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

• 批准号: 9371651
• 负责人: FRANCISCO XAVIER CASTELLANOS
• 金额: $ 44.86万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-09 至 2019-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9371651
• 关键词: Academic skills; Address; Affect; Aftercare; Age; Anterior; Attention deficit hyperactivity disorder; Base of the Brain; 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; System; Testing; Ventral Striatum; Waiting Lists; Youth; age related; arm; base; cingulate cortex; cognitive control; cognitive reappraisal; control trial; 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

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.

项目摘要 响应RFA-MH-16-406的该分阶段创新申请寻求对初始（R61）2年的支持 通过新颖的修饰A进行里程碑式驱动的特定神经元靶标测试的阶段 针对3至5年级小学的儿童的组织技能的治疗方法 在神经发育障碍背景下的组织技能。达到我们建议的里程碑将 触发三年（R33阶段）的触发支持，以确认在较大样本中的目标参与 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 参与和功能结果的变化。组织技能障碍有助于学校失败 以及长期不良的结果，并发生在多种神经发育障碍中。他们是 药物或大多数现有的行为治疗方法不足。组织技能培训 （OST）在先前的对照试验中导致了强大的改进。进一步发展 干预措施，我们试图确定通过有效干预所参与的神经靶标。我们的飞行员数据和 理论考虑支持了固有功能连通性（IFC）的总体假设 背侧扣带回皮层（DACC）和前腹侧纹状体（AVS）之间代表可治疗的 目标。根据初始R61阶段，我们建议估计与干预相关的效果大小 在至少22名具有高质量成像和临床数据的儿童中，DACC-AVS IFC减少了两者 修改前后OST（OST-M）。如果我们遇到提议的里程碑，那就是DACC-AVS的减少 国际金融公司将超过特定的效果大小，并考虑到可观的差异比例 提高组织技能，我们将进入R33阶段。在R33阶段，我们将扩展 这项研究至少要多86名随机分配到OST-M干预措施或等待名单的儿童 提供完整的高质量干预前和后候补成像和临床数据。对于这两个阶段，我们 将获得最新的磁共振成像（MRI）数据，主要关注静止状态 功能性MRI。我们在R33阶段的具体目标是确认随机分组中的目标参与 到OST-M与候补列表小组；检查神经元目标变化与 组织技能和学术水平的临床提高；并确定 通过单独检查基线临床措施并结合使用基线临床措施来提高组织技能 全脑素素的休息状态指数。支持DACC-AVS IFC有效性的证据作为可修改 然后，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 儿童的干预措施。重要的是，即使是负面的结果也将是关于OST“剂量”的信息。 需要获得实质性影响。脑成像的不确定结果仍然会告知贝叶斯先验 为了将来对组织技能障碍的神经基质及其改善的研究。