Characterizing the role of the prefrontal cortex in cognitive control

描述（由申请人提供）：人类和其他灵长类动物具有根据内部存储的目标和环境调整行为的非凡能力。这种灵活性允许复杂的认知，并且已知它依赖于前额皮质（PFC）的功能。因此，PFC功能障碍会损害行动的灵活性，导致冲动、持久和无组织的行为。这种认知缺陷在神经损伤患者（如创伤性脑损伤、中风）以及精神疾病患者（如精神分裂症、注意缺陷多动障碍）中都很明显。相应地，人们对解释组织原理来描述PFC功能也有很大的兴趣。两个这样的原则是：1)PFC是沿着吻侧-尾侧轴组织的，更多的吻侧区域提供了对更多尾侧区域自上而下的分层控制；2) PFC沿着内容的背-腹轴组织，更多的背区维护空间信息，更多的腹区维护身份或物体信息。目前尚不清楚这两个轴是如何相互作用以实现灵活的认知控制的。目前的研究试图通过将工作记忆任务（已知涉及尾侧PFC中可分离的背侧-腹侧网络）与认知控制需求（已知涉及可分离的喙侧-尾侧区域）相结合来填补这一空白。该提案将测试背腹轴在PFC的吻侧区域收敛的假设，允许PFC的吻侧区域（区域10和46）对PFC的特定区域的尾侧区域（区域6/8和44）施加域一般控制。这一假设是从有文献记载的解剖连接模式中得出的。PFC将通过功能磁共振成像（fMRI）、经颅磁刺激（TMS）和局灶性PFC病变患者的研究相结合来探索。这些方法的结合提供了通过神经激活模式记录PFC组织的能力，并通过限定病变的影响测试特定PFC区域的因果功能角色。鉴于PFC在认知控制中的中心地位，我们预计

DESCRIPTION (provided by applicant): Humans and other primates have the remarkable ability to adjust behaviors according to internally stored goals and contexts. This flexibility permits complex cognition and is known to depend upon the functions of the prefrontal cortex (PFC). Accordingly, dysfunction of the PFC impairs flexibility of action leading to impulsive, perseverative, and disorganized behaviors. Such cognitive deficits are evident in patients with neurological damage (e.g. traumatic-brain injury, stroke), as well as in patients with psychiatric disorders (e.g. schizophrenia, attention-deficit hyperactivity disorder). Commensurately, there has been a great deal of interest in explicating organizing principles to describe PFC function. Two such principles are: 1) that the PFC is organized along a rostral-caudal axis with more rostral areas providing hierarchical top-down control over more caudal areas; 2) that the PFC is organized along a dorsal-ventral axis of content with more dorsal areas maintaining spatial information and more ventral areas maintaining identity or object information. What remains unclear is how these two axes interact to achieve flexible cognitive control. The present proposal seeks to fill this gap by coupling working memory tasks that are known to engage dissociable dorsal-ventral networks in the caudal PFC with cognitive control demands that are known to engage dissociable rostral-caudal areas. The proposal will test the hypothesis that the dorsal-ventral axis converges in rostral areas of the PFC allowing rostral areas of the PFC (areas 10 & 46) to exert domain-general control over domain-specific caudal areas of the PFC (areas 6/8 & 44). This hypothesis is drawn from documented patterns of anatomical connectivity. The PFC will be explored through a combination of fMRI, transcranial magnetic stimulation (TMS), and studies of patients with focal PFC lesions. The combination of approaches affords the ability to document the organization of the PFC through patterns of neural activation and test causal functional roles of particular PFC regions through the effect of circumscribed lesions. Given the centrality of the PFC in cognitive control, it is anticipated that elucidating the interaction between the rostral-caudal and dorsal-ventral axes of the PFC will provide critical insight into complex behaviors that require high levels of mental organization.