Prefrontal mechanisms for retrieval and selection in cognitive control

描述（由申请人提供）：拟议的研究调查了当一种情况提供多种可能的反应时灵活和适当的反应能力。这方面的执行功能在许多影响前额皮质（PFC）的疾病中受到损害，导致沟通、计划和决策方面的问题。这项研究的目的是，首先，确定支持这种灵活性的神经基质，其次，探索潜在的神经机制。在判断PFC区域在灵活反应中的作用的相互竞争的理论方面，由于测量方法的缺陷和未能在同一任务中操纵需求，进展受到限制。两项功能磁共振成像研究弥补了这些问题，以便清晰地区分支持受控检索反应的区域，在竞争性任务相关反应（不确定竞争）之间进行选择，以及在面对优势任务无关竞争对手时选择任务相关反应。关于腹侧PFC （VLPFC）在选择与控制检索中的作用存在争议。第一项研究使用新的无混淆测量方法来确定支持这些过程的VLPFC区域。面对优势竞争时的选择已被发现利用了背外侧PFC （DLPFC）和VLPFC区域，但尚未与存在不确定竞争时的选择进行对比。第二项研究将对比这两种形式的竞争。第二个目标是搭建分析层次的桥梁，利用神经网络模型探索支持受控检索和选择的机制。该模型将允许研究NMDA受体、GABA和多巴胺功能的影响，这些功能可能导致精神分裂症、焦虑症和多动症等疾病的认知控制缺陷。更好地了解支持执行功能的神经基质和机制对于开发更好的行为和药物干预来治疗这种认知控制缺陷至关重要。相关性：我们经常面临着从众多选项中选择一个的任务，比如当我们选择单词来表达一个想法时。这种能力在许多疾病中受损，包括多动症、焦虑症和精神分裂症。这些研究探索大脑如何能够在多种选择之间做出选择，以及这些疾病如何影响这种能力，目的是帮助开发新的治疗方法。

DESCRIPTION (provided by applicant): The proposed research investigates the ability to respond flexibly and appropriately when a situation affords multiple possible responses. This aspect of executive function is compromised in many disorders affecting prefrontal cortex (PFC), contributing to problems in communication, planning, and decision-making. The research aims, first, to identify neural substrates supporting this flexibility, and second, to explore potential neural mechanisms. Progress in adjudicating between competing theories of the role of PFC regions in flexible responding has been limited by flawed measures and failure to manipulate demands within the same task. Two fMRI studies remedy these problems, in order to cleanly differentiate regions supporting controlled retrieval of responses, selection between competing task-relevant responses (underdetermined competition), and selection of a task-relevant response in the face of prepotent task-irrelevant competitors. There is debate as to the role of ventrolateral PFC (VLPFC) in selection versus controlled retrieval. The first study uses new unconfounded measures to identify VLPFC regions supporting these processes. Selection in the face of prepotent competition has been found to tap regions of dorsolateral PFC (DLPFC) as well as VLPFC, but has not been contrasted with selection when there is underdetermined competition. A second study will contrast these two forms of competition. The second aim is to bridge levels of analysis, probing the mechanisms supporting controlled retrieval and selection using a neural network model. The model will allow investigation of the effects of NMDA receptor, GABA, and dopamine function which may contribute to cognitive control deficits in conditions such as schizophrenia, anxiety disorders and ADHD. A better understanding of the neural substrates and mechanisms supporting executive function is critical for developing better behavioral and pharmacological interventions to treat such cognitive control deficits. Relevance: We are constantly faced with the task of choosing one option from among many, such as when we select words to express a thought. This ability is impaired in many disorders, including ADHD, anxiety, and schizophrenia. These studies explore how the brain is able to choose between multiple options, and how these disorders may affect this ability, with the goal of aiding development of new treatments.