Induction and Cancellation of Self-Motion Misperception by Asymmetric Rotation in the Light.

Asymmetrical sinusoidal whole-body rotation sequences with half-cycles at different velocities induce self-motion misperception. This is due to an adaptive process of the vestibular system that progressively reduces the perception of slow motion and increases that of fast motion. It was found that perceptual responses were conditioned by four previous cycles of asymmetric rotation in the dark, as the perception of self-motion during slow and fast rotations remained altered for several minutes. Surprisingly, this conditioned misperception remained even when asymmetric stimulation was performed in the light, a state in which vision completely cancels out the perceptual error. This suggests that vision is unable to cancel the misadaptation in the vestibular system but corrects it downstream in the central perceptual processing. Interestingly, the internal vestibular perceptual misperception can be cancelled by a sequence of asymmetric rotations with fast/slow half-cycles in a direction opposite to that of the conditioning asymmetric rotations.

Auditory perception is influenced by the orientation of the trunk relative to a sound source.

The study investigated how hearing depends on the whole body, head and trunk orientation relative to a sound source. In normal hearing humans we examined auditory thresholds and their ability to recognize logatomes (bi-syllabic non-sense words) at different whole body, head and trunk rotation relative to a sound source. We found that auditory threshold was increased and logatome recognition was impaired when the body or the trunk were rotated 40° away from a sound source compared to when the body or the trunk was oriented towards the sound source. Conversely, no effects were seen when only the head was rotated. Further, an increase of thresholds and impairment of logatome recognition were also observed after unilateral vibration of dorsal neck muscles that induces, per se, long-lasting illusory trunk displacement relative to the head. Thus, our findings support the idea that processing of acoustic signals depends on where a sound is located within a reference system defined by the subject's trunk coordinates.

Sensory inflow manipulation induces learning-like phenomena in motor behavior.

PURPOSE: Perceptual and goal-directed behaviors may be improved by repetitive sensory stimulations without practice-based training. Focal muscle vibration (f-MV) modulating the spatiotemporal properties of proprioceptive inflow is well-suited to investigate the effectiveness of sensory stimulation in influencing motor outcomes. Thus, in this study, we verified whether optimized f-MV stimulation patterns might affect motor control of upper limb movements. METHODS: To answer this question, we vibrated the slightly tonically contracted anterior deltoid (AD), posterior deltoid (PD), and pectoralis major muscles in different combinations in forty healthy subjects at a frequency of 100 Hz for 10 min in single or repetitive administrations. We evaluated the vibration effect immediately after f-MV application on upper limb targeted movements tasks, and one week later. We assessed target accuracy, movement mean and peak speed, and normalized Jerk using a 3D optoelectronic motion capture system. Besides, we evaluated AD and PD activity during the tasks using wireless electromyography. RESULTS: We found that f-MV may induce increases (p < 0.05) in movement accuracy, mean speed and smoothness, and changes (p < 0.05) in the electromyographic activity. The main effects of f-MV occurred overtime after repetitive vibration of the AD and PD muscles. CONCLUSION: Thus, in healthy subjects, optimized f-MV stimulation patterns might over time affect the motor control of the upper limb movement. This finding implies that f-MV may improve the individual's ability to produce expected motor outcomes and suggests that it may be used to boost motor skills and learning during training and to support functional recovery in rehabilitation.

Acute inhibition of estradiol synthesis impacts vestibulo-ocular reflex adaptation and cerebellar long-term potentiation in male rats.

The vestibulo-ocular reflex (VOR) adaptation is an ideal model for investigating how the neurosteroid 17 beta-estradiol (E2) contributes to the modification of behavior by regulating synaptic activities. We hypothesized that E2 impacts VOR adaptation by affecting cerebellar synaptic plasticity at the parallel fiber-Purkinje cell (PF) synapse. To verify this hypothesis, we investigated the acute effect of blocking E2 synthesis on gain increases and decreases in adaptation of the VOR in male rats using an oral dose (2.5 mg/kg) of the aromatase inhibitor letrozole. We also assessed the effect of letrozole on synaptic plasticity at the PF synapse in vitro, using cerebellar slices from male rats. We found that letrozole acutely impaired both gain increases and decreases adaptation of the VOR without altering basal ocular-motor performance. Moreover, letrozole prevented long-term potentiation at the PF synapse (PF-LTP) without affecting long-term depression (PF-LTD). Thus, in male rats neurosteroid E2 has a relevant impact on VOR adaptation and affects exclusively PF-LTP. These findings suggest that E2 might regulate changes in VOR adaptation by acting locally on cerebellar and extra-cerebellar synaptic plasticity sites.

Adaptive Changes in the Perception of Fast and Slow Movement at Different Head Positions.

BACKGROUND: This paper examines the subjective sense of orientation during asymmetric body rotations in normal subjects. METHODS: Self-motion perception was investigated in 10 healthy individuals during asymmetric whole-body rotation with different head orientations. Both on-vertical axis and off-vertical axis rotations were employed. Subjects tracked a remembered earth-fixed visual target while rotating in the dark for four cycles of asymmetric rotation (two half-sinusoidal cycles of the same amplitude, but of different duration). RESULTS: The rotations induced a bias in the perception of velocity (more pronounced with fast than with slow motion). At the end of rotation, a marked target position error (TPE) was present. For the on-vertical axis rotations, the TPE was no different if the rotations were performed with a 30° nose-down, a 60° nose-up, or a 90° side-down head tilt. With off-vertical axis rotations, the simultaneous activation of the semicircular canals and otolithic receptors produced a significant increase of TPE for all head positions. DISCUSSIONS: This difference between on-vertical and off-vertical axis rotation was probably partly due to the vestibular transfer function and partly due to different adaptation to the speed of rotation. Such a phenomenon might be generated in different components of the vestibular system. The adaptive process enhancing the perception of dynamic movement around the vertical axis is not related to the specific semicircular canals that are activated; the addition of an otolithic component results in a significant increase of the TPE.Panichi R, Occhigrossi C, Ferraresi A, Faralli M, Lucertini M, Pettorossi VE. Adaptive changes in the perception of fast and slow movement at different head positions. Aerosp Med Hum Perform. 2017; 88(5):463-468.

Self-motion perception and vestibulo-ocular reflex during whole body yaw rotation in standing subjects: the role of head position and neck proprioception.

Self-motion perception and vestibulo-ocular reflex (VOR) were studied during whole body yaw rotation in the dark at different static head positions. Rotations consisted of four cycles of symmetric sinusoidal and asymmetric oscillations. Self-motion perception was evaluated by measuring the ability of subjects to manually track a static remembered target. VOR was recorded separately and the slow phase eye position (SPEP) was computed. Three different head static yaw deviations (active and passive) relative to the trunk (0°, 45° to right and 45° to left) were examined. Active head deviations had a significant effect during asymmetric oscillation: the movement perception was enhanced when the head was kept turned toward the side of body rotation and decreased in the opposite direction. Conversely, passive head deviations had no effect on movement perception. Further, vibration (100 Hz) of the neck muscles splenius capitis and sternocleidomastoideus remarkably influenced perceived rotation during asymmetric oscillation. On the other hand, SPEP of VOR was modulated by active head deviation, but was not influenced by neck muscle vibration. Through its effects on motion perception and reflex gain, head position improved gaze stability and enhanced self-motion perception in the direction of the head deviation.

Noise induced hearing loss and vestibular dysfunction in the guinea pig.

This study analysed the acoustic and vestibular functional and morphological modifications in guinea pigs after acoustic trauma. Animals were exposed to noise (6 kHz, at 120 dB SPL for 60 minutes) and then auditory brainstem responses (ABR) and vestibuloocular reflex (VOR) were measured at 6 hours, 1 day, 3, 7, and 21 days after noise. Western blotting and immunostaining for 4-hydroxy-2-noneal (4-HNE) and vascular endothelial growth factor (VEGF) were performed in the cochlear and vestibular regions at 1 and 7 days after noise exposure. A significant decrease of VOR gain was observed on day 1 and the recovery was completed at day 21. ABR threshold values reached a level of 80 dB at day 1 after trauma reaching a value of about 50 dB SPL on day 21. 4-HNE expression, a marker of lipid peroxidation was strongly increased in the cochlea. In the vestibule, 4-HNE immunoreactivity was faint. However, VEGF was up-regulated both in the cochlea and vestibule. In conclusion, the expression of VEGF in both cochlear and vestibular structures suggests a reparative role with potentially therapeutic implications.

Antioxidant protection against acoustic trauma by coadministration of idebenone and vitamin E.

Idebenone, a synthetic analogue of coenzyme Q, attenuates noise-induced hearing loss by virtue of its antioxidant properties. This study involves a guinea pig model of acoustic trauma where the effectiveness of idebenone is analyzed in comparison with Vitamin E (alpha-tocopherol) that exhibits a potent antioxidant activity in the inner ear. Idebenone and vitamin E were injected intraperitoneally 1 h before noise exposure and once daily for three days; functional and morphological studies were then carried out, respectively, by auditory brainstem responses evaluation, scanning electron microscopy and terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling assay identification of missing and apoptotic cells was also performed. The results showed that the protective effects of idebenone and vitamin E were not additive implying that the two antioxidants may share competitive mechanisms.

Motor performance changes induced by muscle vibration.

The possibility that mechanical stimulation of selected muscles can act directly on the nervous system inducing persistent changes of motor performances was explored. On the basis of literature, stimulating parameters were chosen to stimulate the central nervous system and to avoid muscle fibre injuries. A sinusoidal mechanical vibration was applied, for three consecutive days, on the quadriceps muscle in seven subjects that performed a muscular contraction (VC). The same stimulation paradigm was applied on seven subjects in relaxed muscle condition (VR) and seven subjects were not treated at all (NV). Two sessions (PRE and POST) of isometric and isotonic tests were performed separated for 21 days, in all studied groups 7 days before and 15 days after stimulation, whilst an isokinetic test was performed on VC only. In the isometric test, the time of force development showed a significant decrease only in VC (POST vs PRE mean 27.8%, P < 0.05). In the isotonic test, the subjects' had to perform a fatiguing leg extension against a load. In this condition, the fatigue resistance increased greatly in VC (mean 40.3%, P < 0.001), increased slightly in VR and there was no difference in NV. In Isokinetic test, at several angular velocities, significantly less time was required to reach the force peak (mean 20.2% P < 0.05). The findings could be ascribed to plastic changes in proprioceptive processing, leading to an improvement in knee joint control. Such action delineates a new tool in sports training and in motor rehabilitation.

Protective properties of idebenone in noise-induced hearing loss in the guinea pig.

Idebenone is a synthetic analogue of coenzyme Q10 with antioxidant properties. The present study investigated the antioxidant activity of idebenone in the rescue of acoustic trauma. Noise-induced hearing loss was induced by exposing guinea pigs to a continuous pure tone and idebenone was injected intraperitoneally 1 h before noise exposure and once daily for 3 days. Guinea pigs treated with idebenone showed significantly smaller auditory threshold shifts than unprotected control animals. Missing and apoptotic cells were identified with scanning electron microscopy and terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling assay. Protected animals presented a lesser extent of both apoptotic activation and hair cell loss in the organ of Corti. Our results suggest an antioxidant function of idebenone in protection from noise-induced hearing loss and provide a rationale for exploring therapeutic strategies in humans.

Spatial orientation of periodic alternating drift (PAD).

Sinusoidal vestibular stimulation induces in the intact rabbit in prone position a periodic alternating drift (PAD), evident in the earth horizontal plane when the animal is rotated about the vertical axis but weak in the vertical one when the animal is rotated about the longitudinal axis. It has been hypothesized that these oscillations are related to an intrinsic instability of the velocity storage, due to the length of its time constant. The velocity storage has the longest time constant aligned with the vertical axis, and it changes its orientation with the gravity vector. The present research examined the spatial orientation of PAD in relation to changes of the animal position with respect to gravity. Normal pigmented rabbits were sinusoidally oscillated about their longitudinal axes to evoke vertical eye responses. The stimulation was carried out with the animal in prone position and with the animal in nose-up condition. With the animal in prone position, PAD had a weak vertical component, but an evident horizontal component was visible. When the animal was in nose-up position, the horizontal component of PAD was clearly visible, while the vertical component was negligible. In both stimulation conditions PAD period and peak velocity were not modulated by the stimulus characteristics. These results are consistent with a model of PAD based on an interaction between velocity storage and the cerebellar adaptation-habituation circuit.

Head-body righting reflex from the supine position and preparatory eye movements.

CONCLUSION: Saccular and utricular maculae can provide information on the supine static position, considering that both have pronounced curved structures with hair cells having a variety of polarization vectors that enable them to sense an inverted position and thus direct the righting reflex. OBJECTIVE: The vestibular system is essential for the structuring of motor behaviour, senses linear and angular acceleration and has a strong influence on posture and balance at rest, during locomotion and in head body righting reflexes. MATERIAL AND METHODS: Using guinea pigs in the supine position with a symmetrical head and trunk position, the ocular position was analysed to ascertain whether any ocular movement that occurred would adopt a spatial deviation indicative of the subsequent head and body righting. The characteristics of the righting reflex (direction, latency, duration and velocity) were analysed in guinea pigs from position signals obtained from search coils implanted in the eye, head and pelvis. The animals were kept in a supine position for a few seconds or even minutes with the eyes in a stable primary position and the head and body symmetrical and immobile. RESULTS: The righting reflex took place either immediately or after a slow deviation of the eyes. In both cases the righting sequence (eyes, head, body) was stereotyped and consistent. The direction of head and body righting was along the longitudinal axis of the animal and was either clockwise or anticlockwise and the direction of righting was related to the direction of the eye deviation. The ocular deviation and the direction of deviation that initiated and determined the direction of the righting reflex could be explained by possible otolithic activation.

Low-frequency loud acoustic stimulation and goal-directed arm movements.

OBJECTIVE: To analyse the effects of low-frequency loud acoustic stimulation on goal-directed movements involving the arm. Low-frequency sound stimulation impairs eye stability, evokes a subjective tilt of the visual surround in subjects presenting Tullio's phenomenon and induces, in normal subjects, short-latency evoked potentials in the neck and limb muscles. MATERIAL AND METHODS: Healthy subjects performed goal-directed movements in the horizontal plane with the right (dominant) arm to a fixed 3 degree-wide target positioned at an angle of 30 degrees, with the instruction to perform fast and accurate movements to the target and to hold the final position. This fast-pointing task was performed in association with sound-induced vestibular-otolithic stimulation (110 dB SPL, 500 Hz) in the absence of visual guidance (i.e. pointing at a memorized target in the absence of target or pointer cues). Pointing errors were analysed by computing the constant errors made by the subjects (mean error). Pointing errors were also correlated with movement kinematics (movement duration, peak velocity, time to peak velocity) and with the reaction time of movement. RESULTS: The low-frequency loud acoustic stimulation modified the final position of the arm-pointing task at the memorized target in the absence of vision. CONCLUSION: Goal-directed movements are achieved by means of sensory interactions between visual, somatosensory and vestibular information and the vestibular-otolithic signals contribute to the accuracy of voluntary arm movements.

alpha-Tocopherol protective effects on gentamicin ototoxicity: an experimental study.

Gentamicin, acting as an iron chelator, activates membrane lipid peroxidation (MPL) and induces free radical formation, as observed in vitro and in vivo. Antioxidants, such as alpha-tocopherol, are able to suppress MLP, thus attenuating tissue damage. The present study was designed to investigate the possible protective effects of alpha-tocopherol on gentamicin ototoxicity. The study was carried out on albino guinea pigs (250-350 g). The animals were divided into four groups: group A (n = 4), injected with corn oil daily at a dose of 100 mg/kg body weight intramuscularly (IM); group B (n = 10), treated with corn oil at a dose of 100 mg/kg body weight and gentamicin base at a dose of 100 mg/kg body weight (IM); group C (n = 10). treated with gentamicin alone at a dose of 100 mg/kg body weight (IM); and group D (n = 10), treated with gentamicin at the same dose plus alpha-tocopherol acetate at dose of 100 mg/kg body weight (IM). Electrocochleographic recordings were made from an implanted round-window electrode. All animals were treated for 14 days. The compound action potentials (CAPs) were measured at 2-16 kHz at days 0, 10, 14 and 18 after treatment. Changes in cochlear function were characterized as CAP threshold shifts. Morphological changes were analysed by scanning electron microscopy. Gentamicin induced progressive high-frequency hearing loss of 50-60 dB SPL. alpha-Tocopherol co-therapy slowed the progression of hearing loss. The significant loss of outer hair cells (OHCs) in the cochlear basal turn in gentamicin-treated animals was not observed in the cochleas of animals protected with alpha-tocopherol. This study supports the hypothesis that alpha-tocopherol interferes with gentamicin-induced free radical formation, and suggests that this drug may be useful in protecting OHC function from aminoglycoside ototoxicity, thus reducing hearing loss.

Cisplatin ototoxicity in the guinea pig: vestibular and cochlear damage.

The aim of the present study was to investigate both vestibular and cochlear cisplatin toxicity. Twelve albino guinea pigs were divided into an experimental (n=8) and a control saline group (n=4) and were treated with cisplatin at a daily dose of 2.5 mg/kg for 6 consecutive days. Vestibular dysfunction was evaluated by computing the gain of the vestibular ocular reflex (VOR) evoked by stimulation in the horizontal (HVOR) and vertical (VVOR) planes. Changes in cochlear function were characterised as compound action potential threshold shifts. After the functional testing, tympanic bullae were removed and processed for morphological examination of the sensorineural epithelium. The onset of vestibular functional impairment was observed on the third day, although the VOR gain decrease was not significant. The impairment of the vestibular function progressed until the sixth day becoming statistically significant particularly at VVOR mid frequencies of stimulation. At these frequencies both macula and crista ampullaris functions are involved. Concomitantly a progressive auditory threshold shift was observed at all stimulus frequencies. The decline of the auditory function was statistically significant from the third day of treatment and it was more evident at high frequencies. Morphological observations showed a massive loss of outer hair cells and a degeneration of the organ of Corti in the basal/middle turns and only a slight loss of hair cells of the cristae ampullares and maculae. In conclusion, functional and morphological data provide evidence that the toxic effect of cisplatin is more pronounced in the organ of Corti than in the vestibular epithelium.

Eye instability in the rabbit induced by vestibular stimulation in the vertical plane.

OBJECTIVE: Sinusoidal vestibular stimulation in the horizontal plane induces periodic eye instability in the intact rabbit and the hypothesis of an intrinsically unstable velocity storage mechanism has been conceived. The present research examined the stability of the vestibulo-ocular reflex (VOR) in the vertical plane, considering that the time constant values of vertical and horizontal VORs differ and that separate regions of the vestibulo-cerebellum affect the horizontal and vertical slow VOR components differently. MATERIAL AND METHODS: Normal pigmented rabbits were sinusoidally oscillated in the dark about their vertical and longitudinal axes to evoke horizontal and vertical eye responses. RESULTS: Frequency and peak-to-peak amplitude stimulation parameters ranged from 0.1 to 0.8 Hz and from 5 degrees to 20 degrees, respectively. During horizontal VOR, periodic alternating drift (PAD) was superimposed on the ocular response, and both peak velocity and period were directly correlated with stimulation amplitude. Vestibular stimulation in the vertical plane induced PAD: the period of vertical PAD was shorter and the amplitude smaller than the corresponding horizontal PAD values. A further difference in vertical PAD occurred in the lack of modulation of period and peak velocity by the stimulus amplitude. CONCLUSION: These results support the hypothesis of different instabilities of the velocity storage mechanism in the vertical and horizontal planes, possibly due to separate sensory-motor systems sub-serving the vertical and horizontal VORs.

Protective effects of alpha-tocopherol against gentamicin-induced Oto-vestibulo toxicity: an experimental study.

OBJECTIVE: Free radicals are involved in gentamicin ototoxicity and vestibular dysfunction and it has been demonstrated that free radical scavengers, such as alpha-tocopherol, are able to inactive free radicals, attenuating tissue damage This study was designed to investigate the possible protective effects of alpha-tocopherol against gentamicin-induced oto-vestibulo toxicity. MATERIAL AND METHODS: Adult albino guinea pigs were divided into four groups and were treated for 2 weeks as follows: Group A, controls; Group B, gentamicin plus corn oil; Group C, gentamicin only; and Group D, gentamicin plus alpha-tocopherol. To evaluate vestibular function, the animals underwent sinusoidal oscillations in the dark about their vertical and longitudinal axes to evoke horizontal and vertical vestibulo-ocular reflexes (VORs), respectively. Electrocochleographic recordings were performed using an implanted round window electrode. The compound action potentials (CAPs) at 2, 4, 8 and 16 kHz were measured every 5 days Morphological changes were analysed by means of scanning electron microscopy. RESULTS: Gentamicin induced a consistent reduction in VOR responses and a progressive high-frequency hearing loss of 50-60 dB sound pressure level. Alpha-Tocopherol co-therapy slowed the progression of hearing loss and significantly attenuated the final threshold shifts The impairment of vestibular function was reduced, as evidenced by an increased VOR gain. The massive loss of outer hair cells in the cochlear basal turn and of cristae ampullaris stereocilia in gentamicin-treated animals was not observed in the cochlea of animals protected with alpha-tocopherol. CONCLUSION: This study supports the hypothesis that alpha-tocopherol interferes with gentamicin-induced free radical formation, and suggests that this drug may be useful in preventing aminoglycoside oto-vestibulo toxicity.