Prediction error and motivated actions: Testing a specific mechanism of behavior in ecologically-valid contexts

项目总结 快感缺失是一种常见的心理症状，其病理生理机制尚不清楚。 明白了。此外，快感缺失是一种特别难治疗的症状。潜在因素的识别 因此，机制是至关重要的。快感缺乏症的两个核心特征是动力减弱和受损 强化学习(RL)。然而，到目前为止，人们对快感缺失的这两个组成部分进行了大量的研究。 与世隔绝。这有点令人惊讶，因为动机和关系学习都参与了一个共同的网络 神经底物，包括腹侧纹状体、中脑边缘多巴胺和背侧前扣带核(DACC)。 事实上，一种可能同时引起动机和RL缺陷的机制是异常神经。 预测误差(PE)的编码，大脑用来更新对未来价值的预期的信号 结果。具体地说，PE信号的中断可能导致不适当的更新和低估 努力行动的价值，从而导致动力的降低。因此，这项提案的目标是测试 PE信号中断可能会影响动机行为的假说。这一领域先前工作的一个关键限制 评估动机行为的传统行为范式使用了简单化和僵化的审判方式- 审判结构没有捕捉到动机行动的关键要素。的确，在生活经验中，动力 目标的实现来自于一系列瞬间的决定，这些决定发生在人与目标的互动中 环境。因此，需要更多的自然主义范式和方法。PI将在两个月内填补这一空白 方法，通过1)检查在基于虚拟现实的新范式中干扰PE信号的因果效应 使用抑制性单脉冲经颅磁刺激对dACC，以及2)测试 两周生态瞬间体育行为调控对体育锻炼动机的影响 评估范式。这项工作具有创新性，因为它使用了新颖的、生态有效的方法来研究 动机行为和因果验证特定的神经机制的PE信号和整合 有动机的行为。这项工作的意义在于，体育信号在形成动机行为中的作用 可以作为非享乐性症状的关键机制，并更好地了解其神经 电路可以帮助基于机制的快感缺乏症治疗的未来发展。PI已经组装好了 一个跨学科的团队，将帮助他获得快感缺乏症和晚期神经生物学方面的专业知识 人类行为的计算模型。这个项目是PI发展的绝佳机会 作为一名独立研究人员，在智力和专业上都是如此。

PROJECT SUMMARY Anhedonia is a common psychological symptom, of which the pathophysiological mechanisms are not clearly understood. Moreover, anhedonia is a particularly difficult symptom to treat. The identification of underlying mechanisms is therefore critical. Two core features of anhedonia are reduced motivation and impaired reinforcement learning (RL). To date, however, these two components of anhedonia have been largely studied in isolation. This is somewhat surprising, as both motivation and RL are known to engage a common network of neural substrates, including the ventral striatum, mesolimbic dopamine, and the dorsal anterior cingulate (dACC). Indeed, one proposed mechanism by which both motivational and RL deficits may arise is an abnormal neural encoding of prediction error (PE), a signal with which the brain updates expectations about the value of future outcomes. Specifically, disruptions in PE signals may lead to inappropriate updating and underestimation of the value of effortful actions, thereby leading to reduced motivation. Therefore, the goal of this proposal is to test the hypothesis that disrupted PE signaling may impact motivated behavior. A key limitation of prior work in this area is that traditional behavioral paradigms assessing motivated behaviors have used simplistic and rigid trial-by- trial structures that do not capture critical elements of motivated actions. Indeed, in lived experience, motivation towards a goal emerges from a series of moment-by-moment decisions that occur as one interacts with the environment. Therefore, more naturalistic paradigms and methods are needed. The PI will fill this gap in two ways, by 1) examining the causal effect of disrupting PE signaling during a novel virtual-reality based paradigm using inhibitory single-pulse transcranial magnetic stimulation to the dACC, and 2) testing the effects of a behavioral manipulation of PE on motivation to engage in physical exercise in a two-week ecological momentary assessment paradigm. This work is innovative because it uses novel, ecologically-valid approaches to study motivated behavior and to causally-validate a specific neural mechanism for the integration of PE signals and motivated actions. The significance of this work is that the role of PE signals in shaping motivated behaviors could serve as a key mechanism underlying anhedonic symptoms, and a better understanding of its neural circuitry could aid the future development of mechanism-based treatments for anhedonia. The PI has assembled an interdisciplinary team that will help him to gain expertise in the neurobiology of anhedonia and advanced computational modeling of human behavior. This project represents an excellent opportunity for the PI to develop intellectually and professionally as an independent researcher.