NEUROIMAGING OF INHIBITORY CONTROL AND STIMULANT RESPONSE IN ADHD

ADHD 抑制控制和刺激反应的神经影像

• 批准号: 7627565
• 负责人: STEVEN R. PLISZKA
• 金额: $ 1.41万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-04-01 至 2008-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7627565
• 关键词: Adverse event; Age; Anterior; Area; Attention deficit hyperactivity disorder; Awareness; Brain; Child; Clinical; Cognitive; Computer Retrieval of Information on Scientific Projects Database; Daily; Dose; Event; Functional Magnetic Resonance Imaging; Funding; Grant; Hyperactive behavior; Impulsivity; Institution; Interview; Letters; Lobe; Localized; Measures; Neuropsychological Tests; Oxygen; Parents; Performance; Perfusion; Personal Satisfaction; Pharmaceutical Preparations; Placebos; Process; Psychiatrist; Randomized; Rate; Relative (related person); Research; Research Personnel; Resources; Scanning; Schedule; Score; Signal Transduction; Source; Stimulus; Students; Testing; United States National Institutes of Health; Upper arm; Visit; Week; Weight; atomoxetine; day; impression; improved; inattention; millisecond; neuroimaging; phonology; response; sex; teacher

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. OBJECTIVE: The primary objective will be to that relative to placebo, atomoxetine treated subjects with Attention Deficit Hyperactivity Disorder will show a greater increase in oxygen brain perfusion in the right orbitofrontal lobe and anterior cingulate as they perform tasks involving inhibitory control [as measured by event related functional magnetic resonance imaging (fMRI)]. The secondary objective will be to show that above changes in brain activation will correlate with the degree of clinical improvement as measured by teacher and parent rating scales. STUDY SUBJECTS: The child must meets DISC-P criteria for ADHD-combined, that is, he/she has 6 of the 9 criteria in both the Inattention and Hyperactivity/Impulsivity domains. The subjects academic performance on the Woodcock Johnson is within 1 SD of the mean of his/her full scale IQ and the full scale IQ must be at least 95. The neuropsychological testing should not show any deficit in phonological awareness/processing. The child must be above 1.5 SD of the mean for his/her age and sex on both the Cognitive Problems/Inattention and Hyperactivity factors of both the CTRS-R and CPRS-R. TREATMENT: Subjects will be randomized to receive placebo or atomoxetine for 2 weeks. Recently Michelson et al. (Michelson et al., 2002) showed that once daily atomoxetine was effective in the treatment of ADHD, furthermore robust differences from placebo were observed by weeks 1-2. Subjects in the atomoxetine arm weighing less than 70 kg will started on 0.5 mg/kg/day for 1-3 days, 0.75 mg/kg/day on day 4-5 and 1.2 mg/kg/day on days 6-7. Weight, vital signs and assessment for adverse events will occur on day 7. If the medication is well tolerated, the subject will remain on the 1.2 mg/kg/day for all of week 2. Conners parent and teacher rating scales will be obtained at the end of weeks 1 and 2. At the visit on day 14, the psychiatrist will review the rating scales, interview the parent and child, and obtain the Clinical Global Impression (CGI). A CGI score of 1 (Very Much Improved) or 2 (Much Improved) shall be required to define a child as a responder. A Student T-Test will be used to constrast the mean CGI scores in the atomoxetine and placebo groups. The CTRS and CPRS will be subjected to an ANCOVA comparing the week 2 placebo and atomoxetine scores using the baseline variable as a covariate. The FMRI scan will be scheduled within 3 days of the day 14 visit while the subject remains on the final dose of study medication. EVENT-RELATED fMRI: Children will undergo ER-fMRI during the Stop Signal Task and the Stroop Task to precisely localize activation areas. Inter-trial interval will be 2.0 sec for both tasks. For the Stop Signal Task, GO stimuli will consist of the letters A and B which will appear at the center of the screen for 150 msec. The child presses one button for the letter "A", and a second button for the letter "B". On 25% of the trials, the GO stimulus will be followed by the STOP signal (a red triangle).

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此，可以在其他清晰的条目中表示。列出的机构是 对于中心，这不一定是调查员的机构。 目的：主要目标是相对于安慰剂，原子苷治疗的受试者，患有注意力缺陷多动障碍将显示右眶额叶中的氧气脑灌注量更大，并且在执行涉及抑制性控制的任务时（按事件测量）相关的功能磁共振成像（fMRI）]。 次要目标是表明，大脑激活的上述变化将与通过教师和父母评分量表衡量的临床改善程度相关。 研究对象：孩子必须符合ADHD合并的Disc-P标准，也就是说，在不集中和多动症/冲动性域中，他/她具有9个标准中的6个。 伍德考克·约翰逊（Woodcock Johnson）上的学科学习表现在其全尺度智商的平均值的1个SD之内，并且全尺度智商必须至少95。 儿童在CTRS-R和CPRS-R的认知问题/不集中和多动症因素上都必须高于平均年龄和性别的平均值的1.5 SD。 治疗：受试者将被随机接受安慰剂或阿托莫西​​汀2周。 最近，米歇尔森等人。 （Michelson等，2002）表明，一旦每天的rotomoxetine可以有效地治疗多动症，此外，在第1-2周之前，观察到与安慰剂的稳健差异。 重量低于70公斤的阿托西汀臂中的受试者将以0.5 mg/kg/天的速度开始1-3天，第4-5天的0.75 mg/kg/day和第6-7天的1.2 mg/kg/day开始。 重量，生命体征和对不良事件的评估将在第7天发生。如果在第2周的第2周耐受性良好，则受试者将保留在1.2 mg/kg/day上。CONNERS父母和教师评级量表将在第1和第2周结束。在第14天的访问中，精神科医生将审查评级量表，采访父母和孩子，并获得临床全球印象（CGI）。 CGI得分为1（非常有所改善）或2（改进）需要定义儿童为响应者。学生t检验将用于约束阿托西汀和安慰剂组中的平均CGI分数。 CTR和CPRS将接受ANCOVA，并使用基线变量作为协变量进行比较第2周的安慰剂和阿托莫西汀分数。 功能磁共振成像扫描将安排在第14天访问的3天内，而受试者仍在最终剂量的研究药物治疗中。 与事件相关的fMRI：在停止信号任务和Stroop任务期间，孩子将接受ER-FMRI，以精确定位激活区域。对于这两个任务，审判间隔将为2.0秒。 对于停止信号任务，GO刺激将由字母A和B组成，该字母A和B将出现在屏幕的中心150毫秒。孩子按下字母“ A”的一个按钮，并为字母“ B”按下第二个按钮。 在25％的试验中，GO刺激将随后是停止信号（红色三角形）。