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

项目摘要/摘要 这是对奖励和报酬成熟的神经基础的一系列研究的第二次更新 动机贯穿青春期，这段时期对主要精神变态的出现非常脆弱- 精神疾病(如物质使用障碍、精神分裂症、情绪障碍)，通常受缺乏症的影响 在这些系统中。基于使用功能磁共振成像的前两项赠款的研究结果 (FMRI)、正电子发射断层扫描和奖励学习评估，表明 青春期的奖赏/激励(即，多巴胺能)系统，我们现在建议研究它们对 通过表征习惯形成的发展变化以及与之相关的稳定性来建立成人轨迹 神经活动的程序化。神经认知行为成熟的神经机制-- IRS在人类发育过程中还没有被研究过，它可以为成人的发育轨迹提供独特的见解 都形成了。中心假设是神经行为过程是行为稳定的基础 从青春期到成年期由额叶边缘的特化和神经的稳定所支持 活动。我们将研究192名典型的10-26岁有习惯任务的青少年的fMRI和EEG，以及45名 儿童癫痫患者的脑内脑电检查。在目标1中，我们将描述习惯的神经发展 形成，作为探索如何获得稳定的行为模式，定义成年，哪些啮齿动物模型 已发现仅限于青春期，尚未在人类身上进行研究。我们将使用一种已有的习惯 任务和确定行为和大胆的fMRI活动的发育变化。在AIM2中，我们将描述 额纹状体系统的变化，包括通过大脑非侵入性间接测量多巴胺 组织铁，我们在之前的资助中发现它与多巴胺密切相关，以及功能连接， 我们之前的资助发现，它专门用于青春期，为成年后的神经认知稳定奠定了基础- 胡德。最后，为了了解神经系统是如何在青春期到成年期稳定下来的， 目的3，我们将表征发育变化的振荡和变异性的神经活动的关键 使用脑电(EEG)和脑内立体脑电研究与习惯养成有关的区域 地形图(SEEG)。SEEG将与我们的合作研究员，一位儿科神经外科医生合作进行 世卫组织植入电极，为癫痫切除做准备，为确定癫痫的特征提供了关键数据。 直接影响神经活动的发育性变化。这些研究从未在人类发育过程中进行过 并可以为成人标准化建立的神经机制提供新的证据 轨迹告知这些可能如何导致不适应轨迹，例如在出现的精神病理学中 在从青春期到成年期的过渡过程中。

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.