Multimodal Neurodevelopmental Studies of Cognitive Control and Arousal

描述(由申请人提供)：目前的建议是父母资助的延续，重点是描述青春期认知控制的神经基础。核心认知控制能力在青春期是可用的，但在成年后，其使用的可靠性和灵活性不断提高，以支持最佳决策。这些不成熟似乎是仍在发育和脆弱的神经系统的结果，这可能导致次优决策导致风险增加，并容易出现包括情绪障碍和精神分裂症在内的主要精神疾病。越来越多的文献提供了令人信服的证据，证明青春期认知控制的特定大脑区域的功能不成熟。重要的是，新出现的证据有力地表明，这些可能是大规模和高度专业化的神经网络在功能整合方面不成熟的结果。到目前为止，单峰神经成像方法在空间和时间域上的局限性阻碍了对网络水平功能和整合的研究。我们建议使用多模式方法，其中并行研究使用fMRI来准确识别功能相关的神经区域，使用DTI来表征关键区域之间的白质结构连接，以及使用脑磁图来描述高时间分辨率的神经同步性，这将使我们能够对特定神经网络的出现获得完整和全面的理解(目标1)。此外，决策过程中的局限性往往存在于情感环境中，这在青春期可能特别相关。因此，我们还想调查与情感相关的生理唤醒对认知控制的影响(目标2)。最后，冒险行为不会在青春期结束时终止，而是会持续到大学期间。这表明，关键的神经不成熟可能会持续到年轻的成年期，这一时期还有待探索。有鉴于此，我们建议跟踪受试者中的一个子集，从父母资助到成年，并描述一条为期10年的认知控制轨迹(目标3)。总而言之，这些研究将提供系统层面功能成熟及其脆弱性的综合观点，为青春期规范异常行为的生物学基础和精神病理学的出现提供信息。这一建议在多式联运、横断面和纵向办法方面是新颖的，其影响具有极大的潜力，可以为发展性质的关键方面提供信息。 与公共卫生有关：由于冒险行为以及容易出现包括情绪障碍和精神分裂症在内的主要精神疾病，青春期死亡率增加了100-200%，这是一个公共卫生问题。拟议的项目使用一种创新的多模式神经成像方法来识别认知控制和情绪背后的神经过程，这些过程在青春期不成熟，因此容易受到损害，并有可能为治疗、教育和育儿方法提供信息。

DESCRIPTION (provided by applicant): The current proposal is a continuation from a parent grant focused on characterizing the neural basis of cognitive control through adolescence. Core cognitive control abilities are available during adolescence however there are continued refinements into adulthood in the reliability and flexibility of its use supporting optimal decision making. These immaturities appear to be the result of a still developing and vulnerable neural system that can lead to suboptimal decision making leading to increased risk taking, and susceptibility for the emergence of major psychopathology including mood disorders and schizophrenia. A growing literature has provided compelling evidence for immaturities in the function of specific brain regions underlying cognitive control in adolescence. Importantly, emerging evidence strongly indicates that these may be the result of immaturities in the functional integration of large-scale and highly specialized neural networks. Thus far, investigations of network-level function and integration have been hampered by limitations in spatial and temporal domains in unimodal neuroimaging approaches. We propose to use a multimodal approach where parallel studies using fMRI to accurately identify functionally relevant neural regions, DTI to characterize white matter structural connectivity between key regions, and MEG to delineate neural synchrony at high temporal resolution, will enable us to obtain an integrated and comprehensive understanding of the emergence of specific neural networks underlying behavior (Aim 1). In addition, limitations in decision making are often present in the context of emotional contexts, which may be especially relevant during adolescence. As such, we also want to investigate the effects of affect-related physiological arousal on cognitive control (Aim 2). Finally, risk taking behavior does not terminate at the end of adolescence, persisting through the college years. This suggests that key neural immaturities may continue into young adulthood, a period that is yet to be explored. In light of this, we propose to follow a subset of participants from the parent grant into young adulthood and characterize a trajectory of cognitive control that encompasses 10 years (Aim 3). Together, these studies will provide an integrated view of the maturation of systems level functioning and its vulnerabilities informing the biological bases of normative aberrant behavior in adolescence and the emergence of psychopathology. This proposal is novel in its multimodal, cross sectional and longitudinal approach, the implications of which has enormous potential for informing crucial aspects of the nature of development. PUBLIC HEALTH RELEVANCE: There is a public health concern regarding the 100-200% increase in mortality rate in adolescence contributed to by risk-taking behavior and the vulnerability to the emergence of major psychopathology including mood disorders and schizophrenia. The proposed project uses an innovative multimodal neuroimaging approach to identify the neural processes underlying cognitive control and emotion that are immature in adolescence and therefore vulnerable to impairments and has the potential to inform treatment, educational, and parenting approaches.