Cortical plasticity in type II diabetes mellitus

描述（由申请人提供）：2型糖尿病（DM2）是导致残疾和死亡的主要原因，影响着美国近2600万人。近四分之三的患者神经系统受到与糖尿病相关的损伤，包括行为和认知缺陷，并增加患痴呆症的风险。我们试图推进我们对DM2对大脑皮层影响的神经生物学基础的理解，并开发一种可靠的早期检测和纵向评估方法。我们假设DM2的认知功能障碍与脑皮质可塑性的改变有关，这可以通过经颅磁刺激（TMS）证明。我们建议应用单脉冲和配对脉冲经颅磁刺激来评估DM2患者与匹配的健康对照者的皮质反应性。皮层可塑性的机制将通过评估特定的重复TMS方案（称为θ波爆发刺激（TBS））诱导的皮层反应性的调节来进一步探索。单脉冲经颅磁刺激前后运动反应的比较为人类大脑可塑性提供了一种无创测量方法。认知测试和运动学习任务将被用来证明这种可塑性测量的行为相关性。磁共振成像和磁共振波谱将进一步深入了解神经生理学发现的神经生物学基础。我们的试点研究支持了我们方法的可行性，并为我们的假设提供了支持性证据。因此，我们预计该研究的数据将满足对一种快速、无创、可靠和安全的方法的重要需求，以诊断、评估和跟踪DM2的皮质脑功能障碍。如果成功的话，基于tms的皮质反应性和可塑性测量将为DM2相关脑功能障碍提供可靠和客观的评估，并最终作为评估DM2认知功能障碍的有用生物标志物，为未来临床试验中有效疗法的开发提供信息，并评估治疗反应。

DESCRIPTION (provided by applicant): Type 2 Diabetes Mellitus (DM2) is a major cause of disability and death, affecting nearly 26 million people in the US. Nearly three quarters of those affected have DM-related damage to their nervous system that can include behavioral and cognitive deficits, and increase the risk of dementia. We seek to advance our understanding of the neurobiological substrate for these cortical brain consequences of DM2 and develop a reliable assay for their early detection and longitudinal assessment. We hypothesize that cognitive dysfunction in DM2 is associated with alterations in cortical brain plasticity that can b demonstrated by trans-cranial magnetic stimulation (TMS). We propose to apply single- and paired-pulse TMS to evaluate cortical reactivity in individuals with DM2 as compared with matched, healthy controls. Mechanisms of cortical plasticity will be further explored by assessing the modulation of cortical reactivity induced by a specific repetitive TMS protocol known as theta burst stimulation (TBS). The comparison of the motor responses induced by single-pulse TMS before and following TBS provides a noninvasive measure of brain plasticity in humans. Cognitive testing and a motor learning task will be used to demonstrate the behavioral correlates of this measure of plasticity. Magnetic resonance imaging and magnetic resonance spectroscopy will provide further insights into the neurobiological substrates of the neurophysiologic findings. Our pilot studies support the feasibility of our approach and provide supportive evidence for our hypothesis. We thus anticipate that data from the proposed study will address an important need for a rapid, noninvasive, reliable and safe method to diagnose, evaluate and follow cortical brain dysfunction in DM2. If successful, TMS-based measures of cortical reactivity and plasticity will provide a reliable and objective assessment of DM2-associated brain dysfunction, and eventually serve as useful biomarkers to evaluate cognitive dysfunction in DM2, inform the development of effective therapies and assess treatment response in future clinical trials.