Hierarchical Interactions Supporting Cognitive Control

支持认知控制的分层交互

• 批准号: 10080754
• 负责人: Derek Evan Nee
• 金额: $ 38.2万
• 依托单位: FLORIDA STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-01-06 至 2024-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10080754
• 关键词: Affect; Anatomy; Animal Model; Apical; Area; Attention deficit hyperactivity disorder; Behavior; Behavior Control; Behavioral; Biological Markers; Brain; Brain region; Cognition; Cognitive; Cognitive deficits; Communication; Computational Technique; Coupled; Data; Disease; Disease Progression; Functional Magnetic Resonance Imaging; Functional disorder; Future; Goals; Human; Huntington Disease; Imaging Techniques; Impairment; Impulsivity; Influentials; Lateral; Logic; Measurement; Mediating; Mental disorders; Methodology; Modeling; Monitor; Mood Disorders; Parietal; Parietal Lobe; Parkinson Disease; Patients; Perception; Prefrontal Cortex; Process; Quality of life; Rehabilitation therapy; Resolution; Role; Schizophrenia; Stroke; Substance Addiction; Techniques; Testing; Transcranial magnetic stimulation; Traumatic Brain Injury; Work; base; behavioral impairment; brain behavior; cognitive control; cognitive function; improved; inattention; insight; interest; nervous system disorder; neuroimaging; novel; relating to nervous system; theories

Cognitive control refers to the ability to guide behavior in an intentional and goal-directed manner amidst competing demands. This hallmark of human cognition is supported by the prefrontal (PFC) and posterior parietal cortices (PPC), areas that have undergone extensive evolutionary expansion. The PFC and PPC are central to integrating the present context with plans for the future in order to guide intentional behavior. Accordingly, dysfunction of these regions leads to a wide-variety of deficits including inflexibility, inattention, impulsivity, and disorganization. Such cognitive deficits are evident in numerous psychiatric and neurological disorders such as schizophrenia, attention-deficit hyperactivity disorder, substance addiction, mood disorders, Parkinson’s disease, Huntington’s disease, stroke, and traumatic brain injury. However, impairments in cognitive control are particularly challenging to treat in part due to insufficient mechanistic understanding of the PFC, PPC, and their interactions. To understand and treat disorders of higher-level cognition we need to detail the directed interactions of the PFC and PPC, elucidating functional chains among brain regions and behavior. However, elucidating directed interactions in humans is challenging given limitations of available techniques. Animal models may not translate to the PFC and PPC-mediated abilities that are exceptional in humans. As a result, how the directed interactions of the PFC/PPC mediate higher-level cognition and how they can be manipulated to model dysfunction and move towards rehabilitation remains unclear. This proposal aims to fill this gap using a combination of techniques. Functional magnetic resonance imaging (fMRI) will be coupled with computational techniques to model how directed PFC/PPC interactions support cognitive control. Chief among the interests of this proposal are identification of putative hierarchical organizations with the PFC and PPC that are symbolized by asymmetries of directed influence. Areas at the apex of such hierarchies are predicted to exert widespread influence over other brain areas and cognition. Such apical areas would therefore serve as important biomarkers to monitor for disorder progression, and targets for treatment. Modeled apical roles will be causally validated using interleaved transcranial magnetic stimulation (TMS) and fMRI by examining the impact of focal stimulation on downstream brain areas and behavior. Both continuous theta-burst TMS (cTBS) and intermittent theta-burst TMS (iTBS) will be employed with putative inhibitory and excitatory effects, respectively. It is predicted that cTBS will impair behavior, serving as a model of dysfunction, while iTBS will enhance behavior, serving as a road towards treatment. Aim 1 will estimate hierarchical models in the PFC, validate these models using cTBS, and start the path towards treatment using iTBS. Aim 2 will apply a similar logic to the PPC and contrast the relative efficacy of PFC vs. PPC TMS. Collectively, these aims will provide directed models of PFC/PPC interactions supporting cognitive control, and causal data regarding how targeted manipulation of these networks can hinder or improve control.

认知控制是指在特定环境下有意识地、有目标地引导行为的能力。 相互竞争的需求。人类认知的这一标志得到前额叶 (PFC) 和后顶叶的支持 皮质（PPC），经历了广泛的进化扩张的区域。 PFC 和 PPC 是核心 将当前情况与未来计划相结合，以指导有意行为。因此， 这些区域的功能障碍会导致各种各样的缺陷，包括缺乏灵活性、注意力不集中、冲动和 混乱。这种认知缺陷在许多精神和神经疾病中都很明显，例如 精神分裂症、注意力缺陷多动障碍、物质成瘾、情绪障碍、帕金森病 疾病、亨廷顿舞蹈病、中风和创伤性脑损伤。然而，认知控制障碍 由于对 PFC、PPC 及其机制了解不足，治疗起来特别困难。 互动。为了理解和治疗高级认知障碍，我们需要详细说明定向 PFC 和 PPC 的相互作用，阐明大脑区域和行为之间的功能链。然而， 鉴于现有技术的限制，阐明人类的定向相互作用具有挑战性。动物 模型可能无法转化为人类特有的 PFC 和 PPC 介导的能力。因此， PFC/PPC 的定向相互作用如何介导更高层次的认知以及如何操纵它们 模拟功能障碍并走向康复仍不清楚。 该提案旨在使用多种技术的组合来填补这一空白。功能磁共振成像 (fMRI) 将与计算技术相结合，以模拟如何支持定向 PFC/PPC 交互 认知控制。该提案的主要利益是确定假定的等级制度 具有 PFC 和 PPC 的组织，其标志是直接影响力的不对称。区域位于 预计这种层次结构的顶端会对其他大脑区域和认知产生广泛的影响。这样的 因此，顶端区域将作为监测疾病进展的重要生物标志物，以及治疗的目标 治疗。将使用交错经颅磁刺激对模拟的心尖角色进行因果验证 （TMS）和功能磁共振成像（fMRI），通过检查局灶刺激对下游大脑区域和行为的影响。两个都 连续 theta-burst TMS (cTBS) 和间歇性 theta-burst TMS (iTBS) 将被采用 分别具有抑制作用和兴奋作用。预计cTBS将损害行为，作为模型 功能障碍，而 iTBS 将增强行为，作为治疗的途径。目标 1 将估计 PFC 中的分层模型，使用 cTBS 验证这些模型，并使用以下方法开始治疗之路 iTBS。目标 2 将类似的逻辑应用于 PPC，并对比 PFC 与 PPC TMS 的相对功效。 总的来说，这些目标将提供支持认知控制的 PFC/PPC 交互的定向模型，以及 关于对这些网络进行有针对性的操纵如何阻碍或改善控制的因果数据。