Physiological studies of the vestibulosympathetic reflex in humans

I have previously shown that sinusoidal galvanic vestibular stimulation (sGVS), a means of selectively modulating vestibular afferent activity, can cause partial entrainment of sympathetic outflow to muscle and skin in human subjects. However, GVS influences the firing of afferents from the entire vestibular apparatus, including the semicircular canals. To further identify the source of vestibular input in the generation of vestibulosympathetic reflexes, I conducted a series of studies using sinusoidal linear acceleration of seated subjects (head vertical) to physiologically stimulate the vestibular system. In Study I & II, I tested the hypotheses that selective activation of one set of otolithic organs - those located in the utricle, which are sensitive to displacement in the horizontal axis - could entrain muscle sympathetic nerve activity (MSNA) and skin sympathetic nerve activity (SSNA). Cross-correlation analysis revealed for the 10 subjects in Study I a marked entrainment of SSNA for all types of movements: vestibular modulation was 97±3 % for movements in the X-axis and 91±5 % for displacements in the Y-axis. Furthermore, Study II revealed partial entrainment of MSNA to the sinusoidal stimulus: vestibular modulation was 32±3 % for displacements in the X-axis and 29±3 % in the Y-axis; these were significantly smaller than those evoked in SSNA. In addition, in Study III I examined the capacity for the vestibular utricle to modulate muscle sympathetic nerve activity (MSNA) during sinusoidal linear acceleration at amplitudes below perceptual threshold. Subjects (n=16) were exposed to a range of amplitudes presented in a quasi-random order (1.25, 2.5, 5, 10, 20 and 30 mG), at a constant frequency of 0.2 Hz. Cross-correlation analysis revealed potent sinusoidal modulation of MSNA even at accelerations subjects could not perceive (1.25-5 mG). The modulation index showed a positive linear increase with acceleration amplitude, such that the modulation was significantly higher (25.3 ± 3.7 %) at 30 mG than at 1.25 mG (15.5 ± 1.2 %). Finally, in Study IV I sought to better understand how the brain differentiates between head-only movements that do not require changes in vasomotor tone in the lower limbs from body movements that do require vasomotor changes. As a result, I tested the hypothesis that neck movements modulate MSNA in the lower limbs of humans. Subjects (n=10) lay supine, at rest, during sinusoidal stretching of neck muscles (100 cycles, 35o peak to peak at 0.37 ± 0.02 Hz) and during a ramp-and-hold (17.5o for 54 ± 9 s) static neck muscle stretch, while their heads were held fixed in space. Cross-correlation analysis revealed cyclical modulation of MSNA during sinusoidal neck muscle stretch (modulation index 45.4 ± 5.3%), which was significantly less than the cardiac modulation of MSNA at rest (78.7 ± 4.2%). Overall, by using slow sinusoidal physiological stimuli, evidence accumulated throughout my doctoral candidature emphasizes the role of the utricle, through the vestibulosympathetic reflex, in control of the peripheral vasculature. Moreover, these vestibulosympathetic reflexes can be evoked below perceptual threshold. In addition, through dynamic stimuli of neck proprioceptors my findings also indicate that sensory endings in the neck, as well as vestibular inputs, contribute to cardiovascular control in awake humans via their projections to the vestibular nuclei