Sensory based CNS diagnostics for the clinic

描述（由申请人提供）：目前，在基础神经科学研究和将研究结果转化为日常实践之间存在着巨大的差距。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，才能对特定的神经疾病或障碍产生影响。我们的工作目标是通过开发标准化的感觉测量方法，在系统研究水平上弥合神经科学的差距，这些测量方法不仅可以用于临床或临床研究环境，而且可以直接与通过高分辨率成像和细胞外记录从非人类灵长类动物的感觉皮层直接获得的观察结果相关联。成功开发一个实验模型，迭代评估临床措施和系统中枢神经系统对特定机制改变的反应的关系将是非常重要的。这种对个体中枢神经系统状态的评估可能与动物实验中观察到的系统性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官诊断装置。与此同时，我们根据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，设计了许多方案，这些方案可以快速有效地（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用来研究自闭症患者和非自闭症患者大脑皮层信息处理策略的差异。在这个提议中，我们要问的是，我们为研究患有神经发育障碍的人群而设计的策略是否可以广泛应用于许多神经障碍。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全身性的，如果其他神经系统疾病也发生了全身性的皮层改变，它们是否也能以同样的方式被检测到？许多临床研究领域的概念验证研究表明，这些新开发的指标对系统性皮质改变很敏感。从这些数据中出现的一个问题是，大多数这些神经系统疾病都会导致某种类型的中枢敏化改变，无论原因是什么——无论是神经发育、神经退行性、药理学还是创伤诱发——在这些疾病中，兴奋和抑制之间的平衡都发生了重大变化。这个应用程序建议确定感官知觉指标，类似于那些被用来成功区分自闭症患者和健康对照人群的指标（使用支持向量机评估25分钟9个方案的结果，准确率为90%），是否可以用于可靠地区分-在个体基础上-具有非神经发育性神经障碍的受试者。为了实现这一目标，我们的目标对象来自一个广泛的神经系统疾病类别-慢性疼痛。更具体地说，我们将通过观察诊断为以下疾病之一的疼痛患者的差异和共同点：纤维肌痛、外阴痛、颞下颌关节痛、肠易激综合征和偏头痛。

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.