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.
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.
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