Real-time fMRI Neurofeedback as a novel neurotherapy for children with ADHD

该研究旨在测试一种新的，非药物性的，基于大脑的ADHD治疗方法。注意力缺陷/多动障碍（ADHD）是最常见的儿童疾病之一，其典型特征是注意力不集中和自我控制能力差。过去20年的大脑成像显示，ADHD儿童在参与右下额叶皮层（rIFC）方面存在问题，这是自我控制和注意力的关键区域。ADHD儿童通常用刺激性药物治疗，我们已经证明，这种药物可以增强这个通常未被激活的区域的激活，使其达到正常的功能水平。然而，兴奋剂似乎没有长期影响，与副作用有关，并非所有患者都能耐受。非药物治疗是家长、患者和临床医生的首选，但不是很有效。在这项研究中，我们想测试一种新的治疗方法，通过教导ADHD儿童自我上调rIFC的活动来靶向ADHD中一个关键的大脑活动缺陷。我们假设这种治疗是有效的，因为它针对的是导致行为问题的关键大脑异常。我们计划通过使用功能性磁共振成像神经反馈（fMRI-NF）来实现这一目标。在fMRI-NF中，参与者的大脑活动与视频游戏有关。每当孩子增加或减少大脑目标区域（即rIFC）的大脑活动时，这将驱动视频游戏中的游戏性。通过这种方式，孩子们学会了用自己的大脑活动玩电子游戏，以一种有趣的方式通过试错来增强某些大脑区域的活动。因此，fMRI-NF训练患者实现对大脑激活的意志自我控制。NF使用一种更便宜的方法，使用电生理学（EEG-NF），已被证明在改善ADHD症状方面具有中等但相对长期的效率，长达2年。然而，已经表明fMRI-NF的作用明显更快，并且可以靶向ADHD中受影响的深层皮质区域，例如无法用EEG-NF靶向的rIFC。rtfMRI-NF研究在治疗关键神经功能缺陷和相关行为的其他疾病中具有前景。我们自己的试点可行性rt-fMRI-NF研究表明，31名ADHD儿童在11次8分钟的fMRI-NF治疗中学会了逐步增强rIFC的活性。此外，即使在培训结束时没有反馈，他们也能做到这一点，这表明学习效果可以在没有扫描仪的情况下持续下去。rIFC的自我上调还与ADHD问题的严重程度降低有关，在注意力和自我控制的认知测试中表现更好，并且在自我控制测试期间rIFC的大脑活动更好。我们还表明，他们的行为症状的改善在治疗后11个月保持不变。因此，这项首次在ADHD儿童中测试fMRI-NF的试点研究的结果非常有希望。然而，我们没有包括对照条件，因此不能排除安慰剂效应。因此，我们计划进行一项更大、更明确的研究，以证明ADHD儿童可以在14次8.5分钟的rtfMRI-NF治疗中学会自我上调rIFC的大脑活动。为此，我们将招募100名患有ADHD的儿童，并将他们随机分为实验组（rIFC的NF）和“假”（安慰剂）对照组（他们将从另一名参与者那里获得“非真实”的反馈），以测试这种新的大脑治疗是否会改善ADHD行为，以及大脑活动和注意力和自我控制测试的表现。其目的是开发一种新的，无副作用，非药理学和更持久的ADHD治疗方法，该方法基于神经科学证据，可以治疗ADHD儿童的关键大脑异常，这些异常是他们自我控制能力差和注意力差的基础。

The study aims to test a novel, non-pharmacological, brain-based therapy for ADHD. Attention Deficit/ Hyperactivity Disorder (ADHD) is one of the most prevalent childhood disorders, typified by poor attention and poor self-control. The last 2 decades of brain imaging have shown that ADHD children have problems with engaging the right inferior frontal cortex (rIFC), which is a key region for self-control and attention. ADHD children are treated typically with stimulant medication which we have shown enhances the activation of this normally underactivated region, bringing it to normal functioning levels. However, stimulants seem to have no longer-term effects, are associated with side effects and not tolerated by all patients. Non-pharmacological treatments are preferred by parents, patients and clinicians, but are not very efficient. In this study we want to test a new treatment that targets a key deficient brain activity in ADHD by teaching ADHD children to self-up-regulate the activity of the rIFC. We hypothesise that this treatment will be efficient because it targets the key brain abnormality that is causing the behavioural problems. We plan to achieve this by using functional magnetic resonance imaging Neurofeedback (fMRI-NF). In fMRI-NF the brain activity of the participant is connected to a videogame. Every time the child increases or decreases brain activity in the target region of the brain (i.e. rIFC) this will drive the gameplay in the videogame. This way the child learns to enhance the activity of certain brain regions by trial and error in a playful way by playing the videogame with their own brain activity. fMRI-NF therefore trains patients to achieve volitional self-control over brain activation. NF using a cheaper method, using electrophysiology (EEG-NF), has been shown to have moderate but relatively long-term efficiency in improving ADHD symptoms of up to 2 years. However, it has been shown that fMRI-NF effects are significantly faster and can target deep cortical regions that are affected in ADHD such as rIFC that cannot be targeted with EEG-NF. rtfMRI-NF studies have been promising in other disorders in remediating key neurofunctional deficit and associated behaviours. Our own pilot feasibility rt-fMRI-NF study showed that 31 ADHD children learned to progressively enhance the activity of their rIFC within 11 sessions of 8 min of fMRI-NF. Furthermore, they managed to do this even without the feedback at the end of the training which shows that the learning effect can be sustained without the scanner. The self-upregulation of rIFC was furthermore associated with reduced severity of their ADHD problems, with better performance on cognitive tests of attention and self-control and with better brain activity in rIFC during tests of self-control. We also showed that the improvement of their behavioural symptoms were maintained 11 months after the treatment. The findings of this first pilot study to test fMRI-NF in ADHD children were therefore very promising. However, we did not include a control condition and hence cannot rule out a placebo effect. We therefore plan a larger and more definite study to prove the concept that children with ADHD can learn to self-upregulate brain activity in the rIFC in 14 sessions of 8.5 minutes of rtfMRI-NF. For this purpose, we will recruit 100 children with ADHD and randomise them between an experimental group (NF of rIFC) and a "sham" (placebo) control group (they will receive "non-real" feedback from another participant), to test whether this new brain treatment will improve ADHD behaviour, as well as brain activity and performance on tests of attention and self-control. The aim is to develop a novel, side-effect free, non-pharmacological, and longer-lasting treatment for ADHD that is based on neuroscience evidence remediating the key brain abnormality of ADHD children that is underlying their poor self-control and poor attention.