Causal Role of Cortico-Cerebellar Networks in Working Memory

项目概要/摘要 工作记忆（WM）能够维持短期的心理表征，以支持 正在进行的认知操作，并被认为是在广泛的范围内获得最佳认知表现的基础。 contexts.更好地理解工作记忆的心理和神经机制， 对认知成功和失败的主要决定因素之一的有价值的见解。相当多 的文献试图揭示支持WM的特定脑结构和机制。迄今为止，这 文献主要集中在有限的一组额顶叶皮质区的贡献。 然而，最近的工作，另外牵连部分小脑在WM过程。然而， 我们对小脑在WM中的确切作用的理解存在重大差距。正如先前的工作一样， 主要使用相关测量技术来论证小脑对WM的贡献， 小脑是否真的是维持WM信息所必需的， 无人回应这项研究的目的是利用脑电刺激来研究小脑在WM中的因果作用。 经颅磁刺激（TMS）、功能性磁共振成像（fMRI）和 行为的计算机建模在目标1中，参与者将接受TMS，以扰乱 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 一个需要精确回忆当前空间位置的任务。然后我们将研究这种情况的影响。 从计算模型中得出的参数中断，这些参数指示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，我们将联合收割机TMS与 fMRI检查小脑和皮层区域对WM存储神经标记物的因果影响 在整个大脑中。具体来说，我们将使用贝叶斯生成模型来解码存储在 存储器，以及该位置被编码的不确定性。拟议的实验将使 分离小脑和皮层区域在WM任务执行中的相对作用，从而提供了一个 对WM的神经基础有更细致的理解。一个更完整的描述WM 该系统有可能为旨在治疗广泛的临床疾病的治疗方法的开发提供信息。 WM功能障碍是主要症状的病症。

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.