Dopamine release and blood flow changes during induced epileptic seizures assessed with simultaneous PET-MR-EEG

癫痫是一种脑部疾病。患有癫痫的人会出现癫痫发作，这是大脑短暂的“短路”。在癫痫发作期间，人们可能只是盯着前方而没有反应（“缺席”癫痫发作）。在其他癫痫发作时，他们可能有不正常的运动，或摔倒在地，伤害自己。癫痫是一种常见病，在英国每100人中就有1人患有此病。癫痫患者通常用药物治疗。然而，这些药物只能完全阻止大约三分之二的人癫痫发作。有更多的药物来治疗癫痫是有用的，特别是那些以不同于现有药物的方式起作用的药物。我们并不完全了解癫痫发作是如何开始或停止的。一种可能的机制是神经递质。神经递质是大脑中神经细胞用来相互交流的“信使”。多巴胺就是这样一种神经递质。到目前为止，科学家们已经在他们所研究的所有类型的癫痫中发现了多巴胺信息的变化。在这个项目中，我们想要证明癫痫发作是否会释放大脑中的多巴胺。为此，可能因呼吸困难（换气过度）而引发无害的“失神”发作的患者将被要求在一个特殊的脑部扫描仪内进行。多巴胺的释放可以通过一种强大的脑部扫描技术——正电子发射断层扫描（PET）来观察。PET最近与另一种脑部成像技术——磁共振成像（MRI）相结合，变得更加强大。在英国只有两台这样的PET-MR同时使用的机器。第二个是最近在圣托马斯医院的我们中心安装的。我们将使用核磁共振成像来获取尽可能多的关于病人大脑的信息——它们是什么样子的，它们是如何连接的，以及血液是如何在其中流动的。我们特别感兴趣的是，当志愿者患者出现“失神”发作时，血流是如何变化的。我们还想检查多巴胺的释放是否独立于血流变化。为了准确地知道病人什么时候“失神”发作，我们还需要另一种技术，脑电图。脑电图（EEG）可以让我们看到大脑的电活动，在“失神”发作的一秒到下一秒期间，它的变化非常明显。在过去的几个月里，我们设法在PET-MR扫描仪内记录脑电图，由于内部的强磁场，这是相当困难的。因此我们现在有了PET-MR-EEG扫描仪。PET-MR-EEG将是确定癫痫发作时多巴胺是否释放的理想技术。我们也在努力使这三种技术尽可能快。因此，我们认为我们甚至可以弄清楚多巴胺是在癫痫发作前释放的，还是在癫痫发作后释放的。我们认为癫痫发作后会释放。这意味着多巴胺可以使癫痫停止。这对癫痫患者来说是个好消息，因为制药公司可以开发出通过多巴胺系统起作用的新药。这类药物目前还不存在。另一个好处是，借助非常清晰的核磁共振成像图像，可以准确地显示多巴胺释放的位置。如果我们能找到这么小的大脑区域，那么外科医生就可以用深部脑刺激器瞄准它们，试图阻止癫痫发作。一些科学家还在开发一种系统，可以将少量药物直接释放到一个小的大脑区域，以阻止癫痫发作。癫痫发作有许多不同的类型，但我们相信多巴胺可能是大脑停止癫痫发作的一种通用方式。因此，各种癫痫发作的癫痫患者可能受益于本研究。我们还认为，许多其他科学家将从我们在这项提议中开发的PET-MR-EEG技术中受益。获取同步信息对偏头痛或中风等突发疾病尤为重要，但对正常的大脑工作也同样重要。

Epilepsy is a brain disorder. People with epilepsy have epileptic seizures, which are brief periods of "short-circuiting" in the brain. During seizures, people may simply stare ahead and not be responsive ("absence" seizures). During other seizures, they might have abnormal movements, or fall to the ground, and injure themselves. Epilepsy is a frequent disease, affecting about 1 in 100 people in the UK.People with epilepsy are normally treated with medication (drugs). However, these drugs only completely stop seizures in about 2 out of 3 people. It would be useful to have more drugs to treat epilepsy, particularly drugs that work in different ways to the ones that already exist.We do not understand completely how seizures start - or stop. One possible mechanism is by neurotransmitters. Neurotransmitters are "messengers" that nerve cells in the brain use to talk to each other. Dopamine is such a neurotransmitter. Scientists have shown changes in dopamine messaging in all types of epilepsy they have studied so far.In this project, we want to demonstrate whether seizures release dopamine in the brain. For this, patients who can trigger a harmless "absence" seizure by breathing hard (hyperventilation) will be asked to do so inside a special brain scanner.Dopamine release can be seen with a powerful brain scanning technology, Positron Emission Tomography (PET). PET has recently become even more powerful by combining it with another technique for taking images of the brain, Magnetic Resonance Imaging (MRI). There are only two such simultaneous PET-MR machines in the UK. The second one has recently been installed in our centre at St Thomas' Hospital.We will use MRI to get as much information as we can about patients' brains - what they look like, how they are wired, and how blood flows in them. We are especially interested in how blood flow changes when the volunteer patients have their "absence" seizures. We also want to check whether dopamine release is independent of blood flow changes.In order to know exactly when patients have an "absence" seizure, we need yet another technique, EEG. The EEG (electro-encephalogram) allows us to see the electrical activity in the brain, which changes very clearly during an "absence" seizure from one second to the next. Over the past months, we have managed to record EEG inside the PET-MR scanner, which is quite difficult due to the strong magnetic fields inside. We therefore now have a PET-MR-EEG scanner.PET-MR-EEG will be the ideal technique to work out whether dopamine is released at the time of seizures. We have also worked on making all three techniques as fast as possible. We therefore think that we can even work out whether dopamine is released before the seizures, or after seizures have started.We think it will be released after seizures have started. This would mean that dopamine makes seizures stop. That would be good news for epilepsy patients, because drug companies can then develop new drugs that work through the dopamine system. Such drugs do not currently exist.Another benefit would be to show exactly where dopamine is released thanks to the very clear MRI pictures. If we find such small areas of the brain, then surgeons may be able to target them with deep brain stimulators to try and stop seizures. Some scientists are also developing systems that can release a tiny amount of drug directly into a small brain area to stop seizures.There are many different types of seizures, but we believe that dopamine may be a general way for the brain to stop seizures. Therefore, epilepsy patients with all kinds of seizures may benefit from this research.We also think that many other scientists will benefit from the PET-MR-EEG technique we are developing in this proposal. Getting simultaneous information will be particularly important for diseases which come in attacks, for example migraine or stroke, but also for normal brain workings.