Central Thalamic Deep Brain Stimulation to Regulate Arousal and Cognition

中丘脑深部刺激调节觉醒和认知

基本信息

  • 批准号:
    10606487
  • 负责人:
  • 金额:
    $ 58.89万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2020
  • 资助国家:
    美国
  • 起止时间:
    2020-04-01 至 2025-03-31
  • 项目状态:
    未结题

项目摘要

Deep brain stimulation (DBS) is an established therapy for various movement disorders and is now being investigated to treat a widening range of neurological and neuropsychiatric conditions. However, to fully realize the promise of DBS as a therapy, we need to better understand how it modulates neuronal activity within both the local DBS target and in the brain as a whole. The focus of this proposal is to advance a novel method of field-shaping central thalamic-DBS (fsCT-DBS) to modulate arousal and cognition. Arousal regulation is profoundly impacted in patients with structural brain injuries and is a common and untreated sequelae of many patients suffering from neurodegenerative and neuropsychiatric illnesses. In prior work we discovered a novel method of CT-DBS, where anodes and cathodes are separated across multiple implanted DBS leads within a specific region of the central thalamus, here termed `field-shaping CT-DBS' (fsCT-DBS). Here we will prospectively test and characterize behavioral performance of animals during fsCT-DBS. The central hypothesis to be tested here is that robust regulation of arousal with fsCT-DBS arises through selective delivery of electric stimulation to a specific fiber tract within the central thalamus, the medial aspect of the dorsal thalamic tegmental tract (DTTm). This fiber tract consists of axons originating from central thalamic nuclear groups and brainstem arousal centers that project to the anterior forebrain and are believed to play a crucial role in supporting cognition through the regulation of activity levels and brain-wide communication. The aims of this proposal seek to establish an anatomically accurate predictive biophysical model of the DTTm and to systematically test new modes of fsCT-DBS to enhance the use and capacity of cognitive resources in healthy behaving macaque monkeys. First, state-of-the-art biomedical imaging will be combined with ultrahigh- resolution optical imaging to construct predictive biophysical models of the DTTm. Second, the effects of fsCT- DBS on DTTm recruitment will be measured by comparing performance on a sustained attention/vigilance task and in two paradigms requiring additional cognitive resources, a set-shifting categorization task and a working memory task. The latter two tasks require cognitive flexibility, a faculty that is degraded in the majority of patients with neuropsychiatric disorders and structural brain injuries. Third, the use of adaptive fsCT-DBS will be explored using a new clinical-grade closed-loop DBS device. The identification and predictive biophysical modeling of the local fsCT-DBS target, the DTTm, the use of multipolar field shaping to validate the model predictions through behavior and large-scale physiology, and exploration of close-loop DBS are all highly innovative aspects of this proposal as they will improve our understanding of how to precisely target fsCT-DBS to robustly and reliability regulate anterior forebrain activity and support cognition. The use of healthy non- human primates as a model to validate the proposed approach is essential to guiding and facilitating design specifications for a new clinical-grade fsCT-DBS system for use in humans.
脑深部刺激(DBS)是一种治疗各种运动障碍的既定疗法,目前正在 接受调查,以治疗范围更广的神经和神经精神疾病。然而,要充分认识到 DBS作为一种治疗方法的前景,我们需要更好地了解它是如何调节两者中的神经元活动的 当地星展银行的目标和整个大脑中。这项提议的重点是提出一种新的方法 场整形中枢丘脑-DBS(fsCT-DBS)调节觉醒和认知。唤醒调节是 严重影响结构性脑损伤患者,是许多未经治疗的常见后遗症 患有神经退行性疾病和神经精神疾病的患者。在之前的工作中,我们发现了一部小说 CT-DBS方法,其中阳极和阴极跨多个植入的DBS导线分开 中央丘脑的特定区域,这里称为‘场成形CT-DBS’(fsCT-DBS)。在这里,我们将 前瞻性测试和表征动物在fsCT-DBS期间的行为表现。中环 这里要检验的假设是,fsCT-DBS对觉醒的稳健调节是通过选择性的 将电刺激传递到中央丘脑内的特定纤维束,丘脑的内侧部分 丘脑背侧被盖束(DTTm)该纤维束由起源于中央丘脑的轴突组成。 核团和脑干觉醒中心投射到前脑,据信在 通过调节活动水平和全脑沟通,在支持认知方面发挥关键作用。这个 这项建议的目的是建立一个解剖上准确的DTTm预测生物物理模型,并 系统测试fsCT-DBS的新模式,以提高认知资源的利用率和能力 行为健康的猕猴。首先,最先进的生物医学成像将与超高辐射相结合。 分辨率光学成像以构建DTTm的预测性生物物理模型。第二,fsct的影响-- DBS对DTTM招募的评估将通过比较持续注意力/警觉任务的表现来衡量 在两个需要额外认知资源的范式中,集合转移分类任务和工作 记忆任务。后两项任务需要认知灵活性,这是一种在大多数情况下退化的能力 患有神经精神障碍和结构性脑损伤的患者。第三,自适应fsCT-dbs的使用将 使用一种新的临床级闭环式DBS设备进行探索。生物物理学的鉴定与预测 对局部fsCT-DBS靶标DTTm进行建模,利用多极场整形对模型进行验证 通过行为和大规模生理学的预测,以及对闭环DBS的探索,都是高度高度的 这项提议的创新方面,因为它们将提高我们对如何准确瞄准fsct-dbs的理解。 稳健、可靠地调节前脑活动,支持认知。使用健康的非 以人类灵长类动物为模型来验证所提出的方法对于指导和促进设计是必不可少的 用于人体的新型临床级fsCT-DBS系统规范。

项目成果

期刊论文数量(2)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Selective activation of central thalamic fiber pathway facilitates behavioral performance in healthy non-human primates.
  • DOI:
    10.1038/s41598-021-02270-7
  • 发表时间:
    2021-11-29
  • 期刊:
  • 影响因子:
    4.6
  • 作者:
    Janson AP;Baker JL;Sani I;Purpura KP;Schiff ND;Butson CR
  • 通讯作者:
    Butson CR
Regulation of arousal and performance of a healthy non-human primate using closed-loop central thalamic deep brain stimulation.
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JONATHAN L BAKER其他文献

JONATHAN L BAKER的其他文献

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{{ truncateString('JONATHAN L BAKER', 18)}}的其他基金

Central thalamic deep brain stimulation to regulate arousal and cognition
中枢丘脑深部脑刺激调节觉醒和认知
  • 批准号:
    10372092
  • 财政年份:
    2020
  • 资助金额:
    $ 58.89万
  • 项目类别:
Central thalamic deep brain stimulation to regulate arousal and cognition
中枢丘脑深部脑刺激调节觉醒和认知
  • 批准号:
    9887008
  • 财政年份:
    2020
  • 资助金额:
    $ 58.89万
  • 项目类别:
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