Hierarchical Interactions Supporting Cognitive Control

支持认知控制的分层交互

• 批准号: 10319988
• 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 2025-11-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10319988
• 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.

认知控制指的是在一个有意识的和目标导向的方式指导行为的能力， 竞争的要求。人类认知的这一标志是由前额叶（PFC）和后顶叶（PPF）支持的。 皮质（PPC），经历了广泛的进化扩张的区域。PFC和PPC是 将当前背景与未来计划相结合，以指导有意的行为。因此，委员会认为， 这些区域的功能障碍会导致各种各样的缺陷，包括不稳定性，注意力不集中，冲动， 组织混乱这种认知缺陷在许多精神和神经障碍中是明显的， 精神分裂症，注意力缺陷多动障碍，物质成瘾，情绪障碍，帕金森氏症 疾病、亨廷顿病、中风和创伤性脑损伤。然而，认知控制的障碍是 特别具有挑战性的治疗，部分原因是对PFC，PPC及其机制的理解不足。 交互.为了理解和治疗更高层次的认知障碍，我们需要详细说明定向的 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，在这方面， 由于现有技术的限制，阐明人类中的定向相互作用是具有挑战性的。动物 模型可能无法转化为PFC和PPC介导的能力，而这些能力在人类中是例外的。因此，在本发明中， PFC/PPC的定向相互作用如何介导更高层次的认知，以及它们如何被操纵 来模拟功能障碍并走向康复仍不清楚。 本提案旨在使用各种技术来填补这一空白。功能磁共振成像 （fMRI）将与计算技术相结合，以模拟定向PFC/PPC相互作用如何支持 认知控制这项建议的主要利益是确定假定的等级制度， 组织与PFC和PPC的象征是不对称的直接影响。领域的 这些层次的顶点预计会对其他大脑区域和认知产生广泛的影响。等 因此，心尖区将作为重要的生物标志物来监测疾病进展，并且靶点为 治疗将使用交错经颅磁刺激对模拟心尖作用进行因果验证 (TMS)和功能磁共振成像通过检查局灶刺激对下游大脑区域和行为的影响。两 将采用连续θ突发TMS（cTBS）和间歇θ突发TMS（iTBS）， 抑制和兴奋作用。据预测，cTBS将损害行为，作为一个模型， 功能障碍，而iTBS将增强行为，作为治疗的一条道路。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 iTBS。目标2将对PPC应用类似的逻辑，并对比PFC与PPC TMS的相对有效性。 总的来说，这些目标将提供支持认知控制的PFC/PPC相互作用的定向模型， 关于有针对性地操纵这些网络如何阻碍或改善控制的因果数据。