Chronic electrical stimulation of the contralesional lateral cerebellar nucleus enhances recovery of motor function after cerebral ischemia in rats

Machado, André G.; Baker, Kenneth B.; Schuster, Daniel J.; Butler, Robert S.; Rezai, Ali R.

doi:10.1016/j.brainres.2009.05.007

Cited by 77 publications

(71 citation statements)

References 43 publications

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“…Brain tissue was freeze-sectioned in the transverse plane of electrode penetrations. Every fourth section, each 40 m in thickness, was stained with thionine to reveal cell bodies, whereas its adjacent section was stained with Perls' solution, enhanced by 3,3=-diaminobenzidine (Perls/ DAB), to reveal the ferric iron caused by rupture of small blood vessels or by the electrolytic lesion-associated electrocoagulation (Machado et al 2009;Russo and Bruce 2000). Histology was performed by NeuroScience Associates (Knoxville, TN).…”

Section: Surgeries and Experimental Setupmentioning

confidence: 99%

Frequency-Dependent Spatiotemporal Tuning Properties of Non–Eye Movement Related Vestibular Neurons to Three-Dimensional Translations in Squirrel Monkeys

Chen-Huang

Peterson

2010

Journal of Neurophysiology

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Chen-Huang C, Peterson BW. Frequency-dependent spatiotemporal tuning properties of non-eye movement related vestibular neurons to threedimensional translations in squirrel monkeys. J Neurophysiol 103: 3219-3237, 2010. First published April 7, 2010 doi:10.1152/jn.00904.2009. Responses of vestibular-only translation sensitive (VOTS) neurons in vestibular nuclei of two squirrel monkeys were studied at multiple frequencies to three-dimensional translations and rotations. A novel frequency-dependent spatiotemporal analysis examined in each neuron whether complex models, with unrestricted response dynamics in three-dimensional (3D) space, provided significantly better fits than restricted models following simple, cosine rule. Subsequently, the statistically selected optimal model was used to predict the maximum translation direction, expressed as a unitary vector, Vt max , and its associated sensitivity and phase across frequencies. Simple models were sufficient to quantify the 3D translational responses of 66% of neurons. Most VOTS neurons, complex or simple, exhibited flat-gain or low-pass response dynamics. The Vt max of simple neurons was fixed, whereas that of complex neurons changed with frequency. The spatial distribution of Vt max in simple neurons, which fell within 30°o f either the horizontal plane or/and the sagittal plane, was closely aligned with Vt max of vestibular afferents. In contrast, the frequencydependent Vt max of most complex neurons migrated from the dorsoventral axis at higher frequency toward the horizontal plane, especially the interaural axis, at lower frequency. When the maximum rotation direction was estimated from responses of the same VOTS neurons to 1.2 Hz yaw, pitch, and roll rotations, complex neurons were more likely to respond to rotations activating vertical canals. Responses to 0.15-0.3 Hz linear accelerations produced by inertial or gravitational forces were indistinguishable in most complex neurons but significantly different in most simple neurons. These observations suggest that simple and complex VOTS neurons constitute distinctive vestibular pathways where complex neurons, exhibiting a novel spatiotemporal filtering mechanism in processing otolith-related signals, are well suited to drive tilt-related responses, whereas simple neurons probably mediate pure translation related responses.

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Section: Surgeries and Experimental Setupmentioning

confidence: 99%

Frequency-Dependent Spatiotemporal Tuning Properties of Non–Eye Movement Related Vestibular Neurons to Three-Dimensional Translations in Squirrel Monkeys

Chen-Huang

Peterson

2010

Journal of Neurophysiology

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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 stimulations targeting the thalamus (Th) and periaqueductal gray matter for post-stroke movements and neuropathic pain have demonstrated efficacy in human studies [59][60][61]. Deep brain stimulations in the cerebellar dentate nucleus in rats have also been shown to promote post-stroke recovery and enhance synaptic plasticity and reorganization in the perilesional cortex [62][63][64][65].…”

Section: Current Brain Stimulation Techniques Used To Study Stroke Rementioning

confidence: 99%

“…2). Electrical stimulation of the dentate nucleus in rats has been shown to promote recovery and enhance plasticity [62][63][64][65]. Tracing studies using the rabies virus have indicated that different divisions of the dentate nucleus mediate different functions.…”

Section: Benefits Of Optogeneticsmentioning

confidence: 99%

Optogenetic Approaches to Target Specific Neural Circuits in Post-stroke Recovery

2016

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Stroke is a leading cause of death and disability in the USA, yet treatment options are very limited. Functional recovery can occur after stroke and is attributed, in part, to rewiring of neural connections in areas adjacent to or remotely connected to the infarct. A better understanding of neural circuit rewiring is thus an important step toward developing future therapeutic strategies for stroke recovery. Because stroke disrupts functional connections in peri-infarct and remotely connected regions, it is important to investigate brain-wide network dynamics during post-stroke recovery. Optogenetics is a revolutionary neuroscience tool that uses bioengineered lightsensitive proteins to selectively activate or inhibit specific cell types and neural circuits within milliseconds, allowing greater specificity and temporal precision for dissecting neural circuit mechanisms in diseases. In this review, we discuss the current view of post-stroke remapping and recovery, including recent studies that use optogenetics to investigate neural circuit remapping after stroke, as well as optogenetic stimulation to enhance stroke recovery. Multimodal approaches employing optogenetics in conjunction with other readouts (e.g., in vivo neuroimaging techniques, behavior assays, and next-generation sequencing) will advance our understanding of neural circuit reorganization during post-stroke recovery, as well as provide important insights into which brain circuits to target when designing brain stimulation strategies for future clinical studies.

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Chronic electrical stimulation of the contralesional lateral cerebellar nucleus enhances recovery of motor function after cerebral ischemia in rats

Cited by 77 publications

References 43 publications

Frequency-Dependent Spatiotemporal Tuning Properties of Non–Eye Movement Related Vestibular Neurons to Three-Dimensional Translations in Squirrel Monkeys

Frequency-Dependent Spatiotemporal Tuning Properties of Non–Eye Movement Related Vestibular Neurons to Three-Dimensional Translations in Squirrel Monkeys

Invasive Neurostimulation in Stroke Rehabilitation

Optogenetic Approaches to Target Specific Neural Circuits in Post-stroke Recovery

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