Cortical plasticity in type II diabetes mellitus

II 型糖尿病的皮质可塑性

• 批准号: 8659527
• 负责人: Alvaro Pascual-Leone
• 金额: $ 21.33万
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-05-15 至 2017-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8659527
• 关键词: Address; Adult; Affect; Age; Age-associated memory impairment; American; Animal Model; Atrophic; Autonomic nervous system; Balance training; Behavioral; Biological Assay; Biological Markers; Blood Vessels; Brain; Brain region; Cause of Death; Cephalic; Cessation of life; Clinical Trials; Cognitive; Cognitive deficits; Complication; Data; Dementia; Development; Diabetes Mellitus; Diagnosis; Digestion; Early Diagnosis; Equilibrium; Erectile dysfunction; Evoked Potentials; Facilities and Administrative Costs; Functional disorder; Future; Gender; Glucose; Glutamate Metabolism Pathway; Glutamates; Glycosylated hemoglobin A; Hippocampus (Brain); Human; Hyperglycemia; Hypoglycemia; Image; Impaired cognition; Individual; Insulin; Lead; Learning; Long-Term Potentiation; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Magnetism; Measures; Medical; Metabolism; Methods; Motor; Motor Cortex; Mus; Nerve Degeneration; Nervous System Physiology; Nervous System Trauma; Nervous system structure; Neuraxis; Neurobiology; Non-Insulin-Dependent Diabetes Mellitus; Pain; Participant; Patients; Peripheral; Peripheral Nerves; Physiologic pulse; Pilot Projects; Prediabetes syndrome; Premature Mortality; Protocols documentation; Reaction Time; Recruitment Activity; Resistance; Risk; Role; Sensory; Serial Learning; Stroke; Surrogate Markers; Synapses; Synaptic plasticity; Techniques; Testing; Therapeutic Intervention; Thick; Transcranial magnetic stimulation; United States; Work; aged; base; clinically significant; cognitive function; cost; disability; effective therapy; fasting glucose; insight; motor learning; neurotoxicity; novel; patient population; public health relevance; response; skill acquisition; skills; treatment response; two-dimensional

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.

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，影响了美国近2600万人。受影响的人中有将近四分之三对其神经系统造成了与DM相关的损害，其中可能包括行为和认知缺陷，并增加了痴呆症的风险。我们试图促进对DM2的这些皮质大脑后果的神经生物学底物的理解，并为其早期检测和纵向评估开发可靠的测定法。 我们假设DM2中的认知功能障碍与跨颅磁刺激（TMS）所证明的皮质脑可塑性的改变有关。我们建议与匹配的健康对照组相比，使用单脉冲和配对的脉冲TMS评估DM2个体的皮质反应性。通过评估特定重复的TMS方案（称为theta爆发刺激（TBS））引起的皮质反应性的调节，将进一步探索皮质可塑性的机制。 TBS之前和之后由单脉冲TMS引起的运动反应的比较提供了对人类脑可塑性的无创度量。认知测试和运动学习任务将用于证明这种可塑性度量的行为相关性。磁共振成像和磁共振光谱将为神经生理发现的神经生物学底物提供进一步的见解。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证据。 因此，我们预计拟议的研究的数据将解决对诊断，评估和遵循DM2中皮质脑功能障碍的快速，无创，可靠和安全的方法的重要需求。如果成功，则基于TMS的皮质反应性和可塑性测量方法将为DM2相关的脑功能障碍提供可靠的客观评估，并最终作为评估DM2中认知功能障碍的有用生物标志物，为有效疗法的发展提供了信息，并在未来的临床试验中评估治疗反应。