神经科学的研究和实时功能皮层映射记录人力Electrocorticographic（ECOG）信号

摘要

我们提出了一个收集用于研究目的的人类正在侵入性癫痫监测electrocorticographic信号的方法。我们展示了如何使用数据采集，信号处理和刺激呈现的BCI2000软件平台。具体来说，我们证明，一个实时脑功能映射的的BCI2000基于工具SIGFRIED。

摘要

Neuroimaging studies of human cognitive, sensory, and motor processes are usually based on noninvasive techniques such as electroencephalography (EEG), magnetoencephalography or functional magnetic-resonance imaging. These techniques have either inherently low temporal or low spatial resolution, and suffer from low signal-to-noise ratio and/or poor high-frequency sensitivity. Thus, they are suboptimal for exploring the short-lived spatio-temporal dynamics of many of the underlying brain processes. In contrast, the invasive technique of electrocorticography (ECoG) provides brain signals that have an exceptionally high signal-to-noise ratio, less susceptibility to artifacts than EEG, and a high spatial and temporal resolution (i.e., <1 cm/<1 millisecond, respectively). ECoG involves measurement of electrical brain signals using electrodes that are implanted subdurally on the surface of the brain. Recent studies have shown that ECoG amplitudes in certain frequency bands carry substantial information about task-related activity, such as motor execution and planning¹, auditory processing² and visual-spatial attention³. Most of this information is captured in the high gamma range (around 70-110 Hz). Thus, gamma activity has been proposed as a robust and general indicator of local cortical function^1-5. ECoG can also reveal functional connectivity and resolve finer task-related spatial-temporal dynamics, thereby advancing our understanding of large-scale cortical processes. It has especially proven useful for advancing brain-computer interfacing (BCI) technology for decoding a user's intentions to enhance or improve communication⁶ and control⁷. Nevertheless, human ECoG data are often hard to obtain because of the risks and limitations of the invasive procedures involved, and the need to record within the constraints of clinical settings. Still, clinical monitoring to localize epileptic foci offers a unique and valuable opportunity to collect human ECoG data. We describe our methods for collecting recording ECoG, and demonstrate how to use these signals for important real-time applications such as clinical mapping and brain-computer interfacing. Our example uses the BCI2000 software platform^8,9 and the SIGFRIED¹⁰ method, an application for real-time mapping of brain functions. This procedure yields information that clinicians can subsequently use to guide the complex and laborious process of functional mapping by electrical stimulation.

Prerequisites and Planning:

Patients with drug-resistant partial epilepsy may be candidates for resective surgery of an epileptic focus to minimize the frequency of seizures. Prior to resection, the patients undergo monitoring using subdural electrodes for two purposes: first, to localize the epileptic focus, and second, to identify nearby critical brain areas (i.e., eloquent cortex) where resection could result in long-term functional deficits. To implant electrodes, a craniotomy is performed to open the skull. Then, electrode grids and/or strips are placed on the cortex, usually beneath the dura. A typical grid has a set of 8 x 8 platinum-iridium electrodes of 4 mm diameter (2.3 mm exposed surface) embedded in silicon with an inter-electrode distance of 1cm. A strip typically contains 4 or 6 such electrodes in a single line. The locations for these grids/strips are planned by a team of neurologists and neurosurgeons, and are based on previous EEG monitoring, on a structural MRI of the patient's brain, and on relevant factors of the patient's history. Continuous recording over a period of 5-12 days serves to localize epileptic foci, and electrical stimulation via the implanted electrodes allows clinicians to map eloquent cortex. At the end of the monitoring period, explantation of the electrodes and therapeutic resection are performed together in one procedure.

In addition to its primary clinical purpose, invasive monitoring also provides a unique opportunity to acquire human ECoG data for neuroscientific research. The decision to include a prospective patient in the research is based on the planned location of their electrodes, on the patient's performance scores on neuropsychological assessments, and on their informed consent, which is predicated on their understanding that participation in research is optional and is not related to their treatment. As with all research involving human subjects, the research protocol must be approved by the hospital's institutional review board. The decision to perform individual experimental tasks is made day-by-day, and is contingent on the patient's endurance and willingness to participate. Some or all of the experiments may be prevented by problems with the clinical state of the patient, such as post-operative facial swelling, temporary aphasia, frequent seizures, post-ictal fatigue and confusion, and more general pain or discomfort.

At the Epilepsy Monitoring Unit at Albany Medical Center in Albany, New York, clinical monitoring is implemented around the clock using a 192-channel Nihon-Kohden Neurofax monitoring system. Research recordings are made in collaboration with the Wadsworth Center of the New York State Department of Health in Albany. Signals from the ECoG electrodes are fed simultaneously to the research and the clinical systems via splitter connectors. To ensure that the clinical and research systems do not interfere with each other, the two systems typically use separate grounds. In fact, an epidural strip of electrodes is sometimes implanted to provide a ground for the clinical system. Whether research or clinical recording system, the grounding electrode is chosen to be distant from the predicted epileptic focus and from cortical areas of interest for the research. Our research system consists of eight synchronized 16-channel g.USBamp amplifier/digitizer units (g.tec, Graz, Austria). These were chosen because they are safety-rated and FDA-approved for invasive recordings, they have a very low noise-floor in the high-frequency range in which the signals of interest are found, and they come with an SDK that allows them to be integrated with custom-written research software. In order to capture the high-gamma signal accurately, we acquire signals at 1200Hz sampling rate-considerably higher than that of the typical EEG experiment or that of many clinical monitoring systems. A built-in low-pass filter automatically prevents aliasing of signals higher than the digitizer can capture. The patient's eye gaze is tracked using a monitor with a built-in Tobii T-60 eye-tracking system (Tobii Tech., Stockholm, Sweden). Additional accessories such as joystick, bluetooth Wiimote (Nintendo Co.), data-glove (5^th Dimension Technologies), keyboard, microphone, headphones, or video camera are connected depending on the requirements of the particular experiment.

Data collection, stimulus presentation, synchronization with the different input/output accessories, and real-time analysis and visualization are accomplished using our BCI2000 software^8,9. BCI2000 is a freely available general-purpose software system for real-time biosignal data acquisition, processing and feedback. It includes an array of pre-built modules that can be flexibly configured for many different purposes, and that can be extended by researchers' own code in C++, MATLAB or Python. BCI2000 consists of four modules that communicate with each other via a network-capable protocol: a Source module that handles the acquisition of brain signals from one of 19 different hardware systems from different manufacturers; a Signal Processing module that extracts relevant ECoG features and translates them into output signals; an Application module that delivers stimuli and feedback to the subject; and the Operator module that provides a graphical interface to the investigator.

A number of different experiments may be conducted with any given patient. The priority of experiments will be determined by the location of the particular patient's electrodes. However, we usually begin our experimentation using the SIGFRIED (SIGnal modeling For Realtime Identification and Event Detection) mapping method, which detects and displays significant task-related activity in real time. The resulting functional map allows us to further tailor subsequent experimental protocols and may also prove as a useful starting point for traditional mapping by electrocortical stimulation (ECS).

Although ECS mapping remains the gold standard for predicting the clinical outcome of resection, the process of ECS mapping is time consuming and also has other problems, such as after-discharges or seizures. Thus, a passive functional mapping technique may prove valuable in providing an initial estimate of the locus of eloquent cortex, which may then be confirmed and refined by ECS. The results from our passive SIGFRIED mapping technique have been shown to exhibit substantial concurrence with the results derived using ECS mapping¹⁰.

The protocol described in this paper establishes a general methodology for gathering human ECoG data, before proceeding to illustrate how experiments can be initiated using the BCI2000 software platform. Finally, as a specific example, we describe how to perform passive functional mapping using the BCI2000-based SIGFRIED system.

研究方案

1。电极定位

1. 收集手术前的T1加权结构患者的头部MRI（1.5T或3T）：每片256×256像素，满场，无插补，1毫米层厚，最好是矢状断面。
2. 观察手术植入的电网和钢带。收集原位电极植入的电网和钢带的位置上的数码照片，神经外科医生的笔记。
3. 收集手术后颅骨的X射线图像在高分辨率和脑CT扫描（层厚1毫米，皮肤对皮肤，无角）。
4. 创建一个病人的大脑手术前MRI和合作注册使用电网后植入CT图像的三维皮质模型。用于此目的，我们的咖喱软件包，导出3D皮质结构和电极在MATLAB格式的坐标。从MATLAB中，我们导出影片，显示映射到大脑的电极。我们还米AP电极坐标标准布罗德曼领域使用自动化Talairach图谱。
5. 检讨从三维模型中，X射线图像，照片和票据信息。敲定的电极，并与医院技术人员的工作，以确保电极到分配器修补后，这个号码正是编号方案。还创建了一个原理图绘制在两个方面，如所有的电极位置，可以清楚地区别而不重叠的电极布局。如果你要运行SIGFRIED（见第4节），作为一个BCI2000参数片段保存这两个三维坐标，由ElectrodeLocations参数要求的格式。最后，选择两个电极的位置，有可能是electrocorticographically“沉默”，即，他们是不假定雄辩皮层附近，作为一个初步的地面和参考使用（准备修补蓝色插槽g.USBamps和地面黄色的插座上，各单位的极右）。

2。硬件和软件安装

1. 确保电脑的规格足以处理实验的加工要求。多核心处理器将有可能是必要的，以适应实时数据采集和处理，录像，和其他必要的任务的要求。在1200赫兹128通道的录音和实时分析，我们使用3 GHz四核心机与4 GB的RAM。应连接到一个专用的USB控制器，有别于其他带宽密集型的外围设备，如外部驱动器和数码相机（这可以通过该系统的设备管理器验证），所使用的控制器（S）的放大器。最后，必须有足够的磁盘空间存储多达5 MB每秒的实验数据，归档和备份系统。
2. 设立科研设备（放大器，计算机，实验者的屏幕，keyboARD，扬声器，麦克风和摄像头）一个单一的手推车，可以快速推出和病人的房间里，只有一个电源线插入到墙壁上。移动电脑从房间到另一个房间，使用休眠功能，然后再拔出。病人的视频画面，应该是一个单独的餐桌上或显示器的手臂。考虑到病人很容易发作，使确定的方式推出了，所有的设备可以迅速的情况下，医务人员需要立即获得病人。之前和之后，在病人的房间里使用的设备也应进行消毒杀菌湿巾。
3. 与病人的时间是有限的，和所有程序需要健全和优化，使最好的利用时间。在这方面，BCI2000的灵活性和鲁棒性是非常宝贵的特点。确保实验可以在触摸一个按钮启动。在BCI2000的情况下，使用一个批处理文件来启动正确的组合自动BCI2000模块，所需的命令行选项。 算和gUSBampSource模块是必需的，连同适当SignalProcessing和应用模块，为您的特定实验。使用BCI2000的操作脚本功能，以确保所有必需的参数文件装入自动包括任何具体这个病人，如电极的数量和他们的名字和位置。这种自动化的目的是为了最大限度地减少手动步骤由实验者的数量，从而错误的机会。软件和它的参数需要已完成和测试（或许与脑电图主题）至少有一个或两个星期前植入。执行一个“干”的第一次实验会议的前一天，包括所有的新病人的具体参数，这也是非常可取的。

3。实验性会议确定

1. 选择你的时刻实验记录表明病人，让他们注意到在当天早些时候，前15分钟后重启动。解决游客，吃饭，午睡，医疗程序，以及病人的身体，情绪和认知状态。重要的是建立在地板上的医务人员1融洽，以帮助在优化录音的时间和持续时间。
2. 轮设备到位，连接到电源插座，打开主题的视频画面，并把它连接到计算机，联合国休眠的计算机。
3. 推出BCI2000。启用，随着VisualizeSource参数，按设定配置 。信号查看器打开，让你的脑电图信号质量评估。右键单击观众和高通滤波器设置5赫兹截止。 （此过滤器的设置将只影响可视化，而不是数据收集。）
4. 从电源线噪声干扰：检查是否激活，在观众的陷波滤波器（50 Hz或60 Hz，这取决于你是在哪个国家）信号作出很大的区别吗？如果是这样，尽量减少删除任何未使用的电缆交叉谈话，或查明和消除电源干扰其他来源。如果有必要的参考和地面的改变所用的电极。
5. 如果您正在使用眼睛跟踪器，使用制造商提供的校准软件校准。 BCI2000源模块应与EyetrackerLogger包括延长编制，并应与推出 - LogEyetracker = 1标志的启用，使眼球跟踪数据可以同步获得的脑电图信号。
6. 为了避免分心和干扰，并尽可能减少信号干扰，确保关掉电视，收音机和手机。
7. 给予明确指示，以病人为你要运行的实验。根据主体的任务，准备PowerPoint幻灯片显示任务，建议姿势等，可以证明是有用的。
8. 操作员按下启动开始实验。您每次按下启动或恢复，将创建一个新文件，以避免覆盖以前的数据，该文件将被初始化所有参数值的副本。原始数据，然后将流自动的文件，随着事件标记，直到你按下暂停或实验运行结束。
9. 整个会议期间，监测病人的行为和疑似癫痫的脑电图信号，并随时准备应对医务人员的指示。

4。例如实验会议：SIGFRIED临床BCI2000映射

1. 制备方法：在会议开始之前，你将需要有准备了model.ini文件，它包含的信号处理设置SIGFRIED将用于建立一个模型，并包含一个成对倒数文件（或单独的PRM片段。）BCI2000参数。 SigfriedSigProc模块将用于实时可视化。两个关键参数是ElectrodeLocations，你选择了这名病人的特殊电极，ElectrodeCondition，指定不同的任务将在何种情况下映射指定的2-D的布局。在这个例子中，我们使用的是病人沟通说明简单StimulusPresentation模块，所以还需要适应的刺激参数，我们打算运行的任务。
2. 基线步骤：开始的gUSBampSource，DummySignalProcessing和StimulusPresentationTask的模块，配置从所有网格和1200Hz的带样品脑电图活动，在0.1 Hz的高通滤波。指示主题的放松和保持睁着眼睛一动不动。创纪录的6分钟的基线活动，在一个安静的环境下舒适的照明。
3. 建模步骤：启动data2model_gui工具，并在5赫兹箱FR提取功能OM 70至110赫兹，使用最大熵方法，每500毫秒的数据。按建立模型，以建立一个选定的光谱特征，利用高斯混合的概率模型。
4. 映射步骤：启动gUSBampSource，SigfriedSigProcLAVA和StimulusPresentationTask模块和配置操作加载的概率模型，皮质模型，2 -和3维的电极坐标。指导课题后，开始的映射过程。在这个过程中，一个主题将执行每个任务的10秒的时间，每5重复。在每个任务中，SIGFRIED检测任务有关的脑电图活动，在不断更新2 - 和雄辩皮质三维地图。在2维地图，每个圆圈的大小和发红的代表在这个特殊任务的重要性。具体来说，每个圆圈的大小是成比例的伽玛BA总信号方差的一小部分第二，占任务。这一统计数字是被称为决定系数，或r ^2。它是在范围（0,1），在当前的设置值0.1一般被认为是显着。使用滑块（ 见图1C），可以控制缩放到最大的R ²值的圆圈。在三维地图，R ^2的值映射到不同的颜色，而不是圆的大小。

5。代表结果

图1显示了有代表性的成果，从一个SIGFRIED映射在一个病人会议。病人是一个28岁的右手女性有棘手的本地化相关的左颞癫痫发病中学概括。 ，120 electrocorticographic电极植入硬膜下过左额叶，顶叶和颞叶皮层。侧位X射线（A组）和术中照片（B组）描绘配置正面电网与40个电极，一个高密度的时空网格，68电极和4电极每3条。从记录发作，神经学家本地化的致痫灶和决心，有必要进行手术切除左颞叶，而不惜雄辩的语言皮层。这是顺利完成：在8个月后切除患者已被扣押及无神经功能缺损的评估。被动的映射的过程SIGFRIED确定通过对比任务相关的变化，在听取任务涉及语言功能的皮质。这项研究结果发表在两个接口：一个2维界面（C组），从而使电极的布局清晰，一个三维解剖正确的接口（面板D）。由左到右边的面板听力语言与基线（音）的对比色调与基线（音），听，听口头语言与LIS各自使用不同的以音（语言）。这些粗糙的画面，是接受语言特定的听觉功能。的声音条件，结果表明，在这精英打乱了这名病人接受语言功能（面板一个黄色圆圈标记）的位置很好的协议。

图1。从一个病人的例子结果。小组A显示了一个横向的X射线。黄色圆圈标记，随后确定由大脑皮层电刺激映射在接受语言牵连的电极。 B组是在植入过程中拍摄的照片。 C组显示在原理图的二维布局SIGFRIED测绘成果：每张光盘的大小和发红代表意义的任务在每个电极，相对于基线的参与。面板D，相同的统计数据被映射到一个三维的大脑模型仁德色从病人的MRI红色。

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讨论

脑电图数据收集研究需要临床医生和研究人员之间的密切合作，以高度的多学科团队解决问题，在临床神经病学，神经外科，基础神经科学，计算机科学与电气工程。奖励是脑电图信号，特别是在中高伽玛频率范围（70-110Hz）的幅度，是非常宝贵的。他们不仅提供了认知神经相关科学的见解，感觉和马达在高时空分辨率处理^1-4，但脑电图脑计算机接口的研究也表明，作为一个神经义肢的基...

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