Galvanic Vestibular Stimulation (GVS) Augments Deficient Pedunculopontine Nucleus (PPN) Connectivity in Mild Parkinson's Disease: fMRI Effects of Different Stimuli

Cai, Jiayue; Lee, Soojin; Ba, Fang; Garg, Saurabh; Kim, Laura J; Liu, Aiping; Kim, Diana; Wang, Z Jane; McKeown, Martin J.

doi:10.3389/fnins.2018.00101

Cited by 41 publications

(55 citation statements)

References 76 publications

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“…Bilateral bipolar GVS was applied by a current stimulator (DS5 model, Digitimer Ltd., UK) at both mastoid bones using contact electrodes (E224N‐MR‐HSR‐500, EasyCap GmbH, Herrsching, Germany) as described before (Helmchen et al, ; Woll, Sprenger, & Helmchen, ). This stimulator has also been used and approved in other centers and studies (Cai et al, ; Cyran et al, ). Individual sensory (vestibular) thresholds were obtained by applying 10 s 1 Hz alternating stimulation, that is, low frequency alternating current that passed between the two mastoid electrodes.…”

Section: Methodsmentioning

confidence: 99%

Effects of galvanic vestibular stimulation on resting state brain activity in patients with bilateral vestibulopathy

Helmchen

Machner

Rother

et al. 2020

Human Brain Mapping

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We examined the effect of galvanic vestibular stimulation (GVS) on resting state brain activity using fMRI (rs-fMRI) in patients with bilateral vestibulopathy. Based on our previous findings, we hypothesized that GVS, which excites the vestibular nerve fibers, (a) increases functional connectivity in temporoparietal regions processing vestibular signals, and (b) alleviates abnormal visual-vestibular interaction. Rs-fMRI of 26 patients and 26 age-matched healthy control subjects was compared before and after GVS. The stimulation elicited a motion percept in all participants. Using different analyses (degree centrality, DC; fractional amplitude of low frequency fluctuations [fALFF] and seed-based functional connectivity, FC), group comparisons revealed smaller rs-fMRI in the right Rolandic operculum of patients. After GVS, rs-fMRI increased in the right Rolandic operculum in both groups and in the patients' cerebellar Crus 1 which was related to vestibular hypofunction. GVS elicited a fALFF increase in the visual cortex of patients that was inversely correlated with the patients' rating of perceived dizziness. After GVS, FC between parietoinsular cortex and higher visual areas increased in healthy controls but not in patients. In conclusion, short-term GVS is able to modulate rs-fMRI in healthy controls and BV patients.GVS elicits an increase of the reduced rs-fMRI in the patients' right Rolandic operculum, which may be an important contribution to restore the disturbed visualvestibular interaction. The GVS-induced changes in the cerebellum and the visual cortex were associated with lower dizziness-related handicaps in patients, possibly reflecting beneficial neural plasticity that might subserve visual-vestibular compensation of deficient self-motion perception. K E Y W O R D S bilateral vestibulopathy, galvanic vestibular stimulation, visual-vestibular interaction, fALFF, degree centrality, functional connectivity, rs-fMRI Abbreviations: DC, degree centrality; DHI, dizziness handicap score; fALFF, fractional amplitude of low frequency fluctuations; FC, seed-based functional connectivity; HC, healthy control; IPL, inferior parietal lobule; OP2, core vestibular area of parietal operculum; PIVC, parietoinsular vestibular cortex; ROI, region of interest; SMA, supplementary motor area; SMG, supramarginal gyrus; STG, superior temporal gyrus; VOR, vestibulo-ocular reflex; VSS, vertigo symptom scale.

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Section: Methodsmentioning

confidence: 99%

Effects of galvanic vestibular stimulation on resting state brain activity in patients with bilateral vestibulopathy

Helmchen

Machner

Rother

et al. 2020

Human Brain Mapping

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“…CVS has been used diagnostically for decades, and there have been a number of small studies using CVS in a therapeutic context (e.g., Grabherr et al, 2015;Kolev, 1990;Rode et al, 2002;McGeoch et al, 2008;McGeoch et al, 2009), but diagnostic-style CVS devices, which use water or air to flood the ear canal, are not amenable to home use. Current GVS devices are also not easily adapted for home use because of the need to clean the skin carefully, apply a conductive gel, and affix electrodes over the mastoid bones behind the ears, but an even larger body of work exploring potential clinical applications of GVS exists (e.g., Cai et al, 2018;Hwang et al, 2016;Kataoka et al, 2016;Kerkhoff et al, 2011;Kim et al, 2013;Okada et al, 2015;Pal et al, 2009;Pan et al, 2008;Samoudi et al, 2014;Wilkinson et al, 2014;Yamamoto et al, 2005). The past work with diagnostic-style CVS and research-style GVS devices should be viewed as purely research driven or pre-clinical.…”

Section: Vnmmentioning

confidence: 99%

Sensory Neuromodulation

Black¹,

Rogers²

2018

Preprint

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We describe a model of neurological disease based on dysfunctional brain oscillators.  This is not a new model, but it is not one that is generally appreciated by clinicians.  The value of this model lies in the predictions it makes and the utility it provides in translational applications, in particular for neuromodulation devices.  We provide a perspective on the difference between neuromodulation devices that enforce an externally administered stimulus with devices that provide input to sensory receptors and thus stimulate endogenous sensory networks.  Current forms of clinically applied neuromodulation are of the former type, including devices such as (implanted) deep brain stimulators (DBS) and various, noninvasive methods such as transcranial magnetic stimulation (TMS) and transcranial current methods (tACS, tDCS).  The challenge with these methods is that they are not sensitive to underlying neuronal dynamics and work by applying an empirically derived electrical current waveform to affect dynamical patterns. Neuromodulation of a sensory organ accesses the same pathways that natural environmental stimuli do and, importantly, the modulatory signal will be transformed as it travels through the brain, allowing the modulation input to be consistent with regional dynamics.  We present specific examples of devices that rely on sensory neuromodulation and evaluate the translational potential of these approaches.  We argue that sensory neuromodulation is well suited to probe and, ideally, repair dysfunctional brain oscillators, thus providing a novel therapeutic approach for neurological diseases.

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“…L-DOPA-induced Dyskinesia REM Sleep Behavior Disorder (Childs and Gale, 1983;Moehle et al, 2017) Vestibular System (Afferent) Postural Instability (Cai et al, 2018;Vitale et al, 2011)…”

Section: Author Contributionsmentioning

confidence: 99%

Pedunculopontine Nucleus Degeneration Contributes to Both Motor and Non-Motor Symptoms of Parkinson’s Disease

2020

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Parkinson's disease (PD) is a neurodegenerative disorder characterized by hypokinetic motor features; however, patients also display non-motor symptoms like sleep disorders. The standard treatment for PD is dopamine replacement with L-DOPA; however, symptoms including gait deficits and sleep disorders are unresponsive to L-DOPA. Notably, these symptoms have been linked to aberrant activity in the pedunculopontine nucleus (PPN). Of late, clinical trials involving PPN deep brain stimulation (DBS) have been employed to alleviate gait deficits. Although preclinical evidence implicating PPN cholinergic neurons in gait dysfunction was initially promising, DBS trials fell short of expected outcomes. One reason for the failure of DBS may be that the PPN is a heterogenous nucleus that consists of GABAergic, cholinergic, and glutamatergic neurons that project to a diverse array of brain structures. Second, DBS trials may have been unsuccessful because PPN neurons are susceptible to mitochondrial dysfunction, Lewy body pathology, and degeneration in PD. Therefore, pharmaceutical or gene-therapy strategies targeting specific PPN neuronal populations or projections could better alleviate intractable PD symptoms. Unfortunately, how PPN neuronal populations and their respective projections influence PD motor and non-motor symptoms remains enigmatic. Herein, we discuss normal cellular and neuroanatomical features of the PPN, the differential susceptibility of PPN neurons to PD-related insults, and we give an overview of literature suggesting a role for PPN neurons in motor and sleep deficits in PD. Finally, we identify future approaches directed towards the PPN for the treatment of PD motor and sleep symptoms.

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Galvanic Vestibular Stimulation (GVS) Augments Deficient Pedunculopontine Nucleus (PPN) Connectivity in Mild Parkinson's Disease: fMRI Effects of Different Stimuli

Cited by 41 publications

References 76 publications

Effects of galvanic vestibular stimulation on resting state brain activity in patients with bilateral vestibulopathy

Effects of galvanic vestibular stimulation on resting state brain activity in patients with bilateral vestibulopathy

Sensory Neuromodulation

Pedunculopontine Nucleus Degeneration Contributes to Both Motor and Non-Motor Symptoms of Parkinson’s Disease

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