Effects of DBS on sensorimotor processes

DBS 对感觉运动过程的影响

• 批准号: 6581027
• 负责人: JING-YU CHANG
• 金额: $ 3.85万
• 依托单位: WAKE FOREST UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-12-01 至 2005-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6581027
• 关键词: 6 hydroxydopamine; Parkinson's disease; action potentials; basal ganglia; cooperative study; corpus striatum; disease /disorder model; electrodes; electrophysiology; electrostimulus; immunocytochemistry; injection /infusion; international cooperation; laboratory rat; lenticular nucleus; motor cortex; neural information processing; neuroanatomy; neuromuscular stimulator; neurons; pathologic process; psychomotor reaction time; sensorimotor system; substantia nigra; subthalamus; thalamic nuclei

DESCRIPTION (provided by applicant) Parkinson's disease (PD) is one of the most prevalent neurodegenerative disorders. Reaction time task (RTt), a behavioral test measuring the sensorimotor reaction, is impaired in Parkinsonian patients. Impairment of RTt was also found in the animal model of PD. Lesion of the STN is able to restore the reaction time response that is disrupted by nigrostriatal dopamine lesion in the rat. Deep brain stimulation (DBS) of subthalamic nucleus (STN) has been used increasingly in the clinic to alleviate Parkinsonian syndromes (PS) during the past decade. Lack of behavioral model of rats for DBS research has hampered efforts to understand the neural mechanisms underlying the therapeutic effects of DBS. This proposal will combine advanced chronic, multiple-channel, single unit recording technique with unique DBS methods in the rat to study the neural responses in nigrostriatal dopamine lesioned rats performing RTt. An aim will be to use DBS to restore RT performance as a test of voluntary movement. Sixty-four recording electrodes will be implanted into the motor cortex, the globus pallidus, the STN, and the substantia nigra pars reticulata (SNr) and 4 pair of stimulation electrodes into the STN and SNr. Extracellular spike activity will be recorded simultaneously during RTt. After control sessions are completed, lesion of nigrostriatal dopamine system will be made by injection of 6-OHDA into both sides of striatum. The behavioral and electrophysiologic results after dopamine lesion will be compared with that obtained from the control condition to reveal the effects of dopamine depletion. High frequency stimulation (HFS) of STN and SNr will then be applied during RTt to counteract the adverse effects of dopamine depletion on RTt. This study will illustrate the neural responses mediating different aspects of RTt during the pathophysiological development of PD. The hypothesis that DBS of STN and SNr will restore normal neural processing in the basal ganglia thalamocortical circuit will be tested by analyzing the single and ensemble neural responses during behaviorally effective DBS. The aim of this proposal is to understand the fundamental neural mechanisms underlying the effects of DBS on PD. Incorporating the DBS into the well understood pathophysiological basal ganglia-thalamocortical network model and thus being able to restore normal network function to treat PD is the ultimate goal of this study. This research will be done primarily at Peking University in China as an extension of NIH grant R01-NS43441.

描述（由申请人提供） 帕金森氏病（PD）是最普遍的神经退行性疾病之一。反应时间任务（RTT）是一种测量感觉运动反应的行为测试，在帕金森病患者中受损。在PD动物模型中也发现了RTT的损害。 STN的病变能够恢复大鼠骨纹状体多巴胺病变破坏的反应时间反应。在过去的十年中，在诊所越来越多地使用了丘脑下核（STN）的深脑刺激（DBS），以减轻帕金森氏综合症（PS）。 DBS研究中缺乏大鼠的行为模型阻碍了理解DBS治疗作用的神经机制的努力。该提案将结合高级慢性，多通道单位记录技术与大鼠中独特的DBS方法，以研究进行RTT进行RTT的大型纹状体多巴胺病变的大鼠的神经反应。目的是使用DBS恢复RT性能作为自愿运动的测试。六十四个记录电极将植入运动皮层，球形pallidus，STN和底底nigra pars reticulata（SNR），以及4对刺激电极中的STN和SNR。在RTT期间，将同时记录细胞外峰值活性。控制疗程完成后，将通过在纹状体的两侧注射6-OHDA来制造黑质纹状体多巴胺系统的病变。多巴胺病变后的行为和电生理结果将与从对照条件中获得的结果进行比较，以揭示多巴胺消耗的作用。然后，将在RTT期间应用STN和SNR的高频刺激（HFS），以抵消多巴胺消耗对RTT的不利影响。这项研究将说明PD病理生理发展期间RTT不同方面的神经反应。 STN和SNR的DBS将通过分析行为有效的DBS期间分析单个和集成神经反应的假设，将恢复基底神经节丘脑皮层回路中的正常神经加工的假设。该提案的目的是了解DBS对PD影响的基本神经机制。这项研究的最终目标是将DBS纳入知识熟悉的病理生理基底神经会 - 丘脑皮质网络模型，从而能够恢复正常网络功能以治疗PD是这项研究的最终目标。这项研究将主要在中国北京大学进行，作为NIH赠款R01-NS43441的扩展。