Multiple stimulation parameters influence efficacy of deep brain stimulation in parkinsonian mice

Schor, Jonathan S; Nelson, Alexandra

doi:10.1172/jci122390

Cited by 26 publications

(34 citation statements)

References 27 publications

(32 reference statements)

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“…This is in line with previous studies 44 and thought to result from the supersensitivity of ERK signaling in the 6-OHDA-lesioned hemisphere 45 . Our DBS results mirror a recent study in 6-OHDA-lesioned mice 22 , reporting improved locomotion with no effect on rotational bias. Surprisingly, DBS in mice does not recapitulate the typical motor improvements observed in rats 8,46,47 , although results in rats also vary depending on the intensity and the duration of stimulation [48][49][50] .…”

Section: Discussionsupporting

confidence: 89%

“…4e) but increased the locomotor activity (p = 0.0438; Fig. 5f), in line with a recent report 22 . DBS did not modify asymmetrical locomotor behavior for the cylinder test (n = 12, p = 0.9768; Fig.…”

Section: Dbs Decreases Pathological Hyperactivity Of Pyramidal Cellssupporting

confidence: 93%

“…Several studies, including ours, choose an intensity below the dyskinetic/dystonia threshold, as used in clinical DBS. In mice, dyskinesia is reported in the absence of effect on rotational bias over a large range of parameters studied 22 . The small size of the mouse STN could make it difficult to stimulate efficiently enough to reduce asymmetry without deleterious impact on the pyramidal tract 51 .…”

Section: Discussionmentioning

confidence: 92%

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Deep brain stimulation-guided optogenetic rescue of parkinsonian symptoms

et al. 2020

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Deep brain stimulation (DBS) of the subthalamic nucleus is a symptomatic treatment of Parkinson's disease but benefits only to a minority of patients due to stringent eligibility criteria. To investigate new targets for less invasive therapies, we aimed at elucidating key mechanisms supporting deep brain stimulation efficiency. Here, using in vivo electrophysiology, optogenetics, behavioral tasks and mathematical modeling, we found that subthalamic stimulation normalizes pathological hyperactivity of motor cortex pyramidal cells, while concurrently activating somatostatin and inhibiting parvalbumin interneurons. In vivo opto-activation of cortical somatostatin interneurons alleviates motor symptoms in a parkinsonian mouse model. A computational model highlights that a decrease in pyramidal neuron activity induced by DBS or by a stimulation of cortical somatostatin interneurons can restore information processing capabilities. Overall, these results demonstrate that activation of cortical somatostatin interneurons may constitute a less invasive alternative than subthalamic stimulation.

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Section: Discussionsupporting

confidence: 89%

Section: Dbs Decreases Pathological Hyperactivity Of Pyramidal Cellssupporting

confidence: 93%

Section: Discussionmentioning

confidence: 92%

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Deep brain stimulation-guided optogenetic rescue of parkinsonian symptoms

et al. 2020

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“…Despite the key role that DBS amplitude plays in DBS calibration procedures, multiple surveys have shown that only fine-tuning the amplitude can lead to side effects such as gait problems, movement interruption and speech impairments ( Törnqvist et al, 2005 ; Moreau et al, 2008 ; Tommasi et al, 2008 ; Xie et al, 2012 ; Tripoliti et al, 2014 ; Dayal et al, 2017 ). It has been reported that the total electrical energy delivered (TEED) has a significant impact on STN-DBS treatments ( Schor and Nelson, 2019 ). TEED can be calculated as follows:…”

Section: Discussionmentioning

confidence: 99%

“…where I is the current amplitude, f stimulation frequency, PW pulse-width and Z is the electrode-tissue impedance. A study by Schor and Nelson (2019) has reported that the current amplitude has a linear effect on hemi-PD mice’s movement velocities. Our finding also corroborates a strong linear relationship between the amplitude and all the three features we defined (rotation, area under the curve, and total distance).…”

Section: Discussionmentioning

confidence: 99%

Systematic Evaluation of DBS Parameters in the Hemi-Parkinsonian Rat Model

2020

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Electrical stimulation of the subthalamic nucleus (STN) is clinically employed to ameliorate several symptoms of manifest Parkinson’s Disease (PD). Stimulation parameters utilized by chronically implanted pulse generators comprise biphasic rectangular short (60–100 μs) pulses with a repetition frequency between 130 and 180 Hz. A better insight into the effect of electrical stimulation parameters could potentially reveal new possibilities for the improvement of deep brain stimulation (DBS) as a treatment. To this end, we employed single-sided 6-hydroxidopamine (6-OHDA) lesioning of the medial forebrain bundle (MFB) in rats to systematically investigate alternative stimulation parameters. These hemi-parkinsonian (hemi-PD) rats underwent individualized, ipsilateral electrical stimulation to the STN of the lesioned hemisphere, while the transiently induced contralateral rotational behavior was quantified to assess the effect of DBS parameter variations. The number of induced rotations during 30 s of stimulation was strongly correlated with the amplitude of the stimulation pulses. Despite a general linear relation between DBS frequency and rotational characteristics, a plateau effect was observed in the rotation count throughout the clinically used frequency range. Alternative waveforms to the conventional biphasic rectangular ( Rect ) pulse shapes [Triangular ( Tri ), Sinusoidal ( Sine ), and Sawtooth ( Lin.Dec. )] required higher charges per phase to display similar behavior in rats as compared to the conventional pulse shape. The Euclidean Distance (ED) was used to quantify similarities between different angular trajectories. Overall, our study confirmed that the effect of different amplitude and frequency parameters of STN-DBS in the hemi-PD rat model was similar to those in human PD patients. This shows that induced contralateral rotation is a valuable readout in testing stimulation parameters. Our study supports the call for more pre-clinical studies using this measurement to assess the effect of other DBS parameters such as pulse-width and interphase intervals.

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Iridium Oxide Nanoparticle–Protein Corona Neural Interfaces with Enhanced Electroactivity and Bioactivity Enable Electrically Manipulatable Physical and Chemical Neuronal Activation

Chan

Syu

Wang

et al. 2021

Adv Materials Inter

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Iridium oxide (IrOx) is a promising implantable electrode material owing to its remarkable neural stimulation capacity. However, presently, IrOx electrodes lack biocompatibility and bioactive interactions with nerve tissues. Application of polymeric surface coatings results in a weak physical adhesion at the organic/inorganic interface, which limits their wide‐scale application. Herein, a smart iridium oxide‐plasma protein (IrOx‐PP) electrode with enhanced electroactivity, electrochemical stability, cytocompatibility, and bioactivity that can provide controllable topographical, electrical, and chemical stimuli to enhance neuronal activity is proposed. In the inorganic/organic nanoparticle (NP)‐protein corona structures, the soft NP‐corona led to repeated burst‐to‐zero‐to‐burst PP release, while the hard NP‐corona with an ordered atomic structure enhanced the electrochemical stability and bioactivity. The incorporated PP resulted in a higher current storage capacity, lower impedance, better cell growth, and significant neurite outgrowth compared with those obtained with pristine IrOx. The application of electrical stimulation to IrOx‐PP enabled simultaneous neuromodulation, on‐demand PP release, and cell uptake, with a 2‐fold higher cell density and significant neurite outgrowth on IrOx‐PP than on pristine IrOx. This bioactive inorganic‐organic hybrid electrode with the combined features of physical properties and improved neuromodulation is expected to be a revolutionary platform for efficient and biocompatible neural implantation.

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Multiple stimulation parameters influence efficacy of deep brain stimulation in parkinsonian mice

Cited by 26 publications

References 27 publications

Deep brain stimulation-guided optogenetic rescue of parkinsonian symptoms

Deep brain stimulation-guided optogenetic rescue of parkinsonian symptoms

Systematic Evaluation of DBS Parameters in the Hemi-Parkinsonian Rat Model

Iridium Oxide Nanoparticle–Protein Corona Neural Interfaces with Enhanced Electroactivity and Bioactivity Enable Electrically Manipulatable Physical and Chemical Neuronal Activation

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