Interoception and functional seizures: a mechanistic and diagnostic approach

功能性癫痫看起来像癫痫发作，但与它们不同的是，它们与异常、过度的脑波活动无关。在被诊断为癫痫的1%的人口中，高达20%的人实际上患有功能性癫痫，但我们对功能性癫痫的生物学原因的了解仍然有限。相反，它们被经典地认为有心理学基础。功能性发作和癫痫发作的诊断和鉴别仍然存在问题。黄金标准的诊断是基于患者同时进行视频和脑波(EEG)记录捕捉到典型的癫痫发作。这是昂贵的，并不广泛获得，患者可能在他们的入院期间没有癫痫发作，并且一些癫痫发作可能没有可记录的过度脑电波大脑活动。这可能导致诊断的严重延误、不适当的治疗以及增加患病和过早死亡的比率。对功能性癫痫的神经生物学基础缺乏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和功能性癫痫的新方法，并更好地理解了功能性癫痫发生的方式和原因。内感是一种第六感，它告诉大脑体内正在发生的事情，并代表饥饿或口渴等事物。它还与对疲劳、疼痛、体温或其他内在感觉的感知有关。它可以是有意识的，也可以是无意识的，并影响一个人的思维、感觉和行为方式。可以通过各种方式来研究内部感觉，比如测试一个人检测心跳的准确性，或者使用脑波记录(EEG)来测量当一个人专注于他们的心跳时大脑中发生的电活动。我们在以前的工作中已经表明，功能性癫痫患者认为他们对心跳等内部身体信号有很好的意识，但实际上在测试时，他们的感觉准确性很差。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，当功能性癫痫患者处于身体压力下时，这一客观准确性会发生显着变化。这一发现也反映在我们的工作中，我们发现，与记录的癫痫发作相比，在记录的功能性癫痫发作之前，心跳相关的大脑电活动发生了更大的变化。我们认为大脑曲解了内感觉的变化，从而导致功能性癫痫发作。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，在身体压力前后与心跳相关的脑电活动的变化。身体压力将由冷加压刺激引起，在刺激中，患者被要求将手放在冰水中长达三分钟。我们认为，与癫痫发作患者相比，功能性癫痫患者心跳相关脑电活动的变化会更大。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来区分癫痫和功能性癫痫，而不需要记录实际的癫痫发作。我们还想评估当功能性癫痫患者关注他们的身体信号时，大脑中负责相互感觉的部分更活跃，以及这些大脑区域的活动在物理应激后如何变化。我们将通过扫描来测量这一点，通过血液流动的变化来测量大脑活动。我们还将同时直接记录电脑波和心脏活动。这将让我们了解大脑活动的变化是由一个人更多地关注自己的身体引起的，还是因为他们注意到身体唤醒的变化，如身体压力导致的心跳更快、更强。如果我们能够了解功能性癫痫的机制，我们就可以为这些患者开发新的、有针对性的治疗方法。

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.