Genetic modulation of functional brain activity of attention-deficit/hyperactivity disorder-related working memory process

在第一个资助期内，"基因组成像"初级研究小组开始使用不同的方法，包括功能磁共振成像（fMRI）、近红外光谱（NIRS）和脑电图（EEG），研究与注意力缺陷/多动障碍（ADHD）相关的反应抑制和工作记忆过程的功能神经解剖学。特别是，在一项正在进行的fMRI研究中，我们一直在研究ADHD相关的内在表型反应抑制的神经相关性，目前正在测试大脑活动的遗传调节的假设。下一个资助期的主要目标是在工作记忆子过程（相关信息的注意力调节和不相关信息的抑制）中通过fMRI评估功能性大脑活动，并比较ADHD患者和健康对照者之间的这些功能性大脑活动。此外，我们想分析这种功能性大脑活动的遗传和药理学调制。在初步的EEG和NIRS研究中，我们已经开发了一个足够的范式来研究ADHD相关的内表型工作记忆及其子过程（相关信息的注意力调节和无关信息的抑制）的神经相关性。从EEG和NIRS研究的结果中得出的范例将在40名健康受试者的fMRI研究中进行测试和评估。第二步，我们将比较ADHD患者（60名患者）与健康对照组（60名患者），两组均根据Val 158 Met COMT多态性进行分层。60名ADHD患者将接受两次检查，一次不接受，第二次接受哌醋甲酯或安慰剂治疗6周后。

In the first funding period the Junior Research Group “Genomic Imaging” started to investigate the functional neuroanatomy of response inhibition and working memory processes relevant for attention-deficit/hyperactivity disorder (ADHD) using different methods including functional magnetic resonance imaging (fMRI), near-infrared spectroscopy (NIRS) and electroencephalography (EEG). In particular, in an ongoing fMRI study we have been investigating the neural correlates of the ADHD-related endophenotype response inhibition and are currently testing hypotheses of genetic modulation of brain activity. The primary goals of the next funding period are the assessment of functional brain activity by means of fMRI during working memory sub-processes (attentional modulation of relevant and inhibition of irrelevant information) and compare these functional brain activities between ADHD patients and healthy controls. Additionally we want to analyse the genetic and pharmacological modulation of this functional brain activity. In preliminary EEG and NIRS studies we already have developed an adequate paradigm to investigate the neural correlates of the ADHD-related endophenotype working memory, its sub-processes (attentional modulation of relevant and inhibition of irrelevant information). The paradigm derived from the findings of the EEG and NIRS studies will be tested and evaluated in an fMRI study with 40 healthy subjects. In a second step we will compare ADHD patients (60 patients) with a healthy control group (60 individuals), both groups stratified according to the Val158Met COMT polymorphism. The 60 ADHD patients will be examined two times, in one session without, and in a second session after 6 weeks treatment with methylphenidate or placebo.