Brain plasticity underlying acquisition of new organizational skills in children

大脑可塑性是儿童获得新组织技能的基础

基本信息

批准号：
10222511
负责人：
FRANCISCO XAVIER CASTELLANOS
金额：
$ 84.11万
依托单位：
NEW YORK UNIVERSITY SCHOOL OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-09-01 至 2023-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10222511
关键词：
Academic skills Address Affect Aftercare Age Anterior Attention deficit hyperactivity disorder Base of the Brain Bayesian Method Behavior Therapy Behavior assessment Behavioral Brain Brain imaging Child Clinical Clinical Data Cognitive Therapy Corpus striatum structure Data Dorsal Effectiveness Evidence based intervention Failure Frequencies Functional Magnetic Resonance Imaging Future Goals Image Impairment Intervention Investigational Therapies Life Link MRI Scans Magnetic Resonance Imaging Masks Matched Group Measures Mediating Mediator of activation protein Modeling Modification Neurodevelopmental Disorder Neuronal Plasticity Neurons Outcome Parents Pharmaceutical Preparations Phase Physiological Physiology Progress Reports Randomized Randomized Clinical Trials Rest Sampling School-Age Population Schools Seeds System Testing Ventral Striatum Waiting Lists Youth age related arm base cingulate cortex cognitive control cognitive reappraisal dosage effective intervention elementary school fifth grade functional outcomes improved inattention indexing innovation novel post intervention randomized trial relating to nervous system remediation response screening sex skills skills training trial design young adult

项目摘要

Project Summary This phased innovation application in response to RFA-MH-16-406 seeks support for an initial (R61) 2-year phase for milestone-driven testing of a specific neural target of intervention by a novel modification of a treatment targeting organizational skills in children in 3rd to 5th grades of elementary school who have deficient organizational skills in the context of neurodevelopmental disorders. Attaining our proposed milestones would trigger support for three additional years (R33 phase) to confirm target engagement in a larger sample with random assignment to intervention vs. wait-list control conditions, to assess the relationships between target engagement and changes in functional outcomes. Organizational skills impairments contribute to school failure and to poor long-term outcomes and occur across multiple neurodevelopmental disorders. They are insufficiently addressed by medications or most existing behavioral treatments. Organizational skills training (OST) has resulted in robust, enduring improvements in a prior controlled trial. To further develop this intervention, we seek to identify the neural targets engaged by effective intervention. Our pilot data and theoretical considerations support the overarching hypothesis that intrinsic functional connectivity (iFC) between dorsal anterior cingulate cortex (dACC) and anterior ventral striatum (aVS) represents a treatable target. Accordingly, in the initial R61 phase we propose to estimate the effect size of intervention-related decreases in dACC-aVS iFC in at least 22 children with high-quality imaging and clinical data obtained both before and after modified OST (OST-m). If we meet our proposed milestones that the decrease in dACC-aVS iFC will exceed a specific effect size and account for an appreciable proportion of the variance in the improvement in organizational skills, we would proceed to the R33 phase. In the R33 phase, we would expand the study to obtain at least 86 more children randomized to the OST-m intervention or to wait-list who will provide complete high quality pre- and post-intervention/waitlist imaging and clinical data. For both phases, we will obtain state-of-the-art magnetic resonance imaging (MRI) data with a primary focus on resting-state functional MRI. Our specific aims in the R33 phase are to confirm target engagement in the group randomized to OST-m vs. the waitlist group; to examine the relationship between changes in the neuronal target and clinical improvements in organizational skills and academic proficiency; and to identify moderators of improvement in organizational skills by examining baseline clinical measures alone and in combination with whole-brain voxel-wise resting-state indices. Evidence supporting the validity of dACC-aVS iFC as a modifiable neural target would then support future studies to further enhance the effectiveness of cognitive/behavioral interventions in children. Importantly, even negative results will be informative regarding the OST “dosage” required to attain substantial effects. Inconclusive results from brain imaging would still inform Bayesian priors for future studies of the neural substrates of organizational skills impairments and their amelioration.

项目概要此分阶段创新申请是为了响应 RFA-MH-16-406，寻求对初始 (R61) 2 年期的支持通过对特定神经干预目标进行里程碑驱动测试的阶段针对组织能力有缺陷的小学三至五年级儿童的治疗神经发育障碍背景下的组织技能将达到我们提出的里程碑。触发额外三年的支持（R33 阶段），以确认更大样本中的目标参与度随机分配干预与等待名单控制条件，以评估目标之间的关系参与度和功能结果的变化会导致学业失败。以及不良的长期结果，并发生在多种神经发育障碍中。药物或大多数现有的行为治疗不足以解决这一问题。 (OST) 在之前的对照试验中取得了稳健、持久的改进，以进一步发展这一点。干预，我们寻求确定有效干预所涉及的神经目标和我们的试点数据。理论考虑支持了以下总体假设：内在功能连接（iFC）背侧前扣带皮层 (dACC) 和前腹侧纹状体 (aVS) 之间的损伤是可治疗的因此，在最初的 R61 阶段，我们建议估计干预相关的效应大小。至少 22 名儿童的 dACC-aVS iFC 降低，并获得了高质量影像和临床数据如果我们达到我们提出的里程碑，则 dACC-aVS 会减少。 iFC 将超过特定的效应大小，并在方差中占相当大的比例组织能力的提高，我们将进入R33阶段。该研究的目的是让至少 86 名儿童随机接受 OST-m 干预或列入候补名单，他们将我们为这两个阶段提供完整的高质量干预前和干预后/候补影像和临床数据。将获得最先进的磁共振成像 (MRI) 数据，主要关注静息态我们在 R33 阶段的具体目标是确认随机分组中的目标参与情况。 OST-m 与候补组；检查神经目标的变化与组织技能和学术能力的临床改进；并确定协调者通过单独和结合检查基线临床测量来提高组织技能支持 dACC-aVS iFC 作为可修改方法的有效性的证据。神经目标将支持未来的研究，以进一步提高认知/行为的有效性重要的是，即使是阴性结果也能提供有关 OST“剂量”的信息。获得实质性效果所需的大脑成像的不确定结果仍然可以为贝叶斯先验提供信息。用于未来组织技能损伤的神经基础及其改善的研究。