Epilepsy

Background: Epilepsy affects about 1 percent of the U.S. population. Most people with epilepsy respond well to medicine, but some do not. Researchers want people who have diagnosed or suspected epilepsy to participate in ongoing studies. They want to learn more about clinical care for epilepsy. They want fellows and residents to learn more about the care of people with epilepsy. Objectives: To learn more about seizures and find ways to best treat people with drug-resistant epilepsy. Eligibility: Adults and children ages 8 years and older with diagnosed or suspected epilepsy Design: Participants will be screened with: Physical exam Medical history Questionnaires Participants will have many visits. They may be admitted to the hospital for several weeks. Their medication might be stopped or changed. Participants will have many tests: Blood and urine tests EEG: Wires attached to the head with paste record brain waves. This may be videotaped. Thinking and memory tests MRI: Participants lie on a table that slides in and out of a tube. They perform simple tasks in the tube. MEG: Participants lie on a table and place their head in a helmet to record brain waves. PET scan: Participants lie on a table that slides into a machine. A small amount of radioactive dye is injected into their arm with an IV. For the IV, a small tube is inserted into the arm with a needle. Participants will stay enrolled in this study if they join other epilepsy-related studies. They may be contacted at intervals for follow-up. Their participation will end if they have not been seen clinically for their epilepsy for 3 years.

Background: \- Drug resistant epilepsy is the term used to describe epilepsy that cannot be controlled by medication. Many people whose seizures do not respond to medication will respond to surgical treatment, relieving seizures completely or almost completely in one-half to two-thirds of patients who qualify for surgery. The tests and surgery performed as part of this treatment are not experimental, but researchers are interested in using the data collected as part of routine standard epilepsy care to better understand epilepsy and its treatment. Objectives: \- To use surgery as a treatment for drug resistant epilepsy in children and adults. Eligibility: \- Children and adults at least 8 years of age who have simple or complex partial seizures (seizures that come from one area of the brain) that have not responded to medication, and who are willing to have brain surgery to treat their medically intractable epilepsy. Design: * Participants will be screened with a medical history, physical examination, and neurological examination. Imaging studies, including magnetic resonance imaging and computer-assisted tomography (CT), may also be conducted as part of the screening. Participants who do not need surgery or whose epilepsy cannot be treated surgically will follow up with a primary care physician or neurologist and will not need to return to the National Institutes of Health for this study. * Prior to the surgery, participants will have the following procedures to provide information on the correct surgical approach. * Video electroencephalography monitoring to measure brain activity during normal activities within a 24-hour period. Three to four 15-minute breaks are allowed within this period. * Electrodes placed directly in the brain or on the surface of the brain to measure brain activities and determine the part of the brain that is responsible for the seizures (seizure focus). * Participants will have a surgical procedure at the site of their seizure focus. Brain lesions, abnormal blood vessels, tumors, infections, or other areas of brain abnormality will be either removed or treated in a way that will stop or help prevent the spread of seizures without affecting irreplaceable brain functions, such as the ability to speak, understand, move, feel, or see. * Participants will return for outpatient visits and brain imaging studies 2 months, 1 year, and 2 years after surgery.

The purpose of this research is to address the challenges of correctly monitoring, managing, and diagnosing epilepsy in participants whose seizures are not well captured by standard electroencephalography (EEG) tests and who cannot use or are not able to use more standard monitoring techniques. This research is being done to understand how the Minder System helps physicians make decisions about participant's epilepsy treatment after an actionable event. The Minder System was granted De Novo classification by the U.S. Food and Drug Administration (FDA) and is not investigational. Participants that have completed the DETECT study and received the Minder System previously will consent to join this long-term follow-up observational study. The study will collect information about general wellbeing, use of healthcare services, and experience using the Minder data over time to support long-term epilepsy care. All participants will continue to be followed by their treating physician and undergo assessments and visits every six (6) months until two (2) years after receiving the Minder device.

The purpose of this research is to address the challenges of diagnosing and long-term management of epilepsy in participants whose seizures are not well captured by standard electroencephalography (EEG) tests and who cannot use or are not able to use more standard monitoring techniques. This research will compare the Minder System to standard of care in providing reliable seizure data. The Minder System was granted De Novo classification by the U.S. Food and Drug Administration (FDA) and is not investigational. Participants will consent to join the study and be implanted with the Minder device; or consent to join the study and continue with their Standard of Care (SOC) as a control group. Participants chose to be implanted with the Minder device will have the device implanted under their scalp. After implantation, participants will be randomly assigned to a group where their treating physician will have access to the EEG data collected by the Minder System or a group where their treating physician does not have access to the EEG data collected by the Minder System. Participants receiving the Minder System will not know which group they are in (blinded) until the study ends. All participants will continue to be followed by their treating physician and undergo assessments and visits until enough information is available to determine a treatment plan or the 6-month follow-up visit.

The purpose of this study is to determine effects of Acupuncture on a Patient's mood and cognition,evaluate changes in clinically-reported seizure frequency and severity and analyze effects of Acupuncture on electrographic epileptiform activity stored by the RNS System

Objectives: The overall study objective is to compare the sensitivities and specificities of morphometric analysis techniques using structural MRI images based on pre- and postsurgical localization of epileptic foci in patients undergoing presurgical evaluation for medically refractory epilepsy. To carry out these analyses, we aim to establish an age-stratified normative imaging database using healthy volunteers. Additional objectives are to identify abnormal networks in these patients using resting state fMRI/EEG and MEG/EEG, and to use language and memory fMRI tasks to examine the effects of epileptogenic zones and surgery on cognitive function and the networks associated with these functions. Study population: 300 adults and children (age 8 and older) with uncontrolled focal epilepsy, and 200 age-stratified healthy volunteers. Design: A retrospective and prospective natural history study. Research procedures for patients in this study include neuropsychological testing and 1-4 MRI sessions during presurgical evaluation and an additional 1-3 MRI sessions and neuropsychological testing approximately 12 months post-operatively. Research testing (such as research neuropsychological tests or MRI scanning sequences) will be done during a visit for clinical testing whenever possible, likely reducing the number of required visits. Patients will also have optional MEG and 7T structural imaging. Data will also be obtained from patients who have already undergone epilepsy surgery if they had procedures as outlined in the protocol and are willing to share the data. Healthy volunteers will receive a subset of the pre-operative procedures for patients, requiring at least 3 visits. In order to ensure adequate data acquisition, subjects may be re-scanned up to three times for the portions of the study in which they participated, possibly requiring additional visits. Outcome measures: The main outcomes will be establishment of normative values for morphometric analysis methods in age-stratified normal controls, and comparison of the sensitivity and specificity of these measures to pre- and postsurgical localization of the epileptogenic zone. Secondary outcome measures will include determination of the sensitivity and specificity of source localization using MEG/EEG and resting state fMRI/EEG, and to evaluate changes in activation during rest, as well as language and memory fMRI tasks in patients pre- and postsurgically, to examine the effects of epileptogenic zones and surgery on cognitive function and the networks underlying these functions.

This is a clinical research study for an investigational drug called RAP-219 in adult participants with focal seizures. This study is being conducted to determine if RAP-219 is safe and effective in reducing focal seizure frequency.

Background: \- The blood-brain barrier separates the brain from the rest of the body. Epilepsy is a neurological disease that causes seizures. It can affect this barrier. Researchers think a contrast agent called mangafodipir might be better able to show areas of the brain that epilepsy affects. Objective: \- To see if mangafodipir is well tolerated and safe. To see if magnetic resonance imaging (MRI) using either mangafodipir or gadolinium can show areas of blood-brain barrier breakdown in people with epilepsy. Eligibility: * People ages 18-60 who: * Have epilepsy not controlled by drugs * Prior or concurrent enrollment in 18-N-0066 is required Design: * Participants will be screened with: * Medical history * Physical exam * Blood and urine tests * Participants will have up to 6 visits in 1-3 months. One visit is an inpatient stay lasting 2-10 days. Visits may include: * Video-EEG monitoring for participants with epilepsy * An IV catheter put in place: a needle guides a thin plastic tube into an arm vein. * Getting mangafodipir through the IV. * Getting gadolinium through the IV. * Up to 6 MRI scans over a 10-day period: a magnetic field and radio waves take pictures of the brain. Participants lie on a table that slides into a metal cylinder. They are in the cylinder for 45-90 minutes, lying still for up to 10 minutes at a time. The scanner makes loud knocking sounds. Participants will get earplugs. * A final MRI at least 2 weeks after receiving mangafodipir.

Despite the continuous development of new antiseizure medications over the past 25 years, 30% of patients with epilepsy suffer from drug-resistant seizures and are at risk of epilepsy-related complications, like cognitive dysfunctions, sleep-disordered breathing or Sudden and Unexpected Death in Epilepsy (SUDEP). SUDEP typically occurs during sleep, after a nocturnal seizure, and primarily results from a postictal central respiratory dysfunction in patients with generalized convulsive seizure (GCS), suggesting that interaction between respiratory dysfunction and sleep state may play a role in its pathophysiology. Post-mortem data in SUDEP patients showed alteration of neuronal populations involved in respiratory control in the medulla. Accordingly, pharmacologic strategies aimed at reducing the severity of postictal respiratory dysfunction has appeared as one of the most promising way to prevent SUDEP. However, no encouraging result has hitherto been reported. Interconnections between the complex network that regulates arousal and sleep and the respiratory network are numerous. They primarily include the relation between chemosensitive regulation and arousal system to ensure asphyxia-induced arousal (i.e. arousal to elevated CO2), especially through serotonin (5HT)-dependent connections in brain stem. The link between alterations of the brainstem networks involved in arousal regulation and respiratory dysfunction has not been characterized in patients with epilepsy yet. Like 5HT, adenosine is deeply implicated in the regulation of sleep and central respiratory control. Seizures transiently increase adenosine extracellular levels. Adenosine physiological effects in the brain are mediated through the activation of two types of Adenosine receptors (ARs), A1Rs and A2ARs. Extracellular adenosine promotes sleep via A1R-dependant inhibition of glutamatergic neurons in the basal forebrain, but also via A2AR-dependant activation of neurons in the nucleus accumbens. Respiration is also inhibited by A1R and A2AR. Most importantly, it has been shown that drug-resistant epilepsy is associated with long-term alterations of ARs cortical expression. However, whether or not a similar epilepsy-related plasticity of ARs occurs in the brainstem and may participate to chronic arousal and respiratory dysfunction in epilepsy has never been investigated. Considering the tight interplay between central respiratory control, arousal regulation and brainstem adenosine, the main hypothesis of the BRAVE study is that epilepsy might result in alterations of the distribution of A1Rs in the brainstem structures involved in respiratory regulation and/or arousal control, especially in the brainstem structures involved in respiratory regulation under hypercapnic condition. The study combines clinical respiratory characterization, morphological, functional and metabolic imaging, using the hybrid simultaneous 3T MRI-PET scanner (Siemens Biograph mMR) of the CERMEP. Combining PET with anatomical and functional MR imaging enables non-invasively in vivo mapping of receptor binding and functional neuronal assessment of a physiological task in the entire brain with high spatial resolution. Investigators already performed fMRI study of respiratory centers, showing number of functional changes in brainstem regions participating to the central control of respiration, including reduced activation during breath-holding fMRI, in patients with epilepsy. The BRAVE study will use the same respiratory paradigm as the one used in this past study. PET imaging will be focused on A1R, using \[18F\]CPFPX, a selective A1R antagonist.

Epilepsy affects nearly 600,000 people in France and causes neurological seizures that can lead to lasting impairments and stigma. Physical activity provides many benefits, including improved quality of life, social participation, and reduced stress and seizure frequency. Despite these benefits, people with epilepsy tend to be less active than the general population due to barriers such as fear of seizures during exercise, fatigue, and negative beliefs about the disease. Psychological factors and stigma influence physical activity engagement and affect how the disease is integrated into personal identity, impacting quality of life and treatment adherence. Studying the role of anxiety, stigma, and illness identity, as well as their interaction with physical activity identity, is essential to better understand and promote physical activity among people with epilepsy.

Epilepsy can lead to cognitive impairments, particularly in attention, which may affect daily activities such as driving. Driving plays a key role in maintaining autonomy and is essential for the social and professional integration of people with epilepsy. Therefore, assessing fitness to drive is a major issue for individuals with epilepsy. French legislation governing driving for people with epilepsy clearly outlines the periods during which a person is not permitted to drive. However, the means or methods for evaluating driving fitness in these individuals are not well defined. Currently, assessment is based more on a medical consultation than on a comprehensive evaluation of driving ability. Using a driving simulator in combination with an EEG could be a valuable approach to better assess the impact of epilepsy-related cognitive impairments on driving performance.

In addition to the search for new pharmaceutical or surgical solutions that could improve the therapeutic management of epileptic individuals, it is interesting to ask whether other complementary approaches, such as canine mediation in psychomotor therapy, could enhance the quality of life in this population. However, there is currently no evidence indicating that exposure to animals through mediation sessions would be beneficial for epileptic individuals, particularly regarding their quality of life, anxiety, emotional management, or cognition (such as social cognition). In the absence of current data in this population, it seems pertinent to study the impact of this practice on people with epilepsy. Furthermore, beyond quality of life, it would be valuable to examine whether it also influences anxiety or the frequency of seizures in individuals with epilepsy (a phenomenon reported for epileptic individuals living with a pet dog or a service dog). Canine mediation could help better manage and regulate the emotions of epileptic individuals, as well as improve their self-esteem.

In recent years, the in vivo study of the central nervous system has undergone significant advancement through the implementation of magnetic resonance imaging (MRI)-based neuroimaging techniques. In particular, the advent of high- and ultra-high-field MRI systems has substantially contributed to a deeper understanding of the pathophysiological mechanisms underlying neurological diseases and has supported the development of personalized approaches in medicine. In the field of neuroimaging, the application of MRI techniques to investigate brain function and connectivity in vivo is increasingly expanding at ultra-high magnetic field strength (7T). This research project aims to develop, implement, and optimize advanced techniques to improve image quality through deep learning-based approaches and real-time monitoring of magnetic field fluctuations, with the goal of achieving functional neuroimaging at very high spatial and temporal resolution on a 7T scanner. These techniques will be applied in healthy volunteers to address fundamental questions in basic neuroscience, as well as in clinical populations with central nervous system disorders, including patients with focal epilepsy and patients with congenital brain lesions associated with persistent neurological deficits. The basic neuroscience component will allow investigation of mechanisms of brain function and connectivity between eloquent cortical regions and subcortical structures. In the clinical setting, improved delineation of activation maps in eloquent brain areas and characterization of their reorganization under pathological conditions are expected to enhance personalized therapeutic decision-making and deepen our understanding of neuroplasticity mechanisms, with potential impact on clinical care pathways.

This randomized controlled trial aims to evaluate the effect of a nurse-led, stigma-reduction-based epilepsy education program on perceived/internalized stigma, concealment of epilepsy, and self-management among adults with epilepsy. Participants will be randomly assigned to an intervention group or a control group. The intervention group will receive a structured nurse-led education program consisting of four weekly sessions, each lasting approximately 45-60 minutes. The program will address epilepsy-related knowledge and misconceptions, stigma and self-stigma, disclosure and concealment of epilepsy, communication, medication adherence, seizure triggers, stress management, seizure diaries, and individual self-management planning. The control group will receive routine care without additional structured education during the study period. Outcomes related to epilepsy stigma, concealment, and self-management will be assessed using validated measurement tools.

The goal of this clinical trial is to explore a new type of personalized brain stimulation that works during day time and night time hours using the Medtronic Percept Deep Brain Stimulation (DBS) device in patients with Lennox-Gastaut Syndrome. The main question(s) this study aims to answer is: 1. Does using the personalized DBS reduce motor seizures compared to conventional DBS? 2. Is the number of seizures reported by caregivers different for patients using the personalized DBS? 3. How often do patients using the personalized DBS experience undesired side effects? Researchers will compare the personalized DBS that works night time, personalized DBS device that works during the day time, and conventional DBS. Participants will: 1. Have their seizures and sleep patterns recorded for 3-months 2. Assess their neurocognitive function 3. Answer questionnaires about communication, movement, and sleep quality 4. Wear a sleep headband and seizure warning watch for 5 nights 5. Complete a mood and sleep assessment 6. Have a 3T and possibly 7T MRI 7. Be implanted with stereo-encephalography and undergo 3\~5 days of monitoring 8. Have the stereo-encephalography taken out 9. Receive DBS implantation through surgery and have several months of stimulation and no stimulation periods 10. Have routine clinical visits to check on healing after surgery 11. Have their caregiver help them keep a dairy about their seizures, sleep and quality of life

Epilepsy is a chronic neurological disorder that can significantly affect a person's physical abilities and daily life due to the condition itself and the side effects of anti-epileptic medications. Individuals with epilepsy often experience fatigue, changes in balance, decreased muscle strength, and reduced mobility, which can restrict their activities of daily living and lead to a decline in their overall quality of life.The primary purpose of this observational study is to comprehensively evaluate the functional status and quality of life in individuals diagnosed with epilepsy. To accurately measure these impacts, the study will compare the physical performance, balance, and fatigue levels of epilepsy patients to a healthy control group.The main question this study attempts to answer is: How do functional mobility, balance, fatigue, and quality of life in individuals with epilepsy differ from those of healthy individuals without the condition?By identifying these physical and functional challenges, researchers aim to better understand the relationship between physical capacity and quality of life in this population. Ultimately, the research findings will guide the future development of targeted physiotherapy and rehabilitation programs designed to improve the functional independence and quality of life for individuals living with epilepsy.

Background: Some people with brain tumors have seizures related to the tumor. This is called tumor-related epilepsy. Usually brain tumors are treated by removing as much of the brain tumor as possible without causing problems. Researchers think this may improve the outcome for people with brain tumors. It may completely relieve or greatly reduce the number of seizures they have. Objectives: To evaluate people with brain tumors that are associated with seizures and to offer surgical treatment. Also, to study how surgery affects seizures. Eligibility: People age 8 and older who have a brain tumor with associated seizures. They must be willing to have brain surgery to treat their epilepsy. Design: Participants will be screened with a review of their medical records. Participants will have a medical history and physical exam. Participants will be admitted to the hospital at NIH. They will have Medical history Physical exam Neurological exam Tests of memory, attention, and thinking Questions about their symptoms and quality of life Blood drawn They may also have: MRI or CT scan. They will lie on a table that slides in and out of a machine that takes pictures. For part of the MRI, they will get a dye through an intravenous (IV) catheter. Video electroencephalography monitoring. Electrodes will be placed on the scalp. The participant s brain waves will be recorded while doing normal activities. Participants will be videotaped. Participants will keep a seizure diary before and after surgery. Participants will have surgery to remove their brain tumor and the brain area where their seizures start. They will stay in the hospital up to a week after surgery. Participants have for follow-up visits at NIH. ...

The goal of this study is to learn about the effects of scopolamine (an anticholinergic drug) on areas of the brain involved in memory, and changes it may have on brain activity. The investigators will do this by testing epileptic patients who are already undergoing intracranial surgery for seizure monitoring, and measuring the activity from the brain areas being assessed. The main questions it aims to answer are 1) whether scopolamine changes memory activity solely at encoding (the time when the person perceives and determines to remember an item or event) as has previously been found, or if it also can selectively impact retrieval (when the item or event which has been processed is recalled or remembered), and 2) what the nature of the brain activity changes is. Participants will complete two treatment arms. One of these will be with the drug, and the other will be with a saline solution, so that the participants are unaware which session the actual drug has been received. Patients will complete a verbal and/or spatial task each of the two days. An anesthesiologist will administer either the drug or the saline at a critical point which addresses both of the research questions. Researchers will compare the brain activity between the two treatment arms to determine what brain activity changes, and at what time point during memory formation.

The specific aim of this study is to compare simultaneous assessment of gastric emptying and gastric accommodation in response to a caloric meal In patients who have previously undergone activation of left cervical VNS for the treatment of medication-resistant depression. Our hypothesis is that cervical VNS increases gastric accommodation and accelerates gastric emptying compared to a bank of healthy control data.

This trial is a Phase II randomized, double-blind, placebo controlled multi-site study to evaluate the safety and efficacy of early sirolimus to prevent or delay seizure onset in TSC infants. This study is supported by research funding from the Office of Orphan Products Division (OOPD) of the US Food and Drug Administration (FDA).

This study is to evaluate the effectiveness of targeted Transcranial Electrical Stimulation with Temporal Interference (TES-TI) interventions to boost Non-Rapid Eye Movement (NREM) sleep, decrease seizures and promote emotional health in patients with epilepsy. Up to 24 participants (8 control participants for technical optimization prior to recruitment and 16 patients with epilepsy) will be enrolled and can expect to be on study for up to 24 months.

This Phase 2, randomized, double-blind, placebo-controlled study will evaluate the safety, tolerability, and efficacy of oral AV078 in participants with refractory epilepsy due to tuberous sclerosis complex (TSC). Approximately 42 participants will be randomized in a 5:1 ratio to receive AV078 or placebo. The study will include a Screening Period collecting 4 weeks of pre-treatment Baseline data on seizure frequency, and progress to a 12-week Treatment Period, followed by an in person final follow-up visit approximately 2 weeks after the last dose.

The goal of this study is to learn about the effects of Cobenfy KarXT (xanomeline and trospium chloride) on episodic memory processing, including specific effects on areas of the brain involved in memory and changes it may have on brain activity. The investigators will do this by testing epileptic patients who are already undergoing intracranial surgery for seizure monitoring, and measuring the activity from the brain areas being assessed. The main questions it aims to answer are 1) whether Cobenfy KarXT changes memory activity based on its agonist effect on muscarinic receptors and acetylcholine, and 2) what the nature of these brain activity changes are. This work builds on previous experiments evaluating cholinergic antagonists. Participants will complete two treatment arms. One of these will be with the drug, and the other will be control session. Participants will not be blinded to the study condition. Patients will complete a verbal serial recall and/or associative recognition task each of the two days. An anesthesiologist or patient nurse will administer either the drug or the placebo at a critical point which addresses both of the research questions. Researchers will compare the brain activity between the two treatment arms to determine what brain activity changes, and whether there is an additional behavioral effect on memory.

Epilepsy is a chronic neurological disorder characterized by recurrent unprovoked seizures, but it can also affect the autonomic nervous system and cardiovascular function. Certain anti-epileptic medications and seizure activity may influence cardiac rhythm, beat-to-beat heart rate variability (HRV), and ventricular repolarization (measured by the QT interval). The primary purpose of this study is to evaluate autonomic tone and cardiac electrical conduction in children with epilepsy receiving anti-epileptic drugs by measuring time-domain HRV and the corrected QT (QTc) interval, comparing patients on monotherapy, patients on polytherapy, and healthy controls. A total of 60 children aged 1 to 18 years will be enrolled across three groups: 20 children with epilepsy receiving single-drug therapy (monotherapy), 20 children with epilepsy receiving two or more medications (polytherapy), and 20 healthy children serving as controls. All participants will complete non-invasive assessments during a single visit, including: * Collection of clinical and demographic data (age, sex, epilepsy duration, and medication details) * A standard 12-lead electrocardiogram (ECG) to measure the QT interval and calculate the QTc using Fridericia's formula * A 5-minute continuous resting ECG recorded in a supine position after 10 minutes of quiet rest to calculate time-domain HRV parameters (SDNN, RMSSD, and pNN50) The findings aim to detect early autonomic or electrophysiological alterations, aiding in the understanding of cardiac safety in pediatric epilepsy management.

30% of patients with epilepsy suffer from drug-resistant seizures and have a greater risk of premature mortality than the general population. Among all causes of death, the most frequent is SUDEP, for sudden and unexpected death in epilepsy patients. SUDEP typically occurs after a nocturnal seizure, and primarily results from a postictal central respiratory dysfunction in patients with generalized convulsive seizure (GCS), suggesting the critical role of seizure-related impairment of breathing control, and underscoring the importance of monitoring and preventive interventions during the post-ictal phase. Most of patients with drug-resistant seizures demonstrate transient peri-ictal apnea and hypoxemia especially in the aftermath of a GCS. Experimental and clinical data suggest that most SUDEP primarily result from a fatal seizure-related respiratory arrest 5. Apnea was the primary cause of death in several epilepsy models. In patients whose SUDEP had occurred during long-term video-EEG monitoring, we observed fatal postictal central apnea after a nocturnal GCS in all SUDEP. Accordingly, it is currently hypothesized that in a subgroup of patients, repetition of seizures may contribute to chronic alteration of respiratory regulation which may increase the risk of fatal postictal central respiratory arrest. Central regulation of autonomic function is ensured by the so-called Central Autonomic Network (CAN), which anatomy in humans has primarily been investigated in neuroimaging studies or using intraEEG (iEEG) data in patients with drug-resistant focal epilepsy undergoing presurgical evaluation with intracerebral electrodes. Central regulation of breathing primarily rely on brainstem, especially the preBötzinger complex for rhythm generation and the retrotrapezoid nucleus and dorsal raphe for chemoreception, especially ventilatory response to hypercapnia. However, through an intricated structures connecting these regions, this respiratory signal projects to a network of cortical and subcortical regions mainly including the limbic and sensorimotor cortical areas. Studies in patients undergoing iEEG reinforced the role of limbic and paralimbic structures, with transient central apnea elicited by direct electrical stimulation of amygdala, hippocampus, anterior parahippocampal, and antero-mesial fusiform gyri. However, our group also reported transient hypoxemia could be elicited by cortical direct electrical stimulation outside the temporo-limbic structures, most commonly after stimulation of the perisylvian cortex. Importantly, our group recently showed that involvement of this perisylvian cortex in the epileptogenic zone is a strong risk factor of SUDEP, reinforcing the importance of further studying its integration in the cortical control of respiration. The involvement of cortical control of ventilation is particularly important to ensure expiratory load compensation, a typical situation after GCS, which is associated with airway obstruction, especially when the face is positioned into the pillow. This cortical component of the physiological response to experimental expiratory loads was investigated in healthy subjects through the study of EEG activity during an expiratory load compensation protocol. Accordingly, EEGs were processed by ensemble averaging expiratory time-locked segments and examined for pre-expiratory EEG potentials, defined as a slow negative shift from the baseline signal preceding expiration, and suggestive of cortical preparation of expiration. Expiratory load compensation was associated with EEG premotor potential presumably involving the supplementary motor area. However, because of the limited spatial resolution of scalp EEG, the organization of cortical neural sources involved in this expiratory load compensation or during response to hypercapnia, especially the interaction between the premotor cortex, the sensorimotor cortical areas and the perisylvian cortex is unknown.