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背景调整行为的非凡能力。这种灵活性允许复杂的认知，并且已知依赖于前额叶皮层（PFC）的功能。因此，PFC的功能障碍损害了行动的灵活性，导致冲动、持续和混乱的行为。这种认知缺陷在患有神经损伤（例如创伤性脑损伤、中风）的患者以及患有精神障碍（例如精神分裂症、注意力缺陷多动障碍）的患者中是明显的。相应地，人们对阐明组织原则来描述PFC功能很感兴趣。其中两项原则是：1）前额叶皮层是沿着一个吻-尾轴组织的，更多的吻侧区域提供了对更多的尾侧区域的分层自上而下的控制; 2）前额叶皮层是沿着一个背-腹轴组织的，更多的背侧区域维持空间信息，更多的腹侧区域维持身份或对象信息。目前尚不清楚的是，这两个轴如何相互作用，以实现灵活的认知控制。目前的建议旨在填补这一空白耦合工作记忆任务，已知从事可分离的背腹侧网络在尾侧PFC与认知控制要求，已知从事可分离的喙尾侧区。该提案将测试的假设，即背腹轴收敛在前额叶皮层的吻侧区域，允许前额叶皮层的吻侧区域（区域10和46）施加域一般控制域特定的尾侧区域的前额叶皮层（区域6/8和44）。这一假设是从解剖连接的记录模式得出的。PFC将通过结合fMRI、经颅磁刺激（TMS）和对PFC局灶性病变患者的研究进行探索。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，并通过限制性病变的影响测试特定PFC区域的因果功能作用。考虑到前额叶皮层在认知控制中的中心地位，预计 阐明前额叶皮层的头-尾轴和背-腹轴之间的相互作用，将对需要高水平心理组织的复杂行为提供重要的见解。 公共卫生相关性： 前额叶皮质（PFC）功能障碍对认知功能有有害影响，而认知功能是患者生活质量的最关键决定因素之一。此外，认知和行为缺陷PFC损伤是特别具有挑战性的治疗。阐明PFC的功能组织，预计将提高我们的理解PFC相关的认知障碍，从而导致改善诊断和康复。

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. PUBLIC HEALTH RELEVANCE: Dysfunctions of the prefrontal cortex (PFC) have a deleterious impact on cognitive function, which is one of the most critical determinants of quality of life in patients. Furthermore, cognitie and behavioral deficits from PFC damage are particularly challenging to treat. Elucidating the functional organization of the PFC is expected to enhance our understanding of PFC-related cognitive impairments, thereby leading to improved diagnosis and rehabilitation.