Testing neural mechanisms of sequence monitoring in the frontal cortex across species: integrated fMRI and electrophysiology

测试跨物种额叶皮层序列监测的神经机制：综合功能磁共振成像和电生理学

• 批准号: 10563315
• 负责人: Theresa Marie Desrochers
• 金额: $ 54.17万
• 依托单位: BROWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-04-01 至 2027-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10563315
• 关键词: Activities of Daily Living; Adaptive Behaviors; Anatomy; Area; Back; Basal Ganglia; Behavior; Behavior monitoring; Behavioral; Brain; Cells; Cerebellum; Code; Cognitive; Complex; Computer Models; Data; Disease; Dissociation; Electrophysiology (science); Elements; Foundations; Functional Magnetic Resonance Imaging; Goals; Hippocampus; Human; Knowledge; Lateral; Life; Location; Medial; Memory; Monitor; Monkeys; Motor; Motor Cortex; Motor output; Neurons; Obsessive-Compulsive Disorder; Organism; Patients; Pattern; Play; Population; Positioning Attribute; Prefrontal Cortex; Primates; Process; Reporting; Research; Resolution; Rodent; Role; Series; Signal Transduction; Structure; Temporal Lobe; Testing; Training; Work; behavioral study; experimental study; frontal lobe; member; neglect; neural; neural circuit; neuromechanism; neurophysiology; nonhuman primate; programs; sequence learning; visual information

PROJECT SUMMARY The ultimate goal of this research program is to determine the neural mechanisms of sequence monitoring across species. This knowledge can contribute to understanding new treatments for disorders where sequential behaviors are disrupted, such as obsessive-compulsive disorder (OCD). Daily, we monitor sequences of visual information such as the series of bus or train stops when looking for the correct exit. Sequence monitoring is the active process of tracking the order of subsequent “states” or steps. Monitoring is distinct from other well-studied sequence processes, such as explicit memorization, or potentially more automatic behaviors such as a series of motor outputs (e.g., playing the piano) or statistical sequence learning. However, the monitoring aspects of sequence processing remain largely unknown. The goal of this proposal is to determine the neural mechanisms of nonmotor and nonspatial sequence monitoring across species. Reflecting its importance, a large network of cortical and subcortical areas is implicated in sequence processing, including frontal cortices, premotor cortex, medial temporal lobe, basal ganglia, hippocampus, and cerebellum. When focusing on high-level monitoring of nonmotor and nonspatial sequences by human and nonhuman primates, our Preliminary Data and other evidence indicates that lateral and medial prefrontal cortices (LPFC and MPFC, respectively), play a unique role. However, the specific contributions of each have not been determined. Two key features of sequences (e.g., ABCD) that may be encoded in neural activity are their ordinality or item-in-position associations (C in position 3) and temporal context or item-item associations (B is after A). Behavioral studies indicate that both kinds of information are used to monitor sequences. Previous studies, including our own, have found ordinality encoding in LPFC and MPFC. However, prior work has not established whether temporal encoding may additionally exist in these regions and any coding differences between these areas. We hypothesize MPFC primarily codes ordinality, and LPFC uses signals from MPFC to code ordinality and temporal context. We will directly test these hypotheses by triangulating behavioral, whole brain, and cellular data in studies across species. We will apply the unique capabilities of our lab to study cognitive capabilities across brain areas in behaving monkeys using fMRI (Aim 1), the functional homology and correspondence to more abstract sequential tasks in humans using fMRI (Aim 2), and use these signals to guide electrophysiology in monkeys (Aim 3). Parallel fMRI studies across species will allow us to leverage each for distinct strengths in hypothesis testing: detailed neurophysiology in monkeys, and detailed cognitive studies in humans.

项目概要 该研究计划的最终目标是确定序列监测的神经机制 这些知识有助于理解疾病的新疗法。 行为受到干扰，例如强迫症（OCD） 每天，我们都会监控视觉序列。 寻找正确出口时的一系列公共汽车或火车站等信息是监控的重点。 跟踪后续“状态”或步骤的顺序的主动过程监控不同于其他经过充分研究的过程。 顺序过程，例如显式记忆，或潜在的更自动的行为，例如一系列 然而，运动输出（例如弹钢琴）或统计序列学习的监控方面。 序列处理在很大程度上仍然未知。 该提案的目标是确定非运动和非空间序列的神经机制 皮层和皮层下区域的大型网络反映了其重要性。 参与序列处理，包括额叶皮层、前运动皮层、内侧颞叶、基底皮层 当专注于非运动和非空间的高水平监测时。 人类和非人类灵长类动物的序列，我们的初步数据和其他证据表明横向 和内侧前额皮质（分别为 LPFC 和 MPFC），发挥着独特的作用。 每个序列的贡献尚未确定（例如，ABCD）。 神经活动中编码的是它们的序数或项目位置关联（位置 3 中的 C）和时间关联 上下文或项目与项目之间的关联（B 在 A 之后）。行为研究表明这两种信息都是如此。 以前的研究，包括我们自己的研究，已经在 LPFC 和 LPFC 中发现了序数编码。 然而，先前的工作尚未确定这些中是否还存在时间编码。 我们勇敢地面对 MPFC 主要代码的顺序性，以及这些区域之间的任何编码差异。 LPFC 使用来自 MPFC 的信号来编码序数和时间上下文。 我们将通过对跨研究中的行为、全脑和细胞数据进行三角测量来直接检验这些假设。 我们将利用我们实验室的独特能力来研究跨大脑区域的认知能力。 使用功能磁共振成像（目标 1）观察猴子的行为，功能同源性和对应于更抽象的序列 使用功能磁共振成像（fMRI）在人类中执行任务（目标 2），并使用这些信号指导猴子的电生理学（目标 3）。 跨物种的并行功能磁共振成像研究将使我们能够利用每个物种在假设检验中的独特优势： 猴子的详细神经生理学和人类的详细认知研究。