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

由于神经通路中断，脊髓损伤可导致损伤水平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，在急性期之后几乎没有康复的希望。尽管这些方法受到植入侵入性刺激系统的风险的限制，但最近使用电神经调节的进展在恢复运动功能方面显示出了希望。针对脊髓刺激的非侵入性系统的发展将是一个重大的进步，它允许刺激促进康复，同时避免了与慢性植入相关的风险。目前，非侵入性刺激技术受限于对经皮电荷在底层组织中的分布以及这种电荷分布如何影响底层神经组织的了解不足。我们打算开发一种系统，用于准确预测底层组织中非侵入性传递电荷的分布，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对脊髓产生局灶性刺激。这将为功能恢复提供有针对性的刺激，同时完全消除植入程序和长期植入电子设备带来的风险。我们提出的方法包括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。该项目属于EPSRC医疗保健技术研究领域。我们打算开发一种系统，用于预测当体表施加刺激电流时通过底层脊髓的局部电流，并为脊髓的特定目标区域提供理想的电极位置和刺激参数，从而实现精确刺激。这将使我们能够评估给定的刺激场以及给定的刺激范式对绳级神经网络的影响。利用这个模型，我们打算开发一个系统，针对脊髓内使用非侵入性刺激的特定生理网络。我们将通过检查我们的模型衍生的刺激方案在特定区域通过针对人类志愿者的背柱网络产生局灶性感觉异常的能力，来评估我们的方法在非侵入性地产生所需神经网络的局灶性刺激的能力。这项工作将使我们进一步了解刺激对脊髓的影响。它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建立机制基础。从应用的角度来看，我们期望本工作能够产生一种针对脊髓损伤患者功能恢复的靶向性无创刺激系统，适合于在脊髓损伤患者功能恢复的临床试验中进行正式评估。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，并改善其功能状态和生活质量。通过使用非侵入性技术，消除了植入刺激器的使用障碍和相关风险，使脊髓损伤患者更容易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.