Vestibular Modulation of Sympathetic Nerve Activity to Muscle and Skin in Humans

Abstract

We review the existence of vestibulosympathetic reflexes in humans. While several methods to activate the human vestibular apparatus have been used, galvanic vestibular stimulation (GVS) is a means of selectively modulating vestibular afferent activity via electrodes over the mastoid processes, causing robust vestibular illusions of side-to-side movement. Sinusoidal GVS (sGVS) causes partial entrainment of sympathetic outflow to muscle and skin. Modulation of muscle sympathetic nerve activity (MSNA) from vestibular inputs competes with baroreceptor inputs, with stronger temporal coupling to the vestibular stimulus being observed at frequencies remote from the cardiac frequency; "super entrainment" was observed in some individuals. Low-frequency (<0.2 Hz) sGVS revealed two peaks of modulation per cycle, with bilateral recordings of MSNA or skin sympathetic nerve activity, providing evidence of lateralization of sympathetic outflow during vestibular stimulation. However, it should be noted that GVS influences the firing of afferents from the entire vestibular apparatus, including the semicircular canals. To identify the specific source of vestibular input responsible for the generation of vestibulosympathetic reflexes, we used low-frequency (<0.2 Hz) sinusoidal linear acceleration of seated or supine subjects to, respectively, target the utricular or saccular components of the otoliths. While others had discounted the semicircular canals, we showed that the contributions of the utricle and saccule to the vestibular modulation of MSNA are very similar. Moreover, that modulation of MSNA occurs at accelerations well below levels at which subjects are able to perceive any motion indicates that, like vestibulospinal control of posture, the vestibular system contributes to the control of blood pressure through potent reflexes in humans.

Keywords: galvanic vestibular stimulation; linear acceleration; muscle sympathetic nerve activity; skin sympathetic nerve activity; vestibular system; vestibulosympathetic reflexes.

Figure 1

Spontaneous muscle sympathetic nerve activity (MSNA) presented as the filtered neurogram (nerve) and as an RMS-processed signal (RMS nerve), shown with ECG at rest (A) and during sinusoidal GVS (sGVS) at 0.5 Hz (B–D). Each panel spans a 4 s period. (B–D) Consecutive sequences obtained during sGVS at 0.5 Hz to illustrate the coupling of MSNA to the ECG and to the vestibular input. The rectangles illustrate the relationship between the sympathetic burst and the cardiac rhythm (c) and the vestibular rhythm (v). Reproduced with permission from Bent et al. (46).

Figure 2

Experimental records of muscle sympathetic nerve activity (MSNA) from one subject during sinusoidal GVS (sGVS) at 0.8 Hz, showing super entrainment of MSNA to the sinusoidal vestibular input. The highlighted section in panel (A) is shown expanded in panel (B). (C) Delivery of sGVS to the shoulders (anode on right shoulder, cathode on left). Reproduced with permission from Macefield and James (47).

Figure 3

(A) Cross-correlation histograms of the relationship between muscle sympathetic nerve activity (MSNA) and R-waves of the ECG (white histogram) and autocorrelogram of the ECG (black histogram). (B,C) Cross-correlation histograms between ECG and sinusoidal GVS (sGVS) and respiration (inspiratory peaks) and sGVS. A 0.5 Hz sine wave has been superimposed on the histogram to illustrate the timing of the galvanic vestibular stimulation; it has been inverted for clarity. (D,E) Cross-correlation histograms of MSNA with respect to the vestibular input (GVS), in white, or to a control sine wave (control), in black. Data in panels (A–D) are from the same subject represented in Figure 1; data in panel (E) were obtained from another subject. 20 ms bins in all panels. n = the numbers of counts comprising the histograms. Reproduced with permission from Bent et al. (46).

Figure 4

Cross-correlation histograms between muscle sympathetic nerve activity and sinusoidal GVS in one subject. The thick curve superimposed on the histograms is the smoothed polynomial that was fitted to the data. The sinusoid above represents the galvanic stimulus, delivered at (A) 0.08, (B) 0.13, and (C) 0.18 Hz. Each cross-correlation histogram shows a large peak of modulation (primary peak), associated with the positive peak of the sinusoid, and a smaller peak (secondary peak). The secondary peak was largest at 0.08 Hz and smallest at 0.18 Hz. Reproduced with permission from Hammam et al. (51).

Figure 5

Modulation indices of primary peak of skin sympathetic nerve activity during sinusoidal GVS at different frequencies as a function of whether or not subjects reported nausea. It can be seen that modulation indices were higher in those subjects who reported nausea. Reproduced with permission from Hammam et al. (52).

Figure 6

Bilateral recordings of muscle sympathetic nerve activity, together with ECG, blood pressure, and respiration, during sinusoidal GVS (galvanic vestibular stimulation) at 0.08 Hz in one subject. Overall, sympathetic outflow was similar between the two sides, but close inspection revealed subtle differences. In the expanded sections, the sympathetic bursts have been shifted back 1.25 s in time to account for peripheral conduction delays, allowing those bursts aligned with the cardiac cycle (“c”) or vestibular stimulus (“v”) to be identified. Reproduced with permission from El Sayed et al. (58).

Figure 7

Mean ± SE modulation indices for the primary (dark gray) and secondary (light gray) peaks of modulation of muscle sympathetic nerve activity. Data obtained from 10 subjects. Reproduced with permission from El Sayed et al. (58).

Figure 8

Percentage correct (mean ± SE) detection of motion, and correct detection of the direction of motion, for 16 subjects exposed to sinusoidal linear acceleration at a constant rate of 0.2 Hz but at accelerations ranging from 1.25 to 30 mG. Semi-logarithmic plot of data from 2.5 to 30 mG, with fitted sigmoidal curves shown superimposed. Reproduced with permission from Hammam et al. (74).

Figure 9

Cross-correlation histogram between muscle sympathetic nerve activity and acceleration in the anteroposterior direction for one subject exposed to accelerations of 1.25 mG (A) and 30 mG (B). The histograms have been fitted with a smoothed polynomial. The superimposed sinusoid schematically represents the acceleration profile of the platform: motion in the forward direction is indicated by the positive phase of the sinusoid, which includes the period of acceleration before the peak and deceleration after the peak. Reproduced with permission from Hammam et al. (74).

Figure 10

Mean vestibular (A) and cardiac (B) modulation indices of muscle sympathetic nerve activity as a function of acceleration amplitude; 0 mG = static condition (vestibular modulation = 0 in the absence of a sinusoidal vestibular input). Mean ± SE data from 13 subjects. Reproduced with permission from Hammam et al. (74).

Figure 11

Mean modulation indices (see Methods) calculated from the cross-correlation histograms between muscle sympathetic nerve activity (MSNA) and ECG at rest (cardiac), MSNA and neck angle during sinusoidal neck displacement (neck) and between MSNA and ECG during sinusoidal neck displacement (cardiac + neck). Neck modulation of MSNA was significantly lower than cardiac modulation at rest and cardiac modulation was significantly lower during neck stimulation. *P < 0.05; ***P < 0.001. Reproduced with permission from Bolton et al. (79).