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The Role of a Neural Mechanism for Inhibitory Control in Cognitive Flexibility

抑制控制神经机制在认知灵活性中的作用

基本信息

批准号：
10374950
负责人：
Jan R Wessel
金额：
$ 37.84万
依托单位：
UNIVERSITY OF IOWA
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-04-01 至 2024-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10374950
关键词：
Affect Applications Grants Attention Basal Ganglia Behavior Brain Brain region Cognition Cognitive Conflict (Psychology)Data Disease Electric Stimulation Electroencephalography Event Goals Health Human Impaired cognition Impairment Incidence Individual Interruption Measurement Measures Methods Modeling Motor Motor Activity Neurobehavioral Manifestations Neurodegenerative Disorders Parkinson Disease Patients Process Protocols documentation Psyche structure Quality of life Research Role Scalp structure Sensory Short-Term Memory Symptoms System Techniques Testing Theoretical model Thinking Transcranial magnetic stimulation Translating Work base clinical practice cognitive control cognitive process design experience experimental study flexibility motor control motor disorder motor impairment motor symptom nervous system disorder neural circuit neuromechanism novel public health relevance recruit relating to nervous system response theories

项目摘要

PROJECT SUMMARY Cognitive impairments like over-perserveration, mental rigidity, and cognitive inflexibility accompany several neurological diseases – most prominently, Parkinson's Disease (PD). PD is the second most common neurodegenerative disorder in humans. While it is a predominantly motor disorder, many PD patients experience cognitive symptoms. However, despite the broad incidence of impaired cognitive flexibility in PD and other disorders, little is known about the mechanistic neural underpinnings of this ability in health and disease. Hence, there is a critical need for a mechanistic neural theory of cognitive flexibility. In this grant proposal, we propose to test a working model of this ability, which centers on the role of a fronto-basal ganglia (FBg) brain mechanism for inhibition. We use a converging evidence approach that includes intracranial recordings from the basal ganglia, scalp EEG, motor systems measurements, and brain stimulation. The core hypothesis of the proposed model is that rapid cognitive flexibility depends on a neural mechanism for inhibitory control. Based on extensive pilot data, we propose that this mechanism allows healthy individuals to adaptively disengage from ongoing cognitive processes (working memory, task set representations, attentional focus, etc.). Importantly, the proposed neural mechanism is – until now – largely known as a motor inhibition mechanism: it can serve to stop already initiated actions by recruiting a network of FBg brain regions to inhibit motor activity. The circuitry underlying this inhibitory control mechanism is known to be damaged in PD, which is thought to explain some of its motor symptoms. Our proposal that this mechanism can serve to also inhibit cognition could explain why PD patients overpersevere on outdated cognitive processes: damage to the same mechanism whose malfunction impairs motor inhibition in PD may also impair cognitive flexibility. To test this model, the first of group of studies in this proposal is designed to identify the types of situations in which the inhibitory FBg mechanism is engaged. Specifically, neural and motor signatures of the inhibitory FBg mechanism will be measured across different types of situations that require rapid cognitive control (errors, response-conflict, unexpected perceptual events). The goal is to investigate whether the mechanism is active in a broad array of scenarios that demand rapid cognitive flexibility. The second group of studies aims to investigate the potential inhibitory influence of the FBg mechanism on cognitive representations. Specifically, activity of the FBg mechanism will be measured in a new battery of tasks designed to test how ongoing task set representations and attentional processes are interrupted when necessary. The goal is to test the core proposition of the model, namely, that the FBg mechanism's inhibitory capacity extends beyond the motor system, and can affect active cognitive representations. The final group of studies will test the effects of different types of brain stimulation on the inhibitory FBg mechanism's ability to inhibit ongoing cognitive representations. These studies aim to provide causal evidence for the model and translate it into clinical practice.

项目摘要伴随而来的是过度坚持、精神僵化和认知不灵活等认知障碍几种神经系统疾病-最突出的是帕金森病（PD）。PD是第二常见的神经退行性疾病虽然它是一种主要的运动障碍，但许多PD患者经历认知症状然而，尽管PD和其他疾病中认知灵活性受损的发生率很高，虽然我们对这种能力的机制性神经基础在健康和疾病中的作用知之甚少。因此，我们认为，迫切需要认知灵活性的机械神经理论。在这份拨款申请中，我们建议为了测试这种能力的工作模型，该模型以额基底神经节（FBg）大脑机制的作用为中心用于抑制。我们使用了一种融合证据的方法，包括从基底节到基底节的颅内记录，神经节、头皮EEG、运动系统测量和脑刺激。该模型的核心假设是，快速认知灵活性取决于神经系统的抑制控制机制。基于广泛的试点数据，我们建议，这种机制允许健康个体自适应地脱离正在进行的认知过程（工作记忆，任务集表征，注意力集中等）。重要的是，到目前为止，所提出的神经机制在很大程度上被称为电机抑制机制：它可以通过招募FBg大脑区域的网络来停止已经启动的行动来抑制运动活动这种抑制性控制机制的基础电路已知在PD中受损，这被认为可以解释它的一些运动症状我们的建议是，这一机制还可以抑制认知可以解释为什么PD患者过度坚持过时的认知过程：在PD中，其功能障碍损害运动抑制的相同机制也可能损害认知灵活性。为了检验这一模型，本建议中的第一组研究旨在确定情况的类型其中抑制性FBg机制参与。具体地说，抑制性运动的神经和运动特征 FBg机制将在需要快速认知控制的不同类型的情况下进行测量（错误，反应冲突、意外感知事件）。目的是研究该机制是否在一系列需要快速认知灵活性的场景。第二组研究旨在调查 FBg机制对认知表征的潜在抑制作用。具体而言， FBg机制将在一组新的任务中进行测量，这些任务旨在测试正在进行的任务集表示注意力过程在必要时会被打断。目标是测试模型的核心命题，也就是说，FBg机制的抑制能力超出了运动系统，可以影响主动认知表征最后一组研究将测试不同类型的大脑刺激对抑制性FBg机制抑制持续认知表征的能力。这些研究旨在提供因果证据的模型，并将其转化为临床实践。