A Vestibular Challenge Combined with Calcitonin Gene-Related Peptide (CGRP) Promotes Anxiety-Like Behaviors.

Motion-induced anxiety and agoraphobia are more frequent symptoms in patients with vestibular migraine (VM) than migraine without vertigo. The neuropeptide calcitonin gene-related peptide (CGRP) is a therapeutic target for migraine and VM, but the link between motion hypersensitivity, anxiety, and CGRP is relatively unexplored, especially in preclinical mouse models. To further examine this link, we tested the effects of systemic CGRP and off-vertical axis rotation (OVAR) on elevated plus maze (EPM) and rotarod performance in male and female C57BL/6J mice. Rotarod ability was assessed using two different dowel diameters: mouse dowel (r = 1.5 cm) versus rat dowel (r = 3.5 cm). EPM results indicate that CGRP alone or OVAR alone did not increase anxiety indices. However, the combination of CGRP and OVAR did elicit anxiety-like behavior. On the rotarod, CGRP reduced performance in both sexes on a mouse dowel but had no effect on a rat dowel, whereas OVAR had a significant effect on the rat dowel. These results suggest that only the combination of CGRP with vestibular stimulation induces anxiety-like behavior and that CGRP affects the dynamic balance function in mice depending on the type of challenge presented. These findings suggest that anxiety-like behaviors can be teased out from imbalance behaviors in a mouse model of "migraine." Future studies are aimed to determine if CGRP receptor antagonists that have been effective treating migraineurs and mouse "migraine" models may also reduce the anxiety observed in migraine.

Trauma-Induced Vestibular Dysfunction: Improved Repair Under Local Treatment With α1-Antitrypsin.

AIM: To characterize vestibular recovery in a mouse model of unilateral labyrinthotomy under local AAT and dexamethasone treatment. BACKGROUND: Alpha1-antitrypsin (AAT) is a circulating tissue-protective molecule that rises during inflammatory conditions and promotes inflammatory resolution. Its local concentration in human perilymph inversely correlates with the severity of inner ear dysfunction; concomitantly, mice that overexpress AAT and undergo inner ear trauma rapidly restore vestibular function. Locally applied AAT has yet to be examined in this context, nor has it been directly compared with anti-inflammatory corticosteroid treatment. METHODS: Wild-type mice C57BL/6 underwent a unilateral inner ear injury. Nine microliters of saline, clinical-grade AAT (180 µg/site), dexamethasone (4 mg/site), or both were applied locally on Days 0, 1, and 2 (n = 5/group). Vestibular function was assessed for 7 days. An in vitro human epithelial gap closure assay was performed using A549 cells in the presence of AAT and/or dexamethasone. RESULTS: Upon labyrinthotomy, all groups displayed severe vestibular dysfunction. Saline-treated mice showed the longest impairment. That group and the dexamethasone group displayed partial to no recovery, while AAT-treated mice exhibited complete recovery within 7 days; at this time point, dexamethasone-treated mice exhibited 50% recovery. Objective vestibular testing showed similar outcomes. In vitro, cotreatment with AAT and dexamethasone resulted in a gap closure dynamic that was superior to AAT alone at 6 h and superior to DEX alone at 48 h. CONCLUSION: Locally applied AAT treatment is superior to locally applied dexamethasone in promoting vestibular recovery in vivo. Ongoing studies are exploring the potential advantages of AAT combined with early low-dose dexamethasone therapy.

Histaminergic System and Vestibular Function in Normal and Pathological Conditions.

Most neurotransmitter systems are represented in the central and peripheral vestibular system and are thereby involved both in normal vestibular signal processing and the pathophysiology of vestibular disorders. However, there is a special relationship between the vestibular system and the histaminergic system. The purpose of this review is to document how the histaminergic system interferes with normal and pathological vestibular function. In particular, we will discuss neurobiological mechanisms such as neuroinflammation that involve histamine to modulate and allow restoration of balance function in the situation of a vestibular insult. These adaptive mechanisms represent targets of histaminergic pharmacological compounds capable of restoring vestibular function in pathological situations. The clinical use of drugs targeting the histaminergic system in various vestibular disorders is critically discussed.

The Role of Steroids in the Preservation of Hearing and Vestibular Function in Cochlear Implantation.

OBJECTIVE: Cochlear implant surgery is guided by principles of atraumatic insertion as to protect the inner ear. Previous studies suggest the potential benefit of steroids in patients undergoing cochlear implantation (CI), although the optimal route of administration has yet to be determined. We aim to systematically review the human studies of hearing and vestibular function preservation in patients undergoing CI receiving perioperative steroids and to discuss their role. DATA SOURCES: Search performed in PubMed, EMBASE, and CENTRAL databases in December 2023. REVIEW METHODS: Studies comparing several methods of steroid delivery and conventional management for patients undergoing CI were identified. Primary outcomes included hearing and vestibular function preservation. Secondary outcomes included reported adverse events, routes of steroid administration, and the presence of a control group without steroid administration. RESULTS: A total of 15 studies (N = 659) met inclusion criteria. Methodology, doses, route of steroid administration, and follow-up duration differed between most studies. Audiometric, vestibular, and hearing preservation (HP) results were inconsistent. In 12 studies, perioperative steroids were associated with either increased HP or vestibular function preservation. Only two studies reported adverse events related to oral corticosteroid therapy. CONCLUSIONS: There is a tendency for perioperative steroids to have a positive impact, at least in the short term, on hearing and vestibular function preservation in CI. Topical corticosteroid therapy appears to have a superior risk-benefit profile. There is a need for future carefully designed randomized controlled trials to determine the ideal route of steroid administration and its real impact in the long term. Laryngoscope, 134:3458-3465, 2024.

An in vitro model to assess the peripheral vestibulotoxicity of aromatic solvents.

Epidemiological and experimental studies indicate that a number of aromatic solvents widely used in the industry can affect hearing and balance following chronic exposure. Animal studies demonstrated that long-term exposure to aromatic solvents directly damages the auditory receptor within the inner ear: the cochlea. However, no information is available on their effect on the vestibular receptor, which shares many structural features with the cochlea and is also localized in inner ear. The aim of this study was to use an in vitro approach to assess and compare the vestibular toxicity of different aromatic solvents (toluene, ethylbenzene, styrene and ortho-, meta-, para-xylene), all of which have well known cochleotoxic properties. We used a three-dimensional culture model of rat utricles ("cysts") with preserved functional sensory and secretory epithelia, and containing a potassium-rich (K+) endolymph-like fluid for this study. Variations in K+ concentrations in this model were considered as biomarkers of toxicity of the substances tested. After 72 h exposure, o-xylene, ethylbenzene and styrene decreased the K+ concentration by 78 %, 37 % and 28 %, respectively. O- xylene and styrene both caused histopathological alterations in secretory and sensory epithelial areas after 72 h exposure, whereas no anomalies were observed in ethylbenzene-exposed samples. These in vitro results suggest that some widely used aromatic solvents might have vestibulotoxic properties (o-xylene, styrene and ethylbenzene), whereas others may not (p-xylene, m-xylene, toluene). Our results also indicate that variations in endolymphatic K+ concentration may be a more sensitive marker of vestibular toxicity than histopathological events. Finally, this study suggests that cochleotoxic solvents might not be necessarily vestibulotoxic, and vice versa.

The benefits of betahistine or vestibular rehabilitation (Tetrax biofeedback) on the quality of life and fall risk in patients with Ménière's disease.

OBJECTIVE: This study aimed to evaluate the benefits of betahistine or vestibular rehabilitation (Tetrax biofeedback) on the quality of life and fall risk in patients with Ménière's disease. METHODS: Sixty-six patients with Ménière's disease were randomly divided into three groups: betahistine, Tetrax and control groups. Patients' Dizziness Handicap Index and Tetrax fall index scores were obtained before and after treatment. RESULTS: Patients in the betahistine and Tetrax groups showed significant improvements in Dizziness Handicap Index and fall index scores after treatment versus before treatment (p < 0.05). The improvements in the Tetrax group were significantly greater than those in the betahistine group (p < 0.05). CONCLUSIONS: Betahistine and vestibular rehabilitation (Tetrax biofeedback) improve the quality of life and reduce the risk of falling in patients with Ménière's disease. Vestibular rehabilitation (Tetrax biofeedback) is an effective management method for Ménière's disease.

Direct Delivery of Antisense Oligonucleotides to the Middle and Inner Ear Improves Hearing and Balance in Usher Mice.

Usher syndrome is a syndromic form of hereditary hearing impairment that includes sensorineural hearing loss and delayed-onset retinitis pigmentosa (RP). Type 1 Usher syndrome (USH1) is characterized by congenital profound sensorineural hearing impairment and vestibular areflexia, with adolescent-onset RP. Systemic treatment with antisense oligonucleotides (ASOs) targeting the human USH1C c.216G>A splicing mutation in a knockin mouse model of USH1 restores hearing and balance. Herein, we explore the effect of delivering ASOs locally to the ear to treat hearing and vestibular dysfunction associated with Usher syndrome. Three localized delivery strategies were investigated in USH1C mice: inner ear injection, trans-tympanic membrane injection, and topical tympanic membrane application. We demonstrate, for the first time, that ASOs delivered directly to the ear correct Ush1c expression in inner ear tissue, improve cochlear hair cell transduction currents, restore vestibular afferent irregularity, spontaneous firing rate, and sensitivity to head rotation, and successfully recover hearing thresholds and balance behaviors in USH1C mice. We conclude that local delivery of ASOs to the middle and inner ear reach hair cells and can rescue both hearing and balance. These results also demonstrate the therapeutic potential of ASOs to treat hearing and balance deficits associated with Usher syndrome and other ear diseases.

The evaluation of the use of isotretinoin on vestibular system by using vHIT.

AIM: The aim of the present study was to evaluate the effect of isotretinoin (ISO) on peripheral vestibular system using vHIT. MATERIAL AND METHOD: This is a prospective study in which 30 patients administered ISO treatment with the diagnosis of acne vulgaris was evaluated. Following ear nose and throat, examination, audiological and vestibular evaluations were carried out. vHIT tests were conducted before and three months after the use of ISO (0.5-0.75 mg/kg/day). In addition, all participants underwent perceptual vertigo and dizziness tests before and three months after the use of ISO. RESULTS: In vHIT evaluation of all patients, no overt saccade, covert saccade and spontaneous nystagmus finding was observed. Gain and asymmetry were compared before and after the use of ISO: No significant difference was found between lateral semicircular canal, anterior, and posterior semi-circular and symmetry measurements made before ISO use and those made three months after it (p = 1.00; p = 0.99; p = 0.66). Similarly, there was no significant difference in asymmetry values of vertical semicircular canals measured before ISO and three months after it (p = 0.90; p = 0.76). No statistically significant difference was found in vertigo, nausea and dizziness in terms of responses before and 3 months after ISO use (p = 0.063; p = 0.031; p = 0.063). CONCLUSION: Although the studies demonstrating the effect of ISO on cochlea and symptoms occurring during treatment such as nausea, vomiting and vertigo suggest that it may exert effects on peripheral vestibular system, the present study indicates that it has no short terms effects on structures in peripheral vestibular system and vestibuloocular reflex pathways.

Audiovestibular clinician experiences and opinions about cisplatin vestibulotoxicity.

PURPOSE: Vestibulotoxicity associated with cisplatin chemotherapy is known to exist, but the extent, severity, and impact is unclear from the literature. This study explored knowledge, experiences, and opinions of audiovestibular professionals about cisplatin vestibulotoxicity. METHODS: An online survey was disseminated to clinicians working in the audiovestibular field. RESULTS: Ninety-three respondents participated in the survey. Most professionals were aware of potential vestibulotoxicity associated with cisplatin chemotherapy. Thirty-three percent of the respondents reported that they had seen patients with cisplatin vestibulotoxicity. Forty percent of them were confident in making the diagnosis and in managing the patient in this situation. The prevalence and impact of vestibulotoxicity including practicality of the assessment should be considered when designing an effective vestibulotoxicity screening protocol. CONCLUSION: This study provides a better understanding of cisplatin vestibulotoxicity from the perspectives of audiovestibular clinicians, which will underpin appropriate detection and management of the condition.

Fetal antisense oligonucleotide therapy for congenital deafness and vestibular dysfunction.

Disabling hearing loss impacts ∼466 million individuals worldwide with 34 million children affected. Gene and pharmacotherapeutic strategies to rescue auditory function in mouse models of human deafness are most effective when administered before hearing onset, after which therapeutic efficacy is significantly diminished or lost. We hypothesize that preemptive correction of a mutation in the fetal inner ear prior to maturation of the sensory epithelium will optimally restore sensory function. We previously demonstrated that transuterine microinjection of a splice-switching antisense oligonucleotide (ASO) into the amniotic cavity immediately surrounding the embryo on embryonic day 13-13.5 (E13-13.5) corrected pre-mRNA splicing in the juvenile Usher syndrome type 1c (Ush1c) mouse mutant. Here, we show that this strategy only marginally rescues hearing and partially rescues vestibular function. To improve therapeutic outcomes, we microinjected ASO directly into the E12.5 inner ear. A single intra-otic dose of ASO corrects harmonin RNA splicing, restores harmonin protein expression in sensory hair cell bundles, prevents hair cell loss, improves hearing sensitivity, and ameliorates vestibular dysfunction. Improvements in auditory and vestibular function were sustained well into adulthood. Our results demonstrate that an ASO pharmacotherapeutic administered to a developing organ system in utero preemptively corrects pre-mRNA splicing to abrogate the disease phenotype.

Cellular origin and response of flat epithelium in the vestibular end organs of mice to Atoh1 overexpression.

A flat epithelium (FE) may be found in the vestibular end organs of humans and mice with vestibular dysfunction. However, the pathogenesis of FE is unclear and inducing hair cell (HC) regeneration is challenging, as both HCs and supporting cells (SCs) in vestibular FE are damaged. To determine the cellular origin of vestibular FE and examine its response to Atoh1 overexpression, we fate-mapped vestibular epithelial cells in three transgenic mouse lines (vGlut3-iCreERT2:Rosa26tdTomato, GLAST-CreERT2:Rosa26tdTomato, and Plp-CreERT2:Rosa26tdTomato) after inducing a lesion by administering a high dose of streptomycin. Atoh1 overexpression in vestibular FE was mediated by an adeno-associated virus serotype 8 (AAV8) vector. Suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor, was administered with AAV8 to enhance Atoh1 overexpression. The transduction efficiency and population of myosin VIIa-positive cells were analyzed. A small number of HCs were present in vestibular FE. FE did not show broad GLAST-Cre or Plp-Cre expression, unlike the original SCs. SAHA dramatically enhanced AAV8-mediated exogenous gene overexpression, and Atoh1 overexpression plus SAHA promoted myosin VIIa expression in FE cells. Our data provide insight into FE formation and will facilitate studies of gene therapy for vestibular FE.

c-Fos Expression after Stochastic Vestibular Stimulation and Levodopa in 6-OHDA Hemilesioned Rats.

Near threshold stochastic vestibular stimulation (SVS) enhances postural control and improves other symptoms in neurodegenerative disorders like Parkinson's disease (PD). Improvement of postural control can tentatively be explained by increased responsivity of the vestibular system, but the mechanism behind other effects of near threshold SVS, like improved motor symptoms and cognitive responsiveness in PD, are not known. To better understand the effect of vestibular stimulation on brain activity in PD, c-Fos expression was used as a marker of change in functional activity following SVS in 6-hydroxydopamine (6-OHDA) hemi-lesioned and in sham-lesioned rats. The results were compared with the effect of a single levodopa injection in 6-OHDA hemi-lesioned or saline in sham-lesioned rats. SVS was found to increase c-Fos expression more than levodopa as well as saline in the parvocellular medial vestibular nucleus (MVePC) and more in 6-OHDA hemi-lesioned than in sham-lesioned animals. Furthermore, c-Fos expression increased more in the habenula nucleus (LHb) after SVS than it did after levodopa in 6-OHDA hemilesioned animals and after saline in the sham-lesioned animals. SVS and levodopa induced similar c-Fos expression in several regions, e.g. the caudate putamen (CPu), where saline had no effect. In conclusion there was overlap between SVS-activated areas and levodopa-activated areas, but activation was more pronounced following SVS in the MVePC of 6-OHDA lesioned and in the LHb in both lesioned and sham-lesioned rats.

Evaluation of nephrotoxicity and ototoxicity of aminosidine (paromomycin)-allopurinol combination in dogs with leishmaniosis due to Leishmania infantum: A randomized, blinded, controlled study.

Canine leishmaniosis due to Leishmania infantum is a widespread zoonotic disease. Although aminosidine can be an effective treatment, current therapeutic recommendations do not advocate its use, mainly due to concerns regarding the potential nephrotoxicity and ototoxicity of this drug. The aim of this randomized, blinded, controlled study was to evaluate the nephrotoxicity and ototoxicity of aminosidine-allopurinol combination and compare it with that of meglumine antimonate-allopurinol combination in non-azotemic dogs with leishmaniosis. Forty dogs with leishmaniosis were randomly assigned to be treated with either aminosidine at 15 mg/kg, subcutaneously, once daily for 28 days (group A) or with meglumine antimonate at 100 mg/kg, subcutaneously, once daily for 28 days (group B). In addition to either drug, dogs in both groups were administered allopurinol at 10 mg/kg per os twice daily for 2 months. Kidney function was evaluated through measurement of serum creatinine, urea nitrogen, inorganic phosphorus, and cystatin-c concentrations and complete urinalysis, including protein-to-creatinine ratio, at baseline and after 14, 28, and 60 days from the beginning of the treatment. At the same time points, vestibular and auditory functions were evaluated through neurological examination and brainstem auditory evoked response (BAER) recordings of wave I, wave V, inter-wave I-V latencies, and minimum hearing thresholds. None of the dogs developed clinicopathological evidence of kidney disease during the study. Serum creatinine concentration increased >0.3 mg/dl over baseline in 2 dogs in group A and in 5 dogs in group B. Parameters of kidney function were not significantly different or were improved compared to baseline and the only difference between the two groups was the lower concentration of serum creatinine in group A. None of the dogs developed peripheral vestibular syndrome or hearing impairment. At the end of the study, parameters of auditory function were not significantly different or were improved compared to baseline and there were no differences between the two groups. The results of this study show that the nephrotoxicity and ototoxicity of aminosidine, when administered to non-azotemic dogs with leishmaniosis at 15 mg/kg subcutaneously once daily for 28 days along with allopurinol, is minimal and does not differ from that of meglumine antimonate.

Gentamicin vestibulotoxicity with modern systemic dosing regimens: a prospective study using video-oculography.

Objectives: To determine the incidence of gentamicin vestibulotoxicity with current dosing regimens, and to evaluate the feasibility of routine video-oculography on all patients given gentamicin. Materials and methods: In this prospective incidence study serial horizontal vestibulo-ocular reflex (HVOR) gain measurements were recorded using video-oculography on adult inpatients receiving intravenous gentamicin. The primary outcome was the proportion of patients developing impairment of their HVOR gain. Results: After exclusions, 42 patients were included in the analysis. Three patients (7.1%) developed asymptomatic vestibulotoxicity, exact 95% confidence interval 1.5-19.5%. In two of these patients the deficit resolved within several hours. No patients developed symptomatic vestibulotoxicity. There was no evidence for a generalised reduction in group HVOR gain with time. HVOR gain was not associated with total gentamicin dose, dynamic visual acuity or subjective imbalance. Conclusions and significance: Gentamicin may cause reversible, asymptomatic vestibulotoxicity. Video-oculography may be useful to monitor for vestibulotoxicity in patients treated with gentamcin; however, testing all patients routinely may be challenging.

Impact of 4-aminopyridine on vestibulo-ocular reflex performance.

Vestibulo-ocular reflexes (VOR) are mediated by frequency-tuned pathways that separately transform the different dynamic and static aspects of head motion/position-related sensory signals into extraocular motor commands. Voltage-dependent potassium conductances such as those formed by Kv1.1 are important for the ability of VOR circuit elements to encode highly transient motion components. Here we describe the impact of the Kv1.1 channel blocker 4-aminopyridine (4-AP) on spontaneous and motion-evoked discharge of superior oblique motoneurons. Spike activity was recorded from the motor nerve in isolated preparations of Xenopus laevis tadpoles. Under static conditions, bath application of 1-10 µM 4-AP increased the spontaneous firing rate and provoked repetitive bursts of spikes. During motion stimulation 4-AP also augmented and delayed the peak firing rate suggesting that this drug affects the magnitude and timing of vestibular-evoked eye movements. The exclusive Kv1.1 expression in thick vestibular afferent fibers in larval Xenopus at this developmental stage suggests that the altered extraocular motor output in the presence of 4-AP mainly derives from a firing rate increase of irregular firing vestibular afferents that propagates along the VOR circuitry. Clinically and pharmacologically, the observed 4-AP-mediated increase of peripheral vestibular input under resting and dynamic conditions can contribute to the observed therapeutic effects of 4-AP in downbeat and upbeat nystagmus as well as episodic ataxia type 2, by an indirect increase of cerebellar Purkinje cell discharge.

Quantitative Assessment of Anti-Gravity Reflexes to Evaluate Vestibular Dysfunction in Rats.

The tail-lift reflex and the air-righting reflex are anti-gravity reflexes in rats that depend on vestibular function. To obtain objective and quantitative measures of performance, we recorded these reflexes with slow-motion video in two experiments. In the first experiment, vestibular dysfunction was elicited by acute exposure to 0 (control), 400, 600, or 1000 mg/kg of 3,3'-iminodipropionitrile (IDPN), which causes dose-dependent hair cell degeneration. In the second, rats were exposed to sub-chronic IDPN in the drinking water for 0 (control), 4, or 8 weeks; this causes reversible or irreversible loss of vestibular function depending on exposure time. In the tail-lift test, we obtained the minimum angle defined during the lift and descent maneuver by the nose, the back of the neck, and the base of the tail. In the air-righting test, we obtained the time to right the head. We also obtained vestibular dysfunction ratings (VDRs) using a previously validated behavioral test battery. Each measure, VDR, tail-lift angle, and air-righting time demonstrated dose-dependent loss of vestibular function after acute IDPN and time-dependent loss of vestibular function after sub-chronic IDPN. All measures showed high correlations between each other, and maximal correlation coefficients were found between VDRs and tail-lift angles. In scanning electron microscopy evaluation of the vestibular sensory epithelia, the utricle and the saccule showed diverse pathological outcomes, suggesting that they have a different role in these reflexes. We conclude that these anti-gravity reflexes provide useful objective and quantitative measures of vestibular function in rats that are open to further development.

Acute and chronic effects of single dose memantine after controlled cortical impact injury in adult rats.

BACKGROUND: Altered glutamatergic neurotransmission after traumatic brain injury (TBI) contributes to excitotoxic cell damage and death. Prevention or suppression of such changes is a desirable goal for treatment of TBI. Memantine (3,5-dimethyl-1-adamantanamine), an uncompetitive NMDA receptor antagonist with voltage-dependent open channel blocking kinetics, was reported to be neuroprotective in preclinical models of excitotoxicity, brain ischemia, and in TBI when administered prophylactically, immediately, or within minutes after injury. METHODS: The current study examined effects of memantine administered by single intraperitoneal injection to adult male rats at a more clinically relevant delay of one hour after moderate-severe controlled cortical impact (CCI) injury or sham surgery. Histopathology was assessed on days 1, 7, 21, and 90, vestibulomotor function (beam balance and beam walk) was assessed on days 1-5 and 71-75, and spatial memory (Morris water maze test, MWM) was assessed on days 14-21 and 83-90 after CCI injury or sham surgery. RESULTS: When administered at 10 mg/kg, but not 2.5 or 5 mg/kg, memantine preserved cortical tissue and reduced neuronal degeneration 1 day after injury, and attenuated loss of synaptophysin immunoreactivity in the hippocampus 7 days after injury. No effects of 10 mg/kg memantine were observed on histopathology at 21 and 90 days after CCI injury or sham surgery, or on vestibulomotor function and spatial memory acquisition assessed during any of the testing periods. However, 10 mg/kg memantine resulted in trends for improved search strategy in the MWM memory retention probe trial. CONCLUSIONS: Administration of memantine at a clinically-relevant delay after moderate-severe CCI injury has beneficial effects on acute outcomes, while more significant improvement on subacute and chronic outcomes may require repeated drug administration or its combination with another therapy.

Investigation on the effect of noisy galvanic vestibular stimulation on fine motor skills during a visuomotor task in healthy participants.

Noisy galvanic vestibular stimulation (nGVS) has been shown to improve dynamic walking stability, affect postural responses, enhance balance in healthy subjects, and influence motor performance in individuals with Parkinson's disease. Although the studies to fully characterize the effect of nGVS are still ongoing, stochastic resonance theory which states that the addition of noisy signal may enhance a weak sensory input signals transmission in a non-linear system may provide a possible explanation for the observed positive effects of nGVS. This study explores the effect of nGVS on fine tracking behavior in healthy subjects. Ten healthy participants performed a computer-based visuomotor task by controlling an object with a joystick to follow an amplitude-modulated signal path while simultaneously receiving a sham or pink noise nGVS. The stimulation was generated to have a zero-mean, linearly detrended 1/f-type power spectrum, Gaussian distribution within 0.1-10 Hz range, and a standard deviation (SD) set to 90% based on each participant's cutaneous threshold value. Results show that simultaneous nGVS delivery statistically improved the tracking performance with a decreased root-mean-squared error of 5.71±6.20% (mean±SD), a decreased time delay of 11.88±9.66% (mean±SD), and an increased signal-to-noise ratio of 2.93% (median, interquartile range (IQR) 3.31%). This study showed evidence that nGVS may be beneficial in improving sensorimotor performance during a fine motor tracking task requiring fine wrist movement in healthy subjects. Further research with a more comprehensive subset of tasks is required to fully characterize the effects of nGVS on fine motor skills.

A new immunohistochemical method to evaluate the development of vestibular compensation after unilateral labyrinthectomy in rats.

BACKGROUND: Unilateral labyrinthectomy (UL) causes the disappearance of ipsilateral medial vestibular nuclear (ipsi-MVe) activity and induces spontaneous nystagmus (SN), which disappears during the initial process of vestibular compensation (VC). Ipsi-MVe-activity restores in the late process of VC. OBJECTIVE: We evaluated the late process of VC after UL in rats and examined the effects of thioperamide (H3 antagonist) on VC. MATERIALS AND METHODS: MK801 (NMDA antagonist)-induced Fos-like immunoreactive (-LIR) neurons in contra-MVe, which had been suppressed by NMDA-mediated cerebellar inhibition in UL rats was used as an index. RESULTS: The number of MK801-induced Fos-LIR neurons in contra-MVe gradually decreased to the same level as that of sham-operated rats 14 days after UL. Thioperamide moved the disappearance of the MK801-induced Fos-LIR neurons 2 days earlier. The number of MK801-induced Fos-LIR neurons in thioperamide-treated rats was significantly decreased, compared with that of vehicle rats on days 7 and 12 after UL. But, thioperamide did not influence the decline of SN frequency in UL rats. CONCLUSION: These findings suggested that the number of MK801-induced Fos-LIR neurons in contra-MVe was decreased in concordance with the restoration of ipsi-MVe-activity during the late process of VC after UL and that thioperamide accelerated the late, but not the initial process of VC.