Name: using saccadometry with deep brain stimulation to study normal and pathological brain function
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Dr. Antoniades was supported by the National Institute of Health Research (NIHR) and by the Dementias and Neurodegenerative Diseases Research Network (DENDRON) and by the Wellcome Trust. Dr FitzGerald was supported by the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre.

当地伦理委员会批准了这项研究，并告知同意从参与者获得的第1节详述如下。 1.参赛者同意<ol><li>为参加者提供了详细什么测试环节将包括解释了资料片。 </li><li>当参与者有机会阅读并讨论在研究关系到他们的总兵任何问题，关注或其他事项，通过与他们的同意书，解释了知情同意书上的每个点，并让他们有机会提出任何问题他们可能有。请参与者填写表格。 </li></ol> 2.设置Saccadometer <ol><li>放置在患者的头部的装置中，通过可调节的弹性带固定并搁在鼻梁。因为刺激与头部正好移动，没有头约束是必要的，设备是舒适的WEA河</li><li>让患者在1.5米的平坦雾面屏幕坐。 </li><li>确保环境光线昏暗，这样的刺激（红色光点）都看得清清楚楚。 </li></ol> 3.录制会话扫视注:作为一个例子，测试既prosaccades和antisaccades 8标准的协议，这里描述。这个协议包括五个块:60 prosaccades，40 antisaccades×3和60 prosaccades与块之间1分的休息。会议持续约40分钟。 <ol><li> 2.0秒，在这之后熄灭和的圆周目标之一出现时，随机地向右或左9 -使得对于每个试验显示为1.0的无规船头期间的中心注视目标设置saccadometer。 注:三个目标是在参与者的前方投影到屏幕上的红色光点（见2.2）由内置于saccadometer低功率激光器。该saccadometer AUTomatically接通和关闭，以显示激光器/熄灭在必要的序列的目标。 </li><li>指示该测试包括与块之间一分钟的休息时间五个街区的参与者。 </li><li>在此之前的第一块指示参与者尽可能迅速和准确地移动自己的眼睛，尽量跟着红点从中间跳向一侧或另一并指示他们这样做60次。 </li><li>设置saccadometer生成的60试验序列。按下saccadometer按钮启动的试验（prosaccades）的第一个块。 </li><li>第一块结束后，离开第二块前一分钟差距。重置saccadometer生成的40试验的序列，并朝向中的一个微小间隙结束时，指示参与者为下一个块以相反的方向尽快移动他们的眼睛的红点，并解释说，他们将被要求做到这40次。启动秒审判（antisaccades）OND块。 </li><li>第二块的结束后，留下另外1分钟间隙，重复指令，在步骤3.5，开始的试验（antisaccades）第三块。 </li><li>第三块的结束后，留下另外1分钟间隙，重复指令，在步骤3.5，开始的试验（antisaccades）第四块。 </li><li>第四块完成后，留下一个进一步的1分的差距，并解释说，对于测试的最后一块要求参与者迅速并准确地把他们的眼睛跟着红点从中间跳跃到一侧或其他，正是因为他们在第一块做。 </li><li>重置saccadometer产生的60试验序列，并启动试验（prosaccades）最后的障碍。 </li></ol><img alt="图2" src="/files/ftp_upload/53640/53640fig2.jpg" /> 图2.眼球运动任务。示意图illustrati上示出的跳视的任务的两个例子。蓝色实点表示目标和蓝色虚线圆圈代表固定的区域。 左边显示，其中的主题提示看向目标一prosaccadic任务。 右边显示当受试者被要求从视觉刺激看远的antisaccade 。这就要求在相反方向的扫视更自然prosaccade反应而产生的抑制作用。 <a href="https://www.jove.com/files/ftp_upload/53640/53640fig2large.jpg" target="_blank">请点击此处查看该图的放大版本。</a> 4.深部脑刺激设置注意:对于参与脑深部刺激与刺激系统运行正常， 即进行测试至今，已经获得了一个"关于刺激"数据集。测试现在需要重复与刺激器系统关闭（对于健康对照参与者不DBS系统这部分将不适用）。 <ol><li>切换DBS系统关闭。由受过培训的医务人员做到这一点。允许测试前30分钟。 </li><li>重复扫视测试（步骤3.2 - 3.9），以获得完整的"关刺激"数据集。 </li><li>切换DBS系统重新开机（再次这应该经过适当培训的医务人员来完成）。 </li></ol> 5.数据分析注意:对于参与脑深部刺激与刺激系统运行正常， 即进行测试至今，已经获得了一个"关于刺激"数据集。现在的测试需要重复的刺激系统关闭（健康控制参与者没有这个部分将不适用DBS系统）。 <ol><li>下载从saccadometer的原始数据以供分析的计算机。 </li><li>使用saccadometer的软件程序，以排除扫视distor泰德由闪烁和头部动作，包括扫视延迟，峰值速度，和幅度来计算的变量。 注意:过量的头部运动或闪烁污染的记录是由软件自动删除。 <ol><li>与延迟删除扫视小于80毫秒或大于1000毫秒。 注:扫视延迟计算自动使用基于速度和加速度扫视检测算法。一个扫视的发作被鉴定为当眼睛速度超过5度/秒的阈值的点。 </li></ol></li></ol>

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The authors have nothing to disclose.

在取得良好的质量扫视数据的最关键因素是确保提供给参与者指令是清楚和准确。例如，如果为antisaccadic任务指令是不完全清楚，参与者很可能代替执行prosaccades。录音也可能是被宠坏如果参与者不能清楚地看到刺激或saccadometer无法准确衡量眼位。因此，如果数据似乎是低质量的实验者应检查环境光线不要太亮，而且saccadometer正确地坐在鼻梁。 深部脑刺激使得神经活动的直接...

近年来出现了在使用的反应时间的测量增加兴趣获得有关使1神经决定的高一级的机制的信息的数量和非侵入性的方式。已被广泛研究的反应时间的一种类型是启动一个视觉刺激，被称为扫视延迟的呈现的扫视所花费的时间。扫视是当我们快速，我们的目光从一个地方转移到另一个发生在快速眼球运动。他们是最常见的类型眼球运动的我们做，一般在两三每秒的频率出现。每个扫视实际上是看一个提示的视觉世界，而不是另一个2的决定。 神经通路控制眼球运动已被广泛研究，并相当有据可查3。使用敏感的电子设备，动眼神经功能的各方面可以精确和objectivelÿ量化。这有利于眼睛运动本身的详细研究，但也允许它们被用来作为一种工具来研究神经生理学和病理生理学的其他领域。 眼球运动的测量可以提供关于疾病状态的有用信息。眼跳最近，例如，受到很大关注作为神经变性疾病的潜在生物标志物，包括亨廷顿氏4,5和帕金森氏病6,7，而且它是公认的扫视的反应时间往往比在这些条件下正常慢。扫视测量的潜在用途包括艾滋病诊断和病情跟踪。扫视任务（如快速寻找尽可能朝向突然出现的视觉刺激，以左或右）的范围从简单的prosaccade到更复杂的任务，如antisaccade（尽快看向相反一侧视觉刺激）或内存 - 引导扫视（看朝着一个目标就是不再有）的记忆位置。 深部脑刺激是一种有效的治疗几种神经系统疾病。它最常用于治疗帕金森氏病，包括震颤，强直，运动迟缓，和运动障碍的运动症状。它也可用于其他的运动障碍，包括肌张力障碍和原发性震颤，和不太常用为神经性疼痛，癫痫，和精神病症如强迫症。它是在其中科学家必须在体内的人脑的深层结构的直接电连接，从而提供了实验神经学宝贵的机会的唯一设置。各种目标有刺激取决于所治疗的病症，包括在基底神经节的几个位置，其中许多都参与动眼神经通路。这意味着，一个广泛的研究，可以使用DBS系统递送刺激进行给定的大脑位置和眼睛跟踪装置，记录并分析其影响。根据不同的实验范例，这样的研究可以产生被刺激有关区域的生理信息，该疾病，或者这一机制的DBS是工作在该特定设置的影响。本文介绍了在深部脑刺激患者眼跳运动检测的通用方法。 几种不同类型的眼动追踪设备可用。对于本协议描述的研究使用了便携式saccadometer记录水平眼跳。便携式saccadometers有不需要头枕（ 见图1），这意味着会话的患者帕金森病更舒适，尤其是对于那些有严重的运动障碍患的优点。这里使用的saccadometer是重量轻，大约5厘米宽，10厘米高。该saccadometer measu通过使用直接红外线oculography的水库眼球运动:红外光源和传感器放置在内侧眼角利用光的前面从角膜反射的建立在毫秒间隔眼球的旋转位置。为了获取用于分析高质量的数据的saccadometer应该至少为1kHz与至少一个12位的分辨率的速率采样。在这里使用的saccadometer的视觉刺激三个红13 CD米-2由产生的光点建在低功率激光器，每个斑点对着某些0.1度，与在中线一个点，另两个在±10度（ 即到右和左）。 <img alt="图1" src="/files/ftp_upload/53640/53640fig1.jpg" /> 图1. Saccadometer。头戴式saccadometer附连到弹性带和搁在鼻梁。四微型激光投影视标来说明是粗糙面，和参加者的眼睛运动是用差红外反射换能器上的每个眼的鼻侧测量。由于激光目标与头部移动，头枕不是必需的。 <a href="https://www.jove.com/files/ftp_upload/53640/53640fig1large.jpg" target="_blank">请点击此处查看该图的放大版本。</a>

<table><tbody><tr><td>Saccadometer device</td><td>Ober Consulting Poland</td><td></td><td></td></tr><tr><td>Computer with Windows environment</td><td></td><td></td><td></td></tr><tr><td>Software, Latency Meter for downloading the raw data from the saccadometer</td><td></td><td></td><td></td></tr></tbody></table>

using saccadometry with deep brain stimulation to study normal and pathological brain function

The oculomotor system involves a large number of brain areas including parts of the basal ganglia, and various neurodegenerative diseases including Parkinson's and Huntington's can disrupt it. People with Parkinson's disease, for example, tend to have increased saccadic latencies. Consequently, the quantitative measurement of saccadic eye movements has received considerable attention as a potential biomarker for neurodegenerative conditions. A lot more can be learned about the brain in both health and disease by observing what happens to eye movements when the function of specific brain areas is perturbed. Deep brain stimulation is a surgical intervention used for the management of a range of neurological conditions including Parkinson's disease, in which stimulating electrodes are placed in specific brain areas including several sites in the basal ganglia. Eye movement measurements can then be made with the stimulator systems both off and on and the results compared. With suitable experimental design, this approach can be used to study the pathophysiology of the disease being treated, the mechanism by which DBS exerts it beneficial effects, and even aspects of normal neurophysiology.

图3示出眼扫视运动轨迹的一个例子，从帕金森氏症患者与植入底丘脑核DBS系统。两个图形绘制患者prosaccades与刺激器系统关闭（上图）和接通（下图）。在图表每个跟踪示出了单个扫视， 也就是说，以度眼睛位置从中线（y轴）的距离如何作为时间的函数而变化（x轴）的轨迹。既向左和向右扫视显示在图作为偏转到正度值。零时间是中央的目标消失，?...

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Using Saccadometry with Deep Brain Stimulation to Study Normal and Pathological Brain Function

This paper describes the use of quantitative measurement of eye movements in conjunction with stimulation of focal areas of the deep brain in order to study physiology, pathophysiology, and the mechanisms of deep brain stimulation.

使用Saccadometry与深部脑刺激来研究正常和病理脑功能

The oculomotor system involves a large number of brain areas including parts of the basal ganglia, and various neurodegenerative diseases including ...

using-saccadometry-with-deep-brain-stimulation-to-study-normal

Research

JoVE Journal

Medicine

7.4K 次观看.  The University of Oxford. This paper describes the use of quantitative measurement of eye movements in conjunction with stimulation of focal areas of the deep brain in order to study physiology, pathophysiology, and the mechanisms of deep brain stimulation.

视频: Using Saccadometry with Deep Brain Stimulation to Study Normal and Pathological Brain Function

Intra-Operative Behavioral Tasks in Awake Humans Undergoing Deep Brain Stimulation Surgery

Deep brain stimulation (DBS) is a surgical procedure that directs chronic, high frequency electrical stimulation to specific targets in the brain through implanted electrodes. Deep brain stimulation was first implemented as a therapeutic modality by Benabid et al. in the late 1980s, when he used this technique to stimulate the ventral intermediate nucleus of the thalamus for the treatment of tremor 1. Currently, the procedure is used to treat patients who fail to respond adequately to medical management for diseases such as Parkinson's, dystonia, and essential tremor. The efficacy of this procedure for the treatment of Parkinson's disease has been demonstrated in well-powered, randomized controlled trials 2. Presently, the U.S. Food and Drug Administration has approved DBS as a treatment for patients with medically refractory essential tremor, Parkinson's disease, and dystonia. Additionally, DBS is currently being evaluated for the treatment of other psychiatric and neurological disorders, such as obsessive compulsive disorder, major depressive disorder, and epilepsy. 
DBS has not only been shown to help people by improving their quality of life, it also provides researchers with the unique opportunity to study and understand the human brain. Microelectrode recordings are routinely performed during DBS surgery in order to enhance the precision of anatomical targeting. Firing patterns of individual neurons can therefore be recorded while the subject performs a behavioral task. Early studies using these data focused on descriptive aspects, including firing and burst rates, and frequency modulation 3. More recent studies have focused on cognitive aspects of behavior in relation to neuronal activity 4,5. This article will provide a description of the intra-operative methods used to perform behavioral tasks and record neuronal data with awake patients during DBS cases. Our exposition of the process of acquiring electrophysiological data will illuminate the current scope and limitations of intra-operative human experiments.

Deep brain stimulation surgery offers a unique opportunity to examine information encoding in the awake human brain. This article will describe intra-operative methods used to perform cognitive and behavioral tasks while simultaneously acquiring physiological data such as EMG, single-unit neuronal activity and/or local field potentials.

在接受深部脑刺激手术术中唤醒人类行为任务

Deep brain stimulation (DBS) is a surgical procedure that directs chronic, high frequency electrical stimulation to specific targets in the brain through ...

科研

医学

Combined Invasive Subcortical and Non-invasive Surface Neurophysiological Recordings for the Assessment of Cognitive and Emotional Functions in Humans

In spite of the success in applying non-invasive electroencephalography (EEG), magneto-encephalography (MEG) and functional magnetic resonance imaging (fMRI) for extracting crucial information about the mechanism of the human brain, such methods remain insufficient to provide information about physiological processes reflecting cognitive and emotional functions at the subcortical level. In this respect, modern invasive clinical approaches in humans, such as deep brain stimulation (DBS), offer a tremendous possibility to record subcortical brain activity, namely local field potentials (LFPs) representing coherent activity of neural assemblies from localized basal ganglia or thalamic regions. Notwithstanding the fact that invasive approaches in humans are applied only after medical indication and thus recorded data correspond to altered brain circuits, valuable insight can be gained regarding the presence of intact brain functions in relation to brain oscillatory activity and the pathophysiology of disorders in response to experimental cognitive paradigms. In this direction, a growing number of DBS studies in patients with Parkinson&#39;s disease (PD) target not only motor functions but also higher level processes such as emotions, decision-making, attention, memory and sensory perception. Recent clinical trials also emphasize the role of DBS as an alternative treatment in neuropsychiatric disorders ranging from obsessive compulsive disorder (OCD) to chronic disorders of consciousness (DOC). Consequently, we focus on the use of combined invasive (LFP) and non-invasive (EEG) human brain recordings in assessing the role of cortical-subcortical structures in cognitive and emotional processing trough experimental paradigms (e.g. speech stimuli with emotional connotation or paradigms of cognitive control such as the Flanker task), for patients undergoing DBS treatment.

The present protocol aims at assessing cognitive-emotional functions in the basal ganglia by simultaneous neurophysiological recording of local field potentials and non-invasive brain cortical activity (EEG). The procedure is exemplified by the use of paradigms involving speech stimuli with emotional connotation or the Flanker task involving cognitive control.

在人类联合微创皮层下和非侵入性的表面神经生理学录音认知的评估和情感作用

In spite of the success in applying non-invasive electroencephalography (EEG), magneto-encephalography (MEG) and functional magnetic resonance imaging ...

行为学

A Novel Approach to Assess Motor Outcome of Deep Brain Stimulation Effects in the Hemiparkinsonian Rat: Staircase and Cylinder Test

Deep brain stimulation of the subthalamic nucleus is an effective treatment option for Parkinson&#39;s disease. In our lab we established a protocol to screen different neurostimulation patterns in hemiparkinsonian (unilateral lesioned) rats. It consists of creating a unilateral Parkinson&#39;s lesion by injecting 6-hydroxydopamine (6-OHDA) into the right medial forebrain bundle, implanting chronic stimulation electrodes into the subthalamic nucleus and evaluating motor outcomes at the end of 24 hr periods of cable-bound external neurostimulation. The stimulation was conducted with constant current stimulation. The amplitude was set 20% below the individual threshold for side effects. The motor outcome evaluation was done by the assessment of spontaneous paw use in the cylinder test according to Shallert and by the assessment of skilled reaching in the staircase test according to Montoya. This protocol describes in detail the training in the staircase box, the cylinder test, as well as the use of both in hemiparkinsonian rats. The use of both tests is necessary, because the staircase test seems to be more sensitive for fine motor skill impairment and exhibits greater sensitivity to change during neurostimulation. The combination of the unilateral Parkinson model and the two behavioral tests allows the assessment of different stimulation parameters in a standardized way.

Deep brain stimulation (DBS) is an effective treatment option for Parkinson's disease. We established a study design to screen novel stimulation paradigms in rats. The protocol describes the use of the staircase test and cylinder test for motor outcome assessment in DBS treated hemiparkinsonian rats.

一种新的方法，以评估在帕金森病大鼠脑深部电刺激效应的运动结果:楼梯和缸测试

Deep brain stimulation of the subthalamic nucleus is an effective treatment option for Parkinson&#39;s disease. In our lab we established a protocol to ...

High-resolution Functional Magnetic Resonance Imaging Methods for Human Midbrain

Functional MRI (fMRI) is a widely used tool for non-invasively measuring correlates of human brain activity. However, its use has mostly been focused upon measuring activity on the surface of cerebral cortex rather than in subcortical regions such as midbrain and brainstem. Subcortical fMRI must overcome two challenges: spatial resolution and physiological noise. Here we describe an optimized set of techniques developed to perform high-resolution fMRI in human SC, a structure on the dorsal surface of the midbrain; the methods can also be used to image other brainstem and subcortical structures.
High-resolution (1.2 mm voxels) fMRI of the SC requires a non-conventional approach. The desired spatial sampling is obtained using a multi-shot (interleaved) spiral acquisition1. Since, T2* of SC tissue is longer than in cortex, a correspondingly longer echo time (TE ~ 40 msec) is used to maximize functional contrast. To cover the full extent of the SC, 8-10 slices are obtained. For each session a structural anatomy with the same slice prescription as the fMRI is also obtained, which is used to align the functional data to a high-resolution reference volume.
In a separate session, for each subject, we create a high-resolution (0.7 mm sampling) reference volume using a T1-weighted sequence that gives good tissue contrast. In the reference volume, the midbrain region is segmented using the ITK-SNAP software application2. This segmentation is used to create a 3D surface representation of the midbrain that is both smooth and accurate3. The surface vertices and normals are used to create a map of depth from the midbrain surface within the tissue4.
Functional data is transformed into the coordinate system of the segmented reference volume. Depth associations of the voxels enable the averaging of fMRI time series data within specified depth ranges to improve signal quality. Data is rendered on the 3D surface for visualization.
In our lab we use this technique for measuring topographic maps of visual stimulation and covert and overt visual attention within the SC1. As an example, we demonstrate the topographic representation of polar angle to visual stimulation in SC.

This article describes techniques to perform high-resolution functional magnetic resonance imaging with 1.2 mm sampling in human midbrain and subcortical structures using a 3T scanner. Use of these techniques to resolve topographic maps of visual stimulation in the human superior colliculus (SC) is given as an example.

高分辨率人类中脑功能磁共振成像方法

Functional MRI (fMRI) is a widely used tool for non-invasively measuring correlates of human brain activity. However, its use has mostly been focused upon ...

神经科学

Controlling Parkinson's Disease With Adaptive Deep Brain Stimulation

Adaptive deep brain stimulation (aDBS) has the potential to improve the treatment of Parkinson&#39;s disease by optimizing stimulation in real time according to fluctuating disease and medication state. In the present realization of adaptive DBS we record and stimulate from the DBS electrodes implanted in the subthalamic nucleus of patients with Parkinson&#39;s disease in the early post-operative period. Local field potentials are analogue filtered between 3 and 47 Hz before being passed to a data acquisition unit where they are digitally filtered again around the patient specific beta peak, rectified and smoothed to give an online reading of the beta amplitude. A threshold for beta amplitude is set heuristically, which, if crossed, passes a trigger signal to the stimulator. The stimulator then ramps up stimulation to a pre-determined clinically effective voltage over 250 msec and continues to stimulate until the beta amplitude again falls down below threshold. Stimulation continues in this manner with brief episodes of ramped DBS during periods of heightened beta power.
Clinical efficacy is assessed after a minimum period of stabilization (5 min) through the unblinded and blinded video assessment of motor function using a selection of scores from the Unified Parkinson&#39;s Rating Scale (UPDRS). Recent work has demonstrated a reduction in power consumption with aDBS as well as an improvement in clinical scores compared to conventional DBS. Chronic aDBS could now be trialed in Parkinsonism.

Adaptive deep brain stimulation (aDBS) is effective for Parkinson&#8217;s disease, improving symptoms and reducing power consumption compared to conventional deep brain stimulation (cDBS). In aDBS we track a local field potential biomarker (beta oscillatory amplitude) in real time and use this to control the timing of stimulation.

控制帕金森氏症与自适应深部脑刺激

Adaptive deep brain stimulation (aDBS) has the potential to improve the treatment of Parkinson&#39;s disease by optimizing stimulation in real time ...

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, ...

Targeting Neuronal Fiber Tracts for Deep Brain Stimulation Therapy Using Interactive, Patient-Specific Models

Deep brain stimulation (DBS), which involves insertion of an electrode to deliver stimulation to a localized brain region, is an established therapy for movement disorders and is being applied to a growing number of disorders. Computational modeling has been successfully used to predict the clinical effects of DBS; however, there is a need for novel modeling techniques to keep pace with the growing complexity of DBS devices. These models also need to generate predictions quickly and accurately. The goal of this project is to develop an image processing pipeline to incorporate structural magnetic resonance imaging (MRI) and diffusion weighted imaging (DWI) into an interactive, patient specific model to simulate the effects of DBS. A virtual DBS lead can be placed inside of the patient model, along with active contacts and stimulation settings, where changes in lead position or orientation generate a new finite element mesh and solution of the bioelectric field problem in near real-time, a timespan of approximately 10 seconds. This system also enables the simulation of multiple leads in close proximity to allow for current steering by varying anodes and cathodes on different leads. The techniques presented in this paper reduce the burden of generating and using computational models while providing meaningful feedback about the effects of electrode position, electrode design, and stimulation configurations to researchers or clinicians who may not be modeling experts.

The goal of this project is to develop an interactive, patient-specific modeling pipeline to simulate the effects of deep brain stimulation in near real-time and provide meaningful feedback as to how these devices influence neural activity in the brain.

应用交互式、患者特异性模型对神经纤维束进行深部脑刺激治疗的靶向性

Deep brain stimulation (DBS), which involves insertion of an electrode to deliver stimulation to a localized brain region, is an established therapy for ...

生物工程

Acute In Vivo Electrophysiological Recordings of Local Field Potentials and Multi-unit Activity from the Hyperdirect Pathway in Anesthetized Rats

Converging evidence shows that many neuropsychiatric diseases should be understood as disorders of large-scale neuronal networks. To better understand the pathophysiological basis of these diseases, it is necessary to precisely characterize in which way the processing of information is disturbed between the different neuronal parts of the circuit. Using extracellular in vivo electrophysiological recordings, it is possible to accurately delineate neuronal activity within a neuronal network. The application of this method has several advantages over alternative techniques, e.g., functional magnetic resonance imaging and calcium imaging, as it allows a unique temporal and spatial resolution and does not rely on genetically engineered organisms. However, the use of extracellular in vivo recordings is limited since it is an invasive technique that cannot be universally applied. In this article, a simple and easy to use method is presented with which it is possible to simultaneously record extracellular potentials such as local field potentials and multiunit activity at multiple sites of a network. It is detailed how a precise targeting of subcortical nuclei can be achieved using a combination of stereotactic surgery and online analysis of multi-unit recordings. Thus, it is demonstrated, how a complete network such as the hyperdirect cortico-basal ganglia loop can be studied in anesthetized animals in vivo.

Acute In Vivo Electrophysiological Recordings of Local Field Potentials and Multi-unit Activity from the Hyperdirect Pathway in Anesthetized Rats

In this study, the methodology is presented on how to perform multi-site in vivo electrophysiological recordings from the hyperdirect pathway under urethane anesthesia.

急性<em&gt;体内</em&gt;麻醉大鼠超导途径局部场电位和多单位活动的电生理记录

Converging evidence shows that many neuropsychiatric diseases should be understood as disorders of large-scale neuronal networks. To better understand the ...