Hierarchical Interactions Supporting Cognitive Control

认知控制指的是以有意和目标为导向的方式引导行为的能力 相互竞争的要求。人类认知的这一标志受到前额叶(PFC)和顶叶后叶的支持 大脑皮层(PPC)，经历了广泛进化扩张的区域。PFC和PPC是 将目前的情况与未来的计划结合起来，以指导有意的行为。因此， 这些区域的功能障碍会导致各种各样的缺陷，包括不灵活、注意力不集中、冲动和 组织混乱。这种认知缺陷在许多精神和神经障碍中都很明显，例如 精神分裂症、注意力缺陷多动障碍、物质成瘾、情绪障碍、帕金森氏症 疾病、亨廷顿氏病、中风和创伤性脑损伤。然而，认知控制方面的障碍是 治疗尤其具有挑战性，部分原因是对PFC、PPC和它们的机制了解不足 互动。为了理解和治疗更高水平的认知障碍，我们需要详细说明 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， 鉴于现有技术的局限性，阐明人类之间的定向相互作用是一项具有挑战性的工作。动物 模型可能不会转化为PFC和PPC中介的能力，而这些能力在人类中是特殊的。结果, PFC/PPC的定向交互作用如何调节更高水平的认知，以及它们如何被操纵 如何模拟功能障碍并走向康复仍不清楚。 这项提议旨在使用多种技术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，对定向PFC/PPC交互如何支持进行建模 认知控制。这项提议的主要利益之一是确定假定的等级 具有PFC和PPC的组织，以直接影响的不对称性为象征。的区域 据预测，这种等级结构的顶端将对其他大脑区域和认知产生广泛影响。是这样的 因此，心尖区将成为监测疾病进展的重要生物标志物，并成为 治疗。模拟的心尖角色将使用交错的经颅磁刺激进行因果验证 (TMS)和功能磁共振成像，通过检测焦点刺激对下游脑区和行为的影响。两者都有 连续theta-Burst TMS(CTBS)和间歇性theta-Burst TMS(ITBS)将用于假定 抑制作用和兴奋作用。据预测，CTBS将损害行为，起到示范作用 而ITBS将改善行为，成为一条治疗之路。目标1将估计 PFC中的分层模型，使用CTB验证这些模型，并使用以下方法开始治疗 ITBS。目标2将类似的逻辑应用于PPC，并对比PFC和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交互的定向模型，以及 关于这些网络的定向操纵如何阻碍或改善控制的因果数据。

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.