Dataset Information

Galvanic Vestibular Stimulation Improves Subnetwork Interactions in Parkinson's Disease.

ABSTRACT:

Background

Activating vestibular afferents via galvanic vestibular stimulation (GVS) has been recently shown to have a number of complex motor effects in Parkinson's disease (PD), but the basis of these improvements is unclear. The evaluation of network-level connectivity changes may provide us with greater insights into the mechanisms of GVS efficacy.

Objective

To test the effects of different GVS stimuli on brain subnetwork interactions in both health control (HC) and PD groups using fMRI.

Methods

FMRI data were collected for all participants at baseline (resting state) and under noisy, 1 Hz sinusoidal, and 70-200 Hz multisine GVS. All stimuli were given below sensory threshold, blinding subjects to stimulation. The subnetworks of 15 healthy controls and 27 PD subjects (on medication) were identified in their native space, and their subnetwork interactions were estimated by nonnegative canonical correlation analysis. We then determined if the inferred subnetwork interaction changes were affected by disease and stimulus type and if the stimulus-dependent GVS effects were influenced by demographic features.

Results

At baseline, interactions with the visual-cerebellar network were significantly decreased in the PD group. Sinusoidal and multisine GVS improved (i.e., made values approaching those seen in HC) subnetwork interactions more effectively than noisy GVS stimuli overall. Worsening disease severity, apathy, depression, impaired cognitive function, and increasing age all limited the beneficial effects of GVS.

Conclusions

Vestibular stimulation has widespread system-level brain influences and can improve subnetwork interactions in PD in a stimulus-dependent manner, with the magnitude of such effects associating with demographics and disease status.

SUBMITTER: Liu A

PROVIDER: S-EPMC8137296 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background: Impaired motor vigor (MV) is a critical aspect of Parkinson's disease (PD) pathophysiology. While MV is predominantly encoded in the basal ganglia, deriving (cortical) EEG measures of MV may provide valuable targets for modulation via galvanic vestibular stimulation (GVS). Objective: To find EEG features predictive of MV and examine the effects of high-frequency GVS. Methods: Data were collected from 20 healthy control (HC) and 18 PD adults performing 30 trials total of a squeeze bulb task with sham or multi-sine (50-100 Hz "GVS1" or 100-150 Hz "GVS2") stimuli. For each trial, we determined the time to reach maximum force after a "Go" signal, defined MV as the inverse of this time, and used the EEG data 1-sec prior to this time for prediction. We utilized 53 standard EEG features, including relative spectral power, harmonic parameters, and amplitude and phase of bispectrum corresponding to standard EEG bands from each of 27 EEG channels. We then used LASSO regression to select a sparse set of features to predict MV. The regression weights were examined, and separate band-specific models were developed by including only band-specific features (Delta, Theta, Alpha-low, Alpha-high, Beta, Gamma). The correlation between MV prediction and measured MV was used to assess model performance. Results: Models utilizing broadband EEG features were capable of accurately predicting MV (controls: 75%, PD: 81% of the variance). In controls, all EEG bands performed roughly equally in predicting MV, while in the PD group, the model using only beta band features did not predict MV well compared to other bands. Despite having minimal effects on the EEG feature values themselves, both GVS stimuli had significant effects on MV and profound effects on MV predictability via the EEG. With the GVS1 stimulus, beta-band activity in PD subjects became more closely associated with MV compared to the sham condition. With GVS2 stimulus, MV could no longer be accurately predicted from the EEG. Conclusions: EEG features can be a proxy for MV. However, GVS stimuli have profound effects on the relationship between EEG and MV, possibly via direct vestibulo-basal ganglia connections not measurable by the EEG.

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: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.