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

项目概要 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 明白了。此外，快感缺乏是一种特别难以治疗的症状。底层的识别 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受损 强化学习（RL）。然而，迄今为止，快感缺失的这两个组成部分已得到广泛研究 处于孤立状态。这有点令人惊讶，因为众所周知，动机和强化学习都参与了一个共同的网络 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，一种可能引起动机和强化学习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。具体来说，PE 信号的中断可能会导致不适当的更新和低估 努力行动的价值，从而导致动力降低。因此，本提案的目标是测试 假设PE信号被破坏可能会影响动机行为。该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严格的逐项试验 试验结构没有捕捉动机行动的关键要素。事实上，在生活经验中，动机 实现某个目标的过程是在一个人与外界互动时做出的一系列决策的结果。 环境。因此，需要更加自然主义的范式和方法。 PI 将分两部分填补这一空白 方法，通过 1) 检查在基于虚拟现实的新型范式中破坏 PE 信号传导的因果影响 对 dACC 使用抑制性单脉冲经颅磁刺激，以及 2) 测试 两周生态瞬时体育锻炼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、生态上有效的方法来研究 动机行为并因果地验证 PE 信号整合的特定神经机制 动机的行动。这项工作的意义在于 PE 信号在塑造动机行为中的作用 可以作为快感缺乏症状的关键机制，并更好地理解其神经 电路可以帮助未来开发基于机制的快感缺失治疗方法。 PI已集结 一个跨学科团队将帮助他获得快感缺失和高级神经生物学方面的专业知识 人类行为的计算模型。该项目为PI提供了绝佳的发展机会 作为一名独立研究者，在智力和专业上。

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.