本材料基于美国国家科学基金会研究生研究奖学金计划 （DGE-2140004）、威尔神经枢纽和美国国立卫生研究院 （UH3NS100544） 支持的工作。本材料中表达的任何意见、发现、结论或建议均为作者的观点，并不一定反映美国国家科学基金会、威尔神经中心或美国国立卫生研究院的观点。我们感谢张天娇在平台设计和视频数据整合方面的专家咨询。我们特别感谢患者参与这项研究，并感谢他们对网络安全和平台设计的反馈和建议。

优化神经系统疾病患者的脑深部刺激

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作者没有要披露的利益冲突。

我们分享了多模态数据收集平台的家庭原型设计，以支持神经调控研究的未来研究。该设计是开源和模块化的，因此可以更换任何硬件，并且可以更新或更改任何软件组件，而不会使整个平台崩溃。虽然收集和去标识化神经数据的方法特定于所选的 INS，但行为数据收集的其余方法和整体方法与使用哪种植入式设备无关。我们将该平台部署到帕金森病患者的家中，并在实验和自然时期收集数据。在...

脑深部刺激 （DBS） 通过将电流直接输送到大脑的特定区域来治疗帕金森病 （PD） 等神经系统疾病。据估计，全世界有 850 万例帕金森病病例，当药物不足以控制症状时，DBS 已被证明是一种关键疗法 1,2。然而，DBS 的有效性可能会受到副作用的限制，这些副作用有时由通常以固定振幅、频率和脉冲宽度3 进行的刺激引起。这种开环实施对症状状态的波动没有反应，导致刺激设置与患者不断变化的需求不相适应。DBS进一步受到耗时的刺激参数调整过程的阻碍，目前由临床医生为每个患者手动执行。
自适应 DBS （aDBS） 是一种闭环方法，通过在检测到与症状相关的生物标志物时实时调整刺激参数，被证明是 DBS 的有效下一次迭代 3,4,5。研究表明，丘脑底核 （STN） 中的 β 振荡 （10-30 Hz） 在运动迟缓期间持续发生，运动迟缓是 PD 6,7 的特征。同样，已知皮层中的高伽马振荡 （50-120 Hz） 发生在运动障碍期间，这是一种过度和不自主的运动，在 PD8 中也很常见。最近的工作已经成功地在诊所外长时间施用 aDBS[5]，然而，当患者在家时，在诊所内配置的 aDBS 算法的长期有效性尚未确定。
需要远程系统来捕捉这些动态算法在抑制日常生活中遇到的症状时随时间变化的有效性。虽然 aDBS 的动态刺激方法有可能实现更精确的治疗并减少副作用3,9，但 aDBS 仍然给临床医生带来沉重的负担，需要手动识别每个患者的刺激参数。除了在传统DBS期间已经需要编程的大量参数外，aDBS算法还引入了许多新参数，这些参数也必须仔细调整。这种刺激和算法参数的组合产生了一个巨大的参数空间，其中可能组合的数量难以管理，从而禁止 aDBS 扩展到许多患者10。即使在研究环境中，配置和评估 aDBS 系统所需的额外时间也使得仅在临床中充分优化算法变得困难，并且需要远程更新参数。为了使 aDBS 成为一种可以扩展的治疗方法，必须自动化刺激和算法参数调整。此外，必须在重复试验中分析治疗结果，以将 aDBS 确定为临床外可行的长期治疗。需要一个平台来收集数据以远程评估治疗效果，并远程部署对 aDBS 算法参数的更新。
该协议的目标是为多模态家庭数据收集平台提供可重复使用的设计，以提高临床外的 aDBS 有效性，并使这种治疗能够扩展到更多的个体。据我们所知，这是第一个使用家用摄像机、可穿戴传感器、慢性神经信号记录和患者驱动的反馈来远程评估治疗结果的数据收集平台设计，以评估受控任务和自然行为期间的 aDBS 系统。
该平台是一个硬件和软件组件的生态系统，建立在先前开发的系统5 之上。在初始安装最少的硬件后，它可以完全通过远程访问进行维护，以允许在家中舒适地从人们那里收集多模式数据。一个关键组件是植入式神经刺激系统 （INS）11 ，它感知神经活动并向 STN 提供刺激，并记录胸部植入物的加速度。对于初始部署中使用的植入物，从植入 STN 的双侧导联和植入运动皮层的皮质电图电极记录神经活动。视频记录系统可帮助临床医生监控症状严重程度和治疗效果，其中包括图形用户界面 （GUI），可轻松取消正在进行的记录，以保护患者隐私。对视频进行处理以提取二维 （2D） 或三维 （3D） 位置的运动轨迹，并将智能手表佩戴在双手腕上以捕获角速度和加速度信息。重要的是，所有数据在传输到长期云存储之前都经过加密，并且只能通过虚拟专用网络 （VPN） 访问具有患者身份视频的计算机。该系统包括两种方法，用于对所有数据流进行事后时间对齐，数据用于远程监测患者的运动质量，并识别与症状相关的生物标志物，以改进aDBS算法。这项工作的视频部分展示了数据收集过程和从收集的视频中提取的运动轨迹动画。
许多设计考虑因素指导了协议的开发： 确保数据安全和患者隐私： 收集可识别的患者数据需要在传输和存储时格外小心，以便符合健康保险流通与责任法案 （HIPAA）12,13 遵守并尊重患者在自己家中的隐私。在这个项目中，这是通过设置自定义VPN来实现的，以确保系统计算机之间所有敏感流量的隐私。 刺激参数安全边界： 在尝试可能产生意外效果的 aDBS 算法时，确保患者保持安全至关重要。患者的 INS 必须由临床医生配置，使其具有刺激参数的安全边界，不允许过度刺激或刺激不足产生不安全的影响。使用INS系统11 在本研究中，此功能由临床医生程序员启用。 确保患者否决： 即使在安全参数范围内，症状和刺激反应的每日变化也可能导致患者不愉快的情况，即他们不喜欢被测算法并希望恢复正常的临床开环 DBS。所选的 INS 系统包括一个患者遥测模块 （PTM），允许患者手动更改其刺激组和刺激幅度（以 mA 为单位）。还有一个与INS连接的研究应用程序，用于在数据收集之前对INS进行远程配置14，这也使患者能够中止 aDBS 试验并控制他们的治疗。 捕捉复杂而自然的行为： 视频数据被整合到平台中，使临床医生能够远程监测治疗效果，并从姿势估计中提取运动轨迹以用于研究分析15.虽然可穿戴传感器的侵入性较小，但仅使用可穿戴系统很难捕获整个身体的整个动态运动范围。视频可以同时记录患者随时间推移的整个运动范围及其症状。 系统对患者的可用性： 收集家庭多模式数据需要在患者家中安装和使用多个设备，这可能会给患者带来负担。为了使系统易于使用，同时确保患者控制，在开始记录之前，必须手动打开植入或物理连接到患者的设备（在这种情况下，它包括 INS 系统和智能手表）。对于与患者分开的设备（在这种情况下，它包括从摄像机记录的数据），记录会自动开始和结束，而无需任何患者交互。在 GUI 设计过程中，我们小心翼翼地尽量减少按钮的数量，并避免使用较深的菜单树，以便简化交互。安装完所有设备后，研究协调员向患者展示了如何通过面向患者的 GUI（每个设备的一部分）与所有设备进行交互，例如如何终止任何设备上的记录以及如何输入他们的用药史和症状报告。 数据收集透明度：必须清楚地指示相机何时打开，以便人们知道他们何时被录制，并在需要片刻的隐私时可以暂停录制。为了实现这一点，使用摄像系统应用程序通过面向患者的 GUI 来控制视频录制。当应用程序启动时，GUI 会自动打开，并列出下一次计划录制的时间和日期。当录制正在进行时，会显示一条消息，说明录制计划何时结束。在 GUI 的中央，显示红灯的大图像。该图像显示，每当录制正在进行时，灯光都会亮起，而当录制关闭时，灯光会变为不亮的图像。
该协议详细说明了设计、构建和部署家庭数据收集平台的方法，用于对收集的数据进行完整性和稳健性的质量检查，以及用于未来研究的后处理数据的方法。
<img alt="Figure 1" class="xfigimg" src="/files/ftp_upload/65305/65305fig01.jpg"> 图 1：数据流。 每种模式的数据都是从患者的住所独立收集的，然后进行处理并聚合到单个远程存储端点中。每种模式的数据都会自动发送到远程存储终结点。在团队成员之一的帮助下，可以检索它，检查其有效性，跨模态进行时间调整，以及进行更多特定于模态的预处理。然后，编译后的数据集将上传到远程存储终结点，所有团队成员都可以安全地访问该终结点以进行继续分析。所有具有数据访问权限的机器，尤其是原始视频等敏感数据，都包含在 VPN 中，确保所有数据安全传输并始终加密存储数据。 <a href="https://www.jove.com/files/ftp_upload/65305/65305fig01large.jpg" target="_blank">请点击这里查看此图的较大版本.</a>

<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always">
	<tbody>
		<tr>
			<td>Analysis RCS Data Processing</td>
			<td>OpenMind</td>
			<td></td>
			<td>https://github.com/openmind-consortium/Analysis-rcs-data, open-source</td>
		</tr>
		<tr>
			<td>Apple Watches</td>
			<td>Apple, Inc</td>
			<td></td>
			<td>Use 2 watches for each patient, one on each wrist</td>
		</tr>
		<tr>
			<td>BRIO ULTRA HD PRO BUSINESS WEBCAM</td>
			<td>Logitech</td>
			<td>960-001105</td>
			<td>Used 3 in our platform design&#160;</td>
		</tr>
		<tr>
			<td>DaVinci Resolve video editing software&#160;</td>
			<td>DaVinci Resolve</td>
			<td></td>
			<td>used to support camera calibration</td>
		</tr>
		<tr>
			<td>Dell XPS PC&#160;</td>
			<td>Dell</td>
			<td></td>
			<td>2T hard disk drive, 500GB SSD</td>
		</tr>
		<tr>
			<td>Dropbox</td>
			<td>Dropbox</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>ffmpeg&#160;</td>
			<td>N/A</td>
			<td></td>
			<td>open-source, install to run the Video Recording App</td>
		</tr>
		<tr>
			<td>Gooseneck mounts for webcams</td>
			<td>N/A</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>GPU</td>
			<td>Nvidia</td>
			<td></td>
			<td>A minimum of 8GB GPU memory is recommended to run OpenPose, 12GB is ideal</td>
		</tr>
		<tr>
			<td>Java 11</td>
			<td>Oracle</td>
			<td></td>
			<td>Install to run the Video Recording App</td>
		</tr>
		<tr>
			<td>Microsoft Surface tablet&#160;</td>
			<td>Microsoft</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>NoMachine&#160;</td>
			<td>NoMachine</td>
			<td></td>
			<td>Ideal when using a Linux OS, open-source</td>
		</tr>
		<tr>
			<td>OpenPose&#160;</td>
			<td>N/A</td>
			<td></td>
			<td>open-source</td>
		</tr>
		<tr>
			<td>Rclone file transfer program</td>
			<td>Rclone</td>
			<td></td>
			<td>Encrypts data and copies or moves data to offsite storage, open-source</td>
		</tr>
		<tr>
			<td>StrivePD app</td>
			<td>RuneLabs</td>
			<td></td>
			<td>We installed the app on the Apple Watches to start recordings and upload data to an online portal.</td>
		</tr>
		<tr>
			<td>Summit RC+S neuromodulation system</td>
			<td>Medtronic</td>
			<td></td>
			<td>For investigational use only</td>
		</tr>
		<tr>
			<td>touchscreen-compatible monitor</td>
			<td>N/A</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Video for Linux 2 API</td>
			<td>The Linux Kernel</td>
			<td></td>
			<td>Install if using a Linux OS for video recording&#160;</td>
		</tr>
		<tr>
			<td>Wasabi&#160;</td>
			<td>Wasabi</td>
			<td></td>
			<td>Longterm cloud data storage</td>
		</tr>
		<tr>
			<td>WireGuard VPN Protocol</td>
			<td>WireGuard</td>
			<td></td>
			<td>open-source</td>
		</tr>
	</tbody>
</table>

bringing the clinic home: an at-home multi-modal data collection ecosystem to support adaptive deep brain stimulation

适应性脑深部刺激 （aDBS） 有望改善帕金森病 （PD） 等神经系统疾病的治疗。aDBS使用与症状相关的生物标志物实时调整刺激参数，以更精确地针对症状。为了实现这些动态调整，必须为每个患者确定 aDBS 算法的参数。这需要临床研究人员进行耗时的手动调整，因此很难为单个患者找到最佳配置或扩展到多个患者。此外，当患者在家时，在诊所内配置的 aDBS 算法的长期有效性仍然是一个悬而未决的问题。为了大规模实施这种疗法，需要一种在远程监测治疗结果的同时自动配置aDBS算法参数的方法。在本文中，我们分享了一个家庭数据收集平台的设计，以帮助该领域解决这两个问题。该平台由一个开源的集成硬件和软件生态系统组成，允许在家中收集神经、惯性和多摄像头视频数据。为了确保患者身份数据的隐私，该平台通过虚拟专用网络加密和传输数据。这些方法包括对数据流进行时间对齐和从视频记录中提取姿态估计。为了演示该系统的使用，我们将该平台部署到帕金森病患者的家中，并在 1.5 年的时间里收集了自我指导临床任务和自由行为期间的数据。记录亚治疗、治疗和超治疗刺激幅度的数据，以评估不同治疗条件下的运动症状严重程度。这些时间对齐的数据表明，该平台能够同步家庭多模态数据收集，以进行治疗评估。该系统架构可用于支持自动化 aDBS 研究、收集新数据集以及研究临床外 DBS 治疗对神经系统疾病患者的长期影响。

原型平台设计和部署 我们设计了一个原型平台，并将其部署到单个患者的家中（图 1）。在家中首次安装硬件后，可以对平台进行维护，并完全通过远程访问收集数据。INS 设备、智能手表和摄像头具有面向患者的应用程序，允许患者开始和停止记录。视频采集硬件可在配置批准的计划后启用自动视频录制。患者只需按下视频录制应用程序 GUI 上的按钮即可轻?...

Watch this Scientific Journal Video about Automated Deep Brain Stimulation for Parkinson's Disease - Exploring the Possibilities and Challenges of Home Monitoring at JoVE.com

作者聚焦：帕金森病的自动脑深部刺激 - 探索家庭监测的可能性和挑战 

该协议展示了家庭多模态数据收集平台的原型，该平台支持优化神经运动障碍患者的自适应深部脑刺激（aDBS）的研究。我们还介绍了将该平台部署到帕金森病患者家中一年多的主要发现。

将诊所带回家：支持自适应深部脑刺激的家庭多模态数据收集生态系统

Adaptive deep brain stimulation (aDBS) shows promise for improving treatment for neurological disorders such as Parkinson's disease (PD). aDBS uses ...

我的研究支持在某人舒适的家中自动进行自适应深部脑刺激或ADBS治疗帕金森病。一个问题是，这种疗法是否可以在诊所外长期安全地监测，同时确保患者的隐私。此外，我们正在研究自动调整ADBS参数的可能性，而无需患者返回诊所。ADBS研究需要数据收集平台来准确测量患者日常生活中的运动质量，并远程提供治疗算法的更新。该协议收集了患者在家中自由移动的多种模式，包括视频数据以捕捉孤立的运动学，如手指运动。我们的研究结果使我们能够探索帕金森病在很长一段时间内的变化，它们让我们询问在临床观察之外分析和治疗帕金森病的各种症状需要哪些测量。

bringing-clinic-home-an-at-home-multi-modal-data-collection-ecosystem

Research

JoVE Journal

Neuroscience

Bringing the Clinic Home: An At-Home Multi-Modal Data Collection Ecosystem to Support Adaptive Deep Brain Stimulation

1.1K 次观看.  University of Washington. 我的研究支持在某人舒适的家中自动进行自适应深部脑刺激或ADBS治疗帕金森病。一个问题是，这种疗法是否可以在诊所外长期安全地监测，同时确保患者的隐私。此外，我们正在研究自动调整ADBS参数的可能性，而无需患者返回诊所。ADBS研究需要数据收集平台来准确测量患者日常生活中的运动质量，并远程提供治疗算法的更新。该协议收集了患者在家中自由移动的多种?...

视频: 作者聚焦：帕金森病的自动脑深部刺激 - 探索家庭监测的可能性和挑战 

Combining Transcranial Magnetic Stimulation and fMRI to Examine the Default Mode Network

The default mode network is a group of brain regions that are active when an individual is not focused on the outside world and the brain is at "wakeful rest."1,2,3 It is thought the default mode network corresponds to self-referential or "internal mentation".2,3
It has been hypothesized that, in humans, activity within the default mode network is correlated with certain pathologies (for instance, hyper-activation has been linked to schizophrenia 4,5,6 and autism spectrum disorders 7 whilst hypo-activation of the network has been linked to Alzheimer's and other neurodegenerative diseases 8). As such, noninvasive modulation of this network may represent a potential therapeutic intervention for a number of neurological and psychiatric pathologies linked to abnormal network activation. One possible tool to effect this modulation is Transcranial Magnetic Stimulation: a non-invasive neurostimulatory and neuromodulatory technique that can transiently or lastingly modulate cortical excitability (either increasing or decreasing it) via the application of localized magnetic field pulses.9
In order to explore the default mode network's propensity towards and tolerance of modulation, we will be combining TMS (to the left inferior parietal lobe) with functional magnetic resonance imaging (fMRI). Through this article, we will examine the protocol and considerations necessary to successfully combine these two neuroscientific tools.

In this article, we examine the methodology and considerations relevant to the combination of TMS and fMRI to examine the effects of brain stimulation on the default network.

结合经颅磁刺激和功能磁共振成像检查默认模式网络

The default mode network is a group of brain regions that are active when an individual is not focused on the outside world and the brain is at "wakeful ...

科研

神经科学

TMS: Using the Theta-Burst Protocol to Explore Mechanism of Plasticity in Individuals with Fragile X Syndrome and Autism

Fragile X Syndrome (FXS), also known as Martin-Bell Syndrome, is a genetic abnormality found on the X chromosome.1,2 Individuals suffering from FXS display abnormalities in the expression of FMR1 - a protein required for typical, healthy neural development.3 Recent data has suggested that the loss of this protein can cause the cortex to be hyperexcitable thereby affecting overall patterns of neural plasticity.4,5
In addition, Fragile X shows a strong comorbidity with autism: in fact, 30% of children with FXS are diagnosed with autism, and 2 - 5% of autistic children suffer from FXS.6
Transcranial Magnetic Stimulation (a non-invasive neurostimulatory and neuromodulatory technique that can transiently or lastingly modulate cortical excitability via the application of localized magnetic field pulses 7,8) represents a unique method of exploring plasticity and the manifestations of FXS within affected individuals. More specifically, Theta-Burst Stimulation (TBS), a specific stimulatory protocol shown to modulate cortical plasticity for a duration up to 30 minutes after stimulation cessation in healthy populations, has already proven an efficacious tool in the exploration of abnormal plasticity.9,10 
Recent studies have shown the effects of TBS last considerably longer in individuals on the autistic spectrum - up to 90 minutes.11 This extended effect-duration suggests an underlying abnormality in the brain's natural plasticity state in autistic individuals - similar to the hyperexcitability induced by Fragile X Syndrome.
In this experiment, utilizing single-pulse motor-evoked potentials (MEPs) as our benchmark, we will explore the effects of both intermittent and continuous TBS on cortical plasticity in individuals suffering from FXS and individuals on the Autistic Spectrum.

In this article, we examine the effects of Theta-Burst TMS stimulation on cortical plasticity in individuals suffering from Fragile X syndrome and individuals on the autistic spectrum.

TMS：使用的Theta突发协议，以探索个人与脆性X综合征与孤独症的可塑性Mechasnism

Fragile X Syndrome (FXS), also known as Martin-Bell Syndrome, is a genetic abnormality found on the X chromosome.1,2 Individuals suffering from FXS ...

The NeuroStar TMS Device: Conducting the FDA Approved Protocol for Treatment of Depression

The Neuronetics NeuroStar Transcranial Magnetic Stimulation (TMS) System is a class II medical device that produces brief duration, pulsed magnetic fields. These rapidly alternating fields induce electrical currents within localized, targeted regions of the cortex which are associated with various physiological and functional brain changes.1,2,3
In 2007, O'Reardon et al., utilizing the NeuroStar device, published the results of an industry-sponsored, multisite, randomized, sham-stimulation controlled clinical trial in which 301 patients with major depression, who had previously failed to respond to at least one adequate antidepressant treatment trial, underwent either active or sham TMS over the left dorsolateral prefrontal cortex (DLPFC). The patients, who were medication-free at the time of the study, received TMS five times per week over 4-6 weeks.4
The results demonstrated that a sub-population of patients (those who were relatively less resistant to medication, having failed not more than two good pharmacologic trials) showed a statistically significant improvement on the Montgomery-Asberg Depression Scale (MADRS), the Hamilton Depression Rating Scale (HAMD), and various other outcome measures. In October 2008, supported by these and other similar results5,6,7, Neuronetics obtained the first and only Food and Drug Administration (FDA) approval for the clinical treatment of a specific form of medication-refractory depression using a TMS Therapy device (FDA approval K061053).
In this paper, we will explore the specified FDA approved NeuroStar depression treatment protocol (to be administered only under prescription and by a licensed medical profession in either an in- or outpatient setting).

In this article, we examine the methodology and considerations relevant to the FDA approved depression treatment protocol using the Neuronetics NeuroStar TMS device.

NeuroStar TMS的设备进行美国FDA批准用于治疗抑郁症的议定书“

The Neuronetics NeuroStar Transcranial Magnetic Stimulation (TMS) System is a class II medical device that produces brief duration, pulsed magnetic ...

Deep Brain Stimulation with Simultaneous fMRI in Rodents

In order to visualize the global and downstream neuronal responses to deep brain stimulation (DBS) at various targets, we have developed a protocol for using blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) to image rodents with simultaneous DBS. DBS fMRI presents a number of technical challenges, including accuracy of electrode implantation, MR artifacts created by the electrode, choice of anesthesia and paralytic to minimize any neuronal effects while simultaneously eliminating animal motion, and maintenance of physiological parameters, deviation from which can confound the BOLD signal.&#160;Our laboratory has developed a set of procedures that are capable of overcoming most of these possible issues. For electrical stimulation, a homemade tungsten bipolar microelectrode is used, inserted stereotactically at the stimulation site in the anesthetized subject. In preparation for imaging, rodents are fixed on a plastic headpiece and transferred to the magnet bore. For sedation and paralysis during scanning, a cocktail of dexmedetomidine and pancuronium is continuously infused, along with a minimal dose of isoflurane; this preparation minimizes the BOLD ceiling effect of volatile anesthetics. In this example experiment, stimulation of the subthalamic nucleus (STN) produces BOLD responses which are observed primarily in ipsilateral cortical regions, centered in motor cortex. Simultaneous DBS and fMRI allows the unambiguous modulation of neural circuits dependent on stimulation location and stimulation parameters, and permits observation of neuronal modulations free of regional bias. This technique may be used to explore the downstream effects of modulating neural circuitry at nearly any brain region, with implications for both experimental and clinical DBS.

This protocol describes a standard method for simultaneous functional magnetic resonance imaging and deep brain stimulation in the rodent. The combined use of these experimental tools allows for the exploration of global downstream activity in response to electrical stimulation at virtually any brain target.

深部脑刺激与同步功能磁共振成像在鼠害

In order to visualize the global and downstream neuronal responses to deep brain stimulation (DBS) at various targets, we have developed a protocol for ...

Analysis of Gene Expression Changes in the Rat Hippocampus After Deep Brain Stimulation of the Anterior Thalamic Nucleus

Deep brain stimulation (DBS) surgery, targeting various regions of the brain such as the basal ganglia, thalamus, and subthalamic regions, is an effective treatment for several movement disorders that have failed to respond to medication. Recent progress in the field of DBS surgery has begun to extend the application of this surgical technique to other conditions as diverse as morbid obesity, depression and obsessive compulsive disorder. Despite these expanding indications, little is known about the underlying physiological mechanisms that facilitate the beneficial effects of DBS surgery. One approach to this question is to perform gene expression analysis in neurons that receive the electrical stimulation. Previous studies have shown that neurogenesis in the rat dentate gyrus is elicited in DBS targeting of the anterior nucleus of the thalamus1. DBS surgery targeting the ATN is used widely for treatment refractory epilepsy. It is thus of much interest for us to explore the transcriptional changes induced by electrically stimulating the ATN. In this manuscript, we describe our methodologies for stereotactically-guided DBS surgery targeting the ATN in adult male Wistar rats. We also discuss the subsequent steps for tissue dissection, RNA isolation, cDNA preparation and quantitative RT-PCR for measuring gene expression changes. This method could be applied and modified for stimulating the basal ganglia and other regions of the brain commonly clinically targeted. The gene expression study described here assumes a candidate target gene approach for discovering molecular players that could be directing the mechanism for DBS.

The mechanism underlying the therapeutic effects of Deep Brain Stimulation (DBS) surgery needs investigation. The methods presented in this manuscript describe an experimental approach to examine the cellular events triggered by DBS by analyzing the gene expression profile of candidate genes that can facilitate neurogenesis post DBS surgery.

基因表达的变化大鼠海马后，前丘脑核脑深部刺激分析

Deep brain stimulation (DBS) surgery, targeting various regions of the brain such as the basal ganglia, thalamus, and subthalamic regions, is an effective ...

Microelectrode Guided Implantation of Electrodes into the Subthalamic Nucleus of Rats for Long-term Deep Brain Stimulation

Deep brain stimulation (DBS) is a widely used and effective therapy for several neurologic disorders, such as idiopathic Parkinson&#8217;s disease, dystonia or tremor. DBS is based on the delivery of electrical stimuli to specific deep anatomic structures of the central nervous system. However, the mechanisms underlying the effect of DBS remain enigmatic. This has led to an interest in investigating the impact of DBS in animal models, especially in rats. As DBS is a long-term therapy, research should be focused on molecular-genetic changes of neural circuits that occur several weeks after DBS. Long-term DBS in rats is challenging because the rats move around in their cage, which causes problems in keeping in place the wire leading from the head of the animal to the stimulator. Furthermore, target structures for stimulation in the rat brain are small and therefore electrodes cannot easily be placed at the required position. Thus, a set-up for long-lasting stimulation of rats using platinum/iridium electrodes with an impedance of about 1 M&#937; was developed for this study. An electrode with these specifications allows for not only adequate stimulation but also recording of deep brain structures to identify the target area for DBS. In our set-up, an electrode with a plug for the wire was embedded in dental cement with four anchoring screws secured onto the skull. The wire from the plug to the stimulator was protected by a stainless-steel spring. A swivel was connected to the circuit to prevent the wire from becoming tangled. Overall, this stimulation set-up offers a high degree of free mobility for the rat and enables the head plug, as well as the wire connection between the plug and the stimulator, to retain long-lasting strength.

A method for implanting electrodes into the subthalamic nucleus (STN) of rats is described. Better localization of the STN was achieved by using a microrecording system. Furthermore, a stimulation set-up is presented that is characterized by long-lasting connections between the head of the animal and the stimulator.

微电极引导电极植入到大鼠丘脑底核的长期深部脑刺激

Deep brain stimulation (DBS) is a widely used and effective therapy for several neurologic disorders, such as idiopathic Parkinson&#8217;s disease, ...

An Improved Method for Collection of Cerebrospinal Fluid from Anesthetized Mice

The cerebrospinal fluid (CSF) is a valuable body fluid for analysis in neuroscience research. It is one of the fluids in closest contact with the central nervous system and thus, can be used to analyze the diseased state of the brain or spinal cord without directly accessing these tissues. However, in mice it is difficult to obtain from the cisterna magna due to its closeness to blood vessels, which often contaminate samples. The area for CSF collection in mice is also difficult to dissect to and often only small samples are obtained (maximum of 5-7 &#181;L or less). This protocol describes in detail a technique that improves on current methods of collection to minimize contamination from blood and allow for the abundant collection of CSF (on average 10-15 &#181;L can be collected). This technique can be used with other dissection methods for tissue collection from mice, as it does not impact any tissues during CSF extraction. Thus, the brain and spinal cord are not affected with this technique and remain intact. With greater CSF sample collection and purity, more analyses can be used with this fluid to further aid neuroscience research and better understand diseases affecting the brain and spinal cord.

This protocol describes an improved technique for the abundant collection of cerebrospinal fluid (CSF) with no contamination from blood. With greater sample collection and purity, more analyses can be performed using CSF to further our understanding of diseases that affect the brain and spinal cord.

一种改进的麻醉小鼠脑脊液采集方法

The cerebrospinal fluid (CSF) is a valuable body fluid for analysis in neuroscience research. It is one of the fluids in closest contact with the central ...

In vivo Positron Emission Tomography to Reveal Activity Patterns Induced by Deep Brain Stimulation in Rats

Deep brain stimulation (DBS) is an invasive neurosurgical technique based on the application of electrical pulses to brain structures involved in the patient&#39;s pathophysiology. Despite the long history of DBS, its mechanism of action and appropriate protocols remain unclear, highlighting the need for research aiming to solve these enigmas. In this sense, evaluating the in vivo effects of DBS using functional imaging techniques represents a powerful strategy to determine the impact of stimulation on brain dynamics. Here, an experimental protocol for preclinical models (Wistar rats), combined with a longitudinal study [18F]-fluorodeoxyclucose positron emission tomography (FDG-PET), to assess the acute consequences of DBS on brain metabolism is described. First, animals underwent stereotactic surgery for bilateral implantation of electrodes into the prefrontal cortex. A post-surgical computerized tomography (CT) scan of each animal was acquired to verify electrode placement. After one week of recovery, a first static FDG-PET of each operated animal without stimulation (D1) was acquired, and two days later (D2), a second FDG-PET was acquired while animals were stimulated. For that, the electrodes were connected to an isolated stimulator after administering FDG to the animals. Thus, animals were stimulated during the FDG uptake period (45 min), recording the acute effects of DBS on brain metabolism. Given the exploratory nature of this study, FDG-PET images were analyzed by a voxel-wise approach based on a paired T-test between D1 and D2 studies. Overall, the combination of DBS and imaging studies allows describing the neuromodulation consequences on neural networks, ultimately helping to unravel the conundrums surrounding DBS.

In vivo Positron Emission Tomography to Reveal Activity Patterns Induced by Deep Brain Stimulation in Rats

We describe a preclinical experimental method to evaluate metabolic neuromodulation induced by acute deep brain stimulation with in vivo FDG-PET. This manuscript includes all experimental steps, from stereotaxic surgery to the application of the stimulation treatment and the acquisition, processing, and analysis of PET images.

体内 正电子发射断层扫描揭示大鼠深部脑刺激诱导的活动模式

Deep brain stimulation (DBS) is an invasive neurosurgical technique based on the application of electrical pulses to brain structures involved in the ...

脑深部刺激治疗重度抑郁症

Closed-Loop Neurostimulation for Biomarker-Driven, Personalized Treatment of Major Depressive Disorder

Deep brain stimulation involves the administration of electrical stimulation to targeted brain regions for therapeutic benefit. In the context of major depressive disorder (MDD), most studies to date have administered continuous or open-loop stimulation with promising but mixed results. One factor contributing to these mixed results may stem from when the stimulation is applied. Stimulation administration specific to high-symptom states in a personalized and responsive manner may be more effective at reducing symptoms compared to continuous stimulation and may avoid diminished therapeutic effects related to habituation. Additionally, a lower total duration of stimulation per day is advantageous for reducing device energy consumption. This protocol describes an experimental workflow using a chronically implanted neurostimulation device to achieve closed-loop stimulation for individuals with treatment-refractory MDD. This paradigm hinges on determining a patient-specific neural biomarker that is related to states of high symptoms and programming the device detectors, such that stimulation is triggered by this read-out of symptom state. The described procedures include how to obtain neural recordings concurrent with patient symptom reports, how to use these data in a state-space model approach to differentiate low- and high-symptom states and corresponding neural features, and how to subsequently program and tune the device to deliver closed-loop stimulation therapy.

作者聚焦：闭环深部脑刺激在抑郁症治疗中的治疗益处 

Deep brain stimulation triggered by a patient-specific neural biomarker of a high-symptom state may better control symptoms of major depressive disorder compared to continuous, open-loop stimulation. This protocol provides a workflow for identifying a patient-specific neural biomarker and controlling the delivery of therapeutic stimulation based on the identified biomarker.

闭环神经刺激用于重度抑郁症的生物标志物驱动型个性化治疗

Deep brain stimulation involves the administration of electrical stimulation to targeted brain regions for therapeutic benefit. In the context of major ...