Optimizing pallidofugal modulation of midbrain and thalamic nuclei for treating cognitive-motor signs of Parkinson's disease

优化中脑和丘脑核的苍白球调节以治疗帕金森病的认知运动体征

基本信息

  • 批准号:
    10703249
  • 负责人:
  • 金额:
    $ 33.85万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2021
  • 资助国家:
    美国
  • 起止时间:
    2021-09-17 至 2026-07-31
  • 项目状态:
    未结题

项目摘要

Abstract: Neuroanatomical studies have shown globus pallidus internus (GPi) projection neurons strongly innervate the mesencephalic locomotor region (MLR), centromedian / parafascicular complex (CM/Pf), and lateral habenula (LHb). Abnormal activity patterns within these pallidofugal output nuclei has been hypothesized to contribute to several cognitive-motor signs of Parkinson's disease (PD), including levodopa-resistant gait dysfunction, behavioral set shifting difficulties, and deficits in goal-oriented motivation, respectively. However, little is known about the actual pathophysiological changes that occur in these nuclei with the emergence of Parkinson's disease. Deep brain stimulation (DBS) targeting regions in and around the GPi and subthalamic nucleus (STN) can be highly effective for treating motor signs of PD, but how such targeting affects MLR, CM/Pf, and LHb nuclei and how those effects relate to improvement or worsening of cognitive-motor signs of PD is not well understood. In the preclinical MPTP-treated non-human primate model of PD, Project 3 will investigate the contribution of (1) the GPi ↔ MLR network to parkinsonian gait dysfunction, (2) the GPi → CM/Pf network to difficulties with behavioral set shifting, and (3) the GPi → LHb network to deficits in goal-oriented motivation. This project will leverage our capacity to perform wireless spike and LFP recordings from chronic microdrives during untethered movement and during cognitive-motor tasks relevant to PD. The project will also develop a novel response surface optimization algorithm that uses real-time feature assessments of spike and LFP responses in the MLR, CM/Pf, and LHb to drive DBS targeting of the STN/lenticular fasciculus or GPe/GPi. The settings within the multi-dimensional DBS parameter space that generate the most robust changes in spike rate, spike pattern, spectral power, and/or information encoding within the MLR, CM/Pf, and LHb will be tested in cognitive-motor behavioral tasks that introduce obstacles and vary levels of effort and reward. This study will be critically important for not only better understanding the neural circuitry underlying cognitive-motor symptoms of PD but also to refine DBS methodologies to provide more consistent clinical outcomes with DBS therapies for PD.
文摘:

项目成果

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Matthew Douglas Johnson其他文献

Matthew Douglas Johnson的其他文献

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{{ truncateString('Matthew Douglas Johnson', 18)}}的其他基金

Data and Analysis Core
数据与分析核心
  • 批准号:
    10709639
  • 财政年份:
    2022
  • 资助金额:
    $ 33.85万
  • 项目类别:
Training Program in Translational Neuromodulation
转化神经调节培训计划
  • 批准号:
    10412589
  • 财政年份:
    2022
  • 资助金额:
    $ 33.85万
  • 项目类别:
Training Program in Translational Neuromodulation
转化神经调节培训计划
  • 批准号:
    10659148
  • 财政年份:
    2022
  • 资助金额:
    $ 33.85万
  • 项目类别:
Data and Analysis Core
数据与分析核心
  • 批准号:
    10610559
  • 财政年份:
    2022
  • 资助金额:
    $ 33.85万
  • 项目类别:
A novel electroceutical tool for treatment of kidney-based diseases
一种治疗肾脏疾病的新型电疗法工具
  • 批准号:
    10455432
  • 财政年份:
    2021
  • 资助金额:
    $ 33.85万
  • 项目类别:
Optimizing pallidofugal modulation of midbrain and thalamic nuclei for treating cognitive-motor signs of Parkinson's disease
优化中脑和丘脑核的苍白球调节以治疗帕金森病的认知运动体征
  • 批准号:
    10282964
  • 财政年份:
    2021
  • 资助金额:
    $ 33.85万
  • 项目类别:
A novel electroceutical tool for treatment of kidney-based diseases
一种治疗肾脏疾病的新型电疗法工具
  • 批准号:
    10194764
  • 财政年份:
    2021
  • 资助金额:
    $ 33.85万
  • 项目类别:
Optimizing pallidofugal modulation of midbrain and thalamic nuclei for treating cognitive-motor signs of Parkinson's disease
优化中脑和丘脑核的苍白球调节以治疗帕金森病的认知运动体征
  • 批准号:
    10489838
  • 财政年份:
    2021
  • 资助金额:
    $ 33.85万
  • 项目类别:
Spatiotemporal Optimization of Deep Brain Stimulation for Parkinson's Disease
帕金森病脑深部刺激的时空优化
  • 批准号:
    10680463
  • 财政年份:
    2016
  • 资助金额:
    $ 33.85万
  • 项目类别:
Spatiotemporal optimization of deep brain stimulation for Parkinson's Disease
帕金森病脑深部刺激的时空优化
  • 批准号:
    9278298
  • 财政年份:
    2016
  • 资助金额:
    $ 33.85万
  • 项目类别:

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