Dataset Information

Vestibular stimulation by 2G hypergravity modifies resynchronization in temperature rhythm in rats.

ABSTRACT: Input from the light/dark (LD) cycle constitutes the primary synchronizing stimulus for the suprachiasmatic nucleus (SCN) circadian clock. However, the SCN can also be synchronized by non-photic inputs. Here, we hypothesized that the vestibular system, which detects head motion and orientation relative to gravity, may provide sensory inputs to synchronize circadian rhythmicity. We investigated the resynchronization of core temperature (Tc) circadian rhythm to a six-hour phase advance of the LD cycle (LD?+?6) using hypergravity (2?G) as a vestibular stimulation in control and bilateral vestibular loss (BVL) rats. Three conditions were tested: an LD?+?6 exposure alone, a series of seven 2?G pulses without LD?+?6, and a series of seven one-hour 2?G pulses (once a day) following LD?+?6. First, following LD?+?6, sham rats exposed to 2?G pulses resynchronized earlier than BVL rats (p?=?0.01), and earlier than sham rats exposed to LD?+?6 alone (p?=?0.002). Each 2?G pulse caused an acute drop of Tc in sham rats (-2.8?±?0.3?°C; p?

SUBMITTER: Martin T

PROVIDER: S-EPMC7280278 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Vestibular stimulation by 2G hypergravity modifies resynchronization in temperature rhythm in rats.

Martin Tristan T Bonargent Tristan T Besnard Stéphane S Quarck Gaëlle G Mauvieux Benoit B Pigeon Eric E Denise Pierre P Davenne Damien D

Scientific reports 20200608 1

Input from the light/dark (LD) cycle constitutes the primary synchronizing stimulus for the suprachiasmatic nucleus (SCN) circadian clock. However, the SCN can also be synchronized by non-photic inputs. Here, we hypothesized that the vestibular system, which detects head motion and orientation relative to gravity, may provide sensory inputs to synchronize circadian rhythmicity. We investigated the resynchronization of core temperature (Tc) circadian rhythm to a six-hour phase advance of the LD c ...[more]

PMID: 32514078

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Project description:BACKGROUND: The vestibular system is connected to spinal, cerebellar and cerebral motor control structures and can be selectively activated with external electrodes. The resulting sensation of disturbed balance can be avoided by using stochastic stimulation patterns. Adding noise to the nervous system sometimes improves function. Small clinical trials suggest that stochastic vestibular stimulation (SVS) may improve symptoms in Parkinson's disease. We have investigated this claim and possible mechanisms using the 6-hydroxydopamine (6-OHDA) hemilesion model of Parkinson's disease. METHODOLOGY/PRINCIPAL FINDINGS: Animals were tested in the accelerating rod test and the Montoya staircase test of skilled forelimb use. In 6-OHDA hemilesioned animals, SVS improved rod performance by 56±11 s. At group level L-DOPA treatment had no effect, but positive responders improved time on rod by 60±19 s. Skilled forelimb use was not altered by SVS. To investigate how SVS may influence basal ganglia network activity, intracerebral microdialysis was employed in four regions of interest during and after SVS. In presence of the ?-amino buturic acid (GABA) transporter inhibitor NNC 711, SVS induced an increase in GABA to 150±15% of baseline in the substantia nigra (SN) of unlesioned animals, but had no effect in the pedunculopontine nucleus (PPN), the striatum or the ventromedial thalamus (VM). Dopamine release remained stable in all areas, as did GABA and amine concentrations in the SN of unstimulated controls. Following SVS, a sustained increase in GABA concentrations was observed in the ipsilesional, but not in the contralesional SN of 6-OHDA hemilesioned rats. In contrast, L-DOPA treatment produced a similar increase of GABA in the ipsi- and contra-lesional SN. CONCLUSIONS/SIGNIFICANCE: SVS improves rod performance in a rat model of Parkinson's disease, possibly by increasing nigral GABA release in a dopamine independent way. We propose that SVS could be useful for treating symptoms of Parkinson's disease.

Project description:Objectives: To investigate the ameliorating effects of sinusoidal galvanic vestibular stimulation (GVS) on vestibular compensation from unilateral vestibular deafferentation (UVD) using a mouse model of unilateral labyrinthectomy (UL). Methods: Sixteen male C57BL/6 mice were allocated into two groups that comprise UL groups with GVS (GVS group, n = 9) and without GVS intervention (non-GVS group, n = 7). In the experimental groups, we assessed vestibulo-ocular reflex (VOR) recovery before (baseline) and at 3, 7, and 14 days after surgical unilateral labyrinthectomy. In the GVS group, stimulation was applied for 30 min daily from postoperative days (PODs) 0-4 via electrodes inserted subcutaneously next to both bony labyrinths. Results: Locomotion and VOR were significantly impaired in the non-GVS group compared to baseline. The mean VOR gain of the non-GVS group was attenuated to 0.23 at POD 3 and recovered continuously to the value of 0.54 at POD 14, but did not reach the baseline values at any frequency. GVS intervention significantly accelerated recovery of locomotion, as assessed by the amount of circling and total path length in the open field tasks compared to the non-GVS groups on PODs 3 (p < 0.001 in both amount of circling and total path length) and 7 (p < 0.01 in amount of circling and p < 0.001 in total path length, Mann-Whitney U-test). GVS also significantly improved VOR gain compared to the non-GVS groups at PODs 3 (p < 0.001), 7 (p < 0.001), and 14 (p < 0.001, independent t-tests) during sinusoidal rotations. In addition, the recovery of the phase responses and asymmetry of the VOR was significantly better in the GVS group than in the non-GVS group until 2 weeks after UVD (phase, p = 0.001; symmetry, p < 0.001 at POD 14). Conclusion: Recoveries for UVD-induced locomotion and VOR deficits were accelerated by an early intervention with GVS, which implies that GVS has the potential to improve vestibular compensation in patients with acute unilateral vestibular failure.

Project description:Electrical Vestibular Stimulation (EVS) is a non-invasive technique for activating the vestibular-ocular reflex, evoking mainly a torsional eye movement response. We have previously demonstrated that this response can be used to detect vestibular asymmetry in patients with vestibular schwannoma (VS). Here we perform a direct comparison of EVS with caloric irrigation in this patient group. We studied 30 patients with unilateral VS, alongside an equal number of aged-matched healthy control subjects. EVS current was delivered to the mastoid process in a monaural configuration using a sinusoidal stimulus (2 Hz; ± 2 mA; 10 s), with an electrode placed over the spinous C7 process. Evoked eye movements were recorded from the right eye in darkness using an infra-red sensitive camera while the subject sat relaxed with their head on a chinrest. Ocular torsion was subsequently tracked off-line using iris striations. Each subject separately underwent water caloric irrigation, in accordance with the British Society of Audiology guidelines. For the caloric test, eye movement was recorded in the yaw axis using electro-oculography. For both EVS and calorics, inter-aural response asymmetry was calculated to determine the extent of canal paresis. Both tests revealed impaired vestibular function in the ipsilesional ear of VS patients, with a mean asymmetry ratio of 15 ± 17% and 18 ± 16% for EVS and calorics, respectively. Overall, the caloric test results discriminated controls from patients slightly more effectively than EVS (Cohen's D effect size = 1.44 vs. 1.19). Importantly, there was a significant moderate correlation between the AR values produced by EVS and calorics (r = 0.53, p < 0.01), and no significant difference between mean AR estimates. When questioned, ?85% of participants subjectively preferred the EVS experience, in terms of comfort. Moreover, it took ~15 min to complete, vs. ~1 h for caloric. These results confirm that the results of the EVS test broadly agree with those of caloric irrigation, in terms of detecting vestibular asymmetry. Furthermore, they suggest a higher degree of convenience and patient comfort.

Project description:A dysfunctional vestibular system can be a severe detriment to the quality of life of a patient. Recent studies have shown the feasibility for a vestibular implant to restore rotational sensation via electrical stimulation of vestibular ampullary nerves. However, the optimal stimulation site for selective elicitation of the desired nerve is still unknown. We realized a finite element model on the basis of ?CT scans of a human inner ear and incorporated naturally distributed, artificial neural trajectories. A well-validated neuron model of myelinated fibers was incorporated to predict nerve responses to electrical stimulation. Several virtual electrodes were placed in locations of interest inside the bony labyrinth (intra-labyrinthine) and inside the temporal bone, near the target nerves (extra-labyrinthine), to determine preferred stimulation sites and electrode insertion depths. We investigated various monopolar and bipolar electrode configurations as well as different pulse waveform shapes for their ability to selectively stimulate the target nerve and for their energy consumption. The selectivity was evaluated with an objective measure of the fiber recruitment. Considerable differences of required energy and achievable selectivity between the configurations were observed. Bipolar, intra-labyrinthine electrodes provided the best selectivities but also consumed the highest amount of energy. Bipolar, extra-labyrinthine configurations did not offer any advantages compared to the monopolar approach. No selective stimulation could be performed with the monopolar, intra-labyrinthine approach. The monopolar, extra-labyrinthine electrodes required the least energy for satisfactory selectivities, making it the most promising approach for functional vestibular implants. Different pulse waveform shapes did not affect the achieved selectivity considerably but shorter pulse durations showed consistently a more selective activation of the target nerves. A cathodic, centered triangular waveform shape was identified as the most energy-efficient of the tested shapes. Based on these simulations we are able to recommend the monopolar, extra-labyrinthine stimulation approach with cathodic, centered triangular pulses as good trade-off between selectivity and energy consumption. Future implant designs could benefit from the findings presented here.

Dataset Information

Vestibular stimulation by 2G hypergravity modifies resynchronization in temperature rhythm in rats.

Publications

Vestibular stimulation by 2G hypergravity modifies resynchronization in temperature rhythm in rats.

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