Journal of Vestibular Research

Recent anatomical studies have identified a network of central neural circuits that appear to integrate vestibular and autonomic information. Like vestibulo-ocular and vestibulospinal circuits, these pathways appear to be under inhibitory modulation by distinct regions in the medial aspect of the cerebellar cortex. These central circuits have the potential to explain the known influence of vestibular stimulation on autonomic motor responses through descending effects on brain stem autonomic regions. In a more global context, the extensive convergence of vestibular and autonomic information in both vestibular and autonomic brain regions is consistent with the concept that vestibular and visceral information (for example, blood pooling and visceral proprioception) are used to form a central representation of gravitoinertial parameters during movements. This representation can influence neural circuitry involved in postural control, cardiovascular control, perception of the spatial vertical and emotional or affective responses.

Electrical or natural stimulation of the vestibular system results in changes in blood pressure and respiratory motor output. An increase in excitatory drive on the sympathetic nervous system occurs during nose-up vestibular stimulation in cats; this response is appropriate to offset orthostatic hypotension that could result from nose-up body rotations during movements such as vertical climbing. In addition, transection of the vestibular nerves in anesthetized or awake cats compromises the ability to correct decreases in blood pressure that result from nose-up body tilt. The vestibular system also has influences on respiratory muscles; these effects are appropriate to participate in making adjustments in the activity of respiratory muscles that are necessary to offset mechanical constraints on these muscles that occur during changes in body position. These data thus suggest that the influences of the vestibular system on the autonomic and respiratory systems serve to maintain homeostasis during movement.

The vestibular system, including both the peripheral vestibular system, that is, the labyrinth, and the central vestibular system, is known to influence autonomic function in several ways that have clinical implications. This paper discusses evidence for vestibular influences on autonomic control from normal human subjects, evidence for vestibular influences on autonomic control from patients, clinical implications of vestibulo-autonomic regulation, and speculations regarding possible clinical implications of vestibulo-autonomic control. Situations that provoke vestibular-induced autonomic responses in normal subjects include vestibular laboratory testing, vehicular motion, simulators, and, possibly, exposure to microgravity. Patients with peripheral and central vestibular abnormalities manifest both symptoms and signs of autonomic dysfunction presumably via vestibulo-autonomic connections. Vestibulo-autonomic regulation impacts vestibular diagnostic testing, clinical diagnosis of balance disorders, and treatment of balance disorders. In addition to well-recognized peripheral and central vestibular disorders, anxiety disorders have recently been linked to vestibular dysfunction in a subset of patients. In particular, vestibular dysfunction has been linked to panic disorder and agoraphobia. Vestibular-autonomic connections may form a basis for an association between vestibular dysfunction and panic attacks. The importance of vestibulo-autonomic regulation in the clinical arena is not fully known. Two speculative areas discussed in this paper include vestibular-induced orthostatic intolerance and the role of vestibular-respiratory pathways on sleep apnea.

There is substantial evidence that anatomical connections exist between vestibular and autonomic nuclei. Animal studies have shown functional interactions between the vestibular and autonomic systems. The nature of these interactions, however, is complex and has not been fully defined. Vestibular stimulation has been consistently found to reduce blood pressure in animals. Given the potential interaction between vestibular and autonomic pathways this finding could be explained by a reduction in sympathetic activity. However, rather than sympathetic inhibition, vestibular stimulation has consistently been shown to increase sympathetic outflow in cardiac and splanchnic vascular beds in most experimental models. Several clinical observations suggest that a link between vestibular and autonomic systems may also exist in humans. However, direct evidence for vestibular/autonomic interactions in humans is sparse. Motion sickness has been found to induce forearm vasodilation and reduce baro-reflex gain, and head down neck flexion induces transient forearm and calf vasoconstriction. On the other hand, studies using optokinetic stimulation have found either very small, variable, or inconsistent changes in heart rate and blood pressure, despite substantial symptoms of motion sickness. Furthermore, caloric stimulation severe enough to produce nystagmus, dizziness, and nausea had no effect on sympathetic nerve activity measured directly with microneurography. No effect was observed on heart rate, blood pressure, or plasma norepinephrine. Several factors may explain the apparent discordance of these results, but more research is needed before we can define the potential importance of vestibular input to cardiovascular regulation and orthostatic tolerance in humans.

The carotid-cardiac baroreflex contributes to the prediction of orthostatic tolerance; experimental attenuation of the reflex response leads to orthostatic hypotension in humans and animals. Anecdotal observations indicate that rotational head movements about the vertical axis of the body can also induce orthostatic bradycardia and hypotension through increased parasympathetic activity. We therefore measured the chronotropic response to carotid baroreceptor stimulation in 12 men during varying conditions of vestibulo-oculomotor stimulation to test the hypothesis that stimulation of the semicircular canals associated with head movements in the yaw plane inhibits cardioacceleration through a vagally mediated baroreflex. Carotid-cardiac baroreflex response was assessed by plotting R-R intervals (ms) at each of 8 neck pressure steps with their respective carotid distending pressures (mmHg). Calculated baroreflex gain (maximal slope of the stimulus-response relationship) was measured under 4 experimental conditions: 1) sinusoidal whole-body yaw rotation of the subject in the dark without visual fixation (combined vestibular-oculomotor stimulation); 2) yaw oscillation of the subject while tracking a small head-fixed light moving with the subject (vestibular stimulation without eye movements); 3) subject stationary while fixating on a small light oscillating in yaw at the same frequency, peak acceleration, and velocity as the chair (eye movements without vestibular stimulation); and 4) subject stationary in the dark (no eye or head motion). Head motion alone and with eye movement reduced baseline baroreflex responsiveness to the same stimulus by 30%. Inhibition of cardioacceleration during rotational head movements may have significant impact on functional performance in aerospace environments, particularly in high-performance aircraft pilots during high angular acceleration in aerial combat maneuvers or in astronauts upon return from spaceflight who already have attenuated baroreflex functions.

Inflight and post-landing “immunity” to the “coriolis sickness susceptibility test”, observed during the Skylab M131 experiment, suggests that the otolith organs play a major role in space motion sickness (SMS). This view is supported by the report that ocular counter-torsion asymmetries correlate with SMS incidence and severity. Further data indicate that sensory-motor adaptation to microgravity includes a process whereby central interpretation of otolith signals is biased from “tilt” toward translation. However, unexpected responses to linear acceleration suggest the importance of graviceptors distributed throughout the body in addition to the vestibular otolith organs. Research is needed to assess distributed graviceptor effects.

Space motion sickness is a well-recognized problem for space flight and affects 73% of crewmembers on the first 2 or 3 days of their initial flight. Illness severity is variable, but over half of cases are categorized as moderate to severe. Management has included elimination of provocative activities and delay of critical performance-related procedures such as extra-vehicular activity (EVA) or Shuttle landing during the first three days of missions. Pharmacological treatment strategies have had variable results, but intramuscular promethazine has been the most effective to date with a 90% initial response rate and important reduction in residual symptoms the next flight day. Oral prophylactic treatment of crewmembers with difficulty on prior flights has had mixed results. In order to accommodate more aggressive pharmacologic management, crew medical officers receive additional training in parenteral administration of medications. Preflight medication testing is accomplished to reduce the risk of unexpected performance decrements or idiosyncratic reactions. When possible, treatment is offered in the presleep period to mask potential treatment-related drowsiness. Another phenomenon noted by crewmembers and physicians as flights have lengthened is readaptation difficulty or motion sickness on return to Earth. These problems have included nausea, vomiting, and difficulty with locomotion or coordination upon early exposure to gravity. Since landing and egress are principal concerns during this portion of the flight, these deficits are of operational concern. Postflight therapy has been directed at nausea and vomiting, and meclizine and promethazine are the principal agents used. There has been no official attempt at prophylactic treatment prior to entry. Since there is considerable individual variation in postflight deficit and since adaptation from prior flights seems to persist, it has been recommended that commanders with prior shuttle landing experience be named to flights of extended duration.

Precise regulatory signals are required in order to adjust the cardiovascular and respiratory systems to meet the demands of exercise. Two neural mechanisms, central command and a reflex originating in contracting muscles, are known to play a large role in exercise-associated adjustments in cardiovascular and respiratory activity. The extent to which other regulatory reflexes, such as vestibulo-autonomic reflexes, are able to impact upon the cardiovascular and respiratory systems during exercise is largely unknown. Further, brain regions that may integrate these control mechanisms are only starting to be investigated. We propose that medullary brain nuclei may integrate both exercise and vestibular signals to produce a more coordinated, and therefore efficient, means of adaptation to exercise in a gravitational environment.

Optimal human performance depends upon integrated sensorimotor and cognitive functions, both of which are known to be exquisitely sensitive to loss of sleep. Under the microgravity conditions of space flight, adaptation of both sensorimotor (especially vestibular) and cognitive functions (especially orientation) must occur quickly-and be maintained-despite any concurrent disruptions of sleep that may be caused by microgravity itself, or by the uncomfortable sleeping conditions of the spacecraft. It is the three-way interaction between sleep quality, general work efficiency, and sensorimotor integration that is the subject of this paper and the focus of new work in our laboratory. To record sleep under field conditions including microgravity, we utilize a novel system called the Nightcap that we have developed and extensively tested on normal and sleep-disordered subjects. To perturb the vestibular system in ground-based studies, we utilize a variety of experimental conditions including optokinetic stimulation and both minifying and reversing goggle paradigms that have been extensively studied in relation to plasticity of the vestibulo-ocular reflex. Using these techniques we will test the hypothesis that vestibular adaptation both provokes and is enhanced by REM sleep under both ground-based and space conditions. In this paper we describe preliminary results of some of our studies.

In a study of 18 human subjects, we applied a new technique, estimation of the transfer function between instantaneous lung volume (ILV) and instantaneous heart rate (HR), to assess autonomic activity during motion sickness. Two control recordings of ILV and electrocardiogram (ECG) were made prior to the development of motion sickness. During the first, subjects were seated motionless, and during the second they were seated rotating sinusoidally about an earth vertical axis. Subjects then wore prism goggles that reverse the left-right visual field and performed manual tasks until they developed moderate motion sickness. Finally, ILV and ECG were recorded while subjects maintained a relatively constant level of sickness by intermittent eye closure during rotation with the goggles. Based on analyses of ILV to HR transfer functions from the three conditions, we were unable to demonstrate a change in autonomic control of heart rate due to rotation alone or due to motion sickness. These findings do not support the notion that moderate motion sickness is manifested as a generalized autonomic response.

Responses to linear accelerations in the earth-horizontal plane (typically provoked by tilts of the head or body) are characterized by a stimulus direction that produces the maximal excitation. Although changes in cardiovascular, sympathetic, and respiratory outflow are maximized during pitch, no collection of central vestibular neurons had been identified where pitch responses predominate. In the present study, response properties of neurons in the medial vestibular nucleus were examined in decerebrate cats placed on a turntable. Activation of otolith afferents was provided by constant velocity rotation with the turntable axis tilted 5° from the vertical. Responsive neurons exhibited a sinusoidal modulation in their tiring rate; the optimal excitatory stimulus direction was derived from responses to clockwise and counterclockwise rotations. Many of these neurons were also tested for input from horizontal semicircular canals using 0.5 Hz sinusoidal rotation about an earth-vertical axis. Of 22 tilt-sensitive neurons in the medial vestibular nucleus whose optimal stimulus direction was determined, 9 were best stimulated by pitch, 10 by stimuli in one of the two vertical semicircular canal planes, and 3 by roll. Of the 33 neurons in this nucleus tested for possible convergent inputs from the otolith organs and the horizontal semicircular canals, 8 responded to both the constant velocity (otolith) stimulus and to the sinusoidal rotation, 7 appeared to receive otolith, but not horizontal canal, input, while 18 had a canal, but no otolith, response. Thus, besides serving as a relay for horizontal canal signals, the medial vestibular nucleus may also be an important relay for information about orientation within the sagittal (pitch) plane.