Distributed Versus Focal Cortical Stimulation to Enhance Motor Function and Motor Map Plasticity in a Rodent Model of Ischemia

Boychuk, Jeffery A.; Adkins, DeAnna L.; Kleim, Jeffrey A.

doi:10.1177/1545968310385126

Cited by 43 publications

(50 citation statements)

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“…10,13,36,37,39,41 As seen in Figure 3, we found that motor RT significantly increased the total area of wrist representation in the injured cortex elicited with £100 lA, inclusive of RMC and CMC (F (1,20) = 6.193; p = 0.02), compared to NoRT. The overall increase in wrist representation was mainly driven by a significant expansion of wrist in the RMC (Fig 3B; F (1,20) = 7.69; p = 0.012), although there was an nonsignificant enlargement of wrist representation in CMC, as well (F (1,20) = 2.913; p = 0.104).…”

Section: Intracortical Microstimulation Motor Mapsupporting

confidence: 56%

Combinatorial Motor Training Results in Functional Reorganization of Remaining Motor Cortex after Controlled Cortical Impact in Rats

Combs

Jones

Kozlowski

et al. 2016

Journal of Neurotrauma

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Cortical reorganization subsequent to post-stroke motor rehabilitative training (RT) has been extensively examined in animal models and humans. However, similar studies focused on the effects of motor training after traumatic brain injury (TBI) are lacking. We previously reported that after a moderate/severe TBI in adult male rats, functional improvements in forelimb use were accomplished only with a combination of skilled forelimb reach training and aerobic exercise, with or without nonimpaired forelimb constraint. Thus, the current study was designed to examine the relationship between functional motor cortical map reorganization after experimental TBI and the behavioral improvements resulting from this combinatorial rehabilitative regime. Adult male rats were trained to proficiency on a skilled reaching task, received a unilateral controlled cortical impact (CCI) over the forelimb area of the caudal motor cortex (CMC). Three days post-CCI, animals began RT (n = 13) or no rehabilitative training (NoRT) control procedures (n = 13). The RT group participated in daily skilled reach training, voluntary aerobic exercise, and nonimpaired forelimb constraint. This RT regimen significantly improved impaired forelimb reaching success and normalized reaching strategies, consistent with previous findings. RT also enlarged the area of motor cortical wrist representation, derived by intracortical microstimulation, compared to NoRT. These findings indicate that sufficient RT can greatly improve motor function and improve the functional integrity of remaining motor cortex after a moderate/severe CCI. When compared with findings from stroke models, these findings also suggest that more intense RT may be needed to improve motor function and remodel the injured cortex after TBI.

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Section: Intracortical Microstimulation Motor Mapsupporting

confidence: 56%

Combinatorial Motor Training Results in Functional Reorganization of Remaining Motor Cortex after Controlled Cortical Impact in Rats

Combs

Jones

Kozlowski

et al. 2016

Journal of Neurotrauma

Self Cite

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“…While the relationship between cortical movement representations and behavior is not simple (Boychuk et al, 2011), decreases or increases in motor map size are often accompanied by deficits in fine motor control. Abnormal motor maps and decreased skilled reaching performance have previously been observed following cortical ischemia , repeated seizures , DA depletion (Brown et al, 2011), and high-frequency stimulation intended to saturate cortical excitability (Henderson et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

Serotonin 1A Receptors Alter Expression of Movement Representations

et al. 2013

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Serotonin has a myriad of central functions involving mood, appetite, sleep, and memory and while its release within the spinal cord is particularly important for generating movement, the corresponding role on cortical movement representations (motor maps) is unknown. Using adult rats we determined that pharmacological depletion of serotonin (5-HT) via intracerebroventricular administration of 5,7 dihydroxytryptamine resulted in altered movements of the forelimb in a skilled reaching task as well as higher movement thresholds and smaller maps derived using high-resolution intracortical microstimulation (ICMS). We ruled out the possibility that reduced spinal cord excitability could account for the serotonin depletion-induced changes as we observed an enhanced Hoffman reflex (H-reflex), indicating a hyperexcitable spinal cord. Motor maps derived in 5-HT 1A receptor knock-out mice also showed higher movement thresholds and smaller maps compared with wild-type controls. Direct cortical application of the 5-HT 1A/7 agonist 8-OH-DPAT lowered movement thresholds in vivo and increased map size in 5-HT-depleted rats. In rats, electrical stimulation of the dorsal raphe lowered movement thresholds and this effect could be blocked by direct cortical application of the 5-HT 1A antagonist WAY-100135, indicating that serotonin is primarily acting through the 5-HT 1A receptor. Next we developed a novel in vitro ICMS preparation that allowed us to track layer V pyramidal cell excitability. Bath application of WAY-100135 raised the ICMS current intensity to induce action potential firing whereas the agonist 8-OH-DPAT had the opposite effect. Together our results demonstrate that serotonin, acting through 5-HT 1A receptors, plays an excitatory role in forelimb motor map expression.

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“…For example, although cytoarchitectonic analysis of human precentral fMRI functional magnetic resonance gyrus suggests its volume is 100 times larger than that of rodents, the stimulation contact area in humans is only 4-7 times greater [30]. Is the dramatically variable success of animal versus clinical studies simply a function of a disproportionately smaller percentage volume targeted in humans?…”

Section: Methodologicalmentioning

confidence: 99%

“…Their contribution evidently emerges from substantial (~60 %) and independent projections to corticospinal pathways [56], extensive reciprocal connections with M1 [57], and dense transcallosal connections with their homologues [57]. Although we currently explore how stimulating higher motor areas potentiates vicariation [33], a recent rodent model by Boychuk et al [30] may offer some translational insight. They have discussed that stimulating distributed regions in the periphery of ipsilesional motor cortices is more efficacious than focal stimulation in the interior of M1.…”

Section: Alternate Substrates and Their Role In Recovery: Cortical Sumentioning

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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Distributed Versus Focal Cortical Stimulation to Enhance Motor Function and Motor Map Plasticity in a Rodent Model of Ischemia

Abstract: The results indicate that although both focal and distributed forms of CS/RT promote motor map reorganization only the distributed form of CS/RT enhances motor performance with rehabilitation.

Cited by 43 publications

References 50 publications

Combinatorial Motor Training Results in Functional Reorganization of Remaining Motor Cortex after Controlled Cortical Impact in Rats

Combinatorial Motor Training Results in Functional Reorganization of Remaining Motor Cortex after Controlled Cortical Impact in Rats

Serotonin 1A Receptors Alter Expression of Movement Representations

Invasive Neurostimulation in Stroke Rehabilitation

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