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: 10606470
• 负责人: BEATRIZ LUNA
• 金额: $ 69.33万
• 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/10606470
• 关键词: Acceleration; 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; 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; attenuation; brain tissue; childhood epilepsy; cognitive control; cohort; design; executive function; habit learning; improved; innovation; insight; learned behavior; motivated behavior; motivational processes; neural; neurobehavioral; neurodevelopment; neuromechanism; neurophysiology; neurosurgery; novel; operation; pediatric patients; receptor; recruit; 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.

项目总结/摘要 这是第二次更新的调查线特征的神经基础的成熟的奖励， 青少年时期的动机，一个关键的脆弱性出现的主要精神病患者的时间， OGY（例如，物质使用障碍、精神分裂症、情绪障碍），其通常受到缺乏的影响 在这些系统中。基于前两赠款使用功能性磁共振成像的研究结果， （功能磁共振成像），正电子发射断层扫描和奖励学习评估，表明增强的影响， 奖励/动机（即，多巴胺能）系统在青春期，我们现在建议研究其更广泛的影响， 通过描述习惯形成和相关的稳定性的发展变化来建立成年人的轨迹， 的神经活动。神经机制的基础成熟，以建立神经认知神经元， IOR尚未在人类发展中进行过研究，但可以为成人轨迹提供独特的见解 形成。中心假设是，神经行为过程的基础稳定的行为 从青春期到成年期，额叶边缘的专门化和神经系统的稳定化支持着这种变化。 活动我们将研究192名10-26岁的典型发育中的习惯任务的fMRI和EEG， 小儿癫痫患者的脑内脑电图。在目标1中，我们将描述习惯的神经发育 形成作为一个探针的模式，稳定的行为是如何获得定义成年，其中啮齿动物模型 研究人员发现，这种疾病仅限于青春期，尚未在人类身上进行过研究。我们将使用一个良好的习惯 任务，并确定行为和BOLD功能磁共振成像活动的发展变化。在目标2中，我们将描述 如何改变额纹状体系统，包括使用非侵入性间接测量多巴胺通过大脑， 组织铁，在之前的资助中，我们发现它与多巴胺密切相关，以及功能连接， 我们之前的研究发现，它在青少年时期是专门的，它是成年后神经认知稳定的基础， 胡德。最后，为了了解神经系统是如何从青春期到成年期保持稳定的， 目的3，我们将描述振荡的发展变化，并在关键的神经活动的变异性， 使用脑电图（EEG）和脑内立体电脑， 脑电图（sEEG）。sEEG将与我们的合作研究者（一名儿科神经外科医生）合作进行 谁植入电极，准备切除由于癫痫，提供关键数据，表征去， 直接影响神经活动。这些研究从未在人类发育中进行过 并能提供有关成年人正常行为建立的神经机制的新证据 轨迹告知这些可能导致适应不良的轨迹，例如在精神病理学中， 从青春期到成年期的过渡期。