Interoception and functional seizures: a mechanistic and diagnostic approach

功能性发作看起来像癫痫发作，但与癫痫发作不同的是，它们与异常的、过度的脑电波活动无关。在1%被诊断为癫痫的人群中，高达20%的人实际上患有功能性癫痫发作，然而我们对功能性癫痫发作的生物学原因的了解仍然有限。相反，传统上认为它们有心理学基础。功能性发作与癫痫发作的诊断和鉴别仍然存在问题。一个金标准的诊断是基于病人入院时捕捉一个典型的癫痫发作，并发视频和脑电波（EEG）记录。这是昂贵的，不广泛使用，患者在入院期间可能没有癫痫发作，一些癫痫发作可能没有可记录的过度脑电波脑活动。这可能导致诊断严重延误、治疗不当、发病率上升和过早死亡。缺乏对功能性癫痫发作的神经生物学基础的了解意味着治疗选择有限。在这项研究中，我们提出了一种区分癫痫性和功能性癫痫发作的新方法，并更好地了解功能性癫痫发作的发生方式和原因。内感受是一种第六感，它告诉大脑身体内部发生了什么，并代表饥饿或口渴等情况。它还与对疲劳、疼痛、温度或其他内部感觉的感知有关。它可以是有意识的，也可以是无意识的，影响一个人思考、感觉和行为的方式。内感受可以通过多种方式进行研究，比如测试一个人检测心跳的准确性，或者使用脑电波记录（EEG）来测量当一个人专注于自己的心跳时大脑中发生的电活动。我们在之前的研究中表明，功能性癫痫患者认为他们对心跳等身体内部信号有很好的意识，但实际上在测试时，内感受的准确性很差。这种差异与他们的症状和癫痫发作的频率相对应。我们还表明，当功能性癫痫患者受到生理压力时，这种客观准确性会发生显著变化。这一发现也反映在工作中，我们发现在记录的功能性癫痫发作之前，与记录的癫痫发作相比，心跳相关的脑电活动发生了更大的变化。我们认为大脑误解了内感受的变化，这导致了功能性癫痫发作。在这项研究中，我们想要测量当患者被要求专注于他们的心脏时，在身体压力之前和之后，与心跳相关的脑电活动的变化。身体压力将由冷压力刺激引起，在这种刺激中，患者被要求将他们的手放在冰水中长达三分钟。我们认为，与癫痫发作患者相比，功能性癫痫发作患者的心跳相关脑电活动变化更大。如果我们能证明这一点，这将意味着这可能是一个有用的诊断工具，以区分癫痫和功能性癫痫发作，而不需要实际的癫痫发作记录。我们还想评估，当功能性癫痫患者处理身体信号时，大脑中负责内感受的部分更活跃，以及这些大脑区域的活动在身体压力后如何变化。我们将通过扫描来测量大脑活动，通过血液流动的变化来测量。我们还会同时直接记录脑电波和心脏活动。这将使我们了解大脑活动的变化主要是由一个人更关注自己的身体引起的，还是因为他们注意到身体唤起的变化，比如身体压力引起的更强、更快的心跳。如果我们能了解功能性癫痫发作的机制，我们就能开发出针对这些患者的新型靶向治疗方法。

Functional seizures look like epileptic seizures, but unlike them, they are not associated with abnormal, excessive brainwave activity. Of the 1% of the population diagnosed with epilepsy, up to 20% actually have functional seizures, and yet our understanding of the biological causes of functional seizures remains limited. Instead, they are classically thought to have a psychological basis. The diagnosis and differentiation of functional seizures from epileptic seizures remains problematic. A gold-standard diagnosis is based on admission of a patient to capture a typical seizure with concurrent video and brainwave (EEG) recording. This is costly, not widely available, patients may not have seizures during their admission, and some epileptic seizures may not have recordable excessive brainwave brain activity. This can lead to a significant delay in diagnosis, inappropriate treatments and increased rates of illness and premature death. The lack of understanding of the neurobiological basis of functional seizures means treatment options are limited. In this study we propose a novel way of differentiating epileptic and functional seizures, and a better understanding of how and why functional seizures happen. Interoception is a sixth sense that tells the brain what is happening inside the body and represents things like hunger or thirst. It also relates to perception of things like tiredness, pain, temperature or other internal sensations. It can be conscious or unconscious, and affects the way a person thinks, feels and behaves. Interoception can be studied in various ways such as testing a person's accuracy at detecting their heartbeats, or by using a brainwave recording (EEG) to measure the electrical activity in the brain that occurs when a person focuses on their heartbeat. We have shown in previous work that patients with functional seizures think they have good awareness of internal bodily signals like heartbeats, but actually have poor interoceptive accuracy when tested. This discrepancy corresponds to their symptoms, and the frequency of their seizures. We have also shown that when patients with functional seizures are put under physical stress this objective accuracy changes significantly. This finding is also reflected in work where we found bigger changes in heartbeat related electrical brain activity before recorded functional seizures, compared to recorded epileptic seizures. We think the brain misinterprets changes in interoception, and this causes functional seizures. In this study we want to measure changes in heartbeat related electrical brain activity when patients are asked to focus on their heart, before and after physical stress. The physical stress will be caused by a cold pressor stimulus, in which patients are asked to keep their hand in ice-cold water for up to three minutes. We think the changes in heartbeat related electrical brain activity will be bigger in patients with functional seizures compared to those with epileptic seizures. If we can prove this, it would mean that this could be a useful diagnostic tool to differentiate epileptic and functional seizures, without the need for actual seizures to be recorded.We also want to assess which parts of the brain responsible for interoception are more active when patients with functional seizures are attending to their bodily signals, and how activity in these brain regions changes after physical stress. We will measure this with scans that measure brain activity via changes in blood flow. We will also directly record electrical brainwave and heart activity at the same time. This will allow us to understand whether the changes in brain activity are primarily caused by a person focusing more on their body, or because they notice changes in physical arousal such as a stronger, faster heartbeat caused by the physical stress. If we can understand the mechanisms of functional seizures, we can develop novel, targeted treatments for these patients.