Feedback Learning and L-Dopa in Parkinson's Disease

反馈学习和左旋多巴治疗帕金森病

• 批准号: 7029676
• 负责人: MARK A GLUCK
• 金额: $ 17.39万
• 依托单位: RUTGERS THE STATE UNIV OF NJ NEWARK
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-03-10 至 2007-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7029676
• 关键词: Parkinson' s disease; association learning; behavioral /social science research tag; clinical research; cognition; discrimination learning; drug adverse effect; human middle age (35-64); human old age (65+); human subject; levodopa; neuropsychological tests; patient oriented research; psychopharmacology; sensory feedback

DESCRIPTION (provided by applicant): Many previous studies have shown that patients with Parkinson's disease (PD) suffer from a variety of cognitive deficits. Although early studies of these deficits focused primarily on executive or working memory tasks sensitive to frontal lobe impairment, more recent studies have demonstrated that patients with PD are also impaired on procedural learning tasks acquired incrementally through error-correcting feedback. However, procedural learning in PD patients is strongly influenced by L-Dopa, a dopamine precursor that alleviates motor symptoms by increasing global levels of dopamine. Preliminary data from our lab and others indicate that L-dopa may contribute to some learning deficits in early-stage PD, such that patient performance actually improves when patients are tested off their normal medication. This contrasts markedly with other data showing that L-dopa remediates PD performance on "frontal" tasks. The current proposal focuses on the specific aim of understanding how L-Dopa medication interacts with feedback processing during associative learning by Parkinson's patients. In particular, we will test two specific hypotheses relevant to this aim: Specific Hypothesis #1: Parkinson's patients are more impaired at associative learning through feedback training when on L-Dopa medication than when off-medication. Specific Hypothesis #2: Parkinson's patients, both on and off medication, can learn these same associative tasks normally when trained in an observational rather than feedback format; this is consistent with our prior functional imaging studies in healthy normal subjects which indicate that observational training activates more medial temporal lobe structures, rather than striatal regions, as compared to feedback training. The standard current practice for treating PD is with dopaminergic precursors and agonists, where the efficacy of these drugs is evaluated by assessing relief of motor symptoms. However, a better understanding of how PD and dopaminergic drugs affect cognition may allow treatment to take cognitive symptoms into account when assessing drug efficacy. Thus, the proposed work can provide a framework for future development of treatment programs that address both motor and cognitive functioning. In addition, our proposed studies will lead to behavioral markers that could be useful for assessing individual patients' cognitive symptoms. This will allow doctors to identify optimal dosing and medication combinations for each individual patient that lead to enhanced motor and cognitive functioning.

描述（由申请人提供）：许多先前的研究表明，帕金森氏病（PD）患者患有多种认知缺陷。尽管对这些缺陷的早期研究主要集中在对额叶障碍敏感的执行或工作记忆任务上，但最新的研究表明，PD患者也因通过错误纠正反馈而逐渐获得的程序学习任务受损。但是，PD患者的程序学习受L-DOPA的强烈影响，L-DOPA是一种多巴胺前体，通过增加全球多巴胺水平来减轻运动症状。来自我们实验室和其他实验室的初步数据表明，L-DOPA可能会导致早期PD的某些学习缺陷，因此当患者接受正常药物测试时，患者的表现实际上会有所改善。这与其他数据显着形成鲜明对比，表明L-DOPA补救措施在“额叶”任务上进行了PD性能。当前的提案着重于了解L-DOPA药物如何与帕金森患者联想学习期间的反馈处理相互作用的具体目的。特别是，我们将检验与此目标相关的两个特定假设：特定的假设＃1：帕金森氏病患者在通过反馈培训时在使用L-DOPA药物的反馈培训方面比过度培训时更受损害。具体假设＃2：帕金森氏症患者在药物内和关闭药物方面都可以学习这些相同的联想任务，通常以观察性的而不是反馈格式进行培训。这与我们先前在健康正常受试者中的功能成像研究一致，这表明与反馈训练相比，观察训练会激活更多的内侧颞叶结构，而不是纹状体区域。治疗PD的标准实践是多巴胺能的前体和激动剂，在这些药物的功效中，可以通过评估缓解运动症状来评估这些药物的功效。但是，更好地了解PD和多巴胺能药物如何影响认知可能会使治疗在评估药物疗效时可以考虑认知症状。因此，拟议的工作可以为未来开发的治疗计划提供框架，以解决运动和认知功能。此外，我们提出的研究将导致行为标志物，这些标志物可能有助于评估个别患者的认知症状。这将使医生能够为每个患者确定最佳的剂量和药物组合，从而提高运动和认知功能。