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.

项目摘要 这项研究计划的最终目标是确定整个序列监测的神经机制。 物种这些知识可以有助于理解新的治疗方法， 行为受到干扰，如强迫症（OCD）。每天，我们都在监视 在寻找正确的出口时，您可以查看公共汽车或火车站的序列等信息。序列监测是 跟踪后续“状态”或步骤顺序的主动过程。监测不同于其他研究充分的 序列过程，如明确的记忆，或潜在的更自动的行为，如一系列的 电动机输出（例如，弹钢琴）或统计序列学习。然而，监测方面 序列处理在很大程度上仍是未知的。 本研究的目的是确定非运动和非空间序列的神经机制 跨物种监测。反映其重要性的是，一个由皮层和皮层下区域组成的大型网络， 涉及序列处理，包括额叶皮层，前运动皮层，内侧颞叶，基底 神经节海马和小脑当专注于非运动和非空间的高水平监测时， 我们的初步数据和其他证据表明， 和内侧前额叶皮质（LPFC和MPFC，分别），发挥独特的作用。但具体 各方的贡献尚未确定。序列的两个关键特征（例如，ABCD）那可能是 编码在神经活动中的是它们的顺序或位置关联（位置3中的C）和时间关联（位置3中的C）。 上下文或项目-项目关联（B在A之后）。行为研究表明，这两种信息都是 用于监控序列。以前的研究，包括我们自己的研究，已经发现了LPFC中的序数编码， MPFC。然而，先前的工作还没有确定时间编码是否可以另外存在于这些中。 区域和这些区域之间的任何编码差异。我们假设MPFC主要编码有序性， LPFC使用来自MPFC的信号来编码顺序和时间上下文。 我们将直接测试这些假设三角行为，整个大脑，和细胞数据的研究， 物种我们将应用我们实验室的独特能力来研究大脑各区域的认知能力， 行为猴子使用功能磁共振成像（目的1），功能同源性和对应更抽象的序列 使用功能磁共振成像（目标2）在人类中的任务，并使用这些信号来指导猴子的电生理学（目标3）。 跨物种的平行fMRI研究将使我们能够在假设检验中利用每个物种的不同优势： 详细的猴子神经生理学研究，以及详细的人类认知研究。