BIOCHEMICAL MECHANISMS UNDERLYING IMPAIRED ATTENTION

这项建议涉及潜在的生化机制， 儿童注意力不集中。 主要目的是研究 注意力和相关神经行为过程的成分受到影响 通过药物激活所有多巴胺（DA）受体，仅D1 受体，D2和D3受体，或仅D3受体。 我们建议 研究注意力和相关神经行为的各种成分 在儿童和青少年中使用系统的、多层面的评估方法， 注意力受损的成年人（a）注意力缺陷多动 或（B）伴有和不伴有ADHD的图雷特综合征。 这些人口提供了一个独特的机会， 儿童注意力受损是否有类似的生化基础， 无论其病因如何。 我们将研究几个因素的影响。 不同的药物，包括：a）哌醋甲酯，B）匹莫齐特，c） 溴隐亭和d）培高利特。 两个具体的目标，每个都有自己的一套 的假设将得到解决。 具体目标1（受损的性质 注意）解决了病因之间的关系， 注意力问题和注意力缺陷的模式。 我们将 评估注意力的不同组成部分，包括选择性和持续性 注意力、抑制解除以及短期记忆和精细运动 skills. 目前尚不清楚这些因素如何随不同病因而变化 注意力受损的症状 将解决的假设是：1） ADHD和TS/ADHD受试者在特定的 注意力技能受损，但它们在运动技能方面会有所不同。 TS/ADHD和TS受试者在运动方面都有更大的损伤， skills. 具体目标2（注意力受损的药理学基础， 精细运动技能和冲动）解决DA之间的关系 激活剂和特定认知和运动障碍的改变。 将解决的假设是：1）受损的注意力是 通过激活D1受体而不是通过激活D2和/或D3降低 受体; 2）精细运动技能受D2受体激活的影响， 但不是通过激活D1或D3受体; 3）冲动性降低， 激活D3受体，但不是通过激活D1和/或D2 受体。 这些目标将进行详细的全面分析， 多变量分析 没有研究比较 选择性激活不同的多巴胺受体， 注意力受损的部分。 也没有研究比较 药物对由于不同原因引起的注意力受损儿童的影响 病因学

This proposal addresses potential biochemical mechanisms underlying impaired attention in children. The primary objective is to study how the components of attention and related neurobehavioral processes are affected by drugs which activate either all Dopamine (DA) receptors, just D1 receptors, D2 and D3 receptors, or just D3 receptors. We propose to investigate various components of attention and related neurobehavioral processes using a systematic, multidimensional assessment in children and adults with impaired attention due to (a) attention deficit hyperactivity disorder (ADHD), or (b) Tourettes Syndrome with and without ADHD. Such populations provide a unique opportunity to address the question of whether impaired attention in children has a similar biochemical basis regardless of its etiology. We will investigate the effects of several different drugs including: a) methylphenidate, b) pimozide, c) bromocriptine and d) pergolide. Two specific aims each with their own set of hypotheses will be addressed. Specific Aim 1 (The nature of impaired attention) addresses the relationship between the etiology of the attentional problem and the pattern of attentional deficits. We will assess different components of attention including selective and sustained attention, disinhibition as well as short term memory and fine-motor skills. It is not clear how these factors vary with different etiologies of attentional impairment. The hypotheses that will be addressed are: 1) ADHD and TS/ADHD subjects will not differ in the degree to which particular attentional skills are impaired, but they will differ in the motor skills with both TS/ADHD and TS subjects having a greater impairment in motor skills. Specific Aim 2 (The Pharmacological Basis of Impaired Attention, Fine Motor Skills and Impulsivity) addresses the relationship between DA activators and alterations in specific cognitive and motor impairments. The hypotheses that will be addressed are: 1) impaired attention is reduced by activation of D1 receptors but not by activation of D2 and/or D3 receptors; 2) fine-motor skills are affected by activation of D2 receptors, but not by activation of D1 or D3 receptors; 3) impulsivity is reduced by activation of D3 receptors, but not by the activation of D1 and/or D2 receptors. These objectives will be analyzed with a detailed comprehensive multivariate analysis. There are no studies comparing the effect of selective activation of different dopamine receptors on the various components of impaired attention. There are also no studies comparing the effect of drugs in children with impaired attention due to varying etiologies.