Parker Samuel R, Calvert Jonathan S, Darie Radu, Jang Jaeson, Govindarajan Lakshmi Narasimhan, Angelino Keith, Chitnis Girish, Iyassu Yohannes, Shaaya Elias, Fridley Jared S, Serre Thomas, Borton David A, McLaughlin Bryan L
bioRxiv. 2024 Oct 2:2024.05.29.596250. doi: 10.1101/2024.05.29.596250.
Epidural electrical stimulation (EES) has shown promise as both a clinical therapy and research tool for studying nervous system function. However, available clinical EES paddles are limited to using a small number of contacts due to the burden of wires necessary to connect each contact to the therapeutic delivery device, limiting the treatment area or density of epidural electrode arrays. We aimed to eliminate this burden using advanced on-paddle electronics. We developed a smart EES paddle with a 60-electrode programmable array, addressable using an active electronic multiplexer embedded within the electrode paddle body. The electronics are sealed in novel, ultra-low profile hermetic packaging. We conducted extensive reliability testing on the novel array, including a battery of ISO 10993-1 biocompatibility tests and determination of the hermetic package leak rate. We then evaluated the EES device in vivo, placed on the epidural surface of the ovine lumbosacral spinal cord for 15 months. The active paddle array performed nominally when implanted in sheep for over 15 months and no device-related malfunctions were observed. The onboard multiplexer enabled bespoke electrode arrangements across, and within, experimental sessions. We identified stereotyped responses to stimulation in lower extremity musculature, and examined local field potential responses to EES using high-density recording bipoles. Finally, spatial electrode encoding enabled machine learning models to accurately perform EES parameter inference for unseen stimulation electrodes, reducing the need for extensive training data in future deep models. We report the development and chronic large animal in vivo evaluation of a high-density EES paddle array containing active electronics. Our results provide a foundation for more advanced computation and processing to be integrated directly into devices implanted at the neural interface, opening new avenues for the study of nervous system function and new therapies to treat neural injury and dysfunction.
硬膜外电刺激(EES)已展现出作为临床治疗手段和研究神经系统功能的研究工具的潜力。然而,现有的临床EES极板由于需要将每个触点连接到治疗输送设备的电线负担,仅限于使用少量触点,这限制了硬膜外电极阵列的治疗区域或密度。我们旨在使用先进的极板上电子设备消除这种负担。我们开发了一种智能EES极板,其具有60电极可编程阵列,可通过嵌入电极极板体内的有源电子多路复用器进行寻址。电子设备被密封在新型的超薄密封包装中。我们对新型阵列进行了广泛的可靠性测试,包括一系列ISO 10993-1生物相容性测试以及确定密封包装的泄漏率。然后,我们在体内评估了EES设备,将其放置在绵羊腰骶部脊髓的硬膜外表面15个月。当植入绵羊体内超过15个月时,有源极板阵列表现正常,未观察到与设备相关的故障。板载多路复用器能够在实验过程中进行定制的电极排列,包括跨电极排列和电极内部排列。我们确定了下肢肌肉组织对刺激的定型反应,并使用高密度记录双极电极检查了对EES的局部场电位反应。最后,空间电极编码使机器学习模型能够准确地对未见过的刺激电极进行EES参数推断,减少了未来深度模型中对大量训练数据的需求。我们报告了一种包含有源电子设备的高密度EES极板阵列的开发及其在大型动物体内的长期评估。我们的结果为将更先进的计算和处理直接集成到植入神经接口的设备中奠定了基础,为神经系统功能研究以及治疗神经损伤和功能障碍的新疗法开辟了新途径。
J Neural Eng. 2022-10-18
Brain Sci. 2024-6-27