Striatal Deep Brain Stimulation for Learning Enhancement

描述(由申请者提供)：构成前纹状体的核团在学习和动机中起着关键作用。这些核的错乱与包括抑郁症、药物成瘾和学习障碍在内的一系列疾病有关。我们的假设是，在前纹状体有两种信息处理流，背侧和腹侧，它们发挥着互补但不同的作用。具体地说，我们假设包括尾状核(CD)的背侧流参与联想学习的执行方面，而包括伏隔核(NAC)的腹侧流参与为学习行为的执行提供动机。我们实验室最近的研究表明，间歇性电刺激CD，可以显著提高灵长类动物的视觉-运动学习速度。我们的团队是唯一能够研究这些结构的人，因为我们能够在灵长类动物和人类身上进行生理记录和电刺激。这个项目将测试最重要的假设，即CD和NAC的大脑深层刺激可以用来增强灵长类动物和人类的学习。在实验的第一阶段，我们将使用电刺激来调节灵长类动物联想学习过程中CD和NAC的活动，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中的刺激与CD中的刺激相结合，将导致两种灵长类动物以及随后在人类中的学习增强显著增加。初步数据显示CD和NAC扮演着不同的角色，这与我们提出的假设是一致的。阐明这些核团在学习和动机中的作用将极大地促进我们对大脑的了解；对于治疗对公众健康有极大影响的疾病至关重要。公共卫生相关性：常见的大脑疾病，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(基底节的一部分)的电刺激可以提高学习能力。这项提议的目标是确定目前用于治疗运动障碍的大脑深部刺激是否可以用于增强学习，从而用于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.