Neuro-Marker Discovery for Accurate Localization of the Sub-Thalamic Nucleus for Deep Brain Stimulation

1067488脑深部电刺激（DBS）已成为美国帕金森患者最常见的手术治疗方法。在大脑的丘脑底核（STN）内立体定向植入DBS电极。DBS的临床疗效关键取决于STN的准确定位。目前，STN的初始手术轨迹是通过术前脑立体定向磁共振成像（MRI）确定的。DBS电极的最终位置在手术过程中通过从电生理记录中获得的数据进行修改——以单单元神经元活动（SUA）的形式，来源于多个微电极记录轨迹。然而，由于目前立体定向成像的局限性，微电极记录中SUA的隔离性差，以及人类受试者之间深部脑结构位置的解剖差异，DBS电极在STN内的最佳放置仍然具有挑战性。因此，需要新的技术来自动定位或为神经外科医生提供关于STN定位的额外证据。微电极还可用于记录局部场电位（LFPs），与SUA记录相反，LFPs代表电极尖端周围神经元群体的总体活动。然而，为了在临床上有用，LFP数据中的模式需要转换为另一种模式，以便临床医生能够解释它们。该项目的智力价值在于验证了术中记录的LFP数据可用于识别STN位置的假设。具体来说，该项目将记录连续深度的微观和宏观电极的lfp，因为这些电极被推进到STN。记录的神经数据将离线处理，使用最先进的信号处理和机器学习方法来识别新的神经标记物，这些标记物将用于优化STN中的电极放置。该研究项目将确定并验证与最佳电极定位相对应的特定lfp衍生数据的使用。这个跨学科项目的成果将有助于开发一种新技术，将微电极记录与计算智能融合在一起，以在DBS手术期间定位STN。所提出的研究工具将为设计一种新的DBS手术系统提供有价值的数据，该系统可以被世界各地的外科医生实施。该系统有望通过增强STN定位来缩短手术时间，通过减少所需的微电极记录次数来降低手术出血率，并显著降低DBS电极定位次优率，从而提高刺激效果。此外，拟议的努力旨在解决国家？美国目前在神经技术领域的理工科专业人才短缺。该项目的跨学科性质为研究生的教育提供了一个很好的环境，专注于医疗保健行业和新兴的神经调节领域的仪器使用。

1067488InceDeep brain stimulation (DBS) has become the most common surgical treatment in the U.S. for patients with Parkinson?s disease (PD), and involves the stereotactic implantation of a DBS electrode within the subthalamic nucleus (STN) of the brain. The clinical efficacy of DBS depends critically on accurate localization of the STN. Currently, the initial surgical trajectory to STN is determined by preoperative stereotactic magnetic resonance imaging (MRI) of the brain. The ultimate location of the DBS electrode is then modified during surgery by data obtained from electrophysiological recordings--in the form of single-unit neuronal activity (SUA), derived from multiple microelectrode recording tracks.However, optimal placement of DBS electrodes within STN remains challenging due to current limitations of stereotactic imaging, poor isolation of SUA during microelectrode recordings, and anatomical differences in the location of deep brain structures between human subjects. Consequently, new techniques are required which can automatically localize or provide additional evidence to the neurosurgeon about STN localization. Microelectrodes can also be used to record local field potentials (LFPs) which, in contrast to SUA recordings, represent aggregate activity from populations of neurons surrounding the electrode tip. However, to be clinically useful, patterns in LFP data need to be translated into another modality so that they can be interpreted by the clinician.The intellectual merit of this project resides in testing the hypothesis that LFP data recorded intraoperatively can be used to identify STN location. Specifically, this project will record LFPs from both micro- and macro-electrodes at consecutive depths, as these electrodes are advanced to STN. Recorded neural data will be processed offline, using state-of-the-art signal processing and machine learning methods to identify novel neuro-markers which will be used for the optimization of electrode placement in STN. This research project will identify and validate the use of specific LFP-derived data that correspond to optimal electrode positioning. The results of this interdisciplinary project will enable the development of a new technology for fusing microelectrode recordings with computational intelligence to localize STN during DBS surgery. The proposed research tools will provide valuable data for designing a new DBS surgery system that could be implemented by surgeons around the world. Such a system is expected to reduce the duration of the surgical procedure by enhancing STN localization, reduce the procedural hemorrhage rate by decreasing the number of microelectrode recording passes needed, and significantly decrease the rate of sub-optimal DBS electrode positioning, hence improving efficacy of stimulation. Moreover, the proposed efforts aim to address the nation?s current talent shortage in science and engineering majors in the field of neurotechnology. The interdisciplinary nature of the project offers a great environment for the education of graduate students with a concentration in instrumentation for use in the healthcare industry and the burgeoning field of neuromodulation.