Adolescent striatal neurophysiological maturation underlying the transition to adult stabilization of behavior

青少年纹状体神经生理学成熟是向成人行为稳定过渡的基础

• 批准号: 10363308
• 负责人: BEATRIZ LUNA
• 金额: $ 66.74万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-08-12 至 2027-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10363308
• 关键词: Adolescence; Adolescent; Adult; Age; Animal Model; Attenuated; Behavior; Behavioral; Brain; Buffers; Childhood; Cognition; Collaborations; Corpus striatum structure; Data; Decision Making; Development; Dopamine; Electroencephalography; Epilepsy; Event; Excision; Functional Magnetic Resonance Imaging; Goals; Grant; Habits; Hippocampus (Brain); Human; Human Development; Impairment; Implanted Electrodes; Iron; Lead; Learning; Magnetic Resonance Imaging; Measures; Mediating; Mental disorders; Modeling; Mood Disorders; Motivation; Nature; Neurocognitive; Neurophysiology - biologic function; Neurosurgeon; Operative Surgical Procedures; Participant; Patients; Pediatric cohort; Positron-Emission Tomography; Preparation; Process; Psychopathology; Psychoses; Research Personnel; Rewards; Rodent Model; Role; Schizophrenia; Substance Use Disorder; System; Testing; Time; addiction; age related; brain tissue; childhood epilepsy; cognitive control; cohort; design; executive function; functional magnetic resonance imaging/electroencephalography; habit learning; innovation; insight; learned behavior; motivated behavior; motivational processes; neurobehavioral; neurodevelopment; neuromechanism; neurophysiology; neurosurgery; novel; operation; pediatric patients; receptor; recruit; relating to nervous system; reward processing; young adult

Project Summary/Abstract This is the second renewal on a line of inquiry characterizing the neural basis of the maturation of reward and motivation through the adolescent period, a time of critical vulnerability to the emergence of major psychopathol- ogy (e.g., substance use disorder, schizophrenia, mood disorders), which are typically impacted by deficiencies in these systems. Building on the findings from the first two grants using functional Magnetic Resonance Imaging (fMRI), Positron Emission Tomography, and reward learning assessments, indicating heightened influence of reward/motivation (i.e., dopaminergic) systems in adolescence, we now propose to study their wider effects on establishing adult trajectories by characterizing developmental changes in habit formation and relatedly, stabili- zation of neural activity. The neural mechanisms that underlie maturation to established neurocognitive behav- iors have not been studied in human development and can provide unique insights into how adult trajectories are formed. The central hypothesis is that neurobehavioral processes underlying stabilization of behavior from adolescence to adulthood are supported by frontolimbic specialization and stabilization of neural activity. We will study 192 typically developing 10-26 year-olds with habit tasks in fMRI and EEG, and 45 pediatric epilepsy patients with intracerebral EEG. In Aim 1, we will characterize the neurodevelopment of habit formation as a probe for how modes of stable behavior are acquired defining adulthood, which rodent models have found is limited in adolescence and has not been studied in humans. We will use a well-established habit task and determine developmental changes in behavior and BOLD fMRI activity. In Aim2, we will characterize how changes in frontostriatal systems including using non-invasive indirect measures of dopamine through brain tissue iron, which in the previous grant we found is closely associated with dopamine, and functional connectivity, which our previous grant found specializes through adolescence, underlie neurocognitive stabilization into adult- hood. Finally, in order to understand how neural systems are stabilizing through adolescence into adult- hood, in Aim 3, we will characterize developmental changes in oscillations and in the variability of neural activity in key regions involved in habit formation using electroencephalography (EEG) and intracerebral stereo-eletroenceph- alography (sEEG). sEEG will be performed in collaboration with our co-investigator, a pediatric neurosurgeon who implants electrodes in preparation for resection due to epilepsy, providing critical data for characterizing de- velopmental changes in neural activity directly. These studies have never been performed in human development and can provide novel evidence regarding the neural mechanisms underlying normative establishment of adult trajectories informing how these may lead to maladaptive trajectories such as in psychopathology, which emerges during the transition from adolescence to adulthood.

项目概要/摘要 这是对奖励和成熟的神经基础的研究路线的第二次更新。 青少年时期的动机是一个非常容易出现主要精神病态的时期 ogy（例如物质使用障碍、精神分裂症、情绪障碍），通常受到缺陷的影响 在这些系统中。基于使用功能性磁共振成像的前两项资助的研究结果 （功能磁共振成像）、正电子发射断层扫描和奖励学习评估，表明影响力增强 青春期的奖励/动机（即多巴胺能）系统，我们现在建议研究它们对 通过描述习惯形成的发展变化以及相关的稳定来建立成人轨迹 神经活动的化。成熟到已建立的神经认知行为的神经机制 尚未在人类发展中进行研究，但可以为成人轨迹如何提供独特的见解 被形成。中心假设是行为稳定的神经行为过程 从青春期到成年期都得到额边缘专门化和神经稳定的支持 活动。我们将研究 192 名典型发育中的 10-26 岁儿童，他们在功能磁共振成像和脑电图方面有习惯任务，而 45 小儿癫痫患者脑内脑电图检查。在目标 1 中，我们将描述习惯的神经发育 形成作为如何获得定义成年期的稳定行为模式的探针，啮齿类动物模型 已发现仅限于青春期，尚未在人类中进行研究。我们将使用一个既定的习惯 任务并确定行为和 BOLD fMRI 活动的发育变化。在 Aim2 中，我们将描述 额纹状体系统如何变化，包括通过大脑使用非侵入性间接测量多巴胺 组织铁，在之前的资助中我们发现它与多巴胺和功能连接密切相关， 我们之前的资助发现，它专门针对青春期，是成人神经认知稳定的基础—— 兜帽。最后，为了了解神经系统如何从青春期稳定到成年， 目标 3，我们将表征关键神经活动的振荡和变异性的发育变化 使用脑电图（EEG）和脑内立体脑电图参与习惯形成的区域 异体造影（sEEG）。 sEEG 将与我们的共同研究者、一名儿科神经外科医生合作进行 谁植入电极以准备因癫痫而进行的切除术，为表征癫痫病提供了关键数据 直接影响神经活动的发育变化。这些研究从未在人类发展中进行过 并可以提供关于成人规范建立的神经机制的新证据 轨迹告知这些可能如何导致适应不良轨迹，例如在精神病理学中出现的轨迹 在从青春期到成年的过渡期间。