flat" EGG

signals, computer analysis showed high power 0-1 cpm activity. Therefore,

0-1 cpm activity is not described in detail. Changes in recording

techniques are under study to limit the number of "flats" in the EGG

signal.

Spectra are graphed in a pseudo 3-dimensional plot called a "running

spectral plot". Such a graph was obtained by conducting spectral analyses

on successive segments of the signal, each of which overlaps 75% with the

preceeding and subsequent segments. Each separate spectrum represents 4

minutes of real time, with the first line showing the frequency spectrum

of minutes 1-4, the second represents minutes 2-5 and so on. This

procedure allows easy viewing of frequency changes as a function of time.

(2) Data Analysis

Visual analysis of EGG records was accomplished by counting the

number of waves per minute in each test period. The EGG electrode lead

with the clearest signal and least artifact was chosen for these

analyses.

The same EGG channel was digitized and analyzed by FT (see above).

The FT plots are described qualitatively in the report.

Intraluminal pressures were analyzed by counting the number of

contractions, the amplitude of each contraction, and by determining a

Motility Index (no. of contractions x amplitudes) for each test period.

These data were subjected to statistical analysis (i.e. paired and

unpaired t-tests). P<0.05 was considered significant.

(3) Design

All studies followed the "Protocol A" design shown in Figure 3.

Each subject fasted at least four hours before testing. EGG, respiration

and intraluminal pressures were simultaneously recorded during the

baseline, drum rotation and recovery periods. The subjects indicated the

intensity of nausea experienced during vection by marking a 300mm analog

scale (0 = no symptoms; 300mm = severe nausea, almost vomited) after the

recovery period.

-7-
In several subjects, peripheral venous blood samples were obtained af

after a 30 min rest period (outside the drum), and then at the end of the

15 min baseline period, and 1, 10 and 20 minutes after drum rotation

ceased (i.e. during the recovery period). The latter four samples, then,

were drawn while the subject was within the drum. Also, two symptomatic

subjects who had developed tachygastria returned 8-12 weeks after the

first test and received metoclopramide (20 mg by mouth) before their

second trial of vection.

Results

A. Vection Studies in Healthy Subjects:

1. Relationship of Antroduodenal Contractile Activity and VectionInduced Gastric Dysrhythmias and Motion Sickness (Protocol A4JT

Fifteen healthy men (ages 22 to 37, mean 26.5 yr) entered the vection

protocol with EGG and intraluminal pressure recordings. Time to onset of

vection averaged 1.6 min, range 1-2.5 min. Table I summarize the EGG

frequency responses in these healthy subjects during the vection protocol.

Baseline EGG patterns in the 7 subjects who subsequently developed nausea

during vection showed low amplitude intermittent 3 cpm patterns (i.e. poor

3 cpm activity) or flatline in four subjects, clear 3 cpm pattern in one,

tachygastria in one and respiratory artifact in one. During vectioninduced nausea, tachygastrias were observed in six of the seven subjects;

in the other subject, respiratory rhythms obscured the EGG activity.

First report of nausea occurred after an average of 6.4 min of vection

(range 2-11 min). During the recovery period, 3 cpm patterns returned in

three subjects, but tachygastrias were clearly present in three other

subjects and respiratory artifact continued to predominate in one. Nausea

scores ranged from 29 to 290 indicating the spectrum of intensity of

vection-induced nausea. Other symptoms reported by these subjects

included warmth, sweating, slight headache, dizziness, faster respiration

and "churning" in stomach. (See Appendix A for detailed report of the

evolution of symptoms and EGG frequencies during vection.)

Eight subjects reported no nausea during vection and their EGG

responses are also shown in Table I. Each subject had a clearly

discernible 3 cpm pattern during baseline. During vection, the 3 cpm

pattern was maintained in six of the eight subjects; in one subject,

respiratory rhythms predominated (this subject reported "sweating"); and

in the other subject, a 4-5 cpm tachygastria developed (this subject

reported he was "dizzy"). During recovery, clear 3 cpm patterns were

present in six subjects; a flatline EGG pattern was seen in one subject,

and poor 3 cpm activity was noted in one subject. These latter two

subjects were the ones with sweating and dizziness during vection.

-8-
Figure 4 shows the EGG recording from Subject (6, MD) who developed

nausea during vection: the baseline shows a 3 cpm rhythm; whereas, during

nausea the EGG signal contains narrow-based, sharp peaked waves with 7-8

cpm frequency. The 3 cpm pattern reappears during the recovery period as

nausea disappears. Figure 5 shows the running spectral analysis (RSA) of

the EGG signal from Subject (6, MD). During baseline peaks at 3 cpm are

seen. After 3-4 min of drum rotation the subject reported nausea which

increased in intensity at 8 to 11 minutes of rotation. Several tachygastria peaks are seen during these times. During the recovery phase the

tachygastrias resolved; and little to no 3 cpm activity reappeared during

recovery (Figure 5A). Low frequency components 0-1 cpm are seen throughout

the recording and indicates both low frequency signals and flat portions

of the raw signal.

Figure 6 shows EGG activity in Subject (7, JE) who reported no

symptoms during vection. The EGG rhythm during baseline, vection and

recovery periods remained clear at 3 cpm. Figure 7 shows the RSA of the

entire vection study of Subject (7, JE). Prominent 3 cpm peaks are seen

during baseline; the power at 3 cpm decreased slightly during vection but

the frequency remained clearly 3 cpm. No tachygastrias developed. Also,

fewer 0-1 cpm peaks are seen in Figure 7 reflecting fewer flat portions in

the raw EGG signal.

Intraluminal pressure responses during vection studies in 12 healthy

subjects are summarized in Table 2. Three of the 15 healthy subjects did

not undergo gastric intubation. Thus, the pressure data from five subjects

who developed nausea during vection and seven who did not are presented.

The range of contractile events in the subjects who developed nausea was

marked, ranging from 0 to 42 contractions during the 15 minute baseline

period. During vection, the number of contractions decreased in two subjects, increased in one, and was unchanged in two. Compared with baseline

the average motility index (MI), which takes into account the amplitude of

the contractions, did not change significantly during vection. The mean

number of contractions and MI during recovery were less than during

baseline or vection, but none of the changes reached statistical

significance.

Concerning the seven subjects who had no nausea during vection, the

mean number of contractions and MI during baseline (4.1 and 1089.2,

respectively) decreased during vection (0.9 and 48.3), but the differences

were not significant. Again, the wide range of contractile events (0-12)

and Mis (0-3555) among individual subjects was marked. Contractions and

MI remained decreased during recovery, but the differences were not

significant. Additional comparisons of MI in subjects with nausea versus

those without nausea showed no differences at baseline or during vection.

During the recovery period, the symptomatic group had a significantly

larger MI than the asymptomatic group (710 vs. 35.8 P<0.01). These

results must be interpreted cautiously because subject (1, SK) probably

represents an "outlier" whose values have skewed the means. Despite

Subject (1, SK), the trend is toward decreased number of contractions

during vection, but more studies are needed to determine if the trend is

significant.

-9-
In addition, although large changes in the amplitude of the EGG

signal frequently occurred with tachygastria, no accompanying change in

intraluminal pressures was detected as seen in Figure 4. Thus, the marked

shifts in EGG frequency reflected changes in electrical pacemaker or slow

wave frequencies and not mechanical events.

To summarize: the shifts in baseline EGG frequency to tachygastrias

discriminated 6 of 7 subjects with vection-induced nausea; whereas, intraluminal pressure responses did not. Symptomatic subjects had weaker

baseline 3 cpm patterns than the asymptomatic subjects. Maintenance of 3

cpm was associated with no symptoms during vection in 6 of 8 subjects;

whereas, a wide range of contractile events was also recorded in these

subjects. Thus, changes in gastric rhythms were more susceptible to

vection than changes in gastric contractile events. EGG recordings were

more sensitive than antral pressure recordings in detecting perturbations

in gastric function during vection.

2. Duodenal Contractions and Gastric Dysrhythmias During VectionInduced Nausea.

In one subject the distal pressure transducer inadvertently slipped

into the duodenum during the baseline period. This subject subsequently

developed severe nausea culminating in retching after only 4 minutes of

vection. As shown in Figure 8A, a burst of contractions (approximately

10-1 I/min) is seen in duodenum (DI) at the time of severe nausea and

retching. At the same time, EGG signal is temporarily lost. As duodenal

contractions diminish in amplitude, 8-9 cpm tachygastria becomes apparent

(Figure 8B). During recovery, 3 cpm activity reappears and intraluminal

pressures are quiescent. Figure 9 is the RSA from this same subject. The

8-9 cpm peaks indicate tachygastrias while the peaks at 10 cpm appear to

coincide with the duodenal contraction frequency of 10-11 per min.

Respiratory peaks at 13-14/min are seen. These data indicate rhythmic

duodenal contractions may occur during severe nausea and retching and the

accompanying electrical activity may be detected by RSA of the EGG signal.

Further studies are needed to examine the role of duodenal contractile

activity in severe nausea induced by vection.

3. Vection-Induced Plasma Catecholamine Responses in Nauseated and

Symptom-Free Subjects.

Plasma catecholamine levels were measured by radioenzymatic assay

(13) in subjects who did and did not report nausea during vection; the

EGG records and RSAs from these subjects are shown in Figures 4 and 5 and

6 and 7, respectively. Figure 10 shows the results of the catecholamine

studies. In the subject who developed tachygastria and nausea,

norepinephrine, epinephrine and dopamine were decreased immediately after

vection and at a time when nausea and tachygastria were still present.

The catechol levels returned toward baseline at 10 min and then "overshot"

baseline levels by 44-118%.

-10-
The catecholamines also decreased in the asymptomatic subject who

maintained 3 cpm activity; but, in contrast to the nauseated subject, the

catechol levels remained suppressed during the 20min recovery period.

Although vection-induced motion sickness may be considered "stressful",

classic sympathetic "fight or flight" mediators appear to be suppressed

immediately after vection (see Discussion).

It should be pointed out that a catecholamine profile was also

measured after a 30 min rest period in a chair before the subject

entered the drum to begin the baseline period. From the rest period to

the pre-rotation baseline period, the asymptomatic subject had a 95% and

177% increase in plasma norepinephrine and dopamine, respectively;

whereas, the subject who developed nausea had a 67% and 0% increase in

these two catechols. In other words, the asymptomatic subject appeared

to muster a greater sympathetic nervous system response before vection

than the symptomatic subject. On the other hand, the adrenal epinephrine response during this rest to baseline period was greater in the

nauseated subject (980% increase) than in the symptom-free subject (800%

increase in epinephrine). It is interesting to consider that these

divergent catecholamine responses may have influenced the baseline EGG

patterns (i.e. compare the baseline EGG activity in Figures 4 and 5 (the

nauseated subject) versus the clear 3 cpm patterns in Figures 6 and 7 (the

asymptomatic subject).

4. Effect of Metoclopramide HC1 (Reglan) on Vection-Induced

Tachygastria and Nausea.

Two symptomatic men who developed tachygastria returned for a second

trial 8-12 weeks after the initial vection experiment. Thirty to 45

minutes before vection, 20 mg. of metoclopramide was given by mouth.

With metoclopromide pretreatment, neither subject reported nausea during

the vection period and tachygastrias were reduced. Figure 11 shows the

gastric electromechanical responses to metoclopramide. Intraluminal

pressures were increased during the baseline period (compare Figures 11

and 4; this is the same subject) but were again quiescent during the

vection period. The EGG pattern showed a slightly stronger 3 cpm pattern

during baseline; during vection the EGG configuration changed, but

remained at the 3 cpm frequency, and the subject reported only slight

dizziness. Low amplitude 3 cpm pattern was present during recovery. The

post-metoclopramide RSA is shown in Figure 12 and may be compared with

Figure 5: the number and power of tachygastrias are reduced.

B. Vection Studies in Subjects with Vagotomy and Gastric Resections:

1. Vection-induced motion sickness and gastric dysrhythmias in

patients with vagotomy and various gastric resections.

Seven subjects (3 men and 4 women, ages 34 to 65, mean 50.3 yrs)

were studied as described above. Intraluminal pressures in three

subjects showed no change during vection; this finding, in addition to the

negative results in the healthy subjects, resulted in a decision to

discontinue Intraluminal pressure recordings in the gastric resection

-11-
subjects. One subject failed to experience vection and is not reported.

Of the six subjects who experienced vection, three had Roux-en-Y

anastomoses (vagotomy plus antrectomy), two had vagotomy and pyloroplasty

(V+P) and one had a total gastrectomy.

The symptoms and EGG frequency responses of the postoperative

subjects to the vection protocols are listed in Table 3. Vection was

reported within an average of 2.5 min of drum rotation. Only one of the

six subjects had a predominant 3 cpm pattern during baseline; four

subjects had flatline or 1 cpm pattern and one had an 11 cpm pattern.

During vection all subjects, except the total gastrectomy patient,

reported mild to moderate nausea 4-8 min after onset of vection. Three of

these subjects had a shift to higher EGG frequencies at onset of symptoms:

two had tachygastrias (one Roux-en-Y and one V+P) and one (Roux-en-Y) had

a burst of 3 cpm activity. No obvious EGG changes occurred in the two

other symptomatic subjects. During recovery, the baseline EGG pattern

returned in two of the three symptomatic subjects and remained 5-6 cpm in

one. The EGG patterns during recovery in the other 3 subjects were

similar to their baseline patterns.

Figure 13 shows a composite of EGG segments and the RSA from subject

(1, SM)'s vection experiment. Prominent 3 cpm peaks are seen during

baseline and the inset A shows a sample of the actual EGG signal during

this period. Moderate nausea began after about 4 min of vection and was

associated with a shift to tachygastrias as shown in the RSA and EGG inset

B. During recovery, the tachygastria resolved and 3 cpm patterns in RSA

and EGG signal returned. This pattern in a nauseated postvagotomy subject

was similar to EGG pattern seen in the nauseated subjects with intact

stomachs.

Figure 14 shows the EGG signal from subject (2, MB) with Roux-en-Y

before, during and after vection. Flat, low-frequency wave forms,

presumably a result of the previous gastric surgeries, are seen during

baseline. After approximately 5 min of vection the subject reported

nausea; the EGG signal had shifted to narrow-based, high-amplitude waves

at 8 cpm. The tachygastria continued until drum rotation stopped; during

recovery the baseline EGG pattern was re-established. Figure 15 shows the

RSA of the entire vection experiment of subject (2, MB). As described

further in the figure legend, the computer analysis showed the predominance

of 0-1 cpm frequencies during baseline (almost no 3 cpm peaks), an 8 cpm

peak as well as 10-11 cpm peaks during vection, and resolution of

tachygastrias and return of 1 cpm peaks during recovery.

The EGG signals and RSA from the subject with total gastrectomy

(6, WC) are shown in Figures 16 and 17, respectively. No rhythmic pattern

is discernible during the study periods: the signal is flat with

intermittent low amplitude undulations at frequencies near the respiratory

rate. The total gastrectomy patient was asymptomatic during vection.

(This subject repeated the experiment 8 weeks later and again reported no

symptoms.) The RSA (Figure 17) shows predominance of low frequency

activity (0-1 cpm) although during .vection 8 cpm and 15 cpm peaks emerge

which probably represent jejunal electrical activity and respiratory rate,

respectively.

-12-
Figure 18 shows the catechol responses from subject (2, MB) with

Roux-en-Y who developed nausea and tachygastria (Figures 14 and 15) and

from the total gastrectomy Subject (6, WC) who was symptom-free during

vection (Figures 16 and 17). Plasma samples were obtained as described

above. Immediately after vection, the nauseated subject had 365% and

355% increases in epinephrine and dopamine, respectively, and an 85%

increase in norepinephrine. These findings are consistent with "fight or

flight" sympathetic responses, but are distinctly different from the

catecholamine responses of the subject with nausea and intact stomach

(compare with Figure 10). Furthermore, the patient with total gastrectomy

and no symptoms during vection had a persistent decrease in catecholamines,

a pattern similar to the symptom-free subject with an intact stomach

(compare with Figure 10).

Catecholamines were also measured after the 30 minute rest period

before the subject entered the drum and these values were compared with

the pre-drum rotation catechol measurements. The changes in epinephrine,

norepinephrine and dopamine levels were +35%, -76% and 0%, respectively,

in the Roux-en-Y subject who developed nausea during vection. The lack of

anticipatory sympathetic activation (i.e. norepinephrine and dopamine)

before vection is more pronounced than in the nauseated subject with

normal stomach (see page 11). A 30 min rest period plasma sample was not

obtained in the gastrectomy patient, so similar comparisons cannot be

made.

-13-
VI. Discussion

The significant findings of the Year 1 studies are summarized and

discussed below:

Eighty-six percent of the healthy subjects who reported nausea during

vection developed tachygastrias, whereas most symptom free subjects (75%)

maintained 3 cpm EGG patterns and/or did not develop tachygastrias. In

contrast, contractile activity of the gastric antrum during vection did not

distinguish symptomatic from asymptomatic subjects. A trend toward diminished

contractility during vection was apparent, but the changes did not reach

statistical significance. Nevertheless, the trend was consistent with earlier

studies which showed loss of contractility or peristalses during motion

sickness (1,2). More recent studies have shown loss of gastric muscle contraction during tachygastria (14). As shown in Figure 4, antral contractions

were not seen during the tachygastrias.

No distinct intraluminal pressure changes were found in the symptom-free

subjects, but low amplitude 3 per min contractions may escape detection by

luminal catheter transducers (14). Nevertheless, the EGG pattern remained

clearly 3 cpm in the symptom-free subjects, distinguishing the majority of them

from those who developed nausea. These findings confirm our previous work (3)

and indicate that vection stimuli primarily affect the pacemaker or slow wave

activity of the stomach. Thus, shifts in pacemaker frequency (3 cpm to tachygastria) appear to be more sensitive indicators of vection-induced gastric

dysfunction than antral contractility. (Please see Appendix A for additional

discussion of symptoms of motion sickness and EGG changes.)

Duodenal motility, however, may have a role in the genesis of severe

nausea and in the contractile events which produce retching and vomiting.

Other studies have shown that duodenal contractions accompany nausea induced by

labyrinthine stimulation (15,16). Recent studies in dog show that apomorphine

and chemotherapeutic agents elicit a variety of duodenal and gastric electromechanical events, including reverse peristalsis which involves the duodenum

(17). We observed rhythmic duodenal contractions at the onset of severe nausea

and retching induced by vection, findings consistent with the previous studies

in which nausea was induced by cold calorics or pharmacologic stimuli (15,17).

Thus, vection also represents a potent nauseogenic CNS stimulus in certain

individuals. These findings warrant further evaluation of duodenal contractile

activity during vection.

To summarize: EGG patterns distinguish the majority of symptomatic from

asymptomatic subjects during vection; whereas, antral contractions do not.

Duodenal contractions, however, may indicate severe nausea and imminent

vomiting.

Patients with vagotomy and various gastric resections uniformly experience

nausea during vection, whereas the total gastrectomy patient was symptom-free

during vection.The role of vagal efferent and afferent neural activity in

human motion sickness is unknown. In that scopalamine is effective in treating

symptoms of motion sickness, cholinergic activity in brain stem, vestibular

-14-
nuclei and vestibular sensory organs is considered relevant to the causes of

motion sickness. It is possible that the parasympathetic cholinergic outflow

from these CNS structures to the periphery may affect the gastric myoelectric

activity (i.e. cause shifts to tachygastria and symptoms of epigastric

distress, "queasiness", "churning" stomach, and nausea). As suggested in

Hypothesis 2, if vagal efferent or afferent pathways were activated during

vection or caused gastric dysrhythmias, then vagotomy should prevent these

phenomena. Our studies show that vagotomy did not protect the subjects from

symptoms of vection-induced motion sickness. These findings suggest non-vagal

neural pathways or hormonal mechanisms may mediate the gastric dysrhythmias and

motion sickness symptoms evoked during vection.

In dog and man, acute vagotomy disrupts normal gastric slow wave activity

for several weeks (18,19). It was hypothesized, but never proven, that

postvagotomy gastric dysrhythmias in man were due to "sympathetic

dominance" (19). Interestingly, infusions of epinephrine, prostaglandin E2

and glucagon cause tachygastrias in dog (11). In three of our postvagotomy

subjects, shifts in EGG frequency coincided with onset of nausea and

catecholamines (measured in one subject) were markedly elevated immediately

after vection. Sympathetic pathways as well as hormonal responsiveness would

remain intact in the postoperative stomach remnant. These preliminary findings

suggest adrenal-sympathetic responses to vection may result in gastric

dysrhythmias and motion sickness, at least in some postvagotomy subjects. In

two symptomatic subjects, however, no detectable changes in EGG activity

occurred, suggesting a nongastric locus of symptoms - perhaps jejunal or CNS.

However, it appeared some gastric remnant was required for vection-induced

nausea to occur because only the total gastrectomy patient was symptom-free

during vection.

Do the symptoms of motion sickness in man arise from visual-vestibularcerebellar axis activity within the central nervous system, from peripheral

(i.e. stomach) dysfunction, or from both? If the stomach (or a remnant thereof)

is a critical "target organ" which temporarily dysfunctions (i.e. shifts to

tachygastria) in response to the CNS outflow resulting from vection, then the

absence of that organ should protect the subject from motion sickness symptoms.

Thus, the response of the total gastrectomy subject is intriguing because

during two trials he remained symptom-free during vection. Does total

gastrectomy protect against vection-induced motion sickness in man? Additional

trials with total gastrectomy patients are needed to determine if symptom-free

vection is a characteristic finding.

To summarize: Postvagotomy subjects experienced motion sickness,

indicating vagal pathways do not mediate vection-induced nausea. Thus, the

adrenal-sympathetic axis and/or other mediators (i.e. opioids or

prostaglandins) may contribute to gastric dysrhythmias and vection-induced

symptoms.

The preliminary catecholamine and metoclopramide results reported above

relate to mechanisms and treatment of motion sickness and are discussed below:

The basic mechanisms which mediate the escalating symptoms of motion

sickness remain unclear. A variety of hormones and neurotransmitters have been

measured during motion stimuli (20-22); the motion stimuli used in these

-15-
studies, however, involved vigorous rotation or actual movement of the subjects,

intense physical activities with their own "counterregulatory" responses. In

contrast, the subject who experiences vection is stationary and comfortably

seated; and, the physiologic changes which accompany "motion-sickness" are

responses only to the relatively pure CNS stimulus of vection. Nevertheless,

certain subjects progressively develop sweating, warmth, epigastric distress,

and mild to severe nausea during vection; i.e., the range of symptoms

experienced during motion sickness. Furthermore, the CNS circuitry which

mediates vection may be relevant to space sickness, during which otolithic

function is altered (8,9). Vection experiments have other desirable

characteristics in that the subjects are safe, sensitive physiological signals

such as the EGG may be measured, and blood samples may be obtained quickly and

easily.

Because motion is a stressful stimulus for certain individuals, one might

expect adrenal and sympathetic nervous system activation. Indeed, motion

stimuli which increase G-forces result in abrupt increases in plasma epinephrine

and norepinephrine in man (21). Gastric dysrhythmias after acute vagotomy have

been attributed to sympathetic dominance (19). Moreover, intra-arterial

infusions of epinephrine also caused canine tachygastrias (11). Thus, it is

conceivable that gastric dysrhythmias and motion sickness may be mediated in

part by catecholamine release. Other subjects, however, have no symptoms

during vection; some describe vection as "exhilarating" (personal observation).

Do these subjects, have a different catechol response to vection?

Catecholamine Responses in Healthy Subjects

Divergent plasma catecholamine responses to vection were found in

symptomatic and asymptomatic healthy subjects. The preliminary results showed

decreased catecholamines 1 min after vection in both the nauseated and the

symptom-free subject. However, during the 20 minutes after vection, catechol amines rebounded in the nauseated subject; whereas, they remained

suppressed in the symptom-free subject. These were unexpected findings which

suggested that adrenal and sympathetic neural activity were suppressed during

vection stimuli; this is the opposite sympathetic response measured during

motion stimuli which produces G-forces (21). However, vection is a uniquely

and purely a CNS "motion" stimulus in contrast to experiments in which the

subjects are actually accelerating or moving. Moreover, the rebound catechol

response in the nauseated subject clearly diverged from the sustained catechol

suppression in the symptom-free subject, suggesting that in the symptom-free

subject different neuro-hormonal mediators may have suppressed the adrenalsympathetic axis. How decreased levels of norepinephrine, dopamine and

epinephrine may affect gastric electrical rhythm is unclear; interestingly,

in some patients with idiopathic nausea and vomiting symptoms improve after

lidamidine HCL, an alpha2 agonist (23).

In addition, the symptom-free subject with clear 3 cpm EGG baseline had

"boosted" his pre-vection norepinephrine and dopamine levels 85% and 177%,

respectively; whereas the nauseated subject with weaker 3 cpm baseline

increased these two catechols 67% and 0%, respectively.

-16-
Are "anticipatory" boosts in catechols and enhanced 3 cpm EGG power

related? Does an "unconscious" boost in certain catecho]amines provide

resistance to vection-induced nausea and tachygastria? Traditionally,

sympathetic neural input to the gut is inhibitory. However, sympathetic

cholinergic fibers also innervate the antrum: low level stimuli elicit gastric

contractions; whereas, greater stimulation causes relaxation (24). Perhaps a

specific blend of sympathetic and parasympathetic efferent input to the

corpus-antrum may strengthen 3 cpm rhythms before vection. Then, as shown in

the symptom-free subject (Figure 7), the power at 3 cpm may be decreased, but

is not abolished during vection and tachygastrias do not develop.

The above findings are particularly interesting because amphetamine, a

drug which releases norepinephrine, is effective in reducing motion sickness

(25). The effect of amphetamine on gastric electromechanical activity is

unknown. Interestingly, a recent report by Kohl indicates that a variety of

sympathomimetic drugs are effective anti-motion sickness agents (26). These

drugs may provide the boost in catecholamines (and 3 cpm EGG activity) which

some subjects are unable to recruit naturally prior to motion stimuli.

Additional studies are needed to confirm the differential "anticipatory and

"post vection" catechol responses in healthy subjects.

Catecholamine Responses in Postoperative Subjects

Differential catecholamine responses to vection were also found in

symptom-free and nauseated postoperative subjects. After vection, the

symptom-free total gastrectomy subject had persistently decreased catecholamine

levels, a pattern similar to the symptom-free healthy subject. In contrast,

the Roux-en-Y (antrectomy plus vagotomy) subject with vection-induced nausea

had marked increases in catecholamines one and ten minutes after vection; and,

the epinephrine increase was sustained at 20 minutes post vection. Thus

vection-induced catechol responses in the total gastrectomy subject were the

opposite of responses in the Roux-en-Y subject. Both subjects had vagotomy.

These data imply that some contribution of sympathetic efferent or afferent

neural input to and/or from the stomach remnant modified the catechol response

in the Roux patient. In any case, only the Roux subject had a "fight or

flight" sympathetic response to vection.

Also, the catechol surge in the Roux subject was immediate; whereas, the

surge was delayed in the nauseated subject with intact stomach, suggesting that

the intact vagus and/or antrum may have modified the catecholamine response to

vection. The circuitry is complex; more studies are necessary before

conclusions can be drawn.

Metoclopramide and Vection-induced Nausea

Pretreatment with metoclopramide, a drug which stimulates gastric contractility, prevented vection-induced nausea, stimulated 3 cpm activity, and

reduced but did not eliminate tachygastrias. These preliminary results support

our hypothesis (number 3) that maintenance of 3 cpm activity (and prevention

of tachygastria) may prevent or diminish symptoms of motion sickness. It

is unknown if larger doses of drug could completely abolish tachygastrias.

Metoclopramide increases gastric contractility and decreases nausea and

vomiting in diabetics with gastroparesis (27), but it has not been

-17-
systematically studied as an antimotion sickness agent. Anecdotal reports

indicate metoclopramide diminished the symptom of space sickness and stimulated

bowel sounds (28). Metoclopramide is a dopamine antagonist with indirect

cholinomimetic effect (29). A recent review suggests metoclopramide is a

prejunctional agonist at alpha2 adrenergic or 5-hydroxtryptamine receptors

(30). Does metoclopramide provide a blend of adrenergic and cholinergic

activity needed to increase 3 cpm EGG activity and to resist vection-induced

dysrhythmia? Control of gastric dysrhythmias with prokinetic agents represents

a novel approach to the treatment of motion sickness.

Furthermore, metoclopramide crosses the blood-brain barrier, but investigational gastroprokinetic agents, domperidone and cisapride (31), act

predominantly on the gastrointestinal tract. The effect of these latter drugs

on vection- induced nausea and tachygastria may provide important data

concerning the origins of motion sickness symptoms: central nervous system

versus stomach.

VII. Summary

Responses to vection separated healthy subjects into two groups - those

who experienced nausea and those who remained symptom-free. The symptomatic

group was objectively identified by the onset of tachygastrias. Duodenal

contractions may correlate with severe nausea and retching, but antral

contractions did not distinguish symptomatic from asymptomatic subjects. In

preliminary work, catecholamine responses of symptomatic and asymptomatic

subjects were divergent, indicating differential sympathetic nervous system

responses in the two groups. Catecholamine responses, particularly

"anticipatory" responses, to vection may be relevant to basic mechanisms of

motion sickness. Metoclopramide reduced tachygastrias and prevented nausea.

Pharmacologic control of gastric dysrhythmias with gastroprokinetic drugs

provides a novel rationale and offers multiple therapeutic approaches to the

treatment of motion sickness.

Vagotomy subjects with gastric remnants were uniformly susceptible to

vection-induced nausea, indicating that vagal pathways do not mediate the

symptoms of motion sickness in these subjects. To the contrary, vagotomy

and/or antrectomy appeared to increase the likelihood of motion sickness.

The only operated subject who had no symptoms during vection had a total

gastrectomy. Thus, it appears that the sympathetic nervous system or other

neurohormonal circuits may mediate the gastric dysrhythmias and symptoms evoked

by vection. Preliminary studies in a vagotomy-antrectomy subject showed marked

increases in catecholamines after vection; in contrast, the total gastrectomy

subject had catechol responses similar to the healthy asymptomatic subject.

Thus, vagotomy and/or partial gastrectomy appears to alter the catecholamine

response to vection. Further studies in additional subjects are needed.

Gastric electromechanical responses to vection are relatively "pure"

brain-gut interactions which provide new insights into the gastric component of

motion sickness. The underlying mechanisms which mediate susceptibility to or

resistance to vection-induced nausea may be relevant to the pathophysiology of

motion sickness. A better understanding of these mechanisms will allow more

rational treatment approaches to symptoms arising from a variety of motion

stimuli.

-18-
VIII. References

1. Wolf, S. The relation of gastric function to nausea in man. J Clin

Invest 1943; 22:877-882.

2. McDonough, F.E. and Schneider, M. The effect of motion on roentgenographic appearance of the stomach and small bowel. Gastroenterology

1944; 2:32-45.

3. Stern, R. M., Koch, K. L., Leibowitz, H. W., Lindblad, I. M., Shupert,

C. L., Stewart, W. R. Tachygastria and motion sickness. Aviat. Space

Environ Med 1985; 56:1074-1077.

4. You, C. H., Chey, W.Y., Lee, K. Y., Menguy, R., Bortoff, A. Gastric

and small intestinal myoelectric dysrhythmia associated with

intractable nausea and vomiting. Ann Intern Med 1981; 95:449-451.

5. Telander, R. L., Morgan, K. G., Kreulen, D. L., Schmalz, M. S., Kelly,

K. A., Szurszewski, J. H. Human gastric atony with tachygastria and

gastric retention. Gastroenterology 1978; 75:497-501.

6. Abel!, T. L., Malagelada, J-R. Glucagon - evoked gastric dysrhythmias

in humans shown by an improved electrogastrographic technique.

Gastroenterology 1983; 85:83-91.

7. Hamilton, J. W., Bellahsene, B. E., Reichelderfer, M., Webster, J. H.

and Bass, P. Human electrogastrograms. Comparison of surface and

mucosal recordings. Dig Dis Sci 1986; 31:33-39.

8. Parker, D. E., Reschke, M. F., Arrott, A. T., Homick, J. L.,

Lichtenberg, B. K. Otolith tilt - translation reinterpretation

following prolonged weightlessness: implications for preflight

training. Aviat Space Environ Med 1985; 56:601-606.

9. Young, L. R., Oman, C. M., Watt, D. G. D., Money, K. E., Lichtenberg,

B. K. Spatial orientation in weightlessness and readaptation to

earth's gravity. Science 1984; 225:205-208.

10. Stangellini, V., Malagelada, J-R., Zinsmeister, A. R., Go, V. L. W.,

Kao, P. C. Stress-induced gastroduodenal motor disturbances in

humans: possible humoral mechanisms. Gastroenterology 1983;

85:83-91.

11. Kim, C. H., Azpiroz, F., Malagelada, J-R. Characteristics of

spontaneous and drug-induced gastric dysrhythmias in a chronic canine

model. Gastroenterology 1986; 90:421-427.

12. Electrogastrography: Methodology, Validation and Applications.

Editors: R. M. Stern and K. L. Koch. New York: Praeger, 1985.

-19-
13. Catecholamines radioenzymatic assay kit (Cat-A-Kit-Assay Kit). Upjohn

Diagnostics, The Upjohn Company, Kalamazoo, MI 49001.

14. You, C. H. and Chey, W. Y. Study of electromechanical activity of

the stomach in humans and in dogs with particular attention to

tachygastria. Gastroenterology 1984; 86:1460-1468.

15. Ingelfinger, F. J. and Moss, R. E. The activity of the descending

duodenum during nausea. Am J Physiol 1942; 136:561-566.

16. Thompson, D. 6. and Malagelada, J-R. Vomiting and the small

intestine. Dig Dis Sci 1982; 27:1121-1125.

17. Lang, I. M., Sarna, S. K., Condon, R. E. Gastrointestinal motor

correlates of vomiting in the dog: quantification and characterization as an independent phenomenon. Gastroenterology 1986;

90:40-47.

18. Wilbur, B. G., Kelly, K. A. Effect of proximal gastric, complete

gastric and truncal vagotomy on canine electrical activity, motility

and emptying. Ann of Surg 1973; 178-190.

19. Stoddard, E. J., Smallwood, R. H., Duthie, H. L. Electrical

arrhythmias in the human stomach. GUT 1981; 22:705-712.

20. Stalla, G. K., Doerr, H. D., Bidlingmaier, F., Sippel, B. G.,

VonRestorff, W. Serum levels of 11 steroid hormones following motion

sickness. Aviat Space Environ Med 1985; 56:995-999.

21. Mills, F. J. The endocrinology of stress. Aviat Space Environ Med

1985; 56:642-650.

22. Habermann, J., Eyersmann, T., Ehrhardt, F., Gottsmann, M., Ulbrecht,

G., and Scrida, P. C. Increased urinary excretion of tri-iodothyronine

(To), thyroxine (14) and decreased serum thyreotropic hormone

(TSH) induced by motion sickness. Aviat Space Environ Med 1978;

49:58-61.

23. Sm'nsky, C. A., Martin, J. L., Mathias, J. R. Effect of lidamidine

hydrochloride, a proposed alpha2-adrenergic agonist, in patients

with gastroduodenal motor dysfunction. Gastroenterology 1983;

84:1315. (Abstract)

24. Thomas, J. E. and Baldwin, M. Z. Pathways and mechanisms of

regulation of gastric motility. Handbook of Physiology. Section 6:

Alimentary Canal. Vol. IV. Motility. Editors: C. F. Code and W.

Heidel. Williams and Wilkins Co., Baltimore, Maryland 1982; pp.

25. Wood, C. D. Antimotion sickness and antiemetic drugs. Drugs 1979;

17:471-479.

-20-
26. Kohl, R. L., Calkins, A. C., and Mandell, A. Arousal and stability:

the effects of five new sympathomimetic drugs suggest a new principle

for the prevention of space motion sickness. Aviat Space Environ Med

1986; 57:137-143.

27. Malagelada, J-R., Rees, W. D. W., Mazzotta, L. J., and Go, V. L. W.

Gastric motor abnormalities in diabetic and post-vagotomy gastroparesis: Effect of metoclopramide and bethanecol. Gastroenterology

1980; 78:286-293.

28. Chaikin, A. Sick in space. Science 1984; 84:51-55.

29. Scultz-Deliru, K. Metoclopramide. Gastroenterology 1979;

77:768-779.

30. Fernandez, A. G. and Massingham, R. Peripheral receptor populations

involved in the regulation of gastrointestinal motility and the

pharmacological actions of metoclopramide-like drugs. Life Sci 1985;

36:1-14.

31. Cisapride (R51619): An original gastric and intestinal prokinetic.

Investigational New Drug Brochure. 5th Edition. Nov. 1985. Janssen

Pharmaceutica.

-21-
IX.' Figures and Tables

FIGURE L

OF POOR QUALITY

FIGURE 1.

FIGURE 2.

Illustration of a subject seated within the rotating drum.

Pressure transducer

Surface electrodes

FIGURE 2

Illustration of electrode placement. Electrode 1 is over the

proximal or orad gastric body; Electrode 3 is over the distal

antrum. Reference electrode is not shown. A catheter with

three solid state pressure transducers is positioned in the

distal body and antrum for simultaneous measure of gastric

electromechanical activity.

FIGURE 3.

Baseline

15 min

Protocol A

Drum

Rotation

15 min

-22-

Recovery

15-30 min
TABLE I

Symptoms and Electrogastrogram (EGG) Frequency Responses in

Healthy Subjects With and Without Vection-Induced Nausea

Subjects

w. nausea Baseline

1.

2.

6.

7.

SK

RS

3. MF

4. SH

5. BT

MD

KK

EGG Frequencies (cpm)

Vection

3 (poor"1")

Resp.3 only

5-7

Flat! ine

3 (poor)

3

3 (poor)

5-7

Resp.

5-7

8-10

6-7

6-8

6-8

only

Recovery

5-7

Resp. only

5-7

8-10

3

3

3

Nausea

Score*

29

169

95

73

253

210

290

Subjects

w/o nausea

1. DO

2. MH

3. DS

4. BR

5. MB

6. DW

7. JE

8. PD-A

3

3

3

3

3

3

3

3

3

3

3

3

3

Resp. only

3

4-5

3

3

3

3

3

Flatline

3

3 (poor)

0

0

0

0

0

o

c

*Indicates mm from 0 (no nausea) along a 300 mm line (300 mm = severe

nausea, near vomiting) and reflects intensity of nausea during vection. +Poor indicates low amplitude or intermittent 3 cpm pattern aResp = respiration

 b"sweating" c"dizzy"

-23--
El

, Baseline

tafcy/Xv^

\

 VW*:

Vection

r i. u L . v.

Recovery

ORIGFNAL PAGE bS

f

it

)

Qf POOR QUALITY

in

I"

M!

r "

n

~r

i

I

i

1..-1L

E3

Resp.

A1

•': :M -I l'| » f- •'; -V' • -V4 'U

A2

[ 20 mmHg

FIGURE 4. GASTRIC ELECTROMECHANICAL ACTIVITY IN A HEALTHY SUBJECT WHO DEVELOPED NAUSEA

DURING VECTION. El, E2 and E3 indicate EGG signals simultaneously recorded

from electrodes E1-E3. Minute and electrical standards are shown. The fourth

panel is Respiration (Resp). Al and A2 indicate intraluminal pressures in the

antrum recorded from the distal two pressure transducers. Figures 6, 8 and 11

are set up in similar fashion.

During Baseline, 3 cpm EGG pattern is seen, particularly at E2 and E3.

Intraluminal pressure is quiescent and shows only respiratory artifact. At six

minutes of Vection, the EGG waves are narrow-based with increased amplitude,

the frequency is approximately 6 cpm (i.e. tachygastria), intraluminal pressure

is unchanged, and the subject reported nausea. Ten .minutes into the Recovery

period, low amplitude 3 cpm activity is best seen at E3: intraluminal pressures

remain quiescent. Nausea resolved.

-24-
:ORD- 1. NUMBER OF RECORDS- 42

MAGNITUDE SQUARED

Ci\ILS\NS300.

Drum Off

TIME

i^Vectlon

Drum On

6 9 1 2

Frequency (cpm)

15

FIGURE 5. RUNNING SPECTRAL ANALYSIS OF EGG SIGNALS FROM SUBJECT WITH VECTION-INDUCED NAUSEA. (Same subject as in Figure 4)

Horizontal axis indicates EGG frequency in cpm; vertical axis indicates the power (arbitrary units) of the

EGG signal at the various frequencies; time indicates 4 min of EGG signal - 64S of new data added to the

previous three minutes of data. Similar format used in Figures 7, 9, 15 and 17.

Baseline period before Drum On shows regular 3 cpm peaks and 0-1 cpm activity. During the Vection period

(between Drum On and Drum Off) a wide variety of frequency peaks emerge with particularly high power peaks

at approximately 6 and 9-10 cpm and 13-15 cpm, frequencies representing gastric dysrhythmias and respiratory

rates, respectively. Recovery period (between Drum Off and end of the plot) shows resolution of high power

frequencies, although frequency peaks > 12 cpm persist. Inspection of recovery period is impaired because

of the high peaks during vection. Minimal 3 cpm activity returned during recovery as shown in Figure 5A, a

supplementary plot of the 15 min recovery period only.

-25-
FIGURE 5A. RUNNING SPECTRAL ANALYSIS OF THE RECOVERY PERIOD ONLY FROM FIGURE 5.

STARTING RECORD- 31. NUMBER OF RECORDS- 12

MAGNITUDE SQUARED

Ci \ILS\NS300.

•—Drum Off

3 6 9 12

Frequency (cpm)

15

-26-
ORIGINAL PAGE IS

OF POOR QUALITY

Baseline Vection

FIGURE 6

Recovery

E1

60s

E3— L

Resp.

w\",iVVA;1il

A

A1

A2

20 mmHg

FIGURE 6. GASTRIC ELECTROMECHANICAL ACTIVITY IN A HEALTHY SUBJECT WHO REMAINED SYMPTOM

FREE DURING VECTION. During Baseline, clear 3 cpm EGG signals are seen;

intraluminal pressures are quiescent. During Vection the 3 cpm EGG pattern

remains clear; 3 cpm pattern is also seen during Recovery, although more

respiratory artifact is apparent. Pressures during vection and recovery

were quiescent.

-27-
FIGURE 7

ORJGiJMAL PAGE is

OF POOR QUALITY

STARTING RECORD- 1. NUMBER OF RECORDS- 42

MAGNITUDE SQUARED

C. \ILS\NS161.

*» Drum Off

-Vection

Drum On

6 9 12

Frequency (cpm)

15

FIGURE 7. RUNNING SPECTRAL ANALYSIS OF EGG SIGNAL FROM A HEALTHY SUBJECT WHO

REMAINED SYMPTOM-FREE DURING VECTION (same subject as in Figure 6).

Before onset of drum rotation, an increasingly strong 3 cpm peak is

seen; during Vection, the 3 cpm peak remains clear but decreases

in power and no tachygastrias are seen. Also, at the onset and

offset of drum rotation bursts of low frequency (^ 1 cpm) EGG activity

are seen. During the Recovery period, the power at 3 cpm again

increases slightly.

-28-
TABLE 2

Antral Motility Respones in Healthy

Subjects With and Without Vection-Induced Nausea

Subjects Baseline

w. Nausea Contractions MI

1. SK

2. SH

3. BT

4. KK

5. MD

Mean

iSEM

Subjects

w/o Nausea

1. DJ

2. MH

3. DS

4. BR

5. MB

6. DW

7. JE

Mean

+SEM

42

6

4

0

6

11.6

7.7

10

2

0

12

0

9

0

43

1.9

42,630

390

460

0

780

11,065.0

10,522.0

850

30

0

2,100

0

3,555

0

1,089.2

595.9

Vecti on Recovery

Contractions MI Contractions MI

42

13

1

0

0

11.2

8.0

43,890

910

50

0

0

11,212

10,894

5

12

4

0

0

4.2

2.2

800

1,020

1,020

0

0

710.0

242.3

Nausea

Score

29

73

253

290

210

1

0

0

5

0

1

0

0.9

0.6

5

0

0

275

0

10

0

48.3

45.4

0

0

0

0

1

3

0

0.6

0.4

0

0

0

0

5

195

0

35.8

31.9

0

0

0

0

0

o

a

0

*MI (Motiity Index) = Number of contractions x sum of amplitudes

"•"Indicates mm from 0 (no nausea) along a 300 mm line

(300 mm = severe nausea, near vomiting) and reflects intensity

of nausea during vection.

a"Sweating"

-29-
FIGURE 8A

Baseline Vection

PAGE is J

OF POOR QUALJTY I

E1

E3

60s

Resp.

A2

D1 J 20 mmHg

^

retching

drum stopped

FIGURE 8A. EGG AND ANTRODUODENAL CONTRACTILE RESPONSES TO VECTION IN A HEALTHY

SUBJECT. Dl indicates duodenal pressure; A2 indicates distal antral

pressure. During Baseline, intermittent 3 cpm EGG activity was

present (see E2) and intraluminal pressures were quiet. After 4 min.

of Vection this subject experienced severe nausea and an episode of

retching; the drum was stopped. Irregular EGG activity is temporarily

lost as a rhythmic 11-12 per min burst of 10-15 mmHg duodenal

contractions begin at Dl. The irregular waves at A2 are respiratory.

EGG signal returns with a large amplitude wave (i.e., El and E2).

-30-
Post Vection

FIGURE 8B

Recovery

E1

/ A

 ;1 A

 l '^'1

I I' / '

T Mi^

1 V '</

Resp.

4

; V w V

; \M « .

1 ^ -v

lV

-

'

A2

D1 [20 mmHg

FIGURE 8B. This figure is a continuation of the previous tracing, (8A). In this

immediate post drum rotation period of Recovery, the EGG now shows

high-amplitude, narrow-based signals at 8-10 cpm (i.e. tachygastrias).

Duodenal contractions are diminishing; tachygastria and nausea are

also resolving. By the 12th minute of Recovery, the 3 cpm pattern is

apparent (particularly at El and E2), and duodenal pressures are

quiescent. Nausea has resolved.

-31-
STARTING RECORD- 1. NUMBER OF RECORDS" 31

MAGNITUDE SQUARED

Ci\ILS\NS1999.

Drum Off

^•-Vection

Drum On

6 9 12

Frequency (cpm)

15

FIGURE 9. RUNNING SPECTRAL ANALYSIS OF EGG RECORDING FROM SUBJECT WITH SEVERE NAUSEA AND

RETCHING (same subject as Figure 8A and B). Baseline period before Drum On shows

low power peaks at 3 cpm. Three cpm peaks are suppressed after onset of vection.

Vection lasted only 4 min; the drug was stopped at the time of retching. During the

latter minutes of vection, new frequency peaks at 4, and 8-9 cpm are seen and

represent tachygastrias. The peaks at 10 cpm probably represent duodenal frequency;

the 13-14 cpm peaks represent respiratory rate. During Recovery the tachygastria

peaks resolve and at the end of recovery, low power peaks at 3 cpm are seen.

-32-
FIGURE 10

D

3)

5

5

D

J

5

L

Norepinephrine Epinephrine Dopamine

120 -,

100 -

80 -

60 -

40 -

20 -

0

-20 -

-40 -

-60 -

• Nausea

o No Sx

i

10

i

20

Minutes After Termination of Vection

FIGURE 10. PLASMA CATECHOLAMINE RESPONSES TO VECTION IN HEALTHY SUBJECTS WITH AND WITHOUT NAUSEA.

Percent change in catecholamine levels from baseline to 1, 10 and 20 minutes after

vection are presented. One minute after vection, norepinephrine, epinephrine and

dopamine are suppressed in both subjects. However, in the subject with no symptoms

(No Sx), catechols remain suppressed (See Figures 6 and 7 for this subject's EGG and

RSA patterns). In contrast, catechols rebound above baseline levels in the subject

who had nausea during vection. (See Figures 4 and 5 for this subject's EGG and RSA).

-33-
Baseline I Baseline II Vection

FU.L:-. :

Recovery

E1

ORIGINAL PAGE 55

0E POOR QUAIJTY

—Si

•.••»•.• ! «•.'» < i " ,

•_• .''; ".' • '-• wV " -' J '-< '- I

. ,

• •,' .I •'••/ . • . 11' i >' /* " ''

'» '- J J , u 'J-'J. -. v! u -J. U

A2 --"-J20 mmHg

FIGURE 11. EFFECT OF METOCLOPRAMIDE HCL ON GASTRIC ELECTROMECHANICAL ACTIVITY DURING VECTION.

(Same patient as in Figure 4). The panels are set up as before. Baseline I is

from 10 min after 20 mg of metoclopramide: 3 cpm EGG activity is clearly seen at

E2 and E3. Thirty min after metoclopramide (Baseline II), a 25 mmHg antral

contraction is seen which correlates with the high amplitude, broad-based EGG

wave. During the sixth min. of Vection, the EGG signal has a different configuration but the frequency remains approximately 3 cpm; intraluminal pressures are

quiescent, and subject reported slight dizziness but no nausea. During Recovery

period, weak 3 cpm EGG pattern is seen (El) and antral pressures reflect

respiration. No nausea during vection or recovery.

-34-
RECORD- 1. NUMBER OF RECORDS- 36

MAGNITUDE SQUARED

Ci \ILS\NS144.

Off

TIME

^ Vection

Drum On

6 9 12

Frequency (cpm)

FIGURE 12. RUNNING SPECTRAL ANALYSIS OF EGG RECORDING FROM SUBJECT PRETREATED WITH

METOCLOPRAMIDE BEFORE VECTION (same subject as shown in Figures 4, 5 and 11).

During Baseline low power 3 cpm peaks are seen. As drum rotation and

Vection begin, a prominent 4 cpm peak occurs and is followed by prominent 3 cpm

peaks (arrows). Lower power tachygastrias (5 and 8-9 cpm) are seen. Subject

reported he was "dizzy; not queasy" 2 min before Drum Off. During early Recovery,

3 cpm peaks are suppressed but 3 cpm peaks become more prominent in the late

Recovery period.

-35-
TABLE 3

Symptoms and Electrogastrogram (EGG)

Frequency Responses in

Postoperative Subjects During Vection Protocols

1.

2.

3.

4.

5.

Subject

V + P (SM)

Roux (MB)

Roux (CT)

Roux (LR)

V + P (LB)

EGG Frequencies (cpm)*

Baseline Vection Recovery Sx

6. Gastrectomy (WC)

3

1-3

flatline

11

flatline

flatline

6

5-7

3

11

flatline

flatline

3

1-3

5-6

11

13

10-11

mod nausea, sweating

mod nausea, hot

mod nausea, belching

mild nausea, sweating

mild nausea, sweating

No Sx

cpm +Sx

V+P

Roux

cyles per min

symptoms; subjective estimate of intensity during vection; mod = moderate

vagotomy and pyloroplasty

Roux-en-Y

-36-
STARTING RECORD- 1. NUMBER OF RECORDS- 35

MAGNITUDE SQUARED

Ci \ILS\NS22.

spp^-Drum Off

^rriME

^-Vection

Drum On

9 12

Frequency (cpm)

15

FIGURE 13. COMPOSITE EGG AND RUNNING SPECTRAL ANALYSIS (RSA) FROM A POST VAGOTOMY

AND PYLOROPLASTY SUBJECT. RSA shows strong 3 cpm peaks during baseline.

Actual EGG signal also shows strong 3 cpm pattern (see insert A). Subject

developed moderate nausea after 6 min. of Vection with onset of

tachygastria as shown in EGG signal (insert B) and the loss of 3 cpm peak

in RSA with onset of a spectrum of tachygastria peaks (predominantly 6-7

cpm and 9-10 cpm). Late in the Recovery period the RSA 3 cpm peak

returns; 3 cpm pattern is also seen in the actual EGG signal (insert C).

Nausea has resolved.

-37-
Baseline Vection

FIGURE 14

Recovery

E1

ORIGINAL PAGE 13

OF POOR QUALITY

60s

E2

I 500 V

E3_

v •

Resp.

•Vv

FIGURE 14. VECTION-INDUCED NAUSEA AND GASTRIC MYOELECTRIC RESPONSE TO VECTION IN A

SUBJECT WITH VAGOTOMY AND ANTRECTOMY (Roux-en-Y). Baseline EGG shows

low frequency wave forms; during Vection (min 8 is shown). Highamplitude, narrow-based waves (approximately 8 cpm) are seen and the

subject reported nausea. Tachygastria continued until drum rotation

was stopped. During Recovery, nausea resolved" and low frequency waves

of higher amplitude than baseline returned. Respiratory rate is 18-20/min

during each period.

-38-
FICI;

ORlQSsW PAGE iS

OF POOR QUALITY

STARTING RECORD- 1. NUMBER OF RECORDS- 42

MAGNITUDE SQUARED

Ci \ILS\NS1 1 1.

^-Drum Off

TIME

Vection

Drum On

6 9 12

Frequency (cmp)

15

FIGURE 15. RUNNING SPECTRAL ANALYSIS OF EGG SIGNAL IN A SYMPTOMATIC SUBJECT WITH

VAGOTOMY AND ANTRECTOMY (same subject as in Figure 14). Baseline

period before "Drum On" shows predominant power at low frequencies

(approximately 1 cpm). During Vection an 8 cpm peak develops and with

onset of nausea (approximately min 8) a 10-11 cpm peak temporarily

emerges. The 8 cpm peak persists until drum is turned off. During

Recovery, the low frequency peaks again predominate. No 3 cpm peaks

are seen.

-39-
FIGURE 16

Vection Recovery

E2

E3

Resp.

60s V

1' ,V , .t..r,;

f/f-iriTfaTiT;

FIGURE 16. VECTION-INDUCED GASTRIC MYOELECTRIC ACTIVITY IN A SYMPTOM-FREE SUBJECT

WITH TOTAL GASTRECTOMY. During Baseline, EGG shows a flat line with

some respiratory artifact. During Vection (min 6 is shown), the

subject has no symptoms and the EGG signal continues to reflect

respiration (approximately 15 cpm). During recovery (min 12 is shown),

at 9 cpm pattern presumably from jejunum is seen in E2; the subject

remains symptom-free.

-40-
FIGURE 17

HRECORO- i. NUMBER OF RECORDS- 38

MAGNITUDE SQUARED

Ci\ILS\NS44.

-*— Drum Off

=^^^ Vection

Drum on

6 9 12

Frequency (cpm)

15

FIGURE 17. RUNNING SPECTRAL ANALYSIS OF EGG SIGNAL FROM SUBJECT WITH TOTAL

GASTRECTOMY (same subject as in Figure 16). During Baseline, Vection

and Recovery, low frequency 1-2 cpm peaks predominate and reflect the

relatively flat EGG signal shown in Figure 16. During Vection, however,

9 cpm peaks and 15 cpm peaks emerge, probably reflecting jejunal

activity and respiration, respectively. During Recovery, very little

cyclical activity is present.

-41-
o

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cuc

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i- O_ O ^ evj „ o

co*u-Q) Co

4-«

COC0) I-<(0

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X. Publications Resulting From NASA Support.

Please see Appendix A. Stern, R.M., Koch, K.L., Stewart, W.R. and

Lindblad, I.M. Spectral analysis of tachygastria recorded during motion

sickness. (Submitted to Gastroenterology.)

-43-
Appendi x A

Spectral Analysis of Tachygastria Recorded

During Motion Sickness

Robert M. Stern, Kenneth L. Koch, William R. Stewart,

and Inger M. Lindblad

Departments of Psychology and Medicine, The Pennsylvania

State University, University Park and Hershey, PA

Running Head: Tachygastria and Motion Sickness

Keywords: Tachygastria; Motion Sickness; Electrogastrogram; Gastric

Myoelectric Activity; Visual-Vestibular Mismatch; Running Spectral

Analysis.

Communications, proofs and requests for reprints

should be sent to:

Robert M. Stern, Ph.D.

417 Moore Building

Pennsylvania State University

University Park, PA 16802

This work was supported in part by grant NAG 9-118 from the National

Aeronautics and Space Administration.
Stern - 2

Abstract

The purpose of the present experiment was to study frequency changes in

gastric myoelectric activity of healthy human subjects as a function of

motion sickness brought about by vection or illusory self-motion. Fifteen

fasted healthy human subjects were seated inside a circular vection drum,

the rotation of which produces visual signals of self-motion which are in

conflict with vestibular signals (i.e., mismatched sensory input). An

electrogastrogram was obtained for three 15 min periods: baseline, rotation,

and after drum rotation stopped. Respiration, symptoms volunteered by

subjects, and a continuous measure of intensity of symptoms were recorded.

Five subjects showed a continuation of normal 3 cpm activity during drum

rotation and reported no symptoms of motion sickness. Ten subjects showed

a shift of their dominant gastric frequency from 3 cpm to 5-8 cpm during

drum rotation and reported symptoms of motion sickness. Running spectral

analysis revealed a close correspondence over time between tachygastria

and reports of symptoms of motion sickness.

Keywords: Tachygastria; Motion Sickness; Electrogastfogram; Gastric

Myoelectric Activity; Visual-Vestibular Mismatch; Running

Spectral Analysis.
Stern - 3

Spontaneous tachygastria was first observed in dogs (1,2) in the

1970s and in humans (3) shortly thereafter. Subsequently, tachygastria

has been related to gastric retention (4) and nausea and vomiting (5,6).

Tachygastria has also been observed in healthy fasted subjects (7) and

following ingestion of barium sulfate (8). Abell and Malagelada (9)

evoked tachygastria in healthy human subjects by intravenously infusing

glucagon. In this later study and in other human experiments (6,7,9,10)

gastric myoelectric activity was recorded with mucosal and cutaneous

electrodes and frequency analysis showed good correspondence between the

mucosal and cutaneous signals (electrogastrogram or EGG).

Although most individuals who experience motion sickness describe

symptoms of vague epigastric discomfort and nausea, the relationship

between these symptoms and gastric motility has been neglected for almost

40 years. Two early reports (11,12) demonstrated that decreased gastric

contractions and tone were associated with motion sickness. A more recent

study (13) showed that the stress of the cold-pressor procedure caused

decreased antral contractions and delayed gastric emptying of a standard

meal.

In a preliminary study by the present authors (14) it was shown that

circular vection, i.e., the sense of self-motion in a stationary subject,

produced symptoms of motion sickness in 14 of 21 subjects and in each of

the 14 the EGG frequency shifted from the normal 3 cpm to tachygastria

with frequencies of 5-8 cpm. However, it should be pointed out that in

recent studies of cutaneously-recorded tachygastria (9,14) dysrhythmias

were identified by visual inspection.
Stern - 4

The twofold purpose of the present study was to investigate further

the relationship between onset of tachygastria and onset of the symptoms of

motion sickness and to apply a relatively new method of quantifying gastric

dysrhythmias, running spectral analysis, to the EGG signal.

Lx

Materials and Methods

Volunteers

Fifteen college students were used as subjects, 8 men and 7 women.

They were between 18 and 23 years old and reported no central nervous system

or gastrointestinal diseases or symptoms. Subjects were fasted at least

4 hours before the experiment. The procedure used was approved by the Penn

State Committee on Use of Human Subjects and informed consent was obtained

from each subject.

Electrogastrographic Method

EGG was recorded from cutaneous bipolar electrodes positioned on the

abdominal wall over the antrum. The approximate position of the electrodes

relative to the umbilicus was as follows: 10 cm cephalad from the umbilicus

and 6 cm left, and 4 cm cephalad on the midline of the abdomen. Electrodes

were connected to a Becknan R611 recorder (SensorMedics, Anaheim, Ca.) with a

time constant of 10 sec., high frequency cutoff of .08 Hz, and a paper speed

of 1 mm/sec. Respiration was recorded with a strain-gauge transducer which

was placed around the subject's chest and connected to the Beckman recorder.

Circular Vection Apparatus

Testing was carried out using a circular vection drum. The drum

consisted of a metal cylinder 91.5 cm in height and 76 cm in diameter, the

interior of which was covered with alternating 3.8 cm (5.7 deg.) black and
Stern - 5

6.2 cm (9.3 deg.) white vertical stripes. The drum could be rotated

clockwise or counterclockwise about its vertical axis at various speeds

resulting in illusory self-motion. At the beginning of the experiment,

subjects were seated inside the stationary drum with their heads positioned

in the center of the drum and aligned with the vertical axis. Head

position was maintained throughout the experiment by means of a chinrest.

Procedure

The baseline frequency of the EGG was established during an initial

15-min period while the subject sat within the stationary drum. Following

this baseline period, the drum was rotated at a speed of 60°/s around the

stationary subject for a maximum of 15 min. The EGG and respiration were

recorded continuously during rotation. Subjects were asked to report

when they experienced a sensation of self-motion (circular vection) in

response to the motion of the drum surface and any symptoms of motion

sickness. In addition, the subjects turned -a knob attached to a potentiometer to indicate the intensity of their symptoms (0—no symptoms to

7—near vomiting). One channel of the Beckman polygraph was used to record

the output of the potentiometer. Drum rotation was stopped at the subject's

request if at any point motion sickness symptoms became uncomfortably intense.

Finally, with the subject remaining in the drum, the EGG was recorded an

additional 15 min after the drum was stopped. The EGG signal was

simultaneously recorded on the Beckman and on a Honeywell 5600C FM tape recorder

(Honeywell, Denver, Col.) and was later digitized at a rate of 1 Hz by a DEC

POP 11/34 computer (Digital Equipment Corp., Maynard, Mass.) The digitized

signal was transmitted to an IBM 370/3381 (IBM, White Plains, NY) for spectral

analysis.
Stern - 6

Spectral Analysis

In a general sense, spectral analysis is a method by which a signal

such as the EGG is decomposed into a sum of sinusoidal components. The

spectral analyses shown below were obtained using the BMDP statistical

program PIT (15). Each line represents the spectral density function for

a 256 s section of the EGG signal. The data window for each subsequent

spectral density function included the final 75% or 192 s of the preceeding

window as well as the next 64 s of digitized signal yielding a "running

spectral plot" in which each consecutive line contains 64 s of new information,

Prior to analysis the entire series for each subject was linearly

detrended and mean centered to zero. The first and last 5% of data in each

256 s epoch were tapered using a weighting function. These 256 point series

were then fourier transformed and periodograms formed from the fourier

coefficients. Spectral density estimates were formed from an average of

adjacent periodograms within a bandwidth of .0195 Hz. To summarize, the

pseudo 3-D plots displayed below show the- spectral density at frequencies

from 0 to 15 cycles per minute. Frequency is plotted on the horizontal

axis, time on the vertical axis, and spectral density on the axis which

appears to rise from the surface of the paper.

Results

Effects of Circular Vection on Gastric Electrical Activity

Five of the 15 subjects showed a decrease in power at 3 cpm during drum

rotation but no tachygastria and reported no symptoms of motion sickness.
Stern - 7

The running spectral analysis of the EGG recorded from one of these subjects

is shown in Figure 1. Prior to drum rotation the dominant frequency of

gastric electrical activity was 3 cpm. With the onset of drum rotation

there was attenuation of 3 cpm activity; initiall y 1 cpm activity was

observed but 3 cpm peaks dominate the vection period. After drum rotation

stopped 1 cpm activity increased briefly, followed by the return of 3 cpm

to the level of activity seen prior to drum rotation.

The remaining 10 subjects also showed a dominant frequency of 3 cpm

prior to drum rotation, but all 10 developed tachygastria and symptoms of

motion sickness during drum rotation. Figure 2 shows the running spectral

analysis from a subject who developed tachygastria approximately 5 min after

drum rotation began. This particular subject continued to show tachygastria

5 min after drum offset. Normal 3 cpm activity returned during the final

few minutes of the session. Figure 3 shows a running spectral analysis from

a subject who developed tachygastria after approximately 8 min of drum

rotation. The tachygastria continued for approximately 6 min after the

drum was stopped and was followed by the return of weak 3 cpm activity.

The final example, Figure 4, shows the running spectral analysis from a

subject who developed tachygastria as drum rotation was prematurely stopped

at Min. 7 because of intense symptoms. The tachygastria continued for

approximately 8 min with very weak 3 cpm returning at the end of the session.

Effects of Circular Vection on Symptoms of Motion Sickness

The effects of circular vection on electrogastrographic activity and

symptoms of motion sickness are summarized in Table 1. Five of the subjects

reported no symptoms of motion sickness, the same five who maintained 3 cpm
Stern - 8

peaks and failed to develop tachygastria. One of these subjects, Subject

No. 4, did indicate an intensity of symptoms of 2 (maximum 7) during drum

rotation, but when questioned at the end of the session she reported no

symptoms (see Figure 1). The remaining 10 subjects all reported symptoms

of motion sickness including sweating, salivation, dizziness, headache,

nausea, and stomachache and all 10 developed tachygastria.

Correspondence Between Electrogastrographic Frequency Shifts and Symptoms

As indicated above, 5 subjects reported no symptoms of motion sickness

and maintained 3 cpm activity. The remaining 10 subjects reported symptoms

of motion sickness and developed tachygastria. A correspondence between

the onset of tachygastria and the first reports of symptoms is suggested.

Of the 10 subjects who reported symptoms, in 7 cases the onset of tachygastria

and the first report of symptoms came within 2 min. A very strong temporal

correspondence between onset and resolution of tachygastria and increasing

and decreasing symptoms can be seen in Figures 2-4. For example, in Figure 2,

the subject indicated the start of symptoms at Min. 5 of drum rotation and

the first peaks of tachygastria frequencies began at the same time. In

Figure 3, the subject reported the first symptom, "suddenly felt sick in

stomach," at Min. 8 of drum rotation, the same time that tachygastria

became evident. Because of intense symptoms the subject asked that drum

rotation be stopped at Min. 10. In Figure 4, the subject started to report

symptoms as soon as drum rotation started and indicated that they became

most intense at Min. 7 at which point she asked that drum rotation be

stopped and manifested tachygastria.
Stern - 9

Discussion

The present studies provide new information regarding gastric rhythm

disturbances and motion-sickness symptoms induced by circular vection.

Onset of symptoms during vection was associated with a diminution of 3 cpm

activity and the emergence of tachygastrias ranging from 4-9 cpm.

Asymptomatic subjects may temporarily shift to lower amplitude 3 cpm activity

but do not develop tachygastrias. These results, which were derived from

prospective rating of symptoms during vection and from objective analysis

of the EGG waveforms, confirm and extend previous work (14) linking

tachygastria and symptoms of motion sickness.

Gastric slow waves (also termed electrical control activity) oscillate

at a frequency approximating 3 cpm in man and 5 cpm in dog. Previously,

it was believed that the 3 cpm frequency was omnipresent, but recent work

in healthy subjects revealed spontaneous (7) and glucagon-induced tachygastrias

(9) which were recorded with equal fidelity by cutaneous and mucosal electrodes.

Together with the present studies, these data suggest that slow wave activity

in healthy individuals may intermittently shift into the tachygastria frequency

ranges of 4-9 cpm.

Tachygastrias were originally described in patients with nausea and

vomiting (5,6). The stimulus and cause of the tachygastrias in these patients

are unknown. Nausea and epigastric distress are well-known and prominent

symptoms of motion sickness. Circular vection created a sense of illusory

self-motion in all our subjects. During vection the sensory input from

the visual and vestibular systems is "mismatched," (i.e., visual input

indicates motion; whereas, vestibular input indicates no motion), a circumstance

which leads to symptoms of motion sickness in susceptible subjects (16). Previous
Stern - 10

studies (11,12) have correlated decreased gastric contractility and tone

and motion sickness. Tachygastrias have been associated with decreased

contractility in dogs (1,2,17) and with delayed gastric emptying in a human

subject (4). Thus, the emergence of tachygastria with onset of motion

sickness is consistent with previous literature.

The integration of visual and vestibular sensory signals in brain stem

nuclei is presumably important in the symptomatic outcome in susceptible

individuals. Some healthy individuals experience pleasant sensations,

i.e., exhilaration, during vection while the majority experience

nausea and tachygastria. The neurohumoral mechanisms which mediate

tachygastria are unknown. Sympathetic dominance has been hypothesized to

account for gastric dysrhythmias in man and dog after gastric surgery

(3,8). Infusion of catecholamines including dopamine induce antral dysrhythmias

in dog (17,19,20). Thus, it is possible that the "stress" of the visual-vestibular

mismatch results in catecholamine release, a response which temporarily

suppresses gastric vagal input and precipitates tachygastrias. Consistent

with these findings is the report by Stanghellini et al. (21) who observed

that cold caloric vestibular stimulation caused nausea, decreased antral

contractility and a delay in gastric emptying of a meal. The decrease in

gastric motility caused by vestibular stimulation correlated with increased

levels of plama nonepinephrine and beta-endorphin. Release of such

sympathetic neurotransmitters may also influence gastric electrical rhythm

during vection. The present results show several distinct EGG frequency peaks

during motion sickness symptoms indicating the instability of the slow

wave pacemaker and suggesting the possibility of several and/or wandering

pacemaker foci.
Stern - 11

Of interest, also, are the subjects who do not develop motion sickness

during vection. Does vection elicit minimal activity of sympathetic or

humoral pathways which might disturb slow wave rhythm? Or, in these

asymptomatic subjects, do parasympathetic vagal influences resist shifts

in gastric frequency? in the symptomatic subjects, the 3 cpm EGG pattern

gradually was re-established after the stress of vection ceased, suggesting

the return of baseline conditions, i.e., parasympathetic predominance. Our

studies suggest that strengthening or maintaining 3 cpm EGG patterns may

retard/decrease the onset of tachygastria and motion sickness, a hypothesis

with therapeutic implications.

The methods used in the present study have certain advantages over

those previously used to induce and measure tachygastria and motion sickness.

The circular vection drum described in this report is safe, since the subject

remains stationary, and reliably evokes both tachygastria and symptoms of

motion sickness in approximately 66% of healthy human subjects. The

frequency of tachygastria as measured with the non-invasive EGG, has been

shown to be identical to the frequency recorded with mucosal electrodes (7).

Furthermore, running spectral analysis of EGG recordings together with the

continuous measure of symptom intensity allows for the comprehensive visual

displays shown in Figures 1-4.

In summary, 15 healthy human subjects were exposed to circular vection

and the non-invasive EGG was used to monitor changes in gastric basic

electrical rhythm. Vection produced tachygastria and symptoms of motion

sickness in 10 individuals. Running spectral analysis and the continuous

measure of intensity of symptoms revealed a close correspondence over time

between tachygastria and reports of symptoms of motion sickness.
Stern - 12

References

1. Kelly KA, La Force RC. Pacing the canine stomach with electric stimulation.

Am J Physiol 1972;222:588-94.

2. Code CF, Marlett JA. Modern medical physiology. Canine tachygastria.

Mayo Clin Proc 1974;49:325-32.

3. Stoddard CO, Smallwood RH, Duthie HL. Electrical arrhythmias in

the human stomach. Gut 1981;22:705-12.

4. Telander.RL, Morgan KG, Kreulen DL, Schmalz PF, Kelly.KA, Szurszewski JH.

Human gastric atony with tachygastria and gastric retention.

Gastroenterology 1978;75:497-501.

5. You CH, Lee KY, Chey WY, Menguy R. Electrogastrographic study of

patients with unexplained nausea, bloating, and vomiting.

Gastroenterology 1980;79:311-4.

6. Grashuis JL, van der Schee EJ, Geldof H. Electrogastrography in dog

and man. In: Stern RM, Koch KL, eds. Electrogastrography:

methodology, validation, and applications. New York: Praeger,

1985;57-77.

7. Hamilton JW, Bellahsene B, Reichelderfer M, Webster JG, Bass P.

Human electrogastrograms: Comparison of surface and mucosal

recordings. Dig Dis Sci 1986;31:33-39.

8. Stewart WR, Stern RM, Koch KL. The effects of the ingestion of barium

sulfate on the EGG recorded from healthy human subjects. In:

Stern RM, Koch KL, eds. Electrogastrography: methodology, validation,

and applications. New York: Praeger, 1985;182-193.
bcern - ij

9. Abell TL, Malagelada J-R. Glucagon-evoked gastric dysrhythmias in

humans shown by an improved electrogastrographic technique.

Gastroenterology 'l985;88:1932-40.

10. Abel! TL, Tucker R, Malagelada J-R. Simultaneous gastric electromanometry in man. In: Stern RM, Koch KL, eds. Electrogastrography:

methodology, validation, and application. New York: Praeger, 1985;

78-88.

11. Wolf S. The relation of gastric function to nausea in man. J Clin

Invest 1943;22:877-82.

12. McDonough FE, Schneider M. Effect of motion on roentgenographic

appearance of stomach and small bowel. Gastroenterology 1944;

2:32-45.

13. Thompson DG, Richelson E, Malagelada J-R. Perturbation of gastric

emptying and duodenal motility through the central nervous system.

Gastroenterology 1982 ;83:1200-6.

14. Stern RM, Koch KL, Leibowitz HW, Lindblad IM, Shupert CL, Stewart WR.

Tachygastria and motion sickness. Aviat Space Environ Med 1985;

56:1074-77.

15. Oixon WJ (Ed.). BMOP statistical software. Los Angeles: University

of California Press, 1983.

16. Dichgans J, Brandt T. Optokinetic motion sickness and pseudocoriolos

effects induced by moving visual stimuli: Acta Otolaryngol 1973;

76:339-48.

17. You CH, Chey WY. Study of electromechanical activity of the stomach

in humans and dogs with particular attention to tachygastria.

Gastroenterology 1984;86:1410-8.

18. Wilbur BG, Kelly KA. Effect of proximal gastric, complete gastric and

truncal vagotomy on canine electrical activity, motility and

emptying. Annals of Surg 1973;178:295-303.
Stern - 14

19. Gullikson GW, Okuda H, Shimizu M, Bass P. Electrical arrhythmias

in gastric antrutn of the dog. Am J Physio! 1980;239:G59-68.

20. Kim CH, Azpiroz F, Malagelada J-R. Characteristics of spontaneous

and drug-induced gastric dysrhythmias in a chronic canine model.

Gastroenterology 1986;90:421r7.

21. Stanghellini V, Malagelada J-R, Zinsmeister AR, Go VLW, Kao PC. Stressinduced gastroduodenal motor disturbances in humans: possible

humoral mechanisms. Gastroenterology 1983;85:83-91.
Stern - 15

Table 1. Summary of the Electrogastrographic Activity and Reports of

Symptoms of Motion Sickness in Response to Circular Vection

Subject

Number

1

2

3

4

. 5

6

7

8

9

10

11

12

13

14

15

Sex

F

F

M

F

F

F

F

M

M

M

M

M

M

M

F

Onset of *

Tachygastria.

12

—

7

8

._

4

7

6

3

7

3

'

—

—

3

. First Repor£

of Symptoms

3

—

6

8

—

7

1

5

1

6

3

—

—

—

3

Description of Symptoms

Sweating, dizzy, salivatin.g

None

Dizzy, feeling of loss of control

Suddenly felt sick in stomach

None

Headache, queasy stomach

Sweating, chills, drowsy, headache, stomachache

Sweating, queasy stomach, dizzy

Nausea at beginning of rotation

Chills, dizzy, queasy stomach

Sweating, headache, stomachache

None

None

None

Headache, stomachache

In minutes from start of drum rotation
9

 • Stern - 16

Figure Legends

Figure 1. Running spectral analysis of the EGG of a subject who reported

no specific symptoms of motion sickness. Note strong 3 cpm activity prior

to drum rotation, attenuation during rotation but no tachygastria, and a

return to strong 3 cpm after rotation. As can be seen on the right hand

side of the figure, this subject did report a low level of symptom intensity

(2 out of a possible maximum of 7) but at the completion of the session

denied experiencing any specific symptoms.

Figure 2. Running spectral analysis of the EGG of a subject who reported

that during rotation he was sweating, dizzy and had a queasy stomach.

Whereas 3 and 1 cpm activity dominate the spectral analysis prior to drum

rotation, 6 minutes after the onset of rotation spectral density showed

a peak at 6 cpm with additional activity in the tachygastria range (5-9 cpm).

At approximately this same point in time the subject reported his first

symptoms of motion sickness.

Figure 3. A clear peak of activity at 3 cpm can be seen in the running

spectral analysis of the EGG of this subject prior to drum rotation. With ,

the onset of rotation there was attenuation of the 3 cpm activity until

Min 8 at which time tachygastria began and the subject suddenly felt sick

in the stomach. The subject requested that rotation be stopped at Min 10.

Tachygastria continued for approximately 6 minutes after drum offset and

was followed by a return of weak 3 cpm activity.

Figure 4. Running spectral analysis of the EGG of a subject who showed a

peak of activity at 3 cpm prior to drum rotation and for 6 minutes after

the onset of rotation. At Min 7 the subject reported the intensity of her

symptoms at 6 (out of 7) and asked that rotation be stopped. Tachygastria

appeared at this point and continued for approximately 6 minutes. Weak 3 cpm

activity can be seen at the end of the session.
Symptoms volunteered by subject:

No specific symptoms.

Time in

64 second

intervals

ril l

1 3 5 7 9 11 13 15

FREQUENCY IN CYCLES PER MINUTE
n: Drum CO

Z

HI

Q

off

o

LU

Q.

(/) Drum

on _

Symptoms volunteered by subject:

Hot, queasy, dizzy."

Time in 0

64 second

intervals

T_ I I I i I

1 3 5 7 9 11 13 15

FREQUENCY IN CYCLES PER MINUTE
Symptoms volunteered by subject:

Hot, chills, sleepy.

After drum off,

headache and

stomachache.

Time in

64 second

intervals

1 3 5 7 9 1 1 1 3 1 5

FREQUENCY IN CYCLES PER MINUTE
Symptoms volunteered by subject:

"Suddenly felt sick

in stomach."

Time in

64 second

intervals

-o

O

m

z

c/)

H

1 3 5 7 9 1 1 1 3 1 5

FREQUENCY IN CYCLES PER MINUTE