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The Acute Effects of Time-Varying Caloric Vestibular Stimulation as Assessed With fMRI.

ABSTRACT: We describe preliminary results from the application of time-varying caloric vestibular stimulation (tvCVS) to volunteers during a continuous blood oxygen level dependent (BOLD) functional MRI (fMRI) acquisition, recording baseline, during-tvCVS and post-tvCVS epochs. The modifications necessary to enable the use of this novel device in a 3-Tesla magnetic field are discussed. Independent component analysis (ICA) was used as a model-free method to highlight spatially and temporally coherent brain networks. The ICA results are consistent with tvCVS induction being mediated principally by thermoconvection in the vestibular labyrinth and not by direct thermal effects. The activation of hub networks identified by ICA is consistent with the concept of sensory neuromodulation, which posits that a modulatory signal introduced to a sensory organ is able to traverse the regions innervated (directly and indirectly) by that organ, while being transformed so as to be "matched" to regional neuronal dynamics. The data suggest that regional neurovascular coupling and a systemic cerebral blood flow component account for the BOLD contrast observed. The ability to modulate cerebral hemodynamics is of significant interest. The implications of these initial findings for the use of tvCVS therapeutically are discussed.

SUBMITTER: Black RD

PROVIDER: S-EPMC8381736 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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The Acute Effects of Time-Varying Caloric Vestibular Stimulation as Assessed With fMRI.

Black Robert D RD Bell Ryan P RP Riska Kristal M KM Spankovich Christopher C Peters Richard W RW Lascola Christopher D CD Whitlow Christopher T CT

Frontiers in systems neuroscience 20210809

We describe preliminary results from the application of time-varying caloric vestibular stimulation (tvCVS) to volunteers during a continuous blood oxygen level dependent (BOLD) functional MRI (fMRI) acquisition, recording baseline, during-tvCVS and post-tvCVS epochs. The modifications necessary to enable the use of this novel device in a 3-Tesla magnetic field are discussed. Independent component analysis (ICA) was used as a model-free method to highlight spatially and temporally coherent brain ...[more]

PMID: 34434093

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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:Background: Galvanic vestibular stimulation (GVS) is being increasingly explored as a non-invasive brain stimulation technique to treat symptoms in Parkinson's disease (PD). To date, behavioral GVS effects in PD have been explored with only two stimulus types, direct current and random noise (RN). The interaction between GVS effects and anti-parkinsonian medication is unknown. In the present study, we designed multisine (ms) stimuli and investigated the effects of ms and RN GVS on motor response time. In comparison to the RN stimulus, the ms stimuli contained sinusoidal components only at a set of desired frequencies and the phases were optimized to improve participants' comfort. We hypothesized GVS motor effects were a function of stimulation frequency, and specifically, that band-limited ms-GVS would result in better motor performance than conventionally used broadband RN-GVS. Materials and Methods: Eighteen PD patients (PDMOFF/PDMON: off-/on-levodopa medication) and 20 healthy controls (HC) performed a simple reaction time task while receiving sub-threshold GVS. Each participant underwent nine stimulation conditions: off-stimulation, RN (4-200 Hz), ms-θ (4-8 Hz), ms-α (8-13 Hz), ms-β (13-30 Hz), ms-γ (30-50 Hz), ms-h1 (50-100 Hz), ms-h2 (100-150 Hz), and ms-h3 (150-200 Hz). Results: The ms-γ resulted in shorter response time (RPT) in both PDMOFF and HC groups compared with the RN. In addition, the RPT of the PDMOFF group decreased during the ms-β while the RPT of the HC group decreased during the ms-α, ms-h1, ms-h2, and ms-h3. There was considerable inter-subject variability in the optimum stimulus type, although the frequency range tended to fall within 8-100 Hz. Levodopa medication significantly reduced the baseline RPT of the PD patients. In contrast to the off-medication state, GVS did not significantly change RPT of the PD patients in the on-medication state. Conclusions: Using band-limited ms-GVS, we demonstrated that the GVS frequency for the best RPT varied considerably across participants and was >30 Hz for half of the PDMOFF patients. Moreover, dopaminergic medication was found to influence GVS effects in PD patients. Our results indicate the common "one-size-fits-all" RN approach is suboptimal for PD, and therefore personalized stimuli aiming to address this variability is warranted to improve GVS effects.

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:PurposeIn studies of effects of time-varying drug exposures, adequate adjustment for time-varying covariates is often necessary to properly control for confounding. However, the granularity of the available covariate data may not be sufficiently fine, for example when covariates are measured for participants only when their exposure levels change.MethodsTo illustrate the impact of choices regarding the frequency of measuring time-varying covariates, we simulated data for a large target trial and for large observational studies, varying in covariate measurement design. Covariates were measured never, on a fixed-interval basis, or each time the exposure level switched. For the analysis, it was assumed that covariates remain constant in periods of no measurement. Cumulative survival probabilities for continuous exposure and non-exposure were estimated using inverse probability weighting to adjust for time-varying confounding, with special emphasis on the difference between 5-year event risks.ResultsWith monthly covariate measurements, estimates based on observational data coincided with trial-based estimates, with 5-year risk differences being zero. Without measurement of baseline or post-baseline covariates, this risk difference was estimated to be 49% based on the available observational data. With measurements on a fixed-interval basis only, 5-year risk differences deviated from the null, to 29% for 6-monthly measurements, and with magnitude increasing up to 35% as the interval length increased. Risk difference estimates diverged from the null to as low as -18% when covariates were measured depending on exposure level switching.ConclusionOur simulations highlight the need for careful consideration of time-varying covariates in designing studies on time-varying exposures. We caution against implementing designs with long intervals between measurements. The maximum length required will depend on the rates at which treatments and covariates change, with higher rates requiring shorter measurement intervals.

Dataset Information

The Acute Effects of Time-Varying Caloric Vestibular Stimulation as Assessed With fMRI.

Publications

The Acute Effects of Time-Varying Caloric Vestibular Stimulation as Assessed With fMRI.

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