An fMRI study of the effect of working memory training on ADHD brain dysfunction

描述（由申请人提供）：有证据表明，计算机管理的认知训练可以改善ADHD工作记忆缺陷，并且这种类型的非ADHD训练通过改变前额叶皮层和顶叶的大脑活动来增强正常的工作记忆能力。然而，没有研究描述ADHD患者工作记忆训练后的大脑活动变化，以了解认知缺陷得到纠正时会发生什么神经变化。这项R21探索性研究将检查认知训练治疗在工作记忆，ADHD症状和各种其他执行能力方面的神经基础。该研究将比较n=21名ADHD青少年与工作记忆基线缺陷的证据（即，<1.5SD低于基线时的标准评级）和n=21名人口统计学匹配的非ADHD健康对照参与者。受试者将接受基线神经心理学和功能磁共振成像，包括言语和视觉空间斯滕贝格功能磁共振成像工作记忆任务，5周的日常计算机工作记忆训练，然后进行终点功能磁共振成像和神经和行为变化的认知评估。培训将使用市售Cogmed软件（www.cogmed.com），因为该软件具有一套完善的计算机化工具，对本研究具有许多实际优势。我们的分析将确定ADHD青少年的哪些大脑区域受到工作记忆治疗的影响，并表征基线和终点之间的激活变化模式。我们将研究治疗后的差异激活和激活的大脑区域之间的功能连接的程度，以测试有关治疗收益的可能神经机制的假设。这些分析将提供数据，使我们能够确认治疗机制的神经生物学模型，以便将来研究这种干预措施在ADHD中的有效性。我们还将进行一系列分析，以确定大脑功能的哪些具体变化可能是工作记忆训练对ADHD症状和其他“执行”能力的普遍影响的基础。通过识别任何此类效应的神经相关性，这项研究可以产生关于任何有效ADHD治疗的神经靶点的宝贵信息。这项探索性研究的主要成果将是通过测试理论指导的关于可能的神经可塑性变化的假设来表征ADHD治疗收益的神经基础。这些结果将支持更大的未来研究，旨在更好地了解这种替代治疗ADHD的神经基础，确定可能表示存在可补救的工作记忆缺陷的生物或遗传因素，并最终更好地了解ADHD工作记忆缺陷的病因。 公共卫生相关性：有证据表明，计算机管理的认知训练可以改善ADHD的工作记忆缺陷，并且这种类型的非ADHD训练通过改变前额叶皮层和顶叶的大脑活动来增强正常的工作记忆能力。然而，没有研究描述ADHD患者工作记忆训练后的大脑活动变化，以了解认知缺陷得到纠正时会发生什么神经变化。这项R21探索性研究将检查认知训练治疗在工作记忆，ADHD症状和各种其他执行能力方面的神经基础。

DESCRIPTION (provided by applicant): There is evidence both that computer-administered cognitive training can improve ADHD working memory deficits and that this type of training in non-ADHD enhances normal working memory ability by altering brain activity in prefrontal cortex and the parietal lobe. However, no study has characterized brain activity changes following working memory training in ADHD to understand what neural changes occur when cognitive deficits are remedied. This R21 exploratory study will examine the neural basis of cognitive training treatment gains in working memory, ADHD symptoms, and various other executive abilities. The study will compare n=21 ADHD adolescents with evidence for baseline deficits in working memory (i.e., <1.5 SD below normative ratings at baseline) and n=21 demographically-matched non-ADHD healthy control participants. Participants will undergo baseline neuropsychological and fMRI imaging with verbal and visuospatial Sternberg fMRI working memory tasks, 5 weeks of daily computerized working memory training, and then endpoint fMRI and cognitive evaluation of neural and behavioral changes. Training will utilize commercially-available Cogmed software (www.cogmed.com) as it has a well-developed set of computerized tools, with numerous practical advantages for this study. Our analyses will identify which brain regions in ADHD adolescents are affected by working memory treatment and characterize patterns of activation change between baseline and endpoint. We will examine post-treatment differences in the extent of activation and functional connectivity among activated brain regions to test hypotheses about possible neural mechanisms underlying treatment gains. These analyses will provide data that will permit us to confirm a neurobiological model of the treatment mechanism to permit future studies of this intervention's effectiveness in ADHD. We also will conduct a series of analyses to determine what specific changes in brain function might underlie a generalized effect of working memory training on ADHD symptoms and other 'executive' abilities. By identifying the neural correlates any such effect, this study could yield invaluable information about what the neural targets of any effective ADHD treatment must be. The key accomplishment of this exploratory study will be to characterize the neural basis of treatment gains in ADHD by testing theoretically-guided hypotheses about possible neuroplastic changes. The results will support larger, future studies aimed at better understanding the neural basis of this alternative treatment for ADHD, identifying biological or genetic factors that might denote the presence of a remediable working memory deficit, and ultimately achieving a better understanding of the etiology of ADHD working memory deficits. PUBLIC HEALTH RELEVANCE: There is evidence both that computer-administered cognitive training can improve ADHD working memory deficits and that this type of training in non-ADHD enhances normal working memory ability by altering brain activity in prefrontal cortex and the parietal lobe. However, no study has characterized brain activity changes following working memory training in ADHD to understand what neural changes occur when cognitive deficits are remedied. This R21 exploratory study will examine the neural basis of cognitive training treatment gains in working memory, ADHD symptoms, and various other executive abilities.