Electrophysiological Probes and Treatments in Neurobehavioral Disorders

神经行为障碍的电生理学探测和治疗

• 批准号: 6432942
• 负责人: Eric M Wassermann
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6432942
• 关键词: GABA receptor; brain circulation; brain electrical activity; brain mapping; clinical research; depression; electrostimulus; epilepsy; female; hormone regulation /control mechanism; human subject; human therapy evaluation; language; magnetic field; memory; menstrual cycle; motor cortex; neural information processing; obsessive compulsive disorder; positron emission tomography; radiobiology; GABA receptor; brain circulation; brain electrical activity; brain mapping; clinical research; depression; electrostimulus; epilepsy; female; hormone regulation /control mechanism; human subject; human therapy evaluation; language; magnetic field; memory; menstrual cycle; motor cortex; neural information processing; obsessive compulsive disorder; positron emission tomography; radiobiology

One aim of this project is to use transcranial magnetic stimulation (TMS) of the brain to study physiological changes in different behavioral states and disorders. Since finding evidence of increased cortical excitability in obsessive-compulsive disorder (OCD), we have looked for an association between neurophysiological data and behavioral measures in the general population, using a dimensional approach. We found a highly significant positive association between the tendency to experience negative emotion ("Neuroticism" in the 5-factor personality model) and cortical excitability measured with paired-pulse TMS which reflects cortical GABA-glutamate balance. We hypothesize that a condition of heightened excitability, as exists in high "Neuroticism" individuals, should predispose to the development of long-term potentiation (LTP) of cortical synapses. We are looking for evidence of this with behavioral and electrophysiological tests before and after motor learning, again using a dimensional approach where possible. We further hypothesize that aberrant formation of associative LTP may underlie the development of OCD, focal dystonia, and other disorders and are initiating parallel studies to test these hypotheses. We have also initiated a study of the the possible contribution of genetic polymorphisms to the behavioral and neurophysiological dimensions mentioned above. For instance, we hypothesize that polymorphisms, such as that in the 5-HT transporter promoter region or the 5-HT1A receptor may contribute both to personality and to cortical excitability through their influence on GABAergic activity in the cortex. Other genes under study affect the 5-HT, dopamine, and GABA neurotransmitter systems. TMS measures of cortical excitability may provide intermediate phenotypes for genes affecting neural function and behavior

该项目的目的之一是使用大脑的经颅磁刺激（TMS）研究不同行为状态和疾病的生理变化。自从发现强迫症（OCD）中皮质兴奋性增加的证据以来，我们一直在使用维度方法来寻找神经生理学数据与一般人群中行为度量之间的关联。 我们发现经历负面情绪的趋势（在5因子人格模型中的“神经质”）与用配对脉冲TMS测量的皮质兴奋性之间存在高度显着的正相关，从而反映了皮质的GABA - 谷氨酸平衡。 我们假设存在高度“神经质”个体中的兴奋性的状况，应该倾向于发展皮质突触的长期增强（LTP）。我们正在寻找运动前后的行为和电生理测试的证据，并在可能的情况下再次使用维度方法。 我们进一步假设，相关LTP的异常形成可能是强迫症，局灶性肌张力障碍和其他疾病的发展，并且正在启动并行研究以检验这些假设。我们还开始研究遗传多态性对上述行为和神经生理学维度的可能贡献。 例如，我们假设多态性，例如在5-HT转运蛋白启动子区域或5-HT1A受体中，可能会通过对皮质中GABA能活性的影响来促进人格和皮质兴奋性。 研究中的其他基因会影响5-HT，多巴胺和GABA神经递质系统。皮质兴奋性的TMS度量可能为影响神经功能和行为的基因提供中间表型