Striatal Deep Brain Stimulation for Learning Enhancement

描述（由申请人提供）：构成前纹状体的核在学习和动机中发挥着关键作用。这些细胞核的紊乱与多种疾病有关，包括抑郁症、毒瘾和学习障碍。我们的假设是，前纹状体有两条信息处理流，即背侧和腹侧，它们发挥着互补但不同的作用。具体来说，我们假设背侧流，包括尾状核（Cd），参与联想学习的执行方面，而腹侧流，包括伏隔核（NAc），参与为学习行为的表现提供动力。我们实验室最近的研究表明，镉的间歇性电刺激可以显着提高灵长类动物的视觉运动学习率。我们的团队具有独特的研究这些结构的能力，因为我们能够对灵长类动物和人类进行生理记录和电刺激。该项目将测试一个总体假设，即 Cd 和 NAc 的深部脑刺激可用于增强灵长类动物和人类的学习。在实验的第一阶段，我们将利用电刺激来调节灵长类动物联想学习过程中Cd和NAc的活性，以优化学习增强的参数。在第二阶段，我们将使用植入的 DBS 设备来评估刺激对学习和动机的行为影响。我们预测，NAC 的刺激与 Cd 的刺激相结合将导致灵长类动物以及随后人类的学习能力显着增强。初步数据非常有希望表明 Cd 和 NAc 发挥着不同的作用，与我们提出的假设一致。阐明这些神经核在学习和动机中的作用将显着增进我们对大脑的理解；对于治疗对公共健康有极大影响的疾病至关重要。公众健康相关性：常见的脑部疾病，如中风、创伤性脑损伤和自闭症，会导致学习动作或联想的能力受损。最近的研究表明，纹状体（基底神经节的一部分）的电刺激可以增强学习能力。该提案的目标是确定目前用于治疗运动障碍的深部脑刺激是否可用于增强学习，从而加速或增加脑损伤后的功能恢复。

DESCRIPTION (provided by applicant): The nuclei comprising the anterior striatum play a critical role in learning and motivation. Derangements of these nuclei are implicated in a broad range of diseases including depression, drug addiction, and learning disorders. Our hypothesis is that there are two streams of information processing in the anterior striatum, dorsal and ventral, that perform complementary but different roles. Specifically, we hypothesize that the dorsal stream, which includes the caudate (Cd), is involved in the executive aspects of associative learning, whereas the ventral stream, which includes the nucleus accumbens (NAc), is involved in providing motivation for the performance of learned behaviors. Recent studies in our lab have demonstrated that intermittent electrical stimulation of the Cd, can significantly enhance the rate of visual-motor learning in primates. Our group is uniquely able to investigate these structures because we are able to perform physiological recordings and electrical stimulation in both primates and humans. This project will test the overarching hypothesis that is that deep brain stimulation of the Cd and NAc can be used to enhance learning in primates and humans. In the first stage of experiments, we will we use electrical stimulation to modulate the activity of the Cd and NAc during associative learning in primates, in order to optimize the parameters for learning enhancement. In the second stage, we will use the implanted DBS devices to assess the behavioral effects of stimulation on learning and motivation. We predict that stimulation in the NAC combined with stimulation in the Cd will lead to a dramatic increase in learning enhancement in both primates and subsequently in humans. Preliminary data is very promising suggesting that the Cd and NAc play distinct roles consistent with our proposed hypothesis. Elucidating the role of these nuclei in learning and motivation will significantly advance our understanding of the brain; and is vitally important to treating disorders that have an extremely large impact on public health. PUBLIC HEALTH RELEVANCE: Common brain disorders such as stroke, traumatic brain injury, and autism, result in an impaired ability to learn movements or associations. Recent work has demonstrated that electrical stimulation in the striatum, a part of the basal ganglia, can lead to enhanced learning. The goal of this proposal is to establish whether deep brain stimulation, which is currently used to treat movement disorders, can be used to enhance learning and hence be used to speed or increase functional recovery following brain injury.