Model-driven stimulation for targeted functional restoration in chronic spinal cord injury

脊髓损伤会由于神经通路的中断而导致损伤平面以下的运动和感觉功能丧失。这对生活质量造成了毁灭性的影响，急性期之后几乎没有恢复的希望。使用神经电调节的最新进展在恢复运动功能方面显示出了希望，尽管这些方法受到与植入侵入性刺激系统相关的风险的限制。靶向脊髓刺激的非侵入性系统的开发将是一个重大的进步，允许刺激促进的康复，同时避免与慢性植入相关的风险。目前，非侵入性刺激技术由于缺乏对经皮组织中电荷分布以及这种电荷分布如何影响神经组织的了解而受到限制。我们打算开发一种系统，用于准确预测非侵入性传递的电荷在底层组织中的分布，以及这种刺激对脊髓神经组织的影响。我们假设这项工作将允许我们使用非侵入性技术产生脊髓的局部刺激。这将为功能恢复打开特定靶向刺激的可能性，同时完全消除植入程序和长期植入电子设备带来的风险。我们提出的方法涉及神经解剖学和生理学的计算建模，以建立促进特定功能网络康复的靶向刺激的理论基础。这个项目属于EPSRC医疗保健技术研究领域。我们打算开发一个系统，当刺激电流施加在体表时，预测通过潜在脊髓的局部电流，并得出理想的电极位置和刺激参数到特定的脊髓目标区域，从而实现精确刺激。这将使我们能够评估给定的刺激场，从而给定的刺激范例，将对脊髓水平的神经网络产生的影响。利用这一模型，我们打算开发一种使用非侵入性刺激来靶向脊髓内特定生理网络的系统。我们将通过检测我们的模型衍生刺激方案通过靶向人类志愿者的背柱网络在特定区域产生局灶性感觉的能力来评估我们的方法非侵入性地产生所需神经网络的局灶性刺激的能力。这项工作将使我们能够进一步理解刺激对脊髓的影响。这将提高我们对非侵入性刺激效果的理解，并将为使用非侵入性技术进行靶向刺激奠定机制基础。从应用的角度来看，我们期望这项工作能产生一种有针对性的非侵入性功能恢复刺激系统，适用于脊髓损伤患者功能恢复的临床试验的正式评估。从长远来看，这项工作可能会改善慢性脊髓损伤患者的功能恢复，相关的功能状态和生活质量的改善。通过非侵入性技术的使用，消除了与植入刺激器相关的障碍和风险，使脊髓损伤患者能够更好地获得改善的功能恢复。

Injury to the spinal cord can lead to loss of motor and sensory function below the level of the lesion due to interruption of neural pathways. This has a devastating impact on quality of life, with little prospect of recovery beyond the acute phase. Recent advances using electrical neuromodulation have shown promise in restoring motor function, though these approaches are limited by the risks associated with the implantation of invasive stimulation systems.The development of a non-invasive system for targeted spinal cord stimulation would represent a significant advance by allowing stimulation-facilitated rehabilitation while avoiding the risks associated with chronic implantation. Currently, non-invasive stimulation technologies are limited by a poor understanding of the distribution of transcutaneous electrical charge in the underlying tissues and how this distribution of charge influences the underlying neural tissue. We intend to develop a system for accurately predicting the distribution of a non-invasively delivered electrical charge in the underlying tissue and the effect that this stimulation will have on the neural tissue of the spinal cord. We hypothesise that this work will allow us to generate focal stimulation of the spinal cord using non-invasive techniques. This would open the possibility of specifically targeted stimulation for functional recovery while completely eliminating the risks posed by implantation procedures and the presence of chronically implanted electronic devices.Our proposed methodology involves computational modelling of neural anatomy and physiology to establish the theoretical basis for targeted stimulation for facilitated rehabilitation of specific functional networks. This project falls within the EPSRC Healthcare Technologies research area.We intend to develop a system for predicting local current flow through the underlying spinal cord when stimulation currents are applied at the body surface, and for deriving the ideal electrode locations and stimulation parameters to specifically target areas of spinal cord, allowing precision stimulation.This will allow us to assess the effect that a given stimulation field, and therefore a given stimulation paradigm, will have on cord-level neural networks. Using this model, we intend to develop a system for targeting specific physiological networks within the spinal cord using non-invasive stimulation.We will assess the ability of our approach to generate focal stimulation of desired neural networks non-invasively by examining the ability of our model-derived stimulation protocols to produce focal paraesthesia in defined areas by targeting the dorsal column networks of human volunteers.This work will allow us to further our understanding of the effects of stimulation on the spinal cord. It will improve our understanding of the effects of non-invasive stimulation and will establish a mechanistic basis for targeted stimulation using non-invasive techniques. From an applied perspective, we anticipate this work generating a targeted non-invasive stimulation system for functional restoration, which will be suitable for formal assessment in clinical trials of functional recovery in spinal cord injured patients.In the long term, this work may allow improved functional restoration for patients following chronic spinal cord injury, with an associated improvement in functional status and quality of life. Through the use of non-invasive technology, the barriers to access and risks associated with implanted stimulators are removed, allowing far greater access to improved functional recovery among spinal cord injured patients.