2016 Grace Grant: Effects of Sleep Deprivation
People who live with epilepsy have a wide variety of symptoms and many different kinds of seizures. Similarly, they often have many different triggers—things that can provoke seizures or make them more likely. One of the most common triggers is sleep deprivation.
Researchers, physicians, patients and families will tell you that lack of sleep can often increase the likelihood of seizures, even in patients whose epilepsy is well controlled with medication. Although this problem is well known, scientists and physicians don’t have a lot of knowledge about the relationship between sleep and seizure susceptibility. With a two-year, $100,000 Grace Grant from Lily’s Fund, Dr. Rama Maganti and Associate Professor Mathew Jones will study how sleep deprivation, acute or chronic, alters seizures. They will examine how mechanisms in the brain are altered by sleep deprivation and whether this phenomenon can be prevented.
2014 Grace Grant: Using HD-EEG to Locate Seizures and Pathways
Dr. Giulio Tononi, UW-Madison neuroscientist and psychiatrist, received the inaugural two-year Grace Grant to see if high-density electro encephalograph (HD-EEG) technology can be used to identify the focal point of seizures in the brain, as well as calculate the seizure’s pathway.
Locating that point of origin is critical for patients preparing for brain surgery. The traditional scalp EEG does not provide enough detail, so neurosurgeons must rely on intracranial EEG (electrodes placed directly on the brain itself). This invasive approach increases the risk of infection and other complications.
HD-EEG technology may offer an accurate way to find the source of seizures, without the invasive approach. This method might also predict the pathways of the seizures and how they move across the brain, an under-studied area of epilepsy.
“If high-density EEGs can be used to accurately locate the focal point of seizures, physicians would have an entirely new way to plan for brain surgery. For epilepsy patients, this could minimize the number of tests and avoid invasive monitoring that requires multiple surgeries,” said Tononi.
“Over the next two years, we hope to study at least 20 patients, examining how seizures spread through the brain’s cortex. This is a very novel approach – one that might yield insights on the pathophysiology of seizures,” said Tononi.
Giulio Tononi, UW-Madison neuroscientist and psychiatrist, is working with a two-year Grace Grant to see if high-density electro encephalograph (HD-EEG) technology can identify the focal point of seizures in the brain and calculate the seizure’s pathway. Locating that point of origin is critical for patients preparing for brain surgery. HD-EEG technology has been used extensively in sleep research, but its application in a clinical setting has been limited, due to the tremendous amount of information coming from 250 electrodes simultaneously. Giulio has developed proprietary software that can help interpret that data, in ways that might yield important breakthroughs for epilepsy patients. He and his collaborators have completed HD-EEG recordings in 4 patients, all of whom had epileptic activity captured. They will continue recruiting patients, followed by some careful analysis of the resulting data.
During 2014, the Tononi lab focused on using high density EEG to locate seizures and their pathways. The question: Can HD-EEG locate the source of epileptic seizure for pre-surgical planning? Using this advanced technology, can scientists predict how seizures might move across the brain?
To date, the team has successfully recorded HD-EEGs in 15 patients with refractory epilepsy who were undergoing pre-surgical evaluation. The researchers successfully captured 27 seizures and 1500 spikes during these extended recordings. Using special software to decode massive amounts of data captured by the HD sensor arrays, the lab has detected single events such as spikes, the location of seizure onset, and the pathways the seizures followed.
Using methods developed at the Tononi lab, patients with more than 30 epileptic spikes (11 of the 15 subjects) are being analyzed to assess how individual EEG events travel over the cerebral cortex. These analyses will help scientists better understand how epileptic activity spreads from the seizure onset zone to the rest of the cortex.
The on-scalp HD-EEG data are then compared to traditional intracranial (within the skull) recordings in the same patients to validate results.
Additionally, the team evaluated a distortion of sleep homeostasis (slow-wave, non-REM sleep) in regions of the brain associated with epilepsy onset, and found additional abnormalities.
Due to the success of their recordings and analysis, the team is now in the beginning stages of preparing the first manuscript of this study. They are also applying for an NIH grant to further study epileptic spikes as travelling waves.
Since receiving the first ever $100,000 Grace Grant from Lily’s Fund, Giulio Tononi and Rama Maganti were able to acquire high-density EEG recordings in 20 patients with focal epilepsy at the UW Epilepsy Monitoring Unit. Each recording lasted between 24 and 48 hours, producing a data set that allowed researchers to study how epileptic spikes travel in the brain from their point of origin.
“Our preliminary data show that epileptic spikes do indeed travel across the brain, in a pattern that is consistent across spikes within the same patient, but different from one patient to the other. We plan to use this data to write a first manuscript and to submit a grant to NIH,” says Giulio.
While analyzing the same data acquired with support from Lily’s Fund, the team also uncovered new links between epileptic activity and changes in brain activity during sleep.
“We found that patients with epilepsy show a deeper sleep than healthy controls, and that the depth of sleep is proportional to the amount of seizure activity during wakefulness preceding sleep – as if it was compensating for it. In contrast, epileptic spikes during sleep seem to decrease the efficiency of sleep,” says Rama.
Based on the team’s findings, epilepsy scientists may be able to identify preferential routes of epileptic activity and target those areas of the brain in surgery. Additionally, the new data regarding sleep activity, and how epileptic spikes disrupt sleep, suggest that epilepsy therapy should aim at not only preventing seizures, but also quelling interictal spikes.
Building upon this work at UW-Madison, future epilepsy research might focus on the similarity between epileptic spikes and the spread of seizure activity leading to loss of consciousness. Further studies should also compare results obtained using high-density EEG recordings to those obtained using intracranial recordings.
“We have preliminary data in one epileptic patient, showing that this comparison is feasible. These results open a whole new line of research for our team and others to improve the pre-surgical planning of patients with focal epilepsy,” says Rama . “Knowing how epileptic activity moves across the brain in individual patients could allow more accurate surgical techniques and better outcomes for the patient.”