Sensory based CNS diagnostics for the clinic

临床中基于感觉的中枢神经系统诊断

• 批准号: 8190617
• 负责人: Mark A Tommerdahl
• 金额: $ 21.89万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-01 至 2013-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8190617
• 关键词: Address; Age; Animal Experimentation; Area; Autistic Disorder; Basic Science; Behavior; Brain Concussion; Caregivers; Categories; Cerebrum; Clinic; Clinical; Clinical Research; Data; Databases; Development; Devices; Dextromethorphan; Diagnosis; Diagnostic; Disease; Equilibrium; Evaluation; Experimental Models; Fibromyalgia; GABA Agonists; Genetic; Goals; Health; Image; Individual; Investigation; Laboratory Animals; Lead; Letters; Link; Machine Learning; Measures; Mediating; Methodology; Methods; Metric; Migraine; Molecular; N-Methyl-D-Aspartate Receptors; N-Methylaspartate; Nature; Nerve Degeneration; Neuraxis; Neurodevelopmental Disorder; Neurons; Neurosciences Research; Ophthalmic examination and evaluation; Pain; Patients; Performance; Physiological; Play; Population; Population Control; Primary Health Care; Process; Protocols documentation; Recruitment Activity; Research; Resolution; Role; Route; Sensory; Site; Stimulus; System; Tactile; Techniques; Technology; Temporomandibular Joint Disorders; Testing; Translations; Trauma; Treatment Efficacy; United States National Institutes of Health; Vulvodynia; Work; analytical tool; base; central sensitization; chronic pain; cohort; cost effective; data mining; demographics; design; extracellular; gamma-Aminobutyric Acid; improved; in vivo; information processing; nervous system disorder; neurophysiology; neurotransmission; nonhuman primate; novel; process optimization; protocol development; response; sensory cortex; white matter damage

DESCRIPTION (provided by applicant): There is currently a significant gap that exists between fundamental neuroscience research and translation of the findings of that research into everyday practice. Experimental findings at the genetic, cellular, molecular and systems level often take a fairly long and frequently circuitous route to make an impact on a particular neurological disease or disorder. The goal of our work is to bridge the neuroscientific gap at the systems level of study by developing standardized sensory measures that can be not only utilized in clinical or clinical research settings, but can be directly correlated with the observations obtained directly from sensory cortex in non-human primates via high resolution imaging and extracellular recording. Successful development of an experimental model that iteratively evaluates the relationship of clinical measures and systemic CNS responses to specific mechanistic alterations will be quite significant. Such an evaluation of an individual's CNS status could be directly linked to systemic mechanistic deficiencies or alterations observed in animal experimentation. Towards that goal, we have successfully designed and fabricated a tactile sensory diagnostic device. In parallel with that development, we designed a number of protocols - based on experimental neurophysiological findings from both our non human primate research and that of others - that could be rapidly and efficiently delivered (1-3 minutes) to a number of subject populations. The tactile diagnostic system that we have developed was conceptually designed to investigate differences in cortical information processing strategies between people with autism and people without. In this proposal we ask whether or not the strategy that we have devised for investigating a population with a neurodevelopmental disorder could be broadly applied to a number of neurological disorders. In other words, we consider the changes manifested by the neurodevelpmental disorder autism to be systemic, and if systemic cortical alterations occur in other neurological disorders, could they also be detected in the same manner? Proof-of-concept studies in a number of clinical research areas demonstrated that these newly developed metrics were sensitive to systemic cortical alterations. One question that emerges from this data is that most of these neurological disorders result in some type of altered central sensitization, no matter what the cause - whether it be neurodevelopmental, neurodegenerative, pharmacological or trauma induced - in which there is a significant change in the balance between excitation and inhibition. This application proposes to determine if sensory perceptual metrics, similar to those that were used to successfully distinguish subjects with autism from healthy control populations (with 90% accuracy using SVM to assess the results of a 25 minute battery of 9 protocols), could be used to reliably distinguish - on an individual basis - subjects with neurological disorders that are not neurodevelopmental in nature. Towards this goal, we target subjects from one broad category of neurological disorders - chronic pain. More specifically, we will examine the differences and commonalities from observations of pain patients diagnosed with one of the following: fibromyalgia, vulvodynia, TMJD, IBS and migraine. PUBLIC HEALTH RELEVANCE: The overall goal of the proposed work is to investigate the utility of novel sensory-based methodologies that are currently being used in both basic and clinical research. Recently, utilizing state-of-the-art technology, we built a multi-site tactile stimulator that allows for investigation of central nervous system (CNS) health and advanced methods in sensory perceptual metrics. These metrics have been demonstrated to be sensitive to changes in centrally mediated mechanisms; and systemic alterations of cortical health (via neurodegenerational, neurodevelopmental, pharmacological or trauma induced changes) robustly change the measures. It is anticipated that clinicians will be able to utilize these measures to improve diagnostic performance and enable assessment of efficacy of treatment. The study itself will serve to validate the utility of a number of these measures in several types of pain, specifically fibromyalgia, TMJD, IBS, vulvodynia and migraine. The information from this study could aid in understanding centrally mediated mechanisms that undergo significant alterations with chronic pain.

描述（由申请人提供）：目前，基础神经科学研究与将该研究结果转化为日常实践之间存在重大差距。在遗传、细胞、分子和系统水平上的实验发现往往需要相当长的时间，而且往往是迂回的路线，才能对特定的神经系统疾病或障碍产生影响。我们工作的目标是通过开发标准化的感觉测量来弥合系统水平研究的神经科学差距，这些测量不仅可以用于临床或临床研究环境，而且可以与通过高分辨率成像和细胞外记录直接从非人类灵长类动物的感觉皮层获得的观察结果直接相关。成功开发一个实验模型，反复评估临床措施和系统中枢神经系统反应的关系，以特定的机制改变将是非常重要的。对个体CNS状态的这种评估可能与动物实验中观察到的全身机制缺陷或改变直接相关。 为了实现这一目标，我们已经成功地设计和制造了一个触觉感觉诊断设备。与此同时，我们设计了一些方案-基于我们的非人类灵长类动物研究和其他研究的实验神经生理学发现-可以快速有效地（1-3分钟）传递给许多受试者群体。我们开发的触觉诊断系统在概念上是为了研究自闭症患者和正常人之间皮层信息处理策略的差异。在这个建议中，我们问是否我们设计的策略，调查人口与神经发育障碍可以广泛应用于一些神经系统疾病。换句话说，我们认为神经发育障碍自闭症所表现出的变化是系统性的，如果其他神经系统疾病也发生了系统性皮质改变，它们也可以以同样的方式检测到吗？ 在一些临床研究领域的概念验证研究表明，这些新开发的指标是敏感的系统性皮质改变。从这些数据中出现的一个问题是，这些神经系统疾病中的大多数导致某种类型的中枢敏感化改变，无论是什么原因-无论是神经发育，神经退行性，药理学还是创伤诱导-其中兴奋和抑制之间的平衡发生了显着变化。本申请提出确定感官知觉度量，类似于用于成功区分患有自闭症的受试者与健康对照人群的那些度量（使用SVM评估25分钟的9个方案的结果具有90%的准确度），是否可以用于可靠地区分-在个体基础上-患有本质上不是神经发育的神经障碍的受试者。为了实现这一目标，我们的目标对象从一个广泛的神经系统疾病类别-慢性疼痛。更具体地说，我们将研究的差异和共同点，从观察疼痛患者诊断为以下之一：纤维肌痛，外阴痛，TMJD，IBS和偏头痛。 公共卫生相关性：拟议工作的总体目标是调查目前正在基础和临床研究中使用的新的基于感觉的方法的实用性。最近，利用国家的最先进的技术，我们建立了一个多站点触觉刺激器，允许调查中枢神经系统（CNS）的健康和先进的方法在感官知觉指标。已证明这些指标对中枢介导机制的变化敏感;皮质健康的系统性改变（通过神经退行性、神经发育、药理学或创伤诱导的变化）强烈改变了这些指标。预计临床医生将能够利用这些措施来提高诊断性能，并能够评估治疗效果。这项研究本身将用于验证这些措施在几种类型的疼痛中的效用，特别是纤维肌痛，TMJD，IBS，外阴痛和偏头痛。这项研究的信息有助于理解慢性疼痛发生显著变化的中枢介导机制。