Cortical plasticity in type II diabetes mellitus

描述（由申请人提供）：2型糖尿病（DM2）是残疾和死亡的主要原因，影响美国近2600万人。近四分之三的受影响者对神经系统有DM相关的损害，包括行为和认知缺陷，并增加痴呆症的风险。我们寻求推进我们的理解，这些大脑皮层的DM2后果的神经生物学基板，并开发一个可靠的检测方法，他们的早期检测和纵向评估。 我们假设DM2中的认知功能障碍与大脑皮层可塑性的改变有关，这可以通过经颅磁刺激（TMS）来证明B。我们建议应用单脉冲和双脉冲经颅磁刺激来评估与匹配的健康对照组相比，DM2个体的皮质反应性。皮质可塑性的机制将进一步探讨，通过评估调制的皮质反应性诱导的一个特定的重复TMS协议称为θ爆发刺激（TBS）。在TBS之前和之后由单脉冲TMS诱导的运动反应的比较提供了人类大脑可塑性的非侵入性测量。认知测试和运动学习任务将被用来证明这种可塑性措施的行为相关性。磁共振成像和磁共振波谱将提供进一步的见解神经生理学的发现的神经生物学基板。我们的试点研究支持我们的方法的可行性，并为我们的假设提供支持性证据。 因此，我们预计，从拟议的研究的数据将解决一个重要的需求，快速，无创，可靠和安全的方法来诊断，评估和跟踪大脑皮层功能障碍的DM2。如果成功的话，基于TMS的皮质反应性和可塑性测量将为DM2相关的脑功能障碍提供可靠和客观的评估，并最终作为有用的生物标志物来评估DM2的认知功能障碍，为有效治疗的开发提供信息，并在未来的临床试验中评估治疗反应。

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.