Fabrication and testing of next generation cortical paddle leads for bidirectional neural interfaces

侵入性神经刺激是治疗精神疾病的一种很有前途的疗法，但与当代 神经刺激技术，在最近的临床试验中，许多患者都没有反应。为了改进 疗效，精神病学中的侵入性治疗可能需要更高级的电路层面的了解 紊乱，从而针对特定模式的异常神经活动。为了支持这一概念，短期内 侵入性记录揭示了特定精神症状的潜在生理生物标志物，如 抑郁和焦虑。信号发现和电路分析将通过新的可用的， 可长期植入的神经接口，既能提供神经刺激，又能无线串流感应 外部计算机的电子活动。这些设备--例如响应性神经刺激器(RNS， NeuroPace)或Summit RC+S(美敦力)在精神病学纵向关联方面具有巨大潜力 有神经活动的症状。然而，目前可用于 连接到这些接口对简单、安全的手术放置和信号发现构成了技术障碍。 可用的皮质记录导联具有低通道数(4个触点)和低空间分辨率(1厘米)，并且 机械上不灵活，无法接触到许多皮质区域。在这里，我们通过以下方式解决这个问题 设计、制造和测试具有有利于引线通过的机械性能的皮质引线 通过微创暴露。测试将包括台式测试和短期手术中测试 人体测试。将制造和测试两种引线设计，其中一种具有较低的多站点通道数 皮质记录，另一种，具有当前可用通道数量的两倍(8个触点)和改进的空间 决议。这些线索旨在与峰会RC+S联系，根据与 神经接口制造商。PI为这个项目带来了互补的专业知识：电气工程 有脑铅制造的专长；神经外科/神经生理学的专长是急性和 慢性皮质记录(皮层脑电图术)，用于检测大脑疾病的生理特征。 在这两年的授权期之后，我们预计将进行生物兼容性测试和FDA批准的永久 植入和商业化。拟议的工作将有助于部署新的可用的神经 接口，既用于电路分析，也用于开发“自适应刺激”，其中神经信号 用来自动调节刺激参数，对不断变化的大脑需求做出反应，减少刺激- 引起的不良反应。

Invasive neurostimulation is a promising therapy for psychiatric disease, but with contemporary neurostimulation techniques, many patients in recent clinical trials have been nonresponders. For improved efficacy, invasive therapies in psychiatry may require a more advanced circuit-level understanding of these disorders, so as to target specific patterns of abnormal neural activity. In support of this concept, short term invasive recordings have revealed potential physiological biomarkers of specific psychiatric symptoms such as depression and anxiety. Signal discovery and circuit analysis will be further facilitated by newly available, chronically implantable, neural interfaces that can both deliver neurostimulation and wirelessly stream sensed electrical activity to external computers. These devices – such as the responsive neurostimulaor (RNS, Neuropace) or Summit RC+S (Medtronic) have great potential for longitudinal correlations of psychiatric symptoms with neural activity. However, the permanently implantable cortical leads currently available to attach to these interfaces pose technical barriers to easy, safe surgical placement and signal discovery. Available cortical recording leads have a low channel count (4 contacts) low spatial resolution (1 cm), and are mechanically inflexible, precluding access to many cortical areas. Here, we address this problem by designing, fabricating, and testing cortical leads with mechanical properties favorable for the passage of leads through minimally invasive exposures. Testing will involve both benchtop tests and short term intraoperative human testing. Two lead designs will be fabricated and tested, one with lower channel count for multisite cortical recording, another with double the currently available channel count (8 contacts) and improved spatial resolution. These leads are designed to attach to Summit RC+S, under collaborative agreement with the neural interface manufacturer. The PIs bring complementary expertise to this project: electrical engineering with a specialty in brain lead fabrication; and neurosurgery/neurophysiology with a specialty in acute and chronic cortical recording (electrocorticography) for detection of physiological signatures of brain disorders. After this 2 year grant period, we expect to pursue biocompatibility testing and FDA approval for permanent implantation, and commercialization. The proposed work will facilitate the deployment of newly available neural interfaces, both for circuit analysis and for the development of “adaptive stimuluation”, in which neural signals are used to autoregulate stimulation parameters, to respond to changing brain needs and reduce stimulation- induced adverse effects.