Frequency-dependent modulation of muscle sympathetic nerve activity by sinusoidal galvanic vestibular stimulation in human subjects

We have previously demonstrated that selective modulation of vestibular inputs, via sinusoidal galvanic vestibular stimulation (GVS) delivered at 0.5–0.8 Hz, can cause partial entrainment of muscle sympathetic nerve activity (MSNA). Given that we had seen interaction between the dynamic vestibular input and the normal cardiac-locked MSNA rhythm, we tested the hypothesis that frequencies of GVS remote from the cardiac frequency would cause a greater modulation of MSNA than those around the cardiac frequency. Bipolar binaural sinusoidal GVS (±2 mA, 200 cycles) was applied to the mastoid processes in 11 seated subjects at frequencies of 0.2, 0.5, 0.8, 1.1, 1.4, 1.7 and 2.0 Hz. In all subjects, the stimulation evoked robust vestibular illusions of “rocking in a boat” or “swinging from side to side.” Cross-correlation analysis revealed a cyclic modulation of MSNA at all frequencies, with the modulation index being similar between 1.1 Hz (78.5 ± 3.7%) and 2.0 Hz (77.0 ± 4.3%). However, vestibular modulation of MSNA was significantly stronger at 0.2 Hz (93.1 ± 1.7%) and significantly weaker at 0.8 Hz (67.2 ± 1.8%). The former suggests that low-frequency changes in vestibular input, such as those associated with postural changes, preferentially modulate MSNA; the latter suggests that vestibular inputs compete with the stronger baroreceptor inputs operating at the cardiac rhythm (~0.8 Hz), with vestibular modulation of MSNA being greater when this competition with the baroreceptors is reduced.     

Sinusoidal galvanic vestibular stimulation (sGVS) induces a vasovagal response in the rat

Blood pressure (BP) and heart rate (HR) were studied in isoflurane-anesthetized Long-Evans rats during sinusoidal galvanic vestibular stimulation (sGVS) and sinusoidal oscillation in pitch to characterize vestibular influences on autonomic control of BP and HR. sGVS was delivered binaurally via Ag/AgCl needle electrodes inserted over the mastoids at stimulus frequencies 0.008–0.4 Hz. Two processes affecting BP and HR were induced by sGVS: 1) a transient drop in BP (≈15–20 mmHg) and HR (≈3 beat*s⁻¹), followed by a slow recovery over 1–6 min; and 2) inhibitory modulations in BP (≈4.5 mmHg/g) and HR (≈0.15 beats*s⁻¹/g) twice in each stimulus cycle. The BP and HR modulations were approximately in-phase with each other and were best evoked by low stimulus frequencies. A wavelet analysis indicated significant energies in BP and HR at scales related to twice and four times the stimulus frequency bands. BP and HR were also modulated by oscillation in pitch at frequencies 0.025–0.5 Hz. Sensitivities at 0.025 Hz were ≈4.5 mmHg/g (BP) and ≈0.17 beat*s⁻¹/g (HR) for pitches of 20–90°. The tilt-induced BP and HR modulations were out-of-phase, but the frequencies at which responses were elicited by tilt and sGVS were the same. The results show that the sGVS-induced responses, which likely originate in the otolith organs, can exert a powerful inhibitory effect on both BP and HR at low frequencies. These responses have a striking resemblance to human vasovagal responses. Thus, sGVS-activated rats can potentially serve as a useful experimental model of the vasovagal response in humans.     

Primate disconjugate eye movements during the horizontal AVOR in darkness and a plausible mechanism

Disconjugate eye movements during the horizontal angular vestibulo-ocular reflex (AVOR) evoked in response to steps or pulses of head velocity have been previously reported in lateral eyed animals. In this study, we measured binocular responses to sustained sinusoidal and pseudo-random vestibular stimuli in yaw, delivered in darkness, in both human and monkey. The vestibular stimuli used in our experiments had peak velocities in the range of 120–200°/s, frequencies in the range of 0.17–0.5 Hz, and durations between 60 and 75 s. Our results show a large vergence component to the AVOR response that systematically modulated with head velocity. We also examined our results for temporal–nasal preponderance in slow eye velocity. Although each subject showed some degree of directional preference, we did not find a systematically greater eye velocity for temporal–nasal direction across all subjects. Here, we present these findings and discuss that at least two possible sources could result in disconjugate eye movements during the horizontal rotational VOR in darkness: peripheral and central mechanisms.     

Low-frequency galvanic vestibular stimulation evokes two peaks of modulation in skin sympathetic nerve activity

We have previously shown that sinusoidal galvanic vestibular stimulation (sGVS), delivered bilaterally at 0.2–2.0 Hz, evokes a potent entrainment of sympathetic outflow to muscle and skin. Most recently, we showed that stimulation at 0.08–0.18 Hz generates two bursts of modulation of muscle sympathetic nerve activity (MSNA), more pronounced at 0.08 Hz, which we interpreted as reflecting bilateral projections from the vestibular nuclei to the medullary nuclei responsible for the generation of MSNA. Here, we test the hypothesis that these very low frequencies of sGVS modulate skin sympathetic nerve activity (SSNA) in a similar fashion. SSNA was recorded via tungsten microelectrodes inserted into the left common peroneal nerve in 11 awake-seated subjects. Bipolar binaural sGVS (±2 mA, 100 cycles) was applied to the mastoid processes at 0.08, 0.13 and 0.18 Hz. As with MSNA, cross-correlation analysis revealed two bursts of modulation of SSNA for each cycle of stimulation but, unlike MSNA, this modulation was equally pronounced at all frequencies. These results further support our conclusion that bilateral sGVS causes cyclical modulation of the left and right vestibular nerves and a resultant modulation of sympathetic outflow that reflects the summed activity of bilateral projections from the vestibular nuclei onto, in this case, the primary output nuclei responsible for SSNA—the medullary raphé. Furthermore, these findings emphasise the role of the vestibular system in the control of skin sympathetic outflow, and the cutaneous expression of motion sickness: pallor and sweat release. Indeed, vestibular modulation of SSNA was higher in those subjects reporting nausea than in those who did not report nausea during this low-frequency sGVS.     

Dynamics of the horizontal vestibuloocular reflex after unilateral labyrinthectomy: response to high frequency, high acceleration, and high velocity rotations

Loss of vestibular information from one labyrinth results in a marked asymmetry in the horizontal vestibuloocular reflex (VOR). The results of prior studies suggest that long-term deficits in VOR are more severe in response to rapid impulses than to sinusoidal head movements. The goal of the present study was to investigate the VOR following unilateral labyrinthectomy in response to different stimuli covering the full range of physiologically relevant head movements in macaque monkeys. The VOR was studied 1–39 days post-lesion using transient head perturbations (up to 12,000°/s²), rapid rotations (up to 500°/s), and sinusoidal rotations (up to 15 Hz). In response to rotations with high acceleration or velocity, both contra- and ipsilesional gains remained subnormal. VOR gains decreased as a function of increasing stimulus acceleration or velocity, reaching minimal values of 0.7–0.8 and 0.3–0.4 for contra and ipsilesional rotations, respectively. For sinusoidal rotations with low frequencies and velocities, responses to contralesional stimulation recovered within ∼ 4 days. With increasing velocities and frequencies of rotation, however, the gains of contra- and ipsilesional responses remained subnormal. For each of the most challenging stimuli tested (i.e., 12,000°/s² transient head perturbations, 500°/s fast whole-body rotations and 15 Hz stimulation) no significant compensation was observed in contra- or ipsilesional responses over time. Moreover, we found that gain of the cervico-ocular reflex (COR) remained negligible following unilateral loss indicating that neck reflexes did not contribute to the observed compensation. VOR responses elicited by both sinusoidal and transient rotations following unilateral labyrinthectomy could be described by the same mathematical model. We conclude that the compensated VOR has comparable response dynamics for impulses and sinusoidal head movements.Electronic Supplementary Material Supplementary material is available to authorised users in the online version of this article at .     

Improving balance function using vestibular stochastic resonance: optimizing stimulus characteristics

Stochastic resonance (SR) is a phenomenon whereby the response of a non-linear system to a weak periodic input signal is optimized by the presence of a particular non-zero level of noise. Stochastic resonance using imperceptible stochastic vestibular electrical stimulation, when applied to normal young and elderly subjects, has been shown to significantly improve ocular stabilization reflexes in response to whole-body tilt; improved balance performance during postural disturbances and optimize covariance between the weak input periodic signals introduced via venous blood pressure receptors and the heart rate responses. In our study, 15 subjects stood on a compliant surface with their eyes closed. They were given low-amplitude binaural bipolar stochastic electrical stimulation of the vestibular organs in two frequency ranges of 1–2 and 0–30 Hz over the amplitude range of 0 to ±700 μA. Subjects were instructed to maintain an upright stance during 43-s trials, which consisted of baseline (zero amplitude) and stimulation (non-zero amplitude) periods. Measures of stability of the head and trunk using inertial motion unit sensors attached to these segments and the whole body using a force plate were measured and quantified in the mediolateral plane. Using a multivariate optimization criterion, our results show that the low levels of vestibular stimulation given to the vestibular organs improved balance performance in normal healthy subjects in the range of 5–26% consistent with the stochastic resonance phenomenon. In our study, 8 of 15 and 10 of 15 subjects were responsive for the 1–2- and 0–30-Hz stimulus signals, respectively. The improvement in balance performance did not differ significantly between the stimulations in the two frequency ranges. The amplitude of optimal stimulus for improving balance performance was predominantly in the range of ±100 to ±400 μA. A device based on SR stimulation of the vestibular system might be useful as either a training modality to enhance adaptability or skill acquisition, or as a miniature patch-type stimulator that may be worn by people with disabilities due to aging or disease to improve posture and locomotion function.     

Persistent perceptual delay for head movement onset relative to auditory stimuli of different durations and rise times

The perception of simultaneity between auditory and vestibular information is crucially important for maintaining a coherent representation of the acoustic environment whenever the head moves. It has been recently reported, however, that despite having similar transduction latencies, vestibular stimuli are perceived significantly later than auditory stimuli when simultaneously generated. This suggests that perceptual latency of a head movement is longer than a co-occurring sound. However, these studies paired a vestibular stimulation of long duration (~1 s) and of a continuously changing temporal envelope with a brief (10–50 ms) sound pulse. In the present study, the stimuli were matched for temporal envelope duration and shape. Participants judged the temporal order of the two stimuli, the onset of an active head movement and the onset of brief (50 ms) or long (1,400 ms) sounds with a square- or raised-cosine-shaped envelope. Consistent with previous reports, head movement onset had to precede the onset of a brief sound by about 73 ms in order for the stimuli to be perceived as simultaneous. Head movements paired with long square sounds (~100 ms) were not significantly different than brief sounds. Surprisingly, head movements paired with long raised-cosine sound (~115 ms) had to be presented even earlier than brief stimuli. This additional lead time could not be accounted for by differences in the comparison stimulus characteristics (temporal envelope duration and shape). Rather, differences between sound conditions were found to be attributable to variability in the time for head movement to reach peak velocity: the head moved faster when paired with a brief sound. The persistent lead time required for vestibular stimulation provides further evidence that the perceptual latency of vestibular stimulation is greater than the other senses.     

Low-frequency physiological activation of the vestibular utricle causes biphasic modulation of skin sympathetic nerve activity in humans

We have previously shown that sinusoidal galvanic vestibular stimulation, a means of selectively modulating vestibular afferent activity, can cause partial entrainment of sympathetic outflow to muscle and skin in human subjects. However, it influences the firing of afferents from the entire vestibular apparatus, including the semicircular canals. Here, we tested the hypothesis that selective stimulation of one set of otolithic organs—those located in the utricle, which are sensitive to displacement in the horizontal axis—could entrain sympathetic nerve activity. Skin sympathetic nerve activity (SSNA) was recorded via tungsten microelectrodes inserted into cutaneous fascicles of the common peroneal nerve in 10 awake subjects, seated (head vertical, eyes closed) on a motorised platform. Slow sinusoidal accelerations–decelerations (~4 mG) were applied in the X (antero-posterior) or Y (medio-lateral) direction at 0.08 Hz; composite movements in both directions were also applied. Subjects either reported feeling a vague sense of movement (with no sense of direction) or no movement at all. Nevertheless, cross-correlation analysis revealed 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. For each sinusoidal cycle, there were two major peaks of modulation—one associated with acceleration as the platform moved forward or to the side, and one associated with acceleration in the opposite direction. We interpret these observations as reflecting inertial displacement of the stereocilia within the utricle during acceleration, which causes a robust vestibulosympathetic reflex.     

Vestibular,auditory, and somatic input to the posterior thalamus of the cat

Summary The responses of 157 neural units in the magnocellular (mc) and parvocellular (pc) components of the medial geniculate nucleus (MG) and other nuclei of the posterior (PO) thalamic group were recorded and analyzed. Units were tested for a response to electrical stimulation of the vestibular nerve, natural auditory and electrical cochlear nerve stimulation, and natural stimulation of joint, muscle, and cutaneous receptors of the limbs, trunk, and neck (somatic stimulation). Only 45% of the units responded to these stimuli. Twenty-four percent of the responsive units were multimodal, responding to more than one stimulus. All multimodal units were activated by auditory stimuli. More units responding to vestibular stimulation were found in mcMG than in pcMG or other components of the PO group. Potentials evoked by vestibular nerve stimulation were recorded in all 3 regions with latencies of 5–25 msec. No evidence was found for a thalamic relay from vestibular nerve to cortex in the area investigated, since the recorded latency for activity from vestibular nerve stimulation was longer than the latency of responses recorded in the cortex. This region of the thalamus appears to be important for reception of auditory information and integration with vestibular and somatic modalities.This investigation was supported in part by USPHS Grant NS 11307     

Vestibular and pulse-related modulation of skin sympathetic nerve activity during sinusoidal galvanic vestibular stimulation in human subjects

We have previously shown that sinusoidal galvanic vestibular stimulation (sGVS), a means of a selectively modulating vestibular afferent input without affecting other inputs, can cause partial entrainment of muscle sympathetic nerve activity (MSNA). Given that motion sickness causes sweating and pallor, we tested the hypothesis that sGVS also entrains skin sympathetic nerve activity (SSNA), but that the optimal frequencies are closer to those associated with slow postural changes (0.2 Hz). SSNA was recorded via tungsten microelectrodes inserted into the common peroneal nerve in 11 awake-seated subjects. Bipolar binaural sinusoidal GVS (±2 mA, 200 cycles) was applied to the mastoid processes at frequencies of 0.2, 0.5, 0.8, 1.1, 1.4, 1.7 and 2.0 Hz. All subjects reported strong postural illusions of ‘rocking in a boat’ or ‘swaying in a hammock’. Sinusoidal GVS caused a marked entrainment of SSNA at all frequencies. Measured as the modulation index, vestibular modulation ranged from 81.5 ± 4.0% at 0.2 Hz to 76.6 ± 3.6% at 1.7 Hz; it was significantly weaker at 2.0 Hz (63.2 ± 5.4%). Interestingly, pulse-related modulation of SSNA, which is normally weak, increased significantly during sGVS but was stronger at 0.8 Hz (86.2 ± 2.0%) than at 0.2 Hz (69.3 ± 8.3%), the opposite of the pattern seen with vestibular modulation of MSNA. We conclude that vestibular inputs can entrain the firing of cutaneous sympathetic neurones and increase their normally weak pulse-related rhythmicity.     

Modulation of muscle sympathetic bursts by sinusoidal galvanic vestibular stimulation in human subjects

There is controversy as to whether the vestibulosympathetic reflexes demonstrated in experimental animals actually exist in human subjects. While head-down neck flexion and off-vertical axis rotation can increase muscle sympathetic nerve activity (MSNA) in awake subjects, we recently showed that bipolar galvanic vestibular stimulation (GVS) does not. However, it is possible that our stimuli (2 mA, 1 s)—although capable of causing strong postural and occulomotor responses—were too brief. To address this issue we activated vestibular afferents using continuous sinusoidal (0.5–0.8 Hz, 60–100 cycles, ±2 mA) bipolar binaural GVS in 11 seated subjects. Sinusoidal GVS evoked robust vestibular illusions of “rocking in a boat” or “swinging from side to side.” Cross-correlation analysis revealed a cyclic modulation of MSNA ranging from 31 to 86% across subjects (mean ± SE 58 ± 5%), with total MSNA increasing by 156 ± 19% (P = 0.001). Furthermore, we documented de novo synthesis of sympathetic bursts that were coupled to the sinusoidal input, such that two bursts—rather than the obligatory single burst—could be generated within a cardiac interval. This demonstrates that the human vestibular apparatus exerts a potent facilitatory influence on MSNA that potentially operates independently of the baroreceptor system.     

Quantification of the vestibulo-ocular reflex and visual-vestibular interaction for the purpose of clinical diagnosis

Pseudorandom vestibular rotatory stimuli covering the normal head movement range (0–6 Hz) and power spectrum analysis techniques are used to clinically evaluate the vestibulo-ocular reflex (v.o.r.). Measurements of compensatory eye movements are recorded during fixation of a stationary target, during fixation of a target moving with the subject and in darkness. The gain above 3 Hz quantifies vestibular function under all these conditions. A frequency-dependent v.o.r. asymmetry indicates the side of a peripheral lesion. The fixation suppression curve at medium frequencies quantifies visual-vestibular interaction. Thus the new test is a powerful diagnostic tool applicable to disease of the labyrinth and central vestibular pathways. This test is evaluated on monkeys before unilateral labyrinthectomy and for an extended period of time after.     

Frequency response of human vestibular reflexes characterized by stochastic stimuli

Stochastic vestibular stimulation (SVS) can be used to study the postural responses to unpredictable vestibular perturbations. The present study seeks to determine if stochastic vestibular stimulation elicits lower limb muscular responses and to estimate the frequency characteristics of these vestibulo-motor responses in humans. Fourteen healthy subjects were exposed to unpredictable galvanic currents applied on their mastoid processes while quietly standing (±3 mA, 0–50 Hz). The current amplitude and stimulation configuration as well as the subject's head position relative to their feet were manipulated in order to determine that: (1) the muscle responses evoked by stochastic currents are dependent on the amplitude of the current, (2) the muscle responses evoked by stochastic currents are specific to the percutaneous stimulation of vestibular afferents and (3) the lower limb muscle responses exhibit polarity changes with different head positions as previously described for square-wave galvanic vestibular stimulation (GVS) pulses. Our results revealed significant coherence (between 0 and 20 Hz) and cumulant density functions (peak responses at 65 and 103 ms) between SVS and the lower limbs' postural muscle activity. The polarity of the cumulant density functions corresponded to that of the reflexes elicited by square-wave GVS pulses. The SVS–muscle activity coherence and time cumulant functions were modulated by current amplitude, electrode position and head orientation with respect to the subject's feet. These findings strongly support the vestibular origin of the lower limb muscles evoked by SVS. In addition, specific frequency bandwidths in the stochastic vestibular signal contributed to the early (12–20 Hz) and late components (2–10 Hz) of the SVS-evoked muscular responses. These frequency-dependent SVS-evoked muscle responses support the view that the biphasic muscle response is conveyed by two distinct physiological processes.     

Effects of lesion of the interstitial nucleus of Cajal on vestibular nuclear neurons activated by vertical vestibular stimulation

Summary 1. Experiments were performed in cats anesthetized with nitrous oxide to study the effects of INC lesions on responses of vestibular nuclear neurons during sinusoidal rotations of the head in the vertical (pitch) plane. Responses of neurons in the INC region were recorded during pitch rotations at 0.15 Hz. A great majority of these neurons did not respond to static pitch tilts, and they seemed to respond either to anterior or to posterior semicircular canal inputs with a peak phase lag of 140 deg (re head acceleration). 2. Responses of vestibular nuclei neurons in intact cats were recorded during pitch rotations at the same frequency (0.15 Hz). Neurons that seemed to respond to vertical semicircular canal inputs showed peak phase lags of 90 deg relative to head acceleration, whereas neurons that responded to static pitch tilts showed peak phase shifts near 0 deg. These results indicate that responses of neurons in the INC region lag those of vestibular neurons by about 50 deg, suggesting that the former neurons possess a phase-lagging (i.e. integrated) vestibular signal. 3. Responses of vestibular neurons in cats that had received electrolytic lesions of bilateral INCs 1–2 weeks previously were recorded during pitch rotations at the same frequency (0.15 Hz). Neurons that presumably responded to vertical semicircular canal inputs showed a peak phase lag of 60 deg relative to head acceleration, a significant decrease of the phase lag compared to normal, whereas responses near 0 deg were unchanged. Gain values of individual cells also significantly dropped from 2.07 ± 0.67 spikes · s⁻¹/deg · s⁻²2 (mean ± SD; normal cats) to 1.27 ± 0.68 spikes · s⁻²/deg · s⁻² (INC lesioned cats) at 0.15 Hz. When responses of vestibular neurons were studied during pitch rotations in the range of 0.044–0.49 Hz in these cats, a large decrease of the phase lag was observed at lower frequencies, whereas the slopes of phase lag curves of vestibular neurons in intact cats were rather flat. 4. Procaine infusion into the bilateral INCs not only resulted in a decrease of 20–50 deg in the phase lag in responses of vestibular neurons that had lagged head acceleration by 90–140 deg before procaine infusion, but also dropped the gain of the response to rotation by an average of 31%, whereas responses of neurons that had showed phase shifts near 0 deg were not influenced consistently. Simultaneous recording of the vestibular neurons and the vertical vestibuloocular reflex (VOR) indicated that the phase advance and gain drop of vestibular neurons occurred earlier than those of the VOR. These results exclude the possibility that the change in dynamic response of vestibular neurons after procaine infusion is due to depression of general brain stem activity that may lead to the phase advance of the VOR, and suggest that the decrease of the phase lag and gain drop in responses of the vestibular neurons was caused by removal of the phase-lagging, feedback signal coming from the INC to the vestibular nuclei.     

Reduced input from foot sole skin through cooling differentially modulates the short latency and medium latency vestibular reflex responses to galvanic vestibular stimulation

Sensory afferent information from the skin of the foot sole and information from the vestibular system converge within the central nervous system; however, their mode of interaction remains unknown. The purpose of this study was to investigate the effect of reduced cutaneous foot sole information on the ability of the vestibular system to evoke short latency (SL) and medium latency (ML) lower limb muscle reflex responses. Galvanic vestibular stimulation (GVS; bipolar; binaural; 25 ms; 2 mA square-wave pulse) was applied to standing human subjects (four women, eight men, average age 21.1 ± 3.0 years) both before and after cooling the foot soles in 1°C ice water (15 min initially, followed by 5 min between blocks of 200 GVS pulses). Changes in soleus reflex amplitude were examined. Following ice water immersion, there was a 35.16% increase in the size of the ML response in the soleus muscle when expressed as a percentage of pre-stimulus electromyographic (EMG) activity (control 26.48 ± 4.91%; ice 36.16 ± 6.52%) with no change in size of the SL response (control 7.42 ± 1.12%; ice 8.72 ± 1.10%). These results support the previously proposed dissociation of the SL and ML responses with respect to their circuitry and functions. The results also suggest a greater role for cutaneous-vestibular interaction in the modulation of the ML than the SL response and at a location prior to the motoneuron pool.     

The effects of stochastic galvanic vestibular stimulation on human postural sway

 Galvanic vestibular stimulation serves to modulate the continuous firing level of the peripheral vestibular afferents. It has been shown that the application of sinusoidally varying, bipolar galvanic currents to the vestibular system can lead to sinusoidally varying postural sway. Our objective was to test the hypothesis that stochastic galvanic vestibular stimulation can lead to coherent stochastic postural sway. Bipolar binaural stochastic galvanic vestibular stimulation was applied to nine healthy young subjects. Three different stochastic vestibular stimulation signals, each with a different frequency content (0–1 Hz, 1–2 Hz, and 0–2 Hz), were used. The stimulation level (range 0.4–1.5 mA, peak to peak) was determined on an individual basis. Twenty 60-s trials were conducted on each subject – 15 stimulation trials (5 trials with each stimulation signal) and 5 control (no stimulation) trials. During the trials, subjects stood in a relaxed, upright position with their head facing forward. Postural sway was evaluated by using a force platform to measure the displacements of the center of pressure (COP) under each subject’s feet. Cross-spectral measures were used to quantify the relationship between the applied stimulus and the resulting COP time series. We found significant coherency between the stochastic vestibular stimulation signal and the resulting mediolateral COP time series in the majority of trials in 8 of the 9 subjects tested. The coherency results for each stimulation signal were reproducible from trial to trial, and the highest degree of coherency was found for the 1- to 2-Hz stochastic vestibular stimulation signal. In general, for the nine subjects tested, we did not find consistent significant coherency between the stochastic vestibular stimulation signals and the anteroposterior COP time series. This work demonstrates that, in subjects who are facing forward, bipolar binaural stochastic galvanic stimulation of the vestibular system leads to coherent stochastic mediolateral postural sway, but it does not lead to coherent stochastic anteroposterior postural sway. Our finding that the coherency was highest for the 1- to 2-Hz stochastic vestibular stimulation signal may be due to the intrinsic dynamics of the quasi-static postural control system. In particular, it may result from the effects of the vestibular stimulus simply being superimposed upon the quiet-standing COP displacements. By utilizing stochastic stimulation signals, we ensured that the subjects could not predict a change in the vestibular stimulus. Thus, our findings indicate that subjects can act as ”responders” to galvanic vestibular stimulation. Received: 13 March 1998 / Accepted: 8 October 1998     

Flexion reflex modulation during stepping in human spinal cord injury

The flexion reflex modulation pattern was investigated in nine people with a chronic spinal cord injury during stepping using body weight support on a treadmill and manual assistance by therapists. Body weight support was provided by an upper body harness and was adjusted for each subject to promote the best stepping pattern with the least manual assistance required by the therapists. The flexion reflex was elicited by sural nerve stimulation with a 30 ms pulse train at 1.2–2 times the tibialis anterior reflex threshold. During stepping, stimuli were randomly dispersed across the gait cycle which was divided into 16 equal bins. A long latency (>110 ms) flexion reflex was present in all subjects, while a short (>30 ms) and a medium latency (>70 ms) flexion reflex were present only in three subjects. For each response, the non-stimulated EMG was subtracted from the stimulated EMG at identical time windows and bins, normalized to the maximal corresponding EMG, and significant differences were established with a Wilcoxon rank-sum test. The long latency flexion reflex was facilitated at late stance and during the swing-to-stance transition phase. A reflex depression was present from heel strike until mid-stance and during the swing-to-stance transition phase. The short and medium latency flexion reflexes were depressed during mid-stance followed by facilitation during the stance-to-swing transition phase. Regardless of the latency, facilitatory flexion responses during the swing phase coincided with decreased activity of ipsilateral ankle extensors. The flexion reflex was modulated in a phase dependent manner, a behavior that was absent for the soleus H-reflex in most of these patients (Knikou et al. in Exp Brain Res 193:397–407, 2009). We propose that training should selectively target spinal reflex circuits in which extensor muscles and reflexes are involved in order to maximize sensorimotor recovery in these patients.     

Eye movements during combined pursuit, optokinetic and vestibular stimulation in macaque monkey

 During natural behaviour in a visual environment, smooth pursuit eye movements (SP) usually override the vestibular-ocular reflex (VOR) and the optokinetic reflex (OKR), which stem from head-in-space and scene-relative-to-eye motion, respectively. We investigated the interaction of SP, VOR, and OKR, which is not fully understood to date. Eye movements were recorded in two macaque monkeys while applying various combinations of smooth eye pursuit, vestibular and optokinetic stimuli (sinusoidal horizontal rotations of visual target, chair and optokinetic pattern, respectively, at 0.025, 0.05, 0.1, 0.2, 0.4, and 0.8 Hz, corresponding to peak stimulus velocities of 1.25–40°/s for a standard stimulus of ±8°). Slow eye responses were analysed in terms of gain and phase. During SP at mid-frequencies, the eyes were almost perfectly on target (gain 0.98 at 0.1 Hz), independently of a concurrent vestibular or optokinetic stimulus. Pursuit gain at lower frequencies, although being almost ideal (0.98 at 0.025 Hz with pursuit-only stimulation), became modified by the optokinetic input (gain increase above unity when optokinetic stimulus had the same direction as target, decrease with opposite direction). At higher stimulus frequencies, pursuit gain decreased (down to 0.69 at 0.8 Hz), and the pursuit response became modified by vestibular input (gain increase during functionally synergistic combinations, decrease in antagonistic combinations).Thus, the pursuit system in monkey dominates during SP-OKR-VOR interaction, but it does so effectively only in the mid-frequency range. The results can be described in the form of a simple dynamic model in which it is assumed that the three systems interact by linear summation. In the model SP and OKR dominate VOR in the low- to mid-frequency/velocity range, because they represent closed loop systems with high internal gain values (>>1) at these frequencies/velocities, whereas the VOR represents an open loop system with about unity-gain (up to very high frequencies). SP dominance over OKR is obtained by allowing an ’attentional/volitional’ mechanism to boost SP gain and a predictive mechanism to improve its dynamics. Received: 27 November 1998 / Accepted: 8 March 1999     

Low-frequency sinusoidal galvanic stimulation of the left and right vestibular nerves reveals two peaks of modulation in muscle sympathetic nerve activity

Studies previously performed in our laboratory have shown that sinusoidal galvanic vestibular stimulation (sGVS), a means of selectively modulating vestibular input without affecting other inputs, can cause partial entrainment of muscle sympathetic nerve activity (MSNA) at frequencies ranging from 0.2 to 2.0 Hz. Here we test the effect of sGVS on sympathetic outflow when stimulating the vestibular system at lower frequencies. MSNA was recorded via tungsten microelectrodes inserted into the left common peroneal nerve in 12 awake, seated subjects. Bipolar binaural sinusoidal GVS (±2 mA, 100 cycles) was applied to the mastoid processes at 0.08, 0.13 and 0.18 Hz. Cross-correlation analysis revealed two bursts of modulation of MSNA for each cycle of stimulation. We believe the primary peak is related to the positive phase of the sinusoid, in which the right vestibular nerve is hyperpolarised and the left vestibular nerve depolarised. Furthermore, we believe the secondary peak is related to the negative phase of the sinusoid (depolarisation of the right vestibular nerve and hyperpolarisation of the left vestibular nerve). This was never observed at higher frequencies of stimulation, presumably because at such frequencies there is insufficient time for a second peak to be expressed. The incidence of double peaks of MSNA was highest at 0.08 Hz and lowest at 0.18 Hz. These observations emphasise the role of the vestibular apparatus in the control of blood pressure, and further suggest convergence of bilateral inputs from vestibular nuclei onto the output nuclei from which MSNA originates, the rostral ventrolateral medulla (RVLM).     

Interaction between vestibulo-spinal and corticospinal systems: a combined caloric and transcranial magnetic stimulation study

We investigated the interaction between vestibular and corticospinal stimuli in 8 healthy volunteers. Vestibular stimulation was induced with unilateral ear caloric irrigation (30°C) with subjects supine. Single transcranial magnetic stimulation (TMS) pulses were delivered (double-cone coil, intensities 60–75% maximal output) every 10–20 s during vestibular activation and during baseline. Bilateral surface electromyography (EMG) from splenius capitis, sternocleidomastoid (SCM), obliquus externus abdominis, vastus lateralis, biceps femoris (BF), tibialis anterior and peroneus longus was obtained. During whole-body maximal rotatory voluntary isometric contraction (MRVC), only SCM and BF displayed EMG activation/inhibition patterns indicating axial rotatory action. TMS-induced motor evoked potentials (MEPs) after caloric irrigation revealed that only SCM showed consistent vestibular-mediated excitation/inhibition responses, i.e. an increase in MEP area contralateral to the irrigation and a decrease in MEP area ipsilaterally (+12.7 and −6.3% of the MRVC, respectively). A putative head turn induced by this SCM activity pattern would be in the same direction of the slow-phase eye movement. EMG in the 100 ms preceding TMS showed muscle tone values of approximately 10% of MRVC. After caloric irrigation, these values increased by ca. 2% for all muscles bilaterally and hence cannot explain the direction-specific SCM MEP changes. Thus, SCM MEPs show caloric-induced amplitude modulation indicating that SCM is under both horizontal semicircular canal and corticospinal control. This vestibular modulation of corticospinal SCM control likely occurs at cortical levels. The direction of the MEP modulation indicates a directional coupling between vestibularly induced head and eye movements.