Regulation of arousal and performance of a healthy non-human primate using closed-loop central thalamic deep brain stimulation.
Regulation of arousal and performance of a healthy non-human primate using closed-loop central thalamic deep brain stimulation.
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DOI：
10.1109/ner52421.2023.10123754
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发表时间：
2023-05-19
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影响因子：
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通讯作者：
Denison T
中科院分区：
文献类型：
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作者：
Baker JL;Toth R;Deli A;Zamora M;Fleming JE;Benjaber M;Goerzen D;Ryou JW;Purpura KP;Schiff ND;Denison T
闭环方法在系统神经科学和脑机接口中的应用有望彻底改变我们对大脑的理解，并开发新的神经调节策略来恢复失去的功能。据推测，哺乳动物大脑的前前脑中间电路（AFM）是皮层和纹状体唤醒调节的基础，并支持清醒期间的认知功能。据推测，唤醒调节功能障碍会导致各种神经系统疾病中的认知功能障碍，尤其是在创伤性脑损伤（TBI）后的患者中。几项临床研究探索了在 AFM 内使用每日中央丘脑深部脑刺激 (CT-DBS) 来恢复 TBI 患者的意识和执行注意力。在这项研究中，我们探索了闭环 CT-DBS 的使用，以间歇性调节健康非人类灵长类动物 (NHP) 的 AFM 唤醒，以恢复行为表现。我们使用瞳孔测量和近乎实时的 ECoG 信号分析来间歇性启动闭环 CT-DBS，在这里我们报告了我们增强唤醒和恢复动物表现的能力。然后使用定制的临床级 DBS 设备 DyNeuMo-X 对最初的基于计算机的方法进行了实验验证，DyNeuMo-X 是一个用于快速测试闭环 DBS 的双向研究平台。 DyNeuMo-X 在健康 NHP 中的成功实施支持了采用内部 DyNeuMo 系统（NCT05437393、NCT05197816）正在进行的临床试验，以及我们开发和加速部署新型神经调节方法来治疗结构性脑损伤和其他病因患者认知功能障碍的目标。
Application of closed-loop approaches in systems neuroscience and brain-computer interfaces holds great promise for revolutionizing our understanding of the brain and for developing novel neuromodulation strategies to restore lost function. The anterior forebrain mesocircuit (AFM) of the mammalian brain is hypothesized to underlie arousal regulation of the cortex and striatum, and support cognitive functions during wakefulness. Dysfunction of arousal regulation is hypothesized to contribute to cognitive dysfunctions in various neurological disorders, and most prominently in patients following traumatic brain injury (TBI). Several clinical studies have explored the use of daily central thalamic deep brain stimulation (CT-DBS) within the AFM to restore consciousness and executive attention in TBI patients. In this study, we explored the use of closed-loop CT-DBS in order to episodically regulate arousal of the AFM of a healthy non-human primate (NHP) with the goal of restoring behavioral performance. We used pupillometry and near real-time analysis of ECoG signals to episodically initiate closed-loop CT-DBS and here we report on our ability to enhance arousal and restore the animal's performance. The initial computer based approach was then experimentally validated using a customized clinical-grade DBS device, the DyNeuMo-X, a bi-directional research platform used for rapidly testing closed-loop DBS. The successful implementation of the DyNeuMo-X in a healthy NHP supports ongoing clinical trials employing the internal DyNeuMo system (NCT05437393, NCT05197816) and our goal of developing and accelerating the deployment of novel neuromodulation approaches to treat cognitive dysfunction in patients with structural brain injuries and other etiologies.