Investigating the neural representation of structured sequence viewing in the lateral prefrontal cortex of nonhuman primates

研究非人类灵长类动物外侧前额皮质中结构化序列观察的神经表征

基本信息

批准号：
10451684
负责人：
Theresa Marie Desrochers
金额：
$ 19.88万
依托单位：
BROWN UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-07-15 至 2024-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10451684
关键词：
Anatomy Area Awareness Behavior Brain Cells Corpus striatum structure Data Decision Making Disease Dopamine Electrophysiology (science)Elements Functional Magnetic Resonance Imaging Goals Human Image Individual Knowledge Lateral Lead Life Literature Location Medial Methods Monitor Monkeys Motor Motor output Obsessive-Compulsive Disorder Outcome Pattern Phase Play Population Positioning Attribute Prefrontal Cortex Process Prosencephalon Ramp Research Rewards Schedule Series Signal Transduction Specificity Structure Testing Time Training Transcranial magnetic stimulation Variant Visual awake base blood oxygen level dependent data acquisition deviant expectation flexibility improved indexing neural circuit neuromechanism neurotransmission nonhuman primate programs relating to nervous system response reward anticipation sequence learning theories visual information

项目摘要

PROJECT SUMMARY The ultimate goal of this research program is to determine the neural mechanisms of sequence monitoring. This knowledge can directly 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. Knowledge of higher-order similarities across sequences (e.g., AAAB, &&&@), abstractions, can aid sequence monitoring. For example, understanding the steps required in each turn in a game, or the repetitive pattern in a poem or song, can improve our awareness and processing. Abstract sequence monitoring includes viewing the sequences that possess abstract structure, active monitoring of this structure, and response. Here, we will determine the neural representation of abstract sequential structure using passive structured sequence viewing. We hypothesize that a key element of sequence structure, position, is encoded in the lateral prefrontal cortex (LPFC) with phasic bursts that in aggregate create population ramping. These neural dynamics can uniquely “tag” each serial position in the sequence, supporting monitoring. This prediction is based on prior literature, and on our discovery that increasing (ramping) blood oxygen level-dependent (BOLD) activity in the rostral LPFC of humans is necessary for sequence execution and underlies sequence monitoring (Desrochers et al., 2015a, 2019). During awake fMRI, we observed parallel BOLD ramping in the LPFC of monkeys performing a structured sequence viewing task. We will use these data to specifically target electrophysiological recordings (Desrochers et al., 2015b; Feingold*, Desrochers* et al. 2012). This viewing task also provides robust BOLD responses to viewed sequence deviants and avoids motor and decision-making confounds while providing experimental flexibility. By using these activity patterns to guide neural recordings, we remove the need for anatomy-based assumptions about cross-species homology and can localize data acquisition with sub-region specificity. We will systematically test the hypotheses that sequence position is characterized by successive phasic increases in neural spiking in LPFC (Aim 1), and that neural activity related to sequence position is modulated by the passage of time and reward expectation (Aim 2). Sequence monitoring is fundamental to many natural behaviors. These data are unique in being guided by, and directly relatable-to, fMRI mapping. While hypothesis- driven, any outcome of these recordings from fMRI-identified brain areas will advance our understanding of this crucial process.

项目概要该研究计划的最终目标是确定序列监控的神经机制。知识可以直接有助于理解连续行为障碍的新疗法扰乱，例如强迫症（OCD），我们每天都会监控视觉信息序列。例如在寻找正确出口时的一系列公共汽车或火车站。跟踪后续“状态”或步骤的顺序的过程与其他经过充分研究的过程不同。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。了解序列之间的高阶相似性（例如 AAAB、&&&@）、抽象，可以帮助序列例如，了解游戏中每个回合所需的步骤，或游戏中的重复模式。诗歌或歌曲，可以提高我们的意识和处理能力抽象序列监控包括观看。具有抽象结构的序列、对该结构的主动监控和响应。使用被动结构化序列观察确定抽象序列结构的神经表征。我们发现序列结构的关键元素——位置——是在外侧前额叶皮层中编码的（LPFC）具有阶段性爆发，总体上会产生群体增长，这些神经动力学可以独特地发挥作用。 “标记”序列中的每个序列位置，支持监控。基于我们的发现，增加（增加）血氧水平依赖性（BOLD）活性人类对于序列执行是必要的，并且是序列监控的基础（Desrochers 等人，2015a， 2019）。在清醒的功能磁共振成像期间，我们观察到猴子的 LPFC 中出现了平行的 BOLD 斜坡，这些斜坡执行结构化的操作。我们将使用这些数据来专门针对电生理记录（Desrochers）。等人，2015b；Feingold*，Desrochers* 等人，2012）。查看序列异常并避免运动和决策混淆，同时提供实验通过使用这些活动模式来指导神经记录，我们消除了基于解剖学的需要。关于跨物种同源性的假设，并且可以通过子区域特异性来本地化数据采集。我们将系统地测试序列位置由连续相位表征的假设 LPFC 中的神经尖峰增加（目标 1），并且与序列位置相关的神经活动受到调节通过时间的推移和奖励期望（目标 2）来监控序列对于许多自然现象来说是基础。这些数据在功能磁共振成像映射的指导下是独一无二的，并且与功能磁共振成像映射直接相关。在功能磁共振成像识别的大脑区域的驱动下，这些记录的任何结果都将增进我们对此的理解关键过程。