Characterizing Two Distinct ADHD Neurobiologies with fMRI

这个项目将使用功能磁共振成像(FMRI)来描述两个功能障碍 注意缺陷/多动障碍青少年的理论上可分离的神经认知通路 (ADHD)。ADHD是一种在儿童时期出现的常见疾病，通常导致终生教育、社交和 职业损害。几十年的研究极大地提高了我们对这种疾病的认识 复杂性。到目前为止，还没有研究设法确定一种有效的生物标记物，即单一的 神经心理测试，或准确识别ADHD患者的特定基因特征，部分 因为之前的研究得出了不一致的结论。许多研究人员得出结论，这是 因为ADHD的病因是多因素的，可能是多基因的，涉及许多小的 对大脑功能的影响。一致的证据表明，额纹状体大脑处于低多巴胺能状态 假设导致至少两种形式的神经认知障碍与冲动性ADHD有关的区域 症状损害了在需要抑制反应的测试中的执行能力，并损害了 通过测试评估对延迟加固的不敏感度来衡量动机。虽然这一模式是 在神经心理学证据的支持下，功能神经成像研究尚未完全表征 导致这些认知缺陷的生物病理。很可能，许多不一致的 以前的ADHD神经认知研究结果是通过检测具有不同病理状态的样本得出的。 了解神经生物学异质性的主要来源是未来最重要的一步 对ADHD的研究，最终将帮助临床医生更好地诊断和治疗这种疾病。这个项目寻求 通过研究这两种ADHD神经认知损害的功能神经解剖学特征 神经心理特征、中皮质和中边缘脑功能障碍与候选基因的关系 易感性。参与者将是被诊断为混合型多动症的青少年(需求侧管理314.01) 以及130名人口统计学上匹配的健康对照组。所有参与者都将接受严格的精神病学检查 评估，几个不同认知领域的神经心理评估，fMRI测量 反应抑制和奖赏系统脑活动，以及DAT1、DRD4和其他几个基因分型 与多巴胺相关的遗传标记以前与ADHD有关。这些数据将使我们能够验证 注意缺陷多动障碍患者存在两种不同的脑功能病理改变并阐明它们之间的关系 脑功能、认知能力和基因分型。计划中的项目是高度协作的 功能神经成像、认知测试、临床评估和精神遗传学方面的专家。注意力缺陷/多动障碍的神经生物学基础尚不清楚，因为单一的 对于这种疾病，可靠的生物标志物或决定性的测试尚未确定。有来自认知的证据 对ADHD青少年的研究表明，冲动行为可能源于两种截然不同的神经生物学类型 功能障碍。该项目将使用功能磁共振成像(FMRI)将这两个剖面连接起来 ADHD青少年脑功能异常与特定类型神经心理功能障碍的关系 某些遗传标记，为临床使用这些工具更准确地诊断提供支持 具有生物学意义的ADHD亚型。

This project will use functional magnetic resonance imaging (fMRI) to characterize dysfunction in two theoretically separable neurocognitive pathways in adolescents with Attention-Deficit/Hyperactivity Disorder (ADHD). ADHD is a common disorder arising in childhood that often results in lifelong educational, social, and occupational impairment. Decades of research has greatly refined our appreciation of the disorder's complexity. To date, no study has managed to identify an effective biological marker, a single neuropsychological test, or a specific genetic profile that accurately identifies persons with ADHD, in part because previous studies have produced inconsistent findings. Many researchers have concluded that this is because the etiology of ADHD is multi-factorial, probably polygenetic in nature, involving numerous small influences on brain function. Consistent evidence points to a hypodopaminergic state in frontostriatal brain regions, hypothesized to result in at least two forms of neurocognitive impairment linked to impulsive ADHD symptoms ¿ impaired `executive' performance on tests requiring inhibition of response, and impaired motivation measured by tests assessing insensitivity to delayed reinforcement. Although this model is supported by neuropsychological evidence, functional neuroimaging studies have not yet fully characterized the biological pathology giving rise to these cognitive deficits. It is likely that much of the inconsistency in previous ADHD neurocognitive research results from examining samples with heterogeneous pathologies. Understanding the major sources of neurobiological heterogeneity is the most significant step in future research of ADHD, and ultimately will help clinicians better diagnose and treat the disorder. This project seeks to characterize the functional neuroanatomy of these two ADHD neurocognitive impairments by examining the association of neuropsychological profile, mesocortical and mesolimbic brain dysfunction, and candidate gene susceptibilities. Participants will be 130 adolescents diagnosed with Combined-subtype ADHD (DSM 314.01) and 130 demographically-matched healthy controls. All participants will undergo rigorous psychiatric evaluation, neuropsychological assessment of several different cognitive domains, fMRI measurement of response inhibition and reward system brain activity, and genotyping DAT1, DRD4, plus several other dopamine-related genetic markers previously linked to ADHD. These data will allow us to validate the presence of two separate brain function pathologies in ADHD and to clarify relationships among disordered brain function, cognitive performance and genotype. The planned project is highly collaborative between experts in functional neuroimaging, cognitive testing, clinical assessment and psychiatric genetics. The neurobiological basis of Attention-Deficit/Hyperactivity Disorder is poorly understood because a single reliable biomarker or definitive test for the disorder has yet to be identified. There is evidence from cognitive studies of ADHD youth that impulsive behavior may arise from two markedly different types of neurobiological dysfunction. This project will use functional magnetic resonance imaging (fMRI) to link these two profiles of abnormal brain function in ADHD adolescents to specific types of neuropsychological dysfunction and to certain genetic markers, providing support for the clinical use of these tools to more precisely diagnose biologically-meaningful subtypes of ADHD.