Neurostimulation for Stroke Rehabilitation

 So it is agreed the current ideas on neuroplasticity have no repeatable component.

WHOM is going to solve that problem? Specific names only.

Neurostimulation for Stroke Rehabilitation

Windsor Kwan-Chun Ting^†, Faïza Abdou-Rahaman Fadul^†, Shirley Fecteau and Christian Ethier^*

• Département de Psychiatrie et de Neurosciences, Centre de Recherche CERVO, Université Laval, Québec City, QC, Canada

Neurological injuries such as strokes can lead to important loss in motor function. Thanks to neuronal plasticity, some of the lost functionality may be recovered over time. However, the recovery process is often slow and incomplete, despite the most effective conventional rehabilitation therapies. As we improve our understanding of the rules governing activity-dependent plasticity, neuromodulation interventions are being developed to harness neural plasticity to achieve faster and more complete recovery. Here, we review the principles underlying stimulation-driven plasticity as well as the most commonly used stimulation techniques and approaches. We argue that increased spatiotemporal precision is an important factor to improve the efficacy of neurostimulation and drive a more useful neuronal reorganization. Consequently, closed-loop systems and optogenetic stimulation hold theoretical promise as interventions to promote brain repair after stroke.

Introduction

Stroke often leads to neuronal death and permanent dysfunction. It can cause substantial damage to the motor cortex, hinder motor control, and result in a decreased autonomy and quality of life. Through neural plasticity, the brain has the capability to reorganize by forming new connections among residual neurons, which may compensate at least in part for the lost ones. There is a critical time window of enhanced plasticity for 1–3 months after ischemic stroke, during which both spontaneous and intervention-mediated recovery is maximized (Zeiler and Krakauer, 2013). However, spontaneous reorganization is often maladaptive or insufficient to restore function to pre-insult levels. Building evidence suggests an important role for the relative timing of perisynaptic neuronal activity to drive plasticity (Feldman, 2012). Through neurostimulation, it is possible to induce a causal timing between the firing of two neurons and thereby induce Hebbian spike-timing-dependent plasticity (Markram et al., 1997; Bi and Poo, 1998). For this reason, a growing number of researchers are investigating different neurostimulation approaches with the goal of inducing targeted plastic changes in the nervous system to reduce the consequences of lesions and improve function.

Here, we review the main stimulation approaches and techniques which are being investigated, beginning with an examination of the general principles of stimulation-driven plasticity. Due to the complexity and heterogeneity of nervous system organization, we argue that more targeted stimulation techniques could be more effective in inducing plasticity, and could also result in a neural reorganization with greater functional benefits. Closed-loop stimulation paradigms have an important advantage in this regard, as they rely (at least for the presynaptic component) on naturally occurring patterns of brain activity. Therefore, this approach targets more specifically the neurons involved in voluntary motor control (Ethier et al., 2015). Optogenetic stimulation also has great potential as a tool to stimulate neurons selectively and induce synaptic changes in targeted neuronal subpopulations. This factor could be critical to improving the functional relevance of induced neural plasticity. Its eventual use in humans would pose important practical challenges and require new ethical frameworks. In the meantime, the use of optogenetic and electrical stimulation in animal models will advance our understanding of neural plasticity and recovery mechanisms. We focus on stroke in this review since it is one of the leading causes of death and disability worldwide and current treatments remain scarce. However, the principles of neuronal plasticity discussed, and the new methods available to understand and reshape neuronal connections could theoretically be applied with the appropriate modifications to other types of neurological or psychiatric conditions, providing a unified framework for treatment of brain disease and injury.

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