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Exercise and recovery from vestibular injury
Am J Otolaryngol 3:397-407, 1982
Exercise and Recovery from Vestibular Injury ROBERTH. MATHOG,M.D., ANDSmANB. PEPPARB,M.D. Exercise after vestibular injury is potentially an important modality in the recovery process. In this study, the effects of injury on the vestibular system were examined experimentally in cats. Data from healthy normal cats, labyrinthectomized cats, and labyrinthectomized cats treated with exercise were examined. Evaluation of performance was accomplished with caloric, optokinetic, and sinusoidal acceleration testing. Results in normal cats indicated stable, symmetrical vestibular responses on repetitive testing, without evidence for habituation. Comparison of the experimental groups showed that the animals treated with exercise had a significant difference in terms of recovery. The exercised group demonstrated a diminished directional preponderance, a shorter period of complete asymmetry, and a shorter recovery time, which was 58 to 70 per cent faster than that of the non-exercised group. The authors conclude that a general type of exercise will markedly affect and shorten the recovery pattern in the labyrinthectomized cat. (Key words: Exercise; Labyrinthectomy; Vestibular injury.)
In order to afford patients with vestibular disorders the best treatment possible, it is important to understand the basic science of the vestibular system and what methods are available to affect the function of this system. As a result of vestibular injury from trauma or disease, patients will complain of dizziness or vertigo and demonstrate an abnormal nystagmus, but with time the signs and symptoms are usually reduced and there is a tendency toward recovery. It is apparent that if the clinician were to understand fully h o w the patient recovers and what methods facilitate or retard this process, the care of patients with vestibular disorders could be greatly improved. Many factors such as vision, proprioception, and use and disuse of the vestibular system have been implicated in the recovery process, but from a clinical standpoint, exercise has always appeared to be a potentially important modality. Cawthorne 1'' suggested a series of exercises for patients following labyrinthectomy, while others using similar methods have actually recorded salutary effects, a,4 Unfortunately, the From the Department of Otolaryngology,Wayne State University, Schoolof Medicine, Detroit, Michigan.Received May 14, 1982. Accepted for publication July 12, 1982, Supported by a Deafness Research Foundationgrant. Address correspondence and reprint requests to Dr. Peppard: Otolaryngology 5E-UHC, Wayne State University School of Medicine, 540 East Canfield, Detroit, Michigan 48201.
concepts are not universally accepted, and although some patients are treated with exercise programs, many are conversely treated with rest and vestibular suppressant medications. It has been the purpose of this study to evaluate, through a series of experiments, the effects of exercise during the recovery of the vestibular system from injury. An animal model has been developed for the evaluation of factors that can affect the recovery process. Vestibular responses of healthy normal cats to sinusoidal stimuli have been used to establish norms, and vestibular responses after labyrinthectomy have been compared with those of normal animals. Using these two groups as controls for normal and labyrinthectomized responses, labyrinthectomized cats have been sinusoidally stimulated and evaluated after exercise, and any differences in response from the control groups have been used to study the relative beneficial or inhibitory effects of these factors on the recovery process. BACKGROUND An understanding of the vestibular system is complicated by the multiple interactions of the vestibular pathways and other systems in the brain? -9 Connections to the spinal-motor center, thalamus, cerebral cortex, flocculus, nodulus, uvula and fastigial nuclei of the cerebellum, and autonomic centers of the medulla and the midbrain have been identified. It is also well
0i96-070918211100/0397 $02.20 O W, B. Saunders Co. 397
EXERCISE AND RECOVERY
American Journal
of Otolaryngo]ogy 398
k n o w n that vestibular activity can be modified by input from the midbrain, spinal cord, cerebellum, cerebrum, and brainstem, l~ After injury to the labyrinth, many parts of the central nervous system are involved in the recovery processes. It is presumed that a number of biofeedback conditions occur to bring balance back to the system. The classic responses to vestibular injury are well d e s c r i b e d . Labyrinthectomy in various species of animals initially produces spontaneous nystagmus, with the quick component of the rtystagmus directed to the intact side. In cats, Precht et a l " demonstrated that the spontaneous n y s t a g m u s disappeared after three to four days, but w i t h stimuli of acceleration a distinct asymmetric i n d u c e d nystagmus appeared. About 45 days later the asymmetry disappeared, and the animals w e r e thought to have achieved full compensation. B e c h t e r e w demonstrated that compensation after labyrinthectomy is extremely complex. As cited by Schaefer and Meyer,'" Bechterew showed that spontaneous nystagmus gradually disappeared after an initial labyrinthectomy, but when t h e other labyrinth was destroyed a new spontaneous nystagmus appeared to the opposite side. In similar experiments Magnus ~'~ observed that extirpation of a second labyrinth four days after labyrinthectomy had the same effect as w h e n b o t h labyrinths were removed, but if this extirpation were performed after 11 days a nystagmus occurred to the opposite side. These p h e n o m e n a a p p e a r e d to indicate changing neural p a t h w a y s which were trying to compensate for or overcome the deficit. McCabe 3 has attempted to explain the phenomena: normally "the end-organs are frequency modulators of the resting electrical activity or n e u r o n arcs. When a motion of the head stimulates one end-organ, resulting in a modulation of its activity upwards, the same motion results in a modulation downward on the opposite side." Thus, the effects of stimulating the two sides are equal and opposite and balance is obtained. With injury to the vestibular system the events are altered and the balance is upset. Assuming a destruction of one side, the resultant inactivity of that side leads to relative overactivity of the opposite side. To achieve balance again, the relative over-activity must be reduced and/or t h e activity on the injured side be increased. 14 In experiments designed to elucidate how one
area is suppressed while the other is activated, the contributions of various parts of the central nervous system have been studied. ROLE OF VESTIBULAR NUCLEI. According to McCabe et al. ~4,'5 and Precht and associates," the vestibular nuclei are essential for compensating processes. Vestibular nuclei lose neural activity after they lose their afferent nerve supply, but later this activity is regenerated and counteracts the activity of the opposite side. The development of this activity on the deafferentated side was thought to be a result of elimination of tonic inhibitory influences frmn the interneurons from the contralateral labyrinth and its mediating pathway. '" ROLE OF CEREBELLUM. The importance of the cerebellum in controlling these phenomena is also well known. Carpenter et al. '7 demonstrated that nystagmus was increased following labyrinthectomy when the cerebellum, specifically the fastigial nuclei, was damaged. Also, compensation (which occurred w h e n the nystagmus disappeared) was completely abolished by the destruction of fastigial nuclei. McCabe et al. t4'15 also indicated the importance of the cerebellum, noting that the depression of response on the side contralateral to the labyrinth did not occur in the cerebellectomized animal. ROLE OF SPINAL AFFERENTS AND CEREBRUM.
The spinal afferents are also implicated in the compensation mechanism. In the guinea pig, '~''9 interruption of the thoracic segment of the spinal cord provoked the reappearance of nystagmus elicited by a previously destroyed labyrinth. In this species the nystagmus that had faded away returned after disruption of the spinal afferents. Although the cerebral cortex probably plays a minimal role, anatomic pathways for compensation through the reticular formation and cerebellum have been suggested. Also, according to Azzena '~ and DiGiorgio, 2~ once nystagmus disappears following unilateral labyrinthectomy, destruction of the cerebral cortex will cause reappearance of the eye movement. ROLE Or VISION. The interaction of vision has also been described. After removing vision by keeping labyrinthectomized animals in darkness, various investigators have found a delay in body tilt to return to a normal position and aiso a delay in the disappearance of spontaneous nystagmus, '-'1,22 Others have also observed, in additional experiments, persistence of the spontaneous nystagmus if the animals were kept in darkness?-a,'24 The experiments were interpreted
MATHOGAND PEPPARD as showing that vision "conditions disinhibition of vestibular nuclei spontaneous activity after the critical phase of compensation. ''24 Many of the studies have suggested that visual control is mediated through the cerebellum, and it is thought that this mechanism is important for the learning processes and for compensation to take place. Ito 2~,'-'6 has described a simplified model utilizing the flocculus vestibule-ocular system whereby vision can modify and alter the vestibule-ocular reflex. ROLES OF EXCITANT AND DEPRESSANT DRUGS. Drugs that excite or depress the central nervous system must be important, although interaction and control mechanisms for compensation are not entirely clear. Investigations using chronic experiments are lacking, but short-term preparations have demonstrated a delay in or an acceleration of compensation to vestibular injury by administration of drugs. In the guinea pig, phenobarbital delayed compensation three days or more, while amphetamine accelerated the compensation process.'' Dowd 'T and Crampton "8 have demonstrated similar accelerated effects after administration of amphetamine to habituated animals. These findings have suggested that there is a generalized acceleration of compensation through pharmacologic acceleration of synapses and pathways. ROLE OF EXERCISE. In spite of the interest in and studies of various factors that can affect recovery of the vestibular system, reports on the importance of exercise, with its gross stimulations of the central nervous system, are lacking. Several investigators '-4 have described the effects of exercise, but these case studies have been "mixed" and poorly controlled. Failure to develop satisfactory animal models has also retarded investigations of the relative value of exercise in the recovery of the vestibular system. METHODS
Subjects Animals selected for study were adult healthy experimentally naive cats without evidence of ear infections. Four cats served as normal subjects, three cats had unilateral labyrinthectomy without exercise, and three cats had unilateral labyrinthectomy with exercise. The animals were immobilized during the vestibular and optokinetic tests by insertion of piano wire through holes in the canine teeth,
securing the wire to a special restraint box?" Maxillary restraint was used in cases of broken canine teeth2 ~ All tests were conducted in a light-controlled room separated from the recording equipment.
Stimulation OPTOKINETIC STIMULATION. Cats within a restraint box were centered on a Stille-Werner chair and rotated 24~ After one minute allowed for equilibration, induced eye movements were recorded. The recording was adjusted so that "t mm of pen deflection was converted to 10 degrees of eye movement and provided for calibration of eye movement in degrees per mm during other types of tests. These results were confirmed by an optoldnetic drum rotated around the subject at 24~ CALORIC STIMULATION. Caloric stimulation consisted of 1,000 ml of water at 25~ C (+0.5 ~ C) instilled over 30 seconds into the external auditory canal. The caloric test sequence conducted in total darkness was left ear irrigation followed in 15 minutes by irrigation of the right ear, and followed again in 15 minutes by repeat irrigation of the left ear. Experience with these tests indicated that the first stimulation was quite a shock and that subsequent irrigations provided more stable data. SINUSOIDAL STIMULATION. A Stille-Werner rotating chair (Stille-LKB RS-3/22) was used to produce sinusoidal angular acceleration. S i n u s o i d a l stimuli were selected and randomized at frequencies of 0.01 Hz, 0.05 Hz, and 0.10 Hz with peak velocities of 12~ and 30~ sec for each test frequency. According to a system of randomization, each subject received six complete cycles of acceleration at each frequency and peak velocity combination: 0.10 Hz x 12~ 0.10 Hz x 30~ 0.05 Hz x 12~ 0.05 Hz x 30~ 0.01 Hz x 12~ and 0.01 Hz x 30~ Accelerations were administered with 3-minute rest intervals between tests. During the accelerations the animals were in total darkness and the lateral semicircular canals were positioned in a horizontal plane. RECORDINGS. Eye movements as indicated by changes in corneoretinal potential were detected by subcutaneous needle electrodes placed at the lateral canthi. Nystagmic beats were recorded on a Beckman Type R Dynograph using a time constant of 3 seconds and a paper speed of 25 mm/sec.
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EXERCISE AND RECOVERY
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Behavioral activity was assessed by observation of the animal within and outside of the cage. Animals were observed daily for ability to move purposefully. Falling, broad-based gait, and turning of the body or head were noted. EVALUATION. The slow-phase velocity, amplitude of nystagmic beat, frequency of nystagmic beat, and duration of slow-phase velocity were determined for both caloric and sinusoidal acceleration stimuli7 ~ In evaluation of sinusoidal acceleration derived data included the maximum slow-phase velocity of nystagmus and the factor of directional preponderance. These data were deter-
mined by averaging the maximum slow-phase velocity for five consecutive nystagmic beats at peak velocity for the right and then for the left direction. Using the formula: (VL - V~0/(Vb + V~) x 100% where VL and VR represented the average maximum velocities of the slow components of nystagmus in the left and right directions, the directional p r e p o n d e r a n c e was calculated. Theoretically, perfect symmetry corresponded to zero while complete asymmetry was expressed as 100 per cent, For caloric tests, data were expressed in terms
Volume
3
Number
6
November
1982
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EXERCISE AND RECOVERY
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of percentages of canal paresis and directional preponderances. A standard Jongkees formula was utilized for these calculations. :~2
Procedures
American Journal
of Otolaryngology 402
Following selection of subjects, baseline data were obtained for all animals by recording responses to caloric, optokinetic, and sinusoidal acceleration stimuli. Animals were divided into three groups; I) normal, 2) labyrinthectomy, and 3) labyrinthectomy and exercise. All animals were maintained in cages and tested monthly with caloric tests and weekly with sinusoidal acceleration. All animals were tested for at least 23 weeks, and any subject demonstrating incomplete l a b y r i n t h e c t o m y on caloric tests was excluded from the study.
LABYRINTHECTOMY. Labyrinthectomy was performed on alternating right and left ears of animal subjects after intraperitoneal anesthesia with s o d i u m pentobarbital. The i n n e r ear was approached by a postauricular and inferior auricular entry into the bulla a n d exposure of the oval and r o u n d w i n d o w s . The intervening bony partition between the w i n d o w s was removed and a solution of concentrated streptomycin was instilled into the vestibule. The oval w i n d o w round w i n d o w area was covered with Gelfoam and the t y m p a n i c membrane was placed back into its normal position. Prophylactic antibiotics were a d m i n i s t e r e d a n d the a n i m a l s were observed for two weeks in the animal hospital prior to reentry into the study. Normally animals were maintained in cages except during exercise and vestibular tests. EXERCISE. Those animals that were selected for exercise f o l l o w i n g l a b y r i n t h e c t o m y were rested for two weeks following labyrinthectomy. After confirmation of the destruction of the ear with the caloric tests, cats selected for the exercise groups were r e m o v e d from the cages and exercised for at least five days weekly. For eight hours each cat was encouraged to " r o a m " the
RESULTS
Normal N o r m a t i v e data were c o l l e c t e d from four healthy cats not subjected to labyrinthectomy by repetitive caloric testing and sinusoidal acceleration stimuli. The subjects were evaluated individually and as a group for magnitude of nystagmus, symmetry of response, habituation, and differences in responses with changes in the frequency and velocity of the sinusoidal stimuli. The caloric test responses of a typical subject are described in Figure 1. The m a x i m u m slowphase velocities were similar for stimulation of the left and right ears and, with the exception of one test (during week 6), remained quite constant throughout the 23 weeks of testing. The data revealed that the sequence of testing once every week did not produce evidence of habituation. Repetitive testing with sinusoidal acceleration also revealed a stable vestibular response. Regardless of the frequency or order of stimulation, the response was symmetrical (Fig. 2, A and B). The total amplitudes of responses were somewhat variable (Fig. 3, A and B), but there was little, if any, t e n d e n c y toward a reduced response with repetitive testing, as w o u l d be seen with habituation (Fig. 3, A and B).
Labyrinthectomized Animals In three cats, the adequacy of labyrinthectomy was confirmed by repetitive caloric testing, as shown in Figure 4. Directional preponderance was shifted to 100 per cent and m a i n t a i n e d
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throughout the 23 weeks of testing. All cats in this group, and those to be treated with exercise, had to demonstrate this complete lack of response. When labyrinthectomized cats were evaluated by sinusoidal acceleration stimuli (Fig. 5, A and B), regardless of f r e q u e n c y and velocity of s t i m u l i , there w a s c h a r a c t e r i s t i c c o m p l e t e asymmetry for 12 to 14 weeks, followed by gradual recovery. A l t h o u g h the subjects appeared to walk and carry on normally, there was persistent preponderance of approximately 20 per cent. All animals had spontaneous nystagmus for five to six weeks, but this nystagmus
disappeared and was not used to correct any of the data.
Labyrinthectomy and Exercise In the group of three animals that were treated with exercise following l a b y r i n t h e c t o m y the percentage of directional p r e p o n d e r a n c e was markedly altered. As shown in Figure 6A and B, the period of complete asymmetry was shortened and the recovery times were markedly decreased. Recoveries reached 20 per cent directional preponderance at seven to nine weeks and preponderance approached zero. These phe-
Volume 3 Number 6 N o v e m b e r 1982
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EXERCISE AND RECOVERY lO0
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American Jaurnal
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nomena occurred regardless of the frequency and velocity of sinusoidal angular acceleration. A comparison of the average scores between the two groups of labyrinthectomized animals that were treated with and without exercise is shown in Figure 7, A and B. The data can be treated as a model described by the equation y = ae ~, or by taking the natural logarithm of this equation, in y = In a + fiT. The data can then be plotted in linear fashion as shown in Figure 8, and are significantly different. The least-squares t-test was used to analyze statistical significance. With 95 per cent degree of confidence the curve for the exercised group falls at a rate 58 to 70
per cent faster than that for the non-exercised group. The estimated numbers of weeks to almost complete recovery were 26 weeks for the exercised group and 70 weeks for the non-exercised group. It would be expected that without exercise a cat would take 169 per cent more time for recovery.
DISCUSSION
The development of an animal model to create vestibular injury and measure objective parameters of recovery provides an exceptional op-
MATHOG AND PEPPARD
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p o r t u n i t y to s t u d y the relative effectivenesses of v a r i o u s f a c t o r s in a l t e r i n g t h e r e c o v e r y processes. T h e cat as a laboratory a n i m a l is readily available, easy to l a b y r i n t h e c t o m i z e , a n d testable on a repetitive basis by caloric and angular acceleration m e t h o d s . If testing is p e r f o r m e d only o n c e a w e e k , h a b i t u a t i o n is n o t a factor that c o m p l i c a t e s the analysis. As s h o w n b y the data, a general t y p e of exercise will m a r k e d l y affect the r e c o v e r y patterns of the cat. A s s u m i n g t h a t ease of m o t i o n outside the cage and s y m m e t r y of s i n u s o i d a l acceleration are c o n d i t i o n s a p p r o a c h i n g n o r m a l function, exercise can r e d u c e the r e c o v e r y t i m e for a cat that has u n d e r g o n e l a b y r i n t h e c t o m y . R e c o g n i z i n g that exercise is a gross f o r m of
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s t i m u l a t i o n r e q u i r i n g p r o p r i o c e p t i o n , vision, thought, learning, and m a n y other factors, it is difficult to determine the relative effectiveness of each of these factors. M a n y investigators h a v e already noted the i m p o r t a n c e of vision, 21-~4 and learning models have b e e n proposed. 26 Central n e r v o u s system excitation has b e e n shown to be helpful in some studies. 19 It is n o w essential to consider the animal models, to be able to determ i n e the relative effect of each of these factors, and possibly to determine what factors are essential to the recovery process. As in any animal experiments, one m u s t be cautious in the transfer of information from one species to another. Some clinical data suggest that exercise is important, 1,a,~ but, as in m a n y
Volume 3 Number 6 N o v e m b e r 1982
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EXERCISE AND RECOVERY
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Figure 6, Algebraic model curve for the data, demonstrating significantly improved recovery times for exercise-treated labyrlnthectomized animals as compared with the graup without exercise, P < 0.0"1, least-squares t test.
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t r e a t m e n t s t u d i e s , a p p r o p r i a t e c o n t r o l s are l a c k i n g . C o n s i d e r i n g t h a t t h e r e s u l t s of t h e a n i m a l e x p e r i m e n t s s u p p o r t t h e i m p o r t a n c e of exercise, there s h o u l d be m o r e c r e d e n c e i n utilizing such a treatment program in a clinical setting.
10. 11.
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References
American JournaF of O~olaryngology 406
1. Cawthorne T: The physiological basis for head exercises. J Chart Soc Physiother 1945, pp 106-107 2. Cawthorne T: Vestibular injuries. Proc R Sac Med 39:270-273, 1946. 3. McCabe BF: Labyrinthine exercises in the treatment of diseases characterized by vertigo, Their physiologic basis and methodology. Laryngoscope 80:1429-1433, 1970 4. Hocker HC, Haug CO, Herndon ]W: Treatment of the vertiginous patient using Cawthorne's vestibular exercises. Laryngoscope 84:2065-2072, 1974 5. Bradal A: Anatomical observations on the vestibular nuclei with special reference to the relations to the spinal cord and cerebellum. Acta Otolaryngol suppl 192:24-51, 1964 6. Carpenter MB: Central connections of the vestibular system. Arch Otolaryagol 85:517-520, 1963 7. Nyberg-Hasen R: Origin and termination of fibers fl'om the vestibular nuclei descending in the medial longitudinal fasciculus. J Comp Neurol 122:355-364, 1964 8, Gacek RR: The course and central termination of first order neurons supplying vestibular end-organs in the cat, Acta Otolaryngol suppl 254:1-66, 1969 9. Pompeians O, Watberg F: Descending connections to the
13. 14. 15. 16. 17. 18. 19.
20.
vestibular nuclei. An experimental study in the cat. J Camp Neurol 108:465-503, 1957 Gernandt BE: Central regulation of the vestibular system. Arch Otolaryngol 85:521-526, 1967 Precht W, Shimazu H, Markham CH: A mechanism of central compensation of vestibular function following hemilabyrinthectomy. J Neurophysiol 29:996-1010, 1966 Schaefer KP, Meyer DL: Compensation of vestibular lesions, in: Kornhuber HH (ed.): Handbook of Sensory Physiology: Vestibular System, Psychophysics, Applied Aspects and General Interpretations. Volume 6, Part 2. Berlin, Springer, 1975, pp 463-490 Magnus R: K6rperstellung. Berlin, Springer, 1924, pp 740 McCabe BF, Ryu IH, Sekitani T: Further experiments on vestibular compensation, Laryngoscope 82:381-396, 1972 McCabe BF, Ryu JH: Experiment on vestibular compensation. Laryngoscope 79:1728-1736, 1969 Shimazu H, Precht W: Inhibition of central vestibular neurons from the cantralateral labyrinth and its mediating pathway. ] NeurophysioI 29:467-492, 1966 Carpenter MB, Fabrega H, Clinsmann W: Physiological deficits occurring with lesions of labyrinth and fastigial nuclei. J Neurophysiol 22:222-234, 1959 Azzena GB: Role of the spinal cord in compensating the effects of hemilabyrinthectomy. Arch Ital Biol 107:43-53, 1969 Schaefer KP, Meyer DL: Compensatory mechanisms following labyrinthine lesions in the guinea pig, A simple model of learning, in: Zippel HP [ed.): Memory and Transfer of Information. New York, London, Plenum Press, 1973, pp 203-232. DiGiorgio AM: Effetti di lesloni unilaterali delia carteccia cerebrale sui fenomeni di compenso da hemts-
MATHOG AND PEPPARD
21. 22.
23.
24. 25.
26.
labirintazione. Atti Acc Fisiol Fac Med Siena, Set. XI:2:382-384, 1939 Berthoz A, Jeannerod M, Vital-Durand F, e t a h Development of vestibule-ocular responses in visually deprived kittens. Exp Brain Res 23:425-442, 1975 Putkonen PTS, Courjon ]H, Jeannerod M: Compensation of pastural effects of hemilabyrinthectomy in the cat. A sensory substitution process. Exp Brain Res 28:249-257, 1977 Courjen ]H, [eannerod M, Ossuzio I, e t a h The role of visian in compensation of vestibule ocular reflex after hemilabyrinthectamy in the cat. Exp Brain Res 28:235-248, 1977 Jeannarad M, Magnin M, Schmid R, e t a l . Vestibular habituation to anular velocity steps in the cat. Biel Cybernetics 22:39-48, 1976 Ire M: The vestibulo-cerebellar relationships: vestibuleocular reflex arc and flacculus, in: Naunton R (ed.) The Vestibular System, New York, Academic Press, 1975, pp 129-146 Ire M: Cerebellar learning control of vestibule-ocular
27. 28.
29. 30. 31. 32.
mechanisms, in: Desiraju T (ed.): Transmission of Signals for Conscious Behavior Amsterdam, Elsevier, 1976, pp 1-21 Dowd PJ: Responses of the habituated vestibule-ocular reflex arc to drug stress. School Aerospace Medicine Technical Data Report No, 64-72: 1964, pp 1-24 Crampton GH: Habituation of vestibular nystagmus in the cat during sustained arousal produced by Damphetamine. United States Army Medical Research Lab Report No. 488: 1961, pp 1-11 Henriksson NG, Kohut R, Fernandez C: Studies an habituation of vestibular reflexes. I. Effect of repetitive caloric tests, tkcta Otolaryngol 53:338-349, 1961 Buehler B, Kohut RI, King ME: Maxillary fixation for vestibular testing in the cat. Ann Oral Rhinol Laryngol 80:474-475, 1971 Cassel JC, Mathag RH: Variable slope plotter of nystagmic velocity. Arch Otolaryngol 96:185, 1972 Jongkees LB, Philipzoon AJ: Electronystagmography. Acta Otolaryngol suppl 189:54-56, 1963
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Volume 3 Number 6 November 1982
407
Exercise and Recovery from Vestibular Injury ROBERTH. MATHOG,M.D., ANDSmANB. PEPPARB,M.D. Exercise after vestibular injury is potentially an important modality in the recovery process. In this study, the effects of injury on the vestibular system were examined experimentally in cats. Data from healthy normal cats, labyrinthectomized cats, and labyrinthectomized cats treated with exercise were examined. Evaluation of performance was accomplished with caloric, optokinetic, and sinusoidal acceleration testing. Results in normal cats indicated stable, symmetrical vestibular responses on repetitive testing, without evidence for habituation. Comparison of the experimental groups showed that the animals treated with exercise had a significant difference in terms of recovery. The exercised group demonstrated a diminished directional preponderance, a shorter period of complete asymmetry, and a shorter recovery time, which was 58 to 70 per cent faster than that of the non-exercised group. The authors conclude that a general type of exercise will markedly affect and shorten the recovery pattern in the labyrinthectomized cat. (Key words: Exercise; Labyrinthectomy; Vestibular injury.)
In order to afford patients with vestibular disorders the best treatment possible, it is important to understand the basic science of the vestibular system and what methods are available to affect the function of this system. As a result of vestibular injury from trauma or disease, patients will complain of dizziness or vertigo and demonstrate an abnormal nystagmus, but with time the signs and symptoms are usually reduced and there is a tendency toward recovery. It is apparent that if the clinician were to understand fully h o w the patient recovers and what methods facilitate or retard this process, the care of patients with vestibular disorders could be greatly improved. Many factors such as vision, proprioception, and use and disuse of the vestibular system have been implicated in the recovery process, but from a clinical standpoint, exercise has always appeared to be a potentially important modality. Cawthorne 1'' suggested a series of exercises for patients following labyrinthectomy, while others using similar methods have actually recorded salutary effects, a,4 Unfortunately, the From the Department of Otolaryngology,Wayne State University, Schoolof Medicine, Detroit, Michigan.Received May 14, 1982. Accepted for publication July 12, 1982, Supported by a Deafness Research Foundationgrant. Address correspondence and reprint requests to Dr. Peppard: Otolaryngology 5E-UHC, Wayne State University School of Medicine, 540 East Canfield, Detroit, Michigan 48201.
concepts are not universally accepted, and although some patients are treated with exercise programs, many are conversely treated with rest and vestibular suppressant medications. It has been the purpose of this study to evaluate, through a series of experiments, the effects of exercise during the recovery of the vestibular system from injury. An animal model has been developed for the evaluation of factors that can affect the recovery process. Vestibular responses of healthy normal cats to sinusoidal stimuli have been used to establish norms, and vestibular responses after labyrinthectomy have been compared with those of normal animals. Using these two groups as controls for normal and labyrinthectomized responses, labyrinthectomized cats have been sinusoidally stimulated and evaluated after exercise, and any differences in response from the control groups have been used to study the relative beneficial or inhibitory effects of these factors on the recovery process. BACKGROUND An understanding of the vestibular system is complicated by the multiple interactions of the vestibular pathways and other systems in the brain? -9 Connections to the spinal-motor center, thalamus, cerebral cortex, flocculus, nodulus, uvula and fastigial nuclei of the cerebellum, and autonomic centers of the medulla and the midbrain have been identified. It is also well
0i96-070918211100/0397 $02.20 O W, B. Saunders Co. 397
EXERCISE AND RECOVERY
American Journal
of Otolaryngo]ogy 398
k n o w n that vestibular activity can be modified by input from the midbrain, spinal cord, cerebellum, cerebrum, and brainstem, l~ After injury to the labyrinth, many parts of the central nervous system are involved in the recovery processes. It is presumed that a number of biofeedback conditions occur to bring balance back to the system. The classic responses to vestibular injury are well d e s c r i b e d . Labyrinthectomy in various species of animals initially produces spontaneous nystagmus, with the quick component of the rtystagmus directed to the intact side. In cats, Precht et a l " demonstrated that the spontaneous n y s t a g m u s disappeared after three to four days, but w i t h stimuli of acceleration a distinct asymmetric i n d u c e d nystagmus appeared. About 45 days later the asymmetry disappeared, and the animals w e r e thought to have achieved full compensation. B e c h t e r e w demonstrated that compensation after labyrinthectomy is extremely complex. As cited by Schaefer and Meyer,'" Bechterew showed that spontaneous nystagmus gradually disappeared after an initial labyrinthectomy, but when t h e other labyrinth was destroyed a new spontaneous nystagmus appeared to the opposite side. In similar experiments Magnus ~'~ observed that extirpation of a second labyrinth four days after labyrinthectomy had the same effect as w h e n b o t h labyrinths were removed, but if this extirpation were performed after 11 days a nystagmus occurred to the opposite side. These p h e n o m e n a a p p e a r e d to indicate changing neural p a t h w a y s which were trying to compensate for or overcome the deficit. McCabe 3 has attempted to explain the phenomena: normally "the end-organs are frequency modulators of the resting electrical activity or n e u r o n arcs. When a motion of the head stimulates one end-organ, resulting in a modulation of its activity upwards, the same motion results in a modulation downward on the opposite side." Thus, the effects of stimulating the two sides are equal and opposite and balance is obtained. With injury to the vestibular system the events are altered and the balance is upset. Assuming a destruction of one side, the resultant inactivity of that side leads to relative overactivity of the opposite side. To achieve balance again, the relative over-activity must be reduced and/or t h e activity on the injured side be increased. 14 In experiments designed to elucidate how one
area is suppressed while the other is activated, the contributions of various parts of the central nervous system have been studied. ROLE OF VESTIBULAR NUCLEI. According to McCabe et al. ~4,'5 and Precht and associates," the vestibular nuclei are essential for compensating processes. Vestibular nuclei lose neural activity after they lose their afferent nerve supply, but later this activity is regenerated and counteracts the activity of the opposite side. The development of this activity on the deafferentated side was thought to be a result of elimination of tonic inhibitory influences frmn the interneurons from the contralateral labyrinth and its mediating pathway. '" ROLE OF CEREBELLUM. The importance of the cerebellum in controlling these phenomena is also well known. Carpenter et al. '7 demonstrated that nystagmus was increased following labyrinthectomy when the cerebellum, specifically the fastigial nuclei, was damaged. Also, compensation (which occurred w h e n the nystagmus disappeared) was completely abolished by the destruction of fastigial nuclei. McCabe et al. t4'15 also indicated the importance of the cerebellum, noting that the depression of response on the side contralateral to the labyrinth did not occur in the cerebellectomized animal. ROLE OF SPINAL AFFERENTS AND CEREBRUM.
The spinal afferents are also implicated in the compensation mechanism. In the guinea pig, '~''9 interruption of the thoracic segment of the spinal cord provoked the reappearance of nystagmus elicited by a previously destroyed labyrinth. In this species the nystagmus that had faded away returned after disruption of the spinal afferents. Although the cerebral cortex probably plays a minimal role, anatomic pathways for compensation through the reticular formation and cerebellum have been suggested. Also, according to Azzena '~ and DiGiorgio, 2~ once nystagmus disappears following unilateral labyrinthectomy, destruction of the cerebral cortex will cause reappearance of the eye movement. ROLE Or VISION. The interaction of vision has also been described. After removing vision by keeping labyrinthectomized animals in darkness, various investigators have found a delay in body tilt to return to a normal position and aiso a delay in the disappearance of spontaneous nystagmus, '-'1,22 Others have also observed, in additional experiments, persistence of the spontaneous nystagmus if the animals were kept in darkness?-a,'24 The experiments were interpreted
MATHOGAND PEPPARD as showing that vision "conditions disinhibition of vestibular nuclei spontaneous activity after the critical phase of compensation. ''24 Many of the studies have suggested that visual control is mediated through the cerebellum, and it is thought that this mechanism is important for the learning processes and for compensation to take place. Ito 2~,'-'6 has described a simplified model utilizing the flocculus vestibule-ocular system whereby vision can modify and alter the vestibule-ocular reflex. ROLES OF EXCITANT AND DEPRESSANT DRUGS. Drugs that excite or depress the central nervous system must be important, although interaction and control mechanisms for compensation are not entirely clear. Investigations using chronic experiments are lacking, but short-term preparations have demonstrated a delay in or an acceleration of compensation to vestibular injury by administration of drugs. In the guinea pig, phenobarbital delayed compensation three days or more, while amphetamine accelerated the compensation process.'' Dowd 'T and Crampton "8 have demonstrated similar accelerated effects after administration of amphetamine to habituated animals. These findings have suggested that there is a generalized acceleration of compensation through pharmacologic acceleration of synapses and pathways. ROLE OF EXERCISE. In spite of the interest in and studies of various factors that can affect recovery of the vestibular system, reports on the importance of exercise, with its gross stimulations of the central nervous system, are lacking. Several investigators '-4 have described the effects of exercise, but these case studies have been "mixed" and poorly controlled. Failure to develop satisfactory animal models has also retarded investigations of the relative value of exercise in the recovery of the vestibular system. METHODS
Subjects Animals selected for study were adult healthy experimentally naive cats without evidence of ear infections. Four cats served as normal subjects, three cats had unilateral labyrinthectomy without exercise, and three cats had unilateral labyrinthectomy with exercise. The animals were immobilized during the vestibular and optokinetic tests by insertion of piano wire through holes in the canine teeth,
securing the wire to a special restraint box?" Maxillary restraint was used in cases of broken canine teeth2 ~ All tests were conducted in a light-controlled room separated from the recording equipment.
Stimulation OPTOKINETIC STIMULATION. Cats within a restraint box were centered on a Stille-Werner chair and rotated 24~ After one minute allowed for equilibration, induced eye movements were recorded. The recording was adjusted so that "t mm of pen deflection was converted to 10 degrees of eye movement and provided for calibration of eye movement in degrees per mm during other types of tests. These results were confirmed by an optoldnetic drum rotated around the subject at 24~ CALORIC STIMULATION. Caloric stimulation consisted of 1,000 ml of water at 25~ C (+0.5 ~ C) instilled over 30 seconds into the external auditory canal. The caloric test sequence conducted in total darkness was left ear irrigation followed in 15 minutes by irrigation of the right ear, and followed again in 15 minutes by repeat irrigation of the left ear. Experience with these tests indicated that the first stimulation was quite a shock and that subsequent irrigations provided more stable data. SINUSOIDAL STIMULATION. A Stille-Werner rotating chair (Stille-LKB RS-3/22) was used to produce sinusoidal angular acceleration. S i n u s o i d a l stimuli were selected and randomized at frequencies of 0.01 Hz, 0.05 Hz, and 0.10 Hz with peak velocities of 12~ and 30~ sec for each test frequency. According to a system of randomization, each subject received six complete cycles of acceleration at each frequency and peak velocity combination: 0.10 Hz x 12~ 0.10 Hz x 30~ 0.05 Hz x 12~ 0.05 Hz x 30~ 0.01 Hz x 12~ and 0.01 Hz x 30~ Accelerations were administered with 3-minute rest intervals between tests. During the accelerations the animals were in total darkness and the lateral semicircular canals were positioned in a horizontal plane. RECORDINGS. Eye movements as indicated by changes in corneoretinal potential were detected by subcutaneous needle electrodes placed at the lateral canthi. Nystagmic beats were recorded on a Beckman Type R Dynograph using a time constant of 3 seconds and a paper speed of 25 mm/sec.
VoJume 3 Number 6 November 1982 399
EXERCISE AND RECOVERY
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Behavioral activity was assessed by observation of the animal within and outside of the cage. Animals were observed daily for ability to move purposefully. Falling, broad-based gait, and turning of the body or head were noted. EVALUATION. The slow-phase velocity, amplitude of nystagmic beat, frequency of nystagmic beat, and duration of slow-phase velocity were determined for both caloric and sinusoidal acceleration stimuli7 ~ In evaluation of sinusoidal acceleration derived data included the maximum slow-phase velocity of nystagmus and the factor of directional preponderance. These data were deter-
mined by averaging the maximum slow-phase velocity for five consecutive nystagmic beats at peak velocity for the right and then for the left direction. Using the formula: (VL - V~0/(Vb + V~) x 100% where VL and VR represented the average maximum velocities of the slow components of nystagmus in the left and right directions, the directional p r e p o n d e r a n c e was calculated. Theoretically, perfect symmetry corresponded to zero while complete asymmetry was expressed as 100 per cent, For caloric tests, data were expressed in terms
Volume
3
Number
6
November
1982
401
EXERCISE AND RECOVERY
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of percentages of canal paresis and directional preponderances. A standard Jongkees formula was utilized for these calculations. :~2
Procedures
American Journal
of Otolaryngology 402
Following selection of subjects, baseline data were obtained for all animals by recording responses to caloric, optokinetic, and sinusoidal acceleration stimuli. Animals were divided into three groups; I) normal, 2) labyrinthectomy, and 3) labyrinthectomy and exercise. All animals were maintained in cages and tested monthly with caloric tests and weekly with sinusoidal acceleration. All animals were tested for at least 23 weeks, and any subject demonstrating incomplete l a b y r i n t h e c t o m y on caloric tests was excluded from the study.
LABYRINTHECTOMY. Labyrinthectomy was performed on alternating right and left ears of animal subjects after intraperitoneal anesthesia with s o d i u m pentobarbital. The i n n e r ear was approached by a postauricular and inferior auricular entry into the bulla a n d exposure of the oval and r o u n d w i n d o w s . The intervening bony partition between the w i n d o w s was removed and a solution of concentrated streptomycin was instilled into the vestibule. The oval w i n d o w round w i n d o w area was covered with Gelfoam and the t y m p a n i c membrane was placed back into its normal position. Prophylactic antibiotics were a d m i n i s t e r e d a n d the a n i m a l s were observed for two weeks in the animal hospital prior to reentry into the study. Normally animals were maintained in cages except during exercise and vestibular tests. EXERCISE. Those animals that were selected for exercise f o l l o w i n g l a b y r i n t h e c t o m y were rested for two weeks following labyrinthectomy. After confirmation of the destruction of the ear with the caloric tests, cats selected for the exercise groups were r e m o v e d from the cages and exercised for at least five days weekly. For eight hours each cat was encouraged to " r o a m " the
RESULTS
Normal N o r m a t i v e data were c o l l e c t e d from four healthy cats not subjected to labyrinthectomy by repetitive caloric testing and sinusoidal acceleration stimuli. The subjects were evaluated individually and as a group for magnitude of nystagmus, symmetry of response, habituation, and differences in responses with changes in the frequency and velocity of the sinusoidal stimuli. The caloric test responses of a typical subject are described in Figure 1. The m a x i m u m slowphase velocities were similar for stimulation of the left and right ears and, with the exception of one test (during week 6), remained quite constant throughout the 23 weeks of testing. The data revealed that the sequence of testing once every week did not produce evidence of habituation. Repetitive testing with sinusoidal acceleration also revealed a stable vestibular response. Regardless of the frequency or order of stimulation, the response was symmetrical (Fig. 2, A and B). The total amplitudes of responses were somewhat variable (Fig. 3, A and B), but there was little, if any, t e n d e n c y toward a reduced response with repetitive testing, as w o u l d be seen with habituation (Fig. 3, A and B).
Labyrinthectomized Animals In three cats, the adequacy of labyrinthectomy was confirmed by repetitive caloric testing, as shown in Figure 4. Directional preponderance was shifted to 100 per cent and m a i n t a i n e d
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throughout the 23 weeks of testing. All cats in this group, and those to be treated with exercise, had to demonstrate this complete lack of response. When labyrinthectomized cats were evaluated by sinusoidal acceleration stimuli (Fig. 5, A and B), regardless of f r e q u e n c y and velocity of s t i m u l i , there w a s c h a r a c t e r i s t i c c o m p l e t e asymmetry for 12 to 14 weeks, followed by gradual recovery. A l t h o u g h the subjects appeared to walk and carry on normally, there was persistent preponderance of approximately 20 per cent. All animals had spontaneous nystagmus for five to six weeks, but this nystagmus
disappeared and was not used to correct any of the data.
Labyrinthectomy and Exercise In the group of three animals that were treated with exercise following l a b y r i n t h e c t o m y the percentage of directional p r e p o n d e r a n c e was markedly altered. As shown in Figure 6A and B, the period of complete asymmetry was shortened and the recovery times were markedly decreased. Recoveries reached 20 per cent directional preponderance at seven to nine weeks and preponderance approached zero. These phe-
Volume 3 Number 6 N o v e m b e r 1982
403
EXERCISE AND RECOVERY lO0
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nomena occurred regardless of the frequency and velocity of sinusoidal angular acceleration. A comparison of the average scores between the two groups of labyrinthectomized animals that were treated with and without exercise is shown in Figure 7, A and B. The data can be treated as a model described by the equation y = ae ~, or by taking the natural logarithm of this equation, in y = In a + fiT. The data can then be plotted in linear fashion as shown in Figure 8, and are significantly different. The least-squares t-test was used to analyze statistical significance. With 95 per cent degree of confidence the curve for the exercised group falls at a rate 58 to 70
per cent faster than that for the non-exercised group. The estimated numbers of weeks to almost complete recovery were 26 weeks for the exercised group and 70 weeks for the non-exercised group. It would be expected that without exercise a cat would take 169 per cent more time for recovery.
DISCUSSION
The development of an animal model to create vestibular injury and measure objective parameters of recovery provides an exceptional op-
MATHOG AND PEPPARD
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p o r t u n i t y to s t u d y the relative effectivenesses of v a r i o u s f a c t o r s in a l t e r i n g t h e r e c o v e r y processes. T h e cat as a laboratory a n i m a l is readily available, easy to l a b y r i n t h e c t o m i z e , a n d testable on a repetitive basis by caloric and angular acceleration m e t h o d s . If testing is p e r f o r m e d only o n c e a w e e k , h a b i t u a t i o n is n o t a factor that c o m p l i c a t e s the analysis. As s h o w n b y the data, a general t y p e of exercise will m a r k e d l y affect the r e c o v e r y patterns of the cat. A s s u m i n g t h a t ease of m o t i o n outside the cage and s y m m e t r y of s i n u s o i d a l acceleration are c o n d i t i o n s a p p r o a c h i n g n o r m a l function, exercise can r e d u c e the r e c o v e r y t i m e for a cat that has u n d e r g o n e l a b y r i n t h e c t o m y . R e c o g n i z i n g that exercise is a gross f o r m of
2
4 6 8 Time (Weeks)
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12
14
16
18
20
22
24
s t i m u l a t i o n r e q u i r i n g p r o p r i o c e p t i o n , vision, thought, learning, and m a n y other factors, it is difficult to determine the relative effectiveness of each of these factors. M a n y investigators h a v e already noted the i m p o r t a n c e of vision, 21-~4 and learning models have b e e n proposed. 26 Central n e r v o u s system excitation has b e e n shown to be helpful in some studies. 19 It is n o w essential to consider the animal models, to be able to determ i n e the relative effect of each of these factors, and possibly to determine what factors are essential to the recovery process. As in any animal experiments, one m u s t be cautious in the transfer of information from one species to another. Some clinical data suggest that exercise is important, 1,a,~ but, as in m a n y
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EXERCISE AND RECOVERY
I
Figure 6, Algebraic model curve for the data, demonstrating significantly improved recovery times for exercise-treated labyrlnthectomized animals as compared with the graup without exercise, P < 0.0"1, least-squares t test.
+
t}
5
I0
15 20 25 30 35 40 45 50 55 6Q 65 70 75 80 B5 90 Time (Weeks)
t r e a t m e n t s t u d i e s , a p p r o p r i a t e c o n t r o l s are l a c k i n g . C o n s i d e r i n g t h a t t h e r e s u l t s of t h e a n i m a l e x p e r i m e n t s s u p p o r t t h e i m p o r t a n c e of exercise, there s h o u l d be m o r e c r e d e n c e i n utilizing such a treatment program in a clinical setting.
10. 11.
12.
References
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1. Cawthorne T: The physiological basis for head exercises. J Chart Soc Physiother 1945, pp 106-107 2. Cawthorne T: Vestibular injuries. Proc R Sac Med 39:270-273, 1946. 3. McCabe BF: Labyrinthine exercises in the treatment of diseases characterized by vertigo, Their physiologic basis and methodology. Laryngoscope 80:1429-1433, 1970 4. Hocker HC, Haug CO, Herndon ]W: Treatment of the vertiginous patient using Cawthorne's vestibular exercises. Laryngoscope 84:2065-2072, 1974 5. Bradal A: Anatomical observations on the vestibular nuclei with special reference to the relations to the spinal cord and cerebellum. Acta Otolaryngol suppl 192:24-51, 1964 6. Carpenter MB: Central connections of the vestibular system. Arch Otolaryagol 85:517-520, 1963 7. Nyberg-Hasen R: Origin and termination of fibers fl'om the vestibular nuclei descending in the medial longitudinal fasciculus. J Comp Neurol 122:355-364, 1964 8, Gacek RR: The course and central termination of first order neurons supplying vestibular end-organs in the cat, Acta Otolaryngol suppl 254:1-66, 1969 9. Pompeians O, Watberg F: Descending connections to the
13. 14. 15. 16. 17. 18. 19.
20.
vestibular nuclei. An experimental study in the cat. J Camp Neurol 108:465-503, 1957 Gernandt BE: Central regulation of the vestibular system. Arch Otolaryngol 85:521-526, 1967 Precht W, Shimazu H, Markham CH: A mechanism of central compensation of vestibular function following hemilabyrinthectomy. J Neurophysiol 29:996-1010, 1966 Schaefer KP, Meyer DL: Compensation of vestibular lesions, in: Kornhuber HH (ed.): Handbook of Sensory Physiology: Vestibular System, Psychophysics, Applied Aspects and General Interpretations. Volume 6, Part 2. Berlin, Springer, 1975, pp 463-490 Magnus R: K6rperstellung. Berlin, Springer, 1924, pp 740 McCabe BF, Ryu IH, Sekitani T: Further experiments on vestibular compensation, Laryngoscope 82:381-396, 1972 McCabe BF, Ryu JH: Experiment on vestibular compensation. Laryngoscope 79:1728-1736, 1969 Shimazu H, Precht W: Inhibition of central vestibular neurons from the cantralateral labyrinth and its mediating pathway. ] NeurophysioI 29:467-492, 1966 Carpenter MB, Fabrega H, Clinsmann W: Physiological deficits occurring with lesions of labyrinth and fastigial nuclei. J Neurophysiol 22:222-234, 1959 Azzena GB: Role of the spinal cord in compensating the effects of hemilabyrinthectomy. Arch Ital Biol 107:43-53, 1969 Schaefer KP, Meyer DL: Compensatory mechanisms following labyrinthine lesions in the guinea pig, A simple model of learning, in: Zippel HP [ed.): Memory and Transfer of Information. New York, London, Plenum Press, 1973, pp 203-232. DiGiorgio AM: Effetti di lesloni unilaterali delia carteccia cerebrale sui fenomeni di compenso da hemts-
MATHOG AND PEPPARD
21. 22.
23.
24. 25.
26.
labirintazione. Atti Acc Fisiol Fac Med Siena, Set. XI:2:382-384, 1939 Berthoz A, Jeannerod M, Vital-Durand F, e t a h Development of vestibule-ocular responses in visually deprived kittens. Exp Brain Res 23:425-442, 1975 Putkonen PTS, Courjon ]H, Jeannerod M: Compensation of pastural effects of hemilabyrinthectomy in the cat. A sensory substitution process. Exp Brain Res 28:249-257, 1977 Courjen ]H, [eannerod M, Ossuzio I, e t a h The role of visian in compensation of vestibule ocular reflex after hemilabyrinthectamy in the cat. Exp Brain Res 28:235-248, 1977 Jeannarad M, Magnin M, Schmid R, e t a l . Vestibular habituation to anular velocity steps in the cat. Biel Cybernetics 22:39-48, 1976 Ire M: The vestibulo-cerebellar relationships: vestibuleocular reflex arc and flacculus, in: Naunton R (ed.) The Vestibular System, New York, Academic Press, 1975, pp 129-146 Ire M: Cerebellar learning control of vestibule-ocular
27. 28.
29. 30. 31. 32.
mechanisms, in: Desiraju T (ed.): Transmission of Signals for Conscious Behavior Amsterdam, Elsevier, 1976, pp 1-21 Dowd PJ: Responses of the habituated vestibule-ocular reflex arc to drug stress. School Aerospace Medicine Technical Data Report No, 64-72: 1964, pp 1-24 Crampton GH: Habituation of vestibular nystagmus in the cat during sustained arousal produced by Damphetamine. United States Army Medical Research Lab Report No. 488: 1961, pp 1-11 Henriksson NG, Kohut R, Fernandez C: Studies an habituation of vestibular reflexes. I. Effect of repetitive caloric tests, tkcta Otolaryngol 53:338-349, 1961 Buehler B, Kohut RI, King ME: Maxillary fixation for vestibular testing in the cat. Ann Oral Rhinol Laryngol 80:474-475, 1971 Cassel JC, Mathag RH: Variable slope plotter of nystagmic velocity. Arch Otolaryngol 96:185, 1972 Jongkees LB, Philipzoon AJ: Electronystagmography. Acta Otolaryngol suppl 189:54-56, 1963
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