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

项目摘要 快感缺乏是一种常见的心理症状，其病理生理机制尚不清楚 明白此外，快感缺乏是一种特别难以治疗的症状。 因此，机制至关重要。快感缺失的两个核心特征是动机降低和 强化学习（RL）。然而，迄今为止，对快感缺乏的这两个组成部分进行了大量研究 与世隔绝这有点令人惊讶，因为动机和RL都被称为参与一个共同的网络， 神经基质，包括腹侧纹状体、中脑边缘多巴胺和背侧前扣带回（dACC）。 事实上，一个提出的机制，其中动机和RL赤字可能会出现的是一个异常的神经 预测误差（PE）的编码，这是大脑更新对未来价值的预期的信号。 成果。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，从而导致积极性降低。因此，本提案的目标是测试 假设PE信号中断可能会影响动机行为。这一领域先前工作的一个关键限制是 传统的评估动机行为的行为范式使用了简单和严格的试验， 试验结构不能捕捉动机行为的关键要素。事实上，在生活经验中， 走向一个目标的过程，是在一个人与环境互动时，一系列时刻的决定产生的。 环境因此，需要更多的自然主义范式和方法。PI将在两个方面填补这一空白 方法，通过1）检查在基于虚拟现实的新范例期间中断PE信号传导的因果效应 使用抑制性单脉冲经颅磁刺激dACC，和2）测试的影响， 体育对两周生态瞬间体育锻炼动机的行为调控 评估范式这项工作是创新的，因为它使用新颖的，生态有效的方法来研究 动机行为，并因果验证一个特定的神经机制，为整合PE信号， 动机的行动。这项工作的意义在于，体育信号在塑造动机行为中的作用 可以作为一个关键的机制，潜在的快感缺失症状，并更好地了解其神经 电路可以帮助未来开发基于机制的快感缺乏治疗方法。私家侦探集合了 一个跨学科的团队，这将帮助他获得专业知识，在神经生物学的快感缺乏和先进的 人类行为的计算机建模这个项目是PI发展的绝佳机会 作为一个独立的研究者，

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.