Deep brain stimulation of the lateral cerebellar nucleus produces frequency-specific alterations in motor evoked potentials in the rat in vivo

Baker, Kenneth B.; Schuster, Daniel J.; Cooperrider, Jessica; Machado, André G.

doi:10.1016/j.expneurol.2010.08.019

Cited by 50 publications

(45 citation statements)

References 52 publications

(67 reference statements)

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“…14 Invasive cerebellar stimulation has also been studied. Deep brain stimulation of the cerebello-thalamo-cortical pathway, specifically of the lateral cerebellar nucleus, 119 has been shown in preclinical rodent models to modulate cerebral cortex excitability 7 and improve postischemia motor recovery. 106 More recently, chronic cerebellar DBS demonstrated promotion of long-term potentiation, neuroplasticity, and reparative reorganization.…”

Section: Cerebellar Stimulationmentioning

confidence: 99%

Neurorestoration after stroke

Azad¹,

Veeravagu²,

Steinberg³

2016

FOC

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Recent advancements in stem cell biology and neuromodulation have ushered in a battery of new neurorestorative therapies for ischemic stroke. While the understanding of stroke pathophysiology has matured, the ability to restore patients' quality of life remains inadequate. New therapeutic approaches, including cell transplantation and neurostimulation, focus on reestablishing the circuits disrupted by ischemia through multidimensional mechanisms to improve neuroplasticity and remodeling. The authors provide a broad overview of stroke pathophysiology and existing therapies to highlight the scientific and clinical implications of neurorestorative therapies for stroke.

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Section: Cerebellar Stimulationmentioning

confidence: 99%

Neurorestoration after stroke

Azad¹,

Veeravagu²,

Steinberg³

2016

FOC

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“…One of the possible mechanisms underlying the effects of DTC pathway stimulation on motor recovery and perilesional plasticity is via modulation of cortical excitability and reversal of crossed cerebellar diaschisis [10]. We have recently shown that chronic stimulation of the LCN increases cortical excitability over sustained periods of time in naïve animals, in a frequency-specific fashion [17]. Further, we have shown previously that despite phase-specific interactions with anesthetic agents, the enhanced cortical excitability by LCN stimulation is robust and reproducible in naïve animals [18].…”

Section: Introductionmentioning

confidence: 99%

Modulation of Cortical Motor Evoked Potential After Stroke During Electrical Stimulation of the Lateral Cerebellar Nucleus

et al. 2015

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Background Deep brain stimulation (DBS) targeting the dentato-thalamo-cortical (DTC) pathway at its origin in the lateral cerebellar nucleus (LCN) has been shown to enhance motor recovery in a rodent model of cortical ischemia. LCN DBS also yielded frequency specific changes in motor cortex excitability in the normal brain, indexed by motor evoked potential (MEP) amplitude. Objective To investigate the effect of cortical stroke on cortical motor excitability in a rodent ischemia model and to measure the effects of LCN DBS on post-ischemia excitability as a function of stimulation parameters. Methods Adult Sprague-Dawley rats were divided into two groups: naïve and stroke, with cortical ischemia induced through multiple, unilateral endothelin-1 injections. All animals were implanted with a bipolar electrode in the LCN opposite the affected hemisphere. MEPs were elicited from the affected hemisphere using intracortical microstimulation (ICMS) techniques. Multiple LCN DBS parameters were examined, including isochronal stimulation at 20, 30, 50, and 100 Hz as well as a novel burst stimulation pattern. Results ICMS-evoked MEPs were reduced in stroke (n=10) relative to naïve (n=12) animals. However, both groups showed frequency-dependent augmentation of cortical excitability in response to LCN DBS. In the naïve group, LCN DBS increased MEPs by 22–58%, while in the stroke group, MEPs were enhanced by 9–41% compared to OFF DBS conditions. Conclusions Activation of the DTC pathway increases cortical excitability in both naïve and post-stroke animals. These effects may underlie, at least partially, functional reorganization and therapeutic benefits associated with chronic LCN DBS in post-stroke animals.

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“…By targeting it at its node of origin in the dentate nucleus or the ascending pathway, the majority of the tract can be activated with a single implanted multipolar electrode [69]. Invasive, subthreshold stimulation, delivered chronically at lower frequencies (in the beta range) can generate sustained facilitatory effects upon excitability of M1 [70] and promote recovery of the impaired forelimb to a significantly greater degree than in a control [71,72].…”

Section: Methodological: Targeting Peri-lesional Substrates Even Whilmentioning

confidence: 99%

Invasive Neurostimulation in Stroke Rehabilitation

Plow

Machado

2014

Neurotherapeutics

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The last decade has seen a growing interest in adjuvant treatments that synergistically influence mechanisms underlying rehabilitation of paretic upper limb in stroke. One such approach is invasive neurostimulation of spared cortices at the periphery of a lesion. Studies in animals have shown that during training of paretic limb, adjuvant stimulation targeting the peri-infarct circuitry enhances mechanisms of its reorganization, generating functional advantage. Success of early animal studies and clinical reports, however, failed to translate to a phase III clinical trial. As lesions in humans are diffuse, unlike many animal models, peri-infarct circuitry may not be a feasible, or consistent target across most. Instead, alternate mechanisms, such as changing transcallosal inhibition between hemispheres, or reorganization of other viable regions in motor control, may hold greater potential. Here, we review comprehensive mechanisms of clinical recovery and factors that govern which mechanism(s) become operative when. We suggest novel approaches that take into account a patient's initial clinical-functional state, and findings from neuroimaging and neurophysiology to guide to their most suitable mechanism for ideal targeting. Further, we suggest new localization schemes, and bypass strategies that indirectly target peri-lesional circuitry, and methods that serve to counter technical and theoretical challenge in identifying and stimulating such targets at the periphery of infarcts in humans. Last, we describe how stimulation may modulate mechanisms differentially across varying phases of recovery-a temporal effect that may explain missed advantage in clinical trials and help plan for the next stage. With information presented here, future trials would effectively be able to target patient's specific mechanism(s) with invasive (or noninvasive) neurostimulation for the greatest, most consistent benefit. [2], which remains one of the most important predictors of disability and poor quality of life [3]. Disability adds to the costs of disease management that total $74 billion/ year [4]. Developing methods to effectively alleviate residual deficits will reduce health and economic burden of stroke.Several evidence-based rehabilitative approaches have been developed with prominent ones, including neuromuscular electrical stimulation [5], motor learning [6], robotic training [7] constraint-induced movement therapy [8], and bilateral arm training [9], etc. In spite of extensive therapy, recovery is frequently incomplete [10]. There is a critical need for adjuvant strategies that augment rehabilitative outcomes of paretic hand.The last decade has seen a growing interest in the promise of adjuvant treatments that synergistically influence mechanisms associated with rehabilitation. One such approach is invasive neuromodulation, involving electrical stimulation applied to cortical or subcortical targets spared by stroke. By directly stimulating viable targets, it is believed that potential for plasticity underlying reh...

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Deep brain stimulation of the lateral cerebellar nucleus produces frequency-specific alterations in motor evoked potentials in the rat in vivo

Cited by 50 publications

References 52 publications

Neurorestoration after stroke

Neurorestoration after stroke

Modulation of Cortical Motor Evoked Potential After Stroke During Electrical Stimulation of the Lateral Cerebellar Nucleus

Invasive Neurostimulation in Stroke Rehabilitation

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