Below is the uncorrected machine-read text of this chapter, intended to provide our own search engines and external engines with highly rich, chapter-representative searchable text of each book. Because it is UNCORRECTED material, please consider the following text as a useful but insufficient proxy for the authoritative book pages.
Neural Mechanisms Underlying the Symptomatology of Motion Sickness1 K. E. MONEY AND J. D. WOOD Defence Research Establishment Toronto SUMMARY A review of knowledge about the neural mechanisms of motion sickness is presented, and recent unpublished attempts to increase that knowledge are related. The participation of peripheral afferent nerves, peripheral efferent nerves, and central structures is described and the integrated action of these structures is discussed. The structures that are indispensable for the vomiting of motion sickness are the vestibular apparatus, the vestibular nerve, the vestibular nuclei, the uvula and nodulus of the cerebellum, the chemoceptive emetic trigger zone, the vomiting center, and the somatic pe- ripheral nerves to the respiratory muscles and to the muscles of the abdominal wall. PERIPHERAL AFFERENT NERVES The Vestibular Nerve It is well known that motion sickness does not occur in the absence of a functioning inner ear or after section of its nerve. James reported in 1882 (ref. 1) that none of a group of 15 deaf-mutes who were exposed to rough weather at sea became sick, and it was established in later studies of deaf-mutes (refs. 2 to 6) and in studies of animals subjected to experimental surgery (refs. 7 to 13) that destruction of the vestibular apparatus or section of its nerve confers immunity to motion sickness. It can be said, therefore, that the vestibular nerve is necessary for motion sickness. More specifically, because it has been shown that discrete inactivation of the semicircular canals confers immunity to motion sickness in dogs (ref. 12), it seems likely that, in dogs at 1 DRET Review Paper No. 720. Technical services were provided by A. D. Nicholas and W. J. Watson. Statistical analysis was by Dr. D. M. Sweeney. least, the ampullary nerves are necessary for motion sickness. It is possible, of course, that the nerves to the otolith organs are also neces- sary for motion sickness. Abdominal Afferents Because some kinds of nauseating motions can be expected to cause movement of the viscera, it has been suggested that such move- ments contribute to the nausea and vomiting of motion sickness (refs. 14 to 17). In a study (ref. 18) of 21 dogs, however, denervation of the viscera did not markedly reduce susceptibility to motion sickness. To obtain a measure of their initial susceptibility to motion sickness, the dogs were exposed to swinging at intervals of 1 week or longer, and the duration of swinging required to cause vomiting was recorded. The animals with consistent susceptibility were then subjected to sympathectomy, vagotomy, or both, and the susceptibility was again measured by weekly swinging. None of the animals operated upon exhibited immunity to the vomiting of motion sickness, and a consistent increase in the dura-
36 THE ROLE OF THE VESTIBULAR ORGANS IN SPACE EXPLORATION tion of swinging required to cause vomiting was found in only two of six sympathectomized dogs, in only two of six vagotomized dogs, and in only three of nine both sympathectomized and vagotomized. Because sympathectomy and vagotomy divide the visceral afferent route (as well as the autonomic supply) of most of the gastrointestinal tract, as revealed in the doubly operated dogs by markedly increased thresholds (doses and times) for vomiting to orally admin- istered copper sulfate, it is reasonable to conclude that visceral afferent nerves are not necessary for motion sickness. In fact, it seems unlikely that they play any important role. Afferents From Proprioceptors The receptors of muscles, tendons, and joints have not been investigated for a possible role in motion sickness. These receptors are involved with posture and orientation, and it would be surprising if they were found to be without influence. Afferents From the Eyes The influence of vision on susceptibility to motion sickness can be very important. For example, in a two-pole swing experiment in which the subjects' heads were not fixed, the incidence of motion sickness was found to be 35 percent when the eyes were closed, but only 2 percent when the eyes were open (ref. 19). Vision can also increase the incidence of motion sickness, as shown by experiments in which the subjects were either blindfolded or permitted to view the inside walls of moving capsules (refs. 20 and 21). Indeed, movement of the visual field without any movement of the body can cause signs and symptoms of motion sickness (refs. 22 to 24). Because movement of the visual field has not been effective in persons lacking the peripheral vestibular receptors, it seems possible that vision influences motion sickness through an action on the vestibular system, possibly on the central vestibular structures. Afferents from the retina are not necessary for motion sickness, however, because motion sickness can readily be produced in blindfolded subjects. Similarly, afferents from the external eye muscles were found not to be necessary for motion sickness in three dogs that were swung after injection of Xylocaine behind the eyeballs. The dogs were swung four times at weekly intervals without treatment, to establish the dura- tion of swinging required to cause vomiting. They were then swung after injection of 4 milliliters of 2 percent Xylocaine behind each eyeball. This treatment eliminated vestibular and optokinetic eye movements and caused the pupils to dilate fully, but it had no apparent influence on the duration of swinging required to cause vomiting (table 1). Although it seems clear that afferents from the eye muscles are not necessary for motion sickness, they might in some circumstances play an important role, as do afferents from the retina. PERIPHERAL EFFERENT NERVES The role of efferent nerves in motion sickness has not been investigated in any detail. It has been suggested (ref. 25) on theoretical grounds that the vestibular efferents, by sensitizing the vestibular end organs during motion involving sensory incongruity, increase the afferent activity to the vestibular nuclei and thereby promote the development of motion sickness. Similarly, it seems reasonable to expect that activity in the gamma efferents to muscle spindles would exert an influence, and in view of the importance of head movements in motion sickness (ref. 26), motor nerves which influence head movements probably play a role. The TABLE I.âDurations of Swinging Required To Cause Vomiting, to Nearest Minute, With and Without Xylocaine Behind the Eyeballs * Dog no. Without treatment. With Xylocaine, mm mm 62 9567 12 64 7 12 11 13 7 76 23, 12, 14, 16 10 1 Tests were conducted at intervals of 1 week or more. The 10-minute result with dog 76 was obtained after the 12-minute result and before the 14-minute result; otherwise the results are recorded in chronological order.
NEURAL MECHANISMS IN MOTION SICKNESS 37 efferents to the retina are not necessary for motion sickness, as shown by the dogs that vomited to swinging after application of Xylocaine to the orbits, but they may play an important role in some situations. If vomiting is taken as the criterion of motion sickness, the motor efferents for vomiting are necessary for motion sickness. The Autonomic Nervous System The autonomic nervous system is the efferent nerve supply to smooth muscle and glands. Its role in motion sickness seems to have been grossly exaggerated. Motion sickness, and especially the vomiting of motion sickness, have been described frequently as vegetative or autonomic phenomena (refs. 27 to 33). Vomiting, however, is the expulsion through the mouth of the contents of the stomach and (in some cases) upper intestine. It is ac- complished in mammals primarily by an inte- grated action of the respiratory and somatic abdominal musculature, and not by the muscles of the gastrointestinal tract (ref. 34). The stomach is largely a passive sac during vomiting, and the force for expulsion is supplied by the diaphragm, the intercostal muscles, and the muscles of the abdominal wall. The important motor nerves for vomiting are therefore the phrenic nerve to the diaphragm and the spinal nerves to the intercostal and abdominal muscles. The autonomic supply to the stomach and upper intestine is also active during vomiting, but its contribution is dispensable, because "there is no essential difference in the vomiting act per- formed by normal and gut-denervated animals" (ref. 35). The sensation of nausea, which can be ex- perienced by human subjects after total gastrec- tomy (ref. 34), is probably the conscious aware- ness of unusual activity in the vomiting centers, and there is no reason to regard it as a result of autonomic activity. Therefore, the major parts of the motion-sickness syndrome, nausea and vomiting, cannot be described as autonomic phe- nomena. The pallor and cold sweating of motion sickness can reasonably be considered autonomic phenomena, but only because pallor and sweating are usually controlled by the autonomic nervous system. It is possible, although not likely, that the pallor and sweating of motion sickness are caused by a circulating chemical unrelated to the autonomic mediators; the pharmacological dissection which could answer this question has apparently not been done. In the experiment designed to investigate the role of abdominal afferents in motion sickness (ref. 18), nine susceptible dogs were prepared with sympathectomy and vagotomy. These dogs were, therefore, without the sympathetic division of the autonomic nervous system, and without the parasympathetic supply to the gastrointestinal tract down to the ileocolic valve. Only three of the nine animals were consistently less susceptible to motion sickness postopera- tively, and even these three were not immune. It seems reasonable to conclude from this experi- ment not only that the visceral afferents play no vital role in the vomiting of motion sickness but also that the autonomic supply to the viscera plays no vital role. Theories of motion sickness that depend upon the proximity of the medial vestibular nucleus and the dorsal nucleus of the vagus nerve are scarcely tenable in the light of this experiment. CENTRAL STRUCTURES Vestibular Nuclei Because most vestibular sensory fibers synapse in the vestibular nuclei, and because the vestibu- lar nerve is necessary for motion sickness, the vestibular nuclei are probably necessary for motion sickness. Vestibular Parts of the Cerebellum In four dogs that had consistently vomited to swinging preoperatively, the uvula, nodulus, and pyramis were removed (ref. 36). Two of these dogs did not vomit in any postoperative test, and the other 2 vomited in only one of 9 or 10 postoperative tests. In a later experiment (ref. 11), nine dogs that had consistently vomited to swinging were subjected to partial or complete removal of the uvula and nodulus. Seven of these dogs did not vomit in any postoperative test, one dog vomited in only one postoperative test, and one dog with minimal damage to the
38 THE ROLE OF THE VESTIBULAR ORGANS IN SPACE EXPLORATION uvula and nodulus vomited in all of the four postoperative tests. Additional animals sub- jected to the removal of the pyramis and other nonvestibular parts of the cerebellum retained their preoperative susceptibility to motion sick- ness. It seems clear that the vestibular parts of the cerebellum are necessary for the vomiting of motion sickness in dogs. Chemoceptive Emetic Trigger Zone The chemoceptive emetic trigger zone is located superficially in the caudal part of the floor of the fourth ventricle, dorsolateral to the vagal nuclei (ref. 37). Central emetics such as apomorphine and the cardiac glycosides act, by way of the bloodstream, upon the chemoceptive trigger zone which in turn acts upon the "inte- grative vomiting center" (ref. 34) to cause vomiting. In 12 dogs that had regularly vomited to swinging preoperatively, the chemoceptive trigger zone was destroyed (ref. 37). Two of these dogs vomited in all the postoperative tests after durations of swinging comparable to the preopera- tive durations, but two of them vomited only during some of the postoperative tests and eight of them failed to vomit in all of the postoperative tests. The absence of the chemoceptive trigger zone was confirmed by failure to vomit to apomor- phine and by histology, and the ability of the animals to vomit postoperatively was established by oral administration of copper sulfate. It seems likely that the chemoceptive emetic trigger zone is necessary for motion sickness. Vomiting Center The neural mechanisms responsibile for the coordinated muscular contractions of vomiting are obviously necessary for vomiting. It is not known whether the required coordination is effected by a morphologically distinct "center" having only an integrating function. Cerebrum The cerebrum (telencephalon) does not play a vital role in motion sickness in dogs. One dog that had consistently vomited within 4 to 10 minutes of swinging was decerebrated by removing a wedge of tissue rostral to a plane joining the superior colliculi to a point just behind the mammillary bodies (ref. 38). Its susceptibility was tested again between the 26th and 53d postoperative days, and it vomited in all of the five swing tests administered, within 3 to 9 minutes of swinging. In six other dogs with unilateral removal pf the cerebral cortex, and in six additional dogs with bilateral removal of the cerebral cortex from temporal or occipital or parietal areas, no essential participation by a cortical structure was revealed (ref. 36). Motion sickness in a decorticate man has also been reported (ref. 39). Because the cerebrum is not necessary for motion sickness, it is difficult to escape the con- clusion that psychological factors are not neces- sary for motion sickness. Aside from the ques- tion of necessity, however, the cerebrum and psychological factors can undoubtedly influence the development of motion sickness in man. THE INTEGRATED PICTURE Figure 1 presents an integrated picture of the neural mechanisms of motion sickness. Ap- propriate motion acts on the vestibular apparatus, the proprioceptors, and the eyes. In some cases it also acts on the abdominal viscera, but this is probably not important in motion sickness. Afferents from the eyes are not necessary for motion sickness, but they are known to play an important role in some situations. The struc- tures that can be considered indispensable for the vomiting of motion sickness (in dogs at least) are the vestibular apparatus, the vestibular nerve, the vestibular nuclei, the vestibular part of the cerebellum, the chemoceptive emetic trigger zone, the vomiting center, and the somatic motor nerves to the respiratory muscles and to the muscles of the abdominal wall. Structures that are dispensable are the nerves to the eyes, the nerves to the abdominal viscera, and the cerebral cortex. Following the sequence of events between ap- propriate motion and vomiting, one can see a logical relationship among motion, the vestibular apparatus, the vestibular nerve, the vestibular nuclei, and the vestibular cerebellum; there is an equally logical and well-known relationship among the chemoceptive emetic trigger zone,
NEURAL MECHANISMS IN MOTION SICKNESS 39 APPROPRIATE MOTION VESTIBULAR APPARATUS SKELETAL MUSCLES SKELETAL MUSCLES CEREBELLUM esp. uvu and noduI VESTIBULAR NUCLEI PERIPHERAL NERVOUS SYSTEM EFFERENTS (SOMATIC AND AUTONOMIC) PERIPHERAL NERVOUS SYSTEM EFFERENTS (SOMATIC AND AUTONOMIC) RESPIRATORY CENTER AUTONOMIC CENTERS NEUROHYPOPHYSIS VOMITING CENTER PERIPHERAL NERVOUS SYSTEM EFFERENTS (SOMATIC AND AUTONOMIC) FIGURE 1. â Relationships among anatomical structures involved in motion sickness. Structures joined by the wide shaded lines are indispensable to the vomiting of motion sickness in dogs.
40 THE ROLE OF THE VESTIBULAR ORGANS IN SPACE EXPLORATION the vomiting center, the motor nerves for vomit- ing, and the muscles of vomiting. There is no known reason, however, why the vestibular cerebellum should influence the chemoceptive emetic trigger zone, and therefore the essence of motion sickness is probably to be found here, in the relationship between the vestibular cere- bellum and the chemoceptive trigger zone. The mystery of why motion causes vomiting in a healthy animal is found reflected here in the brain. Because the chemoceptive emetic trigger zone is sensitive to chemicals (ref. 40), and because motion sickness develops so slowly (usually repeated stimulation of the vestibular apparatus is required for a period of several minutes or even hours to cause vomiting), it seems likely that the cause of nausea and vomit- ing in motion sickness is an emetic chemical that accumulates under the influence of the vestibular cerebellum during motion. Babkin and his associates as early as 1943 (refs. 9, 41, and 42) investigated the possibility that circulating acetyl- choline was responsible for motion sickness in dogs. They were unable, however, to demon- strate any increase in blood acetylcholine during motion sickness. ATTEMPT TO ESTABLISH THE HY- POPHYSIS AS A LINK BETWEEN THE VESTIBULAR CEREBELLUM AND THE CHEMOCEPTIVE TRIGGER ZONE Several observations suggest that the neuro- hypophysis secretes an emetic agent during appropriate motion: (1) posterior pituitary extract is an emetic agent (ref. 35); (2) a pituitary-type inhibition of water diuresis occurs with motion sickness, and an antidiuretic substance can be recovered from the urine of subjects who have been motion sick (ref. 43); (3) the cardiovascular response to nauseating motion resembles closely the response to Pitressin injection (ref. 44); (4) the centers which normally control pallor and sweating are intimately associated with the hypothalamic-hypophyseal system. Also, the adrenocortical response in motion sickness (refs. 45 to 47) suggests the possibility that the adenohypophysis plays an important role in motion sickness. The susceptibility of hypophy- sectomized dogs to motion sickness is there- fore of interest. Normal mongrel dogs were tested for suscepti- bility to motion sickness on a motor-driven swing, and dogs that vomited within 20 minutes on the initial exposure were considered suitable for further testing and were subsequently swung at intervals of at least 1 week until they had demonstrated susceptibility at least four con- secutive times. In most cases, more than four preoperative tests were carried out. After the initial test, the maximum duration of swinging was set arbitrarily at 60 minutes, and dogs that did not vomit within 60 minutes of swinging at any preoperative test were discarded from the experi- ment; postoperatively, swing tests were stopped after 60 minutes and failure to vomit by that time was taken as a negative response. After consistent susceptibility to motion sickness had been established, each dog was hypophysecto- mized by the transbuccal approach. In some cases, parts of the hypothalamus were also de- stroyed, by cautery. After recovery from the operation, the surviving animals were again tested for susceptibility to motion sickness at intervals of 1 week or longer, and they were observed for polyuria throughout the remainder of the experiment. No hormones were admin- istered to the animals postoperatively. Seven dogs survived the hypophysectomy and were tested postoperatively. The operations had no consistent effect on the durations of swinging required to produce vomiting (table 2). A Wil- coxan two-sample rank test showed no significant difference between the preoperative and post- operative vomiting times of the seven dogs. Five of the dogs exhibited polyuria following the operation, and in three of these the polyuria was permanent, continuing until the deaths of the animals 6 to 10 weeks postoperatively. Autopsy with an operating microscope confirmed that the pituitary glands had been removed. In this experiment it was not established that either the adenohypophysis or the neurohypoph- ysis was completely ablated in the dogs, but the pituitary glands were removed, and in three of the dogs the neurohypophysis was inactivated, according to the criterion of permanent polyuria
NEURAL MECHANISMS IN MOTION SICKNESS 41 (ref. 48). A dog was considered to have polyuria if its postoperative daily urine output exceeded the preoperative output by more than 1 liter per 10 pounds of body weight. The operations did not have a large or consistent influence on sus- ceptibility to motion sickness, and the results indicate that motion sickness is possible in the absence of the pituitary gland and in the presence of permanent polyuria. It therefore seems un- likely that the hypophysis plays any necessary role in motion sickness in the intact animal. INVESTIGATION OF GAMMA-AMINO- B UTYRIC ACID IN MOTION SICKNESS It has been suggested (ref. 49) that various un- related drugs that are effective against motion sickness have a common action in increasing the level of y-aminobutyric acid in the brain. In terms of the relationship between the vestibular cerebellum and the chemoceptive trigger zone, this would mean that during appropriate motion the vestibular cerebellum causes a decrease in TABLE 2. âDurations of Swinging Required To Produce Vomiting, to Nearest Minute, Before and After Hypophysectomy i Dog no. Preoperative, min Postoperative, min Postoperative polyuria 58 5, 6, 5, 5 15, 14, (died) Transient. 15 9, 8, 7, 6, 8,2 8 5, 5, 5, 5, 7 B200 18 25, 21 53, 19 x,3 x, x, 19, x, 14 B224 6 5, 8 9 4 13, 17, 17, 14, 33 None ISA 12, 14, 6, 5, 4, 5, 4, 5, 6, 8 Permanent. B223 6, 7, 6, 4, 8 5, 4, 6, 5, 7 Permanent. B334 . 4, 11, 11, 11 11, 15 None. 1 Tests were conducted at intervals of 1 week or more and are recorded in chronological order. ' Nonstandard stimulus used inadvertently. 3 Values greater than 60 indicated by "x." TABLE 3.âDurations of Swinging To Cause Vomiting Interval between Date Medication injection Dog no. 4 Dog no. 6 Dog no. 7 1968 swinging, hr and Jan 23 17-30 13-02 8-35 31 15-15 8-50 8:07 Feb. 7 15-43 16-05 11:08 14 15-40 10-00 6-40 21 AOAA 02 mg/kg1 6 7:25 16:40 9:22 28 AOAA, 0 5 mg/kg 6 6:15 15:54 3 0:00 Mar 27 Thio SC 2 mg/kg 2 3 7:15 8-45 Apr. 4 Thio SC, 2 mg/kg 1 13:59 4:37 [In minutes and seconds] 1 AOAA means aminooxyacetic acid. 2 Thio SC means thiosemicarbazide. o means osemcaraze. 3 Dog vomited just before swinging started and again after 5:20 of swinging.
42 THE ROLE OF THE VESTIBULAR ORGANS IN SPACE EXPLORATION the level of y-aminobutyric acid, or, alternatively, that the vestibular cerebellum is unable to exert its influence on the chemoceptive trigger zone in the presence of high concentrations of y- aminobutyric acid. It was therefore of interest to investigate susceptibility to motion sickness in animals in whom the brain level of y-amino- butyric acid had been artificially raised. Three dogs were exposed to swinging motion once each week for 4 weeks to establish the dura- tion of swinging required to induce vomiting. After a further 7-day interval, the dogs were swung again, 6 hours after subcutaneous injec- tion of 0.2 mg/kg of aminooxyacetic acid. This drug is known to raise the level of y-aminobutyric acid in the brain (ref. 50). As indicated in table 3, the injections had no significant effect on the durations of swinging required to cause vomiting. One week later the dogs were swung again, 6 hours after injection of 0.5 mg/kg of amino- oxyacetic acid. As shown in table 3, this dose also had no strong influence, but possibly caused vomiting sooner than without medication. Larger doses of aminooxyacetic acid caused repeated vomiting without any swinging or other motion. The original intention was to study more dogs with aminooxyacetic acid after these preliminary trials, but the results were so discouraging that the decision was made not to continue. Because raising the brain level of y-aminobutyric acid caused vomiting and seemed to promote motion sickness, it was decided to test susceptibility to motion sickness after lowering the brain level of y-aminobutyric acid, which can be accom- plished with thiosemicarbazide (ref. 51). Two of the same dogs (one had become pregnant) were used. No strong influence of 2 mg/kg of thio- semicarbazide was found when testing the ani- mals 3 hours after injection or, again 1 week later, 1 hour after injection (table 3). While the data from this experiment are scarcely conclu- sive, it seems unlikely that the level of y-amino- butyric acid in the brain plays any essential or powerful role in the development of motion sick- ness, and it seems unlikely that anti-motion- sickness drugs act by raising the brain's con- centration of y-aminobutyric acid. The link between the vestibular cerebellum and the chemoceptive trigger zone remains unilluminated. REFERENCES 1. JAMES, WILLIAM: The Sense of Dizziness in Deaf Mutes. Am. J. Otol., vol. 4, 1882, pp. 239-254. 2. MINOR, J. L.: Seasickness: Its Cause and Relief. N.Y. Med. J., vol. 64, 1896, pp. 522-523. 3. REYNOLDS, T. T.: On the Nature and Treatment of Sea- sickness. Lancet, vol. 1, 1884, pp. 1161-1162. 4. SJOBERG, A. A.: Experimental Studies of the Eliciting Mechanism of Sea-sickness. Acta Oto-Laryngol., vol. 13, 1929, pp. 343-347. 5. BROWN, G. L.; MCARDLE, B.; AND MAGLADERY, J. W.: Interim Report on Clinical Investigations Into Air- sickness. FPRC Report 410(a), Research Unit, National Hospital, London, 1941. 6. GRAYBIEL, A.: Vestibular Sickness and Some of Its Implications for Space Flight. Neurological Aspects of Auditory and Vestibular Disorders, W. S. Fields and B. R. Alford, eds., Charles C Thomas, 1964, pp. 248-270. 7. SJOBERG, A. A.: Experimentelle Studien Ober Den Auslosungsmechanismus der Seekrankheit. Acta Oto- Laryngol.. suppl. 14, 1931. pp. 1-136. 8. MCNALLY, W. J.; STUART, E. A.; AND MORTON, G.: Effect of I.abyrinthectomy on Motion Sickness in Animals. Report C748. Appendix M. Proceedings of Conference on Motion Sickness, National Research Council of Canada, Aug. 28, 1942. 9. BABKIN, B. P.; AND BORNSTEIN, M. B.: The Effect of Swinging on the Motility of the Stomach in Dogs. Report C4030. Proceedings, Second Meeting, As- sociation Committee, Naval Medical Research, Na- tional Research Council, Canada, Oct. 1943, pp. 1-8. 10. KURASHVILI, A. E.: Vestibular Reactivity During the Cumulative Action of Slow Centripetal Accelerations. FTD MT-63-179. TT 64 11970. Translation of Zh. Ush., Nos., Gorl. Bol., vol. 22. 1962, pp. 49-55. 11. WANG. S. C.; AND CHINN, H. L: Experimental Motion Sickness in Dogs: Importance of Labyrinth and Ves- tibular Cerebellum. Am. J. Physiol., vol. 185, 1956, pp. 617-623. 12. MONEY, K. E.; AND FRIEDBERG, J.: The Role of the Semicircular Canals in Causation of Motion Sick- ness and Nystagmus in the Dog. Can. J. Physiol. Pharmacol., vol. 42, 1964, pp. 793-801. 13. JOHNSON, W. H.; MEEK, J. C.; AND GRAYBIEL. A.: Effects of Labyrinthectomy on Canal Sickness in Squirrel Monkey. Ann. Otol., vol. 71, 1962, pp. 289-298.
NEURAL MECHANISMS IN MOTION SICKNESS 43 14. IRWIN, J. A.: The Pathology of Sea-sickness. Lancet, vol. 1, Nov. 1881, pp. 907-909. 15. NuNN, P. W. G.: Seasickness: Its Causes and Treat- ments. Lancet, vol. 2, 1881, p. 1037. 16. DESNOES, P. H.: Seasickness. J. Am. Med. Assoc., vol. 86, 1926, pp. 319-324. 17. CASTELLANI, A.: Sea-sickness: A Short General Account. J. Trop. Med., vol. 43, 1940, pp. 63-66. 18. WANG, S. C.; CHINN, H. I.; AND RENZI, A. A.: Experi- mental Motion Sickness in Dogs: Role of Abdominal Visceral Afferents. Am. J. Physiol., vol. 190, Sept. 1957, pp. 578-580. 19. JOHNSON, W. H.; AND TAYLOR, N. B. G.: Some Experi- ments on the Relative Effectiveness of Various Types of Accelerations on Motion Sickness. Aerospace Med., vol. 32,1961, pp. 205-208. 20. MANNING, G. W.; AND STEWART, W. G.: Effect of Body Position on Incidence of Motion Sickness. J. Appl. Physiol., vol. 1, Mar. 1949, pp. 619-628. 21. BROWN, J. H.; AND CRAMPTON, G. H.: Concomitant Visual Stimulation Does Not Alter Habituation of Nystagmic, Oculogyral or Psychophysical Responses of Angular Acceleration. Acta Oto-Laryngol.. vol. 61, 1966. pp. 80-91. 22. WITKIN. H. A.: Perception of Body Position and of the Position of the Visual Field. Psychol. Monogr., vol. 63, 1949, pp. 1-46. 23. CRAMPTON, G. H.; AND YOUNG, F. A.: The Differential Effects of a Rotary Visual Field on Susceptibles and Nonsusceptibles to Motion Sickness. J. Comp. Physiol. Psychol., vol. 46, 1953, pp. 451-453. 24. MILLER, J. W.; AND GOODSON, J. E.: Motion Sickness in a Helicopter Simulator. Aerospace Med., vol. 31, Mar. 1960, pp. 204-212. 25. GlLLINGHAM, K. K.: Training the Vestibule for Aero- space Operations. Central Control of Vestibular Function. Review 8-65. USAF School of Aerospace Medicine, Brooks Air Force Base, Tex., 1965. 26. JOHNSON, W. H.; STUBBS, R. A.; KELK, G. F.; AND FRANKS, W. R.: Stimulus Required to Produce Motion Sickness. 1. Preliminary Report Dealing With Im- portance of Head Movements. J. Aviat. Med., vol. 22, 1951, pp. 365-374. 27. DE WIT, G.: Seasickness (Motion Sickness). A Laby- rinthological Study. Acta Oto-Laryngol., suppl. 108, 1953, pp. 1-56. 28. SPIEGEL, E. A.: Effect of Labyrinthine Reflexes on Vege- tative Nervous System. Arch. Otol., vol. 44, July 1946, pp. 61-72. 29. SPIEGEL, E. A.; AND SOMER, I.: Vestibular Mechanisms. Medical Physics, Otto Glaser, ed.. Year Book Pub- lishers, 1944, pp. 1638-1658. 30. VAN EGMOND, A. A. J.; GROEN, J. J.: AND DE WIT, G.: The Selection of Motion Sickness-Susceptible Indi- viduals. Intern. Record Med., vol. 167, 1954, pp. 651-660. 31. VARTBARONOV, R. A.: Some Vascular Reactions in Man Related to Coriolis Acceleration. Space Flight Phys- iology, Izvest. Akad. Nauk. SSSR, Ser. B. No. 1. 1965. pp. 21-26. (JPRS Translation: 29, 156.) 32. VOYACHEK, W.: Fundamentals of Aviation Medicine. Translated by I. Steiman, Univ. of Toronto Press, 1943. 33. WODAK, E.: Vestibular ausgeliiste vegetative Phanomene und ihre Dissoziationen mit den iibrigen vestibularen Reaktionen. Pract. Oto-Rhino-Laryngol., vol. 18, July 1956, pp. 225-239. 34. CUMMINS, A. J.: The Physiology of Symptoms. III. Nausea and Vomiting. Am. J. Digest. Dis., vol. 3, Oct. 1958, pp. 710-721. 35. BORISON, H. L.; AND WANG, S. C.: Physiology and Phar- macology of Vomiting. Pharmacol. Rev., vol. 5, June 1953, pp. 193-230. 36. BARD, PHILIP: Physiological Investigation of Causes and Nature of Motion Sickness. Report 485, National Re- search Council, Committee on Aviation Medicine, Sept. 1945. 37. WANG, S. C.; AND CHINN, H. I.: Experimental Motion Sickness in Dogs. Functional Importance of Chemo- ceptive Trigger Zone. Am. J. Physiol., vol. 178, 1954, pp. 111-116. 38. BARD, P.; WOOLSEY, C. N.; SNIDER, R. S.; MOUNTCASTLE, V. B.; AND BROMILEY, R. B.: Delineation of Central Nervous Mechanisms Involved in Motion Sickness. Fed. Proc., vol. 6, Mar. 1947, p. 72 (abstract). 39. DOIG, R. K.; WOLF, S.; AND WOLFF, H. G.: Study of Gastric Function in a "Decorticate" Man with Gastric Fistula. Gastroenterol., vol. 23, 1953, pp. 40-44. 40. CHINN, H. L; AND SMITH, P. K.: Motion Sickness. Pharmacol. Rev., vol. 7, Mar. 1955, pp. 33-82. 41. BABKIN, B. P.; AND BORNSTEIN, M. B.: The Effect of Swinging and of Binaural Galvanic Stimulation on the Motility of the Stomach in Dogs. Rev. Can. de Biol., vol. 2, 1943, pp. 336-349. 42. BABKIN, B. P.: DWORKIN, S.; AND SCHACHTER, M.: Experimental Motion Sickness and Attempts at Therapy. Rev. Can. de Biol., vol. 5,1946, pp. 72-85. 43. TAYLOR, N. B. G.; HUNTER, J.; AND JOHNSON, W. H.: Antidiuresis as a Measurement of Laboratory Induced Motion Sickness. Can. J. Biochem. Physiol., vol. 35, 1957, pp. 1017-1027. 44. SUNAHARA, F. A.; JOHNSON, W. H.; AND TAYLOR, N. B.G.: Vestibular Stimulation and Forearm Blood Flow. Can. J. Physiol. Biochem., vol. 42, 1964, pp. 199-207. 45. DAHL, E. V.; FRANKS, J. J.; PRIGMORE, J.R.; AND CRAMER, R. L.: Adrenal Cortical Response in Motion Sickness. Arch. Environ. Health, vol. 7, 1963, pp. 86-91. 46. COLEHOUR, J. K.: Stress Measurements in Normal and Labyrinthine Defective Subjects in Unusual Force Environments. The Role of the Vestibular Organs in the Exploration of Space, NASA SP-77, 1965, pp. 347-355. 47. COLEHOUR, J. K.: AND GRAYBIEL, A.: Biochemical Changes Occurring With Adaptation to Accelerative Forces During Rotation. Aerospace Med., vol. 37, Apr. 1966, pp. 1205-1207. 48. HEINBECKER, P.; AND WHITE, H. L.: Hypothalamico-
44 THE ROLE OF THE VESTIBULAR ORGANS IN SPACE EXPLORATION Hypophyseal System and Its Relation to Water Balance Oxyacetic Acid and Hydroxylamine on Rats Breathing in the Dog. Am. J. Physiol., vol. 133, 1941, pp. 582- Oxygen at High Pressure. J. Neurochem., vol. 12, 593. 1965, pp. 663-669. 49. GIURGEA, C. E.; MOEYERSOONS, F. E.; AND EVRAERD, 51. WOOD, J. D.; WATSON, W. J.; AND STACEY, N. E.: A A. C.: A GABA-Related Hypothesis on the Mechanism Comparative Study of Hyperbaric Oxygen-Induced of Action of the Antimotion Sickness Drugs. Arch. and Drug-Induced Convulsions With Particular Ref- Int. Pharmacodyn., vol. 166, 1967, pp. 238-251. erence to y-aminobutyric Acid Metabolism. J. Neuro- 50. WOOD, J. D.; AND WATSON, W. J.: The Effect of Amino- chem., vol. 13, 1966. pp. 361-370.