NEUROLOGICAL BASIS OF INHIBITORY DEFICITS IN ADHD

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 大量证据表明额叶皮质下环路异常参与了ADHD的病理生理过程；然而，这些异常是否局限于特定的额叶区域(即特定的额叶皮质下环路)，如果是的话，是哪个区域(S)，目前尚不清楚。目前流行的假说认为反应抑制不足是导致ADHD病理生理学的基本特征之一。对动物和人类损伤的研究结果导致许多研究人员得出结论，反应抑制可能特定地局限于腹侧前额叶区域(具有右优势)，因此ADHD可能是该区域发育异常的结果。然而，来自电生理学和成像研究的最新数据支持反应抑制的多领域模型，根据该模型，额叶对反应抑制至关重要的特定区域取决于正在执行的任务的性质(骨骼运动、动眼运动、认知、社会情绪)。此外，来自ADHD神经行为和影像研究的证据表明，额叶内的异常可能并不局限于前额腹区。因此，我们建议研究ADHD存在几个额叶区域异常的假设，每个额叶区域都导致反应抑制的几个平行缺陷之一，涉及骨骼运动、动眼运动、认知和社会情绪领域。Alexander的额叶-皮质下环路模型(Middleton和Strick最近更新，包括骨骼运动、动眼运动、前额背外侧、前扣带回和内侧/外侧眼眶前额环路)将作为这些实验的基础。行为范式、AMRI和功能磁共振成像将用于确定ADHD患者中哪些额叶回路受到影响，以及特定额叶回路内的异常以何种方式与定义ADHD的行为/认知缺陷相关；该方法的一个重要特征是使用扫描仪内外的行为任务(即功能磁共振成像)，这些任务经过精心设计，以探测特定额叶回路的功能。这些发现不仅有助于加深对ADHD病理生理学的理解，还将提高临床医生诊断ADHD并做出针对ADHD患者的针对性干预(药理学、行为和认知)的决定的能力。

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. A preponderance of evidence has implicated abnormalities in frontal-subcortical circuits as contributing to the pathophysiology of ADHD; however whether these abnormalities are localized to a specific frontal region (i.e., a specific frontal-subcortical circuit), and if so, which region(s), remains unclear. Prevailing hypotheses implicate deficient response inhibition as one of the fundamental features driving the pathophysiology of ADHD. Results from studies of lesions in animals and humans led many investigators to conclude that response inhibition may be localized specifically to ventral prefrontal regions (with a right preponderance) and consequently that ADHD may be the result of developmental abnormalities localized to this region. More recent data from electrophysiology and imaging studies, however, have lent support to a multiple-domain model of response inhibition according to which the specific region of the frontal lobe crucial for response inhibition depends on the nature of the task (skeletomotor, oculomotor, cognitive, socioemotional) being performed. Furthermore, evidence from neurobehavioral and imaging studies in ADHD has indicated that abnormalities within the frontal lobe may not be restricted to ventral prefrontal regions. Accordingly, we propose to investigate the hypothesis that in ADHD there exist abnormalities of several frontal lobe regions, each of which contributes to one of several parallel deficits in response inhibition, involving skeletomotor, oculomotor, cognitive, and socioemotional domains. Alexander's model of frontal-subcortical circuits (recently updated by Middleton and Strick to include skeletomotor, oculomotor, dorsolateral prefrontal, anterior cingulate, and medial/lateral orbitofrontal circuits) will serve as a basis for these experiments. Behavioral paradigms, aMRI and fMRI will be used to determine which frontal circuits are affected in ADHD and in what way abnormalities within specific frontal circuits are associated with the behavioral/cognitive deficits that define ADHD; an important feature of the methodology is the use of behavioral tasks both outside and inside the scanner (i.e. fMRI) that have been carefully designed to probe functioning of specific frontal circuits. The findings will not only contribute to increased understanding of the pathophysiology of ADHD, but also improve clinicians' ability to diagnose ADHD and make decisions regarding targeted interventions (pharmacologic, behavioral, and cognitive) for individuals with the disorder.