Causal Role of Cortico-Cerebellar Networks in Working Memory

项目概要/摘要 工作记忆（WM）能够短期维持心理表征，以支持 持续的认知操作，被认为是各种范围内最佳认知表现的基础 上下文。更好地了解 WM 的心理和神经机制可以提供 对认知成功和失败的主要决定因素之一的宝贵见解。充实的身体 许多文献试图揭示支持 WM 的特定大脑结构和机制。迄今为止，这 文献主要集中于有限的额顶皮质区域的贡献。 然而，最近的研究还表明小脑的某些部分参与了 WM 过程。然而，仍然存在 我们对小脑在 WM 中所扮演的确切角色的理解存在很大差距。正如之前的工作所 主要使用相关测量技术来论证小脑对 WM 的贡献，这个问题 小脑对于维持 WM 中的信息是否确实是必要的仍然存在 无人应答。本研究的目的是利用 WM 来研究小脑的因果作用 经颅磁刺激 (TMS)、功能性磁共振成像 (fMRI) 和 行为的计算建模。在目标 1 中，参与者将收到 TMS，以扰乱以下区域的活动： 在表演前的独立会议中对小脑、顶叶皮层和额叶皮层感兴趣 需要精确回忆所呈现的空间位置的任务。然后我们将检查此操作的效果 对源自计算模型的参数的破坏，该计算模型索引了 WM 的不同方面，例如 记忆的保真度或项目被成功编码的概率。在目标 2 中，我们将 TMS 与 fMRI 检查小脑和皮质区域对 WM 存储神经标志物的因果影响 整个大脑。具体来说，我们将使用贝叶斯生成模型来解码存储在 记忆，以及该位置编码的不确定性。拟议的实验将使 小脑和皮质区域在 WM 任务执行中的相对作用的分离，从而提供了 对 WM 的神经基础有更细致的了解。 WM 的更完整表征 系统有潜力为旨在治疗广泛临床疾病的疗法的开发提供信息 WM 功能障碍是主要症状的疾病。

PROJECT SUMMARY/ABSTRACT Working memory (WM) enables the short-term maintenance of mental representations in support of ongoing cognitive operations and is thought to underlie optimal cognitive performance across a wide range of contexts. Achieving a better understanding of the psychological and neural mechanisms of WM can provide valuable insight into one of the primary determinants of both cognitive success and failure. A substantial body of literature has sought to reveal the specific brain structures and mechanisms that support WM. To date, this literature has predominantly focused on the contributions of a limited set of fronto-parietal cortical areas. Recent work, however, additionally implicates portions of the cerebellum in WM processes. Yet, there remain substantial gaps in our understanding of the precise role that the cerebellum plays in WM. As prior work has primarily used correlational measurement techniques to argue for cerebellar contributions to WM, the question of whether the cerebellum is actually necessary for the maintenance of information in WM remains unanswered. The goal of the proposed research is to investigate the causal role of the cerebellum in WM using a combination of transcranial magnetic stimulation (TMS), functional magnetic resonance imaging (fMRI), and computational modeling of behavior. In Aim 1, participants will receive TMS to disrupt activity in regions of interest in cerebellum, parietal cortex, and frontal cortex in independent sessions just prior to the performance of a task that requires precise recall of presented spatial locations. We will then examine the effect of this disruption on parameters derived from a computational model that index distinct aspects of WM, such as the fidelity of memory or the probability that an item is successfully encoded. In Aim 2, we will combine TMS with fMRI to examine the causal influence of cerebellar and cortical areas on neural markers of WM storage throughout the brain. Specifically, we will use a Bayesian generative model to decode the location stored in memory, as well as the uncertainty with which that location is encoded. The proposed experiments will enable the dissociation of the relative roles of cerebellar and cortical areas in WM task performance, thus providing a more nuanced understanding of the neural underpinnings of WM. A more complete characterization of the WM system has the potential to inform the development of therapies aimed at treating a broad range of clinical conditions for which WM dysfunction is a primary symptom.