Interoception and functional seizures: a mechanistic and diagnostic approach

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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.