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 border="0" cellpadding="0" cellspacing="0" width="88">
	<tbody>
		<tr>
			<td>Saccadometer device ( Ober Consulting Poland)</td>
		</tr>
		<tr>
			<td>Computer with Windows environment</td>
		</tr>
		<tr>
			<td>Software, Latency Meter for downloading the raw data from the saccadometer.</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，?...

Watch this Scientific Journal Video about Using Saccadometry with Deep Brain Stimulation to Study Normal and Pathological Brain Function at JoVE.com

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

Eye Tracking Young Children with Autism

The rise of accessible commercial eye-tracking systems has fueled a rapid increase in their use in psychological and psychiatric research. By providing a direct, detailed and objective measure of gaze behavior, eye-tracking has become a valuable tool for examining abnormal perceptual strategies in clinical populations and has been used to identify disorder-specific characteristics1, promote early identification2, and inform treatment3. In particular, investigators of autism spectrum disorders (ASD) have benefited from integrating eye-tracking into their research paradigms4-7. Eye-tracking has largely been used in these studies to reveal mechanisms underlying impaired task performance8 and abnormal brain functioning9, particularly during the processing of social information1,10-11. While older children and adults with ASD comprise the preponderance of research in this area, eye-tracking may be especially useful for studying young children with the disorder as it offers a non-invasive tool for assessing and quantifying early-emerging developmental abnormalities2,12-13. Implementing eye-tracking with young children with ASD, however, is associated with a number of unique challenges, including issues with compliant behavior resulting from specific task demands and disorder-related psychosocial considerations. In this protocol, we detail methodological considerations for optimizing research design, data acquisition and psychometric analysis while eye-tracking young children with ASD. The provided recommendations are also designed to be more broadly applicable for eye-tracking children with other developmental disabilities. By offering guidelines for best practices in these areas based upon lessons derived from our own work, we hope to help other investigators make sound research design and analysis choices while avoiding common pitfalls that can compromise data acquisition while eye-tracking young children with ASD or other developmental difficulties.

Eye tracking has long been used to study gaze patterns in typically-developing individuals, but recent technological advancements have made its use with clinical populations, including autism, more feasible. While eye-tracking young children with autism can offer insight into early symptom manifestations, it involves methodological challenges. Suggestions for best practices are provided.

自闭症幼儿的眼动追踪

The rise of accessible commercial eye-tracking systems has fueled a rapid increase in their use in psychological and psychiatric research. By providing a ...

Isolation of Soluble and Insoluble PrP Oligomers in the Normal Human Brain

The central event in the pathogenesis of prion diseases involves a conversion of the host-encoded cellular prion protein PrPC into its pathogenic isoform PrPSc 1. PrPC is detergent-soluble and sensitive to proteinase K (PK)-digestion, whereas PrPSc forms detergent-insoluble aggregates and is partially resistant to PK2-6. The conversion of PrPC to PrPSc is known to involve a conformational transition of &alpha;-helical to &beta;-sheet structures of the protein. However, the in vivo pathway is still poorly understood. A tentative endogenous PrPSc, intermediate PrP* or "silent prion", has yet to be identified in the uninfected brain7.
Using a combination of biophysical and biochemical approaches, we identified insoluble PrPC aggregates (designated iPrPC) from uninfected mammalian brains and cultured neuronal cells8, 9. Here, we describe detailed procedures of these methods, including ultracentrifugation in detergent buffer, sucrose step gradient sedimentation, size exclusion chromatography, iPrP enrichment by gene 5 protein (g5p) that specifically bind to structurally altered PrP forms10, and PK-treatment. The combination of these approaches isolates not only insoluble PrPSc and PrPC aggregates but also soluble PrPC oligomers from the normal human brain. Since the protocols described here have been used to isolate both PrPSc from infected brains and iPrPC from uninfected brains, they provide us with an opportunity to compare differences in physicochemical features, neurotoxicity, and infectivity between the two isoforms. Such a study will greatly improve our understanding of the infectious proteinaceous pathogens. The physiology and pathophysiology of iPrPC are unclear at present. Notably, in a newly-identified human prion disease termed variably protease-sensitive prionopathy, we found a new PrPSc that shares the immunoreactive behavior and fragmentation with iPrPC 11, 12. Moreover, we recently demonstrated that iPrPC is the main species that interacts with amyloid-&beta; protein in Alzheimer disease13. In the same study, these methods were used to isolate Abeta aggregates and oligomers in Alzheimer's disease13, suggesting their application to non-prion protein aggregates involved in other neurodegenerative disorders.

A new species of cellular prion protein (PrPC) has recently been identified in uninfected human brains using the methods described here. These methods can be used to isolate various PrP species, while some of them are also useful in isolating other misfolded protein aggregates from human brains.

在正常人脑分离的可溶性和不溶性朊蛋白低聚物

The central event in the pathogenesis of prion diseases involves a conversion of the host-encoded cellular prion protein PrPC into its pathogenic isoform ...

A Novel High-resolution In vivo Imaging Technique to Study the Dynamic Response of Intracranial Structures to Tumor Growth and Therapeutics

We have successfully integrated previously established Intracranial window (ICW) technology 1-4 with intravital 2-photon confocal microscopy to develop a novel platform that allows for direct long-term visualization of tissue structure changes intracranially. Imaging at a single cell resolution in a real-time fashion provides supplementary dynamic information beyond that provided by standard end-point histological analysis, which looks solely at 'snap-shot' cross sections of tissue.
Establishing this intravital imaging technique in fluorescent chimeric mice, we are able to image four fluorescent channels simultaneously. By incorporating fluorescently labeled cells, such as GFP+ bone marrow, it is possible to track the fate of these cells studying their long-term migration, integration and differentiation within tissue. Further integration of a secondary reporter cell, such as an mCherry glioma tumor line, allows for characterization of cell:cell interactions. Structural changes in the tissue microenvironment can be highlighted through the addition of intra-vital dyes and antibodies, for example CD31 tagged antibodies and Dextran molecules.
Moreover, we describe the combination of our ICW imaging model with a small animal micro-irradiator that provides stereotactic irradiation, creating a platform through which the dynamic tissue changes that occur following the administration of ionizing irradiation can be assessed.
Current limitations of our model include penetrance of the microscope, which is limited to a depth of up to 900 &mu;m from the sub cortical surface, limiting imaging to the dorsal axis of the brain. The presence of the skull bone makes the ICW a more challenging technical procedure, compared to the more established and utilized chamber models currently used to study mammary tissue and fat pads 5-7. In addition, the ICW provides many challenges when optimizing the imaging.

A Novel High-resolution In vivo Imaging Technique to Study the Dynamic Response of Intracranial Structures to Tumor Growth and Therapeutics

We describe a novel in vivo imaging technique that couples fluorescent chimeric mice with intracranial windows and high-resolution 2-photon microscopy. This imaging platform aids studies of dynamic changes in brain tissue and microvasculature, at a single-cell level, following pathological insults and is adaptable to assess intracranial drug delivery and distribution.

一种新型的高分辨率<em&gt;在体内</em&gt;成像技术研究肿瘤生长及治疗颅内结构的动态响应

We have successfully integrated previously established Intracranial window (ICW) technology 1-4 with intravital 2-photon confocal microscopy to develop a ...

Lesion Explorer: A Video-guided, Standardized Protocol for Accurate and Reliable MRI-derived Volumetrics in Alzheimer's Disease and Normal Elderly

Obtaining in vivo human brain tissue volumetrics from MRI is often complicated by various technical and biological issues. These challenges are exacerbated when significant brain atrophy and age-related white matter changes (e.g. Leukoaraiosis) are present. Lesion Explorer (LE) is an accurate and reliable neuroimaging pipeline specifically developed to address such issues commonly observed on MRI of Alzheimer's disease and normal elderly. The pipeline is a complex set of semi-automatic procedures which has been previously validated in a series of internal and external reliability tests1,2. However, LE's accuracy and reliability is highly dependent on properly trained manual operators to execute commands, identify distinct anatomical landmarks, and manually edit/verify various computer-generated segmentation outputs.
LE can be divided into 3 main components, each requiring a set of commands and manual operations: 1) Brain-Sizer, 2) SABRE, and 3) Lesion-Seg. Brain-Sizer's manual operations involve editing of the automatic skull-stripped total intracranial vault (TIV) extraction mask, designation of ventricular cerebrospinal fluid (vCSF), and removal of subtentorial structures. The SABRE component requires checking of image alignment along the anterior and posterior commissure (ACPC) plane, and identification of several anatomical landmarks required for regional parcellation. Finally, the Lesion-Seg component involves manual checking of the automatic lesion segmentation of subcortical hyperintensities (SH) for false positive errors.
While on-site training of the LE pipeline is preferable, readily available visual teaching tools with interactive training images are a viable alternative. Developed to ensure a high degree of accuracy and reliability, the following is a step-by-step, video-guided, standardized protocol for LE's manual procedures.

Lesion Explorer (LE) is a semi-automatic, image-processing pipeline developed to obtain regional brain tissue and subcortical hyperintensity lesion volumetrics from structural MRI of Alzheimer's disease and normal elderly. To ensure a high level of accuracy and reliability, the following is a video-guided, standardized protocol for LE's manual procedures.

病变资源管理器:一个视频引导，标准化为老年痴呆症准确，可靠的MRI衍生Volumetrics和正常老年人协议

Obtaining in vivo human brain tissue volumetrics from MRI is often complicated by various technical and biological issues. These challenges are ...

Excitotoxic Stimulation of Brain Microslices as an In vitro Model of Stroke

Examining molecular mechanisms involved in neuropathological conditions, such as ischemic stroke, can be difficult when using whole animal systems. As such, primary or &#39;neuronal-like&#39; cell culture systems are commonly utilized. While&#160;these systems are relatively easy to work with, and are useful model systems in which various functional outcomes (such as cell death) can be readily quantified, the examined outcomes and pathways in cultured immature neurons (such as excitotoxicity-mediated cell death pathways) are not necessarily the same as those observed in mature brain, or in intact tissue. Therefore, there is the need to develop models in which cellular mechanisms in mature neural tissue can be examined. We have developed an in vitro technique that can be used to investigate a variety of molecular pathways in intact nervous tissue. The technique described herein utilizes rat cortical tissue, but this technique can be adapted to use tissue from a variety of species (such as mouse, rabbit, guinea pig, and chicken) or brain regions (for example, hippocampus, striatum, etc.). Additionally, a variety of stimulations/treatments can be used (for example, excitotoxic, administration of inhibitors, etc.). In conclusion, the brain slice model described herein can be used to examine a variety of molecular mechanisms involved in excitotoxicity-mediated brain injury.

Excitotoxic Stimulation of Brain Microslices as an In vitro Model of Stroke

We have developed a brain slice model which can be used to examine molecular mechanisms involved in excitotoxicity-mediated brain injury.&#160;This technique generates viable mature brain tissue and reduces animal numbers required for experimentation, whilst keeping the neuronal circuitry, cellular interactions, and postsynaptic compartments partly intact.

脑Microslices的兴奋性刺激作为<em&gt;在体外</em&gt;中风模型

Examining molecular mechanisms involved in neuropathological conditions, such as ischemic stroke, can be difficult when using whole animal systems. As ...

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 ...

A Multimodal Imaging- and Stimulation-based Method of Evaluating Connectivity-related Brain Excitability in Patients with Epilepsy

Resting-state functional connectivity MRI (rs-fcMRI) is a technique that identifies connectivity between different brain regions based on correlations over time in the blood-oxygenation level dependent signal. rs-fcMRI has been applied extensively to identify abnormalities in brain connectivity in different neurologic and psychiatric diseases. However, the relationship among rs-fcMRI connectivity abnormalities, brain electrophysiology and disease state is unknown, in part because the causal significance of alterations in functional connectivity in disease pathophysiology has not been established. Transcranial Magnetic Stimulation (TMS) is a technique that uses electromagnetic induction to noninvasively produce focal changes in cortical activity. When combined with electroencephalography (EEG), TMS can be used to assess the brain's response to external perturbations. Here we provide a protocol for combining rs-fcMRI, TMS and EEG to assess the physiologic significance of alterations in functional connectivity in patients with neuropsychiatric disease. We provide representative results from a previously published study in which rs-fcMRI was used to identify regions with abnormal connectivity in patients with epilepsy due to a malformation of cortical development, periventricular nodular heterotopia (PNH). Stimulation in patients with epilepsy resulted in abnormal TMS-evoked EEG activity relative to stimulation of the same sites in matched healthy control patients, with an abnormal increase in the late component of the TMS-evoked potential, consistent with cortical hyperexcitability. This abnormality was specific to regions with abnormal resting-state functional connectivity. Electrical source analysis in a subject with previously recorded seizures demonstrated that the origin of the abnormal TMS-evoked activity co-localized with the seizure-onset zone, suggesting the presence of an epileptogenic circuit. These results demonstrate how rs-fcMRI, TMS and EEG can be utilized together to identify and understand the physiological significance of abnormal brain connectivity in human diseases.

Resting-state functional-connectivity MRI has identified abnormalities in patients with a wide range of neuropsychiatric disorders, including epilepsy due to malformations of cortical development. Transcranial Magnetic Stimulation in combination with EEG can demonstrate that patients with epilepsy have cortical hyperexcitability in regions with abnormal connectivity.

评价中的连接有关的大脑兴奋患者癫痫多式联运Imaging-和激励为基础的方法

Resting-state functional connectivity MRI (rs-fcMRI) is a technique that identifies connectivity between different brain regions based on correlations ...

Continuous IV Infusion is the Choice Treatment Route for Arginine-vasopressin Receptor Blocker Conivaptan in Mice to Study Stroke-evoked Brain Edema

Stroke is one of the major causes of morbidity and mortality in the world. Stroke is complicated by brain edema and other pathophysiological events. Among the most important players in the development and evolution of stroke-evoked brain edema is the hormone arginine-vasopressin and its receptors, V1a and V2. Recently, the V1a and V2 receptor blocker conivaptan has been attracting attention as a potential drug to reduce brain edema after stroke. However, animal models which involve conivaptan applications in stroke research need to be modified based on feasible routes of administration. Here the outcomes of 48 hr continuous intravenous (IV) are compared with intraperitoneal (IP) conivaptan treatments after experimental stroke in mice. We developed a protocol in which middle cerebral artery occlusion was combined with catheter installation into the jugular vein for IV treatment of conivaptan (0.2 mg) or vehicle. Different cohorts of animals were treated with 0.2 mg bolus of conivaptan or vehicle IP daily. Experimental stroke-evoked brain edema was evaluated in mice after continuous IV and IP treatments. Comparison of the results revealed that the continuous IV administration of conivaptan alleviates post-ischemic brain edema in mice, unlike the IP administration of conivaptan. We conclude that our model can be used for future studies of conivaptan applications in the context of stroke and brain edema.

Our studies have revealed that the beneficial effects of conivaptan are dependent on the method of delivery after experimental stroke in mice. We have developed a research protocol for delivery of the receptor blocker via IV catheter on stroke-evoked brain edema formation in mice.

持续静脉注射是精氨酸加压素受体拮抗剂考尼伐坦的选择治疗途径小鼠来研究中风诱发脑水肿

Stroke is one of the major causes of morbidity and mortality in the world. Stroke is complicated by brain edema and other pathophysiological events. Among ...

Symmetric Bihemispheric Postmortem Brain Cutting to Study Healthy and Pathological Brain Conditions in Humans

Neuropathologists, at times, feel intimidated by the amount of knowledge needed to generate definitive diagnoses for complex neuropsychiatric phenomena described in those patients for whom a brain autopsy has been requested. Although the advancements of biomedical sciences and neuroimaging have revolutionized the neuropsychiatric field, they have also generated the misleading idea that brain autopsies have only a confirmatory value. This false idea created a drastic reduction of autopsy rates and, consequently, a reduced possibility to perform more detailed and extensive neuropathological investigations, which are necessary to comprehend numerous normal and pathological aspects yet unknown of the human brain. The traditional inferential method of correlation between observed neuropsychiatric phenomena and corresponding localization/characterization of their possible neurohistological correlates continues to have an undeniable value. In the context of neuropsychiatric diseases, the traditional clinicopathological method is still the best possible methodology (and often the only available) to link unique neuropsychiatric features to their corresponding neuropathological substrates, since it relies specifically upon the direct physical assessment of brain tissues. The assessment of postmortem brains is based on brain cutting procedures that vary across different neuropathology centers. Brain cuttings are performed in a relatively extensive and systematic way based on the various clinical and academic contingencies present in each institution. A more anatomically inclusive and symmetric bi-hemispheric brain cutting methodology should at least be used for research purposes in human neuropathology to coherently investigate, in depth, normal and pathological conditions with the peculiarities of the human brain (i.e., hemispheric specialization and lateralization for specific functions). Such a method would provide a more comprehensive collection of neuropathologically well-characterized brains available for current and future biotechnological and neuroimaging techniques. We describe a symmetric bi-hemispheric brain cutting procedure for the investigation of hemispheric differences in human brain pathologies and for use with current as well as future biomolecular/neuroimaging techniques.

Organized brain cutting procedures are necessary to correlate specific neuropsychiatric phenomena with definitive neuropathologic diagnoses. Brain cuttings are performed differently based on various clinico-academic contingencies. This protocol describes a symmetric bihemispheric brain cutting procedure to investigate hemispheric differences in human brain pathologies and to maximize current and future biomolecular/neuroimaging techniques.

对称Bihemispheric死后的大脑切割学习健康和病理条件大脑在人

Neuropathologists, at times, feel intimidated by the amount of knowledge needed to generate definitive diagnoses for complex neuropsychiatric phenomena ...

使用Saccadometry与深部脑刺激来研究正常和病理脑功能

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