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.

认知控制是指在有意和目标指导的方式中指导行为的能力 竞争要求。人类认知的标志得到了前额叶（PFC）和后壁的支持 皮质（PPC），具有广泛进化扩张的地区。 PFC和PPC是 将目前的环境与未来计划相结合，以指导有意行为。根据 这些区域的功能障碍导致广泛的定义，包括僵化，注意力不集中，冲动和 混乱。这种认知缺陷是许多精神病和神经系统疾病的证据，例如 精神分裂症，注意力缺陷多动障碍，物质成瘾，情绪障碍，帕金森氏症 疾病，亨廷顿病，中风和脑损伤。但是，认知控制的损害是 特别是由于对PFC，PPC及其的机械理解不足而部分治疗的挑战 互动。要了解和治疗高级认知的疾病，我们需要详细介绍指示的 PFC和PPC的相互作用，阐明了大脑区域和行为之间的功能链。然而， 鉴于可用技术的局限性，阐明人类中的定向相互作用是挑战的。动物 模型可能不会转化为人类特殊的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级别的认知以及如何被操纵 为了建模功能障碍并朝着康复迈进，尚不清楚。 该建议旨在使用多种技术填补这一空白。功能磁共振成像 （fMRI）将与计算技术相结合，以建模如何定向PFC/PPC交互支持 认知控制。该提案的利益中的主要主要是确定推定的层次结构 具有PFC和PPC的组织由有定向影响的不对称象征。区域 预计此类层次结构的顶点将对其他大脑区域和认知产生宽度的影响。 因此 治疗。建模的顶端角色将有时使用交织的经颅磁刺激来验证 （TMS）和fMRI通过检查局灶性刺激对下游大脑区域和行为的影响。两个都 连续的theta-burst TMS（CTB）和间歇性theta-burst TMS（ITB）将由推定的员工。 分别抑制和兴奋作用。可以预测CTB会损害行为，作为模型 功能障碍，虽然ITB将增强行为，并作为通往治疗的道路。 AIM 1将估计 PFC中的分层模型，使用CTB验证这些模型，然后使用 ITB。 AIM 2将应用与PPC相似的逻辑，并将PFC与PPC TMS的相对效率对比。 总的来说，这些目标将提供支持认知控制的PFC/PPC相互作用的指示模型，以及 有关这些网络有针对性操纵的因果数据可以阻碍或改善控制。