MRC Transition Support Award CSF Sanjay Manohar

该奖学金旨在回答四个主要问题：1。多巴胺激动剂对不同类型动机的影响是否不同？抗胆碱能药物能调节健康志愿者的动机吗？腹内侧前额叶损伤后的动机变化是否可以解释为上下文敏感性降低？问题1包含3个实验，完成并发表。我们发现，动机的动态效应可以通过运动过程中的在线纠正反馈来捕捉（Manohar等人）。-多巴胺对两种类型的动机有相反的影响（Grogan, 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, Muhammed, Baig，…Manohar*， Husain*等人。大脑2020)，-多巴胺改善认知流畅性（Ang*， Manohar*等人）。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，…-对工作记忆的影响影响对行为的控制（Fallon, Drew, Muhammed, Manohar & Husain, Cortex 2018），并且-我开发了第一个工作记忆的生理模型，也说明了行动控制（Manohar等人）。《神经科学生物学报》2019年版。这里令人惊讶的新原理是，神经模式会在几秒钟内改变它们的含义，这要求对许多单个神经元数据进行重新评估。这篇论文被4篇主要综述引用，并被邀请进行了演讲（苏黎世、布朗、伦敦大学学院），并成为我的Leverhulme基金的基础。这项工作使我获得了Thomas Willis中级职业研究员奖。这个数据没有回答第二个问题：1。乙酰胆碱是纹状体多巴胺释放的关键调节因子。胆碱能药物能调节动机障碍吗？多巴胺释放可能受内侧前额皮质控制。冷漠和冲动是否在该区域的不同亚区域受损后出现？过渡奖将使我有机会回答这些问题。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.