Local field potentials reveal reward processing and impulse control disorders in Parkinson’s disease

局部场电位揭示帕金森病的奖励处理和冲动控制障碍

基本信息

  • 批准号:
    9760405
  • 负责人:
  • 金额:
    $ 3.92万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2019
  • 资助国家:
    美国
  • 起止时间:
    2019-05-16 至 2022-08-15
  • 项目状态:
    已结题

项目摘要

Project Summary/Abstract This application seeks to characterize the electrophysiological activity of the basal ganglia during reward processing in people with Parkinson’s disease (PD) with and without comorbid impulse control disorders (ICDs). ICDs encompass excessive and uncontrollable behaviors including hypersexuality, pathological gambling, binge eating, compulsive buying, punding (repeating simple activities), and dopamine dysregulation syndrome. They affect up to one-third of PD patients and significantly impact quality of life. Although ICDs were previously attributed to dopamine replacement therapies in PD, an additional iatrogenic etiology is deep brain stimulation (DBS) of the subthalamic nucleus (STN) or globus pallidus internus (GPi) – two FDA-approved and routinely- used DBS targets for the treatment of severe or medication-intolerant PD. Stemming from a lack of pathophysiological insight, there are no reliable strategies to curb these behaviors in PD. Therefore, the treatment of ICDs in PD today remains an unmet medical need. Although the mechanistic underpinnings of ICDs in PD are not fully known, there is a large body of evidence linking dysfunction in reward processing to both subclinical and clinically diagnosed impulsivity in PD. Namely, individuals with ICDs demonstrate a hypersensitivity to reward and a hyposensitivity to loss. Our objective is to identify electrophysiological markers of reward processing in the STN and GPi to characterize the role of these subcortical nuclei as they contribute to ICDs. To that end, we have successfully administered a reward processing game during PD DBS while simultaneously using the implanted STN or GPi DBS electrode as a recording device; we have discovered event- related and oscillatory changes in local field potentials (LFPs) (neuronal population-level activity) specific to reward in the STN and GPi. The central hypothesis of this proposal is that the STN and GPi participate in reward processing – measurable through LFPs – which can be used to differentiate individuals with and without ICDs. In Aim 1, we will examine LFPs in the STN and GPi during a reward processing game in awake, behaving PD patients undergoing DBS neurosurgery. In Aim 2, we will determine if the presence of clinically diagnosed ICDs affects LFPs measured in the STN and GPi during reward processing. This work is significant because it will implicate the basal ganglia in clinically significant reward processing through specific LFP changes. This work is innovative in that it will simultaneously uncover mechanisms of ICDs in PD and motivate novel therapeutic strategies for these disorders, particularly for patients receiving DBS implants.
项目总结/摘要 本申请旨在描述奖励过程中基底神经节的电生理活动 帕金森病(PD)患者与无共病冲动控制障碍(ICD)的处理。 ICD包括过度和无法控制的行为,包括性欲亢进,病态赌博,狂欢 进食、强迫性购买、重复简单活动和多巴胺失调综合征。他们 影响多达三分之一的PD患者,并显著影响生活质量。虽然ICD以前 归因于PD中的多巴胺替代疗法,另一个医源性病因是脑深部电刺激 (DBS)丘脑底核(subthalamic nucleus,缩写为ENA)或苍白球(globus pallidus internus,缩写为GPi)--这两个是FDA批准的,也是常规的-- 使用DBS靶点治疗重度或药物不耐受性PD。由于缺乏 病理生理学的见解,有没有可靠的策略来遏制这些行为在PD。因此 目前,PD中ICD的治疗仍然是未满足的医疗需求。尽管ICD的机械基础 在PD中,还不完全清楚,有大量证据将奖励处理功能障碍与两者联系起来, 亚临床和临床诊断的PD冲动。也就是说,植入ICD的个体表现出 对奖励的超敏反应和对损失的低敏反应。我们的目标是识别电生理标记 的奖励处理的行为,以表征这些皮层下核团的作用,因为它们有助于 到ICD。为此,我们在PD DBS期间成功地管理了奖励处理游戏, 同时使用植入的DBS或GPi DBS电极作为记录设备;我们发现了事件- 局部场电位(LFP)(神经元群体水平活动)的相关和振荡变化, 奖励在GPi和GPi。该提议的核心假设是,GPi和GPi参与了 奖励处理-可通过LFP测量-可用于区分具有和不具有 ICD。在目标1中,我们将研究在清醒、行为和奖励处理游戏中, 接受DBS神经外科手术的PD患者。在目标2中,我们将确定是否存在临床诊断的 ICD会影响奖励处理过程中测量的LFP和GPi。这项工作意义重大,因为它 将通过特定的LFP变化在临床上显著的奖赏处理中牵连基底神经节。这 这项工作是创新的,因为它将同时揭示PD中ICD的机制,并激发新的 这些疾病的治疗策略,特别是对于接受DBS植入物的患者。

项目成果

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Robert Stephen Eisinger其他文献

Robert Stephen Eisinger的其他文献

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{{ truncateString('Robert Stephen Eisinger', 18)}}的其他基金

Local field potentials reveal reward processing and impulse control disorders in Parkinson’s disease
局部场电位揭示帕金森病的奖励处理和冲动控制障碍
  • 批准号:
    10175068
  • 财政年份:
    2019
  • 资助金额:
    $ 3.92万
  • 项目类别:
Local field potentials reveal reward processing and impulse control disorders in Parkinson’s disease
局部场电位揭示帕金森病的奖励处理和冲动控制障碍
  • 批准号:
    10394944
  • 财政年份:
    2019
  • 资助金额:
    $ 3.92万
  • 项目类别:

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