1。除招聘和同意<ol><li>临床评价和丘脑底核（STN）的深部脑刺激难治性帕金森病（DBS）的同意后，每个病人的信息是审查，以确定如果他/她符合的手术研究（定义在一个机构审查的标准董事会批准在马萨诸塞州总医院的协议）。 </li><li>如果确定的主题，符合研究标准，医生的研究组成员（而不是操作系统的外科医生）方法的病人参与研究讨论的可能性。 </li><li>参与研究的同意书，然后检讨和解释这个问题。更重要的是，研究的解释强调，在参与这项研究是自愿的，在任何时候，他/她选择退出参与。此外，它强调的是，他们的讨论，参加或退出在研究有没有对他/她将获得的医疗的影响。 </li><li>如果确定这一主题的理解和同意参与这项研究，他/她签署批准的知情同意，并在研究中招收。 </li></ol> 2。行为训练和钻机安装<ol><li>作为帕金森病的DBS手术的一部分，主题是手术前一天住进了医院。因此，这提供了一个机会，培训行为的任务主体。这个培训是必不可少的，因为它提供了一个时间段，在此期间，主题可以学习来执行任务，并制定其规则的舒适性，消除"学习效果"的困惑（讨论）。 </li><li>手术前的晚上，一个便携式的行为钻机带来主体的病房。 </li><li>该钻机配备具有完全相同的行为的任务，这个问题需要进行一天的手术研究。 <ol><li>在这个例子中，主旨是要求玩一种纸牌游戏，类似"战争"的游戏。在这场比赛中，题目是需要赌，无论他或她的卡是高于计算机（20元或5元）。这项任务的目的是为了检测报酬与风险的STN神经元编码的作用。为了激励主体，他们告诉记者，他们将支付其奖金的比例。 </li><li>由于减少了潜在的组合（以及由此产生的困惑）的手段，只有偶数的一个单一的西装卡使用（例如:2，4，6，8，黑桃10）。因此，潜在的经营成果和任务的期望，可以轻松地计算和分析。 </li><li>在每次试验中，受试者第一次看到屏幕上描绘其随机处理卡，并未知计算机的卡背面。然后屏幕显示两个下注选项，5元和20元。他/她的卡的相对强度的基础上，题目指示下注，按下一个按钮，后，屏幕上显示他/她的卡，并显示计算机的卡。最后的画面明确地描绘赢或输的金额。 </li></ol></li><li>这个题目是可以玩游戏，直到他们完全理解的游戏规则，并执行一个舒适的水平。 </li></ol> 3。术中 - 实验装置<ol><li>一旦这个问题已经定位上手术台，钻机的行为，数据采集和信号处理设备带进了手术室。钻机的定位，必须采取考虑到正常的工作流程和相关手术室设置的不育问题。 </li><li>由于这些钻机的元件组装，并为每个记录会话拆卸，检查所有设备的连接是至关重要的。因此，每个组件连接到数据采集系统，必须检查数据的完整性。这些程序应早期手术，以防止在关键的录音时间来解决这些问题。 <ol><li>首先，启动采集和信号处理设备。将输出的信号处理钻机收购钻机的投入。在本研究的情况下，我们将获得三个额外的细胞动作电位通道对应的三段弧矢导向为主体的大脑将先进的手术过程中的电极。开启一次，以确保采集系统采集的信号放大器之一。 </li><li>安全监视器或舒适的观赏位置使用适当的适配器表。 </li><li>如果采用输入设备（操纵杆，按钮盒，键盘等），此设备的位置，注重从录音将获得一侧大脑偏侧相对。确保主体的手是舒适的位置操作输入设备。考虑到S要求麻醉师ecure另一方面脉冲氧合监测，以确保设备的正常运行。在此任务中，我们使用了一个按钮盒。 </li><li>引导行为的制度，确保行为事件标记被抓获收购钻机。 </li><li>启动行为的任务，并允许主题的任务中发挥几个试验。在这段时间内，确保采集系统捕捉按钮框输入的行为钻机所产生的行为标记。 </li><li>如果所有的连接功能，阻止行为的任务和收购钻机。 </li></ol></li></ol> 4。丘脑底核神经元的分离<ol><li>手术的目的是放置慢性星展成电机的STN地区信息。这个位置是通过立体影像和neuophysiological录音相结合。 </li><li>的立体定向规划和手术本身的细节，当然会有所不同机构之间，但一般的过程是相似的。在我们的机构，一个Cosman - 罗伯茨井立体框架和基准笼应用和头颅CT扫描获得。与基准CT与以前获得在神经导航系统的体积脑部核磁共振成像（StealthStation，Medtronics，明尼阿波利斯，明尼苏达;或BrainLab VectorVision，Feldkirchen，德国）合并。目标的大脑区域的坐标（在这种情况下，STN）转换为基于帧的坐标。在手术室，病人舒适的位置，在一个半倾斜的位置，并prepped和披使用标准的外科技术。左STN坐标编程的框架，这是对病人定位。皮肤切开缩回。置于颅骨钻孔，并创建一个小的硬膜开放。连接到微型硬盘（Microdrive）插管被带进地位和先进的套管尖端直到25毫米以上的目标。 </li><li>一旦插管入脑先进，内部口针都将被删除，并与高阻抗（0.3 - 1兆欧）取代微电极（金控，鲍登，ME）。信号处理钻机的前级放大器连接到每一个电极和差分基准通道连接到外部的套管。 </li><li>放大器在信号处理钻机被打开，细胞外的信号进行评估。此外，每个电极的阻抗是进一步推进到大脑前检查。 </li><li>外科医生的进步缓慢的电极（0.05-0.4毫米步骤），入脑。先进的电极是从对了STN计算目标25毫米。通过电极通过尾状核，丘脑，透明inserta，最后变成了STN轨迹结果。 </li><li>一旦电极已进入了STN，生理学家操纵患者的对侧肢体，确定是否神经信号是电机响应的一种手段。当外科医生和实验者与电极位置感到满意，行为的任务就可以开始。 </li></ol> 5。数据采集<ol><li>开始之前的行为的任务，这是非常重要的文件的微电极的深度和孤立的神经元（S）的电机响应。 </li><li>这个题目，然后指示该任务将开始。确保按钮盒仍然是舒适的位置和显示器完全可见。 </li><li>启动数据采集和收购至少1分钟开始之前的行为任务的基线活动。 </li><li>由于受执行的任务是很重要的监测捕获的数据。随着收购的任何干扰，应停止任务，并纠正问题。 </li><li>在目前的研究，主旨是要求执行120每个STN深入的试验。 </li><li>的任务，可为每个深度的STN执行多次，然而，这些手术的研究（讨论进一步描述）的持续时间有限制。我们限制了实验记录30分钟的时间，以防止病人的不适和不必要的延长手术。此外，受有机会在任何时候拒绝进一步的录音，在这种情况下行为的任务是停止和手术恢复。 </li><li>一旦研究完成后，数据备份和存档以供后续分析。 </li></ol> 6。数据分析<ol><li>首先，神经信号受到歧视穗成单独使用商用软件的时间戳。 </li><li>行为的任务代码，然后分析，并使用Matlab中编写的代码是一致的神经元活动的时间戳。 </li></ol>代表性的成果: 图1描述了从一个单一的STN神经元代表的结果记录在上面所述的战争游戏。的tOP面板描绘四个行为有关的时代的任务为中心的栅格:固定期限，每次试验前，介绍主体的卡，按下按钮，说明这个问题的下注，并介绍电脑的卡。底部面板代表城郊刺激时间直方图（PSTHs）分级（50毫秒箱）。这种神经元不响应有力介绍主题的卡，但增加其发射显着周围的按键。这项活动将持续到计算机的存储卡则透露，在这一点射击下降到基线水平。 <img src="/files/ftp_upload/2156/2156fig1.jpg" alt="图1" /> 图1。代表STN神经元 。栅格（顶部面板）和城郊刺激时间直方图（PSTHs）为中心的行为有关的时代描绘为代表的单STN神经元。这种神经元的发射左右按钮的说明主题的下注推时显着增加。

<ol>
	<li>Benabid, A. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Combined+(thalamotomy+and+stimulation)+stereotactic+surgery+of+the+VIM+thalamic+nucleus+for+bilateral+Parkinson+disease.">Combined (thalamotomy and stimulation) stereotactic surgery of the VIM thalamic nucleus for bilateral Parkinson disease.</a> Appl. Neurophysiol. 50 (1-6), 344-344 (1987).</li><li>Deuschl, G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+randomized+trial+of+deep-brain+stimulation+for+Parkinson's+disease.">A randomized trial of deep-brain stimulation for Parkinson's disease.</a> N. Engl. J. Med. 355 (9), 896-896 (2006).</li><li>Gale, J. T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=From+symphony+to+cacophony:+Pathophysiology+of+the+human+basal+ganglia+in+Parkinson+disease.">From symphony to cacophony: Pathophysiology of the human basal ganglia in Parkinson disease.</a> Neurosci. Biobehav. Rev. , (2007).</li><li>Williams, Z. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Human+anterior+cingulate+neurons+and+the+integration+of+monetary+reward+with+motor+responses.">Human anterior cingulate neurons and the integration of monetary reward with motor responses.</a> Nat. Neurosci. 7 (12), 1370-1370 (2004).</li><li>Zaghloul, K. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Human+substantia+nigra+neurons+encode+unexpected+financial+rewards.">Human substantia nigra neurons encode unexpected financial rewards.</a> Science. 323 (5920), 1496-1496 (2009).</li></ol>

深部脑刺激手术提供了宝贵的机会，在人类大脑研究单个神经元的活动。迄今为止，这个机会已经允许不同深核活动的许多特征的描述性研究。最近，手术的任务变得更加复杂，以解决各方面的行为和认知。当前协议的目的是提供一个成功实施手术的行为任​​务的指导。的目标任务和研究的目的，当然取决于手术有针对性的细胞核。鉴于越来越多的星展手术的应用和相应增加的各种目标，我们?...

*表示，这个项目可以替代通过类似的设备或软件; **表示，替代国家仪器组件都可以使用（参考<a href="www.Monkeylogic.net">www.Monkeylogic.net</a>的兼容性）; ***请以<a href="www.Monkeylogic.net">www.Monkeylogic.net</a> Matlab的具体要求toolboxs。

intra-operative behavioral tasks in awake humans undergoing deep brain stimulation surgery

脑深部刺激（DBS）是一种外科手术，引导长期，高频电刺激大脑中植入电极通过的具体目标。脑深部电刺激已开始实施，作为一个Benabid等治疗方法 。在80年代后期，当他使用这种技术来刺激治疗震颤 1丘脑腹中间核。目前，该过程是用来治疗的患者未能充分应对疾病，如帕金森氏症，肌张力障碍，原发性震颤医疗管理。此过程为治疗帕金森氏病的疗效已被证实在供电，随机对照试验。目前，美国食品和药物管理局已批准星展作为难治的原发性震颤，帕金森氏症，和肌张力障碍患者的治疗。此外，新加坡发展银行（DBS）是目前正在评估其他精神和神经系统疾病的治疗，如强迫症，抑郁症的主要，和癫痫。 星展不仅得到了显示，以帮助人们改善他们的生活质量，还提供独特的机会，学习和了解人类大脑的研究人员。微电极的录音进行例行星展手术期间，以提高解剖定位精度。因此，可以记录单个神经元的放电模式，而受执行行为的任务。使用集中描述的各个方面，包括射击和爆裂率和频率调制3这些数据的早期研究。最近的研究都集中在认知行为方面的有关神经元的活动4,5。本文将提供用于执行行为任务和神经元的数据记录与清醒患者，在星展案件的手术方法的说明。收购电数据的过程中的论述，将照亮我们目前的范围和手术的人体实验的局限性。

Watch this Scientific Journal Video about Intra-Operative Behavioral Tasks in Awake Humans Undergoing Deep Brain Stimulation Surgery at JoVE.com

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

深部脑刺激术，研究人类大脑在清醒信息编码提供了一个独特的机会。本文将介绍手术的方法，用于执行任务的认知和行为，同时获得的生理数据，如肌电图，单神经元单位活动和​​/或当地的场电位。

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 ...

intra-operative-behavioral-tasks-awake-humans-undergoing-deep-brain

Research

JoVE Journal

Medicine

12.9K 次观看.  Harvard Medical School. 深部脑刺激术，研究人类大脑在清醒信息编码提供了一个独特的机会。本文将介绍手术的方法，用于执行任务的认知和行为，同时获得的生理数据，如肌电图，单神经元单位活动和​​/或当地的场电位。

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

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 ...

科研

医学

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 ...

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.

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 ...

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 ...

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 ...

Evaluating the Procedure for Performing Awake Cystometry in a Mouse Model

Awake filling cystometry has been used for a long time to evaluate bladder function in freely moving mice, however, the specific methods used, vary among laboratories. The goal of this study was to describe the microsurgical procedure used to implant an intravesical tube and the experimental technique for recording urinary bladder pressure in an awake, freely moving mouse. In addition, experimental data is presented to show how surgery, as well as tubing type and size, affect lower urinary tract function and recording sensitivity. The effect of tube diameter on pressure recording was assessed in both polyethylene and polyurethane tubing with different internal diameters. Subsequently, the best performing tube from both materials was surgically implanted into the dome of the urinary bladder of male C57BL/6 mice. Twelve-hour, overnight micturition frequency was recorded in healthy, intact animals and animals 2, 3, 5, and 7 days post-surgery. At harvest, bladders were assessed for signs of swelling using gross observation and were subsequently processed for pathological analysis. The greatest extent of bladder swelling was observed on day 2 and 3, which correlated with behavioral voiding data showing significantly impaired bladder function. By day 5, bladder histology and voiding frequency had normalized. Based on the literature and evidence provided by our studies, we propose the following steps for in vivo recording of intravesical pressure and voided volume in an awake mouse: 1) Perform the surgery using an operating microscope and microsurgical tools, 2) Use polyethylene-10 tubing to minimize movement artifacts, and 3) Perform cystometry on post-operative day 5, when bladder swelling resolves.

This study describes the surgical procedures and experimental techniques for performing awake cystometry in a freely moving mouse. In addition, it provides experimental evidence to support its optimization and standardization.

评估在鼠标模型中执行唤醒膀胱测压的过程

Awake filling cystometry has been used for a long time to evaluate bladder function in freely moving mice, however, the specific methods used, vary among ...

A Quantitative Sensory Testing Paradigm to Obtain Measures of Pain Processing in Patients Undergoing Breast Cancer Surgery

Chronic pain following surgery, persistent postsurgical pain, is an important highly prevalent condition contributing to significant symptom burden and lower quality of life. Persistent postsurgical pain is relatively refractory to treatment hence generating a high need for preventive strategies and treatments. Therefore, the identification of patients at risk of developing persistent pain is an area of active ongoing research. Recently it was demonstrated that peri-operative disruptions in central pain processing may be able to predict persistent postsurgical pain at long term follow-up in breast cancer patients. The aim of the current report is to present a short protocol to obtain pain thresholds to different stimuli at multiple sites and a measure of endogenous analgesia in breast cancer patients. We have used this method successfully in a clinical context and detail some representative results from a clinical study.

Persistent postsurgical pain may be related to changes in pain processing. By assessing pain in response to standardized stimuli, changes in pain processing can be elucidated. We present methods to obtain pain thresholds to different stimuli and a measure of endogenous analgesia in patients undergoing breast cancer surgery.

一种定量感官检测方法在乳腺癌手术患者疼痛处理中的研究

Chronic pain following surgery, persistent postsurgical pain, is an important highly prevalent condition contributing to significant symptom burden and ...

Spinal Cord Lateral Hemisection and Asymmetric Behavioral Assessments in Adult Rats

Incomplete spinal cord injury (SCI) often leads to impairments of sensorimotor functions and is clinically the most frequent type of SCI. Human Brown-S&#233;quard syndrome&#160;is a common type of incomplete SCI caused by a lesion to one half of the spinal cord which results in paralysis and loss of&#160;proprioception&#160;on the same (or ipsilesional) side as the injury, and loss of pain and temperature sensation on the opposite (or contralesional) side. Adequate methodologies for producing a spinal cord lateral hemisection (HX) and assessing neurological impairments are essential to establish a reliable animal model of Brown-S&#233;quard syndrome. Although lateral hemisection model plays a pivotal role in basic and translational research, standardized protocols for creating such a hemisection and assessing unilateralized function are lacking. The goal of this study is to describe step-by-step procedures to produce a rat spinal lateral HX at the 9th thoracic (T9) vertebral level. We, then, describe a combined behavior scale for HX (CBS-HX) that provides a simple and sensitive assessment of asymmetric neurological performance for unilateral SCI. The CBS-HX, ranging from 0 to 18, is composed of 4 individual assessments which include unilateral hindlimb stepping (UHS), coupling, contact placing, and grid walking. For CBS-HX, the ipsilateral and contralateral hindlimbs are assessed separately. We found that, after a T9 HX, the ipsilateral hindlimb showed impaired behavior function whereas the contralateral hindlimb showed substantial recovery. The CBS-HX effectively discriminated behavioral functions between ipsilateral and contralateral hindlimbs and detected temporal progression of recovery of the ipsilateral hindlimb. The CBS-HX components can be analyzed separately or in combination with other measures when needed. Although we only provided visual descriptions of the surgical procedures and behavioral assessments of a thoracic HX, the principle may be applied to other incomplete SCIs and at other levels of the injury.

Here we describe surgical procedures to produce a reliable spinal cord lateral hemisection (HX) at the 9th thoracic level in adult rats and neurobehavioral assessments designed for detecting asymmetric deficits after such a unilateral injury.

成年大鼠脊髓侧性横断与不对称行为评估

Incomplete spinal cord injury (SCI) often leads to impairments of sensorimotor functions and is clinically the most frequent type of SCI. Human ...

A Protocol to Acquire the Degenerative Tenocyte from Humans

Tendinopathy, a painful condition that develops in response to tendon degeneration, is on the rise in the developed world due to increasing physical activity and longer life expectancy. Despite its increasing prevalence, the underlying pathogenesis still remains unclear, and treatment is generally symptomatic. Recently, numerous therapeutic options, including growth factors, stem cells, and gene therapy, were investigated in hopes of enhancing the healing potency of the degenerative tendon. However, the majority of these research studies were conducted only on animal models or healthy human tenocytes. Despite some studies using pathological tenocytes, to the best of our knowledge there is currently no protocol describing how to obtain human degenerative tenocytes. The aim of this study is to describe a standard protocol for acquiring human degenerative tenocytes. Initially, the tendon tissue was harvested from a patient with lateral epicondylitis during surgery. Then biopsy samples were taken from the extensor carpi radialis brevis tendon corresponding to structural changes observed at the time of surgery. All of the harvested tendons appeared to be dull, gray, friable, and edematous, which made them visually distinct from the healthy ones. Tenocytes were cultured and used for experiments. Meanwhile, half of the harvested tissues were analyzed histologically, and it was shown that they shared the same key features of tendinopathy (angiofibroblastic dysplasia or hyperplasia). A secondary analysis by immunocytochemistry confirmed that the cultured cells were tenocytes with the majority of the cells having positive stains for mohawk and tenomodulin proteins. The qualities of the degenerative nature of tenocytes were then determined by comparing the cells with the healthy control using a proliferation assay or qRT-PCR. The degenerative tenocyte displayed a higher proliferation rate and similar gene expression patterns of tendinopathy that matched previous reports. Overall, this new protocol might provide a useful tool for future studies of tendinopathy.

In vitro use of degenerative tenocytes is essential when investigating the efficacy of novel treatment on tendinopathy. However, most research studies use only the animal model or a healthy tenocyte. We propose the following protocol to isolate human degenerative tenocytes during surgery.

从人类获得变性 Tenocyte 的一种协议

Tendinopathy, a painful condition that develops in response to tendon degeneration, is on the rise in the developed world due to increasing physical ...