Organization and timecourse of the neural mechanisms for cognitive flexibility

描述(由申请人提供)：拟议研究的长期目标是描述在内部目标导向行为和外部引导行为之间起中介作用的神经机制。当环境信息与当前目标冲突时，如果不加以抑制，可能会导致不适当的行为。例如，未能抑制与毒品有关的线索会导致寻求毒品的行为，并与治疗后的复发有关。此外，在许多精神和神经疾病中都可以观察到这样的失败。然而，大多数研究考察了灵活的、目标导向的行为的潜在神经机制，都依赖于受试者根据明确的线索刺激在任务之间切换的范式。因此，这些范式可能不能完全捕捉到与内部产生的目标或任务选择相关的神经机制。由于初步研究表明，当任务选择明确时，控制过程是以不同的方式招募的 在指导下和参与者控制下，确定这些不同任务选择模式的大脑激活模式的差异是很重要的。在两个主要的实验中，我们的目标是：1)研究内源性和外源性偏向任务选择的神经机制；2)研究后内侧前额叶皮质(PMFC)在任务选择中的作用，该区域的功能组织一直是激烈争论的话题。首先将进行一项平行的磁共振成像(MRI)和事件相关脑电位(ERP)研究，该研究操纵任务选择是在实验者还是受试者控制下(外部控制与内部控制)，并操纵可能偏向任务选择的无关线索的存在(即，任务选择的外部偏见)。我们将考察 当任务选择是外部或内部产生的，以及是否受到外部偏见的影响时，脑区的空间组织(MRI、DTI)和时间进程(ERP)。最后，将进行功能磁共振荟萃分析，以检验pMFC的不同亚区是否构成任务选择、反应选择和反应评估的可分离过程。通过结合多项研究，荟萃分析将产生足够的统计能力来检测这些过程激活模式的细微差异。了解管理内部和外部驱动的任务选择的执行控制的神经机制将提供对年轻人成功和不成功行为原因的更多洞察，将有助于解释成瘾患者线索寻药行为背后的机制(以及在多个临床人群中观察到的认知灵活性中断)，并将促进适用于这些人群的认知训练和康复范例的发展。

DESCRIPTION (provided by applicant): The long-range goal of the proposed study is to characterize the neural mechanisms that mediate between internal goal-directed behavior and externally guided behavior. Failing to suppress environmental information when it conflicts with current goals may lead to inappropriate behaviors. For example, failing to suppress drug-related cues leads to drug seeking behavior, and is associated with relapse following treatment. Further, such failures are observed in many psychiatric and neurological disorders. However, most studies that have examined the underlying neural mechanisms of flexible, goal-directed behavior have relied on paradigms where subjects switch between tasks according to explicit cue stimuli. Therefore, these paradigms may not be able to fully capture the neural mechanisms associated with internally generated goal or task selection. As preliminary studies have suggested that control processes are recruited differentially when the task selection is explicitly instructed versus under participant control, it is important to identify the differences in the pattern of brain activation for these different modes of task selection. In two main experiments, we aim to 1) investigate the neural mechanisms underlying internally generated and externally biased task selection, and 2) examine the role of the posterior medial prefrontal cortex (pMFC), a region whose functional organization has been a topic of intense debate, in task selection. A parallel magnetic resonance imaging (MRI) and event- related brain potential (ERP) study will first be conducted that manipulates whether task selection is under experimenter or subject control (external vs. internal control) and manipulates the presence of irrelevant cues that may bias task selection (i.e., external bias on task selection). We will examine the differences in the spatial organization (MRI, DTI) and timecourse (ERP) of brain regions when task choice is externally or internally generated and under external bias or not. Finally, a functional MRI meta-analysis will be conducted to examine whether distinct subregions of the pMFC underlie separable processes of task selection, response selection, and response evaluation. By combining across multiple studies, the meta-analysis will yield sufficient statistical power to detect subtle differences in the pattern of activation for these processes. Knowledge of the neural mechanisms that govern executive control of internally vs. externally driven task selection will provide additional insight into the causes of successful and unsuccessful behavior in young adults, will help explain the mechanisms that underlie cued drug-seeking behavior in addiction (as well as disrupted cognitive flexibility observed across multiple clinical populations, and will facilitate the development of cognitive training and rehabilitation paradigms applicable to these populations.