Neural Bases of ADHD in Fetal Drug or Alcohol Exposure

产前可卡因（PNCE）和酒精暴露（PNAE）导致持续的行为缺陷，在许多方面类似于注意缺陷多动障碍（ADHD）。虽然这种相似性表明在所有三组中都涉及相似或重叠的神经回路，但特定缺陷的细微差异及其对刺激物的不同反应表明，特定回路和/或非重叠回路的破坏性质存在差异。动物研究表明，PNCE导致多巴胺（DA）神经传递突触后缺陷，这种缺陷对兴奋剂（如安非他明（AMPH）或哌醋甲酯（MPH））难以耐受。在人体研究中，数据就不那么清晰了，这至少在一定程度上反映了识别纯PNCE或PNAE受试者的难度，以及测量电路功能的工具直到最近才出现的事实。该项目将汇集三组研究人员，他们在子宫内接触酒精和可卡因的发育后果、功能和结构神经成像以及多动症方面具有专业知识，其总体目标是描述PNCE和PNAE中多动症行为的神经相关性

Prenatal cocaine (PNCE) and alcohol exposure (PNAE) result in sustained behavioral deficits similar in many respects to attention deficit hyperactivity disorder (ADHD). While this similarity suggests the involvement of similar or overlapping neural circuits in all three groups, subtle differences in the specific deficits and their differential responsiveness to stimulants suggest differences in the nature of the disruptions within a specific circuit and/or disruptions in non-overlapping circuits. Studies in animals suggest that PNCE results in a post-synaptic defect in dopamine (DA) neurotransmission that is refractory to stimulants, such as amphetamine (AMPH) or methylphenidate (MPH). In human studies, the data are less clear, reflecting, at least in part, the difficulty of identifying subjects with pure PNCE or PNAE, and, in part, the fact that tools for measuring circuit function have only recently become available. This project will bring together three groups of researchers with expertise in developmental consequences of alcohol and cocaine exposure in utero, functional and structural neuroimaging, and ADHD, with the overarching goal of characterizing the neural correlates of ADHD behaviors in PNCE and PNAE individuals, using a combination of detailed neurocognitive testing, ERP, and functional, structural, and diffusion tensor (DTI) MRI. We will study a well characterized cohort of 18-year-old, African American adolescents, whose PNCE and PNAE were ascertained prospectively during gestation. This cohort is unique in that recruitment was stratified to minimize the confounding of alcohol and cocaine. The study has the following Specific Aims: 1) To use fMRI to confirm that individuals with PNCE, PNAE, and idiopathic ADHD have a functional impairment in fronto-striatal circuits and that additional circuit dysfunctions contribute to behavioral deficits in PNAE; 2) To test the hypothesis that the circuit defect in PNCE-associated ADHD is postsynaptic and, therefore, unresponsive to MPH; 3) To use structural MRI and DTI to examine the contribution of structural abnormalities to the functional impairment in neural circuitry linked to ADHD-related deficits; 4) To identify the neural correlates of dyscalculia in individuals with PNAE and test the hypothesis that PNAE is characterized by a specific deficit in activation of parietal networks subserving number processing.