CAREER: Stimulation on Demand: Responsive Deep Brain Stimulation for the Treatment of Tourette Syndrome

人类大脑由分布在空间上的众多网络组成，并随着时间的推移而连接，以协调与外部世界的有意义的互动。神经系统疾病破坏了这种相互作用，以及我们对身体的控制。脑深部电刺激（DBS）是在90年代出现的一种治疗运动障碍的神经外科手术。DBS背后的原理是将电极植入大脑深部结构，并注入电脉冲以抑制病理性大脑活动。然而，执行刺激设置程控的临床人员基于可观察到的患者反应做出决策，而不是基于对潜在病理或刺激生理反应的科学理解。PI提出的努力包括研究运动障碍的神经特征，以及刺激的后效，以提供针对患者当前临床状况的治疗方案。预期反应性DBS可改善症状抑制，减少连续刺激的不良影响，并延长DBS植入物的电池寿命。该项目还将为PI实验室的学生提供一个环境，促进神经工程系统设计，临床环境中的数据收集和大规模数据集分析的学习。所有这些技能对于残疾人转化医学应用的发展和下一代生物医学工程师的教育都是多产的。该项目的总体研究目标是使用能够记录人类大脑信号的下一代DBS设备研究神经系统疾病的电生理基础，以便响应性地将刺激传递到大脑的当前病理状态。为此，PI正在研究Tourette综合征的神经生理学，估计每1000名学龄儿童中有3至9名受影响，并开发响应性DBS系统，以改善人类的靶向治疗。将建立在线分类器，从丘脑中央中核和运动皮层的神经活动中检测以抽动秽语综合征为特征的非自愿抽动。DBS参数和神经活动之间的输入输出关系将被研究，以建立逆自适应控制器，将产生最佳的刺激参数。从这个项目和建立的平台中获得的知识可以扩展到其他运动障碍。该教育计划的总体目标是提高学生对STEM领域的兴趣和参与度，并通过一系列针对K-12、本科和研究生教育水平的教育活动来推广工程学研究。该项目将由MCB神经系统集群中的激活和调制计划共同资助，因此有资格获得BioMaps的共同资助。

The human brain consists of numerous networks distributed over space and connected over time to orchestrate meaningful interaction with the external world. Neurological disorders disrupt this interaction, as well as our control over our bodies. Deep brain stimulation (DBS) has emerged in the nineties as a neurosurgical intervention for the treatment of movement disorders. The principle behind DBS is to implant electrodes into deep brain structures and to inject electrical pulses to suppress pathological brain activity. The clinical personnel that perform programming of stimulation settings however, base their decisions on the observable patient responses rather than a scientific understanding of the underlying pathology, or the physiological response to stimulation. The PI's proposed effort includes studying the neural signatures of movement disorders, and the aftereffects of stimulation to provide insight into treatment options that can be tailored to the current clinical condition of the patient. Responsive DBS is expected to provide improved symptom suppression, reduce adverse effects of continuous stimulation, and prolong battery life of DBS implants. This project will also provide students in the PI's lab with an environment that promotes learning in the design of neural engineering systems, data collection in clinical settings, and analysis of large-scale datasets. All of these skills are prolific to the development of translational medicine applications for those suffering from disabilities, and to the education of the next generation of biomedical engineers.The overall research goal of this project is to study the electrophysiological underpinnings of neurological disorders using next generation DBS devices capable of recording brain signals in humans, in order to responsively deliver stimulation to the current pathological state of the brain. To this end, the PI is investigating the neurophysiology of Tourette syndrome, which affects an estimated 3 to 9 school-age children in 1000, and to develop responsive DBS systems for its improved and targeted treatment in humans. Online classifieres will be built to detect involuntary tics that characterize Tourette syndrome from neural activity in the centromedian nucleus of the thalamus and the motor cortex. The input-output relationship between DBS parameters and neural activity will be studied to build inverse adaptive controllers that will yield optimal stimulation parameters. The knowledge gained from this project and the established platform can be extended to other movement disorders. The overall objective of the educational plan is to increase interest and engagement in STEM fields and to proliferate the study of engineering through a series of focused educational activities at the K-12, undergraduate, and graduate education levels.The project will be co-funded by the Activation and Modulation Programs in the Neural Systems cluster of MCB and, therefore, is eligible for BioMaps co-funding.