MRC Transition Support Award CSF Sanjay Manohar

该研究金旨在回答四个主要问题：1。多巴胺受体激动剂对不同类型的动机的影响有差异吗？2.抗胆碱能药物能调节健康志愿者的动机吗？3.腹内侧前额叶损伤后的动机变化是否可以解释为情境敏感性降低？问题1由3个实验组成，已完成并发表。我们建立了-动机的动态效果可以通过运动期间的在线纠正反馈来捕获（Manohar et al. Neuropsychologia 2018），-多巴胺对两种类型的动机具有相反的影响（格罗甘，Sandhu，Hu & Manohar，eLife 2020），-我们可以使用瞳孔测量法预测冲动控制障碍（Drew，Alummed，Baig，... Manohar*，Husain* et al. Brain 2020），-多巴胺改善认知流畅性（Ang*，Manohar* et al. Curr Biol 2018）-多巴胺对工作记忆的不同方面也有相反的影响（Fallon，Kienast，. Manohar & Husain，J. Psychopharmacol. 2019），-对工作记忆的影响会影响对动作的控制（Fallon，Drew，Mummed，Manohar & Husain，Cortex 2018），-我开发了第一个工作记忆的生理模型，也解释了动作控制（Manohar et al. Neurosci Biobeh Rev. 2019）。令人惊讶的新原理是，神经模式在几秒钟内改变了它们的意义，这需要重新评估许多单神经元数据。这篇文章被4篇主要的评论引用，并被邀请参加讲座（苏黎世，布朗大学，伦敦大学学院），并成为我获得Leverhulme基金的基础。这项工作使我获得了托马斯威利斯中级职业研究员奖。乙酰胆碱是纹状体多巴胺释放的关键调节剂。胆碱能药物能调节动机障碍吗？2.多巴胺的释放可能是由内侧前额叶皮质控制的。在这一地区的不同分区受到损害后，是否会出现冷漠和冲动？过渡奖将允许我回答这些问题。数据收集和招聘工作已经开始。我的目标是在2022年申请高级奖学金时出版这两本重要的出版物。

The fellowship aimed to answer four main questions:1. Do dopamine agonists affect different types of motivation differentially?2. Can anticholinergic drugs modulate motivation in healthy volunteers?3. Are motivational changes following ventromedial prefrontal damage explainable as reduced context-sensitivity?Question 1 constituted 3 experiments, which were completed and published. We established that- dynamic effects of motivation can be captured by online corrective feedback during a movement (Manohar et al. Neuropsychologia 2018),- dopamine has opposing effects on two types of motivation (Grogan, Sandhu, Hu & Manohar, eLife 2020), - we can predict impulse control disorders using pupillometry (Drew, Muhammed, Baig, ... Manohar*, Husain* et al. Brain 2020),- dopamine improved cognitive fluency (Ang*, Manohar* et al. Curr Biol 2018)- dopamine also has opposing effects on different aspects of working memory (Fallon, Kienast, ... Manohar & Husain , J. Psychopharmacol. 2019),- the effect on working memory influences control over actions (Fallon, Drew, Muhammed, Manohar & Husain, Cortex 2018),and- I developed the first physiological model of working memory that also accounts for action control (Manohar et al. Neurosci Biobeh Rev. 2019). The surprising new principle here is that neural patterns change their meaning over seconds, calling for re-evaluation of much single-neuron data. This has been cited in 4 major reviews, led to invited talks (Zurich, Brown, UCL) and formed the basis for my Leverhulme grant.This work has led to my being awarded the Thomas Willis Intermediate Career Researcher award.The second two questions are left unanswered by this data: 1. Acetylcholine is a critical regulator of striatal dopamine release. Can cholinergic drugs modulate disorders of motivation?2. Dopamine release may be controlled by medial prefrontal cortex. Do apathy and impulsivity arise after lesions to different subregions within this area?The transition award will permit me to answer these questions. Data collection and recruitment have already begun. I aim to have these two key publications out by the time of applying for a Senior Fellowship in 2022.